Bacillus

Arch Dermatol, 2005 Jan, 141(1), 57 - 9
Absence of Ribosomal RNA of Mycobacterium tuberculosis Complex in Sarcoidosis; Marcoval J et al.; OBJECTIVE: To determine whether Mycobacterium tuberculosis ribosomal RNA (rRNA) is present in fresh tissue specimens from patients with sarcoidosis . DESIGN: A prospective study . SETTING: A university-based hospital.Patients Thirty-five patients diagnosed as having sarcoidosis at the University Hospital of Bellvitge, Barcelona, Spain, were included in the study . Fresh tissue samples with granulomatous inflammation were prospectively collected between 1997 and 2001 from all patients . For each sample tested, approximately 1 negative control was included . MAIN OUTCOME MEASURES: Mycobacterium tuberculosis rRNA was detected using an isothermal enzymatic amplification system of target rRNA of M tuberculosis complex via DNA intermediates . Smears for acid-fast staining and mycobacteriological cultures were also obtained . RESULTS: A total of 78 biopsy specimens (57 skin, 10 lymph node, 3 lacrimal gland, 2 spleen, 2 lung, 2 muscle, 1 bone, and 1 nerve) collected from 74 patients (35 patients with sarcoidosis and 39 control patients) were included in the study . Stains for acid-fast bacilli and mycobacterial cultures were negative for organisms in all cases . Mycobacterium tuberculosis rRNA was not detected in the specimens from any patients with sarcoidosis or in those from control patients whose cultures were negative for organisms . Ribosomal RNA was detected in 6 tissue specimens from patients with cultures that were positive for M tuberculosis and that were processed in parallel to the samples included in the study . CONCLUSIONS: Although previous studies have reported that mycobacterial antigens may play a role in granuloma formation in some patients with sarcoidosis, our results suggest that M tuberculosis cannot be considered to be the etiologic agent of the disease.

Chest, 2005 Jan, 127(1), 205 - 12
Delays in Suspicion and Isolation Among Hospitalized Persons With Pulmonary Tuberculosis at Public and Private US Hospitals During 1996 to 1999; Rozovsky-Weinberger J et al.; BACKGROUND: While prior studies have shown that public and private hospitals differ in their rates of suspicion and isolation of patients who are at risk for tuberculosis (TB), no study has investigated whether this variation is due to differences in the impact of patient case-mix on hospitals or to variations attributable to specific hospital practice patterns . OBJECTIVE: To investigate patient-level and hospital-level factors associated with delays in TB suspicion and isolation among inpatients with pulmonary TB disease . DESIGN: Retrospective cohort study of patients hospitalized with culture-positive pulmonary TB during 1996 to 1999 . SETTING: Patients with culture-proven pulmonary TB treated at three public hospitals (765 patients) and seven not-for-profit private hospitals (172 patients) in Chicago, Los Angeles, and southern Florida that provided care for five or more patients with TB per year during the study period . MEASUREMENTS: Two-day rates (within 48 h from admission) of acid-fast bacilli (AFB) smear orders and 1-day rates (within 24 h from admission) of TB isolation . RESULTS: Two-day rates of ordering AFB smears were > 80% at three public and two private hospitals vs 65 to 75% at five private hospitals . One-day rates of TB isolation at the three public hospitals were 64%, 79%, and 86%, respectively, vs 39 to 58% at the seven private hospitals . Delays of > 2 days in ordering AFB smears were associated with patient-level factors: absence of cough (adjusted odds ratio {AOR}, 6.02; 95% confidence interval {CI}, 3.82 to 9.52), cavitary lung lesion (AOR, 5.17; 95% CI, 1.98 to 13.50), night sweats (AOR, 3.38; 95% CI, 1.90 to 5.99), chills (AOR, 1.70; 95% CI, 1.01 to 2.88), and female gender (AOR, 1.66; 95% CI, 1.06 to 2.60) . Delays of > 1 day in ordering pulmonary isolation were associated with patient-level factors: absence of cough (AOR, 3.40; 95% CI, 2.31 to 5.03), cavitary lung lesion (AOR, 2.66; 95% CI, 1.57 to 4.50), night sweats (AOR, 1.98; 95% CI, 1.35 to 2.92), and history of noninjecting drug use (AOR, 1.86; 95% CI, 1.16 to 2.99) and one hospital-level factor: receiving care at a nonpublic hospital . Even after adjustment for patient-level factors, TB patients at private hospitals were half as likely as those at public hospitals to be placed in pulmonary isolation (AOR, 0.47; 95% CI, 0.30 to 0.72), while odds of suspecting TB in these same patients were similar at both hospitals . CONCLUSION: Private hospitals should order TB isolation for all patients for whom AFB smears are ordered, a policy that has been instituted previously at public hospitals in our study.

Nippon Geka Gakkai Zasshi, 2004 Dec, 105(12), 745 - 50
{Surgical treatment of pulmonary tuberculosis}; Nakajima Y; The indications for the surgical treatment of pulmonary tuberculosis are mainly for multidrug-resistant tuberculosis (MDR-Tb) . In Fukujuji Hospital there have been 91 pulmonary resections for 83 MDR-Tb cases during the past 20 years . Of those resections, upper lobectomies with or without partial resection of other lobes comprised 55%, segmentectomies 10%, and pneumonectomies 30% . The following major postoperative complications occurred: prolonged air leakages in 19%, empyema in 9%, and respiratory failure in 6% . However, there were no operative deaths . After pulmonary resection for MDR-Tb, immediate negative conversion rate of expectoration of tuberculous bacilli was 98%, reexpectoration rate of them was 12%, The final cure rate was 92% . Surgical treatment is worth consideration for the treatment of refractory pulmonary tuberculosis.

Rinsho Shinkeigaku, 2004 Nov, 44(11), 846 - 8
{Bacterial meningitis: determination of pathogens and therapeutic management}; Kamei S; Recent aspects of pathogen determination and therapeutic management are reviewed based on a clinical analysis of 50 of our adult patients with bacterial meningitis (BM) . The sensitivity for detecting pathogens using gram-stained smears and cultures of CSF was high in untreated patients, but low in patients previously treated with antibiotics . Latex agglutination for antibodies of pathogens is rapid and has a potential for determining pathogens in partially treated meningitis . The PCR also has a potential for determining pathogens in pre-treated, culture-negative cases and for detecting whether the bacterial pathogen is resistant or sensitive to antibiotics . The initial empiric regimen of antibiotics has been modified with elevation in the detection rate of drug-resistant bacilli . The proportion of patients undergoing treatment with VCM and/or Carbapenems has recently increased at our department . A combination of dexamethasone under administration of antibiotics has also been established as effective in adult BM . On admission, some patients are difficult to diagnose as BM rather than herpes simplex encephalitis (HSVE) . A serum CRP value of >2.0 mg/dl proved useful for such different diagnosis in our patients . The predictors of a poor outcome based on multivariate logistic analysis in our BM patients were level of unconsciousness and sepsis.

Dis Aquat Organ, 2004 Nov 23, 62(1-2), 121 - 32
Ultrastructure of Mycobacterium marinum granuloma in striped bass Morone saxatilis; Gauthier DT et al.; An emerging epizootic of mycobacteriosis currently threatens striped bass Morone saxatilis populations in Chesapeake Bay, USA . Several species of mycobacteria, including Mycobacterium marinum, species resembling M . avium, M . gordonae, M . peregrinum, M . scrofulaceum and M . terrae, and the new species M . shottsii have been isolated from diseased and healthy bass . In this study, we describe the ultrastructure of developing M . marinum granulomas in experimentally infected bass over a period of 45 wk . The primary host response to injected mycobacteria was formation of large macrophage aggregations containing phagocytosed bacilli . M . marinum were always contained within phagosomes . Close association of lysosomes with mycobacterial phagosomes, as well as the presence of electron-opaque material within phagosomes, suggested phagolysosomal fusion . Development of granulomas involved epithelioid transformation of macrophages, followed by appearance of central necrosis . Desmosomes were present between mature epithelioid cells . The necrotic core region of M . marinum granulomas was separated from overlying epithelioid cells by several layers of flattened, electron-opaque spindle-shaped cells . These cells appeared to be formed by compression of epithelioid cells and, aside from a flattened nucleus, did not possess recognizable organelles . Following the development of well-defined, paucibacillary granulomas, secondary disease was observed . Recrudescence was marked by bacterial replication followed by disruption of granuloma architecture, including loss of epithelioid and spindle cell layers . In advanced recrudescent lesions, normal tissue was replaced by macrophages, fibroblasts, and other inflammatory leukocytes . Large numbers of mycobacteria were observed, both intracellular and suspended in cellular debris.

Eur J Gastroenterol Hepatol, 2005 Jan, 17(1), 27 - 31
Bacterial translocation and its consequences in patients with cirrhosis; Guarner C et al.; Bacterial translocation is the passage of viable bacteria from the intestinal lumen to mesenteric lymph nodes and other extraintestinal sites.Spontaneous bacterial peritonitis is the main clinical consequence of bacterial translocation in cirrhosis.Translocation of bacterial products of viable or non-viable bacteria, such as endotoxin and/or bacterial DNA, through the intestinal wall could stimulate the immune system and the hyperdynamic circulatory state in cirrhosis with clinical consequences that are under evaluation.Bacterial translocation is currently considered the passage of viable gut flora across the intestinal barrier to extraluminal sites . Aerobic Gram-negative bacilli are the most common translocating bacteria . Intestinal bacterial overgrowth, impairment in permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences are the major mechanisms postulated to favour bacterial translocation in cirrhosis . Bacterial translocation is a key step in the pathogenesis of spontaneous bacteraemia and spontaneous bacterial peritonitis in cirrhosis . Translocation of intestinal bacterial products from viable or non-viable bacteria, such as endotoxin and bacterial DNA, has recently been associated with pathophysiological events, such as activation of the immune system and derangement of the hyperdynamic circulatory status in cirrhosis . Clinical consequences of these effects of bacterial products are presently under investigation.

Clin Diagn Lab Immunol, 2005 Jan, 12(1), 130 - 4
Effects of Thalidomide on Intracellular Mycobacterium leprae in Normal and Activated Macrophages; Tadesse A et al.; Thalidomide is an effective drug for the treatment of erythema nodosum leprosum (ENL) . ENL is an inflammatory reaction that may occur in multibacillary leprosy patients . Its cause(s) as well as the mechanism of thalidomide in arresting this condition are not fully understood . It has been suggested that ENL is an immune complex-mediated hypersensitivity precipitated by the release of Mycobacterium leprae from macrophages . The released antigen may complex with precipitating antibodies, initiating complement fixation and the production of inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) . Thalidomide has been shown in vitro to reduce antigen- or mitogen-activated macrophage production of TNF-alpha . We investigated if thalidomide could also influence the viability of intracellular M . leprae . Mouse peritoneal macrophages were infected with M . leprae, activated with gamma interferon and endotoxin, or nonactivated, and treated with thalidomide . Intracellular bacilli were recovered, and metabolic activity was assessed by a radiorespirometric procedure . Thalidomide did not possess antimicrobial action against M . leprae in normal and activated host macrophages . This suggests that thalidomide does not retard the release of mycobacterial antigens, a possible prelude or precipitating factor for ENL . A distinct sequence of events explaining the mechanism of action for thalidomide's successful treatment of ENL has yet to be established.

Bull World Health Organ, 2004 Nov, 82(11), 836 - 843 Epub 2004 Dec 14.
Tuberculosis situation among tribal population of Car Nicobar, India, 15 years after intensive tuberculosis control project and implementation of a national tuberculosis programme; Murhekar MV et al.; OBJECTIVE: To assess the tuberculosis (TB) situation in the tribal community of Car Nicobar island 15 years after the national TB programme was implemented in this area after an intensive phase of TB control in 1986 . METHODS: The entire population of Car Nicobar was enumerated through a house-to-house survey . Children aged <14 years were tuberculin tested and read for reaction sizes . Individuals aged >15 years were asked about the presence of chest symptoms (cough, chest pain, and unexplained fever for two weeks or longer and haemoptysis), and sputum samples were collected from patients with chest symptoms . Sputum samples were examined for presence of acid-fast bacilli . FINDINGS: Among the 4543 children enumerated, 4351 (95.8%) were tuberculin tested and read . Of the 981 children without bacille Calmette-Guerin scars, 161 (16.4%) were infected with TB . A total of 77 cases who were smear-positive for TB were detected from among 10 570 people aged >15 years; the observed smear-positive case prevalence was 728.5 per 100 000 . The standardized prevalence of TB infection, annual risk of TB infection, and prevalence of cases smear-positive for TB were 17.0%, 2.5%, and 735.3 per 100 000, respectively . CONCLUSION: The prevalence of TB infection and smear-positive cases of TB increased significantly between 1986 and 2002 . Such escalation took place despite the implementation of the national TB programme on this island, which was preceded by a set of special anti-TB measures that resulted in sputum conversion in a substantially large proportion of the smear-positive cases prevalent in the community . The most likely reason for the increase seems to be the absence of a district TB programme with enough efficiency to sustain the gains made from the one-time initial phase of special anti-TB measures . High risk of transmission of TB infection currently observed on this island calls for a drastic and sustained improvement in TB control measures.

Infect Genet Evol, 2005 Mar, 5(2), 145 - 56
Mycobacterium tuberculosis molecular evolution in western Mediterranean Islands of Sicily and Sardinia; Sola C et al.; In this study, a total of 204 Mycobacterium tuberculosis DNAs from Sicily (n = 144) and Sardinia (n = 60) were studied by three genotyping methods . Results were analyzed both within and across islands, to define the phylogeographical specificities of the genotypes, look for their diversity and infer a molecular evolutionary scenario . A strong link between geography and tuberculosis genotypes was observed in Sardinia . The results were also matched against a world-wide genetic diversity database to compare the population structure of the tubercle bacilli in the islands . Eight common genotypes between Sicily, Sardinia and continental Italy were found which underlines the influences of the Italian mainland on the population structure on the islands and vice versa . A unified evolutionary scenario of M . tuberculosis evolution was built using numerical taxonomy and maximum parsimony (MP) methods . The finding of multiple families of M . tuberculosis strains (S, T, LAM, Haarlem), their presumed links with the major genetic groups (MGG) of M . tuberculosis complex, supports the view of independent introduction of several ancestral genotypes in Sicily and in Sardinia . We conclude that the two PCR-based genotyping combination (spoligotyping-VNTR) is an excellent tool to reconstruct M . tuberculosis phylogeny, that may be used to construct global and local evolutionary scenarios of the M . tuberculosis complex . The results obtained are paradigmatic of the complex interplay that exists between epidemic dynamics and evolutionary genetics of M . tuberculosis.

Lancet, 2005 Jan 8, 365(9454), 130 - 4
Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study; Zar HJ et al.; BACKGROUND: For microbiological confirmation of diagnosis of pulmonary tuberculosis in young children, sequential gastric lavages are recommended; sputum induction has not been regarded as feasible or useful . We aimed to compare the yield of Mycobacterium tuberculosis from repeated induced sputum with that from gastric lavage in young children from an area with a high rate of HIV and tuberculosis . METHODS: We studied 250 children aged 1 month to 5 years who were admitted for suspected pulmonary tuberculosis in Cape Town, South Africa . Sputum induction and gastric lavage were done on three consecutive days according to a standard procedure . Specimens were stained for acid-fast bacilli; each sample was cultured singly for M tuberculosis . FINDINGS: Median age of children was 13 months (IQR 6-24) . A positive smear or culture for M tuberculosis was obtained from 62 (25%) children; of these, 58 (94%) were positive by culture, whereas almost half (29 {47%}) were smear positive . Samples from induced sputum and gastric lavage were positive in 54 (87%) and 40 (65%) children, respectively (difference in yield 5.6% {1.4-9.8%}, p=0.018) . The yield from one sample from induced sputum was similar to that from three gastric lavages (p=1.0) . Microbiological yield did not differ between HIV-infected and HIV-uninfected children (p=0.17, odds ratio 0.7 {95% CI 0.3-1.3}) . All sputum induction procedures were well tolerated; minor side-effects were increased coughing, epistaxis, vomiting, or wheezing . INTERPRETATION: Sputum induction is safe and useful for microbiological confirmation of tuberculosis in young children . This technique is preferable to gastric lavage for diagnosis of pulmonary tuberculosis in both HIV-infected and HIV-uninfected infants and children.

Korean J Ophthalmol, 2004 Dec, 18(2), 190 - 5
A case of primary lid tuberculosis after upper lid blepharoplasty; Yang JW et al.; Primary lid tuberculosis after lid surgery is a very rare condition and is likely caused by the introduction of bacilli through epithelial injury . Secondary infection, due to direct hematogenous spread or contiguous spread from adjacent structures are more common presentations of lid tuberculosis . The authors experienced a case of primary lid tuberculosis occurring in a 19 year old female after blepharoplasty for making a eyelid crease . Her upper lid skin showed a reddish and non-tender mass lesion measured 3x1 cm, which was diagnosed as the tuberculosis through typical histopathological findings (caseous necrosis), acid-fast bacilli stain and PCR, and treated with anti-tuberculosis medications.

J Clin Microbiol, 2005 Jan, 43(1), 439 - 41
Evaluation of an accelerated protocol for detection of extended-spectrum beta-lactamase-producing gram-negative bacilli from positive blood cultures; Navon-Venezia S et al.; We evaluated a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in gram-negative bloodstream pathogens . Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate . Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel . Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.

J Clin Microbiol, 2005 Jan, 43(1), 174 - 8
Detection and identification of Mycobacterium tuberculosis in joint biopsy specimens by rpoB PCR cloning and sequencing; Yun YJ et al.; Osteoarticular tuberculosis (OAT) is an extrapulmonary tuberculosis and accounts for 1 to 3% of all tuberculosis cases . We used an rpoB PCR-plasmid TA cloning-sequencing method to detect and identify tubercle bacilli in surgical specimens from patients suspected of having OAT . By comparing the similarities of the rpoB sequences determined with those in GenBank, Mycobacterium tuberculosis was detected in 23 of 43 samples . Three of the 23 positive samples had mutations at codon 531, which are commonly observed in rifampin-resistant M . tuberculosis strains . Our results suggest that the rpoB PCR-TA cloning-sequencing method developed, which detects M . tuberculosis and which simultaneously determines its rifampin susceptibility, can also be used efficiently for the diagnosis of OAT.

Zhonghua Jie He He Hu Xi Za Zhi, 2004 Nov, 27(11), 767 - 70
{Clinical features of 23 cases of AIDS complicated by tuberculosis.}; Yuan J et al.; OBJECTIVE: To discuss the clinical features, treatment and prognosis of patients with AIDS complicated by tuberculosis(TB) . METHODS: The clinical features of 23 patients with AIDS complicated by tuberculosis admitted from 1997 to July 2004 were retrospectively analyzed . RESULTS: Of the 23 patients, most (94.3%) were young or middle-aged, and 11 (47.8%) died within half a year . The main HIV transmission was via sexual contact in 15 (65.2%) patients . Loss of body weight by 5 - 15 kg was present in all patients, cough for over 1 month in 15 (65.2%), and multiple opportunistic infections were complicated in most cases . Out of the 23 cases, 14 (60.9%) showed only pulmonary TB, and 8 (34.8%) showed lymph node TB . In 12 cases with infiltrated pulmonary TB, X-ray showed bilateral infiltration and no cavity formation was found . Slightly positive PPD test was found in 2 (8.7%) cases, and positive acid-fast bacilli was detected in sputum in 1 case (4.4%) . The pre-treatment CD(4)(+) cell number in 23 patients was much lower than that in AIDS patients without complicated TB (P < 0.05) . The pre-treatment CD(4)(+) cell number in patients died shortly after diagnosis was much lower than that in survived patients (P < 0.05) . The HIV RNA level in the 23 patients was much higher than that in patients without complication of TB (P < 0.05) . The mortality in patients treated with therapy against both TB and HIV was much lower than that in patients untreated or treated only with anti-TB therapy (P < 0.05) . CONCLUSIONS: For patients with AIDS complicated by TB, the high negative rate in PPD test and the atypical chest X-ray manifestations are common . However, lymph node TB is quite common with high mortality . The pre-treatment CD(4)(+) level decreases significantly, and is associated with mortality . The TB bacilli may accelerate HIV virus duplication . It is suggested that the patients be treated with a combination of anti-TB and anti-HIV therapies.

Kekkaku, 2004 Oct, 79(10), 587 - 604
{Reform of Japan's NTP and its technical perspectives}; Mori T; The 1951 Tuberculosis Control Law of Japan is now faced with tremendous changes that have occurred during the last 50 years in tuberculosis epidemiology and in the environment in tuberculosis control implementation . The law is also challenged with the shift of the paradigm for the National Tuberculosis (TB) Programme . In order to respond properly to these changes, the Tuberculosis Panel of the Health Science Council of the Ministry of Health, Labor and Welfare submitted its report for the amendment of the law in March 2002 . Based on this report, a new Tuberculosis Control Law was passed in Parliament last June, and related decrees of the Cabinet and the Ministry are now being revised in preparation for it's enactment in April 2005 . In this special lecture, the main points and framework of the revisions were discussed with the perspective of the development of new technical innovations relevant to each area of the revised TB control legislation . 1 . Case detection . There will be a shift from the current "indiscriminate" screening scheme to a selective one regarding periodic mass health examination . Only subjects aged 65 or older will be eligible for the screening, supplemented with selected occupational groups who are considered to be at a higher risk of TB, or may be a danger to others if they develop TB, such as health-care providers and school teachers . In addition, local autonomies are responsible for offering screening to the socio-economic high-risk populations, such as homeless people, slum residents, day laborers, and/or workers in small businesses . This means that the efforts of the autonomies are critical for the new system to be effective . The extra-ordinary examination will be limited to only the patient's contacts, and will be mandatory for those contacts so they cannot refuse to be examined by the Health Center . The public services used in the contact investigations will be greatly facilitated by such new technologies as DNA fingerprinting of TB bacilli and a new diagnostic of TB infection using whole-blood interferon-gamma determination (QuantiFERON) . The quality of clinical diagnosis and monitoring of treatment should also be improved by introducing an external quality assurance system of commercial laboratory services . 2 . Chemoprophylaxis . Although not explicitly defined in the new legislation, the expansion and improvement of chemoprophylaxis to cover anyone with any risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago . These technical innovations in diagnosis of TB infection will be very helpful . Development of new drug regimens for the preventive treatment is also badly needed . 3 . Immunization . Prior to the amendment of the Law, the BCG vaccination of students entering primary and junior high schools has been already abandoned . In order to encourage the early primary vaccination for infants, the new Law will adopt the direct vaccination scheme in which babies will be given the BCG vaccine without tuberculin testing . This program will be implemented safely, only if it is given to young babies, e.g., less than one year old, as defined by the decree . It is essential to maintain the high level of vaccination coverage under the new program . The autonomy may encounter difficulty mobilizing client babies shortly after their birth (only one year, as compared with the current four years) . To avoid the possible, though very rare, adverse health effects due to the vaccination of infected babies, careful questioning should be conducted regarding the risk of exposure to infection prior to vaccination . A ready course of treatment and examinations for abnormal reactions after vaccination (Koch's phenomenon) is also warranted . 4 . Treatment and patient care: The revised Law clearly states the governmental responsibility for treating TB patients in close cooperation with a doctor . This is an important legal basis for the expansion of the DOTS Japan version . While the development of new anti-tuberculosis drugs will be realized in the near future, Japan still has to overcome the issue of improper practice of treatment, as well as the government's slow process for approving new drugs to be used for multi-drug resistant TB and non-tuberculous mycobacterioses . 5 . Prefectural TB Control Plan: In order to resolve the problems specific to the respective prefectures in terms of epidemiological parameters or available resources, the new Law requests every prefecture to develop its own TB control plan . In order for the new TB Control Law to be effective, strong government commitment supported by technological innovation is mandatory . It is for that reason that the Japanese Society of Tuberculosis should aggressively join the global movement to stop TB along with the general public of Japan.

Kekkaku, 2004 Oct, 79(10), 569 - 71
{A case of pulmonary tuberculosis in late stage of pregnancy}; Nakanishi N et al.; A 28-year-old woman who was a nurse was admitted to our hospital because her sputum was positive for M . tuberculosis . She was pregnancy of 35 weeks . First, she was administered INH, RFP, PZA and was treated with cesarean section on the 21st day after starting tuberculosis chemotherapy . The operation was done in operating room of negative pressure ventilation . The patient returned to the tuberculosis ward, and the newborn infant entered to a newborn nursery room after confirming negative tubercle bacilli in amnionic fluid by PCR examination . EB was added to the regimen of chemotherapy after childbirth . In general hospitals, infection control is an important issue as seen in this case.

Indian J Pediatr, 2004 Dec, 71(12), 1063 - 8
Tuberculin sensitivity among children vaccinated with BCG under universal immunization programme; Chadha VK et al.; A tuberculin survey was conducted among 45988 children with BCG scar and 54227 children without BCG scar between 1-9 years of age and residing in selected rural areas of three defined zones of India . About 45-60% of the BCG-vaccinated children elicited reactions < 5 mm in size and about 70-80% had reactions < 10 mm . Therefore, in the majority of children (showing tuberculin reaction of < 10 mm), BCG-induced tuberculin sensitivity does not interfere with interpretation of tuberculin test . The study also revealed that a proportion of reactions among BCG vaccinated children in 5-9 mm, 10-14 mm and 15-19 mm range may be attributable to BCG vaccination . Therefore, reactions between 10-14 mm and especially 15-19 mm among the vaccinated children must be interpreted carefully . However, 19 mm was observed as the upper limit for BCG induced tuberculin sensitivity and all reactions >- 20 mm in size may be considered to be due to infection with tubercle bacilli, irrespective of the BCG vaccination status.

Clin Lab Sci, 2001 Spring, 14(2), 85 - 8
Modified Middlebrook 7H9 broth for the rapid detection of mycobacteria; Flournoy D et al.; OBJECTIVE: To compare the growth of acid-fast bacilli on classically formulated Lowenstein-Jensen media and Middlebrook 7H11 agar to modified Middlebrook 7H9 broth . DESIGN: Microbiology culture results were evaluated to determine the number of days required to detect growth of acid-fast bacilli from clinical specimens inoculated on different media . DATA: Three thousand one hundred fifty-seven acid fast bacilli cultures were performed from May 1996 through May 1999 . There were 140 positive cultures . Initial growth was detected only on Lowenstein-Jensen medium and/or Middlebrook 7H11 agar for 108 cultures, Lowenstein-Jensen medium and/or Middlebrook 7H11 agar and 7H9 for 12 cultures, and only modified Middlebrook 7H9 broth for 20 cultures . Of the 20 cultures that were initially detected only in 7H9, 11 grew in a mean time of 21.1 days compared with 32.5 days for the later growing solid media . The remaining nine grew in a mean time of 26.0 days but did not grow on solid media within the eight-week incubation period . Mycobacterium avium grew in a higher proportion of broth than solid medium cultures, suggesting a preference for the broth . CONCLUSION: The modified Middlebrook 7H9 broth was inexpensive to prepare, allowed for quick and easy growth interpretation, required no special appliances, e.g., ultraviolet light, and allowed for faster growth of some cultures . Although Lowenstein-Jensen medium and Middlebrook 7H11 agar remained the main-stays of our routine acid fast bacilli culture protocol, modified Middlebrook 7H9 broth provided earlier or additional positive results in 14% of the positive cultures . We recommend the use of modified Middlebrook 7H9 broth as described in this paper for improving early detection of acid fast bacilli by culture.

Med Mal Infect, 2004 Aug-Sep, 34(8-9), 375 - 81
{Treatment of tuberculosis-disease}
{Treatment of latent tuberculosis-infection: aiming at a change of practices in France}
{No authors listed}

Treatment indications for tuberculosis-infection depend on each case, but also on public health policy in each country . This policy usually made at the national level depends on tuberculosis epidemiology of the population concerned and on the country's socio-economic level of development, and more especially of its health system . Eradicating tuberculosis, in the Fifties, by treating all the sick patients or those only infected by the tuberculosis bacillus failed due to the context . Public health decision makers and large world organizations propose more realistic objectives, aiming at gradually eradicating the disease then the infection in each country by defining specific objectives for each one according to the local requirements . Thus, in developing countries, only a part of TB patients is diagnosed and treated: "those who carry enough bacilli to be positive on direct examination (BAAR+) and who thus present with the disease and are risk for their relatives" . In countries with intermediate development, the recommendation is to treat all the cases of tuberculosis-disease, but not to treat tuberculosis-infection.

Rev Port Pneumol, 2004 Sep-Oct, 10(5), 383 - 91
{Endobronchial tuberculosis -- clinical and bronchoscopic features}; Sucena M et al.; Endobronchial tuberculosis (ET) is a serious complication of pulmonary tuberculosis and is a major cause of morbidity . The aim of our retrospective study was to characterize the clinical, radiological, microbiological and bronchoscopic features of ET . Between January 1999 and June 2002 a total of 14 patients were diagnosed as having ET in our hospital . There were 8 (57%) men and 6 women with a median age of 39.6 +/- 18.1 years (range from 20 to 78 years) . Cough was the most common complain and it was present in 71.4% of patients . Only 5 patients were sputum smear positive . Five patients (35.7%) had parenchymal infiltration and this was the most common roentgenographic appearance . Forms of ET were classified into subtypes: actively caseating (n=4), granular (n=3), tumorous (n=3), edematous-hyperemic (n=2) and ulcerative (n=2) . The upper lobes were affected in 9 (64.3%) patients . Nine patients had involvement of the left bronchial tree, 3 of the right and in 2 there were bilateral lesions . The diagnosis could be established in 11 (78.6%) cases by bronchial biopsy . All patients had positive bronchial lavage cultures for acid-fast bacilli . Clinical manifestations and roentgenographic appearance of ET are not specific and so bronchoscopy is mandatory for the prompt diagnosis and follow-up of its evolution.

Leuk Lymphoma, 2005 Mar, 46(3), 471 - 5
Hodgkin's lymphoma and tuberculosis coexistence in cervical lymph nodes; Centkowski P et al.; We describe the case of a 47-year-old man admitted to the Department of Hematology because of fever, enlarged cervical and supraclavicular lymph nodes, hepatosplenomegaly and non-specific lung infiltrations . The histopathological examination of the cervical lymph node revealed Hodgkin's lymphoma (HL) NS type I . Clinical evaluation revealed stage IVB according to Ann Arbor classification and the presence of 5 unfavorable prognostic factors according to the International Prognostic Index . Despite BEACOPP chemotherapy (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), the enlarged lymph nodes, lung infiltrations and fever persisted . Microbiological and serological tests did not lead to the identification of any viral or bacterial pathogens . Bronchoscopy showed chronic inflammation and post-tuberculosis (TB) scars in bronchi without acid-fast bacilli in bronchoalveolar lavage (BAL) in culture and polymerase chain reaction (PCR) tests . However, the biopsy of the supraclavicular lymph node revealed multiple, caseating and necrotizing granulomatous lesions with scattered Reed - Sternberg (R - S) cells . The auramin staining presented acid-fast bacilli and allowed the diagnosis of productive and caseating TB coexisting with HL . The 4 tuberculostatics regimen and ABVD chemotherapy (adriamycin, bleomycin, vincristine, dacarbazine) resulted in a complete clinical response after 3 months of treatment . In conclusion, the association between HL and TB must be considered, especially in countries where the latter is endemic . The diagnosis may be difficult due to similarities in the clinical course, laboratory tests and imaging procedures.

Clin Infect Dis, 2005 Jan 1, 40(1), 58 - 66 Epub 2004 Dec 08.
Measurement of immunoglobulin G against Mycobacterial antigen A60 in patients with cystic fibrosis and lung infection due to Mycobacterium abscessus; Ferroni A et al.; BACKGROUND: The diagnosis and prognosis of lung infections due to the emerging nontuberculous mycobacterium (NTM) Mycobacterium abscessus are difficult to establish in children with cystic fibrosis . METHODS: We evaluated the usefulness of an enzyme-linked immunosorbent assay for detecting serum IgG antibodies against the ubiquitous mycobacterial antigen A60 . RESULTS: A total of 186 patients with cystic fibrosis (mean age+/-SD, 12.0+/-5.0 years) were studied, including 15 M . abscessus-positive patients who fulfilled American Thoracic Society (ATS) criteria for NTM infection (M . abscessus-infected patients), 7 M . abscessus-positive patients who did not fulfill ATS criteria, 20 patients positive for various other NTM who did not fulfill ATS criteria, and 144 NTM-negative control patients; mean IgG titers (+/-SD) for these 4 groups were 718+/-342 U, 193+/-113 U, 129+/-49 U, and 121+/-53 U, respectively (M . abscessus-infected patients vs . each of the other groups, P<.005) . The A60 IgG test was both sensitive (approximately 87%) and specific (approximately 95%) if adapted cutoff values were used (150 U and 250 U for patients aged <or=10 years and patients aged >10 years, respectively) and correlated well with results of acid-fast bacilli smears . CONCLUSION: Measurement of anti-A60 IgG may be useful for both the diagnosis and assessment of activity of M . abscessus lung infection in persons with cystic fibrosis.

Cytojournal . 2004 Dec 21;1(1):6 {Epub ahead of print}
FNAC OF Bacillus- Calmette-Guerin lymphadenitis masquerading as langerhans cell histiocytosis; Gupta N et al.; Bacillus Calmette Guerin (BCG) lymphadenitis is a well known entity . Disseminated BCG infection usually presents as generalized lymphadenopathy, skin rash and hepatosplenomegaly and at times, can pose a diagnostic challenge to clinicians . There are only a few published studies on the cytological findings of BCG lymphadenitis . In this letter we report the fine needle aspiration cytology (FNAC) of BCG lymphadenitis clinically masquerading as Langerhans cell histiocytosis (LCH) . FNA smears showed sheets of foamy macrophages and many polymorphs in a dirty necrotic background with many macrophages as well as polymorphs showing negatively stained rod like structures within their cytoplasm . Zeihl Neelson stain revealed that these cells were heavily loaded with acid fast bacilli (AFB) . In the index case, AFB were also seen within the cytoplasm of polymorphs, which has not been documented earlier in the literature.

Med Princ Pract, 2005 Jan-Feb, 14(1), 55 - 7
Listeria monocytogenes meningitis in an immunocompetent adult patient; Jamal WY et al.; OBJECTIVE: To report an interesting case of meningitis caused by Listeria monocytogenes in an immunocompetent adult . PATIENT AND METHODS: A previously healthy 25-year-old man presented with typical clinical features of meningitis . Cerebrospinal fluid (CSF) was obtained on the day of admission for biochemical and microbiological investigations . In addition, blood was also taken for culture and hematological studies . Antibiotic susceptibility test was performed using the Etest method . Microscopic examination of the CSF showed pleocytosis, which was predominantly lymphocytic, while the biochemical investigation revealed raised concentrations of protein and lactic acid as well as decreased glucose concentration . A 24-hour culture yielded pure growth of gram-positive bacilli identified by standard methods as L . monocytogenes . It was susceptible to ampicillin and trimethoprim-sulfamethoxazole . The patient was treated with intravenous ampicillin combined with gentamicin and made a complete recovery . CONCLUSION: This presentation describes an unusual case of meningitis caused by L . monocytogenes in a previously healthy young adult with no risk factor . Only a few similar cases have been reported in the literature.

J Vet Med B Infect Dis Vet Public Health, 2004 Dec, 51(10), 464 - 6
Disseminated Mycobacterium avium-intracellulare Infection in a Persian Cat; Knippel A et al.; Summary This report describes a disseminated infection with mycobacteria of the avium/intracellulare complex in a Persian cat in the absence of cutaneous lesions . Postmortem examination revealed severe granulomatous inflammation with numerous intrahistiocytic acid-fast bacilli in multiple organs . A gastrointestinal port of entry seems likely, as the ileocaecal lymph node was most severely affected.

Eur J Clin Microbiol Infect Dis, 2004 Dec, 23(12), 892 - 8
Accuracy of identification and susceptibility results by direct inoculation of Vitek 2 cards from positive BACTEC cultures; Kerremans JJ et al.; Rapid identification of bacteria and prompt acquisition of susceptibility results are valuable for patient care . The objective of the present study was to determine the accuracy of direct inoculation of Vitek 2 cards from positive BACTEC cultures compared to inoculation of the cards from subculture plates . Positive BACTEC cultures sampled between March 2001 and June 2002 were included . The results of direct inoculation were compared with the results of inoculation of Vitek 2 cards from subcultures . Of 161 gram-negative bacilli, 129 (80%) were correctly identified by direct inoculation compared to 145 of 161 (90%) by subculture . Susceptibility testing was performed on 2,862 antibiotic-isolate combinations . The essential agreement was 98.7% . The number of very major, major, and minor errors was 1 (0.2% of resistant strains), 1 (0.04% of susceptible strains), and 68, respectively . Direct identification of Staphylococcus spp . was not performed, but antimicrobial susceptibility was tested using 6,042 antibiotic-isolate combinations . The essential agreement was 95.2% . The number of very major, major, and minor errors was 73 (4.5% of resistant strains), 32 (0.8% of susceptible strains), and 106, respectively . Eighty-four percent of the very major errors occurred with trimethoprim-sulfamethoxazole . The results show that direct inoculation of Vitek cards is valuable as a rapid routine method for identification and susceptibility testing of gram-negative bacilli . For Staphylococcus spp., the susceptibility results obtained after direct inoculation of Vitek 2 cards are also acceptable except for those obtained with trimethoprim-sulfamethoxazole . Susceptibility results for this antibiotic, if obtained using direct inoculation, should not be reported to the clinician.

Indian J Chest Dis Allied Sci, 2000 Oct-Dec, 42(4), 325 - 39
Prevalence of pulmonary nocardiosis in a tuberculosis hospital in Amritsar, Punjab; Singh M et al.; The prevalence of pulmonary nocardiosis in a tuberculosis and chest diseases hospital in Amritsar is reported . Of 1510 sputum samples cultured from 1016 patients, 67 sputa originating from 16 patients were found to be positive for the Nocardia asteroides species complex . Based upon repeated isolation of N . asteroides from the respiratory tract, its microscopic demonstration in KOH wet mounts or stained smears of sputum and clinical evaluation of patients, 14 cases of pulmonary nocardiosis were diagnosed . This gave a prevalence of 1.4% pulmonary nocardiosis in the tuberculosis hospital . The prevalence of the disease was found to be 1.3% in the males as against 1.5% in the females . Of the various clinical categories of patients investigated, pulmonary tuberculosis with sputum negative for acid-fast bacilli (AFB) yielded the highest prevalence of 3.2%, followed by 1.3%, 1.2%, 1.1% and 0.5% in pneumonia, chronic obstructive pulmonary disease (COPD), bronchiectasis and pulmonary tuberculosis with sputum positive for AFB, respectively . Type IV cutaneous hypersensitivity to nocardin was observed in 19 of 908 (2%) patients tested, whereas only a solitary positive reactor was found among 260 healthy volunteers . Twelve of 19 nocardin positive reactors (63%) had unequivocally proven pulmonary nocardiosis . The nocardin skin test gave false negative results in two nocardiosis patients . More comprehensive investigations are warranted in order to evaluate the nocardin skin test as an additional aid for the diagnosis of nocardiosis . Barring a solitary exception, the nocardiosis patients were successfully treated with sulphadiazine or trimethoprim-sulphamethoxazole (TMP-SMZ) combination . To the best of our knowledge, this is the largest series of pulmonary nocardiosis patients in a prospective study as yet reported from India . The observations underscore the point that nocardiosis warrants greater attention in the differential diagnosis of bronchopulmonary diseases.

Am J Clin Oncol, 2004 Oct, 27(5), 522 - 8
The influence of intravesical therapy on progression of superficial transitional cell carcinoma of the bladder: a metaanalytic comparison of chemotherapy versus bacilli Calmette-Guerin immunotherapy; Huncharek M et al.; OBJECTIVE: Currently, the true impact of intravesical chemotherapy or immunotherapy (bacilli Calmette-Guerin {BCG}) on the rate of progression of superficial transitional cell carcinoma of the bladder to muscle invasive disease is unclear . A metaanalysis was performed to statistically compare the efficacy of these treatments in preventing tumor progression in this disease setting . METHODS: A prospective protocol outlining the metaanalysis noted here was developed followed by a thorough search of the existing published literature using strict eligibility criteria . Eight randomized, controlled trials were found that met protocol specifications . These reports contained data on 2427 patients who were statistically pooled using a fixed-effects model (Peto) . The outcome of interest was the proportion of patients progressing to muscle invasive or metastatic disease expressed as a summary odds ratio (ORp) . An ORp greater than unity favored BCG versus chemotherapy . RESULTS: Initial pooling of these 8 trials gave a nonstatistically significant summary odds ratio of 1.24 (0.95-1.61) without evidence of statistical heterogeneity . Analysis by drug type showed significant attenuation of the ORp when the effects of mitomycin C were compared with BCG, ie, 1.04 (0.76-1.42) suggesting that: 1) mitomycin is probably more active than the other chemotherapeutics used in the available trials and 2) BCG is not clearly superior to mitomycin C . Sensitivity analyses also demonstrated that failure to control for prior intravesical drug treatment in all but 2 of the analyzed studies produces a spurious result favoring BCG over intravesical chemotherapy . CONCLUSION: The available data fail to support a clear superiority of intravesical BCG over intravesical chemotherapy in preventing progression of superficial transitional cell carcinoma of the bladder . Mitomycin C appears more effective than the other commonly used drugs, and failure to control for prior intravesical chemotherapy in most of available studies results in a spurious finding of greater clinic effect of BCG over chemotherapy.

Semin Ophthalmol, 2004, 19(3-4), 101 - 4
Clinicopathologic case report: scleral buckle associated nontuberculous mycobacterial scleritis; Nielsen J et al.; Nontuberculous mycobacterial (NTM) infections have become increasingly important in ophthalmology, particularly with keratorefractive surgery . We report a case of scleral buckle associated NTM scleritis occurring in a 69-year-old male after silicone sponge explant removal . Purulent scleral ulceration with nodule formation persisted despite topical antimicrobial therapy, buckle removal, and surgical debridement . Eventually, tissue biopsy revealed noncasseating granulomas with acid-fast bacilli that were identified in culture as Mycobacterium chelonae . The infection resolved only after administration of systemic antibiotics . NTM are important pathogens in scleral buckle associated scleritis and should be considered in persistent cases . Surgical therapy remains the cornerstone of therapy, but antimicrobials, particularly newer fourth generation fluoroqunilones, may have an important role in treating scleral buckle associated NTM scleritis.

Indian Heart J, 2004 Jul-Aug, 56(4), 299 - 306
Homograft valve bank: our experience in valve banking; Verghese S et al.; BACKGROUND: A cardiac homograft valve bank with cryopreservation facility was established at the Institute of Cardiovascular Diseases, Madras Medical Mission, Chennai in July 1995 . METHODS AND RESULTS: During the last 7 1/2 years of its existence, from July 1995 to March 2003, 588 hearts were processed . The valves harvested were 390 aortic, 400 pulmonary and 39 others including mitral valve, aortic conduits, pericardium etc.; 176 (29.9%) hearts were discarded for various reasons which included failure to sterilize, HBV, HIV, HCV, treponema pallidum hemagglutination test positivity, atheromatous/fatty streaks, incompetent valves, and dissection mistakes . The valves were sterilized using an antibiotic cocktail of vancomycin, amikacin, streptomycin, cefotaxime and amphotericin B in Hank's balanced salt solution . Of the 585 valves issued for clinical use, 247 were aortic, 323 pulmonary and 15 others (mitral valve, pericardium, conduits) . Gram negative bacilli were the predominant contaminants from the hearts during the first half (July 1995 to February 1999) and gram positive organisms were the predominant contaminants during the later half (March 1999 to March 2003) of the study period . A variety of fungal contaminants like candida, aspergillus, penicillium and other fungi were also isolated from the homograft hearts at procurement . The valves were used most commonly for Rastelli procedure/right ventricular-pulmonary artery conduit (48.71%) followed by Ross procedure (23.41%) . The other procedures were aortic valve replacement (6.15%), truncus repair (5.81%), unifocalization with conduit repair (6.49%), aortoplasty (0.512%), left ventricular-pulmonary artery conduit (0.512%), pulmonary valve replacement (0.512%), aneurysm repair (0.34%), Norwood repair (0.34%), mitral valve replacement (0.17%) and other procedures (7%) . CONCLUSIONS: We have established a viable and functioning cardiac homograft valve bank to suit Indian conditions and till date, have issued 585 homograft valves for clinical use.

ORL J Otorhinolaryngol Relat Spec, 2004, 66(5), 275 - 80
Mycobacterial cervical lymphadenitis; Bayazit YA et al.; Cervical lymphadenitis is the most common head and neck manifestation of mycobacterial infections . The incidence of mycobacterial cervical lymphadenitis has increased . It may be the manifestation of a systemic tuberculous disease or a unique clinical entity localized to neck . It remains a diagnostic and therapeutic challenge because it mimics other pathologic processes and yields inconsistent physical and laboratory findings . A high index of suspicion is needed for the diagnosis of mycobacterial cervical lymphadenitis . A unilateral single or multiple painless lump, mostly located in posterior cervical or supraclavicular region can occur . A thorough history and physical examination, tuberculin test, staining for acid-fast bacilli, radiologic examination, fine-needle aspiration and PCR will be instrumental in arriving at an early diagnosis early institution of treatment before a final diagnosis can be made by biopsy and culture . It is important to differentiate tuberculous from nontuberculous mycobacterial cervical lymphadenitis because their treatment protocols are different . Tuberculous adenitis is best treated as a systemic disease with antituberculosis medication . Atypical infections can be addressed as local infections and are amenable to surgical therapy .

Int J Tuberc Lung Dis, 2004 Nov, 8(11), 1330 - 6
The cost of medical care and people's health-seeking behaviour before being suspected of tuberculosis in three local health systems, Nicaragua; Macq J et al.; OBJECTIVE: To assess the medical costs incurred by users and delay between first contact with a care provider and sputum test for acid-fast bacilli (AFB) in three areas of Nicaragua . METHODS: Directed interviews of consecutive series of tuberculosis (TB) suspects whose sputum had been examined for AFB . RESULTS: Of 252 TB suspects interviewed, 52% used more than one type of care giver and 35% used private practitioners . As a consequence, 18%, 21% and 29% of the interviewees in Carazo, El Viejo and Matagalpa, respectively, spent more than 1 month of the country's median income per inhabitant on medical care between the first visit to a care provider and the first sputum examination . Furthermore, more than 3 months elapsed on that part of the care pathway for 30%, 17% and 3% of interviewees in Matagalpa, El Viejo and Carazo, respectively . CONCLUSION: This study sheds light on the costs and delays incurred by TB suspects before reaching a laboratory for sputum smear examination . Both costs are lower for those suspects who exclusively use first-line governmental health services (FLGHS) . This has been relatively little documented in Latin America to date and could be used as an argument to develop strategies to strengthen the credibility of FLGHS.

Eur Respir J, 2004 Dec, 24(6), 1044 - 51
On the nature of Mycobacterium tuberculosis-latent bacilli; Cardona PJ et al.; Mycobacterium tuberculosis-latent bacilli are microorganisms that adapt to stressful conditions generated by the infected host against them . By slowing metabolism or becoming dormant, they may counterbalance these conditions and appear as silent to the immune system . Moreover, the dynamic turnover of the infected cells provokes a constant reactivation of the latent bacilli when the environmental conditions are favourable, or an activation after being dormant in necrotic and fibrotic lesions for a long period of time . Since there is no in vivo nor in vitro evidence for quick resuscitation of dormant bacilli, the current authors strongly favour the possibility that latent tuberculosis infection can be maintained for no longer than approximately 10 yrs, which is, nowadays, a time period very close to that considered for "primary" tuberculosis . This concept may also be helpful for newer epidemiological considerations regarding the real impact of reinfection in tuberculosis.

J Coll Physicians Surg Pak, 2003 Dec, 13(12), 694 - 6
Clinical and morphological evaluation of tuberculous peripheral lymphadenopathy; Hussain M et al.; OBJECTIVE: To analyze clinical presentations in patients of tuberculous peripheral lymphadenopathy . DESIGN: a descriptive observational study . PLACE AND DURATION OF STUDY: Department of Chest medicine, Jinnah Postgraduate Medical Centre and National Institute of Child Health from January to June 2002 . SUBJECTS AND METHODS: Patients presenting with peripheral lymphadenopathy with the confirmed diagnosis of tuberculous were included in the study . The diagnosis of tuberculosis was made on finding acid fast bacilli on smear examination and / or histological demonstration of caseating epithelioid cell granulomas in the specimen obtained by fine needle aspiration cytology (FNAC) or excision biopsy . Patients in whom definite diagnosis of tuberculosis was not established on the basis of microscopy or histopathology examination were excluded from the study . History and physical examination findings were recorded on pre-designed proforma . RESULTS: the maximum number of patients (68.75 %) was in pediatric age group . The duration of illness was more than a year in 43.75% of the patients . Cervical region was the commonest affected in 70.83 % patients . In majority of cases (89.58 %) glands were multiple and in 66.7% glands were matted . In 83% cases diagnosis was achieved by FNAC subjected for cytology and acid fast bacilte (AFB) smear examination . CONCLUSION: In local setting tuberculous etiology should be strongly suspected in a young patient presenting with peripheral lymphadenopathy, with prolonged duration of illness, and involvement of cervical glands with multiple and matted appearance . FNA is a reliable tool of diagnosis.

Transpl Infect Dis, 2004 Sep, 6(3), 132 - 5
Successful kidney re-transplantation in a patient with previous allograft kidney tuberculosis; Siu YP et al.; Opportunistic infections, and in particular tuberculosis (TB), carry substantial morbidity and mortality in solid organ transplant recipients . We report a 39-year-old man who underwent a cadaveric renal transplant . Three months postoperatively, he was diagnosed to have tuberculous infection of his graft kidney manifested as fever and renal impairment . The diagnosis was confirmed by renal biopsy, which showed granuloma formation and positive stain for acid-fast bacilli (AFB) . His systemic symptoms responded well to a complete course of anti-tuberculous therapy, but his renal function continued to deteriorate . Graft nephrectomy was performed and the patient underwent a second kidney transplant 1 year later . He remained well and asymptomatic thereafter . No signs of recurrence of tuberculous infection were noted up until the present time . This case illustrates that TB remains an important threat to transplant recipients . Although reactivation of dormant TB is the usual mode of infection, acquisition from the donor graft is also possible . The latter may account for the infection in our case, as our patient had a negative tuberculin skin test and normal chest radiograph prior to transplant . The identification of AFB in the kidney graft less than 3 months postoperatively also suggested that causal relationship . While diagnosing TB in post-transplant recipients is difficult and may require renal biopsy, as in our case, treatment on the other hand is no different from the standard protocols . However, no consensus has been reached on the safety of re-transplantation . Also, the need for graft nephrectomy and chemoprophylaxis remains unclear.

Nihon Kokyuki Gakkai Zasshi, 2004 Oct, 42(10), 919 - 23
{A case of bronchial ulcer due to infection by Mycobacterium abscessus}; Kasai S et al.; We present a rare case of tracheobronchitis caused by Mycobacterium abscessus . The patient was a 79-year-old man with a previous history of tuberculosis . For smear examinations, he repeatedly expectorated many acid-fast bacilli . Bronchoscopic examination revealed the presence of ulceration on the lower end of the trachea and extending to the right main bronchus . Mycobacterial cultures were used to grow Mycobacterium abscessus . Following an antimicrobial regimen of clarithromycin, amikacin, and cefoxitin, the patient exhibited marked improvement . After initial multidrug therapy, the patient was placed on clarithromycin for 10 months . No relapse has occurred to date.

Int J Antimicrob Agents, 2004 Dec, 24(6), 599 - 604
Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub-therapeutic dose against experimental tuberculosis; Sharma A et al.; The present study was designed to evaluate the chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) (PLG) nanoparticles (NP) encapsulating three front-line antitubercular drugs (ATDs: rifampicin, RIF; isoniazid, INH and pyrazinamide, PZA) at 2/3rd therapeutic dose . PLG nanoparticles prepared by the double emulsion and solvent evaporation technique were administered orally at 2/3rd therapeutic dose to guinea pigs . A single oral administration of the formulation resulted in sustained drug levels in the plasma for 7-12 days and in the organs for 11-14 days with a significant improvement in mean residence time as well as drug bioavailability . The administration of PLG nanoparticles every 10 days (five doses) to Mycobacterium tuberculosis H(37)Rv infected guinea pigs led to undetectable bacilli in the organs, as did 46 conventional doses . Therefore, nanoparticle based antitubercular chemotherapy forms a sound basis for a reduction in dosing frequency and also offers the possibility of reducing the drug dosage.

Kekkaku, 2004 Sep, 79(9), 531 - 5
{A case of pubic tuberculous osteomyelitis and pericarditis during anti-tuberculosis chemotherapy}; Ohkouchi M et al.; 56 year-old man was referred to the department of orthopedics in our hospital for further investigation on right inguinal pain . The patient was initially diagnosed as bacterial myelitis in right pubic bone and was treated with antibiotics . Since his symptom did not improve, the curettage was performed . Histological examination of the pubic bone obtained during the operation showed epithelioid cell granulomas with caseous necrosis, supporting the diagnosis of tuberculous osteomyelitis . Chest X-ray film revealed small nodular lesions in both upper lung fields . Sputum was positive for acid-fast bacilli and Amplified Mycobacterium Tuberculosis Direct Test (TB-MTD) was positive . The diagnosis of pubic tuberculous osteitis and pulmonary tuberculosis was confirmed . Specimens from the pubic bone and sputum were both culture positive for Mycobacterium tuberculosis, and bacilli were sensitive to anti-tuberculosis drugs . The antituberculosis chemotherapy was started with INH, RFP, SM and PZA . Symptoms had gradually improved, however 3 months after starting treatment, high fever developed and chest X-ray revealed heart enlargement and bilateral pleural effusion . Pericardial effusion showed exudative nature with lymphocyte predominancy and high level of ADA, 98.4 U/l . Pleural effusion was transudate . TB-MTD and culture were negative both in pericardial and pleural effusion . Paradoxical reaction was thought to be the cause of pericarditis . TB chemotherapy was continued and pericardial drainage was performed . One month later, fever improved, and pleural effusion and pericardial effusion disappeared . Transient elevated transaminase was observed, and was thought to be the side effect of anti TB drugs . All symptoms gradually improved, and he was discharged after 6 months TB chemotherapy.

Kekkaku, 2004 Sep, 79(9), 509 - 18
{Transmission of tuberculosis (I)}; Aoki M; BCG vaccination has been given to infants and children so extensively and repeatedly for more than 55 years in Japan that it is very difficult, or often impossible to diagnose tuberculosis infection by tuberculin testing . On the other hand, as the treatment of latent tuberculosis infection has become more and more important recently, diagnosis of infection is becoming more and more important at the occasions of contact survey . However, understanding of the health care workers about transmission of tuberculosis is incomplete frequently at present . This is the reason why the author has written this review . The author has described on the history of the progress of droplet nuclei infection theory, infectivity of tuberculosis by bacteriological status of the patients, importance of cough, susceptibility of the host, and environmental factor concerning transmission of tubercle bacilli in this issue.

BMC Infect Dis . 2004 Nov 17;4(1):51.
Mycobacterium tuberculosis from chronic murine infections that grows in liquid but not on solid medium; Dhillon J et al.; BACKGROUND: Old, stationary cultures of Mycobacterium tuberculosis contain a majority of bacteria that can grow in broth cultures but cannot grow on solid medium plates . These may be in a non-replicating, dormant growth phase . We hypothesised that a similar population might be present in chronic, murine tuberculosis . METHODS: Estimates of the numbers of viable M . tuberculosis, strain H37Rv, in the spleens and lungs of mice in a 7-day acute infection and in a 10-month chronic infection were made by conventional plate counts and, as broth counts, by noting presence or absence of growth in serial replicate dilutions in liquid medium . RESULTS: Plate and broth counts in 6 mice gave similar mean values in the acute infection, 7 days after infection . However, the broth counts were much higher in 36 mice with a chronic infection at 10 months . Broth counts averaged 5.290 log10 cfu /organ from spleens and 5.523 log10 cfu/organ from lungs, while plate counts were 3.858 log10 cfu/organ from spleens and 3.662 log10 cfu/organ from lungs, indicating that the total bacterial population contained only 3.7% bacilli in spleens and 1.4% bacilli in lungs, capable of growth on plates . CONCLUSION: The proportion growing on plates might be a measure of the "dormancy" of the bacilli equally applicable to cultural and animal models.

Eur J Radiol, 2004 Dec, 52(3), 300 - 9
Tuberculous arthritis of the appendicular skeleton: MR imaging appearances; Parmar H et al.; Tuberculosis {TB} of the appendicular skeleton is an uncommon infection caused by the tuberculous bacilli and constitutes only 1-3% of all tuberculosis infections . MR imaging features of tuberculous arthritis include bone marrow oedema, cortical erosions, synovitis, joint effusion, tenosynovitis, soft tissue collections, and myositis . These imaging features are at times non-specific, but in the correct clinical context help in diagnosis of tuberculosis . We present the various pathological manifestations of TB arthritis involving the different joints of appendicular skeleton and discuss their MR imaging appearances.

J Mol Biol, 2004 Dec 3, 344(4), 907 - 18
Highly ordered supra-molecular organization of the mycobacterial lipoarabinomannans in solution . Evidence of a relationship between supra-molecular organization and biological activity; Riviere M et al.; The complex mycobacterial mannosylated lipoarabinomannans (ManLAMs) are currently considered to be the major virulence factors of the pathogenic Mycobacterium tuberculosis . The recognition and the interaction of ManLAMs with immune system receptors have been shown to promote M.tuberculosis phagocytosis but also to down-regulate the bactericidal immune response of the host in favor of the survival of the pathogenic bacilli . To date these original biological activities were mainly associated to the presence of mannose residues capping the non-reducing ends of the ramified polysaccharide moiety of these complex lipoglycans . However, we demonstrated recently that the molecular recognition of ManLAM terminal mannose units by human pulmonary surfactant protein A (hSP-A) carbohydrate recognition domains depends on the presence of the lipid moiety of the ManLAMs as proposed by Sidobre et al . in 2002 . Thus, we investigated the putative role of the ManLAM aglycon moiety . The data presented here, indicate that the hydrophobic aglycon part of ManLAM is associated to a characteristic concentration-dependent supra-molecular organization of these complex molecules . Furthermore, we observed that the deacylated ManLAMs or the lipid-free mannosylated arabinomannans, which do not exhibit characteristic ManLAM activities, do not display this supra-molecular organization . These observations strongly suggest that the ManLAMs immunomodulatory activities might be associated to their particular organization . Finally, the determination of the critical micellar concentration of ManLAMs obviously supports the notion that this supra-molecular organization may be responsible for the specific biological activities of these complex molecules.

Curr Pharm Des, 2004, 10(26), 3285 - 95
Predictive in vitro models of the sterilizing activity of anti-tuberculosis drugs; Mitchison DA et al.; Sterilizing drugs kill Mycobacterium tuberculosis that persists during chemotherapy . Predictive models should mimic the conditions causing persistence in the lesions of cavitary disease, and should grade current anti-tuberculosis drugs according to their sterilizing activity determined in clinical trials . Models should start with old, stationary cultures grown micro-aerophilically . In these, persistent bacilli occur in different populations in which there is no appreciable cell division . Population 1 . Grows in liquid culture medium but not on solid medium . Killed by rifampicin . Population 2 . Grows on solid culture medium . Killed by rifampicin . Population 3 . Grows in liquid medium but not on solid medium . Tolerant of rifampicin . Population 4 . Bacilli from Cornell model mice, after treatment with pyrazinamide and isoniazid, cannot grow in liquid or on solid culture medium . Some of these populations are incorporated in models which start with 100-day liquid medium cultures . In model 1 (population 2) the new drug is added and colony counted after 7 days incubation . In models 2 and 3, 100 mg/L rifampicin is added to the 100-day culture when the bacilli lose their ability to grow on solid culture medium (population 3) . After re-suspension in rifampicin-free liquid medium for 7 days, the bacilli recover growth on solid medium, when a colony count is done . The new drug is added during incubation with rifampicin in model 3 and at the start of recovery in drug-free medium in model 2 . Models 1 and 3 grade isoniazid, rifampicin and pyrazinamide according to their sterilizing activity determined by clinical trials.

Curr Pharm Des, 2004, 10(26), 3239 - 62
Prospects for clinical introduction of nitroimidazole antibiotics for the treatment of tuberculosis; Barry CE 3rd et al.; Nitroaromatic antibiotics have a long and controversial history in human and veterinary medicine . This controversy lies behind the presumption of many pharmaceutical companies that nitroaromatic compounds should be filtered from the list of drug-like compounds but stands at odds with the remarkably safe clinical record of use of such compounds . In this review, we will describe the whole-cell structure-activity relationships that have been reported for antimycobacterial nitroimidazoles as well as the available in vivo data supporting efficacy with a particular emphasis on nitroimidazo{2,1-b}oxazines such as PA-824 . We will also explore the unique potential of such compounds to shorten the course of tuberculosis therapy by exerting a bactericidal effect on non-replicating bacilli . We will consider the mode of action of such compounds in sensitive organisms and discuss the mechanisms by which resistance may emerge . Finally, we will review the pharmacokinetics, toxicology and laboratory and animal studies linking nitroimidazoles with carcinogenicity and mutagenicity and assess the prospects for the clinical introduction of nitroimidazoles for the treatment of tuberculosis.

Eur J Heart Fail, 2004 Oct, 6(6), 753 - 6
NT-brain natriuretic peptide levels in pleural fluid distinguish between pleural transudates and exudates; Tomcsanyi J et al.; BACKGROUND: Pleural effusion is not pathognomic and distinguishing between transudates and exudates often presents a diagnostic dilemma . The purpose of our study was to examine whether the inclusion of pleural fluid brain natriuretic peptide (BNP) measurement into the analysis improves the diagnostic accuracy of pleural effusion . METHODS: The pleural effusion of 14 patients with CHF (group A) and 14 subjects with different pleural pathology (group B) were analyzed . Samples of pleural fluid and serum were obtained from all patients on admission and biochemical analysis, bacterial and fungal culture, acid-fast bacilli smear and culture and cytology were performed on the pleural fluid . In vitro quantitative determination of N-terminal pro-Brain natriuretic peptide (NT-proBNP) in serum and pleural fluid were performed by electrochemiluminescence immunoassay proBNP method on an Elecsys 2010 (Roche) analyzer . RESULTS: The median NT-proBNP levels in groups A and B were 6295 pg/ml and 276 pg/ml, respectively: (P=0.0001) . There was no overlap between the two groups . While the Light's criteria had a sensitivity of 93% and specificity of 43% for transudates, the pleural fluid NT-proBNP level accurately differentiated between the two groups . CONCLUSIONS: The pleural NT-proBNP levels were elevated in all patients who had transudate . Therefore if the NT-proBNP levels of pleural effusion are within the normal range, transudate resulting from congestive heart failure can be ruled out . Our results suggest that the inclusion of pleural fluid NT-proBNP measurement in the routine diagnostic panel would enhance discrimination among the different causes of pleural effusions.

Med J Malaysia, 2004 Mar, 59(1), 56 - 64
Pulmonary tuberculosis--a review of clinical features and diagnosis in 232 cases; Ismail Y; The diagnosis of pulmonary tuberculosis is often delayed due to atypical clinical features and difficulty in obtaining positive bacteriology . We reviewed 232 cases of pulmonary tuberculosis diagnosed in Kedah Medical Centre, Alor Setar from January 1998 to December 2002 . All age groups were affected with a male predominance (Male:Female ratio = 60:40) . Risk factors include underlying diabetes mellitus (17.7%), positive family history (16.8%) and previous tuberculosis (5.2%) . Nearly half (45.3%) of patients had symptoms for more than one year . Only 22% of patients had typical symptoms of tuberculosis (prolonged recurrent fever, cough, anorexia and weight loss), whilst others presented with haemoptysis, chronic cough, COPD, bronchiectasis, general ill-health, pyrexia of unknown origin or pleural effusion without other systemic symptoms . Fifteen percent of the patients presented with extrapulmonary diagnosis . Ninety percent of the patients had previous medical consultations but 40% had no chest radiograph or sputum examination done . The chest radiographs showed 'typical' changes of tuberculosis in 62% while in the other 38% the radiological features were 'not typical' . Sputum direct smear was positive for acid-fast bacilli in only 22.8% of patients and 11.2% were diagnosed base on positive sputum culture . Sputum may be negative even in patients with typical clinical presentations and chest radiograph changes . Bronchial washing improved the diagnosis rate being positive in 49.1% of cases (24.1% by direct smear and the other 25.0% by culture) . In 16.8% of cases, the diagnosis was based on a good response to empirical anti-tuberculosis therapy in patients with clinical and radiological features characteristic of tuberculosis . In conclusions, the clinical and radiological manifestations of pulmonary tuberculosis may be atypical . Sputum is often negative and bronchoscopy with washings for Mycobacterium culture gives a higher yield for diagnosis . In highly probable cases, empirical therapy with antituberculosis drugs should be considered because it is safe and beneficial.

World J Gastroenterol, 2004 Dec 15, 10(24), 3647 - 9
Diagnosis of abdominal tuberculosis: experience from 11 cases and review of the literature; Uzunkoy A et al.; AIM: To analyze the experience within our hospital and to review the literature so as to establish the best means of diagnosis of abdominal tuberculosis . METHODS: The records of 11 patients (4 males, 7 females, mean age 39 years, range 18-65 years) diagnosed with abdominal tuberculosis in Harran University Hospital between January 1996 and October 2003 were analyzed retrospectively and the literature was reviewed . RESULTS: Ascites was present in all cases . Other common findings were weight loss (81%), weakness (81%), abdominal mass (72%), abdominal pain (72%), abdominal distension (63%), anorexia (45%) and night sweat (36%) . The average hemoglobin was 8.2 g/dL and the average ESR was 50 mm/h (range 30-125) . Elevated levels of cancer antigen CA-125 were determined in four patients . Abdominal ultrasound showed abnormalities in all cases: ascites in all, tuboovarian mass in five, omental thickening in 3, and enlarged lymph nodes (mesenteric, para-aortic) in 2 . CT scans showed ascites in all, pelvic mass in 5, retroperitoneal lymphadenopathy in 4, mesenteric stranding in 4, omental stranding in 3, bowel wall thickening in 2 and mesenteric lymphadenopathy in 2 . Only one patient had a chest radiograph suggestive of a new TB lesion . Two had a positive family history of pulmonary TB . None had acid-fast bacilli (AFB) in the sputum and the tuberculin test was positive in only two . Laparotomy was performed in 6 cases, laparoscopy in 4 and ultrasound-guided fine needle aspiration in 2 . In those patients subjected to operation, the findings were multiple diffuse involvement of the visceral and parietal peritoneum, white 'miliary nodules' or plaques, enlarged lymph nodes, ascites, 'violin string' fibrinous strands, and omental thickening . Biopsy specimens showed granulomas, while ascitic fluid showed numerous lymphocytes . Both were negative for acid-fast bacilli by staining . PCR of ascitic fluid was positive for Mycobacterium tuberculosis (M . tuberculosis) in all cases . CONCLUSION: Abdominal TB should be considered in all cases with ascites . Our experience suggests that PCR of ascitic fluid obtained by ultrasound-guided fine needle aspiration is a reliable method for its diagnosis and should at least be attempted before surgical intervention.

Pneumologie, 2004 Nov, 58(11), 773 - 6
{Tuberculosis induced by Bacillus Calmette-Guerin immuno-prophylaxis -- case study}; Frickmann H et al.; We describe a case of miliary tuberculosis induced by Bacillus Calmette-Guerin (BCG) as a complication of an infection after BCG-instillation therapy into the bladder because of bladder carcinoma . Bacilli surely entered blood circulation via an urethral lesion because of a difficult catheterisation . The 60 year old patient was administered to the hospital with septic temperature 4 four days after BCG instillation . CT showed a miliary patten and the diagnosis was confirmed by bronchoscopy: transbronchial biopsy showed granulomatous infiltration and an acid-fast rod-bacterium was detected in bronchial slime . Symptoms vanished after a consequent antituberculous triple therapy regime and the patient left hospital in a good general state of health.

Am J Respir Crit Care Med . 2004 Nov 5; {Epub ahead of print}
Systemic Inflammatory Response and Progression to Severe Sepsis in Critically Ill Infected Patients; Alberti C et al.; Rationale: The systemic inflammatory response syndrome (SIRS) has low specificity to identify infected patients at risk of worsening to severe sepsis or shock . Objective: To examine the incidence of and risk factors for worsening sepsis in infected patients . Methods: A one-year inception cohort study in 28 intensive care units of patients (n=1,531) having a first episode of infection on admission or during the stay . Measurements and main results: The cumulative incidence of progression to severe sepsis or shock was 20% and 24% at days 10 and 30, respectively . Variables independently associated {hazard ratio, HR} with worsening sepsis included: temperature >38.2 degrees C {1.6}, heart rate >120/min {1.3}, systolic blood pressure <110 mmHg {1.5}, platelets <150.109/L {1.5}, serum sodium >145 mMol/L {1.5}, bilirubin >30 microMol/L {1.3}, mechanical ventilation {1.5}, and 5 variables characterizing infection (pneumonia {HR 1.5}, peritonitis {1.5}, primary bacteremia {1.8}, and infection with gram positive cocci {1.3} or aerobic gram negative bacilli {1.4}) . The 12 weighted variables were included in a score (RISSC, ranging from 0 to 49), summarized in 4 classes of 'low' (score 0 to 8) and 'moderate' (8.5 - 16) risk (9% and 17% probability of worsening, respectively), and of 'high' (16.5 to 24) and 'very high' (score > 24) risk (31% and 55% probability, respectively) . Conclusions: One of four patients presenting with infection/sepsis worsen to severe sepsis or shock . A score estimating this risk, using objectively defined criteria for SIRS, could be used by physicians to stratify patients for clinical management and to test new interventions.

J Clin Microbiol, 2004 Nov, 42(11), 5053 - 7
Mycobacterium africanum genotyping using novel spacer oligonucleotides in the direct repeat locus; Brudey K et al.; This study involves a first evaluation of 25 novel spacer oligonucleotides in addition to the 43 routine spacers for molecular characterization of a panel of 65 isolates of tubercle bacilli from different geographic origins that were initially classified as Mycobacterium africanum based on phenotypic characters . The 68-spacer format defined four additional patterns, and three groups were identified . The relatively homogeneous groups A1 and A2 included strains from West Africa, and A3-1 included strains from East Africa . The presence of deletion region RD9 confirmed the reclassification of the M . africanum subtype II spoligopattern within group A3-1 as Mycobacterium tuberculosis . These isolates may represent a diverging branch of M . tuberculosis in Africa . The use of new spacers also suggested an undergoing evolution of M . africanum subtype I in West Africa . Our results showed that the strain differentiation within the M . tuberculosis complex is improved by using novel spacers, and extensive studies using new-generation spoligotyping may be helpful to better understand the evolution of M . africanum.

Int J Tuberc Lung Dis, 2004 Oct, 8(10), 1234 - 41
Quality assessment of smear microscopy for acid-fast bacilli in the Argentine tuberculosis laboratory network, 1983-2001; Kusznierz GF et al.; SETTING: Tuberculosis Laboratory Network, Argentina . OBJECTIVES: 1) To evaluate the technical quality of smear microscopy for acid-fast bacilli (AFB) supervised in 1983-2001, and 2) to analyse the effect of procedural errors on the results . DESIGN: Registers of technical evaluation results for AFB microscopy were analysed . The quality of specimens, smears, staining and readings were evaluated, as was the relationship between these parameters . RESULTS: The proportion of good quality specimens was considered acceptable . A direct relationship was demonstrated between positivity in results and mucopurulent sputum . The proportion of thin smears was relatively high . Positivity and bacillary count were lower in thin smears . Staining quality was considered good . The average agreement in readings throughout the country was 98% . Nevertheless, the false-positive rate was considered significant, and 46% of false-positive results were associated with defective staining . CONCLUSIONS: The technical quality and agreement in the laboratory network were satisfactory . Nevertheless, improvements need to be made in the following: the quality of the smears, staining and reading, coverage, decentralisation of supervision, the slide selection method and data registration . Operational research on the storage and preservation of slides is also necessary.

Gene Ther . 2004 Nov 04; {Epub ahead of print}
Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice; Silva CL et al.; Tuberculosis (TB) remains a threat for public health, killing around 3 million people a year . Despite the fact that most cases can be cured with antibiotics, the treatment is long and patients relapse if chemotherapy is not continued for at least 6 months . Thus, a better characterization of the working principles of the immune system in TB and identification of new immunotherapeutic products for the development of shorter regimens of treatment are essential to achieve an effective management of this disease . In the present work, we demonstrate that immunotherapy with a plasmid DNA encoding the Mycobacterium leprae 65 kDa heat-shock protein (hsp65) in order to boost the efficiency of the immune system, is a valuable adjunct to antibacterial chemotherapy to shorten the duration of treatment, improve the treatment of latent TB infection and be effective against multidrug-resistant bacilli (MDR-TB) . We also showed that the use of DNA-hsp65 alone or in combination with other drugs influence the pathway of the immune response or other types of inflammatory responses and should augment our ability to alter the course of immune response/inflammation as needed, evidencing an important target for immunization or drug intervention.Gene Therapy advance online publication, 4 November 2004; doi:10.1038/sj.gt.3302418.

Niger J Med, 2004 Oct-Dec, 13(4), 393 - 7
HIV sero-prevalence among newly diagnosed adult pulmonary tuberculosis patients in Sagamu; Daniel OJ et al.; BACKGRBUND: The association between Tuberculosis (TB) and Human immunodeficiency virus (HIV) has been described in several studies . TB was well represented in the first description of AIDS in Africa . In 1999, 25% of TB cases were attributable to the spread of HIV/AIDS . Frequencies of between 54-79% were recorded in medical in-patients in our hospital . The objective of the study is to assess the frequency of HIV in TB outpatients attending the tuberculosis and leprosy control centre in Sagamu . METHODS: A cross-sectional study of adult tuberculosis patients admitted into the DOTS programme of the TB and leprosy control centre, Olabisi Onabanjo University Teaching Hospital, Sagamu between January 2001 and December 2002 was undertaken . Free anti tuberculosis drugs were provided by the German leprosy Relief Association . Data was collected using interviewer-administered questionnaire . HIV screening, packed cell volume and sputum microscopy for acid fast bacilli were carried out on all patients . RESULTS: A total of 269 cases of pulmonary T.B were registered at the clinic of which 40 (14.9%) were HIV sero-positive . The peak age prevalence was in the 3d decade accounting for 42.5% of cases, followed by 32.5% in the 2rd decade . There was a statistically significant difference in the bacillary count and packed cell volume between HIV positive and negative TB patients . The mean weight at presentation, sputum positivity rate and sputum conversion rate at the end of two months of therapy was similar in both HIV positive and negative TB patients . CONCLUSION: This study has demonstrated a frequency of 14.9% of HIV sero-prevalence amongst our TB population . Efforts should be intensified to ensure adherence to INH prophylaxis among HIV infected individuals in TB endemic areas as well as strengthening preventive measures.

Niger J Med, 2004 Oct-Dec, 13(4), 388 - 92
Tuberculosis in Rivers state: autopsy and surgical pathology study in the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt (1990-2002); Seleye-Fubara D et al.; BACKGROUND: A 13 year (1st January 1990 - 31st December 2002) retrospective study of 138 surgical and autopsy specimens diagnosed as Tuberculosis (Tb) was studied in Port Harcourt, based on the age, sex, affected tissue and the immune status of the patients . METHOD: The tissues were initially fixed in 10% formal saline, processed and embedded in paraffin wax . The tissue were sectioned, mounted on glass slide and stained with hematoxylin and eosin (H & E) . In some cases (12.3%) special stains were used to confirm the bacilli and to exclude parasitic or fungal agents . The immune status and the causes of death were extracted from the request forms, case notes and autopsy reports . RESULTS: Of the 138 specimens, 37 (26.8%) and 101(73.2%) were obtained from autopsy and surgery respectively . Male to female ratio was 2:1 . The youngest was a 3 year old male and the eldest was a 83 year old female . Children below 11 years contributed the highest specimens at autopsy while the highest frequency of surgical specimens were removed from 41-50 years age group (23.8%) . The commonest cause of death was pulmonary tuberculosis with respiratory failure . The commonest tissue affected was the lymph node presenting either singly or matted together . Primary tuberculosis accounted for 15.9% (22) of cases while secondary tuberculosis was 116 (84.1%) presenting in different forms . HIV screening was positive in 39 (28.3%) cases . CONCLUSION: Despite the preventive measures and treatment of tuberculosis, the disease is still on the increase in this environment . The upsurge may be associated with HIV infection and immunodeficiency . It is therefore necessary to screen all tuberculosis patients for possible HIV positivity.

Otolaryngol Head Neck Surg, 2004 Nov, 131(5), 762 - 4
Nasopharyngeal tuberculosis: manifestations between 1991 and 2000; Srirompotong S et al.; OBJECTIVES/HYPOTHESIS: To present the clinical manifestation of nasopharyngeal tuberculosis . STUDY DESIGN: Clinical analysis of 23 patients with pathologically confirmed nasopharyngeal tuberculosis was carried out retrospectively . SETTING: Srinagarind Hospital, Khon Kaen University . Thailand . RESULTS: The most common presenting symptom was cervical lymphadenopathy (91.3%) . The common locations of nodes were the superior and middle cervical . The abnormalities of the nasopharynx were found in 16 patients . The pathological findings were caseous granuloma with positive acid-fast bacilli (AFB) in 15 cases, caseous granuloma with negative AFB in 3 cases, and chronic granulomatous inflammation with negative AFB in 5 cases . Pulmonary tuberculosis was found in 8 of 18 patients . Sixteen patients who received complete treatment responded well . CONCLUSION: Nasopharyngeal tuberculosis commonly presents with cervical lymphadenopathy . The differential diagnosis of tuberculosis from nasopharyngeal carcinoma is difficult . In the patients who have cervical lymphadenopathy and no other identified causes, biopsy of nasopharynx would give an additive information for diagnosis.

Indian J Med Res, 2004 Oct, 120(4), 418 - 28
Newer diagnostic techniques for tuberculosis; Katoch VM; Diagnosis of tuberculosis is mainly based on clinical features, histopathology, demonstration of acid fast bacilli (AFB) and isolation of Mycobacterium tuberculosis from the clinical specimens . These techniques have limitations of speed, sensitivity and specificity . During the last two decades several rapid techniques for detection of early growth (5-14 days as compared to 2-8 wk with conventional methods) have been described which can help in obtaining the culture and sensitivity reports relatively early . Prominent among such methods are BACTEC, mycobacterial growth indicator tuber (MGIT), Septi-chek, MB/ BacT systems . This growth can be established by rapid methods based on lipid analysis and specific gene probes, PCR-RFLP methods and ribosomal RNA sequencing . Advances in knowledge about genetic structure of tubercle bacillus helped develop gene probes and gene amplification methods for identification and detection of tubercle bacillus, from culture or directly in clinical specimens and molecular detection of drug resistance . While the gene probes can help in rapid identification of isolates, gene amplification methods (PCR as well as isothermal) developed for diagnosis of tuberculosis are demonstrably highly sensitive specially in culture negative specimens from different paucibacillary forms of disease . With these molecular methods drug resistant mutants for drugs like rifampicin can be detected with reasonable certainty within hours . These gene probes, gene amplification methods and in situ approaches offer unparalleled capability to enhance the diagnosis of tuberculosis in near future.

Indian J Med Res, 2004 Oct, 120(4), 290 - 304
Infections due to non-tuberculous mycobacteria (NTM); Katoch VM; The membership list of genus mycobacterium is ever expanding and it has grown to 95 in year 2003 . While leprosy and tuberculosis are specific diseases caused by mycobacteria, other members are usually saprophytes but can be opportunistic and at times deadly pathogens . These other mycobacteria are referred to as atypical mycobacteria, non-tuberculous mycobacteria (NTM) or mycobacteria other than tubercle bacilli (MOTT) . These organisms can produce localized disease in the lungs, lymph glands, skin, wounds or bone . Occasionally they may produce disseminated disease . Of the more than 90 known species of NTM, about one third have been associated with disease in humans . The species causing human disease are : Mycobacterium avium, M . intracellulare, M . kansasii, M . paratuberculosis, M . scrofulaceum, M . simiae, M . habana, M . interjectum, M . xenopi, M . heckeshornense, M . szulgai, M . fortuitum, M . immunogenum, M . chelonae, M . marinum, M . genavense, M . haemophilum, M . celatum, M . conspicuum, M . malmoense, M . ulcerans, M . smegmatis, M . wolinskyi, M . goodii, M . thermoresistible, M . neoaurum, M . vaccae, M.palustre, M . elephantis, M . bohemicam and M . septicum . Isolation of these mycobacteria from representative specimens and their rapid identification is very important as the treatment strategy for tuberculosis and other mycobacterioses is different . Several biochemical, chemical (lipid) and molecular techniques have been developed for rapid identification of these species . Along with suggestive clinical features, poor response to antitubercular treatment and repeated isolation of the organisms from the clinical specimens these techniques can help in establishing correct diagnosis . Further, many drugs like rifampicin, rifabutin, ethambutol, clofazimine, amikacin, new generation quinolones and macrolides effective against mycobacterial infections are available that can be used in appropriate combinations and dosage to treat these infections.

Indian J Med Res, 2004 Oct, 120(4), 233 - 47
Molecular epidemiology of tuberculosis; Narayanan S; Molecular epidemiology (ME), a blend of molecular biology and epidemiology, is very useful to study the spread of tubercle bacilli in mini epidemics, outbreaks, to analyse the transmission dynamics of tuberculosis (TB) and to determine the risk factors for TB transmission in a community . ME has a great role in distinguishing between exogenous reinfection and endogenous reactivation . In the laboratory, molecular epidemiology can be used to identify cross contamination . Many new DNA typing methods have been introduced after the initial introduction of restriction fragment length polymorphism (RFLP) in 1993 . An internationally accepted, standardized protocol for RFLP typing of the Mycobacterium tuberculosis complex using IS6110 was published in 1993 and is still used today . Most of the newer DNA typing methods are PCR based and microarray based methods are also available . This will enable individual strains of M . tuberculosis or clonal groups to be identified by specific phenotypic traits . ME will continue to be a useful tool in future to measure the impact of any public health intervention strategy for control of tuberculosis in the community.

Indian J Med Res, 2004 Oct, 120(4), 213 - 32
Immunology of tuberculosis; Raja A; Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease . The review attempts to summarize the information available on host immune response to Mycobacterium tuberculosis . Since the main route of entry of the causative agent is the respiratory route, alveolar macrophages are the important cell types, which combat the pathogen . Various aspects of macrophage-mycobacterium interactions and the role of macrophage in host response such as binding of M . tuberculosis to macrophages via surface receptors, phagosome-lysosome fusion, mycobacterial growth inhibition/killing through free radical based mechanisms such as reactive oxygen and nitrogen intermediates; cytokine-mediated mechanisms; recruitment of accessory immune cells for local inflammatory response and presentation of antigens to T cells for development of acquired immunity have been described . The role of macrophage apoptosis in containing the growth of the bacilli is also discussed . The role of other components of innate immune response such as natural resistance associated macrophage protein (Nramp), neutrophils, and natural killer cells has been discussed . The specific acquired immune response through CD4 T cells, mainly responsible for protective Th1 cytokines and through CD8 cells bringing about cytotoxicity, also has been described . The role of CD-1 restricted CD8(+) T cells and non-MHC restricted gamma/deltaT cells has been described although it is incompletely understood at the present time . Humoral immune response is seen though not implicated in protection . The value of cytokine therapy has also been reviewed . Influence of the host human leucocyte antigens (HLA) on the susceptibility to disease is discussed . Mycobacteria are endowed with mechanisms through which they can evade the onslaught of host defense response . These mechanisms are discussed including diminishing the ability of antigen presenting cells to present antigens to CD4(+) T cells; production of suppressive cytokines; escape from fused phagosomes and inducing T cell apoptosis . The review brings out the complexity of the host-pathogen interaction and underlines the importance of identifying the mechanisms involved in protection, in order to design vaccine strategies and find out surrogate markers to be measured as in vitro correlate of protective immunity.

Indian J Med Res, 2004 Oct, 120(4), 207 - 12
Genomics of Mycobacterium tuberculosis: old threats & new trends; Ahmed N et al.; Tuberculosis (TB) has been declared as a global health emergency by the World Health Organization (WHO) . This has been mainly due to the emergence of multiple drug resistant strains and the synergy between tubercle bacilli and the human immunodeficiency virus (HIV) . Genomic analysis of strains for outbreak investigations is in vogue for about a decade now . However, information available from whole genome sequencing efforts and comparative genomics of laboratory and field strains is likely to revolutionize efforts towards understanding molecular pathogenesis and dissemination dynamics of this dreaded disease . Genomic information is also going to fuel discovery projects where new targets will be identified and explored towards a new drug for TB . Besides this, efforts of information technologists, chemists, population biologists, freelance workers, media persons, non-governmental organizations and administrators to needed to handle the problem of tuberculosis to prevent it from becoming a pandemic.

J Small Anim Pract, 2004 Oct, 45(10), 485 - 94
Infections of the subcutis and skin of dogs caused by rapidly growing mycobacteria; Malik R et al.; Nine dogs with panniculitis due to rapidly growing mycobacteria (RGM) were examined over 17 years . Dogs were two to 15 years; five were male, four were female . All were obese or in good condition . Antecedent injury, typically a dog bite or vehicular trauma, could be identified in some patients, while one bitch had hyperadrenocorticism . Infections involved different locations, although the cervicothoracic region, dorsum or flank were most often affected . Patients were systemically well, apart from one dog with pyrexia and two with pain or lameness . Cytology demonstrated pyogranulomatous inflammation, but in only one case was it possible to see acid-fast bacilli (AFB) in smears . Histology demonstrated chronic active pyogranulomatous panniculitis and dermatitis; AFB could be detected in only four specimens . Culture of aspirates or resected tissues demonstrated RGM in all cases, comprising six Mycobacterium smegmatis group and three Mycobacterium fortuitum group isolates . Resection of infected tissues, perioperative injectable antimicrobials and long courses of oral antimicrobials chosen according to susceptibility data generally effected a cure, although some cases recurred.

Rev Inst Med Trop Sao Paulo, 2004 Sep-Oct, 46(5), 291 - 4 Epub 2004 Oct 22.
Orbital tuberculosis diagnosed by immunohistochemistry: case reports; Oliveira BF et al.; PURPOSE: To describe three cases of orbital tuberculosis, with their clinical characteristics and respective diagnostic procedures, showing the importance of histopathology for the correct diagnosis . PATIENTS AND METHODS: Three patients diagnosed and treated for orbital tuberculosis, in the "Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo" during the years of 1999 and 2001 . RESULTS: All of the patients were female and referred a chronic evolution of swelling of one eyelid associated or not with other symptoms . They had not HIV infection . Two of them had positive epidemiology for tuberculosis . However, the search for systemic evidence of the disease and staining for bacilli (Ziehl-Neelsen method) were negative in all three patients . In all the cases, only the biopsy with immunohistochemical analysis could confirm the diagnosis . COMMENTS: Orbital involvement is a rare ocular manifestation of tuberculosis . Even in a tertiary hospital, few cases, if any, are diagnosed per year . However, the global incidence and prevalence of M . tuberculosis infections is not under control yet, and it has been a serious public health problem . Thus, one must be aware of the possibility of tuberculosis among the orbital diseases.

J Clin Pathol, 2004 Nov, 57(11), 1185 - 92
Molecular strain identification of the Mycobacterium tuberculosis complex in archival tissue samples; Zink AR et al.; AIMS: To investigate the use of different molecular analyses that can identify distinct strains of human pathogenic mycobacteria in formalin fixed and paraffin wax embedded archival tissue samples to see whether it is possible to differentiate between the members of the Mycobacterium tuberculosis complex (M tuberculosis, M bovis, M africanum, M microti, or M canettii) and/or substrains in a high number of samples . This would be of interest for identifying individual infection traits and superinfection by different mycobacterial strains . METHODS: Forty nine archival tissue samples with clinically and/or histologically suspected tuberculosis infection were subjected to molecular DNA analysis . RESULTS: The molecular analysis revealed the presence of M tuberculosis complex DNA in 20 samples, whereas acid fast bacilli could be detected by Ziehl-Neelsen staining in only eight samples . All IS6110 positive samples were further characterised by spoligotyping and seven cases provided M tuberculosis specific signatures, whereas M bovis specific signatures were obtained in four cases . The analysis of mtp40, oxyR, and pncA partial gene sequences confirmed the presence of M tuberculosis in six cases and M bovis in one case . The amplification and sequencing of four further genetic regions (katG, gyrA, TbD1, RD9) characterised six "modern" M tuberculosis strains belonging to genetic groups 2 or 3 . CONCLUSION: This study provides clear evidence that archival paraffin wax embedded material can be used for further studies on the strain identification of M tuberculosis complex strains and can therefore unequivocally be used for the study of the epidemiology and evolution of tuberculosis pathogens.

Lepr Rev, 2004 Sep, 75(3), 242 - 53
Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a Brazilian referral centre; Jardim MR et al.; Nineteen patients with pure neural leprosy were analysed with clinical examination, electroneuromyography and histopathology of nerve biopsies . Clinical examination showed sensory loss (78.9%), paresis (78.9%), nerve enlargement (68.4%) and nerve pain (42.1%) . Electroneuromyographic study revealed an axonal pattern in 18 patients (94.7%) and a demyelinating pattern in one (0.5%) . Mononeuropathy multiplex was the most frequent presentation (78.9%), followed by mononeuropathy simplex (10.5%) and polyneuropathy (10.5%) . The histopathological study showed the presence of inflammatory infiltrate composed of epithelioid granuloma (42.1%), mononuclear infiltrate (36.8%) or macrophages positive for bacilli (21%) . Fibrosis was present in 78.9% of the biopsies . Examination of semithin sections revealed, besides inflammatory infiltrate, myelinated fibre loss (94.7%), remyelination (42%), axonal degeneration (10%) as well as regeneration (31.5%) . Based on these results, the pathogenesis of leprosy neuropathy in this group of patients is briefly discussed.

Commun Dis Intell, 2003, 27(4), 459 - 65
Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2002: a report of the Australian Mycobacterium Reference Laboratory Network; Lumb R et al.; The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2002 . A total of 712 cases were identified by bacteriology, representing an annual reporting rate of 3.6 cases of laboratory-confirmed tuberculosis per 100,000 population . The most commonly encountered culture-positive specimens were sputum (n=325), lymph node (n=142) and bronchoscopy (n=100) . Smears containing acid fast bacilli were present in sputum (53.2%), bronchoscopy (37.9%) and lymph node (21.2%) . Eight children (male n=3, female n=5) under 10 years of age had bacteriologically-confirmed tuberculosis . A total of 55 isolates (7.7%) of M . tuberculosis were resistant to at least one of the standard anti-tuberculosis agents . Resistance to at least isoniazid and/or rifampicin was noted for 53 isolates (7.4%), with multidrug-resistance (MDRTB) observed in 12 (1.9%) isolates . Of the 12 MDRTB isolates, eight were from the respiratory tract and five were from smear positive specimens . Of the patients with drug resistant M . tuberculosis isolates, 51/55 (92.7%) were classified as having initial resistance, none had acquired resistance during treatment in Australia . The country of birth was known for 54 of 55 such patients; four were Australian-born, and 50 (90.9%) had migrated from a total of 17 countries . Nucleic acid amplification testing (NAAT) was performed on 139 (19.5%) of the 712 culture-positive specimens . Of smear positive respiratory specimens, 74/80 (92.5%) were NAAT positive . For smear negative respiratory specimens, 12/17 (70.6%) reported a NAAT positive result . Importantly, false-negative NAAT results were obtained from 1/16 and 5/64 of smear positive bronchoscopy and sputum specimens respectively.

Antimicrob Agents Chemother, 2004 Nov, 48(11), 4293 - 300
Rapid direct detection of multiple rifampin and isoniazid resistance mutations in Mycobacterium tuberculosis in respiratory samples by real-time PCR; Marin M et al.; Rapid detection of resistance in Mycobacterium tuberculosis can optimize the efficacy of antituberculous therapy and control the transmission of resistant M . tuberculosis strains . Real-time PCR has minimized the time required to obtain the susceptibility pattern of M . tuberculosis strains, but little effort has been made to adapt this rapid technique to the direct detection of resistance from clinical samples . In this study, we adapted and evaluated a real-time PCR design for direct detection of resistance mutations in clinical respiratory samples . The real-time PCR was evaluated with (i) 11 clinical respiratory samples harboring bacilli resistant to isoniazid (INH) and/or rifampin (RIF), (ii) 10 culture-negative sputa spiked with a set of strains encoding 14 different resistance mutations in 10 independent codons, and (iii) 16 sputa harboring susceptible strains . The results obtained with this real-time PCR design completely agreed with DNA sequencing data . In all sputa harboring resistant M . tuberculosis strains, the mutation encoding resistance was successfully detected . No mutation was detected in any of the susceptible sputa . The test was applied only to smear-positive specimens and succeeded in detecting a bacterial load equivalent to 10(3) CFU/ml in sputum samples (10 acid-fast bacilli/line) . The analytical specificity of this method was proved with a set of 14 different non-M . tuberculosis bacteria . This real-time PCR design is an adequate method for the specific and rapid detection of RIF and INH resistance in smear-positive clinical respiratory samples.

BMC Infect Dis . 2004 Oct 22;4(1):44.
Adjuvant interferon gamma in patients with drug - resistant pulmonary tuberculosis: a pilot study; Suarez-Mendez R et al.; BACKGROUND: Tuberculosis (TB) is increasing in the world and drug-resistant (DR) disease beckons new treatments . METHODS: To evaluate the action of interferon (IFN) gamma as immunoadjuvant to chemotherapy on pulmonary DR-TB patients, a pilot, open label clinical trial was carried out in the Cuban reference ward for the management of this disease . The eight subjects existing in the country at the moment received, as in-patients, 1 x 10(6) IU of recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to the indicated chemotherapy, according to their antibiograms and WHO guidelines . Sputum samples collection for direct smear observation and culture as well as routine clinical and thorax radiography assessments were done monthly . RESULTS: Sputum smears and cultures became negative for acid-fast-bacilli before three months of treatment in all patients . Lesion size was reduced at the end of 6 months treatment; the lesions disappeared in one case . Clinical improvement was also evident; body mass index increased in general . Interferon gamma was well tolerated . Few adverse events were registered, mostly mild; fever and arthralgias prevailed . CONCLUSIONS: These data suggest that IFN gamma is useful and well tolerated as adjunctive therapy in patients with DR-TB . Further controlled clinical trials are encouraged.

Nihon Kokyuki Gakkai Zasshi, 2004 Sep, 42(9), 831 - 6
{A case of pulmonary Mycobacterium intracellulare infectious disease with a solitary pulmonary nodule in the peripheral lung field}; Kobashi Y et al.; A 63-year-old woman was admitted to our hospital because of a solitary nodule (20 x 20 mm) in the right S3 which was first detected during a health examination . Because radiological findings for the nodule, such as pleural indentation and spicula on chest CT led us to suspect a pulmonary adenocarcinoma, we could not completely rule out lung cancer and performed a bronchoscopic examination on the third day after admission . However, no definite diagnosis could be made . Therefore, video-assisted thoracic surgery (VATS) was performed, and a caseating epitheloid granuloma with acid-fast bacilli was found . Initially, we administered antituberculous drugs for pulmonary tuberculoma, but then changed to combined chemotherapy using RFP, EB, CAM and SM after identification of Mycobacterium intracellulare by a culture test of resected tissue . We report a rare case with a solitary nodule caused by pulmonary Mycobacterium intracellulare infectious disease which is indicative of lung cancer.

Intern Med, 2004 Sep, 43(9), 855 - 60
Pulmonary Mycobacterium avium disease with a solitary pulmonary nodule requiring differentiation from recurrence of pulmonary adenocarcinoma; Kobashi Y et al.; A 56-year-old man with a past history of surgical resection of a primary pulmonary adenocarcinoma in the right upper lobe was admitted to our hospital because of a rapidly increasing solitary nodule (50x30 mm) in the right S5 followed on the chest computed tomography (CT) for three months . Although we suspected recurrence of the pulmonary adenocarcinoma and performed a CT-guided lung biopsy, we could not make a definite diagnosis . Therefore, to rule out recurrence of the primary pulmonary adenocarcinoma completely, a partial surgical resection of the right middle lobe was performed and a caseating epitheloid granuloma with acid-fast bacilli was found . As the causative pathogen, Mycobacterium avium complex (MAC) disease should be considered in the differential diagnosis of a rapidly increasing solitary nodule through this peculiar case of pulmonary MAC disease.

J Microbiol Immunol Infect, 2004 Oct, 37(5), 295 - 300
Drug resistance of Mycobacterium tuberculosis complex in central Taiwan; Liu CE et al.; The prevalence of drug resistance to Mycobacterium tuberculosis complex (MTBC) shows marked geographic difference and is the key to determining drugs of choice for the initial treatment of tuberculosis (TB) . This retrospective study investigated the MTBC resistance rate and its contributing factors based on the review of medical records from a hospital in central Taiwan . TB culture and antimicrobial susceptibility test were performed using the BACTEC MGIT 960 System . Isoniazid, rifampin, ethambutol and streptomycin were tested . Molecular detection of MTBC using BDProbeTec ET kits was conducted in positive culture media containing acid-fast bacilli . Between July 2001 and June 2002, 974 (12.4%) strains of MTBC were isolated from 7892 clinical specimens from 513 patients . They included 348 males and 165 females with mean age of 66.1 +/- 15.6 years and 63.4 +/- 19.2 years, respectively . Sixty one percent of patients were older than 64 years of age . The overall resistance rate to 1 or more drugs was 22.4% (n = 115) . The number of strains resistant to individual drugs was 86 (16.8%) to isoniazid, 25 (4.9%) to rifampin, 21 (4.1%) to ethambutol, and 63 (12.3%) to streptomycin . Twenty (3.9%) isolates were resistant to at least isoniazid and rifampin . A history of anti-TB treatment was associated with drug resistance (36.8% vs 20.6%, p=0.0056) . Only 22 (4.3%) patients were tested for HIV antibodies and the results were all negative . The prevalence of resistance to anti-TB drugs remains high in Taiwan and is associated with a previous history of anti-TB treatment . Retreatment may contribute to an increased prevalence of multiple drug resistance.

Biomedica, 2004 Jun, 24(2), 133 - 9
{Relapses after multibacillary leprosy treatment}; Rodriguez G et al.; Leprosy relapses are mainly due to bacillary persistence and diamino-diphenyl-sulphone (DDS) monotherapy . Case histories were examined for 33 patients with lepromatous leprosy (LL), diagnosed 7-48 years before the relapse and treated only with DDS during 4 to 38 years . Twenty-eight patients received irregular non-supervised polychemotherapy (PCT) since 1983 . Five patients received only DDS, and presented relapses 13-20 years after the treatment was stopped . Relapses were diagnosed by clinical methods, including the reappearance of lesions or presence of new anesthetic areas . All cases were confirmed by bacilloscopy, and a subset of 20 cases by skin biopsy . Four patients presented indeterminate leprosy (IL) and one patient borderline tuberculoid leprosy (BT) in the biopsy . The latter 5 demonstrated presence of intraneural bacilli; the remainder were LL . Two patients relapsed even with PCT treatment . The others were cured with supervised PCT . Predisposing factors for relapses were as follows: DDS monotherapy, irregular PCT with inadequate dosage, unsupervised treatment, treatment uncompliance, and inadequate relationship between the patient and the health staff . Inspections for relapse in leprosy is recommended for in all multibacillary patients that were treated with DDS . The clinical appearance of new lesions or new anesthetic zones, the bacilloscopy and skin biopsy, used together, are effective in establishing the presence of relapses.

Biomedica, 2004 Jun, 24 Supp 1, 165 - 87
{Gene inactivation in Mycobacterium tuberculosis and its use in tuberculosis control and prevention}; Chacon O et al.; Availability of the M . tuberculosis genome sequence and the development of sophisticated systems for genetic manipulation of bacilli offer the potential for new and effective tools to prevent and control tuberculosis . Efficient methods to inactivate mycobacterial genes have been developed . These methods have become the cornerstone for the application and development of mycobacterial functional genomics . Specific mutants are generated to establish the role of targetted genes associated with mycobacterial physiology and pathogenesis . Gene inactivation, supported directly or indirectly by the deciphering of the mycobacterial genome, has permitted the generation of large numbers of M . tuberculosis mutants . Analysis of these mutants has (in some cases) established relationships between gene products and their role in mycobacterial physiology and pathogenesis.

Biomedica, 2004 Jun, 24 Supp 1, 73 - 9
{Initial drug resistance as a threat for tuberculosis control: the case of Buenaventura, Colombia}; Moreira CA et al.; In 2001, Buenaventura, Colombia, the rate of smear-positive pulmonary tuberculosis was of 66 per 100,000 inhabitants . The poor control of the tuberculosis in this city during the last 10 years and the inadequate use of first-line anti-tuberculosis drugs was an opportune situation for the development of high resistance to these drugs . Two surveys of initial resistance to first-line antituberculosis drugs were conducted in new cases of pulmonary TB, in the city of Buenaventura--the first from August 1, of 1997 to January 31 of 1998 and the second from November 15, of 2000 to November 15, 2001 . The method of multiple proportions was used to determine drug susceptibility . Mycobacterium tuberculosis was isolated in 93% and 55% of the new cases of lung TB during each respective period . The initial resistance to at least one drug was 25% (9/36) and 32% (23/72), respectively . The initial multi-drug resistance (defined as resistance to at least isoniazid and rifampicin) was 6% for both surveys . This demonstrates the dissemination of multidrug-resistant bacilli and shows the need for surveillance of resistance to antituberculosis drugs in control of the disease, particularly in those areas where the TB control program has been erratically applied . In areas where multi-drug resistant TB occurs, the control strategy should be enhanced with the careful introduction of second-line drugs.

Mikrobiyol Bul, 2004 Jul, 38(3), 193 - 201
{Comparison of Cobas Amplicor system and microscopic examination with bactec radiometric method for the detection of Mycobacterium tuberculosis in clinical samples}; Alp A et al.; Tuberculosis is still a major health problem all around the world . Since the patients with tuberculosis spread the infection by means of aerosols containing tuberculosis bacilli, it is critically important to detect these patients and start the treatment as soon as possible . Therefore there is a need for highly sensitive and specific reliable diagnostic methods . In this study, Ehrlich-Ziehl-Neelsen (EZN) staining method and Cobas Amplicor system were evaluated for the diagnosis of tuberculosis in comparison with the standard reference Bactec radiometric method . A total of 2098 clinical samples collected between July 2002 and February 2004 in Clinical Microbiology Laboratory of Hacettepe University Adult Hospital, were studied by Bactec radiometric system for diagnosis of tuberculosis and M . tuberculosis was detected in 107 (5.1%) samples . The specificity, sensitivity, positive and negative predictive values of EZN staining method were found to be 98.5%, 42.9%, 62.1% and 96.9%, respectively . The specificity, sensitivity, positive and negative predictive values of Cobas Amplicor system were detected as 99.3%, 67.3%, 83.5% and 98.4%, respectively . These results were in concordance with the results of previous studies . In conclusion, microscopic examination and nucleic acid amplification methods should always be used together with culture methods for the laboratory diagnosis of tuberculosis.

Am J Ophthalmol, 2004 Oct, 138(4), 663 - 4
Microbiologic spectrum and susceptibility of isolates in scleral buckle infection in India; Pathengay A et al.; PURPOSE: To present the microbial spectrum and susceptibility of isolates in scleral buckle infections in India . DESIGN: Retrospective case series . METHOD: Seventy-three isolates from 55 eyes with scleral buckle infection were studied . RESULTS: The isolates included 30 gram-positive cocci (41.1%), 15 acid-fast bacilli (20.5%), 11 fungi (15.1%), 10 gram-positive bacilli (13.7%), and 7 gram-negative bacilli (9.6%) . Eighteen eyes (32.7%) had polymicrobial infections . Gram-positive, gram-negative, and acid-fast isolates were most commonly susceptible to vancomycin (93%), ciprofloxacin (86%), and amikacin (80%), respectively . CONCLUSION: This large single-center study indicates the high prevalence of fungal, acid-fast organisms and polymicrobial organisms in buckle infections.

Int J Lepr Other Mycobact Dis, 2004 Sep, 72(3), 296 - 305
In situ hybridization in the histological diagnosis of early and clinically suspect leprosy; Natrajan M et al.; The present study tests the utility of the in situ hybridization procedure for M . leprae rRNA in the histological diagnosis of early leprosy and clinically suspect leprosy, both diagnostically demanding situations . The histological confirmation obtained with routine histopathology (Haematoxylin-Eosin staining for studying morphologic alterations and Fite-Faraco staining for demonstration of acid-fast bacilli) were 32% for early leprosy and 25% for clinically suspect leprosy . With performance of the in situ hybridization on the histologically unconfirmed cases, the positivity rates obtained were 58.8% and 55%, respectively . The results of the study confirm the utility of the procedure in the diagnostically difficult situations of early and suspect leprosy, and it is proposed that the procedure be employed in situations of clinical doubt.

Enferm Infecc Microbiol Clin, 2004 Oct, 22(8), 462 - 6
{Clinical and microbiological characteristics of neutropenic enterocolitis in adults with blood cancer in the National Cancer Institute of Bogota D.C . (Colombia)}; Cardona AF et al.; OBJECTIVES: This study describes the clinical, epidemiological and microbiological characteristics of adult patients with blood cancer and neutropenic enterocolitis treated in the Instituto Nacional de Cancerologia (National Cancer Institute) in Bogota, Colombia . METHODS: The clinical histories of 692 adult patients hospitalized in the Instituto Nacional de Cancerologia between 1997 and 2001 with a diagnosis of leukemia or lymphoma were reviewed . Thirty-five of these cases met the criteria for probable or confirmed neutropenic enterocolitis . RESULTS: Twenty-two cases were confirmed and the remaining 13 were probable neutropenic enterocolitis . All patients were undergoing chemotherapy and all presented watery diarrhea and abdominal pain . In addition, 17% had melena and 25% severe vomiting . Eight of 26 stool cultures (30%) and 17 of 32 (58%) blood cultures were positive for potentially pathogenic microorganisms, particularly gram-negative bacilli . Three patients with probable neutropenic enterocolitis and ten confirmed cases died (37%); mortality was higher among patients who were managed surgically . CONCLUSION: Neutropenic colitis presents as a multifactorial syndrome in patients with blood cancer undergoing cytotoxic therapy with agents such as cytosine arabinoside, etoposide, vincristine, cyclophosphamide and corticoids . This highly lethal complication is partly due to infections caused by gram-negative bacilli.

J Gastroenterol Hepatol, 2004 Nov, 19(11), 1240 - 6
Gastrointestinal luminal tuberculosis: establishing the diagnosis; Patel N et al.; BACKGROUND AND AIM: To study the profile of gastrointestinal luminal tuberculosis (GITB) patients who have been treated on a confirmed and a presumptive diagnosis . METHODS: A total of 260 patients who had an initial diagnosis of GITB were included in this retrospective analysis . Clinical, radiologic, endoscopic, histopathologic and microbiologic features of these patients were studied in detail . RESULTS: GITB was confirmed in 66.5% patients (cGITB), while 29.5% had presumed GITB (pGITB) . In 3.9% patients, Crohn's disease (CD) was misdiagnosed initially as GITB . There was no significant difference in the clinical and radiologic features except a higher incidence of a radiologically abnormal ileocecal region in cGITB patients . Endoscopic biopsies from ulcerated masses and ulcers had the highest yield of confirmation (100% and 68%, respectively) when subjected to histopathology, acid-fast bacilli smear and culture studies . Confirmed diagnosis was obtained in 100% of cases occurring in the upper gastrointestinal tract, 66% of cases in the ileocecal region/colon and 40% of cases that had small bowel involvement . In 21% of cases, extraluminal sites helped to confirm the diagnosis . As the presence of diarrhea, bleeding, fistulae, perianal disease and extraintestinal manifestations favored a diagnosis of CD, the presence of these features initially or on subsequent follow up helped to minimize the misdiagnosis of GITB . CONCLUSIONS: As a differential diagnosis, CD must be ruled out before starting treatment for GITB . In our study, an intense search for histologic and microbiologic proof of the presence of TB from luminal and extraluminal sites established the diagnosis in 66.5% of cases . Surgery for establishing the diagnosis should be reserved for complicated cases.

Pediatr Allergy Immunol, 2004 Oct, 15(5), 415 - 20
Effect of BCG vaccination in asthmatic schoolchildren; Vargas MH et al.; Recent studies have explored the effect of Bacilli Calmette-Guerin (BCG) or Mycobacterium vaccae vaccination in asthmatic patients, yielding conflicting results . We investigated the effect of BCG vaccination in asthmatic schoolchildren, especially focusing on the cytokine pattern released by mononuclear cells . After a 1-yr run-in period, 67 asthmatic schoolchildren received intradermal immunization with BCG (33 patients) or placebo (34 patients) . Both groups were followed during 1 yr . Serum immunoglobulin E (IgE) levels did not change after BCG (407.1 +/- 86.6 vs . 415.1 +/- 86.7 IU/ml, mean +/- s.e.m.), but increased after placebo (406.7 +/- 67.0 vs . 619.7 +/- 90.7 IU/ml, p = 0.001) administration . Interleukin (IL)-4 and interferon (IFN)-gamma measured in the supernatant of stimulated cultured blood mononuclear cells did not change in the BCG group (10.8 +/- 2.3 vs . 17.9 +/- 5.7 pg/ml, and 348.6 +/- 118.0 vs . 354.8 +/- 139.0 pg/ml, respectively), while in the control group IL-4 increased (from 6.7 +/- 1.3 to 16.1 +/- 6.0 pg/ml, p < 0.05), and IFN-gamma decreased (from 279.9 +/- 82.1 to 232.1 +/- 109.6 pg/ml, p = 0.01) . In comparison with their initial status, most patients maintained the same asthma severity and the same proportion of emergency room visits at the end of the study . The proportion of those in whom asthma improved or worsened was the same in both groups . We concluded that, contrary to the common hypothesis, BCG vaccination in asthmatic children was unable to cause a long-term reinforcement of Th(1) response, although it could avoid the increased Th(2) response observed in control patients.

Expert Rev Anti Infect Ther, 2004 Apr, 2(2), 245 - 51
Endobronchial tuberculosis; Rikimaru T; Endobronchial tuberculosis is defined as tuberculous infection of the tracheobronchial tree . Although clinical features differ between various types and stages of endobronchial tuberculosis, common symptoms are cough, hemoptysis, sputum production, wheezing, chest pain, fever and dyspnea . Endobronchial tuberculosis is difficult to diagnose, because the lesion is not evident in the chest radiograph . Computerized tomography is very useful in evaluating bronchial lesions such as stenosis or obstruction . The most important goal of treatment in active endobronchial tuberculosis is the eradication of tubercle bacilli . The second most important goal is prevention of bronchial stenosis . Corticosteroid therapy for prevention of bronchial stenosis in endobronchial tuberculosis remains controversial, but the best results are associated with minimal delay in the initiation of steroid treatment . In inactive disease, treatment to restore full patency is appropriate . As steroids or other medication are unable to reverse stenosis from fibrous disease, airway patency must be restored mechanically by surgery or endobronchial intervention . Aerosol therapy with streptomycin and corticosteroids is useful in treatment against active endobronchial tuberculosis . Time to healing of ulcerous lesions is shorter, and bronchial stenosis is less severe in patients on aerosol therapy . Progression to bronchial stenosis may be prevented if the therapy is initiated as soon as possible.

Acta Orthop Belg, 2004 Aug, 70(4), 386 - 8
Nocardia farcinica arthritis of the knee . A case report; Audenaert E et al.; Nocardia is a gram positive, aerobic branched actinomycete; it is an ubiquitous soil saprophyte . As an infecting agent it has been increasingly identified in humans, especially in immuno-suppressed hosts . Nocardia as a cause of septic arthritis is very unusual . The described genus was Nocardia asteroides in nearly all previously reported cases . We report an unusual case of spontaneous Nocardia farcinica septic arthritis of the left knee in a 68-year-old man, who was under systemic corticosteroids for chronic obstructive pulmonary disease . The diagnosis was rapidly made by Gram and acid-fast stains and later confirmed by culture . PCR was used to identify the subtype . The patient was treated successfully with sulphametaxazole-trimethoprim for six months . Our case re-emphasises, especially in the immuno-compromised patient, the importance of performing fungal and acid-fast bacilli cultures, besides the most common bacterial cultures for aerobic and anaerobic organisms, in order to identify less common organisms and to initiate early and adequate treatment.

Int J Urol, 2004 Oct, 11(10), 931 - 3
Tuberculid of the penis with a scab on the nodule; Yonemura S et al.; Tuberculids of the penis are extremely rare . The clinical features of tuberculids of the penis have been reported as ulceration or scars . We have experienced a case of tuberculid of the penis that appeared as a scab on nodule . A 56-year-old man presented with a 4-month history of a painless subcutaneous nodule at the glans penis . Pathological findings of the nodule showed granulomatous inflammation . Tuberculin tests were strongly positive, but tubercle bacilli could not be detected . The diagnosis was tuberculid of the penis and the patient received antituberculosis chemotherapy . The present paper reports an interesting and rare case of tuberculid of the penis with a scab on nodule.

BMC Public Health . 2004 Oct 11;4(1):45.
Surveillance of antimicrobial resistance at a tertiary hospital in Tanzania; Blomberg B et al.; BACKGROUND: Antimicrobial resistance is particularly harmful to infectious disease management in low-income countries since expensive second-line drugs are not readily available . The objective of this study was to implement and evaluate a computerized system for surveillance of antimicrobial resistance at a tertiary hospital in Tanzania . METHODS: A computerized surveillance system for antimicrobial susceptibility (WHONET) was implemented at the national referral hospital in Tanzania in 1998 . The antimicrobial susceptibilities of all clinical bacterial isolates received during an 18 months' period were recorded and analyzed . RESULTS: The surveillance system was successfully implemented at the hospital . This activity increased the focus on antimicrobial resistance issues and on laboratory quality assurance issues . The study identified specific nosocomial problems in the hospital and led to the initiation of other prospective studies on prevalence and antimicrobial susceptibility of bacterial infections . Furthermore, the study provided useful data on antimicrobial patterns in bacterial isolates from the hospital . Gram-negative bacteria displayed high rates of resistance to common inexpensive antibiotics such as ampicillin, tetracycline and trimethoprim-sulfamethoxazole, leaving fluoroquinolones as the only reliable oral drugs against common Gram-negative bacilli . Gentamicin and third generation cephalosporins remain useful for parenteral therapy . CONCLUSION: The surveillance system is a low-cost tool to generate valuable information on antimicrobial resistance, which can be used to prepare locally applicable recommendations on antimicrobial use . The system pinpoints relevant nosocomial problems and can be used to efficiently plan further research . The surveillance system also functions as a quality assurance tool, bringing attention to methodological issues in identification and susceptibility testing.

Annu Rev Pharmacol Toxicol . 2004 Oct 07; {Epub ahead of print}
The Magic Bullets and Tuberculosis Drug Targets; Zhang Y; Modern chemotherapy has played a major role in our control of tuberculosis . Yet tuberculosis still remains a leading infectious disease worldwide, largely owing to persistence of tubercle bacillus and inadequacy of the current chemotherapy . The increasing emergence of drug-resistant tuberculosis along with the HIV pandemic threatens disease control and highlights both the need to understand how our current drugs work and the need to develop new and more effective drugs . This review provides a brief historical account of tuberculosis drugs, examines the problem of current chemotherapy, discusses the targets of current tuberculosis drugs, focuses on some promising new drug candidates, and proposes a range of novel drug targets for intervention . Finally, this review addresses the problem of conventional drug screens based on inhibition of replicating bacilli and the challenge to develop drugs that target nonreplicating persistent bacilli . A new generation of drugs that target persistent bacilli is needed for more effective treatment of tuberculosis . Expected online publication date for the Annual Review of Pharmacology and Toxicology Volume 45 is January 6, 2005 . Please see for revised estimates.

J Med Assoc Thai, 2004 Aug, 87(8), 988 - 91
Mucoepidermoid carcinoma of the lung presenting as a cavitary lesion; Tanvetyanon T et al.; The authors describe a 62-year-old female patient who presented with a progressively enlarging cavitary lesion in the right upper lobe of the lung . Acid-fast bacilli were recovered from a bronchial washing fluid and identified as Mycobacterium tuberculosis . She received antituberculous therapy for 5 months without improvement in her clinical symptoms and chest radiograph . A lobectomy was performed and pathological review demonstrated a high-grade mucoepidermoid lung carcinoma with extensive central necrosis . Staging revealed metastases in her left adrenal gland, kidney and spine . High-grade mucoepidermoid carcinoma of the lung may present as a cavitary lesion . The presence of M . tuberculosis should not preclude clinicians from pursuing adequate diagnostic procedures for a possible malignant lesion.

Rev Argent Microbiol, 2004 Apr-Jun, 36(2), 75 - 7
{Necrotizing lymphadenitis caused by Nocardia asteroides in a healthy girl}; Baroni MR et al.; A case of a healthy girl with a trauma in her right leg is described . Twelve hours later she developed fever and pain in the inguinal region . Two days later, she was admitted to the Hospital, and there, an aspiration of pus from the lymph node was performed, and this sample was sent for culture . The Gram smear showed gram-positive filamentous bacilli and when Kinyoun was used they were observed as weakly acid fast rods . After four days of incubation under aerobic conditions, white and hemolitic colonies were seen on human blood agar plates . Biochemical tests as urea hydrolysis and gelatin liquefaction were performed . To complete the identification it was sent to a reference laboratory, INEI-ANLIS Dr . Carlos G . Malbran, where the isolate was confirmed as Nocardia asteroides sensu stricto . The patient was treated with intravenous cephalotin with good evolution . Therapy was followed with oral trimethoprim-sulfamethoxazole . This case is the first report of a Nocardia infection in the Hospital de Ninos de Santa Fe . The fact that N . asteroides was isolated from an immunologically competent girl should be highlighted . This species is uncommon in children and it is rare in our region . In addition, N . asteroides infections are usually seen in pulmonary disease and rarely producing cutaneous infections.

Rev Esp Quimioter, 2004 Jun, 17(2), 189 - 92
{A study of clinical response to antibiotic treatment in subjects with chronic bacterial prostatitis}; Gutierrez J et al.; A study was carried out on the clinical response to antibiotics in 105 patients with chronic bacterial prostatitis . Two groups of patients were compared in a retrospective study . The results of rectal examination, ultrasound scan, microbiological analysis, and response to different antibiotic therapy regimens were compared . There was a high incidence of perineal-testicular pain and sexual potency reduction; prostate congestion and pain on rectal examination were frequently reported . All the patients had positive microbial cultures, with Gram-negative microorganisms being predominantly isolated . Following the administration of different antibiotic therapy regimens, symptoms either disappeared or diminished, irrespective of whether positive cultures remained . A poorer clinical response was observed in patients with positive prostate ultrasound and rectal examination, and with isolated Gram-negative bacilli . No differences were observed between either group in clinical response to different antimicrobial regimens.

Phytochemistry, 2004 Oct, 65(19), 2661 - 5
Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between the microorganisms and plants; Shibano M et al.; 1-Deoxynojirimycin is a glycosidase-inhibitory alkaloid obtained from several plants and microorganisms . Administration experiments using {1-(13C)} glucose in the higher plant Commelina communis and 13C NMR spectroscopic analyses of products suggested that 1-deoxynojirimycin was biosynthesized through a different route compared with that in Streptomyces and Bacilli microorganisms.

Crit Rev Food Sci Nutr, 2004, 44(4), 205 - 21
The microbiology of cocoa fermentation and its role in chocolate quality; Schwan RF et al.; The first stage of chocolate production consists of a natural, seven-day microbial fermentation of the pectinaceous pulp surrounding beans of the tree Theobroma cacao . There is a microbial succession of a wide range of yeasts, lactic-acid, and acetic-acid bacteria during which high temperatures of up to 50 degrees C and microbial products, such as ethanol, lactic acid, and acetic acid, kill the beans and cause production of flavor precursors . Over-fermentation leads to a rise in bacilli and filamentous fungi that can cause off-flavors . The physiological roles of the predominant micro-organisms are now reasonably well understood and the crucial importance of a well-ordered microbial succession in cocoa aroma has been established . It has been possible to use a synthetic microbial cocktail inoculum of just 5 species, including members of the 3 principal groups, to mimic the natural fermentation process and yield good quality chocolate . Reduction of the amount of pectin by physical or mechanical means can also lead to an improved fermentation in reduced time and the juice can be used as a high-value byproduct . To improve the quality of the processed beans, more research is needed on pectinase production by yeasts, better depulping, fermenter design, and the use of starter cultures.

J Pak Med Assoc, 2004 Aug, 54(8), 413 - 5
Prevalence of pulmonary tuberculosis in Karachi central prison; Rao NA; OBJECTIVE: To determine the extent of pulmonary tuberculosis among prisoners in Karachi central jail, so that strategy for targeted intervention can be planned . METHOD: This prospective observational study was done at Karachi central prison from 7-2-2002 to 14-2-2002 . A team of doctors, laboratory and x-ray technicians visited the central prison . Patients who had symptoms suggestive of pulmonary tuberculosis were included in the study . Their chest x-ray was taken in the jail and three "spot specimens" of sputum were collected for three consecutive days . The sputum specimens were processed at the laboratory of Ojha Institute of Chest Diseases, Karachi . RESULTS: Out of 4870 prisoners, 79 (1.62%) were pulmonary tuberculosis suspects . All were male and their mean age was 32 (22-75) years . Sixteen suspects already diagnosed were on anti-tuberculosis treatment (ATT) while 11 suspects gave history of ATT in the past for incomplete duration varying from 3-4 weeks to 3 months either regularly or irregularly . Twenty-two (28%) suspects were not expectorating while fifty-seven (72%) submitted the sputum for AFB (Acid Fast Bacilli), of which only one was smear positive . Radiologically, 39 (49%) chest x-rays including those of 22 who were not expectorating were normal . Eight (10%) showed healed lesion . Thirty-two (40.5%) chest x-rays were suggestive of active pulmonary tuberculosis, so clinically and radiologically 32 prisoners were suffering from active pulmonary tuberculosis . The prevalence of active pulmonary tuberculosis in jail population determined by using the formula, number of persons with active TB in jail divided by the total number of persons booked into jail was 657 per 100,000, which is 3.75 times higher than general population . CONCLUSION: Pulmonary tuberculosis is 3.75 times more common than general population in Karachi central prison and concrete efforts are needed to eradicate tuberculosis from this segment of population . The integration of provincial TB control program with that of jail health services is urgently required.

J Vet Diagn Invest, 2004 Sep, 16(5), 448 - 53
Use of conventional and real-time polymerase chain reaction for confirmation of Mycobacterium avium subsp . paratuberculosis in a broth-based culture system ESP II; Kim SG et al.; The ESP II Culture System (ESP II), a broth-based culture system, has been modified and optimized for culturing Mycobacterium avium subsp . paratuberculosis (M . paratuberculosis) in animal feces since 2000 . Conventional and real-time polymerase chain reaction (PCR) assays based on the IS900 sequence were performed as confirmatory tests for M . paratuberculosis in ESP II liquid culture medium . There were no differences between test results of conventional and real-time PCR assays . During the 5-week incubation period, if acid-fast bacilli (AFB) were detected in ESP culture-positive samples, IS900 PCR assays were performed to confirm whether those AFB were M . paratuberculosis . At the end of the 5-week incubation, AF staining was performed on all ESP II-negative cultures to screen any false-negative cultures; IS900 PCR assays were performed on AFB-positive cultures . During a period of 1 year, of a total of 18,499 ESP II cultures, 2,814 (15.2%) PCR confirmation assays were performed . Of those, 2,259 (80%) were both ESP and PCR positive; 104 (4%) were ESP positive and PCR negative; 423 (15%) were ESP negative and PCR positive; 28 (1%) were both ESP and PCR negative . The AF-staining step after the 5-week incubation produced 423 (15%) more PCR-positive cultures . Of a total of 2,814 AFB-positive cultures, 132 (5%) were not confirmed as M . paratuberculosis . Further studies are needed for speciation of non-M . paratuberculosis isolates.

Nihon Kokyuki Gakkai Zasshi, 2004 Aug, 42(8), 755 - 9
{Case of multi-drug resistant tuberculosis complicated with bronchoesophageal fistula}; Hatakeyama N et al.; A 71-year-old man visited the surgical department of our hospital due to back pain in November, 1999 . Esophagogram showed bronchoesophageal fistula and a plain chest radiograph showed a nodular shadow in the left upper area with left pleural effusion . As the symptom disappeared on treatment with an antimicrobial agent, he was followed up as an outpatient . In August, 2001, he presented to the Respiratory Department of our hospital with low-grade fever and productive cough . Since tubercle bacilli were detected in a sputum culture, combined treatment with antituberculous chemotherapy was started . But, none of the symptoms were improved . These bacilli were identified as being multi-drug-resistant . After the chemotherapy regimen was changed, the symptoms disappeared and the esophagorespiratory fistula was closed . We report a rare case of esophagorespiratory fistula with multi-drug resistant tuberculosis, which was improved by chemotherapy.

J Ayub Med Coll Abbottabad, 2004 Apr-Jun, 16(2), 73 - 4
A young man with hoarseness of voice; Qidwai W et al.; A 45 year-old driver presented with a two months history of hoarseness, fever, productive cough, anorexia and weight loss . He chewed tobacco . He was previously seen and treated without benefit by a family Physician and two ear, nose and throat consultants . Crackles were heard in the left scapular region . An X-Ray of the chest showed a right apical cavity, perihilar infiltrates and blunting of left costophrenic angle . His sputum smear showed acid fast bacilli . A high index of suspicion for tuberculosis is recommended while dealing with such cases . Complete recovery of patient's voice with anti-tubercular therapy confirmed it was a case of laryngeal tuberculosis.

Int J Tuberc Lung Dis, 2004 Sep, 8(9), 1142 - 6
Identification of a familial cluster of pulmonary Mycobacterium bovis disease; LoBue PA et al.; SETTING: Local public health department . DESIGN: Retrospective review of a cluster of three pulmonary Mycobacterium bovis cases occurring in a family, with genotyping of M . bovis strains isolated from the family members . RESULTS: The genotypes of the M . bovis isolates were identical, as determined by three different methods: IS6110 restriction fragment length polymorphism, spoligoytping and mycobacterial interspersed repetitive units-variable number tandem repeat analyses . CONCLUSION: The identification of three acid-fast bacilli (AFB) smear-positive pulmonary M . bovis cases, presenting in a single family and caused by an identical strain, suggests that person-to-person transmission of this organism may have occurred, although infection of one or more family members through ingestion of a contaminated dairy product could not be excluded.

Diagn Cytopathol, 2004 Oct, 31(4), 204 - 6
Fine-needle aspiration cytology in tuberculous lymphadenitis of patients with and without HIV infection; Nayak S et al.; A study of the cytologic features and role of fine-needle aspiration cytology (FNAC) in tuberculous lymphadenitis (TBL) of 21 patients with HIV (group 1) and 21 patients without HIV (group 2) infection was undertaken . Four cytologic patterns were observed, of which necrotizing lymphadenitis (42.9%) and necrotizing suppurative lymphadenitis (28.6%) were predominant in group 1 while necrotizing granulomatous lymphadenitis (47.7%) and granulomatous lymphadenitis (23.8%) were more common in group 2 . No pattern was found specific for either group . Zeihl-Neelsen-stained cytology smears of group 1 showed a much higher percentage of positively (61.9%) and a higher density of acid-fast bacilli than group 2 . Definitive diagnoses of TBL on FNAC could be provided in 61.9% of group 1 as against 9.5% of group 2 . The need for culture or biopsy for definitive diagnosis was higher in group 2 . In suspected TBL, diagnostic efficacy can be improved and the need for surgical biopsy reduced if material collected on FNA is also used for culture . 2004 Wiley-Liss, Inc.

J Ultrasound Med, 2004 Oct, 23(10), 1275 - 81
Tuberculosis of the parotid gland: sonographic manifestations and sonographically guided aspiration; Chou YH et al.; OBJECTIVE: Involvement of the parotid gland by tuberculosis (TB) is rare . If treated properly, the prognosis of TB of the parotid gland is good . In this retrospective study, we report our experience with sonography and sonographically guided aspiration in the diagnosis of parotid TB . METHODS: Over 12 years, 9 adults (mean age, 48 years) with parotid gland TB had been examined with high-resolution sonography and color Doppler sonography for their clinical problems of swelling on the mandibular angle . Sonographically guided fine-needle aspiration was done for cytologic study, stains for acid-fast bacilli, and cultures for mycobacterium . RESULTS: The sonographic patterns were classified as chiefly the parenchymal type (4 patients) and chiefly the periparotid type (5 patients) . The parenchymal type appeared as a diffusely enlarged, comparatively hypoechoic gland (compared with the contralateral asymptomatic gland), with or without focal intraparotid nearly anechoic zones, which might have a cavity or cavities within it . The periparotid type appeared as hypoechoic nodules located in the peripheral zone of the hyperechoic parotid gland, consistent with enlarged periglandular lymph nodes . The diagnosis of parotid TB was made in 8 of 9 patients on the basis of sonographically guided aspiration for acid-fast bacilli stains, cytologic study, and cultures for mycobacterium . CONCLUSIONS: Sonographic examination contributes substantially in the diagnosis of parotid TB infection . In the presence of diffuse parotid echo pattern changes with periparotid lymphadenopathy, and with or without focal hypoechoic zones, TB infection should be differentiated . Sonographically guided fine-needle aspiration may provide further diagnostic information by means of stains, cultures, and cytologic study.

Korean J Gastroenterol, 2004 Sep, 44(3), 153 - 9
{The usefulness of colonoscopic biopsy in the diagnosis of intestinal tuberculosis and pattern of concomitant extra-intestinal tuberculosis}; Lee YJ et al.; BACKGROUND/AIMS: Intestinal tuberculosis can be difficult to diagnose because it may mimic many other intestinal diseases . The aim of this study was to evaluate the diagnostic yield of colonoscopic biopsy and frequency of concomittent extra-intestinal tuberculosis in intestinal tuberculosis . METHODS: The medical records of 225 consecutive patients with intestinal tuberculosis (81 men, 144 women; mean age 40.6 yrs) were analyzed retrospectively . RESULTS: Histological examination of colonoscopic biopsy specimens revealed granulomas in 163 (72.4%) of the 225 patients . However, caseous necrosis was found in only 25 (11.1%) patients, and acid-fast bacilli (AFB) were noted in 39 (17.3%) of the 225 patients . Mycobacterium tuberculosis was isolated from the culture of biopsy specimens in 52 (29.3%) of 177 patients . Eighty-four patients (37.3%) had concomitant extra-intestinal tuberculosis and 67 (29.8%) showed active pulmonary tuberculosis . Histological examination of the biopsy specimens enabled the diagnosis of intestinal tuberculosis by the presence of either caseating granulomas or AFB in 52 (23.1%) patients . Combination of histological examination and Mycobacterium culture established the diagnosis in 87 (38.7%) patients . Before getting the result of Mycobacterium culture, the diagnosis could be made, by either histological examination or the presence of extra-intestinal tuberculosis in 107 (47.6%) patients . Combination of caseating granulomas, AFB staining, Mycobacterium culture, and the presence of extra-intestinal tuberculosis resulted in the diagnosis in 126 (56.0%) patients . CONCLUSIONS: To increase the diagnostic yield, AFB staining and Mycobacterium culture should be routinely performed on biopsy specimens in addition to routine histological examination for caseating granulomas.

Infect Immun, 2004 Oct, 72(10), 5712 - 21
The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli; Rivera-Marrero CA et al.; Cathepsin G (CatG) is a serine protease found in the azurophilic granules of monocytes that is known to have antimicrobial properties, but its role in Mycobacterium tuberculosis infection is unknown . We found that M . tuberculosis infection of human THP-1 monocytic cells induced the down-regulation of CatG mRNA expression, as demonstrated by gene array analysis and reverse transcription-PCR . This was associated with a concomitant decrease in CatG protein and enzymatic activity . In contrast, the expression of lysosomal cathepsins B and D was up-regulated in infected cells . This effect was also observed when THP-1 cells were induced to differentiate into adherent macrophages by exposure to bacterial lipopolysaccharide (LPS) . In agreement with this, CatG expression was null in adherent macrophages isolated from bronchoalveolar lavages and normal blood . We wanted to determine if the down-regulation of CatG would be relevant to M . tuberculosis infection . First, we found that addition of CatG to THP-1 cells prior to infection resulted in decreased bacillary viability, presumably due to extracellular killing of bacilli . However, pretreatment of cells with LPS, which decreases intracellular CatG expression, resulted in increased bacillary viability . Second, we found that CatG cationic peptides killed M . tuberculosis bacilli and were five- to sevenfold more bactericidal than full-length CatG . These observations suggest that M . tuberculosis infection of human monocytic cells results in a "cathepsin switch" with down-regulation of CatG rendering M . tuberculosis bacilli more viable . Therefore, the down-regulation of CatG in macrophages is advantageous to M . tuberculosis bacilli and possibly is an important mechanism by which M . tuberculosis is able to evade the host immune defenses.

Tohoku J Exp Med, 2004 Oct, 204(2), 135 - 45
Pulmonary tuberculosis in spontaneously diabetic goto kakizaki rats; Sugawara I et al.; As a clinical association is thought to exist between diabetes and tuberculosis, this study was set up to examine whether GK/Jcl diabetic rats are more susceptible to Mycobacterium tuberculosis infection than non-diabetic rats . GK/Jcl diabetic rats were infected aerially with M . tuberculosis and their capacity to control mycobacterial growth, granuloma formation, cytokine secretion by alveolar macrophages and nitric oxide (NO) production was examined . The rats developed large granulomas but not necrotic lesions in their lungs, liver or spleen . This is consistent with a significant increase in number of colony-forming units of M . tuberculosis in the lungs (p<0.01) . Expression levels of interferon-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 mRNA were lower in GK/Jcl diabetic rats than those in control Wistar rats . Alveolar macrophages from GK/Jcl rats secreted less TNF-alpha and IL-12, and produced less NO compared with those from Wistar rats . No significant difference was observed between phagocytosis of tubercle bacilli by alveolar macrophages from GK/Jcl or Wistar rats . These data show that there is a close association between experimental tuberculosis and diabetes in animals, and that alveolar macrophages from GK/Jcl diabetic rats are not fully activated by M . tuberculosis infection .

Microb Drug Resist, 2004 Fall, 10(3), 239 - 42
Activity of rifampin against Mycobacterium tuberculosis in a reference center; Ruiz P et al.; Rifampin is a bactericidal antibiotic that acts both on extra- and intracellular bacilli . It inhibits RNA synthesis by binding to the beta-subunit in the RNA polymerase . A study was conducted on rifampin resistance from 1993 to 2002 with 1,794 Mycobacterium tuberculosis strains submitted to Mycobacteria Reference Center, Cordoba, Spain . A total of 1,460 of these strains came from pulmonary specimens and 235 from extrapulmonary specimens . All strains were identified by conventional morphological, bacteriological, biochemical, genetic, and chromatographic methods . For 99 strains, the source was not indicated . Initially, the BACTEC 460 TB system was used for antibiotic sensitivity testing . Since 1996, the ESP II system was also used . The strains ATCC27294 (sensitive to streptomycin, rifampin, ethambutol, and isoniazid) and ATCC38838 (resistant to rifampin) were used as controls . The resistance degree detected was 10.03%, of which 1.2% and 8.7% corresponded to primary and secondary resistances, respectively . A total of 137 strains showed multiresistance . The surveillance of resistance and of the potential factors that may lead to an increase in resistance is thus warranted . Copyright Mary Ann Liebert, Inc.

Res Microbiol, 2004 Oct, 155(8), 647 - 54
Data mining of Mycobacterium tuberculosis complex genotyping results using mycobacterial interspersed repetitive units validates the clonal structure of spoligotyping-defined families; Ferdinand S et al.; Recently, a combination of spoligotyping and bioinformatics was proposed as a potential tool for defining major circulating clades of tuberculosis bacilli . In the present study, we attempted to validate the above mentioned classification using a new high-throughput marker, named mycobacterial interspersed repetitive units (MIRUs) . Using 12 MIRU loci and spoligotyping, we performed data mining of results on clinical isolates of the Mycobacterium tuberculosis complex representative of global mycobacterial allelic diversity . Knowledge rules permitting automatic labeling of major M . tuberculosis families were defined . Using this strategy, MIRU 24 appeared to be most appropriate for classifying our dataset . The Bovis family was shown to be perfectly classified by a maximum of 3 MIRUs, followed by Africanum and East African Indian (EAI) families by 4 MIRUs, the Beijing family by 6 MIRUs, Haarlem and X families by 8 MIRUs, the T family by 9, and the Latin-American and Mediterranean (LAM) family by 10 MIRUs . Considering the hierarchy of family divergence, our results corroborate a recent suggestion that EAI is the ancestral family followed by Africanum and Bovis . On the other hand, T, X, LAM and Haarlem families appear to be of more recent evolution . These results indicate that data mining of MIRUs is a valuable new tool for analyzing the evolutionary dynamics of the M . tuberculosis complex, and for monitoring an infectious disease such as tuberculosis.

Scand J Immunol, 2004 Oct, 60(4), 329 - 37
The effect of iron on the expression of cytokines in macrophages infected with Mycobacterium tuberculosis; Serafin-Lopez J et al.; Iron is known to play an important role in different bacterial infections and, in particular, in their development . One example is infection with Mycobacterium tuberculosis where iron contributes to growth and survival of the bacteria within the host cell . The majority of studies performed on tuberculosis have focused on the direct effect of iron on bacterial growth; however, little is known about how iron modifies the mycobacterial-host interaction . In order to address this, we have investigated the effect of iron on intracellular growth of M . tuberculosis in J774 macrophages and the molecular mechanisms that are affected during this interaction . We observed that iron modifies intracellular growth of the mycobacteria and that their growth kinetics was modified from that observed for the extracellular situation in the presence of iron . Similarly, when iron was present during the infection, there was a reduced release of tumour necrosis factor-alpha and it was related to a higher number of bacilli inside the host cell and low expression of interleukin-1 (IL-1) and IL-6 mRNA . Hence, this work demonstrates that iron, besides promoting mycobacterial growth, also regulates the relationship between macrophage and bacteria.

Plant Biol (Stuttg), 2004 Sep, 6(5), 629 - 42
Microbial populations and activities in the rhizoplane of rock-weathering desert plants . I . Root colonization and weathering of igneous rocks; Puente ME et al.; Dense layers of bacteria and fungi in the rhizoplane of three species of cactus (Pachycereus pringlei, Stenocereus thurberi, Opuntia cholla) and a wild fig tree (Ficus palmeri) growing in rocks devoid of soil were revealed by bright-field and fluorescence microscopy and field emission scanning electron microscopy . These desert plants are responsible for rock weathering in an ancient lava flow at La Purisima-San Isidro and in sedimentary rock in the Sierra de La Paz, both in Baja California Sur, Mexico . The dominant bacterial groups colonizing the rhizoplane were fluorescent pseudomonads and bacilli . Seven of these bacterial species were identified by the 16S rRNA molecular method . Unidentified fungal and actimomycete species were also present . Some of the root-colonizing microorganisms fixed in vitro N(2), produced volatile and non-volatile organic acids that subsequently reduced the pH of the rock medium in which the bacteria grew, and significantly dissolved insoluble phosphates, extrusive igneous rock, marble, and limestone . The bacteria were able to release significant amounts of useful minerals, such as P, K, Mg, Mn, Fe, Cu, and Zn from the rocks and were thermo-tolerant, halo-tolerant, and drought-tolerant . The microbial community survived in the rhizoplane of cacti during the annual 10-month dry season . This study indicates that rhizoplane bacteria on cacti roots in rock may be involved in chemical weathering in hot, subtropical deserts.

Muscle Nerve, 2004 Oct, 30(4), 393 - 409
Leprosy and the peripheral nervous system: basic and clinical aspects; Ooi WW et al.; Leprosy is one of the most common causes of nontraumatic peripheral neuropathy in the developing world . The causative agent, Mycobacterium leprae, has a predilection for Schwann cells, where the organism multiplies unimpeded by organism-specific host immunity, resulting in destruction of myelin, secondary inflammatory changes, and destruction of the nerve architecture . The cardinal diagnostic features of leprosy are anesthetic skin lesions, neuropathy, and positive skin smears for the bacilli . However, patients may rarely present without skin lesions in pure neuritic leprosy . Electrodiagnostic findings early in the disease reveal demyelinating features, such as slowing of conduction velocity and prolongation of latencies, but as the disease progresses secondary axonal damage commonly ensues . Electrodiagnostic studies are also useful to monitor for toxicity secondary to therapy, particularly thalidomide-associated neuropathy . Nerve biopsy of a sensory cutaneous nerve is sometimes essential to confirm a diagnosis of leprosy . Significant advances in understanding of the pathogenesis, mapping of the genome, and other advances in molecular biology may result in better preventive and therapeutic modalities, and the goal of eradicating leprosy as a global problem may yet be realized.

J Clin Microbiol, 2004 Sep, 42(9), 4067 - 71
Evaluation of the new VITEK 2 card for identification of clinically relevant gram-negative rods; Funke G et al.; The VITEK 2 card for gram-negative bacteria (bioMerieux,Marcy-l'Etoile, France) has been redesigned to improve the identification of fermenting and nonfermenting bacilli . Forty-seven biochemical tests, including 19 enzymatic tests, are present in the new card and interpreted in a kinetic mode . Final identification results are available within 10 h . The database allows the identification of 159 different taxa . Six hundred fifty-five gram-negative rods (GNR; 511 fermenters and 144 nonfermenters), representing 54 taxa, were tested . Strains were taken from fresh routine primary isolation plates (n = 157), from stored routine plates (n = 301), and from stock cultures (n = 197) . Six hundred thirty-seven strains (97.3%) were correctly identified to the species level, 14 strains (2.1%) gave low discrimination results requiring additional tests, and 4 strains (0.6%) gave discordant results; not a single strain remained unidentified . Nearly 92% of all isolates were correctly identified within 7 h of incubation . The robustness of the system was demonstrated by the fact that strains were grown on four different agar media before testing . The system may also have the potential to be applied directly to primary isolation plates, since in this instance 96.2% of 157 GNR were correctly identified and 3.8% gave low discrimination results . The new VITEK 2 card for gram-negative bacteria seems to be a promising new tool for routine, rapid identification of GNR.

Rev Soc Bras Med Trop, 2004 Sep-Oct, 37(5), 384 - 90 Epub 2004 Sep 03.
{Erythema nodosum leprosum case series report: clinical profile, immunological basis and treatment implemented in health services}; Guerra JG et al.; Erythema nodosum leprosum is an acute inflammatory event in the chronic course of leprosy . It is considered an immunological disorder and an important cause of morbidity and disability . We evaluate the clinical profile, serology and histopathology 58 erythema nodosum leprosum patients sequentially recruited, from July- December 2000, in an endemic area in Central Brazil (Goias State) . Half of the reactins were considered severe and 66% of the cases had the first episode of reaction during specific treatment . The majority of patients and controls were positive to anti-PGL-I IgM . The more frequent histopathological findings in erythema nodosum leprosum were presence of intracellular acid-fast bacilli, perivascular/peradnexial mononuclear inflammatory infiltrate, and neural aggression . Ninety six percent of the patients were treated with systemic steroid in the first episode . The results point out to the association between ENL and neuritis and the rare adoption of thalidomide as a solely medication in the health services.

J Appl Microbiol, 2004, 97(4), 766 - 73
Identification of extracellular enzyme producing alkalophilic bacilli from Izmir province by 16S-ITS rDNA RFLP; Akbalik G et al.; AIMS: To screen industrially important extracellular enzymes from the newly isolated alkalophilic bacilli and to characterize them by phenotypic and 16S-internal transcribed spacer (ITS) rDNA restriction pattern analysis . METHODS AND RESULTS: Three different environmental samples, soil, leather and horse faeces, were collected within the province of Izmir . Isolates grown on Horikoshi-I medium for 24 h at 37 degrees C were screened for extracellular enzyme activity by using eight different substrates: birchwood xylan, carboxymethylcellulose, casein, citrus pectin, polygalacturonic acid, soluble starch, and Tween 20 and 80 . In total, 115 extracellular enzyme-producing bacilli were obtained . Casein was hydrolysed by 78%, soluble starch by 67%, citrus pectin by 63%, polygalacturonic acid by 62%, Tween 20 by 34%, birchwood xylan by 16%, Tween 80 by 12%, and carboxymethylcellulose by 3% of the isolates . The isolates were differentiated into 19 distinct homology groups by the 16S-ITS rDNA restriction pattern analysis . CONCLUSIONS: Eight different extracellular enzyme activities were determined in 115 endospore forming bacilli . The largest 16S-ITS rDNA homology group (HT1) included 36% of the isolates, 98% of which degraded casein, polygalacturonic acid, pectin and starch . SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report on the characterization of the industrial enzyme-producing alkalophilic bacilli by 16S-ITS rDNA restriction fragment length polymorphism (RFLP) . Restriction profiles of 64% of the isolates were found to be different from those of five reference strains used.

Clin Infect Dis, 2004 Aug 15, 39(4), 517 - 25 Epub 2004 Aug 03.
Infected bilomas in liver transplant recipients: clinical features, optimal management, and risk factors for mortality; Safdar N et al.; BACKGROUND: Infected hepatic fluid collections (bilomas) are a major infectious complication of liver transplantation . Limited data exist on management and outcome of biloma . METHODS: We report a cohort study of 57 liver transplant recipients with posttransplantation bilomas undertaken to identify the clinical features of biloma, management strategies, and outcome . RESULTS: Fever (44%) and abdominal pain (40%) were the most common presenting symptoms, but one-third of patients were asymptomatic; 79% had elevated hepatic enzyme levels . Patients without hepatic artery thrombosis (HAT) had the highest rates of resolution with percutaneous drainage and anti-infective therapy (64%) . Retransplantation was necessary in 64% of patients with HAT and biloma . Independent predictors of resolution with nonsurgical therapy were absence of HAT (odds ratio {OR} 7.69; P=.01) and absence of Candida (OR, 9.09; P=.02) or enterococcal infection (OR, 7.69; P=.03) . Patients with bilomas had significantly greater mortality (Cox proportional hazard ratio {HR}, 2.38; P=.008, by log rank test) and graft loss (HR, 4.31; P<.0001) . Predictors of mortality by multivariable analysis included renal insufficiency (OR, 12.51; P=.02) or infection with Candida species (OR, 4.93; P=.03) or gram-negative bacilli (OR, 9.12; P=.01) . CONCLUSION: Posttransplantation biloma should be suspected in patients with fever or abdominal pain or abnormalities of hepatic enzymes, and it can be confirmed by computerized tomography and radiographically guided aspiration . Bilomas are most likely to be successfully treated nonsurgically in patients without HAT and without Candida or enterococcus infection.

J Exp Med, 2004 Sep 6, 200(5), 647 - 57
Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice; Karakousis PC et al.; Mycobacterium tuberculosis residing within pulmonary granulomas and cavities represents an important reservoir of persistent organisms during human latent tuberculosis infection . We present a novel in vivo model of tuberculosis involving the encapsulation of bacilli in semidiffusible hollow fibers that are implanted subcutaneously into mice . Granulomatous lesions develop around these hollow fibers, and in this microenvironment, the organisms demonstrate an altered physiologic state characterized by stationary-state colony-forming unit counts and decreased metabolic activity . Moreover, these organisms show an antimicrobial susceptibility pattern similar to persistent bacilli in current models of tuberculosis chemotherapy in that they are more susceptible to the sterilizing drug, rifampin, than to the bactericidal drug isoniazid . We used this model of extracellular persistence within host granulomas to study both gene expression patterns and mutant survival patterns . Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that rel(Mtb) is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas . Interestingly, the dormancy phenotype of extracellular M . tuberculosis within host granulomas appears to be immune mediated and interferon-gamma dependent.

Drugs Today (Barc), 2004 Jun, 40(6), 487 - 500
Advances in molecular targets and chemotherapy of tuberculosis; Kumari S et al.; The need for newer, effective drugs with different modes of action against tuberculosis is great, despite the numerous drugs in clinical use and the development of Bacilli Calmette-Guerin (BCG) vaccine . Three major goals should be considered in the development of new antituberculosis drugs: 1) they should be fast acting to reduce the long duration of treatment, thereby avoiding drug toxicity; 2) they should be active against both sensitive and resistant strains of tubercle bacilli; and 3) they should possess significant activity against dormant bacilli, which represent the stage affecting one-third of the world's tuberculosis patients . This review provides an overview of important current drugs, novel targets for the development of antituberculosis agents and future drug candidates .

Dermatol Online J . 2004 Jul 15;10(1):17.
Leprous osteitis presenting as bone cyst and erosions; Dave S et al.; A 30-year-old man presented to the Hansen outpatient department with swelling and ulceration of toes for 2 months and swelling of the right fifth and fourth fingers and the left second finger for 1 month . In addition to skin lesions of lepromatous leprosy (subpolar type), there was nontender, non-fluctuant swelling of the right fifth and fourth fingers and left second finger . Skin over the right fifth finger showed sinus-like openings with associated purulent discharge . He also had swelling and ulceration of second left toe . Slit-skin smear (SSS) showed a bacterial index of 6+ from the ear lobes and cutaneous nodules, 4+ from the patch, and 3+ from normal skin . Modified Ziehl-Neelsen staining of the discharge extruding from the sinuses on the right fifth finger also showed abundant acid-fast bacilli . Radiography of the hands and feet showed lytic lesions in the distal epimetaphyseal region o proximal phalanx of the right fifth finger and left second finger and erosion of distal end of proximal phalanges of both second toes . Histopathological examination of biopsy specimen from the patch (back) showed features of lepromatous leprosy, and Fite-Faraco stain for tissue acid-fast bacteria (AFB) was strongly positive . Fine-needle-aspiration cytology (FNAC) from the lytic lesion in the bone also showed predominantly foamy macrophages with strongly positive staining for AFB with a few interspersed lymphocytes, epithelioid cells and Langhans giant cells . On the basis of these features, a clinical diagnosis of subpolar lepromatous leprosy with leprous osteitis was made . In today's clinical era of improved case detection and prompt treatment with effective multidrug regimens, advanced bone changes are rarely encountered . We describe this case of lepromatous leprosy that developed cavitating lesions of the phalanges of the hand, seen on x-ray as well-defined bone cyst and erosions.

An Med Interna, 2004 Jul, 21(7), 334 - 6
{One case of pneumonia with Arcanobacterium pyogenes}; Hermida Amejeiras A et al.; Arcanobacterium pyogenes is an anaerobic Gram-positive bacilli and it is a part of the normal flora in many domestic animals . A . pyogenes is a rare cause of pyogenic infections in humans and most of cases reported are questionable since there was failure to definitively identify the pathogen . A man with no past medical history presented with respiratory infection . The blood sample collected confirmed an Arcanobacterium pyogenes . It was necessary the addition of clarytromycin to the initial empirical treatment with cefotaxime, to the complete recovery . This case provide further evidence that A . pyogenes can be a pathogen in humans even in absence of predisposing illness.

Cell Microbiol, 2004 Oct, 6(10), 973 - 85
Modulation of cellular phosphatidylinositol 3-phosphate levels in primary macrophages affects heat-killed but not viable Mycobacterium avium's transport through the phagosome maturation process; Kelley VA et al.; Most disease causing mycobacteria are intramacrophage pathogens which replicate within nonacidified phagosomes that can interact with the early endosomal network but fail to mature to a phagolysosome . The mycobacterial phagosome retain some proteins required for fusion with endocytic vesicles including Rab5 but lack others such as early endosomal autoantigen 1 (EEA1) . As the membrane lipid phosphatidylinositol 3-phosphate (PtdIns-3-P) is required for EEA1 membrane association and phagosome maturation, it may be a potential target of pathogenic mycobacteria . To test this hypothesis, macrophage cellular levels of PtdIns-3-P were altered by retroviral introduction of the type III Phosphoinositide 3-Kinase (VPS34) and the PtdIns-3-P phosphatase myotubularin 1 (MTM1) . By utilizing the PtdIns-3-P-specific probes FYVE and PX coupled to EGFP (EGFP-2-FYVE and EGFP-PX, respectively), the expression of PtdIns-3-P on the mycobacterial phagosome was addressed . All phagosomes containing viable Mycobacterium avium stained positive for EGFP-2-FYVE and EGFP-PX despite obvious differences in PtdIns-3-P concentrations in cells expressing MTM1 or VPS34 . Altering PtdIns-3-P cellular concentrations did not affect trafficking of live bacilli . However, a significant increase in the transport of killed bacilli to a late endosomal/lysosomal compartment was observed in VPS34-compared to MTM1-transduced macrophages . Therefore, although overexpression of PdtIns-3-P in macrophages can facilitate phagosome maturation, its effect on phagosomes containing viable M . avium was negligible.

Am J Med, 2004 Sep 1, 117(5), 353 - 6
Cases from the Osler Medical Service at Johns Hopkins University . Diagnosis: P . carinii pneumonia and primary pulmonary sporotrichosis; Losman JA et al.; PRESENTING FEATURES: A 53-year-old man who had human immunodeficiency virus (HIV) presented to the Johns Hopkins Hospital with a 3-month history of increasing dysphagia, cough, dyspnea, chest pain, and an episode of syncope . His past medical history was notable for oral and presumptive esophageal candidiasis that was treated with fluconazole 6 months prior to presentation . Three months prior to presentation, he discontinued his medications, and his symptoms of dysphagia recurred . During that time he developed intermittent fevers and chills, progressively worsening dyspnea on exertion, and a cough productive of white sputum . He also reported a 40-lb weight loss over the past 3 months . On the day prior to presentation, he had chest pain and shortness of breath followed by weakness, dizziness, and a brief syncopal episode . He denied orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, jaundice, hemoptysis, hematemesis, melena, hematochezia, or diarrhea . There was no history of alcohol use, and he stopped smoking tobacco approximately 1 month previously . He smoked cocaine but denied injection drug use . The patient had never been on antiretroviral therapy and had never had his CD4 count or viral load measured . On physical examination, the patient was a thin, cachectic man who appeared older than his stated age . His vital signs were notable for blood pressure of 102/69 mm Hg, resting tachycardia of 102 beats per minute, resting oxygen saturation of 92% on room air, normal resting respiratory rate, and a temperature of 38.1 degrees C . His oropharynx was clear, with no signs of thrush or mucosal ulcers . His pulmonary examination was notable for diminished breath sounds in the lower lung fields bilaterally . Cardiac, abdominal, and neurologic examinations were normal . His skin was intact, with no visible petechiae, rashes, nodules, or ulcers . Laboratory studies showed a total white blood cell count of 3.2 x 10(3)/microL, with a total lymphocyte count of 330/microL, hematocrit of 30.2%, a serum sodium level of 129 mEq/L, and a serum lactate dehydrogenase level of 219 IU/L . The patient had an absolute CD4 count of 8 cells/mm3 and a HIV viral load of 86,457 copies/mL . His arterial blood gas on room air had a pH of 7.51, a PCO2 of 33 mm Hg, and a PO2 of 55 mm Hg . Electrocardiogram and serial serum cardiac enzymes were normal . A chest radiograph showed bilateral upper lobe patchy infiltrates with left upper lobe consolidation . Computed tomographic (CT) scan of the chest with contrast showed bilateral ground glass infiltrates with focal consolidation (Figure 1) and no evidence of pulmonary embolism . Induced sputum was negative for Pneumocystis carinii, fungi, or acid-fast bacilli . A bronchoalveolar lavage was performed . What is the diagnosis?

Intern Med, 2004 Jul, 43(7), 566 - 70
Whipple's disease: the first Japanese case diagnosed by electron microscopy and polymerase chain reaction; Yogi T et al.; A 52-year-old man presented with diarrhea and 20 kg weight loss in one year . Enteroscopy showed diffuse yellow-white shaggy mucosa in the duodenum and jejunum . Biopsies of the duodenal mucosa revealed massive infiltration within the lamina propria by foamy macrophages strongly positive for periodic acid-Schiff stain . Electron microscopy demonstrated numerous bacilli within macrophages of the lamina propria . Tropheryma whipplei DNA was detected by polymerase chain reaction . The definitive diagnosis of Whipple's disease was made . Antibiotic therapy dramatically improved his clinical picture . This is the first Japanese case with Whipple's disease diagnosed by electron microscopy and polymerase chain reaction.

Am J Otolaryngol, 2004 Sep-Oct, 25(5), 329 - 33
Management of otogenic lateral sinus thrombosis; Seven H et al.; PURPOSE: Lateral sinus thrombosis (LST) is a rare but potentially devastating complication of otitis media . We review the clinical presentation, evaluation, management, operative findings, and outcomes of this serious complication . MATERIAL AND METHODS: A retrospective chart review was performed at a teaching hospital of all patients diagnosed with an otogenic lateral sinus thrombosis between 1992 and 2002 . Data on patients with otogenic LST were collected and analyzed . RESULTS: Eleven patients were identified with a diagnosis of lateral sinus thrombosis, and all had a chronic otitis media . The most common presenting symptoms were headache, otalgia, and fever . Radiologic evaluation included computed tomography scan, magnetic resonance imaging, or magnetic resonance venography . All patients had radiographic evidence of LST preoperatively . The thrombosed sinus was on the right side in 6 patients and on the left side in 5 patients . The majority of patients (8 of 11) had a second concomitant intracranial complication . All patients underwent a mastoidectomy . The thrombus was removal in 7 cases, whereas only needle aspiration of the sinus was performed in 4 cases . Gram-negative bacilli and anaerobes were the most common organisms . There were no deaths but sequelae included VI nerve palsy, ataxia, and dead ear . CONCLUSION: LST as a complication of otogenic infections may still pose a serious threat that warrants immediate attention and care . It is frequently associated with other intracranial complications . Contrast-enhanced computed tomography scan and magnetic resonance imaging plays a major role in determining diagnosis and treatment plans . The availability of broad-spectrum antibiotics has improved our management significantly . Conservative surgical intervention including eradication of all perisinus infection and needle aspiration of the sinus seems to be effective.

Vet Clin Pathol, 2004, 33(3), 177 - 81
Mycobacterium tuberculosis infection in a dog from Africa; Turinelli V et al.; A 4-year-old male Boxer dog with a history of vomiting, diarrhea, and weight loss moved from West Africa to Lyon, France, where it was further evaluated . Radiographs revealed pleural effusion and enlargement of tracheobronchial lymph nodes and liver . Cytologic examination of the pleural effusion and a fine needle aspirate specimen of the liver showed mixed mononuclear inflammation with nonstaining rod structures within epithelioid histiocytes . At necropsy, the main gross pathologic findings were exudative pleuritis, nodular hepatitis, and infarcts and caseous nodules in the kidneys . The main histologic lesions were granulomatous hepatitis, granulomatous pneumonia, fibrinous leukocytic pleuritis, necrotic and fibro-calcified granulomatous lymphadenitis, and granulomatous nephritis . A Ziehl-Neelsen stain applied to both cytologic and histologic samples was positive for acid-fast bacilli . Bacterial culture of the pleural fluid was positive for Mycobacterium tuberculosis . Cytology is a valuable tool in the diagnosis of this important zoonotic disease.

Vaccine, 2004 Sep 9, 22(27-28), 3649 - 57
10-12 years follow-up of highly bacillated BL/LL leprosy patients on combined chemotherapy and immunotherapy; Katoch K et al.; This study reports the follow-up results of 36 highly bacillated untreated BL/LL cases who were serially allocated to three treatment groups . Group I patients received a modified WHO regimen (Rifampicin 600 mg once a month supervised, 50 mg of Clofazimine and 100 mg of Dapsone daily unsupervised) and BCG 0.1 mg per dose 6 monthly; group II patients received the same multi-drug treatment (MDT) and Mw (2 x 10(8) killed bacilli per dose) 6 monthly: group III patients received the same MDT with 0.1 ml of distilled water 6 monthly and acted as a control . Treatment was continued till smear negativity . All these three groups were comparable by their initial clinical score, bacteriological index (BI), viable bacilli as assessed by the mouse foot pad (MFP), bacillary adenosine triphosphate (ATP) content and also histologically at the time of starting treatment . All these parameters were evaluated every 6 months . The vaccines were well tolerated . All the patients in group I became smear negative by 3.5 years, in group II in 3 years whereas those in group III took 5 years . The incidence of reactions was the same in all the groups during the first 2 years, however, patients of group III (MDT + placebo) continued to have reactions up to 3 years . No viable bacilli could be detected in the local and distal sites as estimated by MFP and bacillary ATP after 12 months in both the immunotherapy groups . These could be detected in patients on MDT alone up to 24 months of therapy . Histologically patients in both the immunotherapy groups (groups I and II) showed accelerated granuloma clearance, histological upgrading and non-specific healing without granuloma formation both at the local and distal sites and this was achieved much earlier compared to the MDT + placebo group . Thus, by the addition of immunotherapy the effective treatment period of achieving bacteriological negativity could be reduced by about 40%, time period of reactions reduced by 33% and there were no reactions and/or relapses in the 10-12 years post-treatment follow-up.

Diagn Microbiol Infect Dis, 2004 Aug, 49(4), 255 - 63
Eggerthella hongkongensis sp . nov . and eggerthella sinensis sp . nov., two novel Eggerthella species, account for half of the cases of Eggerthella bacteremia; Lau SK et al.; Eggerthella, one of the human gut flora, was rarely reported to cause bacteremia in the literature . We describe the application of 16S ribosomal RNA gene sequencing in defining the epidemiology and clinical significance of Eggerthella bacteremia during a 4-year period . Among 55 clinically significant blood culture isolates of anaerobic Gram-positive bacilli, 5 were identified as E . lenta and 5 belonged to 2 novel Eggerthella species, proposed as E . hongkongensis and E . sinensis, respectively . The 10 patients with Eggerthella bacteremia were adults, and 9 had underlying diseases . In all cases, the source of the bacteremia was likely from endogenous flora . Septic shock was a complication in 4 patients, and 3 patients died . The present study suggests that Eggerthella bacteremia is much more common than expected and is associated with significant morbidity and mortality . Moreover, the 2 novel species account for half of the cases of Eggerthella bacteremia.

Zhonghua Shao Shang Za Zhi, 2004 Apr, 20(2), 95 - 7
{Changes in plasma levels of LPS, TNFalpha and IL-6 in burn patients with severe infection treated with Imipenem or Cefoperazone}; Wang HM et al.; OBJECTIVE: To observe the changes in plasma levels of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in burn patients with severe infection treated with Imipenem or Cefoperazone . METHODS: Thirteen severe burn patients infected with gram negative bacilli were enrolled in the study in which 7 were treated with IPM and 6 with CPZ . Venous blood samples were harvested before and 2, 12, 24, 48 and 72 hours after the use of antibiotic for the determination of the plasma levels of LPS, TNF-alpha and IL-6, and correlative analysis was carried out among all the factors in regard to their changes . RESULTS: The plasma levels of LPS in both groups were elevated 2 hours after the injection of either antibiotic, but it was more obvious in patients with CPZ when compared with that before treatment (13.95 +/- 5.44 pg/ml), and the levels were much higher than that after IPM (P < 0.05) . The plasma LPS level declined thereafter . The plasma TNF-alpha level in CPZ group was 0.86 +/- 0.16 ng/ml at 2 hours after the use of antibiotic, and it was much higher than that before the use of the drug, and it was higher compared with IPM group . (P < 0.01) . But there was no change in the plasma IL-6 level in all the patients at all the time points before and after the use of either drug . The plasma TNF-alpha levels in the two groups were positively correlated with the plasma levels of LPS and IL-6 . CONCLUSION: The release of LPS and TNF-alpha from bacteria could be induced by the administration of different kinds of antibiotics in the management of burn patients infected by gram negative bacilli in different releasing amounts . And the TNF-alpha production was correlated with the release of LPS and IL-6.

Immunology, 2004 Sep, 113(1), 130 - 8
Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: activation of CD8+ cells, interferon-gamma recovery and reduction of lung injury; Bonato VL et al.; A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis . In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65 . We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice . After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated . Our results show that the most significant effect of pHSP65 was the stimulation of CD8+ lung cell activation, interferon-gamma recovery and reduction of lung injury . There was also partial restoration of the production of tumour necrosis factor-alpha . Treatment with pcDNA3 vector also induced an immune stimulatory effect . However, only infected pHSP65-treated mice were able to produce significant levels of interferon-gamma and to restrict the growth of bacilli.

J Gen Virol, 2004 Sep, 85(Pt 9), 2603 - 13
Inhibition of human immunodeficiency virus type 1 replication by Z-100, an immunomodulator extracted from human-type tubercle bacilli, in macrophages; Emori Y et al.; Z-100 is an arabinomannan extracted from Mycobacterium tuberculosis that has various immunomodulatory activities, such as the induction of interleukin 12, interferon gamma (IFN-gamma) and beta-chemokines . The effects of Z-100 on human immunodeficiency virus type 1 (HIV-1) replication in human monocyte-derived macrophages (MDMs) are investigated in this paper . In MDMs, Z-100 markedly suppressed the replication of not only macrophage-tropic (M-tropic) HIV-1 strain (HIV-1JR-CSF), but also HIV-1 pseudotypes that possessed amphotropic Moloney murine leukemia virus or vesicular stomatitis virus G envelopes . Z-100 was found to inhibit HIV-1 expression, even when added 24 h after infection . In addition, it substantially inhibited the expression of the pNL43lucDeltaenv vector (in which the env gene is defective and the nef gene is replaced with the firefly luciferase gene) when this vector was transfected directly into MDMs . These findings suggest that Z-100 inhibits virus replication, mainly at HIV-1 transcription . However, Z-100 also downregulated expression of the cell surface receptors CD4 and CCR5 in MDMs, suggesting some inhibitory effect on HIV-1 entry . Further experiments revealed that Z-100 induced IFN-beta production in these cells, resulting in induction of the 16-kDa CCAAT/enhancer binding protein (C/EBP) beta transcription factor that represses HIV-1 long terminal repeat transcription . These effects were alleviated by SB 203580, a specific inhibitor of p38 mitogen-activated protein kinases (MAPK), indicating that the p38 MAPK signalling pathway was involved in Z-100-induced repression of HIV-1 replication in MDMs . These findings suggest that Z-100 might be a useful immunomodulator for control of HIV-1 infection.

Aliment Pharmacol Ther, 2004 Jul, 20 Suppl 1, 125 - 30
Expression of leptin in two-layered culture of gastric mucous cells and fibroblasts: effect of Helicobacter pylori attachment; Nakamura M et al.; BACKGROUND: Our recent histochemical studies have revealed an increase in myofibroblasts and in leptin and its receptor in endothelial cells, and myofibroblasts in Helicobacter pylori-infected human and Mongolian gerbil fundic mucosa . AIM: The present study was undertaken to clarify the H . pylori-induced interaction between leptin in cultured gastric surface mucous cells and fibroblasts . METHODS: GSM06 cells were incubated with an air- liquid interface on a collagen gel layer containing mouse fibroblast cell line L929 . Medium containing H . pylori bacilli (ATCC43504) at 10-100 times higher concentration than the GSM06 cells was added from the luminal side and the localization of leptin was observed by immunohistochemistry . The transformation of L929 cells to myofibroblasts was detected by electron microscopy and PR 2D3 immunoreactivity . RESULTS: L929 cells in the control group showed a spindle shape with scarce cytoplasm . In the H . pylori-treated group, L929 cells showed features characteristic of myofibroblasts, and most GSM06 and L929 cells showed leptin immunoreactivity . In contrast, L929 cells incubated with H . pylori alone did not undergo this differentiation . CONCLUSIONS: Attachment of H . pylori to surface epithelial cells caused conversion of fibroblasts to myofibroblasts . We suggest that leptin plays a role in this transformation.

BMC Infect Dis . 2004 Aug 05;4(1):24.
Meningitis due to Fusobacterium necrophorum in an adult; Garimella S et al.; BACKGROUND: Fusobacterium necrophorum may cause a number of clinical syndromes, collectively known as necrobacillosis . Meningitis is a significant cause of mortality, rarely reported in the adult population . CASE PRESENTATION: We report a fatal case of meningitis, caused by Fusobacterium necrophorum, secondary to otitis media in an alcoholic male . Diagnosis was delayed due to the typical slow growth of the organism . The clinical course was complicated by encephalitis and by hydrocephalus . The patient failed to respond to metronidazole and penicillin . The patient died on day 12 from increased intracranial pressure and brain stem infarction . CONCLUSIONS: This case emphasizes the need for a high index of clinical suspicion to make the diagnosis of Fusobacterium necrophorum meningitis . We recommend the use of appropriate anaerobic culture techniques and antimicrobial coverage for anaerobic organisms when the gram stain shows gram negative bacilli.

Ethiop Med J, 2003 Oct, 41(4), 311 - 8
Tuberculous meningitis in a district hospital from Southern Ethiopia; Degefie T; In order to describe the clinical presentation, immediate outcome and risk factors associated with Tuberculous meningitis (TBM), 28 children with TBM were analyzed . The male to female ratio was 1.5:1 . The mean age of the cases was 8 years (range 5 months-14 years) . Nineteen (67%) of the patients were not vaccinated for Tuberculosis (TB) . Nineteen (67%) patients had exposure to adults with pulmonary TB of which 14 (50%) were family members . Among these were four children who were vaccinated and their age range was from 7 month to 8 years . Thirteen (40%) were seen by health professionals with in three months before symptoms related to TBM, the mean duration of symptoms before seeking medical advice was 3.2 months . Using the weight height percentage of median, sixteen (57%) had malnutrition . Twenty (71%) patients were in stage three of TBM at presentation . Eleven (38%) had positive reaction to Mantoux test and 25 (89%) had abnormal chest radiography the most common finding being hilar lymphadenopathy . CSF (Cerebro Spinal Fluid) total cell count showed pleocytosis of < 200 in all but two cases (71%), and raised protein level on quantitative determination . Acid Fast Bacilli (AFB) test done in seven patients, was positive in two (29%) cases . One (4%) direct sputum smear and gastric aspirate culture were positive . Thirteen 13 (46%) patients died despite treatment and 9 (64%) had severe neurological complications . Delay at presentation advanced stage of TBM and unvaccinated state for tuberculosis were closely associated with poor outcome (P<0.05) . Hence health workers who treat children should maintain high index of suspicion at all times and evaluate for TBM . The value of prophylaxis for children who have close contact with infectious cases should be evaluated in Ethiopia.

DNA Cell Biol, 2004 Jul, 23(7), 450 - 6
Combined DNA vaccines formulated in DDA enhance protective immunity against tuberculosis; Cai H et al.; This study evaluated the adjuvant Dimethyldioctyldecyl Ammonium Bromide (DDA) effect on the protective immunity induced by a combination of plasmids containing genes encoding antigens Ag85B, MPT-83, and ESAT-6 from Mycobacterium tuberculosis . The combined DNA vaccines in DDA resulted in significant increases in both specific IgG and splenic T-cell-derived Th1-type cytokine gamma interferon (IFN-gamma) production in response to the three purified antigens when compared to that of combined DNA vaccines in saline . Vaccines in DDA increased the protective efficacy of mice challenged with M . tuberculosis H37Rv as measured by reduced relative CFU counts in their lungs . Mice immunized with the combined DNA vaccines were shown to limit the growth of tubercle bacilli both in lungs and in spleens . Histopathological analyses showed that vaccinated mice had substantially improved postinfection lung pathology relative to the controls . We suggest that our combination of antigens together with DDA formulation may provide a new insight into tuberculosis prevention.

Microbiol Res, 2004, 159(2), 141 - 6
Microbial diversity of soil from two hot springs in Uttaranchal Himalaya; Kumar B et al.; Soil samples collected from two hot springs, Soldhar and Ringigad, both located in the Garhwal region of Uttaranchal Himalaya were analysed for their physical, chemical and microbial components . The alkaline pH, total absence of carbon and nitrogen, and high temperature were features common to soil samples from both sites . The Soldhar samples contained higher amounts of Cu, Fe and Mn . Ringigad soil was devoid of Cu, but had much higher phosphate . While the optimum incubation temperature for isolating the maximum microbial counts from soil samples from the two sites was 50 degrees C, microbial growth in broth was also observed when incubated at 80 degrees C . Microscopic examination revealed three types of microbial populations, i.e., bacteria, yeast and filamentous organisms . The soil samples were found to be dominated by spore forming rods . Out of 58 aerobic isolates, 53 were gram positive bacilli . Gram positive anaerobic oval rods were also observed up to 60 degrees C . Soil dilution plates revealed the presence of antagonistic and phosphate solubilizing populations.

Mikrobiyol Bul, 2004 Jan-Apr, 38(1-2), 155 - 67
{Mycobacterium tuberculosis virulence factors and its immune evasion mechanisms}; Colakoglu S; One-third of the world population is infected with Mycobacterium tuberculosis . When tuberculosis develops, the disease localization, severity, and outcome are highly variable between different individuals . The various manifestations of infection with M . tuberculosis reflect the balance between the bacilli and host defense mechanisms, in which the quality of host defense determines the outcome . Recent studies have identified several mycobacterial cell wall components that may be involved in the key steps of pathogenicity . M . tuberculosis is successful as a pathogen because of its ability to persist in an immunocompetent host . This bacterium lives within the macrophages . Hosts infected with M . tuberculosis mount a strong immune response . This response is usually sufficient to prevent progression to active disease . The strong immune response can control, but not eliminate the bacilli, indicating that M . tuberculosis has evolved mechanisms to modulate or avoid detection by the host immune response . Recent advances have improved our understanding of how M . tuberculosis evades two major antimicrobial mechanisms of macrophages; phagolysosome fusion and the production of toxic reactive nitrogen intermediates (RNI) . In this review, the recent evidence of M . tuberculosis evasion from phagolysosome fusion and RNI toxicity, as well as prevention of the recognition of infected macrophages by CD4+ T lymphocytes by inhibiting MHC class II presentation, were discussed.

Kekkaku, 2004 Jun, 79(6), 381 - 6
{Tuberculin skin test reaction of health-care workers exposed to tuberculosis infection}; Tsukishima E et al.; OBJECTIVE: The objective of this study was to describe tuberculin skin test (TST) of health-care workers who had had contacts with a tuberculosis patient and to investigate whether the distributions of the size of TST were different by sputum-smear status of index cases and medical procedures done to the patient . SUBJECTS: Health-care workers who were exposed to tuberculosis infection through contact with patients before diagnosis of tuberculosis were included in this study . Index cases had pulmonary tuberculosis with positive sputum smear and were registered at Sapporo Public Health Office from April 2001 to March 2002 . Subjects without past history of BCG (bacilli Calmette-Guerin) vaccinacion were excluded, and final study subjects were 415 (52 male and 363 female, mean age 29.1 years) . METHOD: Characteristics of index cases and contact status were obtained from the registration cards of tuberculosis cases at Sapporo Public Health Office . Subjects were divided into two or more categories by the characteristics of index cases and the contact status . Distributions of TST of the subjects in different categories were compared . RESULTS: Contacts with patients received tracheal aspiration showed significantly larger TST reaction than contacts with patients not receiving tracheal aspiration . Among contacts with patients showing minimum to moderately positive sputum-smear, TST reaction was significantly larger in contacts with patients received tracheal aspiration (mean diameter of erythema 35.8 mm) than those not receiving tracheal aspiration (24.8 mm) . In contrast, among contacts with patients of severely positive sputum-smear, TST reaction was not significantly different between contacts of patients received tracheal aspiration (35.3 mm) and not receiving tracheal aspiration (33.1 mm) . CONCLUSION: TST was significantly stronger in contacts with a tuberculosis patient received tracheal aspiration, which indicates medical procedures such as tracheal aspiration increases the risk of tuberculosis infection in health-care workers.

J Med Assoc Thai, 2004 Jun, 87(6), 709 - 12
Mycobacterial skin infections: comparison between histopathologic features and detection of acid fast bacilli in pathologic section; Mahaisavariya P et al.; BACKGROUND: Detection of acid fast bacilli (AFB) in chronic granulomatous inflammation is an important clue for mycobacterial infection . DESIGN: A retrospective review of 104 pathologic sections (from 1994 to 2001) of suspected cases of mycobacterial (tuberculous and nontuberculous) skin infections to study histopathologic features and the correlation with the presence of AFB in the section was performed . RESULTS: All cases showed granulomatous inflammations that can be categorized into 4 types: mixed cell, suppurative, tuberculoid and palisading granuloma . AFB was found in 32 sections (30.77%) . Ninety five specimens from 104 specimens were simultaneously cultured . AFB positive cases yielded higher positive cultural results, 17 from 29 cases (58.62%) compared to the AFB negative group, 23 from 66 cases, (34.85%) . Mixed cell granuloma was the most common histologic feature, but suppurative granuloma was the most common histological feature (56.25%) in which AFB could be found, which was statistically significantly different from other types of granuloma . Tuberculoid granuloma was more common in the AFB negative group (20.83%) compared to the AFB positive group (9.37%) but the difference was not statistically significant . In cases that AFB could not be found, the inflammation tended to be located in the upper half of the dermis . CONCLUSION: AFB can be more frequently detected in suppurative granuloma that might be located in any portion of the dermis . This finding was not species specific.

Immunology, 2004 Aug, 112(4), 661 - 8
Airways infection with virulent Mycobacterium tuberculosis delays the influx of dendritic cells and the expression of costimulatory molecules in mediastinal lymph nodes; Garcia-Romo GS et al.; Despite tuberculosis resurgence and extensive dendritic cell (DC) research, there are no in vivo studies evaluating DC within regional lymphoid tissue during airways infection with virulent Mycobacterium tuberculosis (Mtb) H37Rv . Using DC-specific antibodies, immunocytochemistry, flow cytometry and Ziehl-Neelsen (ZN) for bacilli staining, we searched for Mtb and DC changes within mediastinal lymph nodes, after intratracheal (ITT) inoculation of virulent Mtb . ZN and immunocytochemistry in frozen and paraffin sections of mediastinal lymph nodes identified Mtb until day 14 after ITT inoculation, associated with CD11c(+) and Dec205(+) DC . Analysing CD11c, MHC-CII, and Dec205 combinations by flow cytometry in MLN suspensions revealed that CD11c(+)/MHC-CII(+) and CD11c(+)/Dec205(+) DC did not increase until day 14, peaked on day 21, and sharply declined by day 28 . No changes were seen in control, saline-inoculated animals . The costimulatory molecules evaluated in CD11c(+) DCs followed a similar trend; the CD80 increase was negligible, slightly surpassed by CD40 . CD86 increased earlier and the three markers peaked at day 21, declining by day 28 . While antigen-specific proliferation was not evident for MLN CD4(+) T cells at 2 weeks postinfection, delayed-type hypersensitivity responses upon ITT inoculation revealed that, as early as day 3 and 7, both the priming and peripheral systemic immune responses were clearly established, persisting until days 14-21 . While airways infection with virulent Mtb triggers an early, systemic peripheral response maintained for three weeks, this seems dissociated from regional events within mediastinal lymph nodes, such as antigen-specific T-cell reactivity and a delay in the influx and local activation of DC.

J Pak Med Assoc, 2004 May, 54(5), 285 - 8
Pulmonary infiltrates during chemotherapy-induced febrile neutropenia: incidence, patterns and outcomes; Gangat N et al.; OBJECTIVE: To analyze the incidence, etiologies, radiographic patterns, and clinical outcomes of adult leukemics with prolonged febrile neutropenia and pneumonia . METHODS: A retrospective study was conducted at a tertiary care hospital . The medical records of adult patients with acute myeloid leukemia diagnosed between January 1989 and June 2000 and undergoing induction chemotherapy were included . Only the patients who presented with a pulmonary infiltrate, secondary leukemia (e.g., transformed chronic myeloid leukemia underlying myelodysplastic syndrome, or disease following alkylating agent therapy) were included and those developing infiltrates following consolidation chemotherapy were excluded . RESULTS: A total of 124 patients were admitted to the hospital with a diagnosis of AML during the study period . Thirty-one patients were excluded; 93 patients received induction chemotherapy and were included in the study analysis . The median age was 36 years (15 - 70 years); 58 males and 35 females . Sixty two percent patients received Cytosine Arabinoside (Ara-C), 17% received Etoposide, 11% received Ara-C and Mitoxantrone, and 6% received All-trans-retinoic Acid . The mean onset and duration of neutropenia were 5 and 15 days, respectively . Pulmonary infiltrates were identified during 45% of neutropenic episodes . A presumptive causative organism was isolated from 50% of patients with an infiltrate: Gram-positive bacteria were most common (47%) followed by Gram-negative bacilli (33%) and fungi (20%) . Survival data were available for 88 patients; median disease free survival for the entire cohort was 7 months . Male sex (p=0.015), onset of neutropenia (p=0.02) and bilateral distribution of an infiltrate (p=0.03) were statistically significant predictors of early mortality . For patients with and without pneumonia, the median disease-free interval and overall survival were 2.5 and 4.6 months and 9 and 13 months (p=0.038 and p=0.095) respectively . CONCLUSION: Neutropenia occurred at a mean of 5.0 after initiation of induction chemotherapy . The majority of patients had bilateral pulmonary infiltrates . Male sex, onset of neutropenia and bilateral distribution of an infiltrate were found to be statistically significant predictors of early mortality.

Rev Port Pneumol . 2003 Nov;IX(5 Suppl 1):15.
{A singular case of tuberculosis}; Carlos L et al.; Male patient, 50 years old, african, HIV Theta, smoker, heavy etanolic habits, low socioeconomic status . He was admitted to our department due to fever, night sweats, cough, sputum, weight loss (20Kg/3M), anorexia, weakness which started 2 months before, followed by: nausea, vomiting, abdominal distension and pain . Physical examination showed: few crakles; hepatomegaly . Chest x-ray: diffuse bilateral alveolointerstitial infiltrate . Abdominal ultrasonography: hepatomegaly; ascites . Paracenteses: chylous ascites; lymphocytic pleocytosis; tuberculin skin test + . Sputum bacteriological analysis: M . tuberculosis . Acute inflammatory parameters increased; CT thoracic scan: right upper lobe consolidation; bilateral nodular opacities, left pleural effusion, peritoneal fluid; heterogeneous hepatomegaly; mesenteric fat infiltration and parietal thickening . He started diarrhea and strong abdominal pain . The colonoscopy showed terminal ileo partial stenosis, inflammatory process; sigmoid ulcers . Histology: lymphocytic inflammatory infiltrate and epithelioid granulomas with giant multinucleated cells . Few acid-fast bacilli (ZN) . He was treated with HRZE since 2 nd day of hospitalization . At 47 th day the abdominal pain increased . The bowel transit demonstrated ileocecal wall ulcerations, mucosal irregularity and decreased motility . He started prednisolone 40 mg/day . The clinical manifestations and nutritional status improved significantly . Final diagnosis: Pulmonary, Gastrointestinal and Peritoneal Tuberculosis . Involvement of the gastrointestinal tract and peritoneum is rare now-a-days, usually arising from hematogeneous dissemination.

Int J Tuberc Lung Dis, 2004 Jul, 8(7), 896 - 8
Unrecognised tuberculosis in HIV-infected patients: sputum culture is a useful tool; Swaminathan S et al.; Diagnosis of tuberculosis is challenging, especially in human immunodeficiency virus (HIV) positive persons who may have atypical clinical and radiographic features . We report the isolation of Mycobacterium tuberculosis from sputum samples of 10 (4%) HIV-positive persons who were asymptomatic with normal chest radiographs and negative sputum smears for acid-fast bacilli . Six of them had strongly positive tuberculin reactions while four were severely immunosuppressed . Our observation highlights the utility of routine sputum culture in the diagnosis of tuberculosis in high-risk individuals.

Int J Tuberc Lung Dis, 2004 Jul, 8(7), 824 - 8
Smear examination of two specimens for diagnosis of pulmonary tuberculosis in Tiruvallur District, south India; Gopi PG et al.; SETTINGS: A general hospital and three peripheral health institutions (PHI) in Tiruvallur District, south India . OBJECTIVE: To validate the case detection strategy for diagnosis of pulmonary tuberculosis by smear microscopy of two sputum specimens versus three . METHODS: In the Revised National Tuberculosis Control Programme (RNTCP), three smears from every symptomatic patient attending the PHI were examined for acid-fast bacilli (AFB) by Ziehl-Neelsen (ZN) microscopy . The data from the Tuberculosis Laboratory Registers from the above centres were analysed . RESULTS: Of 7843 chest symptomatics who had provided three sputum specimens for examination, 895 (11.4%) were smear-positive on at least two specimens . Examination of two specimens--first spot and early morning specimens (837, 93.5%) or early morning and second spot specimens (843, 94.2%)--yielded the highest number of cases . CONCLUSION: The examination of two sputum smears (one spot and an early morning) is as effective as examination of three smears.

Int J Tuberc Lung Dis, 2004 Jul, 8(7), 816 - 23
Scanty AFB smears: what's in a name?
Van Deun A, Salim AH, Cooreman E, Daru P, Das AP, Aung KJ, Rieder HL.
SETTING: A tuberculosis control project in Bangladesh . OBJECTIVE: To document the frequency and diagnostic value of smears with scanty acid-fast bacilli (AFB) (IUATLD/WHO scale, < 10/100 high power fields), and to assess the appropriateness of the current positivity threshold . DESIGN: Analysis of databases of laboratory registers, patient records and the diagnostic yield of sputum collection strategies . RESULTS: Scanty smears constituted about 10% of suspect and almost 50% of follow-up smears . In suspect series, 10% of scanty 1-9/100 were not confirmed by another positive or scanty AFB sputum, compared to 7.5% of results at the current cut-off value of 10/100 . Considering such results as positive by adopting a lower cut-off as low as the 1/100 used in the ATS scale added 1.5% false positives at the most . In return, the gain in confirmed positive cases was up to 10%, and that in positive results exceeded the incremental yield of the third diagnostic sputum . Significance of scanty follow-up smears at the end of the intensive phase was suggested by their association with treatment failure and unfavourable outcome overall . CONCLUSIONS: Scanty results (IUATLD/WHO scale) are not rare and should not be ignored . Adoption of a considerably lower positivity threshold would be appropriate in control programmes where basic conditions for reliable AFB microscopy, including regular quality assessment, are present.

Nucleic Acids Res, 2004 Jul 16, 32(13), 3781 - 91 Print 2004.
Where does bacterial replication start? Rules for predicting the oriC region; Mackiewicz P et al.; Three methods, based on DNA asymmetry, the distribution of DnaA boxes and dnaA gene location, were applied to identify the putative replication origins in 120 chromosomes . The chromosomes were classified according to the agreement of these methods and the applicability of these methods was evaluated . DNA asymmetry is the most universal method of putative oriC identification in bacterial chromosomes, but it should be applied together with other methods to achieve better prediction . The three methods identify the same region as a putative origin in all Bacilli and Clostridia, many Actinobacteria and gamma Proteobacteria . The organization of clusters of DnaA boxes was analysed in detail . For 76 chromosomes, a DNA fragment containing multiple DnaA boxes was identified as a putative origin region . Most bacterial chromosomes exhibit an overrepresentation of DnaA boxes; many of them contain at least two clusters of DnaA boxes in the vicinity of the oriC region . The additional clusters of DnaA boxes are probably involved in controlling replication initiation . Surprisingly, the characteristic features of the initiation of replication, i.e . a cluster of DnaA boxes, a dnaA gene and a switch in asymmetry, were not found in some of the analysed chromosomes, particularly those of obligatory intracellular parasites or endosymbionts . This is presumably connected with many mechanisms disturbing DNA asymmetry, translocation or disappearance of the dnaA gene and decay of the Escherichia coli perfect DnaA box pattern.

Int J Exp Pathol, 2004 Jun, 85(3), 135 - 45
In situ analysis of lung antigen-presenting cells during murine pulmonary infection with virulent Mycobacterium tuberculosis; Pedroza-Gonzalez A et al.; Scarce information exists about the role of lung antigen-presenting cells (APCs) in vivo during pulmonary tuberculosis . As APCs activate cellular immunity, following intratracheal inoculation with virulent Mycobacterium tuberculosis, we assessed in situ lung APC recruitment, distribution, granuloma involvement, morphology and mycobacterial burden by using MHC-CII, CD14, scavenger receptor class A (SRA), the murine dendritic cell (DC)-restricted marker CD11c and Ziehl-Neelsen staining . CD11c(+) DC and CD14(+) cell recruitment into lungs appeared by day 14, continuing until day 60 . MHC-CII(+) cells increased since day 7, persisting until day 60 . Thus, virulent mycobacteria delays (14-21 days) lung APC recruitment compared to model antigens and nonvirulent bacilli (24-48 h) . Regarding granuloma constitution, highly bacillary CD14(+) and SRA(+) cells were centrally located . MHC-CII(+) cells were more peripheral, with less mycobacteria . CD11c(+) cells were heterogeneously distributed within granulomas, with scarce bacilli . When labelling lung suspensions for MHC-CII and classifying cells as macrophages or DC, then staining for Ziehl-Neelsen, a remarkable segregation was found regarding bacillary burden . Most macrophage-like cells contained numerous bacilli, while DC had no or scarce mycobacteria . This implies differential APC contributions in situ during pulmonary tuberculosis regarding mycobacterial uptake, granuloma involvement and perhaps bacillary growth.

Mol Microbiol, 2004 Aug, 53(3), 829 - 42
Dimer-induced signal propagation in Spo0A; Muchova K et al.; Spo0A, the response regulator protein controlling the initiation of sporulation in Bacillus, has two distinct domains, an N-terminal phosphoacceptor (or receiver) domain and a C-terminal DNA-binding (or effector) domain . The phosphoacceptor domain mediates dimerization of Spo0A on phosphorylation . A comparison of the crystal structures of phosphorylated and unphosphorylated response regulators suggests a mechanism of activation in which structural changes originating at the phosphorylatable aspartate extend to the alpha4beta5alpha5 surface of the protein . In particular, the data show an important role in downstream signalling for a conserved aromatic residue (Phe-105 in Spo0A), the conformation of which alters upon phosphorylation . In this study, we have prepared a Phe-105 to Ala mutant to probe the contribution of this residue to Spo0A function . We have also made an alanine substitution of the neighbouring residue Tyr-104 that is absolutely conserved in the Spo0As of spore-forming Bacilli . The spo0A(Y104A) and spo0A(F105A) alleles severely impair sporulation in vivo . In vitro phosphorylation of the purified proteins by phosphoramidate is unaffected, but dimerization and DNA binding are abolished by the mutations . We have identified intragenic suppressor mutations of spo0A(F105A) and shown that these second-site mutations in the purified proteins restore phosphorylation-dependent dimer formation . Our data support a model in which dimerization and signal transduction between the two domains of Spo0A are mediated principally by the alpha4beta5alpha5 signalling surface in the receiver domain .

Int J Vitam Nutr Res, 2004 Mar, 74(2), 144 - 6
Nutrient supplementation as adjunct therapy in pulmonary tuberculosis; Chandra RK; The study examined the effect of supplementation with multivitamins and trace elements on microbiological and radiological recovery in patients with pulmonary tuberculosis . Forty-four patients aged 28-50 years were diagnosed with active pulmonary tuberculosis based on X-ray of the chest and smear examination of the sputum for the presence of acid-fast bacilli . They were all treated for six months with a standard anti-tuberculosis regimen that has been found to be effective worldwide for disease control . The subjects were randomized to receive either a multivitamin-trace element supplement or a placebo containing calcium . The two groups were matched on all relevant confounding variables . At two months into the treatment, the group that was supplemented with a multivitamin-trace element preparation showed a significant reduction in the number of individuals with sputum smear positive for acid-fast bacillus: two out of 22 individuals, compared with seven out of 22 among placebo-treated controls (p = 0.028, Fisher's test) . It is concluded that patients with tuberculosis should be supplemented with a suitable micronutrient preparation that contains optimum amounts of all vitamins and trace elements that have been documented to enhance the immune response.

Bull Soc Pathol Exot, 2004 May, 97(2), 127 - 8
{Analysis of the diagnostic criteria used in childhood tuberculosis in a Cote d'Ivoire hospital}; Adonis-Koffy L et al.; Based on a retrospective study the authors analyzed the diagnostic criteria used in pediatric department in Yopougon CHU (teaching hospital), from January 1996 to December 2002 . Fifty children, aged of 1 month to 15 years, have been studied . The tuberculosis contact was found in 18% . The diagnosis of tuberculosis was accurate in 32% and it was based on presumptive arguments in 68% . The pulmonary examination and pulmonary radiographs seem to be good criteria for the tuberculosis diagnosis . The pulmonary examination found an abnormality in 96%, and the radiographs found a pathological picture in 85% of cases . The skin test was positive in 42% . The Ziehl-Neelsen coloration was used to look for the acid-fast bacilli and it was positive in 41% . But the two last examinations were not reliable in the case of HIV infection . The skin test which is very important for the diagnosis of tuberculosis is often negative among HIV infected children because of their anergy . On the other hand, the Ziehl-Neelsen coloration is based on the recognition of the acid-fast bacillus, which is not specific of the Mycobacterium tuberculosis . In our area the prevalence of HIV/AIDS is high, the atypical pneumonia with Mycobacterium were also frequent and may reveal a wrong positive diagnosis for the tuberculosis diagnosis, as they are also acid-fast bacillus.

Kaohsiung J Med Sci, 2004 Jun, 20(6), 302 - 7
Molecular and histopathologic evidence for systemic infection by Mycobacterium bovis in a patient with tuberculous enteritis, peritonitis, and meningitis: a case report; Wei CY et al.; Mycobacterium bovis infection has been reported in several patients with AIDS in other countries . The prevalence of tuberculosis in Taiwan is higher than the World Health Organization standard . However, reports of M . bovis infection are rare . A 47-year-old male had the habit of drinking uncooked fresh deer's blood and unpasteurized deer's milk . He suffered from acute abdominal pain and underwent emergency laparotomy . Pathology demonstrated tuberculosis enteritis with colon perforation . The molecular diagnosis by nested polymerase chain reaction assay and single-strand conformation polymorphism assay showed M . bovis infection in the small intestine, mesenteric lymph nodes, and cerebrospinal fluid (CSF) . Our results suggest that the most likely portal of entry of M . bovis is the gastrointestinal rather than the respiratory tract . Ingested M . bovis from unpasteurized deer's milk probably entered the mucosal macrophages of the intestine and then the draining mesenteric lymph nodes . As immunity declined, bacilli from the mesenteric lymph nodes disseminated to other organs and into the CSF.

Endocr Pract, 2002 Sep-Oct, 8(5), 365 - 9
Addisonian crisis and tuberculous epididymo-orchitis; Kon YC et al.; OBJECTIVE: To describe a case of acute primary adrenal insufficiency in which tuberculosis was subsequently detected as the etiologic factor when the patient presented with tuberculous epididymo-orchitis . METHODS: A case of acute primary adrenal insufficiency associated with bilaterally enlarged adrenal glands is reported, along with the subsequent finding of a scrotal mass diagnosed as tuberculous epididymo-orchitis . Diagnosis, adrenal function, and results of imaging studies after institution of antituberculous treatment are discussed . RESULTS: A 41-year-old Egyptian man, who had immigrated to the United States 5 years previously, had acute psychosis and addisonian crisis . A substantially increased early morning level of plasma adrenocorticotropic hormone and a low level of serum cortisol confirmed the diagnosis of primary adrenal insufficiency . Both adrenal glands were enlarged but without calcification on computed tomography . A previous bacille Calmette-Guerin vaccination complicated the interpretation of a positive tuberculin skin test result . Both lungs were clear on chest radiography and computed tomography . Seven months later, the patient had a left scrotal mass and underwent radical orchiectomy . Examination of the pathology specimen showed caseous granulomatous inflammation and necrosis, and acid-fast bacilli were identified . Culture was positive for Mycobacterium tuberculosis . CONCLUSION: In a patient from a country where tuberculosis is endemic, tuberculosis should be considered in the differential diagnosis when primary adrenal insufficiency is detected, especially in association with enlarged or calcified adrenal glands . Extra-adrenal tuberculous involvement should be actively sought because it may provide indirect microbiologic or histologic clues . Other than the lungs, special attention should be paid to the genitourinary system.

Minerva Pediatr, 2004 Feb, 56(1), 119 - 22
{Scrofuloderma . a clinical case}; Forgione P et al.; Scrofuloderma is a form of colliquative cutaneous tuberculosis resulting from the spread of an underlying focus, generally represented by lymphnodes; osteoarticular tubercular locations or epididimus locations can also lead to ulcerative cutaneous involvement . We report the case of a female patient aged 12 who had been in Italy for 15 days following her arrival from Marocco . In the left clavicular region she presented an ulcerated lesion with palpable lymphnodes on the corresponding side of the neck . Histopathological examination of one of the involved lymphnodes suggested a mycobacteriosis; differential diagnosis was carried out between MAIS (M . avium, M . intracellulare, M . scrofulaceum) group mycobacteria infection and tuberculosis . Bacteriological research in the lymphnode of alcohol-acid resistant bacilli gave a negative result, while cultural examination and protein chain reaction pointed to M . tuberculosis . The patient was subjected to combined treatment based on rifampycin, isoniazide, etambutolol and pyrazinamide . At the present time, tuberculosis is an important public health problem in developing countries . In western countries such as the United Kingdom, which have been open to immigration for a longer time, scrofuloderma is present with higher prevalence in immigrants from Asia and Africa; in these immigrant populations, this tubercular form involves a wide age segment between the ages of 10 and 50 . In the autochthonous population the highest incidence is in subjects aged more than 50 . In Italy too, extra-communitary immigration has also contributed, with a delay compared to other western countries, to bring tuberculosis back into the public eye after a period of decades during which it was wrongly considered to have disappeared.

Chest, 2004 Jul, 126(1), 259 - 67
Transbronchial needle aspiration in diagnosing intrathoracic tuberculous lymphadenitis; Bilaceroglu S et al.; STUDY OBJECTIVE: To assess the role of transbronchial needle aspiration (TBNA) in diagnosing intrathoracic tuberculous lymphadenitis (TB-LA) . METHODS: In a tertiary referral center for thoracic medicine and surgery, using a CT scan as a guide, transbronchial aspirates were obtained with a 19-gauge flexible histology needle in consecutively enrolled patients with sputum smears negative for acid-fast bacilli, and with isolated mediastinal or hilar adenopathy suspicious for tuberculosis (TB) . RESULTS: Of 84 eligible patients who were all found to be HIV-negative, 63 (75%) cases of TB were diagnosed by TBNA (histology, 48 patients {76%}; cytology, 9 patients {14%}; and bacteriologic studies, 21 patients {33%; smear, 8 patients; culture, 17 patients}) . TBNA was used to diagnose sarcoidosis in two patients, angioimmunoblastic lymphadenopathy in one patient, and Hodgkin lymphoma in one patient . In the 17 TBNA-negative patients, the results of transthoracic needle aspiration were positive in 12 patients (TB, nine patients; lung cancer, two patients; sarcoidosis, one patient), the results of mediastinoscopy were positive in three patients (TB, two patients; Hodgkin lymphoma, one patient), and the results of thoracotomy were positive in two patients (TB, two patients) . Thus, 76 patients had TB, and all responded to anti-TB treatment . TB was corroborated by culture or histology of another specimen obtained from subsequently developed lesions in 40 patients (53%) during anti-TB treatment or posttreatment follow-up . TBNA was immediately diagnostic in 59 patients (78%), and exclusively in 52 patients (68%), among all bronchoscopic procedures and prebronchoscopic sputum studies . Sensitivity, specificity, positive and negative predictive values, and accuracy of TBNA for TB were 83%, 100%, 100%, 38%, and 85%, respectively . The only complication, self-limiting hemorrhage of < 30 mL volume, occurred in 65 patients (77%), with a volume of < 5 mL in 59 patients (70%) . CONCLUSION: TBNA is efficient and safe in the bacteriologic and pathologic diagnosis of intrathoracic TB-LA in HIV-negative and sputum smear-negative patients.

Indian J Med Res, 2004 Jun, 119(6), 259 - 66
Detecting mycobacteraemia for diagnosing tuberculosis; David ST et al.; BACKGROUND & OBJECTIVES: In human immunodeficiency virus (HIV) infected persons with pulmonary tuberculosis (TB), sputum may not always show acid fast bacilli (AFB) . Moreover, in most cases of suspected extrapulmonary TB (irrespective of HIV status) mycobacteria-containing material is not readily available for investigation . This study evaluated whether blood culture for Mycobacterium tuberculosis bacteraemia (mycobacteraemia) help in diagnosing TB in such cases . METHODS: A total of 93 consecutive subjects with a clinical diagnosis of tuberculosis with or without laboratory confirmation, 42 with and 38 without coexisting HIV infection, and 13 patients with HIV infection without clinical evidence of TB were enrolled . Mycobacterial blood cultures were done using lysis centrifugation technique followed by subculturing onto the modified Lowenstein-Jenson medium (LJ-1) and Selective Kirchner's medium followed by subculturing onto the modified Lowenstein-Jenson medium (LJ-2, LJ-3) . RESULTS: Of the 15 (16.2%) subjects with evidence of mycobacteremia in 4 (26.7%) blood was the first/ only source of diagnosing TB . Among 80 patients with clinical diagnosis of TB whether supported by laboratory tests or not, 14 (17.5%) had mycobacteraemia . Among the 21 HIV infected patients with laboratory proven TB, 9 (43%) had mycobacteraemia . INTERPRETATION & CONCLUSION: Blood culture appears to be a useful additional test to diagnose TB in persons with HIV infection . In patients without HIV infection, but with clinical picture compatible with TB, blood culture for mycobacteraemia may occasionally help in the diagnosis . We recommend the use of the lysis centrifugation technique followed by direct smear of the sediment along with inoculation of the sediment into both modified Lowenstein-Jenson medium and the Selective Kirchner's medium with subsequent subculturing onto the modified Lowenstein-Jenson medium for mycobacterial blood culture for detecting mycobacteraemia.

J Clin Microbiol, 2004 Jul, 42(7), 3369 - 70
Septic arthritis of the knee due to Fusobacterium necrophorum; Sonsale PD et al.; Gram-negative, anaerobic bacilli are unusual organisms to be isolated in cases of acute septic arthritis . We report the isolation of Fusobacterium necrophorum from joint aspirate in a case of acute septic arthritis, which presented 3 weeks after the drainage of a dental abscess.

J Clin Microbiol, 2004 Jul, 42(7), 3284 - 7
LightCycler-based differentiation of Mycobacterium abscessus and Mycobacterium chelonae; Sedlacek L et al.; In this study we introduce a rapid procedure to identify Mycobacterium abscessus (types I and II) and M . chelonae using LightCycler-based analysis of the hsp65 gene . Results from 36 clinical strains were compared with hsp65 gene restriction analysis and biochemical profiles of bacilli . As all three methods yielded identical results for each isolate, this procedure offers an excellent alternative to previously established nucleic acid amplification-based techniques for the diagnosis of mycobacterial diseases.

J Clin Microbiol, 2004 Jul, 42(7), 3240 - 7
Molecular genotyping of a large, multicentric collection of tubercle bacilli indicates geographical partitioning of strain variation and has implications for global epidemiology of Mycobacterium tuberculosis; Ahmed N et al.; Tuberculosis continues to be a major killer disease, despite an all-out effort launched against it in the postgenomic era . We describe here the population structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more than 1,100 independent isolates from 11 different countries . The bacterial strains were genotyped based on a total of 136 +/- 1 different FAFLP markers at the genome sequence interface, with details on IS6110 profiles, drug resistance status, clinicopathological observations, and host status integrated into the analysis process . The strains were found to cluster with possible geographic affinities, including the parameters of host species type, IS6110 profile, and drug susceptibility status . Of the five most commonly amplified fragment sets (or amplitypes), type A predominated in strains of mixed origin, deposited in The Netherlands; type B was exclusively observed for Indian isolates; type C was found mainly in strains from Peru and Australia; and types D and E predominated in European strains from France and Italy . The amplitypes were independent of certain large sequence polymorphisms representing two important deletions, TbD1 and Rd9 . It appears that M . tuberculosis has a high genomic diversity with a possible geographic evolution . This may have occurred due to specific genomic deletions and synonymous substitutions selected rigorously against host defenses and environmental stresses on an evolutionary timescale . The genotypic data reported here are additionally significant for genotype-phenotype correlations and for determining whether pathogen diversity is a reflection f the host population diversity.

J Clin Microbiol, 2004 Jul, 42(7), 3036 - 40
Improved sensitivity of nucleic acid amplification for rapid diagnosis of tuberculous meningitis; Johansen IS et al.; Early diagnosis of tuberculous meningitis (TBM) is essential for a positive outcome; but present microbiological diagnostic techniques are insensitive, slow, or laborious . We evaluated the standard BDProbeTec ET strand displacement amplification method (the standard ProbeTec method) for the detection of Mycobacterium tuberculosis complex organisms in parallel with the ProbeTec method with a modified pretreatment procedure with 101 prospectively collected cerebrospinal fluid specimens from 94 patients with suspected TBM . By the modified method, the sample-washing step was omitted . A definitive diagnosis was attained by culture . Thirteen specimens from 12 patients were culture positive for M . tuberculosis complex organisms; three specimens (23%) were microscopy positive for acid-fast bacilli . Among the culture-positive specimens, the standard ProbeTec method was positive for 8 (61.5%) and the modified assay was positive for 10 (76.9%) . The overall specificity by both procedures was 98.8% compared to the results of culture . After discrepancy analysis, conducted by reviewing the patients' previous laboratory data, the specificity increased to 100% . If the cutoff value for respiratory specimens was adjusted from the recommended value of 3,400 to 1,000, the sensitivity of the modified procedure increased to 84.7%, with unchanged specificity . Results were obtained in 3 to 4 h . The new pretreatment procedure with the ProbeTec assay described here provides a rapid, simple, and sensitive tool for the diagnosis of TBM.

Tuberk Toraks, 2004, 52(2), 145 - 9
{The value of bronchial lavage in patients with radiologically suggestive pulmonary tuberculosis with no sputum production and gastric lavage smear negativity}; Kartaloglu Z et al.; We assessed whether acid-fast bacilli (AFB) investigation in bronchial lavage (BL) contributes to diagnosis in patients with gastric lavage smear negative and radiologically suggestive of pulmonary tuberculosis . Eighty-three patients were recruited for the study, five cases were excluded due to diagnosis of inactive disease or non-tuberculosis disease . The remaining 78 patients were evaluated . All patients were unable to expectorate sputum and their gastric lavages were negative for AFB . BL was performed for the detection of Mycobacterium tuberculosis in all patients . Bronchial lavage smear were positive in 15.4%(12 patients) . BL culture positivity was 58.3%(42 patients) and gastric lavage culture positivity was 33.3%(26 patients) . Eighteen cases had both gastric lavage and BL culture positivity . BL culture was positive in 24 cases who had gastric lavage culture negativity . We suggest that in cases who do not produce sputum and whose gastric lavage smears are negative; BL should be performed for diagnosis of pulmonary tuberculosis.

Vet Pathol, 2004 Jul, 41(4), 433 - 7
Invasive ability of Escherichia coli O18 isolated from swine neonatal diarrhea; Wada Y et al.; Neonatal diarrhea occurred at two swine breeding farms in Hokkaido . Ten piglets aged 2 to 4 days were examined . Grossly, significant changes were confined to the small intestine . The mucous membrane was muddy and thickened . The intraluminal contents from the jejunum to the colon were liquid and yellow . In the small intestine, numerous Gram-negative bacilli preferentially adhered to the apex of villi . The mucosa was erosive with villous atrophy . There were bacilli also in the lamina propria and in the cytoplasm of degenerated enterocytes . Nonhemolytic Escherichia coli strains, belonging to serogroup E . coli O18 and possessing K88 fimbriae, were isolated from the small intestine . They could not be classified into any of the diarrheagenic E . coli groups because of the absence of genes of LT, STh, STp, VT1, VT2, eae, invE, and ipaH . After inoculation of the isolates on HEp-2 cells, some bacilli were engulfed by cytoplasmic projections resembling membrane ruffles and subsequently were localized in cytoplasmic vacuoles or free in the cytoplasm . These findings support the view that the present E . coli O18 is a new invasive strain enteropathogenic to piglets.

Vet Pathol, 2004 Jul, 41(4), 388 - 97
Detection of mycobacteria and chlamydiae in granulomatous inflammation of reptiles: a retrospective study; Soldati G et al.; A retrospective study on reptile tissues presenting with granulomatous inflammation was performed to detect the possible presence of mycobacteria and chlamydiae in these lesions . Ninety cases including 48 snakes, 27 chelonians, and 15 lizards were selected . Mycobacteria were detected by Ziehl-Neelsen (ZN) staining and a broad-range polymerase chain reaction (PCR) followed by DNA sequencing . To detect chlamydiae, immunohistochemistry with monoclonal antibodies against chlamydial lipopolysaccharide (LPS) and a Chlamydiales order-specific PCR and sequencing were applied . Acid-fast bacilli were found in 14 cases (15.6%) by ZN staining and in 23 cases (25.6%) by PCR . Sequence analysis revealed the presence of Mycobacteria other than Mycobacterium tuberculosis complex (MOTT) . Chlamydial LPS antigen was observed within granulomas from five samples (5.6%), whereas the PCR screen revealed 58 positive cases (64.4%) . Of these, 9 cases (10%) showed 98-99% similarity to Chlamydophila (Cp.) pneumoniae and 49 cases (54.4%) displayed a high similarity (88-97%) to the newly described "Chlamydia-like" microorganisms Parachlamydia acanthamoebae and Simkania negevensis . Results from this study confirm, on the one hand, that MOTT are probably the most important infectious etiology for granulomatous inflammation in reptiles . On the other hand, they indicate that chlamydia infects reptiles and that Cp . pneumoniae should be considered an etiological agent of granulomatous lesions of reptiles . Because both MOTT and Cp . pneumoniae are human pathogens, the potential of zoonotic transmission from reptiles to humans has to be considered . In contrast, the significance of Chlamydia-like isolates remains completely open, and further studies are needed to evaluate their role.

J Antimicrob Chemother, 2004 Aug, 54(2), 538 - 41 Epub 2004 Jul 01.
Real-time PCR for universal antibiotic susceptibility testing; Rolain JM et al.; OBJECTIVES: Determination of bacterial antimicrobial susceptibility is usually performed using phenotypic methods . In this study, we developed a universal 16S rRNA and rpoB quantitative PCR assay for susceptibility testing of bacteria commonly isolated in clinical microbiology laboratories . METHODS: Antibiotic susceptibilities for 24 bacterial strains of various species were tested by real-time quantitative PCR assay and by conventional methods . Quantification of DNA copies of either the 16S RNA genes or rpoB were recorded over time in the presence or absence of antibiotics to determine the bacterial growth kinetics and the optimal testing time . RESULTS: Molecular results for antibiotic susceptibility or resistance were in accordance with those obtained using a standard macrodilution broth assay . The method was reproducible, sensitive and rapid (2 h for Gram-negative bacilli and 4 h for Gram-positive cocci) . Moreover, this assay was also able to determine the antibiotic susceptibilities of fastidious bacteria, such as mycobacteria, within 5 days . CONCLUSIONS: These results demonstrate that molecular detection of bacteria could be more rapid than phenotypic methods for antibiotic susceptibility testing.

J Coll Physicians Surg Pak, 2004 Feb, 14(2), 105 - 7
Genus and species-specific IgG and IgM antibodies for pulmonary tuberculosis; Butt T et al.; OBJECTIVE: To evaluate three different enzyme immunoassays for serological diagnosis of pulmonary tuberculosis and to compare their diagnostic accuracy in different combinations . DESIGN: A non-interventional comparative study . PLACE AND DURATION OF STUDY: The study was carried out at the Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi between April and September 2001 . SUBJECTS AND METHODS: Sera from patients suffering from pulmonary tuberculosis (n=94) with sputum positive for acid fast bacilli (AFB) and sera from control group of healthy individuals (n=90) with sputum negative for AFB were tested by Pathozyme-Myco G EIA, Pathozyme-TB Complex Plus EIA and Pathozyme Myco M EIA kits for the genus-specific IgG and IgM, and the species-specific IgG antibodies against antigens of Mycobacterium tuberculosis . RESULTS: The detection of IgG against genus-specific antigens by Pathozyme-Myco G had a sensitivity of 46% and a specificity of 93%, of IgG against species-specific antigens by Pathozyme-TB Complex Plus had a sensitivity of 64% and specificity of 97% and of IgM against genus-specific antigens by Pathozyme Myco M had a sensitivity of 67% and specificity of 98% . When the results of these immunoassays were evaluated in combination, their sensitivity improved . Combination of genus-specific IgM and species-specific IgG yielded best results with a sensitivity of 87% and specificity of 93% . CONCLUSION: The sensitivity of serological diagnosis of tuberculosis is low, but it can be increased by utilizing a combination of several antigens.

J Coll Physicians Surg Pak, 2004 Apr, 14(4), 221 - 4
Primary sinonasal tuberculosis in north-west Pakistan; Nawaz G et al.; OBJECTIVE: To record the frequency of primary involvement of nose and paranasal sinuses with tuberculosis in today's situation in the north-west region of Pakistan . DESIGN: An observational study . PLACE AND DURATION OF STUDY: The Department of ENT and Head and Neck Surgery, Khyber Teaching Hospital, Peshawar from 1986 to 1996 . PATIENTS AND METHODS: A total of ten cases of primary sinonasal tuberculosis were included . The inclusion criteria were biopsy and acid-fast bacilli (AFB) examination after Ziel Neelsen (ZN) staining . Patients were put on anti-tuberculous chemotherapy . Response to the therapy and compliance of the patients were studied through follow up . Patients were admitted and offered surgical treatment wherever needed . RESULTS: The primary sinonasal tuberculosis affected mainly young adults (18-60 years), both genders almost equally . Majority (80%) of the patients belonged to far-flung rural areas and all (100%) were poor . More frequent presenting features were granular lesion and mass in the nose (40%), epistaxis (30%), septal perforation (30%), external deformity (30%), palpable cervical lymph nodes (30%) and others . All the cases were diagnosed microscopically . Compliance to treatment was not good . CONCLUSION: The incidence of primary tuberculosis of nose and paranasal sinuses has risen in the recent past . The patients manifested no evidence of pulmonary tuberculosis.

Int J Hematol, 2004 May, 79(4), 334 - 6
Tuberculosis-associated hemophagocytic syndrome in a hemodialysis patient with protracted fever; Chien CC et al.; Hemophagocytic syndrome (HPS) is a clinicopathological reflection of uncontrolled activation of macrophages . To our knowledge, only a few cases of tuberculosis-associated HPS in hemodialysis have been reported in the English literature . We report a case of tuberculosis-associated HPS during hemodialysis . Bone marrow aspiration showed histiocytosis with hemophagocytosis; in addition, results of acid-fast staining and polymerase chain reaction showed the presence of acid-fast bacilli . Mycobacterium tuberculosis was subsequently cultured from sputum . The patient received late treatment with antituberculosis agents combined with intravenous immunoglobulin and had a poor response . On the basis of the results in this case, we recommend early bone marrow and tuberculous examination for patients undergoing maintenance hemodialysis who have fever of unknown origin.

J Eukaryot Microbiol, 2004 May-Jun, 51(3), 291 - 300
Symbiotic innovation in the oxymonad Streblomastix strix; Leander BS et al.; Streblomastix strix is an enigmatic oxymonad found exclusively in the hindgut of the damp-wood termite Zootermopsis . Streblomastix has a number of unusual morphological characters and forms a complex but poorly understood symbiosis with epibiotic bacteria . Here we described the ultrastructure of S . strix, with emphasis on the axial cytoskeleton and cell-cell associations, in its normal state and when treated with antibiotics . In untreated cells, epibiotic bacteria were orderly arranged end-to-end on six or seven longitudinal vanes, giving S . strix a stellate appearance in transverse section . The epibiotic bacteria were unusually long bacilli of at least three different morphotypes . Bacteria adhered to the oxymonad host by distinct cell-cell junctions that protruded between the poles of adjacent epibiotic bacteria . Treating termites with the antibiotic carbenicillin led to the loss of most (but not all) of the bacteria and the transformation of S . strix from a long slender cell to a teardrop-shaped cell, where the axostyle was compacted and became bifurcated near the posterior end.

Int J Lepr Other Mycobact Dis, 2004 Mar, 72(1), 16 - 26
IL-10 treatment of macrophages bolsters intracellular survival of Mycobacterium leprae; Fukutomi Y et al.; In these studies, metabolically active Mycobacterium leprae were maintained for as long as 8 weeks in monolayer cultures of mouse peritoneal macrophages (MPhi) . Supplemental IL-10, but not TGF-beta, bolstered, directly or indirectly, M . leprae metabolism in mouse MPhi . In the cell culture system temperature setting is extremely important and 31 to 33 degrees C incubation temperature was more permissive than 37 degrees C . Acid fast staining and transmission electron microscopy (TEM) of intracellular M . leprae revealed visible elongation of bacilli cultured under the above ideal conditions.

Expert Opin Pharmacother, 2004 Jul, 5(7), 1463 - 70
Therapeutic management of endobronchial tuberculosis; Rikimaru T; Endobronchial tuberculosis (EBTB) is defined as tuberculous infection of the tracheobronchial tree . Common symptoms are cough, haemoptysis, sputum production, wheezing, chest pain and fever in active disease and dyspnoea and wheezing in the fibrous stage . This form of tuberculosis is difficult to diagnose because the lesion is not evident in the chest radiograph, frequently delaying treatment . Computed tomography is very useful in evaluating bronchial lesions such as stenosis or obstruction . The most important goal of treatment in active EBTB is eradication of tubercle bacilli . The second most important goal is prevention of bronchial stenosis . Corticosteroid therapy for the prevention of bronchial stenosis in EBTB remains controversial . However, the healing time of ulcerous lesions was shorter and bronchial stenosis was less severe, in patients treated with aerosol therapy, consisting of streptomycin 100 mg, a corticosteroid (dexamethasone 0.5 mg) and naphazoline 0.1 mg administered twice-daily along with conventional oral therapy . In inactive disease, treatment to restore full patency is appropriate . As steroids or other medications are unable to reverse stenosis from fibrous disease, airway patency must be restored mechanically by surgery or endobronchial intervention . Effectiveness and complications remain important issues with the mechanical techniques as use and evaluation continue . Corticosteroid therapy for prevention of bronchial stenosis in EBTB remains controversial . Our observations suggest that progression of bronchial stenosis can be prevented in patients who are treated with aerosol therapy with corticosteroids.

Kekkaku, 2004 May, 79(5), 355 - 9
{A study on cases developed pulmonary tuberculosis after receiving gastrectomy}; Yagi T et al.; OBJECTIVE: Patients who had undergone gastric resection are considered to be high risk of developing tuberculosis . We investigated the factors leading to pulmonary tuberculosis after gastrectomy . MATERIALS AND METHODS: We retrospectively examined 654 pulmonary tuberculosis patients discharged from Chiba-East National Hospital from January 1999 to December 2001 . RESULTS: Fifty-five patients (31-84 years old, mean 63.5 +/- 12.5 years, 48 males and 7 females) had the history of gastric resection . The proportion of patients receiving gastrectomy among patients with pulmonary tuberculosis was 8.4 percent . The mean age of patients received gastric resection was 50.2 +/- 16.6 years, and the mean interval from gastrectomy to the development of pulmonary tuberculosis was 13.6 +/- 11.0 years . On admission to our hospital, 34 out of 55 cases were smear positive by sputum examination for acid-fast bacilli and 39 cases had cavitary lesions on chest X-ray . Gastrectomy was done due to carcinoma of the stomach in 31 cases, peptic ulcer in 21 cases, adenomatous polyp in two cases, and accidental injury in one case . Out of total 55 cases, 52 patients improved, but three cases died of pulmonary tuberculosis . None had the recurrence of carcinoma of the stomach . Body weight, Body mass index, Prognostic nutritional index (PNI; 10 x serum albumin concentration + 0.005 x peripheral lymphocyte count) which was proposed by Onodera, serum albumin level and serum total cholesterol level were lower in the gastrectomy group than in the non-gastrectomy group . The odds ratio of developing tuberculosis among gastrectomy patients compared with the appropriate controls in 30 to 59 year-old-men was 3.8 . CONCLUSION: This study confirms that gastrectomy is one of the risk factors of developing tuberculosis in 30 to 59 year-old-men . However, whether gastrectomy in itself is a risk factor or whether it is secondarily associated with another risk factor such as underweight status and/or inadequate nutrition following surgery remains unclear.

Kekkaku, 2004 May, 79(5), 349 - 54
{Tuberculous lymphadenitis: a clinical study of 23 cases}; Ueda T et al.; INTRODUCTION: Tuberculous lymphadenitis is a relatively rare disease in adults . In the absence of pulmonary tuberculosis, tuberculous lymphadenitis is very difficult to differentiate from other diseases . We described our experiences of patients with tuberculous lymphadenitis . RESULTS: We diagnosed 23 patients with tuberculous lymphadenitis out of 207 patients with tuberculosis . Their ages ranged from 18 to 99 years (mean, 45.7 years), and the male-to-female ratio was 7:16 . The most common complaints were cervical mass and fever . With the exception of two patients, all diagnosed patients had a strong positive skin test to tuberculin . Observing the site of affected lymph nodes, 16 patients had cervical node involvement, 3 patients had axillary node involvement, 7 patients had mediastinal node involvement, 3 patients had hilar node involvement, 3 patients had abdominal node involvement, and 1 patient had inguinal node involvement . Fifteen patients had neither hilar nor mediastinal node involvement . Eleven patients had no tuberculous lesions other than lymphadenitis . Seven patients underwent biopsy of the lymph nodes . Four of these patients had the evidence of acid-fast bacilli . The remaining three patients were also diagnosed histologically . Five patients underwent fine needle aspiration . Two of them had the evidence of acid-fast bacilli . Acid-fast bacilli were detected in 10 out of 16 sputum samples and in 1 out of 2 pleural effusion samples . Five patients were diagnosed clinically by image (Computed tomography etc.) and by therapeutic effect . Eleven cases underwent contrast-enhanced computed tomography (CT) of the lymph nodes . Seven cases showed central low attenuation with peripheral rim enhancement, whereas the other four cases showed homogeneous attenuation . All patients received chemotherapy for a mean duration of 14.5 months (range, 6-30 years) with apparent improvement, but 1 patient relapsed . CONCLUSION: Tuberculous lymphadenitis remains one of important targets for the differential diagnosis of lymphadenopathy . It is essential that a peripheral lymph node biopsy be performed and examined either histologically and/or microbiologically . A tuberculin skin test and contrast-enhanced CT imaging should also be performed.

Rev Chir Orthop Reparatrice Appar Mot, 2004 Jun, 90(4), 337 - 45
{Tuberculosis of the wrist . Symptoms and outcome in eleven cases}; Benchakroun M et al.; PURPOSE OF THE STUDY: We present our experience with a rare localization of tuberculosis, the wrist, focusing on symptoms and outcome after treatment . MATERIAL AND METHODS: Our series included eleven patients, eight men and three women, mean age 42 Years, who presented tuberculosis of the wrist . Tuberculosis was known in four patients who were being treated and a context of tuberculosis was recognized in three others . One patient on long-term corticosteroid therapy was immunodepressed . Mean time from symptom onset to consultation was fifteen months indicating a slow and progressive disease process . An inflammatory syndrome was noted in nine patients . Based on the standard x-rays, the David-Chausse classification was: stage I n=1; stage II n=1; stage III n=3; stage IV n=4 . The AP view of the wrist was normal in two patients . Diagnosis of tuberculosis was confirmed on the surgical biopsy specimen which revealed epithelio-gigantocellulary granuloma with caseous necrosis . In only five patients Koch bacilli developed in culture on Lowenstein-Jensen . Patients were given anti-tuberculous antibiotics and the wrist was immobilized in a plaster splint . RESULTS: Mean follow-up was two years . The disease course was blunted by the antituberculosis treatment . Surgical drainage was only required to clear abscesses . Wrist stiffness was frequent and had a significant functional impact . DISCUSSION: These eleven cases of a rare localization of tuberculosis illustrate the slow progressive course of clinical symptoms and radiological signs of tuberculosis, emphasizing the difficulties encountered in establishing early diagnosis of such isolated non-abscessed localizations . Anti-tuberculous treatment is effective but the functional outcome depends on early diagnosis before the development of radiological evidence of joint destruction.

Ocul Immunol Inflamm, 2004 Mar, 12(1), 65 - 7
A case of infected scleral buckle with Mycobacterium chelonae associated with chronic intraocular inflammation; Oz O et al.; PURPOSE: To describe a unique case of chronic intraocular inflammation secondary to scleral buckle infection with Mycobacterium chelonae that was successfully treated with buckle explantation . METHODS: Case report . RESULTS: A 59-year-old male with a history of retinal detachment repair at the age of 41 presented with chronic, recurrent intraocular inflammation responsive to topical corticosteroids . Conjunctival erosion with exposure of the scleral buckle occurred five months after initial presentation . The scleral buckle was removed and cultured . After three weeks of postoperative topical tobramycin and dexamethasone treatment, the patient has remained symptom-free without medications . The explanted material grew acid-fast bacilli later identified as M . chelonae . CONCLUSIONS: This case describes a new finding of chronic intraocular inflammation associated with a scleral buckle infected with M . chelonae and the successful resolution of extraocular infection and intraocular inflammation after buckle removal.

Tuberculosis (Edinb), 2004, 84(3-4), 228 - 38
Stationary phase gene expression of Mycobacterium tuberculosis following a progressive nutrient depletion: a model for persistent organisms?
Hampshire T, Soneji S, Bacon J, James BW, Hinds J, Laing K, Stabler RA, Marsh PD, Butcher PD.
The majority of individuals infected with TB develop a latent infection, in which organisms survive within the body while evading the host immune system . Such persistent bacilli are capable of surviving several months of combinatorial antibiotic treatment . Evidence suggests that stationary phase bacteria adapt to increase their tolerance to environmental stresses . We have developed a unique in vitro model of dormancy based on the characterization of a single, large volume fermenter culture of M . tuberculosis, as it adapts to stationary phase . Cells are maintained in controlled and defined aerobic conditions (50% dissolved oxygen tension), using probes that measure dissolved oxygen tension, temperature, and pH . Microarray analysis has been used in conjunction with viability and nutrient depletion assays to dissect differential gene expression . Following exponential phase growth the gradual depletion of glucose/glycerol resulted in a small population of survivors that were characterized for periods in excess of 100 days . Bacilli adapting to nutrient depletion displayed characteristics associated with persistence in vivo, including entry into a non-replicative state and the up-regulation of genes involved in beta-oxidation of fatty acids and virulence . A reduced population of non-replicating bacilli went on to adapt sufficiently to re-initiate cellular division.

Tuberculosis (Edinb), 2004, 84(3-4), 218 - 27
Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy; Voskuil MI et al.; The innate mechanisms used by Mycobacterium tuberculosis to persist during periods of non-proliferation are central to understanding the physiology of the bacilli during latent disease . We have used whole genome expression profiling to expose adaptive mechanisms initiated by M . tuberculosis in two common models of M . tuberculosis non-proliferation . The first of these models was a standard growth curve in which gene expression changes were followed from exponential growth through the transition to stationary phase . In the second model, we followed the adaptive process of M . tuberculosis during transition from aerobic growth to a state of anaerobic non-replicating persistence . The most striking finding from these experiments was the strong induction of the entire DosR "dormancy" regulon over approximately 20 days during the long transition to an anaerobic state . This is contrasted by the muted overall response to aerated stationary phase with only a partial dormancy regulon response . From the results presented here we conclude that the respiration-limited environment of the oxygen-depleted NRP model recreates at least one fundamental factor for which the genome of M . tuberculosis encodes a decisive adaptive program.

Rev Port Pneumol, 2004 Mar-Apr, 10(2), 135 - 44
{Tuberculosis . Future perspectives}; Marques Gomes MJ; Tuberculosis remains a major health problem around the world and its incidence is growing 0.4% each year . There are 2 billions of infected, 8.4 millions new cases every year and 16 million patients . The association of VIH and tuberculosis, the increasing number of multidrug resistance, failure of health systems, greater mobility of people, poverty, wars and social exclusion, are the major causes of the epidemiological situation . Faster, more specific and sensible diagnostic methods are being investigated . Some of them use molecular biology techniques, some uses radioisotopes and some others are based on colour and fluorescence modifications of dyes . New drugs, new routes of administration and ways for increasing compliance are under investigation . More potent drugs, with greater biodisponibility and adequate pharmacokinetics for shorter treatments for multidrug and latent forms of bacilli are needed . New vaccines are under investigations, namely Adjuvant Subunits Vaccines, DNA Vaccines DNA, no micobacterianos vectors, and attenuated living vaccines are being tested . Finally some considerations are made concerning the need of global committement to win the fight against tuberculosis in the near future.

Neurol Med Chir (Tokyo), 2004 May, 44(5), 266 - 8
Intramedullary spinal tuberculoma--case report; Torii H et al.; A healthy 33-year-old man presented with an intramedullary tuberculoma of the thoracic spinal cord manifesting as a 2-month history of progressive paraparesis and sphincter dysfunction . Magnetic resonance imaging showed ring enhancement of the intramedullary thoracic lesion with perifocal edema . General physical examination was unremarkable with no signs of inflammation except for a positive finding by the tuberculin skin test . Total resection of the intramedullary mass was performed through a posterior myelotomy following T11-12 laminectomy . Histological examination revealed a granulomatous lesion that contained Langhans giant cells, inflammatory cells, and caseating necrosis . Acid-fast bacilli staining of the specimens was positive, and cultures grew Mycobacterium tuberculosis . Postoperatively, the paraparesis and sphincter dysfunction improved sufficiently for the patient to return to his ordinary activities . Intramedullary spinal tuberculoma is rare, but must be considered in the differential diagnosis of spinal cord compression.

Eur J Dermatol, 2004 Mar-Apr, 14(2), 123 - 4
Dermatomyositis with tuberculous fasciitis; Yoshida Y et al.; A case of dermatomyositis with tuberculous fasciitis is described . A 69-year-old Japanese man treated with prednisolone for dermatomyositis developed erythema and bilateral swelling of arms and forearms . A diagnosis of tuberculous fasciitis was confirmed by the presence of acid-fast bacilli in a biopsy specimen and the growth of Mycobacterium tuberculosis from tissue cultures . The unusual presenting clinical features resulted in delayed diagnosis . We emphasize that tuberculous fasciitis should be considered in an immunocompromised patient who is treated with steroids, especially if the results of initial treatment are not satisfactory . Copyright John Libbey Eurotext 2003.

Zhonghua Jie He He Hu Xi Za Zhi, 2004 May, 27(5), 324 - 7
{A study on the Th1/Th2 cytokines in the pathogenesis of human tuberculous pleuritis}; Li YH et al.; OBJECTIVE: To evaluate the distribution characteristics of Th1-type cytokines (IFN-gamma and IL-2) and Th2-type cytokines (IL-4 and IL-10) in the serum and the pleural effusion in patients with pleural tuberculosis, therefore to gain insight into the possible role of the local and the systemic Th1/Th2 cell-mediated immune response in the pathogenesis of human pleural tuberculosis . METHODS: The concentrations of IFN-gamma, IL-2, IL-4, and IL-10 in the serum and the pleural effusion of patients with pleural tuberculosis (Group pleuritis) were measured with enzyme linked immuno-sorbent assay (ELISA) . The serum levels of the four cytokines were compared with those of patients with pulmonary tuberculosis (Group tuberculosis) and of healthy controls with positive reaction to PPD skin test (Group healthy) . RESULTS: (1) The median concentrations of IFN-gamma, IL-2, IL-4, and IL-10 in serum were 118.60 ng/L, 0.00 ng/L, 1.49 ng/L, and 0.00 ng/L respectively in Group pleuritis, 265.75 ng/L, 18.03 ng/L, 16.00 ng/L, and 0.00 ng/L respectively in Group tuberculosis; and 221.70 ng/L, 18.52 ng/L, 16.00 ng/L, and 0.00 ng/L respectively in Group healthy . (2) For IFN-gamma and IL-2, there existed no statistical differences among the three groups (K-W chi(2) value was 1.15 and 4.68, P > 0.05); For IL-4 and IL-10, there existed no statistical differences between Group tuberculosis and Group healthy (Mann-Whitney Z value was -0.27 and -1.93, P > 0.05), but the level of IL-4 in Group pleuritis was lower than that in Group tuberculosis (Mann-Whitney Z value was -2.84, P < 0.01) . (3) The ratio of the median of IFN-gamma to IL-4 in serum was 27.93 in Group pleuritis, 21.72 in Group tuberculosis, and 10.82 in Group healthy respectively . There existed no statistical difference among the three groups (K-W chi(2) value was 4.18, P > 0.05) . (4) The median concentrations of IFN-gamma, IL-2, IL-4, and IL-10 in pleural effusion of Group pleuritis were 823.37 ng/L, 43.76 ng/L, 26 ng/L and 38.69 ng/L respectively, each being statistically higher than that in the serum (Wilcoxon Signed Rank test Z value was -4.34, -2.82, -3.29 and -5.15, P < 0.05) . CONCLUSIONS: Immunocompetent persons including patients with pleural tuberculosis, with pulmonary tuberculosis or the healthy with positive results to PPD test, showed similar systemic Th1 response to Mycobacterium bacilli . Due to the relatively lower level of systemic Th2 response, patients with pleural tuberculosis had higher systemic Th1/Th2 level and the enhancement of local Th1 and Th2 responses in the pleural cavity was a pathophysiologic characteristic of human pleural tuberculosis . Both Th1 and Th2 responses might play an important role in the pathogenesis of human pleural tuberculosis.

J Infect Dis, 2004 Jul 1, 190(1), 99 - 106 Epub 2004 May 28.
Genetic polymorphism in Mycobacterium tuberculosis isolates from patients with chronic multidrug-resistant tuberculosis; Post FA et al.; Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem because treatment is complicated, cure rates are well below those for drug-susceptible tuberculosis (TB), and patients may remain infectious for months or years, despite receiving the best available therapy . To gain a better understanding of MDR-TB, we characterized serial isolates recovered from 13 human immunodeficiency virus-negative patients with MDR-TB, by use of IS6110 restriction fragment-length polymorphism analysis, spacer oligonucleotide genotyping (i.e., "spoligotyping"), and sequencing of rpoB, katG, mabA-inhA (including promoter), pncA, embB, rpsL, rrs, and gyrA . For all 13 patients, chronic MDR-TB was caused by a single strain of Mycobacterium tuberculosis; 8 (62%) of the 13 strains identified as the cause of MDR-TB belonged to the W-Beijing family . The sputum-derived isolates of 4 (31%) of the 13 patients had acquired additional drug-resistance mutations during the study . In these 4 patients, heterogeneous populations of bacilli with different resistance mutations, as well as mixtures of drug-susceptible and drug-resistant genotypes, were observed . This genetic heterogeneity may require treatment targeted at both drug-resistant and drug-susceptible phenotypes.

Acta Cytol, 2004 May-Jun, 48(3), 337 - 40
Utility of repeat fine needle aspiration in acute suppurative lesions . Follow-up of 263 cases; Kumar N et al.; OBJECTIVE: To determine the clinical value of repeat fine needle aspiration (FNA) as a follow-up strategy in the management of patients in India, clinically suspected of having tuberculosis (TB) but showing a cytologic picture of acute suppuration . STUDY DESIGN: Repeat aspirates from 263 patients presenting with lymph node or soft tissue masses were analyzed . The previous FNA of these cases had shown acute inflammatory exudate but no epithelioid granuloma or acid-fast bacilli (AFB) . RESULTS: The repeat FNA helped to detect 55% additional cases of TB within a period of 8 weeks; 67% of them were diagnosed in the second and third weeks . Diagnostic yield rose to 59% after the third FNA . AFB were detected in 34 (13.3%) cases that showed a low bacterial load . In addition, nontubercular lesions, such as epidermal inclusion cyst (4), cysticercosis (3), sialadenitis (2) and metastatic carcinoma (8), were diagnosed . CONCLUSION: All cases showing acute suppuration without granulomas or AFB on the first FNA should be reevaluated by follow-up FNA and staining for AFB . This will enhance the diagnostic yield of tuberculosis in developing countries, where molecular diagnostics are too costly or unavailable . This procedure is cost effective as compared to biopsy and culture . In addition to tuberculosis, many unexpected nontubercular lesions may also be unmasked . Repeat FNA reduces sampling and screening errors, improves sensitivity and helps to study the evolution of epithelioid granulomas.

Swiss Med Wkly, 2004 Apr 17, 134(15-16), 221 - 2
Mycobacterium bohemicum--a cause of paediatric cervical lymphadenitis; Schulzke S et al.; We report on two toddlers suffering from Mycobacterium bohemicum lymphadenitis . Acid-fast bacilli were cultured from submandibular lymph nodes and identified by molecular methods as Mycobacterium bohemicum . Surgical treatment was successful and complemented by oral treatment with clarithromycin and rifampicin.

J Immunol, 2004 Jun 15, 172(12), 7771 - 9
An in vitro model for the lepromatous leprosy granuloma: fate of Mycobacterium leprae from target macrophages after interaction with normal and activated effector macrophages; Hagge DA et al.; The lepromatous leprosy granuloma is a dynamic entity requiring a steady influx of macrophages (Mphi) for its maintenance . We have developed an in vitro model to study the fate of Mycobacterium leprae in a LL lesion, with and without immunotherapeutic intervention . Target cells, consisting of granuloma Mphi harvested from the footpads of M . leprae-infected athymic nu/nu mice, were cocultured with normal or IFN-gamma-activated (ACT) effector Mphi . The bacilli were recovered and assessed for viability by radiorespirometry . M . leprae recovered from target Mphi possessed high metabolic activity, indicating a viable state in this uncultivable organism . M . leprae recovered from target Mphi incubated with normal effector Mphi exhibited significantly higher metabolism . In contrast, bacilli recovered from target Mphi cocultured with ACT effector Mphi displayed a markedly decreased metabolic activity . Inhibition by ACT Mphi required an E:T ratio of at least 5:1, a coculture incubation period of 3-5 days, and the production of reactive nitrogen intermediates, but not reactive oxygen intermediates . Neither IFN-gamma nor TNF-alpha were required during the cocultivation period . However, cell-to-cell contact between the target and effector Mphi was necessary for augmentation of M . leprae metabolism by normal effector Mphi as well as for inhibition of M . leprae by ACT effector Mphi . Conventional fluorescence microscopy and confocal fluorescence microscopy revealed that the bacilli from the target Mphi were acquired by the effector Mphi . Thus, the state of Mphi infiltrating the granuloma may markedly affect the viability of M . leprae residing in Mphi in the lepromatous lesion.

Microbiology, 2004 Jun, 150(Pt 6), 1681 - 6
The Mycobacterium tuberculosis cysD and cysNC genes form a stress-induced operon that encodes a tri-functional sulfate-activating complex; Pinto R et al.; Sulfur metabolism has been implicated in the virulence, antibiotic resistance and anti-oxidant defence of Mycobacterium tuberculosis . Despite its human disease relevance, sulfur metabolism in mycobacteria has not yet been fully characterized . ATP sulfurylase catalyses the synthesis of activated sulfate (adenosine 5'-phosphosulfate, APS), the first step in the reductive assimilation of sulfate . Expression of the M . tuberculosis cysD gene, predicted to encode the adenylyl-transferase subunit of ATP sulfurylase, is upregulated by the bacilli inside its preferred host, the macrophage . This study demonstrates that cysD and cysNC orthologues exist in M . tuberculosis and constitute an operon whose expression is induced by sulfur limitation and repressed by the presence of cysteine, a major end-product of sulfur assimilation . The cysDNC genes are also induced upon exposure to oxidative stress, suggesting regulation of sulfur assimilation by M . tuberculosis in response to toxic oxidants . To ensure that the cysDNC operon encoded the activities predicted by its primary sequence, and to begin to characterize the products of the operon, they were expressed in Escherichia coli, purified to homogeneity, and tested for their catalytic activities . The CysD and CysNC proteins were shown to form a multifunctional enzyme complex that exhibits the three linked catalytic activities that constitute the sulfate activation pathway.

J Clin Microbiol, 2004 Jun, 42(6), 2558 - 65
Genotypic variation and stability of four variable-number tandem repeats and their suitability for discriminating strains of Mycobacterium leprae; Truman R et al.; It has not been possible to distinguish different strains of Mycobacterium leprae according to their genetic sequence . However, the genome contains several variable-number tandem repeats (VNTR), which have been used effectively in strain typing of other bacteria . To determine their suitability for differentiating M . leprae, we developed PCR systems to amplify 5 different VNTR loci and examined a battery of 12 M . leprae strains derived from patients in different regions of the United States, Brazil, Mexico, and the Philippines, as well as from wild armadillos and a sooty mangabey monkey . We found diversity at four VNTR (D = 0.74), but one system (C(16)G(8)) failed to yield reproducible results . Alleles for the GAA VNTR varied in length from 10 to 16 copies, those for AT(17) varied in length from 10 to 15 copies, those for GTA varied in length from 9 to 12 copies, and those for TA(18) varied in length from 13 to 20 copies . Relatively little variation was seen with interspecies transfer of bacilli or during short-term passage of strains in nude mice or armadillos . The TA(18) locus was more polymorphic than other VNTR, and genotypic variation was more common after long-term expansion in armadillos . Most strain genotypes remained fairly stable in passage, but strain Thai-53 showed remarkable variability . Statistical cluster analysis segregated strains and passage samples appropriately but did not reveal any particular genotype associable with different regions or hosts of origin . VNTR polymorphisms can be used effectively to discriminate M . leprae strains . Inclusion of additional loci and other elements will likely lead to a robust typing system that can be used in community-based epidemiological studies and select clinical applications.

Zhonghua Nei Ke Za Zhi, 2004 May, 43(5), 325 - 8
{A prospective cohort study of risk factors for ventilator-associated pneumonia in intensive care unit}; Li HY et al.; OBJECTIVE: To study the risk factors of ventilator-associated pneumonia (VAP) in intensive care unit (ICU), in order to offer basic epidemiological data for the prevention of VAP in ICU . METHODS: A prospective cohort study on VAP was carried out in intubated or tracheotomied patients in ICU of Fudan University Zhongshan Hospital from Dec.1999 to Feb . 2001 . Single factor analysis and muti-variable logistic regression analysis were adopted to identify the possible risk factors of VAP . RESULTS: (1) Ninety-eight patients were enrolled in this study, of which 52 were diagnosed as having VAP . The incidence of VAP was 53.1% . The incidence of VAP was 32.4 cases per 1000 intubation days . (2) Single factor analysis showed that history of chronic obstructive pulmonary emphysema, use of H2-receptor blocker, the days of antibiotic use, the types of antibiotics, enteral feeding, APACHEII scores, the duration of mechanic ventilation, pH of gastric juice, hypoalbuminemia, tracheotomy, reintubation, colonization of gram negative bacilli in oropharynx, and conscious disturbance were related to the occurrence of VAP . (3) Multi-variable logistic analysis showed statistical significance in combination of over two types of antibiotics (OR = 7.59, 95% CI 4.31 - 38.29), reintubation (OR = 4.73, 95% CI 2.33 - 11.67), APACHE II scores over 15 (OR = 2.02, 95% CI 1.59 - 26.74), pH of gastric juice over 4 (OR = 1.23, 95% CI 1.02 - 1.54) and prolongation of mechanic ventilation (OR = 1.15, 95% CI 1.01 - 3.75) . CONCLUSIONS: Various factors contributed to VAP in ICU . Further clinical trials are needed for evidence of the above-mentioned possible risk factors.

Sichuan Da Xue Xue Bao Yi Xue Ban, 2004 May, 35(3), 340 - 2
{Study on the inducible expression of toll-like receptors in human bladder cell line}; Li X et al.; OBJECTIVE: To investigate and compare the expression of Toll-like receptors (TLRs) in human bladder cells under the stimulus of Escherichia coli (E . coli) versus that under the stimulus of Bacillus Calmette-Guerin (BCG) . METHODS: Human bladder cancer cell line T24 was cultured for 1 hour under the stimuli of various doses (bacillus-cell ratio) of E . coli and BCG respectively . The levels of expression of TLR-2 and TLR-4 mRNA in T24 cells were assessed by RT-PCR method . RESULTS: By comparison with control, there was no difference observed on the expression of either TLR-2 or TLR-4 in T24 cells under the stimulus of E . coli . The expression level of either TLR-2 or TLR-4 was increased under the stimulus of BCG in a dose-dependent manner . The effects reached the highest level when the dose of BCG was 10 bacilli per cell . CONCLUSION: There exist different expression patterns of TLRs in bladder transitional cells under the different stimuli of E . coli and BCG respectively.

Clin Lab Med, 2004 Jun, 24(2), 363 - 80
Antibiotic-resistant gram-negative bacteria in hospitalized children; Toltzis P; Antibiotic-resistant Gram-negative bacilli are a prominent and growing problem among hospitalized children . Epidemics caused by these organisms have been implicated in many outbreaks in children's hospitals, primarily in neonatal intensive care units . These epidemics are characterized by efficient patient-to-patient transmission of the outbreak clone via the hands of caregivers and through exposure of contaminated inanimate sources . The epidemiology of these resistant organisms in pediatric hospitals during endemic periods is more complex . The isolates cultured from hospitalized individuals in the absence of an outbreak usually are unique to each individual and are derived from the patient's endogenous flora or other disparate sources . As in adults, chronic care facilities for children represent significant reservoirs of antibiotic-resistant bacilli that are circulated back into the acute care hospital environment when the child becomes ill.

Surg Today, 2004, 34(6), 537 - 41
Tuberculous gastric perforation: report of a case; Sharma D et al.; A 21-year-old woman presented with a 2-day history of acute abdominal pain . Contrast-enhanced computed tomography (CT) showed a perforation in the lesser curve of the stomach . The patient suffered a bout of hematemesis, following which an endoscopy showed a bleeding blood vessel at the edge of the perforation . We performed an emergency distal gastrectomy, including the ulcer site . Histopathological examination revealed tuberculous granulation tissue and acid-fast bacilli in the ulcer . The patient was given antituberculosis therapy (ATT) postoperatively, and was well when last seen 1 year 5 months after surgery . We analyzed the clinical data of five cases of tuberculous gastric perforation (TGP), reported between 1948 and 2003, including our patient . The patients ranged in age from 21 to 45 years, with a mean age of 36.8 years (SD +/- 10.21), and a male to female ratio of 3 : 2 . The diagnosis was confirmed by surgery or autopsy . Abdominal lymphadenopathy was present in all patients . Gastrectomy was performed in four patients, and two were given ATT . All four patients in the previous reports died of their disease.

Nihon Kokyuki Gakkai Zasshi, 2004 May, 42(5), 440 - 5
{A case of infected bulla caused by Mycobacterium kansasii}; Minami S et al.; A 62-year-old man was referred to our hospital because of persistent sub-fever . A pulmonary fungal infection was suspected owing to the elevation of the serum-D-glucan level . Since a chest radiograph and a CT scan revealed intrabullous fluid in the right upper lobe, percutaneous needle aspiration was performed . Although acid-fast bacilli smears of the sputum and intrabullous fluid were negative, their cultures were found to be positive thereafter . M . kansasii was isolated and identified . After chemotherapy with antituberculous drugs, sub-fever improved and intrabullous fluid disappeared completely . Infected bulla caused by mycobacteria is very rare.

Nihon Kokyuki Gakkai Zasshi, 2004 May, 42(5), 424 - 8
{A case of M . fortuitum lung disease with small-cell lung cancer}; Kobayashi K et al.; A 58-year-old man was admitted to our hospital because of an abnormal shadow found on chest radiography . Chest radiographs and chest CT on admission showed a bulla with a niveau and infiltration in the right upper lobe . Smear of sputum and bronchial lavage were negative for acid-fast bacilli . Despite treatment with meropenem and clindamycin, the infiltrating shadow worsened . Since bronchial lavage and sputum culture were positive for M . fortuitum, these drugs were replaced with minocycline and imipenem . Thereafter, the shadow on the chest radiograph improved . After discharge, outpatient treatment with clarithromycin and levofloxacin was continued . After 4 months, the residual tumor shadow in the right upper lobe gradually grew . When a CT-guided transcutaneous needle lung biopsy was undertaken, malignant cells were found . Right upper lobectomy was performed . Pathological examination of the lesion demonstrated small-cell lung cancer . If a lesion does not change after nontuberculous mycobacteria treatment, the physician should consider other lesions such as lung cancer.

Kekkaku, 2004 Apr, 79(4), 313 - 20
{Four cases of Mycobacterium xenopi pulmonary disease}; Minami S et al.; Mycobacterium xenopi is very rare pathogen in Japan . We reported herein four cases of M . xenopi pulmonary disease . These patients were all male and their ages ranged from 53 to 72 . They all had past history of pulmonary tuberculosis, including two cases who had been also treated for Mycobacterium kansasii pulmonary disease later . The bacilli could be cultured in Mycobacteria Growth Indicator Tube (MGIT) system from 10 sputum samples, but they could not be cultured on Ogawa egg media except for two samples . All four cases fulfilled the criteria for the diagnosis of nontuberculous mycobacteria pulmonary disease proposed by the Japanese Society for Tuberculosis . Combination chemotherapy including isoniazid, rifampicin, and ethambutol was started in all four cases when mycobacteria were detected under tentative diagnosis of the relapse of tuberculosis or Mycobacterium kansasii disease . Sputum converted to culture negative by the chemotherapy in two cases . In one case, the chemotherapeutic regimen was changed to rifampicin, ethambutol, and clarithromycin after the bacteriological identification of M . xenopi, and the new regimen was found to be effective . In the final case, both of the regimens were finally ineffective.

Kekkaku, 2004 Apr, 79(4), 297 - 300
{The clinical features of ultra-old tuberculosis patients in our hospital}; Yano S et al.; PURPOSE: To examine the clinical features of ultra-old patients over 85 years of age who were admitted to our hospital for tuberculosis treatment . METHODS: Clinical features of tuberculosis patients over 85 years of age who were admitted to our hospital from January, 1996 to May, 2003 were analyzed in relation to their disease status, complications and prognosis . RESULTS: They showed a high tuberculin negative rate (26.2%) and a low rate of cavity formation (21.8%), and the smear positive rate of tubercle bacilli was not high (51.2%) . As to the complications, cerebrovascular disorders were overwhelmingly high (62.2%) and the death rate due to side effects of drugs was high . The sputum smear positive rate was higher (70%) among patients from nursing home . CONCLUSION: The diagnosis of tuberculosis was often delayed with high mortality rate due to side effects of drugs among ultra-old patients and tuberculosis infection control measures to contacts are often needed.

Am J Med Sci, 2004 May, 327(5), 258 - 61
Tenosynovitis caused by Mycobacterium kansasii associated with a dog bite; Southern PM Jr; A 68-year-old man with adult-onset diabetes mellitus suffered an accidental puncture wound to the palm of his hand while playing with his pet dog . He received cephalosporin prophylaxis for 1 week . No inflammation occurred . Six months later, a mass developed near his elbow . It was removed . Histopathology revealed granulomas containing acid-fast bacilli (AFB) . No culture was done . Swelling and decreased motion of the wrist and fingers developed . Magnetic resonance imaging revealed inflammation of the flexor compartment of the hand, wrist, and forearm . Surgical incision and drainage yielded purulent material, granulomatous inflammation, with AFB . Cultures yielded Mycobacterium kansasii . Several surgical procedures were required; M kansasii was recovered . He received isoniazid and rifampin for 1 year and prolonged rehabilitation . After 4 years, he was relatively asymptomatic, with good function of wrist and fingers . We believe this to be the first report of tenosynovitis caused by M kansasii in association with a dog bite.

J Dermatol, 2004 Feb, 31(2), 119 - 23
Leprosy with Guillain Barre Syndrome: a new neurologic manifestation?
Grover C, Kubba S, Nanda S, Kumar V, Reddy BS.
A 19-year-old female patient of lepromatous leprosy with Type II reaction, on multidrug therapy and prednisolone, presented with acute onset flaccid quadriparesis . The cerebrospinal fluid examination revealed albumino-cytologic dissociation . Nerve biopsy showed infiltration with lepra bacilli, features of vasculitis, and demyelination . There were no other identifiable precipitating factors for Guillain Barre Syndrome in this patient . Her condition improved without any steroid therapy . This case emphasizes the hypothesis that cell injury caused by Type II reaction can expose neural antigens and incite an autoimmune reaction in the form of Guillain Barre Syndrome.

FEMS Microbiol Lett, 2004 Jun 1, 235(1), 191 - 8
Tubercle bacilli generate a novel cell wall-associated pigment after long-term anaerobic culture; Cunningham AF et al.; Many cases of tuberculosis result from reactivation of previously acquired latent infections . Models to study such persister forms often involve gradual depletion of oxygen during culture as poor aeration is a characteristic of non-progressive TB granulomas . Anaerobically cultured bacilli develop a thickened outer-most cell wall layer . Here, we analyzed this layer from anaerobically cultured Mycobacterium tuberculosis and Mycobacterium bovis BCG . By six weeks of anaerobiosis a pigment was detected at levels > 60-fold higher in anaerobic than aerobic bacilli . This pigment was responsible for the electron-dense appearance of the thickened cell wall layer and gave an electrospray mass spectrometry peak at 409 Da (M+Na)+ or (M+H)+ . We termed this pigment APP1, anaerobically produced pigment 1, the first pigment identified in M . tuberculosis.

Bull Hosp Jt Dis, 2003, 61(3-4), 145 - 7
Tuberculous pseudotumor of the proximal end of the fibula . A case report; Abdelwahab IF et al.; A 72-year-old asian woman who had immigrated from Vietnam 10 years ago presented with a soft tissue mass around the proximal fibula . Conventional radiographs and magnetic resonance imaging demonstrated a destructive lesion of the head of the fibula with an intact superior tibiofibular joint and an abscess surrounding the destroyed bone . Histopathology obtained by a CT-guided needle biopsy revealed necrotizing epithelioid granulomata without demonstrating acid-fast bacilli . However, culture grew Mycobacterium tuberculosis . When tuberculosis affects the end of a long tubular bone, the adjacent synovial joint is usually involved . Cases where joint involvement does not occur are extremely rare and unusual . We report such a case.

Am J Trop Med Hyg, 2004 May, 70(5), 520 - 6
Buruli ulcer disease in Cameroon rediscovered; Noeske J et al.; To assess the magnitude of the Buruli ulcer (BU) problem in Cameroon, we conducted a cross-sectional survey in the Nyong River basin and identified on clinical grounds a total of 436 cases of active or inactive BU (202 and 234, respectively) . Swab specimens were taken from 162 active cases with ulcerative lesions and in 135 of these (83.3%) the clinical diagnosis was confirmed by the IS2404 polymerase chain reaction . Most lesions (93%) were located on the extremities, with lower limbs being twice as commonly involved as upper limbs . The age of patients with active BU ranged from 2 to 90 years with a median age of 14.5 years . Vaccination with bacilli Calmette-Guerin appeared to protect children against more severe forms of BU with multiple lesions . We conclude that in Cameroon BU is endemic, at least in the study area, and that a comprehensive control program for BU in Cameroon is urgently needed.

Am J Infect Control, 2004 May, 32(3), 135 - 41
Prospective study of the impact of open and closed infusion systems on rates of central venous catheter-associated bacteremia; Rosenthal VD et al.; OBJECTIVE: We sought to ascertain the effect of switching from an open infusion system to a closed system on rates and sequelae of central venous catheter (CVC)-associated bloodstream infection in the intensive care department (ICU) of 2 hospitals in Argentina . METHODS: A prospective, controlled, time-series, cohort trial was undertaken in adult patients admitted to 4 level-III adult ICUs in Buenos Aires, Argentina, who had a CVC in place for at least 24 hours . Rates of CVC-associated bloodstream infection during a period of active surveillance with an open system (baseline; externally vented, semirigid, noncollapsible, 1-port plastic bottles) were compared with rates after switching to a closed system (intervention; nonvented, collapsible, 2-port plastic bags) . RESULTS: Between August 1999 and March 2002, 992 patients in the ICU with CVCs were enrolled . Patients during each study period (open system, 608; closed system, 384) were similar with respect to sex, severity-of-illness score, and prevalence of diabetes and cancer . Compliance with handwashing and CVC site care was also similar during the 2 study periods . The incidence of CVC-associated bacteremia during use of the closed system was significantly lower than during use of the open system (2.36 vs 6.52/1000 catheter-days, relative risk=0.36, 95% confidence interval=0.14-0.94, P=.02); bacteremias caused by gram-negative bacilli declined by 64% . In all, 17 patients with catheter-associated bacteremia died during the period when the open system was in use (2.8%), versus only 1 (0.2%) during use of the closed system (relative risk 0.09, P=.003) . The calculated cost savings in the 20 hospital-month intervention period was $53,768 and 130.9 ICU days . CONCLUSION: Adoption of a closed infusion system resulted in major reductions in the incidence of catheter-associated bacteremia, related mortality, and cost . Because most Latin American hospitals still use externally vented fluid containers, switching to nonvented bags could substantially reduce rates of nosocomial bacteremia.

Artif Organs, 2004 Jun, 28(6), 590 - 2
The bactericidal effects of electrolyzed oxidizing water on bacterial strains involved in hospital infections; Vorobjeva NV et al.; The study is designed to investigate bactericidal actions of electrolyzed oxidizing water on hospital infections . Ten of the most common opportunistic pathogens are used for this study . Cultures are inoculated in 4.5 mL of electrolyzed oxidizing (EO) water or 4.5 mL of sterile deionized water (control), and incubated for 0, 0.5, and 5 min at room temperature . At the exposure time of 30 s the EO water completely inactivates all of the bacterial strains, with the exception of vegetative cells and spores of bacilli which need 5 min to be killed . The results indicate that electrolyzed oxidizing water may be a useful disinfectant for hospital infections, but its clinical application has still to be evaluated.

J Antimicrob Chemother, 2004 Jun, 53 Suppl 2, ii37 - 50
Complicated infections of skin and skin structures: when the infection is more than skin deep; DiNubile MJ et al.; Skin and skin-structure infections are common, and range from minor pyodermas to severe necrotizing infections . Complicated infections are defined as involving abnormal skin or wounds, occurring in compromised hosts, or requiring surgical intervention . Classification schemes for these infections are varied and confusing . Distinguishing characteristics include the aetiological agent(s), clinical context and findings, depth of tissue involvement and rate of progression . The most common pathogens are aerobic Gram-positive cocci, but complicated infections frequently involve Gram-negative bacilli and anaerobic bacteria . Initial antibiotic therapy is usually empirical, and later modified by the results of stains and cultures of wound specimens . Broad-spectrum coverage is frequently needed for complicated infections . Ertapenem is a once-a-day parenteral Group 1 carbapenem antibiotic, recently licensed in the USA and Europe, which may assume an important role in treating some complicated skin and skin-structure infections . Surgical debridement is important for many complicated infections, and is the critical element in managing necrotizing fasciitis and myonecrosis.

An R Acad Nac Med (Madr), 2003, 120(4), 717 - 26; discussion 726-8
{Evolution of bacterial resistance to antibiotics}; Gomez-Lus Lafita R; Bacterial resistance to antibiotics is often plasmid-mediated and the associated genes encoded by transposable elements . These elements play a central role in evolution by providing mechanisms for the generation of diversity and, in conjuntion with DNA transfer systems, for the dissemination of resistance to other bacteria . Resistance to antibiotics in gram-negative bacilli is most commonly mediated by R plasmids and by genes carried by transposons and integrons . In gram-positive cocci the conjugative transposons are fundamental for antibiotic resistance . Acquired multiple R in S . pneumoniae can result from the presence of transposon Tn1545, which carries determinants erm (B), tet (M), aph(3')-III, and catpC194.

FEMS Immunol Med Microbiol, 2004 Jun 1, 41(2), 93 - 100
Antibody bound to the surface antigen MPB83 of Mycobacterium bovis enhances survival against high dose and low dose challenge; Chambers MA et al.; Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium bovis is a significant disease of man and animals . Whilst cellular immunity is the major immunological component required for protection against these organisms, recent reports have suggested that monoclonal antibodies can modify infection with M . tuberculosis . To test whether the same was true for M . bovis infection, we determined the effect of preincubation of M . bovis with a monoclonal antibody on subsequent intravenous infection of mice . Antibodies bound to the surface of M . bovis increased the survival time of mice infected with M . bovis and changed the morphology of granulomas and the distribution of acid-fast bacilli in the lung . These studies suggest that antibodies directed to the surface of virulent mycobacteria can modulate their virulence in vivo.

Tuberk Toraks, 2003, 51(4), 405 - 9
{The value of fiberoptic bronchoscopy in diagnosis of smear negative pulmonary tuberculosis}; Yuksekol I et al.; Although mycobacterial culture positivity is the gold standart for the diagnosis, the initial approach to the diagnosis of pulmonary tuberculosis (PTbc) is the detection of acid-fast bacilli (AFB) in respiratory specimens as recommended by the World Health Organization . But the physicians have to make a decision for the patients whose sputum smears are negative or who can not produce sputum . Waiting for culture results with radiological follow up or empirical antituberculous therapy are the standart options . In our study we aimed to assess the diagnostic yield of fiberoptic bronchoscopy in patients, suspected to have tuberculosis, whose sputum smears were negative or who could not produce sputum . Fifty six patients who suspected to have PTbc with sputum smear negative were enrolled in the study (fiberoptic bronchoscopy and selective bronchial washings were done to all patients . Bronchial washings were obtained from the affected parts) . Mucosal biopsies were done in patients in where endobronchial abnormalities were noted . Transbronchial biopsies were done in selected patients from the radiological localizations . Ziehl-Nielsen staining and culture in Lowenstein-Jensen medium were the microbiological studies . Typical granulomas were expected to detect on histopathologic examination . Bronchoscopic lavage smears were positive for Mycobacterium tuberculosis in 13 (23%) patients . Twenty eight (50%) patients had positive culture . Histopathological results confirmed tuberculosis in eight of 20 patients who had undergone mucosal biopsies, four of seven of transbronchial biopsies, two of three of needle aspiration biopsies . By bronchoscopic proceduresearly diagnosis was performed in 27 (48.21%) patients . We concluded that fiberoptic bronchoscopy has an important role in the diagnosis of patients suspected to have tuberculosis, whose sputum smears were negative or who could not produce sputum . It is useful and necessary in selected cases.

Int J Syst Evol Microbiol, 2004 May, 54(Pt 3), 871 - 5
Phylogeny of Firmicutes with special reference to Mycoplasma (Mollicutes) as inferred from phosphoglycerate kinase amino acid sequence data; Wolf M et al.; The phylogenetic position of the Mollicutes has been re-examined by using phosphoglycerate kinase (Pgk) amino acid sequences . Hitherto unpublished sequences from Mycoplasma mycoides subsp . mycoides, Mycoplasma hyopneumoniae and Spiroplasma citri were included in the analysis . Phylogenetic trees based on Pgk data indicated a monophyletic origin for the Mollicutes within the Firmicutes, whereas Bacilli (Firmicutes) and Clostridia (Firmicutes) appeared to be paraphyletic . With two exceptions, i.e . Thermotoga (Thermotogae) and Fusobacterium (Fusobacteria), which clustered within the Firmicutes, comparative analyses show that at a low taxonomic level, the resolved phylogenetic relationships that were inferred from both the Pgk protein and 16S rRNA gene sequence data are congruent.

Med Hypotheses, 2004, 62(6), 889 - 93
Bacteriophages: antibacterials with a future?
Broxmeyer L.
The hypothesis as to whether a benign species of bacteria could kill a virulent kind has to this point been untested . Recently it was shown that in the macrophage, bacteriophages, when properly introduced through a nonvirulent microbe, had a killing rate for virulent AIDS Mycobacterium tuberculosis and Mycobacterium avium far in excess of modern day antibiotics . The study in effect brought a natural phenomena, lysogeny, whereby one bacterial colony kills another thru phage weaponry, to bear in the conquest of hard-to-kill, antibiotic resistant pathogens . This killing occurred intracellularly, within the white blood cell using Mycobacterium smegmatis, a benign bacterial species found generally in smegma secretions from human genitalia as well as soil, dust and water, and first identified in 1884 . The subsequent treatment of M . avium-infected, as well as M . tuberculosis-infected RAW 264.7 macrophages, with M . smegmatis transiently infected with TM4 resulted in a unexpectedly large time- and titer-dependent reduction in the number of viable intracellular bacilli . In addition, the M . smegmatis vacuole harboring TM4 fused with the M . avium vacuole in macrophages . These results suggested a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.

Neuropathology, 2004 Jun, 24(2), 149 - 52
Nonvasculitic autoimmune inflammatory meningoencephalitis; Josephs KA et al.; Caselli and colleagues described five cases with encephalopathy, progressive cognitive decline, ataxia, abnormal CSF studies and steroid responsiveness, and proposed the term non-vasculitic autoimmune inflammatory meningoencephalitis (NAIM) . Many of these cases had brain biopsy showing mild leptomeningeal perivascular lymphocytic inflammation, however, none of the cases had a post-mortem . Nonvasculitic autoimmune mediated meningoencephalitis has been described in patients with Sjogren's syndrome, systemic lupus erythematosus and, more recently, with Hashimoto's disease . The present study is the first post-mortem report of a case with a clinical diagnosis of NAIM . Neuropathological examination revealed a panencephalitis with intact vessel walls . T and B immunostaining showed a mixture of T and B cells . The findings were not consistent with other reported findings in collagen vascular diseases including Sjogren's syndrome, CNS vasculitis or Hashimoto's encephalopathy . There was no evidence of neoplasia, bacteria, acid-fast bacilli, fungi or atypical infectious agents . This is the first post-mortem report of a case with a clinical diagnosis of NAIM and demonstrates a panencephalitis without evidence of a vasculitis . The pathology seems unique, however, Sjogren and Hashimoto's encephalopathy might be variants of NAIM.

Int J Tuberc Lung Dis, 2004 Feb, 8(2), 248 - 52
Reduced detection by Ziehl-Neelsen method of acid-fast bacilli in sputum samples preserved in cetylpyridinium chloride solution; Selvakumar N et al.; SETTING: Twelve health facilities implementing the DOTS strategy, and the Tuberculosis Research Centre (TRC), Chennai, India . OBJECTIVE: To determine the detection rates using Ziehl-Neelsen (ZN) and auramine-phenol to stain acid-fast bacilli (AFB) in sputum samples stored in cetylpyridinium chloride (CPC) solution . METHODS: Two smears were prepared from each of 988 sputum samples collected in CPC and randomly allocated, one to ZN and the other to auramine-phenol staining . All samples were processed for culture of Mycobacterium tuberculosis . RESULTS: A significantly higher proportion of samples were negative using the ZN method compared to the auramine-phenol method (74.5% vs . 61.8%, McNamara's paired chi2 test; P < 0.001) . Among 377 samples that were positive using auramine-phenol, 44% were negative using ZN . There were more culture-positive, smear-negative samples in ZN (52.7%) than in auramine-phenol (30%); the difference attained statistical significance (McNemar's paired chi2 test; P < 0.00004) . Using ZN, of the 104 smears made immediately after collection, 52 were positive for AFB, of which only 35 (67.3%) were positive after storage in CPC; the reduction in the number of positive smears attained statistical significance (McNemar's paired chi2 test; P = 0.004) . CONCLUSION: Detection of AFB in sputum samples preserved in CPC is significantly reduced using ZN staining.

Hum Pathol, 2004 May, 35(5), 571 - 5
Viability of mycobacteria in formalin-fixed lungs; Gerston KF et al.; It is generally accepted that the risk of contracting tuberculosis is relatively high among medical laboratory workers and pathologists . Nevertheless, there is an assumption that once tissue is fixed in formalin, the risk for transmission and subsequent infection of mycobacteria is greatly reduced, if not altogether eliminated . To test the viability of potentially infectious mycobacteria in formalin-fixed tissue, tissue specimens from autopsy lungs fixed in formalin were cultured for mycobacteria . Of 138 cases with histologic evidence of acid-fast bacilli, 12 grew mycobacteria, including 3 Mycobacterium tuberculosis isolates, suggesting that there is a risk of contracting tuberculosis from tissue that has been fixed in formalin, if aerosolization or accidental inoculation should occur.

Int J Tuberc Lung Dis, 2004 May, 8(5), 537 - 44
The annual risk of tuberculous infection in the eastern zone of India; Chadha VK et al.; SETTING: Rural and urban areas of eight selected districts in the eastern zone of India . OBJECTIVES: To estimate the annual risk of tuberculous infection (ARTI) . STUDY DESIGN: A community-based, cross-sectional tuberculin survey was conducted among children aged 1-9 years residing in a sample of rural and urban areas . Stratified two-stage cluster sampling was adopted for selection of rural and urban clusters . A total of 40964 children in 515 clusters underwent tuberculin testing and reading with 1TU PPD RT23 with Tween 80; the maximum transverse diameter of induration was measured about 72 h after the test . RESULTS: A bacille Calmette-Guerin (BCG) scar was observed in 51.5% of the test-read children . The frequency distribution of tuberculin reaction size among 19332 children without BCG scar was found to be bimodal, with the mode of reactions attributable to infection with tubercle bacilli at 20 mm . The prevalence of infection was estimated as 6.9% . The ARTI computed from the estimated prevalence was 1.3% . Children residing in the urban areas were found to be at a significantly higher risk of infection than those residing in rural areas . CONCLUSION: The high rate of ARTI in the eastern zone of India suggests a need for committed, sustained action in provision of quality tuberculosis control services.

Microbiology, 2004 May, 150(Pt 5), 1397 - 404
Strains of Bacillus cereus vary in the phenotypic adaptation of their membrane lipid composition in response to low water activity, reduced temperature and growth in rice starch; Haque MA et al.; The phenotypic adaptation of membrane lipids in seven strains of the food-poisoning bacterium Bacillus cereus, isolated from Bangladeshi rice, is reported in relation to their ability to grow under conditions of low water activity (a(w)), reduced temperature and the presence of soluble rice starch . The strains have different membrane phospholipid head-group and fatty acyl compositions, and they display individual differences in their responses to both low a(w) and reduced temperature . The extent of the increase in anionic membrane lipids in response to low a(w) varies from strain to strain, is solute specific and in one strain does not occur . Growth is stimulated by the presence of soluble rice starch and results in a large rise in the proportion of diphosphatidylglycerol (DPG) at the expense of phosphatidylglycerol (PG), without any change in the proportion of total anionic phospholipids . Growth at 15 degrees C compared with 37 degrees C increases the proportions of DPG and phosphatidylethanolamine at the expense of PG . At the lower temperature there are changes in phospholipid fatty acyl composition characteristic of those expected to maintain membrane fluidity, including increases in the amount of total branched fatty acids and the anteiso-/iso-branched ratio, and a decrease in the equivalent chain-length, but there are strain differences in how those changes were achieved . In contrast to some other bacilli, there are persistent large increases in the proportions of unsaturated fatty acyl chains in phospholipids during growth at 15 degrees C.

Cardiovasc Intervent Radiol, 2004 May-Jun, 27(3), 226 - 30 Epub 2004 May 04.
CT-guided transthoracic core biopsy for pulmonary tuberculosis: diagnostic value of the histopathological findings in the specimen; Fukuda H et al.; We evaluated the value of CT-guided transthoracic core biopsy for the diagnosis of mycobacterial pulmonary nodules . The 30 subjects in this study had pulmonary nodules that had been either diagnosed histopathologically as tuberculosis or were suspected as tuberculosis based on a specimen obtained by CT-guided transthoracic core biopsy . The histopathological findings, the existence of acid-fast bacilli in the biopsy specimens, and the clinical course of the patients after the biopsy were reviewed retrospectively . Two of the three histological findings for tuberculosis that included epithelioid cells, multinucleated giant cells and caseous necrosis were observed in 21 of the nodules which were therefore diagnosed as histological tuberculosis . Six of these 21 nodules were positive for acid-fast bacilli, confirming the diagnosis of tuberculosis . Thirteen of the 21 nodules did not contain acid-fast bacilli but decreased in size in response to antituberculous treatment and were therefore diagnosed as clinical tuberculosis . Seven nodules with only caseous necrosis were diagnosed as suspected tuberculosis, with a final diagnosis of tuberculosis being made in 4 of the nodules and a diagnosis of old tuberculosis in 2 nodules . Two nodules with only multinucleated giant cells were diagnosed as suspected tuberculosis with 1 of these nodules being diagnosed finally as tuberculosis and the other nodule as a nonspecific granuloma . When any two of the three following histopathological findings--epithelioid cells, multinucleated giant cells or caseous necrosis--are observed in a specimen obtained by CT-guided transthoracic core biopsy, the diagnosis of tuberculosis can be established without the detection of acid-fast bacilli or Mycobacterium tuberculosis.

Acta Paediatr, 2004 Mar, 93(3), 311 - 5
Detection of Mycobacterium tuberculosis in gastric aspirate and sputum collected from Ethiopian HIV-positive and HIV-negative children in a mixed in- and outpatient setting; Berggren Palme I et al.; AIM: To investigate, through a prospective study, the detection rate of Mycobacterium tuberculosis in sputa and gastric aspirate from tuberculous children in a low-income country with high prevalence of tuberculosis and an increasing HIV epidemic . METHODS: Gastric aspirates and/or sputum samples were collected from 355 children with pulmonary tuberculosis as follows: from 136 children under 5 y only gastric aspirate was taken, for 159 children aged 5 to 9 y both methods were used, and for 60 children over 10 y only sputum was analysed . The diagnosis of tuberculosis was based on clinical data, tuberculin test and chest radiography . All children were tested for HIV infection . RESULTS: Direct microscopy for acid-fast bacilli was positive for 55 (15%) and mycobacterial culture for 183 (52%) children . The proportion of positive cultures was similar in all age groups . Among the 5 to 9 year-old children who could produce a sputum sample, sputum gave just as good culture yield of M . tuberculosis as gastric aspirate . Of the clinical or radiological findings only weight loss was associated with a higher yield . Repeat gastric aspirate increased the culture yield by 6% . Mycobacterial culture from HIV-positive children gave lower yield compared with HIV-negative children . CONCLUSION: Our data suggest that one gastric aspirate for children less than 6 y and three sputum samples for the older children collected at an outpatient TB clinic, is enough to provide a close to 50% yield of M . tuberculosis available for culture and further analyses . However, with an increasing prevalence of HIV, this detection rate may be reduced.

J Oral Maxillofac Surg, 2004 May, 62(5), 567 - 70
Prophylaxis with cefazolin plus clindamycin in clean-contaminated maxillofacial surgery; Lazzarini L et al.; PURPOSE: Infections after maxillofacial surgery are usually due to aerobic and anaerobic gram-positive cocci and gram-negative bacilli . Various antimicrobials, including cephalosporins, beta-lactams/beta-lactamase inhibitors, aminoglycosides, lincosamides, and fluoroquinolones, have been tested for use for perioperative prophylaxis in maxillofacial surgery . However, the best regimen has not been determined . We tested the safety and the efficacy of clindamycin plus cefazolin as perioperative prophylaxis for patients undergoing major maxillofacial procedures . PATIENTS AND METHODS: Intravenous cefazolin and clindamycin in 3 doses were administered to 155 patients undergoing major maxillofacial procedures . After surgery, patients were monitored for the presence of infection and side effects . RESULTS: No patient experienced a fever or infection after surgery . No side effects related to these antibiotics were observed . CONCLUSIONS: The antibiotics used as prophylaxis in maxillofacial surgery should possess an adequate coverage against gram-positive aerobic and anaerobic cocci as well as gram-negative bacilli . Prophylaxis with cefazolin plus clindamycin in major maxillofacial seems safe and effective.

Arq Neuropsiquiatr, 2004 Mar, 62(1), 139 - 43 Epub 2004 Apr 28.
Acute hemorrhagic leukoencephalitis mimicking herpes simplex encephalitis: case report; Martins HM et al.; Acute hemorrhagic leukoencephalitis (AHLE) is a more severe form of acute disseminated encephalomyelitis (ADEM) characterized by a fulminant clinical course and the presence of hemorrhagic necrosis of the white matter . We report the case of a 57-year-old woman who developed delirium following a respiratory infection . Magnetic resonance imaging of the brain disclosed signal abnormalities in the frontal and temporal lobes, usually found in herpes simplex encephalitis (HSE) . Gram stain, India ink and acid-fast bacilli staining were all negative in CSF as was a polymerase chain reaction (PCR) for herpes simplex virus . A diagnosis of AHLE was made and the patient was treated with i.v . methylprednisolone 1g/day for 5 days . Despite treatment, the patient developed several neurological sequelae compatible with the severity of her illness.

Med Dosw Mikrobiol, 2003, 55(4), 333 - 42
{Adhesive properties and antibiotic resistance of Klebsiella strains isolated from gastrointestinal tracts of children hospitalised in Wroclaw nad Opole}; Maczynska B et al.; Gram negative Klebsiella bacilli present many pathogenic properties, which determine their ability to survive and rapid spreading in hospital environment . There are many factors responsible for the pathogenicity of Klebsiella strains: capsule, fimbriae, nonfimbrial adhesins, lipopolysaccharide of the cell wall and extracellular secreted exotoxins . Klebsiella strains are etiological agents of different nosocomial infections but also colonized gastrointestinal and respiratory tracts . The aim of our work were adhesive properties and antibiotic resistance of Klebsiella strains isolated from stool of hospitalized children, according to source of potential nosocomial infections--100 Klebsiella strains from Wroclaw and 76 strains from Opole, isolated in cases of diarrhea . The resistance of this strains to different group of antibiotics, the expression of ESBL enzymes, the activity in hemagglutination and their ability to adherence to different cell lines were tested . The highest resistance of all strains to aminopenicillins was observed . The production of ESBL was highest in strains from Opole (51% strains) then in Wroclaw (9%) . In both hospital units, ESBL+ strains were resistant to aminoglicosides and cotrimoxazol but sensitive to ciprofloxacine . Using hemagglutination method the types of fimbriae were defined . Above 90% investigated Klebsiella strains showed the presence of fimbriae (in Wroclaw more strains simultaneously expressed fimbriae type 1 and 3, in Opole mainly fimbriae type 3) . Over 70% strains demonstrated the high level of adherence to cell lines . Only several strains showed the low level or the lack of adhesion . These results suggested that among Klebsiella strains in gastrointestinal tract were presented multiresistant strains with high ability to adherence, which may be potential source of nosocomial infections.

J Am Acad Dermatol, 2004 May, 50(5 Suppl), S110 - 3
Cutaneous miliary tuberculosis in two patients with HIV infection; High WA et al.; Cutaneous manifestations of miliary tuberculosis are rare . We report two patients with previously unknown advanced human immunodeficiency virus (HIV) infection, who presented with respiratory collapse and an erythematous papulopustular skin eruption . Skin biopsies demonstrated focal dermal microabscess in one patient, and a subcorneal vesicle with an underlying dermal microabscess in the other . Despite the lack of granulomatous inflammation, acid-fast bacilli (AFB) and Fite stains demonstrated numerous acid-fast bacilli, and Mycobacterium tuberculosis was subsequently isolated in either skin and/or sputum cultures . Pulmonary involvement was present in both cases, but was sufficiently diffuse and atypical so as not to be specific for tuberculosis upon initial clinical and radiographic examination . Our two cases illustrate the importance of careful skin examination in patients with HIV infection, since cutaneous dissemination can be an easily overlooked sign of miliary tuberculosis.

J Bacteriol, 2004 May, 186(9), 2856 - 61
A promoter mutation causes differential nitrate reductase activity of Mycobacterium tuberculosis and Mycobacterium bovis; Stermann M et al.; The recent publication of the genome sequence of Mycobacterium bovis showed >99.95% identity to M . tuberculosis . No genes unique to M . bovis were found . Instead numerous single-nucleotide polymorphisms (SNPs) were identified . This has led to the hypothesis that differential gene expression due to SNPs might explain the differences between the human and bovine tubercle bacilli . One phenotypic distinction between M . tuberculosis and M . bovis is nitrate reduction, which not only is an essential diagnostic tool but also contributes to mycobacterial pathogenesis . We previously showed that narGHJI encodes a nitrate reductase in both M . tuberculosis and M . bovis and that NarGHJI-mediated nitrate reductase activity was substantially higher in the human tubercle bacillus . In the present study we used a genetic approach to demonstrate that an SNP within the promoter of the nitrate reductase gene cluster narGHJI is responsible for the different nitrate reductase activity of M . tuberculosis and M . bovis . This is the first example of an SNP that leads to differential gene expression between the human and bovine tubercle bacilli.

Aust Vet J, 2003 Jan-Feb, 81(1-2), 36 - 41
Cytological examination and physical characteristics of the anal sacs in 17 clinically normal dogs; Robson DC et al.; OBJECTIVE: To quantify numbers of leucocytes, keratinocytes and microorganisms in, as well as the turgidity, colour and consistency of, anal sac exudates in clinically normal dogs . DESIGN: Selection criteria were formed based on the absence of clinical signs associated with anal sac disease, and the absence of factors potentially affecting colonic flora . Anal sacs were palpated for turgidity then expressed onto a swab, where colour and consistency were noted . A squash preparation made from any exudate was heat fixed and stained with modified Wright's stain . Eight representative 1000x oil immersion fields from each were examined for leucocytes, erythrocytes, keratinocytes, bacteria and yeast . Results were summarised, and cytological counts grouped into quartiles (minimal, few, moderate, numerous) . Due to the multivariate nature of the study and limited subject numbers, further significant statistical analysis could not be performed . RESULTS: Seventeen dogs satisfied the selection criteria . The physical characteristics of the exudate and sac varied, though 31/34 sacs were empty or soft, 22/27 exudates were light or dark brown and 19/27 exudates were a thin liquid . Total leucocyte, keratinocyte and bacilli counts were extremely variable . Yeasts were present in 26/208 microscopic fields examined cytologically . Only 5/208 fields showed numerous cocci . A single instance of intracellular bacteria and a single erythrocyte were noted following examination of all fields . CONCLUSION: In this study, the characteristics of normal anal sacs and their exudate varied but greater than 70% showed similar features . Exudate cytology was highly variable, though yeasts were uncommon, and intracellular cocci and erythrocytes extremely rare.

Ophthal Plast Reconstr Surg, 2004 Mar, 20(2), 168 - 70
Bacillary angiomatosis with cytomegaloviral and mycobacterial infections of the palpebral conjunctiva in a patient with AIDS; Edmonson BC et al.; We report the clinical and histopathologic findings of bacillary angiomatosis involving the palpebral conjunctiva with concomitant infection by cytomegalovirus and Mycobacterium species in a patient with acquired immune deficiency syndrome . After debulking, the conjunctival tissue was studied with the use of light and electron microscopy; stains for bacteria, acid-fast bacilli, and Bartonella species; and immunohistochemical studies for cytomegalovirus and herpes simplex virus . We observed the typical histopathologic findings of bacillary angiomatosis, the presence of bacilli stained by the Steiner and Steiner method, and the electron microscopic demonstration of bacilli consistent with Bartonella species . Immunohistochemistry confirmed infection with cytomegalovirus, which had been suggested by characteristic cytologic abnormalities . Acid-fast bacilli were also found in the excised tissue . Patients with bacillary angiomatosis of the conjunctiva may have infections with multiple additional microorganisms.

J Chemother, 2004 Feb, 16(1), 94 - 7
Clostridial orthopedic infections: case reports and review of the literature; Lazzarini L et al.; Clostridia are anaerobic Gram-positive bacilli that can be isolated from the soil and the intestinal tract of humans . These microorganisms are recognized as the cause of devastating soft tissue infections, such as cellulitis, myositis, and gas gangrene . However, such bacteria may also be involved in various postoperative orthopedic infections, including prosthetic joint infection . We present three clinical cases of clostridial orthopedic infection and review the related medical literature.

J Physiol Pharmacol, 2003 Dec, 54 Suppl 3, 183 - 92
History and current status of Polish gastroenterological pathology; Stachura J et al.; The present paper summarizes the contribution of Polish investigators to the development of gastroentrology, and especially pathology of the gastrointestinal tract . We called to mind meritorius scientifists among the 19(th)-century and modern pathologists . Especially interesting are discoveries of Browicz, being the first, who described thyphus bacilli and shortly after Kupffer - fagocytozing cells in the liver . Noteworthy are detailed description of tumorous lesions being the contribution to oncological pathology of the gastrointestinal tract as well as the reports on congenital malformations (i.e . esophageal fistulas) . Moreover we remind the investigators dealing with pathology of gastric ulcer disease, its pathogenesis and mechanisms of healing . Of great importance was also the discovery of regeneration existing also outside the mucosal surfaces . In the paper, besides the above-mentioned Tadeusz Browicz investigations of professors: Lesniowski, Ciechanowski, Kowalczykowa, Stachura, Konturek are called to mind.

Dis Colon Rectum, 2004 Jun, 47(6), 937 - 9 Epub 2004 Apr 13.
Sarcoidosis presenting as colonic polyposis: report of a case; Veitch AM et al.; A 47-year-old, West Indian male was referred for investigation of mild iron-deficiency anemia . He was asymptomatic . Two years earlier, he had an episode of transient facial weakness and a separate episode of diplopia . Gastroscopy and duodenal biopsies were normal . Barium enema demonstrated multiple small polyps throughout the colon . At colonoscopy, these polyps had the appearance of adenomatous polyps . Histology revealed noncaseous epithelioid granulomas . There were no acid-fast bacilli, no intervening colitis, and no features of Crohn's disease on small-bowel radiology . Chest x-ray demonstrated bilateral hilar lymphadenopathy . A diagnosis of sarcoidosis with colonic involvement has been made . Sarcoid has been described at various sites in the gastrointestinal tract, presenting with stricturing or ulceration . There have been no previous reports of sarcoidosis presenting as discreet colonic polyps.

Int Urol Nephrol, 2003, 35(2), 203 - 5
Tuberculous orchiepididymitis diagnosed by nucleic acid amplification test: a case report; Barisic Z et al.; Symptoms of tuberculous orchiepididymitis in a 39-year-old male started with swelling of left scrotum, followed by fistula formation with suppurative discharge . There was no any improvement produced by antibiotics . Surgical extirpation of inflammatory destroyed testicle and epidydimis was performed . Presence of tubercle bacilli was not shown by bacteriological analysis of testicle tissue . Tuberculous etiology was suggested after histopathological examination of testis and epididymis . Exudate from surgical wound was examined on presence of Mycobacterium tuberculosis DNA . Etiology of orchiepididymitis was proved by positive assay and inflammatory process was completely cured by antituberculotics therapy . By this report it was clearly shown that sometimes only molecular methods could confirm etiology of inflammatory process.

Indian J Chest Dis Allied Sci, 2004 Apr-Jun, 46(2), 99 - 103
A comparative study of clinico-radiological spectrum of tuberculosis among HIV seropositive and HIV seronegative patients; Prasad R et al.; BACKGROUND: A study to determine the prevalence of human immunodeficiency virus (HIV) infection among tuberculosis patients and to compare the clinico-radiological spectrum of tuberculosis among HIV seropositive and seronegative patients was carried out in the Department of TB and Chest Diseases, CSM Medical University, Lucknow (Uttar Pradesh), India . METHODS: A total of 1105 radiologically and/or bacteriologically confirmed patients of tuberculosis were screened for HIV infection during the years 1995 to 1997 and from 2000-2001 . RESULTS: Out of a total 1105 patients screened, 31(2.8%) were found to be HIV seropositive . Tuberculin positivity was less among HIV seropositive patients as compared to HIV seronegative patients (22.6% vs 76.4%; p < 0.001) . There was no statistically significant difference in sputum smear positivity for acid-fast bacilli (AFB) among HIV seropositive and seronegative patients . Among HIV seropositive patients, mid and lower zone involvement, exudative lesions and mediastinal lymphadenopathy was more common as compared to the seronegative patients . CONCLUSION: HIV seropositivity rates among tuberculosis patients was 2.8 percent . The presentation of tuberculosis was more often atypical among these patients.

Lepr Rev, 2004 Mar, 75(1), 40 - 9
Colorimetric microtitre plate hybridization assay for the detection of Mycobacterium leprae 16S rRNA in clinical specimens; Haile Y et al.; We have developed a colorimetric microtitre plate hybridization assay in order to simplify detection of Mycobacterium leprae in clinical specimens . This system detects the products amplified by a sensitive RT-PCR assay targeting a species-specific sequence of the bacterial 16S rRNA . The assay detected as few as 10 bacilli isolated from infected nude mouse lymph nodes or human skin biopsies . Sensitivity for diagnosis of clinical specimens was assessed for 58 tissue biopsies from untreated leprosy patients . The assay detected M . leprae RT-PCR products in 100% of biopsies from patients with multibacillary disease and 80% of biopsies from patients with paucibacillary disease, for an overall sensitivity of 91.3% . The test was highly specific as no RT-PCR products were amplified from skin biopsies of normal individuals or patients with skin diseases other than leprosy . The colorimetric assay is faster, more sensitive, and simplifies detection of RT-PCR products compared to Southern blot analysis . It may be useful for diagnosis of difficult cases of leprosy, and, since RNA is rapidly degraded after cell death, it may be appropriate for assessing response to therapy and for distinguishing relapse from reaction.

J Clin Microbiol, 2004 Apr, 42(4), 1818 - 21
Generalized tuberculosis in llamas (Lama glama) due to Mycobacterium microti; Oevermann A et al.; Necropsy of two llamas revealed numerous caseous nodules containing abundant acid-fast bacilli (AFB) in various organs . The AFB were identified by spoligotyping as Mycobacterium microti, vole type . Infection caused by M . microti should be considered in the differential diagnosis of debilitating diseases in New World camelids.

J Clin Microbiol, 2004 Apr, 42(4), 1585 - 9
Direct detection of rifampin- and isoniazid-resistant Mycobacterium tuberculosis in auramine-rhodamine-positive sputum specimens by real-time PCR; Ruiz M et al.; Our objective was to evaluate the feasibility of a molecular assay based on a real-time PCR technique, carried out with a LightCycler instrument (Roche Biochemicals), to identify Mycobacterium tuberculosis bacilli and to detect rifampin and isoniazid resistance in DNA extracts from sputum samples . We studied three genes: rpoB, which is associated with rifampin resistance, and katG and inhA, which are associated with isoniazid resistance . A total of 205 sputum samples collected from 108 patients diagnosed with pulmonary tuberculosis with positive auramine-rhodamine-staining (AR) sputum samples, were tested . The sensitivities of the LightCycler PCR assay for the positive AR specimens was 97.5% (200 of 205) for rpoB and inhA genes and 96.5% (198 of 205) for the katG gene . For the total number of patients tested, the sensitivity was 100% (108 of 108 patients) for rifampin, whereas the sensitivity was 98.1% (106 of 108 patients) for isoniazid . Full agreement was found with the Bactec MGIT 960 method and the genotype inferred from the LightCycler data for rifampin . The phenotypic method for isoniazid reported 13 resistant strains (> or = 0.1 microg/ml) . In seven (53.8%) strains there was a concordance between both methods, but we found that six (46.2%) strains reported as resistant by the phenotypic method were determined to be susceptible by real-time PCR . For the 75 strains reported as susceptible by the phenotypic method, the concordance with the LightCycler data was 100% . Our results demonstrate that rifampin-resistant M . tuberculosis could be detected in DNA extracted from auramine-rhodamine-positive sputum samples in a single-tube assay that took less than 3 h to perform for a collection of auramine-rhodamine-positive specimens obtained from patients with culture-documented pulmonary tuberculosis . Similarly, this occurs in half of the isoniazid-resistant M . tuberculosis DNA extracted from auramine-rhodamine-positive specimens.

Vet Microbiol, 2004 Apr 19, 99(3-4), 281 - 5
Mycobacterium nonchromogenicum in nasal mucus from cattle in a herd infected with bovine tuberculosis; McCorry TP et al.; Skin test negative cattle from a herd containing an unusually high proportion (194/382) of tuberculin skin test positive cattle were investigated for remaining Mycobacterium bovis infected animals . Blood samples from the skin test negative cattle, analysed by an antibody ELISA and an interferon-gamma assay, were mostly test negative for M . bovis . Radiometric culture of nasal mucus samples from 48 of the cattle yielded 22 culture positives with acid-fast bacilli and cording in 6 of these . Subculture on solid media was successful for 7, including 2 with cording of the 22 radiometric culture positives . Mycobacterium tuberculosis complex DNA probe testing using the Accuprobe (Gen-Probe, Inc.) and M . tuberculosis complex-specific PCR amplification, performed on the solid media subcultures, were negative . 16S rRNA PCR and sequence analysis were successful for 6 of the 7 solid media subcultures obtained and revealed the presence of Mycobacterium nonchromogenicum in all 6 subcultures . This is the first report of M . nonchromogenicum in nasal mucus of cattle . The observation highlights the importance of integrating definitive tests such as the PCR for diagnosis of bovine tuberculosis and indicates a possible zoonotic risk.

Braz J Med Biol Res, 2004 Apr, 37(4), 485 - 92 Epub 2004 Mar 23.
Experimental murine mycobacteriosis: evaluation of the functional activity of alveolar macrophages in thalidomide- treated mice; Arruda MS et al.; Thalidomide is a selective inhibitor of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in mycobacterial death mechanisms . We investigated the role of this drug in the functional activity of alveolar macrophages in the presence of infection induced by intranasal inoculation of Mycobacterium avium in thalidomide-treated and untreated adult Swiss mice . Sixty animals were inoculated with 5 x 10(6) M . avium by the respiratory route . Thirty animals received daily thalidomide (30 mg/kg mouse) and 30 received water by gavage up to sacrifice . Ten non-inoculated mice were used as a control group . Lots of animals from each group were evaluated until 6 weeks after inoculation . Infection resulted in an increased total number of inflammatory cells as well as increased activity of pulmonary macrophages . Histologically, intranasal inoculation of bacilli resulted in small mononuclear infiltrates located at the periphery of the organ . Culture of lung fragments revealed the presence of bacilli only at the beginning and at the end of the experimental period . Thalidomide administration did not affect the microbiological or histological features of the infection . Thalidomide-treated and untreated animals showed the same amount of M . avium colonies 3 weeks after infection . Although it did not affect bacillary clearance, thalidomide administration resulted in a decreased percent of spread cells and release of hydrogen peroxide, suggesting that factors other than TNF-alpha play a role in the killing of mycobacteria by alveolar macrophages . Thalidomide administration also reduced the number of spread cells among resident macrophages, suggesting a direct effect of the drug on this phenomenon.

Zhonghua Wai Ke Za Zhi, 2004 Feb 7, 42(3), 177 - 81
{Study on Toll-like receptors expression and cytokine production induced by bacillus Calmette-Guerin in human bladder cancer cell}; Li X et al.; OBJECTIVE: To investigate the effect of bacillus Calmette-Guerin (BCG) on Toll-like receptors (TLRs) expression and cytokine production in human bladder cancer cell line T24 . METHODS: Human transitional carcinoma cell line T24 was cultured in RPMI1640 medium with 10% FBS, BCG was added into the cell culture with various doses in bacteria-cell ratio . After T24 cells were stimulated by BCG for 1 hour, total RNA of cells was extracted . RT-PCR procedure was conducted with the primer of TLR-2 and TLR-4, and the products were analyzed with agarose gels electrophoresis . Then the expression of TLR-2 and TLR-4 in T24 cells was assessed by the analyzing system of gel imaging . After the stimulation culture for 12 hours, the supernatant of cells was collected . The levels of IL-4 and IL-12 in each sample were assayed by ELISA method . RESULTS: The expression level of either TLR-2 or TLR-4 was increased by the stimulation of BCG in a dose-dependent manner, the effects reached the maximal level at the dose of BCG as 10 bacilli per cell . The production of IL-12 in T24 cells was also increased gradually by the stimulation of BCG in a dose-dependent manner, and the dose of BCG obtained maximal effect was 10 bacilli per cell, which is coincident with the results observed in the expression of TLRs . There was no difference showed on the production of IL-4 between T24 cells stimulated with BCG and control . CONCLUSIONS: The stimulation of BCG not only up-regulated the expression of TLR-2 and TLR-4, but also increased the production of IL-12 in bladder cancer T24 cell line . The expression of TLRs and the production of cytokine in bladder cancer cells may be related to the BCG-induced immunol response to human bladder cancer.

Clin Microbiol Infect, 2004 Apr, 10(4), 332 - 4
Evaluation of the BDProbeTec strand displacement amplification assay in comparison with the AMTD II direct test for rapid diagnosis of tuberculosis; Visca P et al.; The BDProbeTec MTB assay for direct detection of Mycobacterium tuberculosis was evaluated in comparison with the AMTD-II assay on 94 samples from different patients with clinical suspicion of tuberculosis . Using a combination of culture on Lowenstein-Jensen medium (with or without preculture in BACTEC 9000) and clinical diagnosis as the standard, BDProbeTec MTB showed high sensitivity and specificity (96.1% and 100%, respectively), similar to AMTD-II (96.1% and 97.1%, respectively), with significantly higher sensitivity than the Ziehl-Neelsen stain for acid-fast bacilli (73%, p < 0.05).

Cell Microbiol, 2004 May, 6(5), 423 - 33
An in vitro dual model of mycobacterial granulomas to investigate the molecular interactions between mycobacteria and human host cells; Puissegur MP et al.; In the majority of individuals infected with Mycobacterium tuberculosis, the bacilli cause a long-term asymptomatic infection called latent tuberculosis, a state during which the bacilli reside within granulomas . Latently infected individuals have around 10% risk of progression to clinical disease at a later stage . Determining the state of the mycobacteria and the host cells during this latent phase, i.e . within the granulomas, would greatly improve our understanding of the physiopathology of tuberculosis, and thus enable the development of new therapeutic means to treat the one-third of the world's population who are latently infected . We have developed an in vitro model of human mycobacterial granulomas, enabling the cellular and molecular analysis of the very first steps in the host granulomatous response to either mycobacterial compounds or live mycobacterial species . In vitro mycobacterial granulomas mimic natural granulomas very well, with the progressive recruitment of macrophages around live bacilli or mycobacterial antigen-coated beads, their differentiation into multinucleated giant cells and epithelioid cells, and the final recruitment of a ring of activated lymphocytes . Besides morphological similarities, in vitro granulomas also functionally resemble natural ones, with the development of intense cellular co-operation and intracellular mycobactericidal activities.

Riv Biol, 2003 Sep-Dec, 96(3), 491 - 5
The antimycobacterial effect of honey: an in vitro study; Asadi-Pooya AA et al.; Avicenna recommended honey in the treatment of tuberculosis . Honey has potent bactericidal activity against many pathogenic organisms, but its antimycobacterial effect has never been studied . In this study the antimycobacterial effect of honey was evaluated in vitro . Standard Lowenstein-Jenson media and L-J media containing various concentrations of honey were prepared . Two bacilli from positive cultures and two from positive smears of the affected patients were inoculated on each of the prepared plates . It was demonstrated that the growth of mycobacteria was inhibited by adding 10% honey to the media . Mycobacteria did not grow in culture media containing 10% and 20% honey while it grew in culture media containing 5%, 2.5% and 1% honey . The good antimycobacterial effect, sterility, low cost, and easy availability of honey makes it an ideal antimycobacterial agent.

J Vet Diagn Invest, 2004 Mar, 16(2), 145 - 9
Erysipelothrix septicemia in a little blue penguin (Eudyptula minor); Boerner L et al.; On June 25, 2002, aquarium veterinarians treated a 5-year-old, male little blue penguin (Eudyptula minor) that was acutely recumbent and dull, with inappetence of 24-hour duration . The penguin died within 10 minutes of presentation despite emergency resuscitation efforts . Gross pathologic findings consisted of pulmonary congestion and intestinal hemorrhage . Histopathologic findings included necrosis of tips of intestinal villi, increased numbers of mononuclear cells in pulmonary interstitium and hepatic sinusoids, and gram-positive bacteria in systemic microvasculature . Transmission electron microscopic examination revealed short gram-positive bacilli located in lumina of glomerular capillaries and in cytoplasm of mononuclear phagocytic cells in the lung and liver . Erysipelothrix rhusiopathiae was recovered from the lung, liver, and intestine by bacteriologic culture . Amplicons from polymerase chain reaction (PCR) tests using Erysipelothrix genus-specific primers and total genomic DNA extracted from formalin-fixed, paraffin-embedded tissue sections of lung and intestine demonstrated 99% nucleotide sequence identity with 16S small-subunit ribosomal DNA of E . rhusiopathiae and E . tonsillarum . The source of infection was speculated to be fish in the diet; however, repeated attempts to detect Erysipelothrix spp . from the mucous layer of food fish using bacteriologic culture and PCR were unsuccessful . This is the first report of erysipelas in a captive aquatic bird . Details of the isolation of E . rhusiopathiae and the application of molecular testing to identify Erysipelothrix DNA in formalin-fixed, paraffin-embedded tissue sections are given.

Intensive Care Med, 2004 May, 30(5), 965 - 71 Epub 2004 Mar 30.
Predictive factors of intensive care unit admission in patients with haematological malignancies and pneumonia; Gruson D et al.; OBJECTIVE: To describe early signs at the onset of pneumonia occurring in the haematology ward which could be associated with a transfer to the ICU . DESIGN: A 13-month preliminary prospective observational cohort study . SETTING: Department of haematology and (32-bed) medical intensive care unit (ICU) . PATIENTS: Fifty-three of 302 patients hospitalised in the haematology ward who developed presumptive clinical evidence of pneumonia were enrolled . MEASUREMENTS AND RESULTS: At the onset of the clinical evidence of pneumonia (day 1), we compared variables between patients requiring an ICU admission and those who did not . Twenty-four patients (45%) required a transfer to the ICU . Factors associated with ICU admission were: numbers of involved quadrants: 2.3 vs 1, P=0.001 and oxygenation parameters (initial level of O(2) supplementation: 3.5 vs 0.9 l/min, P<0.05), the presence of hepatic failure (58% vs 10%, P<0.01), Gram-negative bacilli isolated in blood culture (7 vs 1, P=0.01) . In the multivariate analysis, a decrease of 10% in the SaO(2) and the requirement of nasal supplementary O(2) at the onset of acute respiratory failure increased the risk of admission to MICU, respectively, by 18 and by 14 . The overall 6-month mortality rate of the 53 patients was 28% . CONCLUSION: Parameters of oxygenation and radiological score could be associated with this transfer on day 1 of the onset of pneumonia occurrence . A further study should evaluate an earlier selection of this type of patient, followed by an "early" admission to the MICU, in order to improve ICU outcome.

Can J Microbiol, 2004 Feb, 50(2), 97 - 105
Expression and purification of immunologically reactive DPPD, a recombinant Mycobacterium tuberculosis skin test antigen, using Mycobacterium smegmatis and Escherichia coli host cells; Liu C et al.; DPPD is a Mycobacterium tuberculosis recombinant antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both guinea pigs and humans infected with M . tuberculosis . In addition, earlier clinical studies with DPPD suggested that this molecule could improve the specificity of the tuberculin skin test, which is used as an important aid for the diagnosis of tuberculosis . However, these studies could only be performed with DPPD engineered as a fusion molecule with another Mycobacterium spp . protein because no expression of DPPD could be achieved as a single molecule or as a conventional fusion protein in any commercial system . Although recombinant fusion proteins are in general suitable for several biological studies, they are by definition not ideal for studies involving highly purified and defined polypeptide sequences . Here, we report two alternative approaches for the expression of immunologically reactive recombinant genuine DPPD . The first approach used the rapidly growing, nonpathogenic Mycobacterium smegmatis as host cells transformed with the pSMT3 plasmid vector containing the full-length DPPD gene . The second approach used Escherichia coli transformed with the pET-17b plasmid vector containing the DPPD gene engineered in a three-copy fusion manner in tandem with itself . Though at low levels, expression and purification of immunologically reactive DPPD in M . smegmatis could be achieved . More abundant expression and purification of DPPD as a homo-trimer molecule was achieved in E . coli (> or =2 mg/L of bacterial broth cultures) . Interestingly, expression could only be achieved in host cells transformed with the DPPD gene containing its leader peptide . However, the expressed proteins lacked the leader sequence, which indicates that processing of the M . tuberculosis DPPD gene was accurately achieved and necessary in both M . smegmatis and E . coli . More importantly, the delayed type hypersensitivity reactions elicited by purified molecules in guinea pigs infected with M . tuberculosis were indistinguishable from that elicited by purified protein derivative . Because the DPPD gene is present only in the tuberculosis-complex organisms of the Mycobacterium genus, these highly purified molecules should be helpful in identifying individuals sensitized with tubercle bacilli.

J Mol Biol, 2004 Apr 16, 338(1), 43 - 53
The interaction of RNA with TRAP: the role of triplet repeats and separating spacer nucleotides; Hopcroft NH et al.; The trp RNA-binding attenuation protein (TRAP) regulates expression of the tryptophan biosynthetic genes in several Bacilli by binding to the leader region of the nascent trp mRNA, inhibiting continued transcription . The 11 subunit TRAP molecule is active in complex with tryptophan, and binds consequently an RNA target segment consisting of 11 (G/U)AG triplets, each separated by two or three non-conserved "spacer" nucleotides . Here, we report the first crystal structures of TRAP in a complex with RNA containing UAG triplets separated by two nucleotides and in a complex with RNA containing GAG triplets separated by three nucleotides . Comparison with known structures of TRAP-RNA complexes shows that both substitution of G-1 with U-1 in the triplet and addition of an extra spacer nucleotide lead to a more flexible complex . This suggests an explanation why, in the trp leader RNA, all three-nucleotide spacer regions are followed by a G-1 nucleotide . Taken together, the structures demonstrate that RNA binding to TRAP is mediated by specific interactions involving the A-2 and G-3 nucleotides of the triplet . This is accompanied by the disruption of stacking interactions between the bases of the other nucleotides, contributing to the increase in entropy that drives binding.

Clin Imaging, 2004 Mar-Apr, 28(2), 119 - 23
Relationship between CT findings of pulmonary tuberculosis and the number of acid-fast bacilli on sputum smears; Matsuoka S et al.; PURPOSE: To investigate the relationship between computed tomography (CT) findings in patients with active pulmonary tuberculosis (PTB) and the number of acid-fast bacilli (AFB) on sputum smears . Methods: We reviewed CT scans of 173 patients with active PTB . The patients were divided into groups according to the number of AFB on sputum smears as follows: A, negative (n = 40); B, doubtful (n = 21); C, + (n = 34); and D, ++ or greater (n = 78) . The presence or absence and the number of lobes that included micronodules, nodules, consolidation and cavitation, the number of cavities and the maximum diameter of the cavity lumen were noted . RESULTS: The frequency of micronodules and nodules did not significantly differ among the four groups . In contrast, the frequency of consolidation and cavitation increased with the number of AFB (P < .0001) . Differences in the number of lobes involving micronodules, nodules, consolidation and cavitation were significant between Group D and the other groups (P < .0001), but not between Groups A or B and C . The number and maximum size of cavities significantly differed between Group D and the other groups (P < .0001) . Conclusions: CT findings correlated with the number of AFB in sputum smears to some extent . However, CT findings do not reliably discriminate between smear-negative patients and those with very few AFB excreting smear-positive patients.

Dig Liver Dis, 2004 Mar, 36(3), 199 - 204
Tuberculous peritonitis of the wet ascitic type: clinical features and diagnostic value of image-guided peritoneal biopsy; Vardareli E et al.; BACKGROUND: Abdominal tuberculosis is still a medical problem in developing countries . AIMS: To analyse the clinical, laboratory, ultrasonography and computed tomography findings and to discuss the diagnostic approach of 19 patients with peritoneal tuberculosis . PATIENTS: Nineteen patients diagnosed in our department, with peritoneal tuberculosis (8 female, 11 male; mean age: 47.89 +/- 4.3 years) between 1996 and 2002, were studied retrospectively . METHODS: All clinical, laboratory, radiological findings, and diagnostic methods were reviewed . RESULTS: The most common symptoms and signs of the disease in these patients were abdominal pain, ascites, weight loss and night sweats . On conducting skin test, eight patients (42%) were found to be positive, while all the patients had elevated serum cancer antigen 125 levels, but acid-resistant bacilli could not be demonstrated on the direct preparation . In three patients (15.78%), the ascitic fluid culture was positive . The most common ultrasonographic and computed tomographic findings were ascites, septation in the ascites, peritoneal thickening, mesenteric and omental involvement . An abnormal chest X-ray, suggestive of previous tuberculosis was present in three patients . Diagnosis was made by image-guided percutaneous peritoneal biopsy in 18/19, and by histological examination of biopsy specimens obtained via laparoscopy in 1/19 . Laparoscopy was only performed in 1 of the 19 patients due to lack of sufficient material for histological diagnosis by percutaneous biopsy . Of the biopsy specimens, 84% revealed caseating granulomas, while 16% were non-caseating . Acid-fast bacilli were seen on the Ziehl-Neelsen stain in 18 patients . CONCLUSIONS: Peritoneal tuberculosis should be considered in the differential diagnosis of exudative ascites . Image-guided percutaneous peritoneal biopsy seems to be a sufficient, safe and inexpensive method for diagnosis of peritoneal tuberculosis.

Rev Soc Bras Med Trop, 2004 Jan-Feb, 37(1), 46 - 50 Epub 2004 Mar 19.
Characteristics of pulmonary tuberculosis in HIV seropositive and seronegative patients in a Northeastern region of Brazil; Liberato IR et al.; The aim of this study was to analyse the clinical, epidemiological and bacteriological features present in 60 pulmonary tuberculosis patients who were also infected with human immunodeficiency virus (HIV) and to compare these with 120 TB patients who were not infected with HIV . The patients with pulmonary tuberculosis and HIV coinfection were mostly male (p = 0.001), showed a higher frequency of weight loss >10 kilos (p <0.001), had a higher rate of non-reaction result to the tuberculin skin test (p <0.001), a higher frequency of negative sputum smear examination for acid-fast bacilli (p = 0.001) and negative sputum culture for Mycobacterium tuberculosis (p = 0.001) . Treatment failure was more common in those who were HIV positive (p <0.000) . No higher frequency of resistance to antituberculosis drugs was found to be associated with TB/HIV coinfection (p = 0.407) . Association between extrapulmonary and pulmonary tuberculosis was more frequent in those seropositive to HIV than those without HIV virus, 30% and 1.6% respectively . These findings showed a predominance of atypical clinical laboratory features in co-infected patients, and suggest that health care personnel should consider the possibility this diagnosis.

Infect Immun, 2004 Apr, 72(4), 2420 - 4
Effect of growth state on transcription levels of genes encoding major secreted antigens of Mycobacterium tuberculosis in the mouse lung; Shi L et al.; Arrest of the multiplication of Mycobacterium tuberculosis caused by expression of adaptive immunity in mouse lung was accompanied by a 10- to 20-fold decrease in levels of mRNAs encoding the secreted Ag85 complex and 38-kDa lipoprotein . esat-6 mRNA levels were high throughout infection . The data imply that multiplying and nonreplicating tubercle bacilli have different antigen compositions.

Vet Microbiol, 2004 Mar 5, 98(3-4), 285 - 95
Isolation and identification of mycobacteria in New World primates maintained in captivity; Alfonso R et al.; The presence of several Mycobacterium species was determined in 68 New World monkeys kept captive in the Cali Zoo . One hundred and thirty-three gastric lavage and blood samples were evaluated for mycobacterial presence by Ziehl-Neelsen (ZN) staining, culture and PCR amplification of the Mycobacterium tuberculosis Mtp40 species-specific gene . Mycobacteria other than tuberculosis (MOTT) were identified by PCR restriction fragment length polymorphism (RFLP) . Different species of mycobacteria were detected in 65% of the primate population studied by Alpha Antigen PCR . Eleven percent were positive for Mtp40 PCR amplification, being diagnosed as having M . tuberculosis, and acid-fast bacilli were observed in 23% by ZN staining . MOTT were isolated from samples taken from 37 primates by culturing; according to the RFLP analysis, three strains were classified as belonging to the MAISS complex (Mycobacterium avium-intracellulare-scrofulaceum-simiae) and eight more, isolated from soil inside the cages, were categorized as environmental contaminants . Mycobacterium spp . were detected in 13 different New World primate species showing that PCR amplification of the Mtp40 gene is a better tool than culture for M . tuberculosis detection in captive animals and that RFLP is a useful technique for MOTT identification.

Infez Med, 1995 Mar, 3(1), 38 - 44
{Tuberculosis and HIV infection in Guinea Bissau . Epidemiological audit and assessment of survival}; Sabbatani S et al.; The authors briefly report the epidemiological status of HIV-1 and HIV-2 infections among patients affected by tuberculosis in Guinea Bissau and evaluate the therapeutic follow up in 177 patients contemporarily affected by TBC and HIV-2 infection . The evaluation of the surviving times has been done according to the Kaplan-Meier curve by considering the following determinants: 1) sex; 2) sputum positive for acid-fast bacilli; 3) age range: A) 10-30 years - B) 31-45 years - C) more than 45 years . The total number days/person was 1417 . The drop out was moderate . The serum prevalence for HIV-2 in patients affected by tuberculosis in Guinea Bissau is about 20% but in the last two years HIV-1 infection is increasing . There is no significant difference in the surviving curves due to the sex . Tbc-HIV-2+ patients have a longer survival than tbc-HIV-1+ patients reported by European and North America epidemiological data . The present epidemiological data were obtained in an African environment and, due to the low financial support, it was not possible to correlate them with the immunological and microbiological ones.

J Immunol, 2004 Apr 1, 172(7), 4592 - 8
Mycobacterium tuberculosis resides in nonacidified vacuoles in endocytically competent alveolar macrophages from patients with tuberculosis and HIV infection; Mwandumba HC et al.; Alveolar macrophages (AM) are the first professional phagocytes encountered by aerosols containing infections in the lungs, and their phagocytic capacity may be affected by these infections or environmental particles . The aim of this study was to evaluate the innate endocytic and phagocytic properties of human AM obtained from patients with pulmonary tuberculosis and to characterize the vacuoles in which Mycobacterium tuberculosis bacilli reside in vivo . AM were obtained by bronchoalveolar lavage from patients with suspected tuberculosis and from asymptomatic volunteers (controls) . Clinical case definitions were based on mycobacterial culture of respiratory specimens and HIV serology . To assess phagocytosis, endocytosis, and acidification of the endosomal system, AM were cultured with IgG-coated polystyrene beads, dextran, and a pH-sensitive reporter (3-(2,4-dinitroanilino)-3-amino-N-methyldipropylamine) and were evaluated by light and immunoelectron microscopy . Cells from 89 patients and 10 controls were studied . We found no significant difference between the two groups in the ability of AM either to ingest beads and dextran or to deliver them to acidified lysosomes . In AM from patients with tuberculosis, the bacilli were located in vacuoles that failed to accumulate endocytosed material and were not acidified . We concluded that AM from patients with tuberculosis and HIV infections were competent to endocytose and phagocytose material and to deliver the material to functional, acidified lysosomes . M . tuberculosis residing in these AM arrests the progression of their phagosomes, which fail to fuse with acidified lysosomes . This confirms, for the first time in humans with tuberculosis and HIV, the conclusions from previous animal and in vitro studies.

J Biol Chem, 2004 May 28, 279(22), 23082 - 7 Epub 2004 Mar 19.
Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis; Roberts DM et al.; Current estimates indicate that nearly a third of the world's population is latently infected with Mycobacterium tuberculosis . Reduced oxygen tension and nitric oxide exposure are two conditions encountered by bacilli in vivo that may promote latency . In vitro exposure to hypoxia or nitric oxide results in bacterial stasis with concomitant induction of a 47-gene regulon controlled by the transcription factor DosR . In this report we demonstrate that both the dosS gene adjacent to dosR and another gene, dosT (Rv2027c), encode sensor kinases, each of which can autophosphorylate at a conserved histidine and then transfer phosphate to an aspartate residue of DosR . Mutant bacteria lacking both sensors are unable to activate expression of DosR-regulated genes . These data indicate that DosR/DosS/DosT comprise a two-component signaling system that is required for the M . tuberculosis genetic response to hypoxia and nitric oxide, two conditions that produce reversible growth arrest in vitro and may contribute to latency in vivo.

Kekkaku, 2004 Feb, 79(2), 33 - 7
{The value of proper sputum collection instruction in detection of acid-fast bacillus}; Hirooka T et al.; PURPOSE: This study was conducted to assess clinically whether intervention with instruction applying respiratory rehabilitation method for expectorating sputum was useful or not to obtain more suitable sputum for smear examination of acid-fast bacilli . SUBJECT: All specimens examined were sputa obtained from 163 patients without the instruction group and 161 patients with the instruction group, who visited our outpatients clinic during one year from September 1, 2000 to August 31, 2001 and the following one year, respectively . METHOD: Gross appearance of the sputum according to Miller & Jones' classification (M1, M2, P1-P3) and smear positive rate by fluorescence staining method after N-Acetyl-L-cysteine-NaOH treatment and centrifugation were compared between the two groups . RESULTS: M1 and P1 sputa were 21.5% and 21.5% in the no instruction group, while those were 8.1%, 36.6% in the instruction group . Difference in M2, P2 and P3 sputa were not significant between the groups . Smear positive rate was 10.4% in the no instruction group, while it was 21.1% in the instruction group . According to gross appearance of M2, P1 and P2, positive rate was 11.1%, 11.4% and 30.8% in the no instruction group, and 17.7%, 28.8%, and 26.3% in the instruction group . Chest roentogenographic findings judged by type (cavitary and non-cavitary) and extent of the pulmonary lesions of these smear positive cases (17 in the no instruction group and 34 with the instruction group), revealed that the no instruction group consisted of more predominantly severer disease with cavity and moderately or far advanced lesions as compared with the instruction group . CONSIDERATION: We could exclude that the difference in gross appearance and smear-positive rate of the sputum specimen between groups without and with the instruction might be due to differences in disease severity between the two groups with and without the instruction . CONCLUSION: The instruction for sputum expectoration seems to be useful to increase positive rate in the smear examination of acid-fast bacilli.

Indian J Pathol Microbiol, 2003 Jul, 46(3), 521 - 3
Enhanced detection of Mycobacteria stained with rhodamine auramine at 37 degrees C; Sethi S et al.; Sputum smear microscopy is the most efficient and rapid technique for detection of acid-fast bacilli (AFB) . Fluorochrome method of staining is preferred for Mycobacteria in the overburdened laboratories as the fluorescing bacilli are more readily detected than the fuchsin stained bacilli in shorter period of time . A total of 300 sputum samples obtained from suspected cases of Tuberculosis were collected and were subjected to staining by rhodamine auramine at 37 degrees C and also at room temperature (conventional method) . The smears were then blindly evaluated . Fifty-eight samples were positive by both methods and 5 were positive at 37 degrees C only . Staining at 37 degrees C increased the smear positivity by 8.6% over conventional staining at room temperature . No smears were positive only with staining at room temperature alone . Out of 58 smears positive by both methods, 25 had equal number of AFB in both smears, 22 had more AFB in smear stained at 37 degrees C and 11 had greater number of AFB in smears stained at room temperature . Our study, therefore, indicates that rhodamine auramine staining at 37 degrees C is superior to conventional auramine method at room temperature for detecting AFB in sputum smears.

Indian J Pathol Microbiol, 2003 Jul, 46(3), 511 - 4
Role of ELISA in H . pylori detection and its correlation with urease test; Gupta P et al.; Helicobacter pylori is one of the most common chronic bacterial infection in humans linked to acid peptic diseases, gastric carcinomas and lymphomas . The bacilli produces large amounts of urease and this property has formed the basis of detection of H . pylori by the Christensen's urease test . Where endoscopy is not clinically indicated, serology may be used to establish the diagnosis . This study was undertaken to diagnose H . pylori with the help of Christensen's urease test on endoscopic biopsy specimens & correlated with the detection in Sera, of IgG antibodies against H . pylori, by ELISA technique . The study was conducted on 100 patients suffering from acid peptic disorders out of which 40 (40%) tested positive for H . pylori both by urease and serology . Christensen's urease and ELISA were found to have sensitivities of 85.7% & 90.9% and specificities of 96% and 87.5% respectively . Christensen's urease was taken as a standard method of diagnosis and its correlation with ELISA worked out to (+1) which meant there was a strong positive association between both the tests . Hence either test could be used for primary diagnosis of H . pylori instead of histopathological study and/or culture of H . pylori.

Indian J Pathol Microbiol, 2003 Apr, 46(2), 261 - 4
Seroreactivity of 31 kDa and 41 kDa mycobacterial secretory proteins isolated from culture filtrate in extra pulmonary tuberculosis; Banerjee S et al.; Despite rapid advances in molecular genetics for detection of mycobacteria, it is clear that interest in serodiagnosis remains high, especially for those situations in which a specimen may not contain the infecting agent in particular in extrapulmonary tuberculosis . Immune response to excretory-secretory (ES) proteins of Mycobacterium tuberculosis (M.tb) has been of diagnostic interest in tuberculosis . In earlier study from our laboratory, a secretory protein M.tb ES-31 has been shown to have diagnostic potential in pulmonary tuberculosis . Further, another M.tb H37Ra ES protein (ES-41) was isolated and purified by trichloroacetic acid solubilization followed by Fast Performance Liquid Chromatography (FPLC) . These two protein fractions viz ES-31 and ES-41 secreted by M.tb H37 Ra bacilli were employed in stick indirect penicillinase ELISA to study seroreactivity in extra pulmonary tuberculosis namely tuberculous lymphadenopathy, tuberculous meningitis, abdominal tuberculosis and bone & joint tuberculosis . While using ES-31 antigen 88% (22/25) of tuberculous lymphadenopathy and 90% (9/10) of tuberculous meningitis cases showed positive reaction for tuberculous IgG antibody, ES-41 showed 80% positivity in both groups . In abdominal and bone & joint tuberculosis cases, ES-41 antigen showed better sensitivity of 81.5% (22/27) and 84.6% (22/26) respectively in IgG antibody detection compared to 70% (19/27) and 69.2% (18/26) shown by ES-31 . This study is of interest that different antigen protein fractions of M.tb exhibit differential seroreactivity, as ES-31 protein showed good potential in detecting tuberculous IgG antibodies in tuberculous lymphadenopathy (TBLN) & tuberculous meningitis (TBM), while ES-41 in abdominal and bone & joint tuberculosis cases.

Infect Genet Evol, 2004 Mar, 4(1), 5 - 14
Phylogenetic reconstruction of Mycobacterium tuberculosis within four settings of the Caribbean region: tree comparative analyse and first appraisal on their phylogeography; Duchene V et al.; In order to compare phylogenetic methods and to reconstruct the evolutionary history of the tubercle bacilli, a set of macro-array-based genotyping data of Mycobacterium tuberculosis clinical isolates (called spoligotyping for spacer oligonucleotide typing, which assays the variability of the Direct Repeat -DR- locus), was analyzed in four settings of the Caribbean region (Guadeloupe, Martinique, Cuba and Haiti) . A set of 47 alleles, split into 26 shared and 21 unique alleles) representative of 321 individual M . tuberculosis clinical isolates from patients residing in the above regions was studied . The following methods (and software in brackets) were investigated: numerical taxonomy distance methods (TAXOTRON), maximum parsimony procedure (PAUP), median-joining networks (NETWORK), and nested clade analysis (GEODIS) . Results using these methods were analyzed, compared and discussed . The latter method (GEODIS) was investigated in detail by introducing geographical data together with genetic variability results to detect a link between population structure and population history, and to test the null hypothesis of no association between geography and genotypes . Irrespective of the methods used, our findings demonstrate that a core structure of four families (or clades) of M . tuberculosis strains is highly prevalent within the islands studied, indirectly reflecting passed colonization history of these different settings . Specificity of M . tuberculosis genotypes in each of the islands is discussed in the light of their respective colonial and contemporary histories.

Ophthalmology, 2004 Feb, 111(2), 291 - 6
Tubercular preseptal cellulitis in children: a presenting feature of underlying systemic tuberculosis; Raina UK et al.; OBJECTIVE: To present the clinical findings in 7 patients with preseptal cellulitis caused by tuberculosis . DESIGN: Retrospective noncomparative interventional case series . PARTICIPANTS: Seven patients . METHODS: Review of clinical findings, course, diagnostic tools, and management of 7 cases with tubercular preseptal cellulitis . MAIN OUTCOME MEASURES: Healing of local and systemic lesions, cosmetic correction . RESULTS: The presenting features of tuberculosis included lid abscess formation in 5 cases, with spontaneous fistulization in 2 patients . Two cases were initially seen with a cicatricial ectropion of the upper lid . A history of a lid swelling with spontaneous fistulization was present in both cases . Nonresponsiveness of the lesions to systemic antibiotics led to a detailed evaluation of the patients, and evidence of an underlying active or healed systemic focus was present in all the cases . Acid-fast bacilli from pus from the discharging sinuses were identified in only 1 case, and in another patient, a biopsy specimen of the submandibular lymph node showed caseation necrosis . In the other cases, the diagnosis was presumptive from a strongly reactive Mantoux test, raised erythrocyte sedimentation rate, and the presence of a systemic focus . All the patients showed a dramatic response with antitubercular treatment, with complete healing of lesions . Two patients had a residual cicatricial ectropion, which was corrected surgically in both cases . CONCLUSIONS: Preseptal or lid involvement can be the presenting feature of tuberculosis and a marker for underlying systemic focus in children . Spontaneous fistulization of the abscess, minimal inflammatory signs, nonresponsiveness to antibiotic therapy, tethering to the underlying structures and skin, and the presence of a cicatricial ectropion should alert the clinician to look for an alternate diagnosis . The lid presentation might be a marker of an underlying systemic focus; therefore, awareness of the many faces of tuberculosis is important for ophthalmologists.

Ann Acad Med Singapore, 2004 Jan, 33(1), 95 - 9
Transmission of tuberculosis from patient to healthcare workers in the anaesthesia context; Teo DT et al.; INTRODUCTION: Pulmonary tuberculosis (PTB) is prevalent in our population . We report an incident of healthcare workers (HCWs) suspected of being infected by a patient with undiagnosed active PTB in the operating theatre . CLINICAL PICTURE: A 60-year-old patient admitted for intestinal obstruction, underwent an emergency laparotomy . Preoperative chest X-ray (CXR) showed diffuse reticular-nodular shadowing and postoperative sputum was positive for acid-fast bacilli . TREATMENT: The patient was isolated and treated for active tuberculosis . The anaesthetist and her assistants in the operating theatre that day were referred to the infectious disease physician and some were started on tuberculosis prophylaxis . OUTCOME: The patient and the HCWs involved recovered . CONCLUSION: Thus, all PTB-susceptible patients with suggestive CXR should be treated as potentially infective . Adequate personnel protection should include highly efficient facemasks and shields . Risk of patient-to-patient transmission of tuberculosis through the anaesthetic circuit is low if effective bacterial/viral filters are used.

Yonsei Med J, 2004 Feb 29, 45(1), 169 - 73
M . chelonae soft tissue infection spreading to osteomyelitis; Kim RS et al.; A previously healthy, 54-year-old woman presented with Mycobacterium chelonae soft tissue infection and osteomyelitis of her left lower leg . The infection had started from soft tissue emerging at the medial aspect of the distal femur and had spread through the bone because of delayed diagnosis . The largely indolent, 8-month course to diagnosis was attributable to unremarkable clinical manifestations combined with a low index of suspicion such as immunocompetent patient and/or inadequate finding of acid-fast bacilli in a lesion smear, characteristic histopathological features, and culture techniques . Soft tissue infection and osteomyelitis were successfully treated without surgical intervention and with a 6-month course of chemotherapy.

J Clin Microbiol, 2004 Mar, 42(3), 1136 - 41
Rapid serodiagnosis of active pulmonary Mycobacterium tuberculosis by analysis of results from multiple antigen-specific tests; Okuda Y et al.; We have prospectively analyzed three antigens for serodiagnosis of tuberculosis (TB) . These antigens were tuberculous glycolipid antigen, lypoarabinomannan polysaccharide antigen, and antigen 60 (A60), which was derived from purified protein derivatives . Of the 131 patients with active pulmonary TB, 57 were both smear and culture negative and 14 had chronic active pulmonary TB that remained smear positive for >12 months of chemotherapy . One hundred twenty healthy adults were controls . The percentages of patients positive in all three tests were 58.8% for smear-positive active pulmonary TB and 71.4% for chronic active pulmonary TB . When the results of the three serodiagnostic tests were evaluated in combination, the sensitivity increased to 91.5% in patients with active pulmonary TB and to 86.0% in smear- and culture-negative patients . The false-positive rate of the three-test combination was 12.5% in the healthy control groups . In conclusion, it was not possible to detect all of the antibodies against antigenic substances in the cell walls of the tuberculous bacilli in the sera of all TB patients by using available serodiagnostic tests . However, the combined use of tests with three separate antigens maximizes the effectiveness of serodiagnosis.

Nippon Ronen Igakkai Zasshi, 2004 Jan, 41(1), 117 - 20
{A case of tuberculous pyometrium concurrent with tuberculous pleurisy}; Hashida H et al.; An 84-year-old woman began to have low fever below 38 degrees C with slight lassitude from June 19, 2002 . Despite oral administration of Clarithromycin for 3 days, the fever did not subside and the lassitude increased, so she was admitted to our department . While inflammatory findings were noticed, the cause was not identified by blood and imaging examinations (thoracoabdominal CT, etc.) . Although her tuberculin reaction was positive, symptoms indicative of pulmonary tuberculosis were absent . Administration of Cefotiam and Imipenem Cilastatin sodium was ineffective . Pyometra was diagnosed . After drainage, the uterine cavity was washed every day . On the basis of culture of fluid retained a few colonies of Gram-negative bacteria were isolated, but were not identified, Cefpirome was administered, whereupon the fever subsided gradually, but mild inflammatory findings remained . Even after discharge on July 24, the retention increased, so drainage and washing were done repeatedly . However, mild inflammatory findings persisted . She began to have a fever from September 17 and was readmitted . After admission, administration of Flomoxef sodium was started, but no improvement was seen . A small amount of hydrothorax appeared on the left . Thoracocentesis yielded a bloody, slightly turbid exudative . Acid-fast staining and Mycobacterium tuberculosis specific PCR of pleural effusion were negative, but adenosindeaminase was 87.4 U/l . Therefore, a diagnosis of tuberculous pleurisy was made . DNA/PCR of tubercle bacilli in the fluid retained in the uterus was positive, and re-retention was prevented by administration of anti-tuberculosis drugs . These findings suggest a strong possibility of tubercle bacillus having been the causative bacteria . Particularly in the case of the elderly, it appears important that pyometra be included in differential diagnosis as the cause of fever even without gynecological symptoms and that tubercle bacillus be considered the causative bacterium.

J Antimicrob Chemother, 2004 Apr, 53(4), 635 - 40 Epub 2004 Mar 03.
Chemotherapeutic potential of alginate-chitosan microspheres as anti-tubercular drug carriers; Pandey R et al.; OBJECTIVES: This study was designed to develop alginate-chitosan microspheres as drug carriers to reduce dose/dosing frequency in the management of tuberculosis (TB), which otherwise demands prolonged chemotherapy . METHODS: Alginate-chitosan microspheres encapsulating three frontline anti-tuberculous drugs (ATDs), rifampicin, isoniazid and pyrazinamide, were formulated . A therapeutic dose and a half-therapeutic dose of the microsphere-encapsulated ATDs were orally administered to guinea pigs for pharmacokinetic/chemotherapeutic evaluations, respectively . RESULTS: The drug encapsulation efficiency ranged from 65% to 85% with a loading of 220-280 mg of drug per gram microspheres . Administration of a single oral dose of the microspheres to guinea pigs resulted in sustained drug levels in the plasma for 7 days and in the organs for 9 days . The half-life and mean residence time of the drugs were increased 13- to 15-fold by microsphere encapsulation, along with an enhanced relative/absolute bioavailability . The sustained release and increase in bioavailability were also observed with a sub-therapeutic dose of the microspheres . In Mycobacterium tuberculosis H37Rv-infected guinea pigs, administration of a therapeutic dose of microspheres spaced 10 days apart produced a clearance of bacilli equivalent to conventional treatment for 6 weeks . The most important observation, however, was the documentation of therapeutic benefit with a half-therapeutic dose of the microspheres administered weekly . CONCLUSION: Alginate-chitosan microspheres hold promise as a potential natural polymer-based oral ATD carrier for better management of TB.

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