J Infect Dis, 1998 Dec, 178(6), 1795 - 8 Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities . The Genital Ulcer Disease Surveillance Group; Mertz KJ et al.; To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city . Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV . H . ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%) . T . pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%) . HSV was detected in >/=50% of specimens from all cities except Memphis (42%) . HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%) . These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities. J Infect Dis, 1998 Dec, 178(6), 1688 - 97 The immune response to Haemophilus ducreyi resembles a delayed-type hypersensitivity reaction throughout experimental infection of human subjects; Palmer KL et al.; Previous work in 3 subjects infected for 2 weeks indicated that experimental infection with Haemophilus ducreyi recruits CD4 cells to the skin at the pustular stage of disease . In order to describe the kinetics of the host response, 23 subjects were infected at 2 sites with a standardized dose of H . ducreyi . Subjects were biopsied 1 or 4 days after inoculation or when they developed a painful pustular lesion (days 7-14) . Papules and pustules contained a predominant T cell infiltrate that consisted of CD45RO and CD4 cells of the alpha beta lineage . Both papules and pustules contained mixed or T helper 1 type cytokine mRNA and interleukin-8 and tumor necrosis factor-alpha mRNA . Although the subjects had no history of chancroid, their immune responses resembled delayed-type hypersensitivity reactions that occurred within 24 h of inoculation and persisted throughout the course of experimental infection. J Infect Dis, 1998 Dec, 178(6), 1684 - 7 Standardization of the experimental model of Haemophilus ducreyi infection in human subjects; Al-Tawfiq JA et al.; Human volunteers were challenged with Haemophilus ducreyi . Twenty subjects were inoculated with 2 doses (approximately 30 cfu) of live and 1 dose of heat-killed bacteria at 3 sites on the arm . Eight subjects were assigned to biopsy 1 or 4 days after inoculation, and 12 were biopsied after they developed a painful pustular lesion or were followed until disease resolved . Papules developed at 95% of 40 sites infected with live bacteria (95% confidence interval {CI}, 83 . 1%-99.4%) . In 24 sites followed to end point, 27% of the papules resolved, 69% (95% CI, 47.1%-86.6%) evolved into pustules, and 4% remained at the papular stage . Recovery rates of H . ducreyi from surface cultures ranged from 13% to 41% . H . ducreyi was recovered from biopsies of 12 of 15 pustules and 1 of 7 papules, suggesting that H . ducreyi replicates between the papular and pustular stages of disease. Pediatr Allergy Immunol, 1998 Aug, 9(3), 156 - 60 Protective immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children who failed to respond to prior invasive H . influenzae type b disease; Berthet F et al.; A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for protective immunogenicity in 25 previously PRP-unimmunized children who had failed to develop protective PRP antibody levels (< 1 microg/ml) after prior invasive Hib disease at median age 10 months . Children under 21 months of age at time of PRP-T immunization received one, two or three doses . Serum was obtained for total PRP antibody, complement mediated bactericidal activity and specific IgG1 and IgG2 PRP antibodies before (n = 25), 1 to 2 months (n = 24) and > 5 months (n = 13) after completed vaccination . One to 2 months after immunization, all but one patient developed > 1 microg/ml of antibody (geometric mean level 50.7 microg/ ml) . The non-responder developed protective antibody levels when tested at 6 months after vaccination . Twenty out of 22 sera had detectable complement mediated bactericidal activity (median dilution titer 1:24), 1-2 months after vaccination . Three patients failed to demonstrate PRP antibodies in the IgG1 or IgG2 subclasses, although two of them had protective (> 1 microg/ml) total antibody levels . The second post immunization sera showed persistence of the total PRP antibody levels (geometric mean level 38.2 microg/ml) as well as of the bactericidal activity (median dilution titer 1:32) . Conclusion: PRP-T conjugate vaccine is able to elicit a protective immune response in children who have low or unmeasurable PRP antibody levels after a systemic Hib infection. Rev Cubana Med Trop, 1995, 47(3), 189 - 94 {A growth supplement for "fastidious germs"}; Tamargo Martinez I et al.; A growth supplement for "fastidious germs" was produced at the Laboratory of Acute Respiratory Infections of "Pedro Kouri" Institute of Tropical Medicine . This supplement was studied by computerized optic spectrophotometry, and chemical composition was determined . The efficacy of this supplement for the culture of Haemophilus influenzae type b, was evidenced using 100 strains, and it was proven that it can be used in concentrations raging from 1 to 10%. J Bacteriol, 1998 Nov, 180(22), 6013 - 22 Haemophilus ducreyi secretes a filamentous hemagglutinin-like protein; Ward CK et al.; We have identified two extremely large open reading frames (ORFs) in Haemophilus ducreyi 35000, lspA1 and lspA2, each of which encodes a predicted protein product whose N-terminal half is approximately 43% similar to the N-terminal half of Bordetella pertussis filamentous hemagglutinin (FhaB) . To the best of our knowledge, lspA1 (12,500 nucleotides {nt}) and lspA2 (14,800 nt) are among the largest prokaryotic ORFs identified to date . The predicted proteins, LspA1 and LspA2, are 86% identical overall to each other and also have limited amino acid sequence similarity at their N termini to other secreted bacterial proteins, including certain hemolysins . Southern blot analysis indicated that lspA1 and lspA2 sequences were present in 15 other geographically diverse H . ducreyi strains . Reverse transcriptase PCR analysis of total RNA isolated from H . ducreyi 35000 grown in liquid medium, grown on solid agar medium, and isolated from lesions of H . ducreyi-infected rabbits indicated that lspA1 and lspA2 were transcribed both in vitro and in vivo . A 260-kDa protein present in culture supernatant from eight virulent H . ducreyi strains reacted with both polyclonal serum from rabbits infected with H . ducreyi 35000 and a monoclonal antibody predicted to bind both LspA1 and LspA2 . This 260-kDa protein in H . ducreyi 35000 culture supernatant was shown to be the protein product of the lspA1 ORF based on its reactivity with a monoclonal antibody specific for LspA1 . Four H . ducreyi strains, previously shown to be avirulent in the temperature-dependent rabbit model for chancroid, did not produce either LspA1 or LspA2 in vitro . This finding raised the possibility that LspA1, LspA2, or both may be involved in the ability of H . ducreyi to cause lesions in this animal model. Zentralbl Bakteriol, 1995 Oct, 282(4), 449 - 56 An immunodominant epitope on 40 kilodalton outer membrane protein is conserved among different strains of Haemophilus (Histophilus) somnus; Silva SV et al.; Four murine monoclonal antibodies (mAb) were constructed against Haemophilus (Histophilus) somnus, an important bovine pathogen, and used to analyze immunologically significant antigenic determinants on these organisms . These mAbs specifically recognized immunodominant epitopes present on the 40 kilodalton (kD) fraction of the major outer membrane protein (OMP) of H . somnus . The 9D3 IgG1 kappa mAb recognized an immunodominant epitope on the 40 kD major outer membrane protein that is conserved or shared among all the three strains (septicemic, respiratory and uro-genital) of H . somnus . Two IgM kappa mAbs (4D6 and 10C2) recognized epitope(s) on the 40 kD OMP from septicemic and respiratory strains of H . somnus but none from the whole bacterial cell preparations . Another IgM kappa mAb 9D2 recognized an antigenic determinant on the 40 kD protein from the OMP as well as a whole bacterial cell preparation of a septicemic strain of H . somnus . These data demonstrate that, at least, three immunologically significant antigenic determinants on H . somnus are defined by mAbs against this bovine pathogen . Importantly, these studies suggest that the epitope present on the 40 kD major OMP, recognized by the 9D3 mAb, is immunodominant and conserved among septicemic, respiratory and urogenital strains, and is, therefore, suitable for further investigating its use in the development of an immunodiagnostic assay and also as a recombinant vaccine. Vet Microbiol, 1998 Aug 28, 63(1), 39 - 48 Development of a PCR test for identification of Haemophilus somnus in pure and mixed cultures; Angen O et al.; Based on the 16S rRNA sequences of a collection of well-characterized strains of Haemophilus somnus a set of primers was selected as candidates for a species-specific PCR test . All investigated H . somnus strains were found positive in the test, including 12 strains earlier found to represent H . somnus by DNA-DNA hybridization as well as representatives of the 16 ribotypes previously described within this species . The specificity of the test was evaluated on a broad collection of strains within the family Pasteurellaceae and on other Gram positive and negative species . None of these strains gave rise to an amplicon in the PCR test . The performance of the test on mixed cultures was evaluated by adding P . multocida to serial dilutions of H . somnus and incubating the agarplates for 1 and 2 days . This showed that the PCR test applied to the harvest from an agarplate can be expected to detect a single colony of H . somnus in the presence of 10(9) CFU of P . multocida even after 2 days of incubation . In conclusion, the present PCR test has been shown to represent a specific test for identification of H . somnus both in pure and mixed cultures . It represents a quick, sensitive and reliable method for identification of bacteria belonging to this phenotypically heterogeneous and often slow growing species. Med Clin (Barc), 1998 Sep 19, 111(8), 294 - 7 {Haemophilus influenzae meningitis in adults: analysis of 12 cases}; Domingo P et al.; Haemophilus influenzae is an infrequent etiologic agent of bacterial meningitis in adult patients . In the last 12 years, it was the cause in 12 out of 238 cases (5.0%) of acute bacterial meningitis in adults . There were 5 men and 7 women with a mean age (SD) of 45.4 (16) years (range: 18-68 years) . Seven patients (60%) had a communication between subarachnoid space and skin surface or mucosal cavities, and five (41.7%) had otitis or sinusitis . Most of the strains (9/12) were serotype b . Only one patient (8.3%) developed severe neurologic and extra-neurologic complications, and was the one who died . One of the survivors (9.1%) had partial deafness . H . influenzae is not a negligible cause of bacterial meningitis in adults . Moreover, its detection has been increasing in the last years . Patients with a cerebrospinal fluid leak, otitis or sinusitis are at high risk . The outcome is usually favorable if an early adequate therapy is given. APMIS, 1998 Sep, 106(9), 858 - 68 Intra- and interstrain differences of virulence among nontypeable Haemophilus influenzae strains; Melhus A et al.; Nontypeable Haemophilus influenzae (NTHi) is sometimes the causative agent of invasive diseases, and it has been suggested that there may be differences in virulence among NTHi strains . Whilst studying clinical isolates of NTHi in a rat model of acute otitis media, intra- and interstrain differences in virulence were observed . Two strains with suddenly reduced capacity to cause middle ear infections and one highly virulent strain with dose requirements comparable only to encapsulated H . influenzae strains were further investigated, together with 15 other H . influenzae strains . The strains were characterized by analyzing the lipopolysaccharide, the outer membrane proteins, the hemagglutinating ability, and the polymerase chain reaction products after amplification of a gene sequence associated with encapsulation . The pathogenic capacity was assessed in two different in vivo models . It was found that the two strains with reduced pathogenic capacity could regain their virulence after animal passage . The LPS analysis and the results from the chicken embryo model suggested that the observed change in virulence might be associated with the lipopolysaccharide . For the non-animal-passaged strain 3655 there were indications that an undefined factor(s) contributed to its relatively potent virulence . As all three strains lacked genes necessary for encapsulation, in no case could any part of the increased virulence be attributed to the expression of small amounts of capsule. J Infect Dis, 1998 Oct, 178(4), 1067 - 74 Stimulation of the adherence of Haemophilus influenzae to human lung epithelial cells by antimicrobial neutrophil defensins; Gorter AD et al.; Patients with chronic obstructive pulmonary disease (COPD) frequently have recurrent lower respiratory tract infections with nonencapsulated Haemophilus influenzae . The infected mucosa of these patients is infiltrated with neutrophils, which upon activation may release antimicrobial peptides, including defensins . It was shown that defensins isolated from neutrophils or from sputum samples of COPD patients did not kill H . influenzae from these patients, but they did stimulate its adherence to human bronchial epithelial cells in a time- and dose-dependent manner . Maximal stimulation was observed after 3 h in the presence of > or = 10 micrograms/mL defensins, resulting in 65 +/- 36 cfu/cell (61-fold increase) . The enhanced adherence was not solely due to charge effects and was specifically blocked by alpha 1-proteinase inhibitor . Because adherence is the first step in the onset of respiratory tract infections, our findings indicate that neutrophil defensins likely contribute to the pathogenesis of H . influenzae infection in the lower respiratory tract. J Infect Dis, 1998 Oct, 178(4), 1060 - 6 An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: high prevalence of chancroid and human immunodeficiency virus infection; Mertz KJ et al.; In 1994, an apparent outbreak of atypical genital ulcers was noted by clinicians at the sexually transmitted disease clinic in Jackson, Mississippi . Of 143 patients with ulcers tested with a multiplex polymerase chain reaction (PCR) assay, 56 (39%) were positive for Haemophilus ducreyi, 44 (31%) for herpes simplex virus, and 27 (19%) for Treponema pallidum; 12 (8%) were positive for > 1 organism . Of 136 patients tested for human immunodeficiency virus (HIV) by serology, 14 (10%) were HIV-seropositive, compared with none of 200 patients without ulcers (P < .001) . HIV-1 DNA was detected by PCR in ulcers of 6 (50%) of 12 HIV-positive patients . Multivariate analysis indicated that men with chancroid were significantly more likely than male patients without ulcers to report sex with a crack cocaine user, exchange of money or drugs for sex, and multiple sex partners . The strong association between genital ulcers and HIV infection in this population highlights the urgency of preventing genital ulcers in the southern United States. Int J Pediatr Otorhinolaryngol, 1998 Sep 15, 45(1), 77 - 82 Treatment of children with secretory otitis media (SOM) with amoxicillin and clavulanic acid (Spektramox) or penicillin-V (Primcillin) . Bacteriological findings in the nasopharynx before and after treatment; Balle V et al.; A total of 386 children, aged 1-10, with secretory otitis media for at least 3 months were randomly allocated to 2 or 4 weeks' treatment with penicillin-V (Primcillin) or amoxicillin + clavulanic acid (Spektramox) . Spektramox was superior (p < 0.01) to Primcillin in eradicating Haemophilus influenzae and Branhamella catarrhalis from the nasopharynx . No difference was noted for Streptococcus pneumoniae and haemolytic streptococci, gr . A, B, C, G . No increase in the number of beta-lactamase-producing bacteria was noted after treatment . The nasopharynx was recolonized with the same bacteria within 4 weeks from cessation of treatment. Pediatr Infect Dis J, 1998 Oct, 17(10), 913 - 8 Oral tetravalent rotavirus vaccine can be successfully coadministered with oral poliovirus vaccine and a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b vaccine . US Rhesus Rotavirus Vaccine Study Group; Markwick AJ et al.; AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens . METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age . Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo . Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose . RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H . influenzae type b were not statistically different between RV-TV and placebo recipients . The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found . The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients . There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients . CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines . Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age. Pediatr Infect Dis J, 1998 Oct, 17(10), 885 - 90 Pathogens isolated during treatment failures in otitis; Gehanno P et al.; OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure . METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months . Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media . The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%) . The average duration of antibiotic therapy was 6.9 +/- 2.65 days . Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid . RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates . In 60 children (32.3%) the culture of the ear pus was sterile . Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers . Thirty-six patients were infected by S . pneumoniae with penicillin MIC > or =1 mg/l . In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S . pneumoniae . Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively) . Penicillin resistance was mainly associated with serogroups 23 and 14 . CONCLUSIONS: Penicillin-resistant S . pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region. J Otolaryngol, 1998, 27 Suppl 2, 26 - 36 Medical therapy of otitis media: use, abuse, efficacy, and morbidity; Bitnun A et al.; OBJECTIVE: Otitis media (OM) is one of the most common paediatric disorders encountered by primary care physicians . Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the principal pathogens responsible for OM . As a result of the increasing prevalence of antimicrobial resistance, the use of antimicrobial therapy in OM has come under close scrutiny . Amoxicillin remains the most appropriate option for initial empiric therapy of acute otitis media (AOM) . The duration of therapy required for AOM depends on the age of the patient, the severity of disease, and the route of administration . In most cases, particularly in children older than 5 years of age, a 5-day course of antibiotic therapy should suffice . Antibiotic therapy is not required in most cases of otitis media with effusion (OME) and should be reserved for those with bilateral effusions persisting for longer than 3 months associated with significant hearing loss . Antibiotic prophylaxis for recurrent AOM should be minimized . Myringotomy with or without tympanostomy tube placement is an important therapeutic option in those with OME and recurrent AOM . Active immunization against S . pneumoniae and Influenza A is likely to play an increasingly important role in the prevention of OM. Chemotherapy, 1998 Sep, 44 Suppl 1, 19 - 23 Cefixime in the treatment of upper respiratory tract infections and otitis media; de Lalla F; An increasing number of clinical failures has been noted after treatment of upper respiratory tract infection and acute otitis media with conventional antibiotics . At present, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-hemolytic streptococcus (GABHS) are the bacterial pathogens most frequently responsible for these infections . Although GABHS has so far not developed penicillin resistance, the frequency of bacteriological failures with either benzathine penicillin or penicillin V has increased . Firstly, a number of hypotheses have been put forward to explain this, including poor patient compliance and inactivation by beta-lactamase-producing oropharyngeal flora . Secondly, this has added to the demand for new agents to treat resistant streptococci . Cefixime, an orally active third-generation cephalosporin, has attracted considerable attention following the results of numerous clinical studies . Comparative studies between cefixime and conventional antibiotics for the treatment of upper respiratory tract infections and otitis media are summarized. Chemotherapy, 1998 Sep, 44 Suppl 1, 1 - 5 Overview of the clinical features of cefixime; Adam D; Third-generation cephalosporins in oral formulations have become an increasingly important first-line choice against common bacterial infections . Cefixime is one such agent, which possesses excellent efficacy against a broad spectrum of pathogens, including Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis . Clinical success rates are similar to cefaclor, clarithromycin, and other cephalosporins . Importantly, cefixime also possesses excellent activity against beta-lactamase-producing strains . The pharmacodynamic features of the drug include a half-life of 3-4 h and a Cmax of 4.4 microg/ml, well above the MIC90 for susceptible pathogens, permitting once-daily dosing . In this brief overview, the bacteriological and clinical efficacy of cefixime is discussed, as well as its indications. Can J Vet Res, 1998 Oct, 62(4), 262 - 7 The association of titers to Haemophilus somnus, and other putative pathogens, with the occurrence of bovine respiratory disease and weight gain in feedlot calves; Martin SW et al.; Serum samples were obtained from 602 calves (from 19 groups in four feedlots: three in Ontario, and one in Alberta) upon arrival at the feedlot and 28 d later . Of these calves, 202 developed bovine respiratory disease (BRD) and 400 did not develop BRD . Based on high antibody titers noted upon arrival, we infer that most calves were exposed to Haemophilus somnus prior to arrival at the feedlot . Within a group, calves with high titers on arrival had a reduced risk of developing BRD later . Most calves did not experience titer increases after arrival; however, calves that had stable or increasing titers had a relatively low risk of contracting BRD . The calves at greatest risk of BRD were those with titers on arrival of less than 6.8 units and subsequent titer decreases of more than 1 unit . The effects of both the titer on arrival and the titer change after arrival were stable when the serologic effects of a number of viruses and Mycoplasma agents were considered . Neither antibody titer on arrival nor titer change was related to weight gain differences among calves . Calves with BRD or calves with lower weight on arrival had decreased weight gains in the first 28-day feeding period . The high titers on arrival may have protected most calves against further infection with H . somnus . However, since the calves that developed BRD had large titer increases to a number of viruses and to Pasteurella haemolytica, while having decreased antibody titers to H . somnus, we infer that the existing antibodies were "used up" in combatting the agents, including H . somnus, which may have "caused" the BRD . Calves which were able to increase their antibody levels to H . somnus tended to have a reduced risk of BRD. Can J Vet Res, 1998 Oct, 62(4), 251 - 6 Effect of porcine reproductive and respiratory syndrome virus infection on the clearance of Haemophilus parasuis by porcine alveolar macrophages; Solano GI et al.; Porcine reproductive and respiratory syndrome virus (PRRSV) infection in young piglets is frequently associated with secondary infection due to various pathogens, especially those of the respiratory tract . One of the most important mechanisms in respiratory diseases is related to the alteration of function of porcine alveolar macrophages (PAMs) . The objective of this study was to determine how PRRS virus infection affects the capabilities of PAMs in the phagocytosis and destruction of Haemophilus parasuis . Phagocytosis percentages were determined in vitro and ex vivo, after collected PAMs were directly exposed to the virus of if PAMs were collected from piglets previously infected with PRRSV . In vitro experiments demonstrated that H . parasuis uptake by PAMs is only increased in the early stages of PRRSV infection (2 h post-infection) . In contrast, in the ex vivo experiments it was shown that PAMs from PRRSV-infected piglets do not seem to change in their phagocytic rate until the later stages of infection . Together with a decrease in the phagocytic rate, a marked decrease in the functional ability of PAMs to kill bacteria was observed 7 d post-infection . It is hypothesized that when animals are exposed to PRRSV, there is a marked decrease in the functional ability of PAMs to kill bacteria through the release of superoxide anion, indicating a possible negative effect of the virus, at least at the macrophage level. Antimicrob Agents Chemother, 1998 Nov, 42(11), 3032 - 4 Activity of HMR 3647 compared to those of five agents against Haemophilus influenzae and moraxella catarrhalis by MIC determination and time-kill assay; Pankuch GA et al.; The microdilution MICs of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, and pristinamycin against 50/90% of 249 Haemophilus influenzae and 50 Moraxella catarrhalis isolates were 2/4, 0.06/0.125; 8/16, 0.25/0.25; 2/4, 0.06/0.125; 16/16, 0.25/0.25; 32/>32, 1/2; and 2/4, 0.5/0.5 microg/ml . Azithromycin was bactericidal against all 10 H . influenzae and 3 of 5 M . catarrhalis isolates and HMR 3647, erythromycin A, clarithromycin, roxithromycin, and pristinamycin were bacteriostatic, against all 15 strains after 24 h at the MIC. Antimicrob Agents Chemother, 1998 Nov, 42(11), 3000 - 1 Bacteriostatic and bactericidal in vitro activities of clarithromycin and erythromycin against periodontopathic Actinobacillus actinomycetemcomitans; Piccolomini R et al.; The susceptibilities of 87 periodontitis-associated strains of Actinobacillus actinomycetemcomitans to clarithromycin and erythromycin were determined by standard methodology recommended for Haemophilus influenzae . For clarithromycin the MIC at which 90% of the isolates were inhibited was </=2.0 microg/ml and the minimal bactericidal concentration at which 90% of the strains were killed was </=4.0 microg/ml, suggesting that it would be a candidate for therapeutic trials in patients with periodontitis. Antimicrob Agents Chemother, 1998 Nov, 42(11), 2956 - 60 Activities of new fluoroquinolones against fluoroquinolone-resistant pathogens of the lower respiratory tract; Piddock LJ et al.; The activities of six new fluoroquinolones (moxifloxacin, grepafloxacin, gatifloxacin, trovafloxacin, clinafloxacin, and levofloxacin) compared with those of sparfloxacin and ciprofloxacin with or without reserpine (20 microg/ml) were determined for 19 Streptococcus pneumoniae isolates, 5 Haemophilus sp . isolates, and 10 Pseudomonas aeruginosa isolates with decreased susceptibility to ciprofloxacin from patients with clinically confirmed lower respiratory tract infections . Based upon the MICs at which 50% of isolates were inhibited (MIC50s) and MIC90s, the most active agent was clinafloxacin, followed by (in order of decreasing activity) trovafloxacin, moxifloxacin, gatifloxacin, sparfloxacin, and grepafloxacin . Except for clinafloxacin (and gatifloxacin and trovafloxacin for H . influenzae), none of the new agents had improved activities compared with that of ciprofloxacin for P . aeruginosa and H . influenzae . A variable reserpine effect was observed for ciprofloxacin and S . pneumoniae; however, for 9 of 19 (47%) isolates the MIC of ciprofloxacin was decreased by at least fourfold, suggesting the presence of an efflux pump contributing to the resistance phenotype . The laboratory parC (Ser79) mutant strain of S . pneumoniae required eightfold more ciprofloxacin for inhibition than the wild-type strain, but there was no change in the MIC of sparfloxacin and only a 1-dilution increase in the MICs of the other agents . For efflux pump mutant S . pneumoniae the activities of all the newer agents, except for levofloxacin, were reduced . Except for clinafloxacin, all second-step laboratory mutants required at least 2 microg of all fluoroquinolones per ml for inhibition. Int J Clin Pract, 1998 Jul-Aug, 52(5), 289 - 97 Short-course cefuroxime axetil therapy in the treatment of acute exacerbations of chronic bronchitis; Langan C et al.; The efficacy and safety of a five-day course of cefuroxime axetil (250 mg b.d.) and a seven-day course of clarithromycin (250 mg b.d.) were compared in a large double-blind, randomised, multinational study involving 684 patients with acute exacerbations of chronic bronchitis . In an intent-to-treat analysis, the post-treatment clinical responses to each treatment were comparable (82%) and rates at follow-up were similar: 64% on cefuroxime axetil and 61% on clarithromycin . Pre-treatment pathogens were isolated from a total of 192 patients, Haemophilus influenzae being the most common . Overall pathogen eradication rates were similar for both treatments . Both treatments were well tolerated . In conclusion, a five-day course of cefuroxime axetil is clinically equivalent to a seven-day course of clarithromycin in the treatment of acute exacerbations of chronic bronchitis, and may have potential socioeconomic benefits. Nippon Jibiinkoka Gakkai Kaiho, 1998 Sep, 101(9), 1093 - 8 {The role of IL-1 beta in murine model of otitis media with effusion}; Kurono Y et al.; Recent studies have demonstrated the presence of inflammatory cytokines such as IL-1 beta, TNF-alpha, IL-6, and IL-8 in the middle ear effusion (MEE) of patients with otitis media with effusion (OME) . IL-1 beta is known to be produced from macrophages and monocytes in an early stage of inflammation by stimulation with microorganisms and endotoxins . Also, these studies have shown that endotoxins frequently are found in MEE and can induce OME in experimental animal model . These findings suggest that endotoxins in MEE cause a chain reaction of cytokines through IL-1 beta . However, the precise role of IL-1 beta in the pathogenesis of OME has not yet been clarified . In the present study, a murine model of OME was developed by intra-tympanic injection with endotoxin or recombinant mouse IL-1 beta (rIL-1 beta) and the effects of IL-1 beta on the production of MEE were investigated . OME was induced in specific pathogen-free male BALB/c mice by intra-tympanic inoculation with endotoxin purified from nontypeable Haemophilus influenzae or with rIL-1 beta . The presence of MEE in the subjects was observed through the ear drum under a microscope and samples of MEE were collected by aspiration and washing with phosphate-buffered saline . The concentrations of IL-1 beta in each sample of MEE were determined by ELISA and the histological changes were compared . The mice inoculated with endotoxin showed signs of the production of MEE and it was noted that the levels of IL-1 beta in MEE were significantly increased on day 3 . Intra-tympanic inoculation with rIL-1 beta also produced MEE and these cytological findings of MEE as well as the histological findings of middle ear mucosa were similar to those found in the endotoxin-induced OME . Further, the influence of anti-IL-1 receptor antibodies on the production of OME was examined 3 days after intra-tympanic injection with anti-IL-1 receptor antibodies together with endotoxin or rIL-1 beta . The incidence of OME was lower in mice injected with anti-IL-1 receptor antibodies than that in mice injected with endotoxin or rIL-1 beta only . These findings suggest that IL-1 beta may play an important role in the pathogenesis of OME. Vaccine, 1998 Dec, 16(20), 1976 - 81 Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age; Aristegui J et al.; This double-blind, randomised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine (DTPa-HBV) co-administered with three lots of Haemophilus influenzae type b conjugate (Hib) vaccine in one injection, as a primary vaccination course in healthy infants at 2, 4 and 6 months of age . 269 infants (8-11 weeks of age) were randomly allocated to three groups to receive DTPa-HBV/Hib vaccines, concomitantly with oral polio vaccine . Blood samples for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects . Local and general symptoms were recorded by parents on diary cards . All vaccinees had post-vaccination protective anti-D and anti-T (> or = 0.1 IU ml-1) antibodies, and 98% had protective anti-HBs antibody titres (> or = 10 mIU ml-1) . There were no statistically significant differences between groups in post-vaccination anti-D, anti-T, anti-HBs antibody geometric mean titres (GMT), these being 3.49 IU ml-1, 5.92 IU ml-1 and 1109 mIU ml-1, respectively . All subjects responded to three pertussis components, i.e . pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) . Although statistically significant differences in GMTs of anti-PT, anti-FHA and anti-PRN were found between groups, these were not believed to be of any clinical relevance as the minimum GMTs were 60, 193 and 230 EL.U ml-1 for anti-PT, anti-FHA and anti-PRN, respectively . There were no statistically significant differences in anti-PRP antibody GMT (4.05 micrograms ml-1) between groups, 100% and 85% of subjects having titres > or = 0.15 and 1.0 microgram ml-1, respectively . No symptoms were reported for one third of the subjects . Fever (> 38 degrees C) was reported after 16% of doses, with < 1% having > 39.5 degrees C . Almost all local and general symptoms were mild or moderate, and lasted less than 48 h . No subject dropped out due to a severe adverse reaction . The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe, well-tolerated and immunogenic for all vaccine components. Vaccine, 1998 Dec, 16(20), 1950 - 6 Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzae after intranasal immunization with outer membrane protein P6 and cholera toxin; Hotomi M et al.; Nontypeable Haemophilus influenzae (NTHi) is one of the leading pathogens in otitis media . Studies of vaccines against NTHi have focused on outer membrane proteins (OMPs) . One outer membrane protein P6 is highly conserved among strains and is an attractive candidate for a subunit bacterial vaccine . In this study, mucosal immunity induced by intranasal immunization with P6 and cholera toxin (CT) was investigated in a mouse model . Intranasal immunization with P6 and CT evoked a good mucosal IgA as well as a systemic IgG response against P6 . On the other hand, intranasal immunization with P6 alone induced a weak mucosal IgA response . Enzyme linked immunospot assay detected anti-P6 specific antibody producing cells in the nasopharyngeal mucosa of immunized mice . The protective response of intranasal immunization was demonstrated by enhancement of nasopharyngeal clearance of NTHi and inhibition of adherence of NTHi to cultured human epithelial cells . Based on these results, intranasal immunization with P6 and CT may be an effective approach to protect human from H . influenzae infections in the upper respiratory tract. Vaccine, 1998 Nov, 16(19), 1885 - 97 Addressing the challenges to immunization practice with an economic algorithm for vaccine selection; Weniger BG et al.; The biotechnology revolution is producing a growing bounty of new vaccines which pose difficult choices in selecting among many products . Some major public and private purchasers of vaccine may offer individual physicians and clinics their choice in assembling vaccine inventories . Others might purchase only a limited stock of products that would satisfactorily immunize a typical child . In either case, current vaccine selection decisions are based principally on purchase price alone without systematic consideration of other factors of fiscal consequence . As a potential tool for decision making, we developed an economic algorithm for vaccine selection that would minimize the overall costs of disease control through immunization by considering: (1) purchase price, (2) number of doses needed, (3) preparation time, (4) route of administration, (5) cold storage needs, (6) shelf life, (7) earliest age of full immunity, (8) adverse events frequency, and (9) efficacy of protection . To demonstrate the algorithm, variables (1) to (4) above were incorporated into a pilot binary-integer linear programming model that satisfied the recommended immunization schedule for diphtheria, tetanus, pertussis, Haemophilus influenzae b, and hepatitis B, using eleven vaccines (DTaP, DTaP-Hib, Hib, HepB and Hib-HepB) from four manufacturers . Five (or six) opportunities to vaccinate were modeled at (1), 2, 4, 6, 12-18, and 60 months of life, assuming US$40 per clinic visit, $15 per injection, and $0.50 per minute of nurse preparation time . Vaccine costs were varied using actual March and September 1997 US Federal vaccine prices, as well as estimates for unpriced new vaccines . Over 16,000 distinct vaccine stocking lists by vaccine type and brand were possible . Including a 1-month visit, the lowest-cost 'solution' of the algorithm was $529.41 per child in the March cost-assumption case, and $490.32 in the September one (both included four doses of DTaP-Hib, three HepB, and one DTaP) . Without a 1-month visit, the lowest-cost solution in the March case cost $486.67 (four DTaP, two Hib-HepB, one DTaP-Hib, and one HepB), while the September case cost $450.32 (four DTaP-Hib, three HepB, and one DTaP) . Ensuring at least one product was selected from each of the four manufacturers increased costs about $13.00, and the needed injections rose from eight to nine . The most economical selection of vaccines to use cannot be intuitively predicted, as permutations are large and solutions are sensitive to minor changes in costs and constraints . A transparent, objective selection method that weighs the economic value of distinguishing features among competing vaccines might offer the 'best value' to vaccine purchasers, while also creating strong market incentives for continuing innovation and competition in the vaccine industry. Vaccine, 1998 Nov, 16(19), 1842 - 9 Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine; Fusco PC et al.; In anticipation of future combination vaccines, a recombinant class 3 porin (rPorB) of group B meningococci was evaluated as an alternative carrier protein for a Haemophilus influenzae type b (Hib) polyribosylribotol phosphate (PRP) conjugate vaccine . The use of rPorB may avoid undesirable immunologic interactions among vaccine components, including epitopic suppression from conventional carriers (e.g . tetanus toxoid {TT}), as well as provide desirable immunomodulatory effects . Rats were found to be more reliable and consistent than mice or guinea pigs for studying antibody responses to the Hib conjugates . Different Hib conjugates, Hib-TT and Hib-rPorB, consisting of PRP conjugated by reductive amination to TT or rPorB, were compared in rats . Commercially available, licensed vaccines, HbOC (HibTITER) and PRP-T (OmniHib), were used as reference controls . Maximum geometric mean ELISA IgG titers were obtained in rats after only two doses, showing booster effects for all . However, Hib-rPorB immunization consistently resulted in responses that were 1-2 orders of magnitude greater than those for the other conjugates, including the licensed control vaccines . A maximum 4600-fold rise was observed for Hib-rPorB after two doses, and, unlike the other conjugates, a 100% response rate was always achieved without adjuvant . These results warrant further investigation of Hib-rPorB in combination with DTaP. Rev Esp Quimioter, 1998 Sep, 11(3), 245 - 50 {Ampicillin-sulbactam activity against respiratory isolates of Haemophilus influenzae}; Cisterna R et al.; A study was conducted on the in vitro activity of ampicillin/sulbactam against 100 respiratory strains of Haemophilus influenzae (45 betalactamase positive and 55 betalactamase negative strains) simultaneously isolated during 1997 in 6 Spanish hospitals: Hospital Clinico San Carlos (Madrid), Hospital de Cruces de Basurto (Bilbao), Hospital La Fe (Valencia), Hospital Virgen Macarena (Seville), Hospital de Bellvitge (Barcelona) and Hospital Clinico Universitario (Salamanca) . It was studied in comparison to amoxicillin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and ciprofloxacin . The MIC breakpoints used for the interpretation of data were those published by the National Committee for Clinical Laboratory Standards in 1997 . All of the strains tested were susceptible to ampicillin/sulbactam, amoxicillin/clavulanic acid, cefuroxime and ciprofloxacin . The rate of resistance to clarithromycin was 55.5% for betalactamase positive strains and 38 . 2% for betalactamase negative strains . A total of 23.6% of the betalactamase negative strains were resistant or showed intermediate susceptibility to amoxicillin but were susceptible to betalactam/betalactamase inhibitor combinations and cefuroxime. Rev Esp Quimioter, 1998 Jun, 11(2), 132 - 8 {Prospective and comparative study between cefuroxime, ceftriaxone and amoxicillin-clavulanic acid in the treatment of community-acquired pneumonia}; Sanchez ME et al.; Among community-acquired infections, pneumonia is still a large health problem which is of great interest mainly due its high mortality and morbidity . From 1991 to 1997, 409 patients who had been diagnosed with community-acquired pneumonia and had been admitted to the internal medicine service of a university hospital were prospectively studied . The patients were classified into three groups according to the random antibiotic treatment they had received (ceftriaxone, cefuroxime or amoxicillin-clavulanic acid) . The initial characteristics of the patients with regard to epidemiology, clinical description and critical situation were similar in all the groups studied . A total of 36.9% of the cases were documented microbiologically, with the most frequently isolated pathogens being Streptococcus pneumoniae and Haemophilus influenzae . The recovery rate was 92.2% and three patients had a recurrence of pneumonia . Global mortality was 5.8% . No statistically significant differences were found in the evolution of patients treated with cefuroxime, ceftriaxone or amoxicillin-clavulanic acid, with the latter representing an empirical treatment of choice for community-acquired pneumonia. Rev Esp Quimioter, 1998 Mar, 11(1), 47 - 51 {In vitro activity of trovafloxacin in 238 respiratory pathogens.}; Alarcon T et al.; The in vitro activity of trovafloxacin against 238 clinical isolates obtained from respiratory specimens were compared with ciprofloxacin . Fifty-four Haemophilus influenzae, 58 Streptococcus pneumoniae, 40 Moraxella catarrhalis, 21 Streptococcus pyogenes, 25 Klebsiella pneumoniae and 40 Staphylococcus aureus (21 methicillin resistant and 19 methicillin susceptible) were studied . The MIC was determined following NCCLS recommendations . Ciprofloxacin and trovafloxacin MIC90 was 0.016 mg/l and 0.016 mg/l for H . influenzae, 4 mg/l and 0 . 25 mg/l for S . pneumoniae, </=0.008 mg/l and </=0.008 mg/l for M . catarrhalis, 0.5 mg/l and 0.064 mg/l for S . pyogenes, 0.064 mg/l and 0.25 mg/l for K . pneumoniae, 16 mg/l and 0.5 mg/l for methicillin-resistant S . aureus and 2 mg/l and 0.032 mg/l for methicillin-susceptible S . aureus . According to this data, trovafloxacin showed better in vitro activity than ciprofloxacin in the Gram-positive pathogen studied and similar activity against the Gram-negatives tested. Presse Med, 1998 Sep 26, 27(28), 1440 - 1 {Would ampicillin alone again be enough for treating community-acquired pneumonias?}; Bedos JP; MORE THAN SEMANTICS: The complexity of the problem raised by this apparently simple question becomes apparent if one examines the meanings behind the words . STILL SUFFICIENT: Globally, the frequency of pathogens known to cause community-acquired pneumonia has changed little over time: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumoniae . The real question is the emergence of S . Pneumoniae resistant strains . Currently, the frequency of penicillin or ampicillin resistant strains (less then 10%) is not associated with an increased rate of treatment failure or mortality . "High" doses (150-200 MU/kg/d for penicillin or 2 g t.i.d . for ampicillin) can still be expected to control suspected or certain resistant pneumococcal pneumonia . STILL SUFFICIENT: Would other antimicrobials be more effective? In France, "consensual" use of amoxicillin (1 g t.i.d.) "covers" 98% of the situations as resistant strains are found in only 2% of the adult cases . Thus, the lower frequency of pneumococcal resistance to cefotaxime or ceftriaxone (less than 0.5%) would not warrant their use in most cases of community-acquired pneumococcal pneumonia . Inversely, combination regimens with ampicillin or amoxicillin and cefotaxime or ceftriaxone or the amoxicillin-clavulanic acid association at standard doses provide good therapeutic alternatives for empirical prescriptions in cases with a high risk of infection other than pneumococcal infection (H.influenzae, methicillin-sensitive Staphylococcus aureus) . The remarkable anti-pneumococcal activity of imipenem, vancomycin and teicoplanin should, for the time being, be reserved for selected patients with cross allergic reactions to penicillins and cephalosporins . EMPIRICAL REGIMENS: In case of severe community-acquired pneumonia, a combination regimen should be the rule in order to "cover" as many bacteria as possible . In the "healthy" adult under 60 years of age, amoxicillin combined with a macrolide or a fluoroquinolone can be recommended . OUTLOOK: Bacteriological efficacy is not synonymous with cure . Secondary inflammatory processes and subsequent septic shock remain a major challenge. Chest, 1998 Oct, 114(4), 1129 - 36 Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and mortality; Singh N et al.; A prospective cohort study of 129 consecutive patients developing pulmonary infiltrates in the surgical ICU was conducted to determine the predictors and outcome of pulmonary infiltrates . Most common etiologies of pulmonary infiltrates were pneumonia (30%), pulmonary edema (29%), acute lung injury (15%), and atelectasis (13%) . Enteral nutrition was associated with a significantly lower incidence of acute lung injury as compared with pneumonia (22% vs 58%, p = 0.012) . Patients with liver disease were significantly more likely to have pulmonary infiltrates due to acute lung injury as compared with other etiologies (p = 0.02) . Clinical pulmonary infection score (Pugin score) > 6 virtually excluded acute lung injury, pulmonary edema, or atelectasis as etiologies of pulmonary infiltrates . Nosocomial Haemophilus/pneumococcal pneumonia occurred significantly earlier in the ICU as compared with Gram-negative (p = 0.05) or methicillin-resistant Staphylococcus aureus pneumonia (p = 0.01) . Pneumonia in trauma patients was significantly more likely to be due to Haemophilus/pneumococcus as compared with all other ICU patients (54% vs 0%, p = 0.0004) . These data have implications for treatment of patients with nosocomial pneumonia in the ICU. Diagn Microbiol Infect Dis, 1998 Sep, 32(1), 45 - 50 BAY 12-8039, a novel fluoroquinolone . Activity against important respiratory tract pathogens; Biedenbach DJ et al.; BAY 12-8039 or moxifloxacin is a new 8-methoxyquinolone with documented, improved activity against Gram-positive cocci and anaerobic bacteria . This study tested 1250 commonly isolated respiratory tract pathogens (251 Moraxella catarrhalis, 499 Haemophilus influenzae, 500 Streptococcus pneumoniae) from 1996-1997 clinical infections at more than 30 medical centers . Among the M . catarrhalis strains (81% beta-lactamase-positive) the BAY 12-8039 MIC90 was 0.06 microgram/mL, a potency equal to ofloxacin but less than all other tested fluoroquinolones (ciprofloxacin, clinafloxacin, levofloxacin, sparfloxacin, trovafloxacin) . The H . influenzae strains were generally less susceptible to BAY 12-8039 (MIC90, 0.03 microgram/mL) than the tested fluoroquinolones, and the other comparison compounds were less active overall . All S . pneumoniae strains were susceptible to BAY 12-8039 at < or = 0.25 microgram/mL (MIC90, 0.06-0.12 microgram/mL), a value equal-potent to trovafloxacin . This new fluoroquinolone, BAY 12-8039, appears promising for the treatment of community-acquired respiratory tract infections caused by common bacterial species. Diagn Microbiol Infect Dis, 1998 Sep, 32(1), 27 - 32 Haemophilus influenzae meningitis in adults; Tang LM et al.; Haemophilus influenzae meningitis is rare in adults . We reviewed the microbiological records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted to Chang Gung Memorial Hospital from January 1978 to May 1996 . Haemophilus influenzae meningitis was found in six adult patients, accounting for 1.8% of 326 bacteriologically proven adult cases of meningitis diagnosed between January 1984 and May 1996 . Predisposing conditions included head trauma and/or neurosurgical procedure in four patients and an extracranial extension of a pituitary adenoma in a diabetic patient . None of them had altered consciousness on the day of treatment . A CSF cell count less than 500 x 10(6) leukocytes/liter was noted in three patients . Antibiotic therapy was successful in all patients . Thus, predisposing conditions, particularly head trauma and/or neurosurgical procedure, are commonly present in adult patients with H . influenzae meningitis . Patients with the infection may have a low cellular count in the CSF that may be readily misinterpreted as meningitis caused by other pathogens. Diagn Microbiol Infect Dis, 1998 Sep, 32(1), 15 - 9 Antigenuria in Gambian infants following immunization with a Haemophilus influenzae type b polyribosylribitol phosphate-tetanus toxoid protein conjugate (PRP-T) vaccine; Adegbola RA et al.; During a Haemophilus influenzae type b (Hib)-conjugate vaccine trial, the prevalence and duration of antigenuria after vaccination was studied in 102 Gambian infants aged 51 to 175 days . Urine samples were collected at 0, 1, 3, 7, 14, 21 and 28 days postvaccination and tested for Hib antigen by latex agglutination using Biomerieux and Directigen reagent kits . Biomerieux positive reactions were found in 6 of 247 (2.4%) samples from vaccinated children and in 8 of 199 (4.0%) from nonvaccinated children (chi 2 = 0.47; 1 df; p = 0.5) . In contrast, Directigen positive reactions were obtained with 86/242 samples (35.5%) from vaccinated children and from 28/190 (14.7%) from non-vaccinated children (chi 2 = 22.7; 1 df; p < 0.0001) . The highest rate of antigenuria was detected in samples collected on Day 7 after vaccination when 24 of 30 (80%) were positive . Antigenuria following vaccination was frequent and may complicate the use of this test as a means of diagnosing invasive Hib disease in vaccinated children. Antibiot Khimioter, 1998, 43(9), 19 - 23 {Clinical significance of fungal and microbial associations and antibacterial therapy for treatment of chronic inflammatory respiratory tract diseases in children}; Platonova MM et al.; Microbiological examination applied to 270 children with chronic inflammatory and relapsing respiratory tract diseases revealed that by the frequency of the etiologically significant organisms the main pathogens isolated from the bronchial secretion belonged to Haemophilus influenzae, then followed Streptococcus pneumoniae and the less frequent isolates belonged to Branhamella catarrhalis characterized by high susceptibility to the 2nd and 3rd generation cephalosporins, erythromycin and azithromycin . Mycological investigation of the oral mucus and sputum from the patients revealed high frequency of Candida, mainly C.albicans . The fungi were most frequent and abundant in the children with chronic pulmonary diseases and congenital immune deficiency and in the children with bronchial asthma and asthmatic bronchitis, as well as in the children with exacerbation of the chronic disease, especially with bronchial obstruction . The antibacterial therapy with semisynthetic penicillins, cephalosporins and macrolides led to an increase in the number of the Candida carriers and in the biological material contamination level . The fungal contamination of the host was mainly observed after the use of the penicillins and cephalosporins . Chronic Candida carriers were detected among the patients with chronic inflammatory diseases of the lungs . The diseases in such patients were particularly severe . There were also detected children with colonization resistance to Candida . In the latter cases the chronic process was more favourable . The data made it possible to recommend a more differential use of the antibacterial and antimycotic drugs in the treatment of children with chronic inflammatory diseases of the bronchopulmonary system. Arch Pediatr, 1998 Sep, 5(9), 1036 - 40 {Immunization schedule in the European Union}; Ovetchkine P et al.; All nations that are part of the European Union share the same aim for the control and eradication of vaccine-preventable diseases . However, there are differences in child immunization strategies and schedules between nations, depending upon health care systems, immunization habits and epidemiology of infectious diseases . All nations immunize children against diphtheria, tetanus, poliomyelitis, measles, rubella and mumps . Immunization against pertussis, Haemophilus influenzae, hepatitis B and tuberculosis are not systematically applied. Berl Munch Tierarztl Wochenschr, 1998 Sep, 111(9), 321 - 5 {Determination of C-reactive protein and neopterin in serum of diseased and bacterially infected swine}; Schrodl W et al.; The parameters C-reactive protein (CRP) and neopterin, which are associated with immunological reactions, were investigated in serum of healthy, diseased and with Haemophilus parasuis infected pigs . When comparing diseased young pigs with healthy young pigs significant increases of the CRP- and neopterin concentrations can be seen . The increase of the CRP-concentration was most remarkable . After the infection of SPF-piglets with Haemophilus parasuis, significantly decreased neopterin concentrations and increased CRP concentrations were determined in comparison with non-infected animals . The animals with the symptoms of arthritis and disorders of the central nervous system showed the lowest neopterin concentrations and the highest concentrations of CRP . It seems that CRP and neopterin are interesting serum parameters in pigs with regard to the recognition of immunological reactions after illness or infection. Cent Eur J Public Health, 1998 Aug, 6(3), 225 - 30 Analysis of bacterial meningitis during 1992-1996 in Poland; Tyski S et al.; Retrospective study of bacterial meningitis cases was performed by analysis of filled questionnaires received from 38 different hospitals located in 27 out of 49 provinces of Poland . Obtained data allowed to indicate that S . epidermidis, N . meningitidis, S . pneumoniae and H . influenzae were the most common bacterial strains isolated from cerebrospinal fluid of meningitis patients during the last five years . Besides data analysis performed, some strains of N . meningitidis (n = 97), H . influenzae (n = 28) and S . pneumoniae (n = 39) isolated from cerebrospinal fluid of meningitis patients hospitalized in different places in Poland sent by cooperating hospital laboratories (1995-1996), were phenotypically characterized . Neisseria meningitidis B:22:P1.14 was the most common isolate phenotype during the investigated time period . Streptococcus pneumoniae of twenty different serological types were isolated . Type 1 was the dominant--18% of strains . All but one Haemophilus influenzae strains isolated from cerebrospinal fluid belonged to serological type b . Biotyping showed presence of only two types: I and II, 39.3% and 60.7% of isolates respectively . The sensitivity of collected strains to selected antimicrobial agents (penicillin, cefotaxime, ceftriaxone, sulphametoxazol, chloramphenicol, tetracycline, ciprofloxacin, rifampin and erythromycin) used in treatment and prophylaxis of bacterial meningitis was investigated . Minimum inhibitory concentrations were determined by agar dilution method or with the use of E-tests . All investigated strains but one N . meningitidis, were not resistant to penicillin (MIC < or = 1 microgram/ml). Ear Nose Throat J, 1998 Sep, 77(9), 748 - 9, 752-3, 757-8 passim Mucosal immunity and bacteriology of the eustachian tube; Sorensen CH et al.; The pathogenesis of otitis media is a multifaceted process that is not completely understood . Eustachian tube dysfunction plays a central but uncertain role, as do viral and bacterial microorganisms . Of the latter, the three most important are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis . This article reviews the various mechanisms of infection and the immune system's response to them. Ophthalmology, 1998 Oct, 105(10), 1902 - 5; discussion 1905-6 Preseptal and orbital cellulitis in childhood . A changing microbiologic spectrum; Donahue SP et al.; OBJECTIVE: The authors sought to determine whether the microbiologic spectrum of preseptal and orbital cellulitis had changed over the past decade . DESIGN: A retrospective chart review of all inpatient and outpatient children with an ICD-9 diagnosis of preseptal or orbital cellulitis seen at Vanderbilt University Medical Center since the introduction of the Haemophilus influenzae type-B (HiB) vaccine (1986-1996) . MAIN OUTCOME MEASURES: Blood and abscess cultures from children with preseptal and orbital cellulitis were tabulated . RESULTS: During this period, 70 cases of preseptal cellulitis were seen . Blood cultures were obtained in 59 cases; only 6 were positive . Five cultures grew Streptococcus species . The one positive H . influenzae culture occurred in 1987 in a child who did not receive the HiB vaccine . There have been no new patients with preseptal cellulitis and H . influenzae bacteremia at Vanderbilt for 10 years . There were ten cases of orbital cellulitis, of which blood or abscess or both were cultured in eight . Six cases had positive cultures . Four cultures grew Streptococcus species . The other two grew H . influenzae and mixed H . influenzae/gram-positive cocci . CONCLUSION: The incidence of hemophilus-associated bacteremia in patients with preseptal cellulitis has decreased dramatically over the past 10 years . Streptococcus species now are the predominant cause . Orbital cellulitis due to H . influenzae may still occur, but it is much less likely . A more conservative approach to the diagnosis and management of preseptal and orbital cellulitis may be warranted. Monaldi Arch Chest Dis, 1998 Jun, 53(3), 262 - 7 Airways microbial flora in COPD patients in stable clinical conditions and during exacerbations: a bronchoscopic investigation; Pela R et al.; Patients affected with chronic obstructive pulmonary disease (COPD) undergo frequent exacerbations of their illness characterized by increased cough and expectoration . The precise aetiology of these episodes often remains unknown . In the absence of clinical or radiographic signs of pneumonia, bacterial or viral cultures of sputum usually provide little useful information . Thus, we performed fibreoptic bronchoscopy using a protected specimen brush (PSB) to obtain uncontaminated secretions for culture from 56 patients with COPD, 16 with stable clinical conditions and 40 affected with exacerbations of the disease . The aim of our study was to evaluate bronchial microbial flora by quantitative aerobic and anaerobic culture of each specimen . Twenty five subjects (45%), 4 (16%) in stable state and 21 (84%) with COPD exacerbations, had specimens which gave rise to significant bacterial growth (> 10(3) colony forming units.mL-1) . The predominant bacteria were Streptococcus pneumoniae (in 10 cases) and alpha-haemolytic streptococci (in 6 cases); other bacteria found were coagulase-negative staphylococci and Branhamella catarralis in (2 cases each), and Proteus mirabilis, Haemophilus influenzae, Pseudomonas aeruginosa, Aerococcus viridans and Chromobacterium violaceum (each in a single case only) . Although significant bacterial growth was more frequently found in patients with chronic obstructive pulmonary disease exacerbations and in those with a higher degree of bronchial inflammation, the differences between the two groups of patients were not statistically significant . Nevertheless, the results obtained in our study confirm the validity of and the need for reliable sampling methods (like the protected specimen brush) to demonstrate significant bacterial colonization of the airways in chronic obstructive pulmonary disease patients. Am J Health Syst Pharm, 1998 Sep 15, 55(18), 1881 - 97; quiz 1932-3 Otitis media: focus on antimicrobial resistance and new treatment options; Hoppe HL et al.; Antimicrobial resistance among organisms that cause acute otitis media (AOM) and new approaches in the prevention and treatment of AOM are discussed . Organisms commonly responsible for causing AOM include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . The evolution of pneumococcal resistance to penicillins, erythromycin, trimethoprim-sulfamethoxazole, and oral cephalosporins may require treatment with agents such as vancomycin or rifampin in certain patients . H . influenzae and M . catarrhalis are becoming increasingly resistant to penicillins, trimethoprim-sulfamethoxazole, oral cephalosporins, and macrolides . Mechanisms of resistance include changes in penicillin-binding proteins, production of beta-lactamase, alterations in target enzymes, and inhibition of drug access to the site of action . Because of changing resistance patterns and the limited spectra of activity of many currently available antimicrobials, new antimicrobials have been developed in the hope of improving therapy . While amoxicillin and trimethoprim-sulfamethoxazole are appropriate first-line agents, children at risk for resistant infections may be treated initially with cefuroxime axetil, cefpodoxime proxetil, cefprozil, or amoxicillin-clavulanate . After local resistance patterns, patient adherence to therapy, in vitro data, and cost factors have been weighed, other agents to consider include loracarbef, clarithromycin, azithromycin, and ceftriaxone . Along with the efforts to improve treatment, research is focusing on the prevention of otitis media with bacterial and viral vaccines . The emergence of resistant strains of organisms causing AOM has complicated its treatment. Infect Immun, 1998 Nov, 66(11), 5450 - 6 Murine immune responses to Neisseria meningitidis group C capsular polysaccharide and a thymus-dependent toxoid conjugate vaccine; Rubinstein LJ et al.; The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens in infants and young children as a result of the delayed response to PS antigens during ontogeny . The development of polysaccharide-protein conjugate vaccines for Haemophilus influenzae type b, which have proven to be efficacious in this age group, has led to active development by a number of investigators of conjugate vaccines for other diseases . We describe here the response of several mouse strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to tetanus toxoid (MCPS-TT) and the same response in BALB/c mice as a model of the immune consequences of conjugate vaccine immunization . The use of a conjugate vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1 . A response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey when choosing a mouse model for a vaccine . The marked increase in IgG1 antibody titer was accompanied by a large increase in bactericidal activity of sera from these animals . Animals primed with the conjugate vaccine demonstrated a booster response after secondary immunization with either the MCPS or the conjugate . The ability to produce a boosted IgG1 anti-MCPS response to the MCPS can be transferred to adoptive recipients by B cells alone from mice primed with MCPS-TT but not mice primed with MCPS alone . These data indicate that in BALB/c mice a single immunization with MCPS-TT is sufficient to induce a shift to IgG1 and generate a memory B-cell population that does not require T cells for boosting. Microbiology, 1998 Sep, 144 ( Pt 9), 2531 - 8 Cloning of the haemocin locus of Haemophilus influenzae type b and assessment of the role of haemocin in virulence; Murley YM et al.; The bacteriocin haemocin (HMC) is produced by most type b strains of Haemophilus influenzae, including strains determined to be genetically diverse, and is toxic to virtually all non-type b strains of H . influenzae, both encapsulated and non-encapsulated . Examination of the deduced amino acid sequences of several genes upstream of the previously identified HMC immunity gene (hmcI) revealed several features common to class II bacteriocins of certain Gram-positive bacteria . Mutagenesis of the open reading frame immediately upstream of hmcI resulted in a loss of the HMC production phenotype . When an HMC-producing strai of H . influenzae and the HMC-deficient isogenic mutant were compared for invasion on the infant-rat model, the HMC-producing strain was found to invade significantly earlier; however, a significantly higher number of rats infected with the isogenic mutant became bacteraemic as compared with those infected with the HMC-producing parent. Microbiology, 1998 Sep, 144 ( Pt 9), 2525 - 30 An in silico evaluation of Tn916 as a tool for generalized mutagenesis in Haemophilus influenzae Rd; Hosking SL et al.; The transposon Tn916 was evaluated as a tool for generalized mutagenesis of the genome of Haemophilus influenzae . This was achieved in silico by searching the genome sequence of H . influenzae Rd for the published Tn916 target site consensus sequence 5' TT/ATTTT(N)6AAAAAA/TA . This search identified 16 putative target sites . In subsequent experiments, integration of Tn916 did not occur at any of these sites . Using the nucleotide sequences of these observed integration sites, a new consensus sequence, 5' TTTTT(N)xAAAAA (4 < or = x < or = 7), was derived . This sequence reflects the curve-twist-curve DNA topology which is a feature common to all Tn916 integration sites . A search of the H . influenzae Rd genome using the new consensus sequence identified 167 potential target sites, representing approximately 1% of the total genome . Only 80 of these sites were located within ORFs . The presence of such a limited number of target sites places severe constraints on the use of Tn916 as a tool for generalized mutagenesis of the genome of H . influenzae. Otolaryngol Head Neck Surg, 1998 Oct, 119(4), 357 - 60 Sinusitis in neurologically impaired children; Brook I et al.; The microbiologic features of infected sinus aspirates in nine children with neurologic impairment were studied . Anaerobic bacteria, always mixed with aerobic and facultative bacteria, were isolated in 6 (67%) aspirates and aerobic bacteria only in 3 (33%) . There were 24 bacterial isolates, 12 aerobic or facultative and 12 anaerobic . The predominant aerobic isolates were Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus (2 each) and Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (1 each) . The predominant anaerobes were Prevotella sp . (5), Peptostreptococcus sp . (4), Fusobacterium nucleatum (2), and Bacteroides fragilis (1) . Beta-lactamase-producing bacteria were isolated from 8 (89%) patients . Organisms similar to those recovered from the sinuses were also isolated from tracheostomy site and gastrostomy wound aspirates in five of seven instances . This study demonstrates the uniqueness of the microbiologic features of sinusitis in neurologically impaired children, in which, in addition to the organisms known to cause infection in children without neurologic impairment, facultative and anaerobic gram-negative organisms that can colonize other body sites are predominant. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S207 - 10 Characterization of immune response as an indicator of Haemophilus influenzae type b vaccine efficacy; Madore DV; Quantitation of antibodies to Haemophilus influenzae type b (Hib) polysaccharide has been an active area of investigation associated with the development of polysaccharide and subsequently polysaccharide-protein conjugate vaccines . These clinical studies indicate that there are several serologic parameters associated with Hib vaccine efficacy in infants . Efficacious vaccines elicit polysaccharide-specific antibodies in infants; they prime the immune system for an anamnestic response; the immune response is long-lived through the period of greatest risk for disease; and the elicited antibodies have functional activity as demonstrated in bactericidal and opsonophagocytic assays or protection in an infant rat challenge model . The immune response to different Hib vaccines varies both quantitatively and qualitatively . With the introduction of routine Hib vaccine immunization, vaccine performance can rely on these serologic parameters . Quantitative serologic assays, the radio-antigen binding and enzyme-linked immunosorbent assays, have been developed and standardized . The quality of the antigen as well as optimization of all assay steps and reagents are key to ensuring specific and reproducible antibody quantitation. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S204 - 7 Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines; Slack MP et al.; We report an enhanced prospective survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H . influenzae type b (Hib) vaccination program . During the prevaccination period the majority of cases of invasive H . influenzae were caused by type b; most (89%) of these infections occurred in children <5 years of age and the most common presentation was meningitis . Since the introduction of routine immunization of infants with conjugate Hib vaccine, there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children <5 years of age . This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs . The number of infections caused by non-type b H . influenzae has shown a small but progressive increase over the same period, emphasizing the need for continued surveillance . There was no increase in the number of infections caused by other serotypes . Diagnostic category varied with both age and serotype but was not affected by vaccine introduction; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S198 - 203 A nationwide prospective surveillance study in Israel to document pediatric invasive infections, with an emphasis on Haemophilus influenzae type b infections . Israeli Pediatric Bacteremia and Meningitis Group; Dagan R et al.; BACKGROUND AND METHODS: An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to document childhood invasive infections caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis . This study enabled us to document the effect on childhood invasive Hib disease of the introduction of conjugate Hib vaccines to Israel . RESULTS: The incidence of invasive Hib disease before the age of 5 years dropped from 34 per 100000 before initiation of immunization to < 5 per 100000 in 1995 and is projected to be <4 in 1996 . After <2 years, when various conjugate vaccines had been available in the private sector alone and had achieved partial coverage only, the Israeli Ministry of Health decided to add Hib conjugate vaccine to the regular infant immunization program, free of charge, effective for all infants born after January 1, 1994 . The vaccine chosen was Hib polysaccharide linked to outer membrane protein complex of N . meningitidis B . Vaccine coverage has exceeded 90% of all infants born since January 1, 1994 . Efficacy and effectiveness during the first 34 months of the program (January 1, 1994, to October 31, 1996) were 95.4 and 99.7%, respectively, for all invasive Hib disease and 97 and 99.4%, respectively, for Hib meningitis . CONCLUSION: The described ongoing surveillance program showed the existence and extent of Hib problems in Israel and documented the success of the immunization program in essentially eliminating the disease in Israel. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S195 - 8 The rationale for population-based surveillance for Haemophilus influenzae type b meningitis; Levine OS et al.; Although Haemophilus influenzae type b (Hib) conjugate vaccines have been spectacularly successful, nearly eradicating Hib disease in countries where used routinely, they are relatively expensive . In many countries the incidence of Haemophilus influenzae type b (Hib) disease is uncertain, and it is unclear whether the local burden of Hib disease warrants the costs of adding Hib vaccine to the routine immunization program . Population-based surveillance to assess the local burden of Hib disease can help decision makers with this process . Although pneumonia is more common than meningitis, surveillance for Hib meningitis and invasive disease is likely to be more feasible and efficient than surveillance for Hib pneumonia . Standardization of laboratory methods for the isolation and identification of H . influenzae from CSF specimens is essential to successful surveillance . Should a country decide to introduce Hib conjugate vaccine as a routine immunization, population-based surveillance data collected before and after the introduction of vaccine can be used to monitor its impact . Finally population-based surveillance for bacterial meningitis also can provide information on the incidence of pneumococcal and meningococcal infections and on serogroup or serotype distributions that will be important when evaluating the new vaccines for those pathogens that are being developed. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S192 - 4 The etiology of bacterial pneumonia and meningitis in Vietnam; Tran TT et al.; BACKGROUND: To date no studies on the incidence of Haemophilus influenzae type b (Hib) disease, Hib carrier rates in infants and children or the proportion of bacterial meningitis cases caused by Hib in Vietnam have been performed . The availability of safe and highly effective Hib vaccines makes such information important . METHODS: The bacterial etiology of a sample of infants and children with pneumonia and meningitis seen at Pediatric Hospital No . 1 in Ho Chi Minh City was studied by culture and latex agglutination of blood, cerebrospinal fluid, urine and pleural fluid . The carriage rate of pneumococci and Hib was studied in a sample of outpatient children . RESULTS: Hib caused 53% of 34 culture-proven bacterial meningitis cases and pneumococci caused 18% . Of 31 meningitis cases diagnosed by latex agglutination, 39% were caused by Hib and 55% by pneumococci . Ninety percent of cases of Hib meningitis occurred in children <1 year of age . Fifty percent of meningitis cases were associated with acute respiratory infection . In 213 bacteremic pneumonia cases 92.5% of blood cultures grew Streptococcus pneumoniae and only 1% grew Hib . The carrier rate of Hib in outpatients <5 years of age with upper respiratory tract infection increased from 2% to 7.6% between 1993 and 1996 . CONCLUSION: Hib is the most frequent cause of meningitis in infants and children admitted to hospitals in South Vietnam . Ninety percent of Hib meningitis cases occur in patients < 1 year of age . Bacteremic Hib pneumonia in Vietnam is rare . The results suggest that Hib is the major cause of meningitis in Vietnam but do not permit conclusions regarding its true incidence . The carrier rate of Hib in children <5 years of age in Vietnam has increased to approximately 7% since 1993. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S189 - 90 Haemophilus influenzae meningitis in Malaysia; Hussain IH et al.; OBJECTIVE: To determine the pattern of postneonatal childhood meningitis in Malaysia . METHODS: Retrospective cross-sectional study involving five pediatric departments in Malaysia . RESULTS: There were 435 cases of clinical meningitis admitted to the five centers . More than 90% of the patients were <5 years old, and one-half were <6 months of age . The estimated overall incidence of childhood meningitis in the first 5 years of life was 76.7 per 100000 per year . However, of the 435 cases only 71 (16.3%) fulfilled laboratory diagnostic criteria and in only 58 of these was an organism isolated . Nearly one-half (48%) of all bacteriologically proved cases were caused by Haemophilus influenzae type b (Hib) . The mortality rate was 12.5% and 21 patients (30%) suffered neurologic sequelae . CONCLUSIONS: More than one-half of all cases of culture-positive childhood bacterial meningitis were caused by Hib, although successful isolation of a pathogen occurred in only a small proportion of cases . For this reason the true incidence of Hib meningitis in Malaysia remains unknown . These findings are consistent with previous studies in Malaysia. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S185 - 9 Epidemiology of systemic Haemophilus influenzae disease in Korean children; Lee HJ; BACKGROUND: There is a wide variation in the incidence and clinical characteristics of invasive infections by Haemophilus influenzae type b (Hib) among different populations . Characterizing the clinical significance in a particular community is essential for the development of vaccine policy . Data on the clinical significance of Hib in Asian children, including epidemiology and clinical spectrum, are quite limited . OBJECTIVE: To characterize invasive H . influenzae infections in Korean children in terms of clinical spectrum and frequency as an etiologic agent of bacterial meningitis and to review literature that may be helpful in understanding the epidemiology of H . influenzae disease in Far East Asian children, including Koreans . METHODS: Invasive infections by H . influenzae, Streptococcus pneumoniae and Neisseria meningitidis diagnosed at the Seoul National University Children's Hospital from 1986 to 1996 were reviewed . Conventional culture and the latex particle agglutination test were used in addition for diagnosis . A detailed literature review was undertaken to trace relevant information that may be helpful in understanding the epidemiology of invasive Hib disease among Far East Asian children . RESULTS: A total of 169 invasive infections were identified: 48 H . influenzae; 116 S . pneumoniae; and 5 N . meningitidis . Of the 48 H . influenzae infections 36 developed in apparently healthy children: 25 meningitis; 8 bacteremia; 2 pneumonia; and 1 epiglottitis . Forty-four percent of H . influenzae meningitis developed in infants < 1 year of age, and 92% occurred in children <5 years of age . H . influenzae was the cause of 58% of bacterial meningitis in infants and 62% in children <5 years old . CONCLUSION: The limited data suggest that the incidence of H . influenzae meningitis may be lower in Korean than in US children . Prospective population-based studies are needed urgently in Asian countries, including Korea. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S183 - 5 Childhood bacterial meningitis in Japan; Kamiya H et al.; Haemophilus influenzae type b (Hib) vaccines currently are not used in Japan, but interest in preventing H . influenzae disease by immunization has grown . We performed a retrospective survey for bacterial meningitis in 6 prefectures of Japan . Questionnaires requested the age, sex, clinical outcome and identity of the etiologic organism, if known, of all patients with meningitis younger than 16 years of age who were admitted during calendar year 1994 . Of 876 hospitals within the 6 study prefectures, 363 (41.4%) returned a completed questionnaire . There were 1769 cases of meningitis reported, of which 160 (9%) were considered bacterial in origin . H . influenzae was the most common cause of bacterial meningitis, accounting for 68 cases (43%) . Sixty-six cases (97%) of H . influenzae meningitis occurred in children 4 years of age or younger, and 27 (40%) occurred in children <1 year of age . Calculated incidence rates based on the population of children 4 years of age or less for each prefecture ranged from 3.4 to 9.9 cases per 100000 (mean, 4.7 cases/100000) . H . influenzae is the most common cause of meningitis in Japan, and the estimated incidence rates from this study are very similar to those previously reported from Japan . More comprehensive, prospective surveillance studies will be needed to define better the incidence of Hib meningitis and to aid in making rational decisions regarding the use of Hib vaccination in Japan. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S179 - 82 A population-based survey of Haemophilus influenzae type b nasopharyngeal carriage prevalence in Lombok Island, Indonesia; Gessner BD et al.; BACKGROUND: The Haemophilus influenzae type b (Hib) nasopharyngeal carriage prevalence and invasive disease incidence rates are unknown in Indonesia; consequently Hib vaccine is not included in the routine vaccine schedule . METHODS: To determine carriage prevalence we conducted a population-based, island-wide prospective study of a systematic sample of 484 children 0 to 2 years of age in Lombok, Indonesia . We conducted a risk factor questionnaire and determined serotypes and antibiotic sensitivity patterns . RESULTS: We identified 155 H . influenzae isolates, of which 22 were type b and 12 were encapsulated but not type b . The age- and population-weighted Hib carriage prevalence, adjusted for the sampling design, was 4.6% (95% confidence interval, 3.7 to 5.5%) . Children younger than 6 months of age had a carriage prevalence less than one-half that of older children, and carriage varied within the four administrative regions of the island; otherwise no risk factors for Hib carriage were identified . All Hib specimens were sensitive to ampicillin and 20 (91%) were sensitive to chloramphenicol . CONCLUSIONS: The Hib carriage prevalence in Lombok is similar to that found in developed countries before vaccine introduction . This suggests that further studies should proceed to determine whether Lombok has invasive disease rates as high as those that justified vaccine introduction in developed countries. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S176 - 8 Epidemiologic study of bacterial meningitis in Jakarta and Tangerang: preliminary report; Pusponegoro HD et al.; OBJECTIVE: To identify the cause of bacterial meningitis in children >1 month of age and <5 years of age in several hospitals in Jakarta and Tangerang, Indonesia . METHODS: Hospital-based, prospective surveillance study of 100 subjects between 1 month and 5 years of age . Subjects meeting inclusion criteria were evaluated for clinical and laboratory findings of bacterial meningitis . RESULTS: Of 16 subjects enrolled thus far, 11 have been diagnosed as bacterial meningitis . Of these 11, 6 had positive cerebrospinal fluid (CSF) cultures (2 with Haemophilus influenzae and one each with Neisseria meningitidis, Staphylococcus aureus, Klebsiella ozaenae and Escherichia coli) . Three of the 6 had positive latex agglutination tests (LAT; 2 H . influenzae and 1 N . meningitidis); LAT was negative for all 10 with negative CSF culture . CSF Gram-stained smear was positive only for the subject with E . coli . CONCLUSIONS: The number of children admitted with bacterial meningitis has been declining, perhaps because of early treatment with antibiotics in the community . Of culture-positive cases 33% have been caused by H . influenzae, but this result is based on few patients thus far . LAT has correlated well with culture, whereas Gram stain has had low sensitivity, perhaps reflecting deficiencies in technique. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S172 - 5 Invasive Haemophilus influenzae disease in India: a preliminary report of prospective multihospital surveillance . IBIS (Invasive Bacterial Infections Surveillance) Group; Steinhoff MC; OBJECTIVE: To determine the frequency, clinical characteristics and outcome of acute invasive infections caused by Haemophilus influenzae . DESIGN: Prospective hospital-based surveillance . SETTING: Six large academic referral hospitals in India . PARTICIPANTS: Three thousand four hundred forty-one patients from infancy to adulthood with pneumonia, meningitis or suspected bacterial sepsis . RESULTS: Preliminary data from 24 months of surveillance are presented . There were 58 H . influenzae isolates, of which 96% were serotype b . Nearly all isolates were from infants and children <5 years old, and most of the childhood isolates were from infants <1 year of age . Meningitis cases accounted for 69% of isolates . Overall case fatality was 11% . More than 50% of isolates were resistant to chloramphenicol, and up to 40% were resistant to ampicillin, trimethoprim-sulfamethoxazole or erythromycin . There was no resistance to third-generation cephalosporins . CONCLUSIONS: These preliminary data from six hospitals suggest a substantial burden of severe, preventable H . influenzae infections in India . The distribution of clinical syndromes and the ages of our Hib patients are fairly similar to data from North America and Europe. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S169 - 71 Haemophilus influenzae disease in children in India: a hospital perspective; John TJ et al.; We review and summarize published information on diseases caused by Haemophilus influenzae in India and unpublished data from our center covering more than three decades . Since the mid-1950s H . influenzae has been the most common cause of pyogenic meningitis in children admitted to our hospital, accounting for one-third to one-half of cases . Information from other centers in India has been scanty; the lower frequency of isolation of Haemophilus in studies in some centers may be caused by unsatisfactory media and culture methods . The annual numbers of admissions for pyogenic meningitis in our hospital have been quite similar to the numbers of cases of poliomyelitis . Assuming that the similar numbers of children hospitalized with these two diseases indicate similar incidence rates in the community and taking into account the frequency of Haemophilus isolations in pyogenic meningitis, we estimate that there may be as many as 75 to 100 cases of meningitis caused by this organism per year per 100000 children <5 years of age . Although pneumonia caused by H . influenzae has been recognized in a few studies, information is too scanty to attempt the estimation of incidence . Pus-producing infections caused by Haemophilus are rare . Epiglottitis caused by Haemophilus does not seem to occur in India . In recent years we have found that most invasive Haemophilus infections are caused by H . influenzae type b (Hib); other types or untypable strains are infrequent . An increasing prevalence of resistance to chloramphenicol and ampicillin has been recognized in our center and elsewhere . Thus from a hospital perspective, primary prevention by using Hib vaccine seems to be a rational and beneficial intervention . Community-based studies to measure the disease burden of Hib are urgently needed for a more satisfactory assessment of the need for, and cost benefit of, Hib immunization of all infants. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S165 - 9 Haemophilus influenzae type b infections in Hong Kong; Lau YL et al.; A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b (Hib) diseases in Hong Kong established that the annual incidence for children <5 years old was 2.7 per 100000 {95% confidence interval (CI), 2.0 to 3.5} . However, the corresponding annual incidence in Vietnamese refugees in Hong Kong was 42.7 per 100000 (95% CI 17.2 to 87.9), giving a relative risk of 18.5 (95% CI 8.3 to 41.0) . The nasopharyngeal carriage rate of Hib was zero in 621 healthy Chinese children and 1.3% (95% CI 0.04 to 2.63%) in 300 healthy Vietnamese refugees 2 months to 5 years old in Hong Kong . The corresponding carriage rate of nontypable H . influenzae was 5.8% (95% CI 1.4 to 7.6%) in Chinese and 65.4% (95% CI 58.9 to 69.8) in Vietnamese . In a larger study of 1812 healthy Chinese children between 6 months and 5 years of age investigated by throat swabs, again no Hib was isolated but 141 children (7.8%) were found to be carriers of nontype b H . influenzae . In a study of 596 healthy Chinese children and adults, 25% had the protective level of anti-Hib antibody of >0.15 microg/ml by 1 year and 90% had reached >0.15 microg/ml by 6 years of age . There was some evidence that these "natural" antibodies against Hib in Hong Kong Chinese were cross-reacting antibodies against antigens on other encapsulated bacteria. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S159 - 65 Study on Haemophilus influenzae type b diseases in China: the past, present and future; Yang Y et al.; Meningitis caused by Haemophilus influenzae type b (Hib) is a common and serious disease for which there now are WHO-certified vaccines that are recommended for universal infant immunization in North America and European countries . If these vaccines are to be recommended in Asia, it is necessary to know the incidence, age distribution and clinical outcome of Hib meningitis and other systemic infections in this region . Data on Hib disease in China are scanty . Hib meningitis was common during the 1950s in China, accounting for up to 16% of all of pyogenic meningitis (up to 38% of cases were caused by unknown pathogens), despite severe epidemics of meningococcal meningitis during that period . Since 1989 we have conducted hospital- and community-based etiologic and epidemiologic studies of bacterial meningitis . Hib accounts for 30 to 50% of bacterial meningitis in China . The incidence of Hib meningitis in Hefei City was 10.4 per 100000 children <5 years, a result relatively lower than in the West but higher than the rate of 2.7 found in a retrospective study in Hong Kong . Pneumonia is the primary cause of death for Chinese children . From 1991 to 1993 the average mortality of children<5 years because of pneumonia was 1563.2 per 100000 . To achieve the goal of reducing the death rate of children by one-third by the year 2000, greater efforts should be made to reduce the mortality of children with pneumonia . Our preliminary study showed that about one-fourth to one-third of cases of pneumonia in Chinese children might be caused by Hib . Therefore Hib vaccination for infants and children in China might be an effective and valuable procedure to achieve the goal. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S152 - 9 An assessment of the value of Haemophilus influenzae type b conjugate vaccine in Asia; Miller MA; Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia . Although invasive Hib disease has been reduced substantially wherever Hib conjugate vaccines have been introduced into routine childhood immunization schedules, these vaccines are more costly compared with the vaccines routinely used in the Expanded Program for Immunization . Consequently a model was constructed to compare the expected burden of Hib disease with and without a national vaccine program for various Asian countries . Cost of the vaccine program, expected benefits of reduced deaths and savings from prevented disease treatment were assessed for each country based on the model assumptions . Model outcomes were expressed as a net cost, cost per death prevented and cost per disability-adjusted life year for each country and economic stratum . With the assumption of a disease burden of meningitis and pneumonia comparable with that observed in other regions, the model predicts that 668000 cases of Hib pneumonia and 136000 cases of Hib meningitis would occur annually in this cohort resulting in 156000 deaths . Based on current vaccination coverage rates for the individual countries, the model predicted that approximately 136000 (87%) Hib deaths could be prevented annually with incorporation of Hib vaccine into the Expanded Program for Immunization . For each of the countries considered, routine vaccination with Hib would cost between 0.1 and 3.0% of per capita gross national product per child <5 years of age . Although Hib vaccine would be considered a cost-effective public health intervention, it may be cost-prohibitive to implement in the lowest income countries without initial donor assistance. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S148 - 51 Need for Haemophilus influenzae type b vaccination in Asia as evidenced by epidemiology of bacterial meningitis; Peltola H; OBJECTIVE: To evaluate the role of Haemophilus influenzae type b (Hib) infections in Asia by scrutinizing data on Hib meningitis . DESIGN: A comprehensive literature search was performed in English and other languages . Special attention was paid to the age group of 0 to 4 years, in which the great majority of Hib meningitis occurs . RESULTS: Twenty studies from as many countries indicated Hib to be a major pathogen in childhood meningitis . In series comprising nearly 2000 patients, Hib was responsible for at least 50% of cases in one-third of series and for at least 25% in three-fourths of series investigated and was the leading pathogen overall . The countries in South and Southeast Asia differed from the Middle East and East Asia in having a greater incidence of meningitis during the first 6 months of life; the proportions were 50 to 60% vs . 10 to 30%, respectively (P < 0.001) . CONCLUSIONS: Despite lacking data from many areas, belief in a paucity of Hib disease in Asia is not supported by the existing data; and because meningitis represents only 50 to 75% of all classical Hib manifestations and some cases occur after the age of 4 years, vaccination is warranted . The cumulative age curves suggest that conjugates with good immunogenic potential should be used, especially in South and Southeast Asia. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S139 - 48 The introduction of routine Haemophilus influenzae type b conjugate vaccine in Chile: a framework for evaluating new vaccines in newly industrializing countries; Lagos R et al.; OBJECTIVE: To determine the burden of Haemophilus influenzae type b (Hib) disease, the safety and immunogenicity of Hib conjugate vaccine, the practicality of combining Hib conjugate and diphtheria-tetanus-pertussis vaccines and the effectiveness of routine vaccination . STUDY DESIGNS: A series of studies were carried out involving infants and children in Santiago, Chile . The study designs included retrospective surveillance, cost-benefit analysis, randomized placebo-controlled trials of safety and immunogenicity and a Phase IV postlicensure evaluation of vaccine effectiveness . RESULTS: The studies included in this stepwise process showed that Hib invasive disease was a significant public health problem with a substantial economic burden; that combining Hib conjugate and diphtheria-tetanus-pertussis vaccines was practical, safe and elicited a strong immunologic response; and that the combined formulation afforded a high level of protection against invasive Hib disease (90% effectiveness) . CONCLUSIONS: In July, 1996, Chile became only the third newly industrializing country to introduce routine Hib conjugate vaccination . New vaccines, such as Hib conjugates, will be more expensive than existing ones . The stepwise process used in Chile may serve as an example for the evaluation of new vaccines in nonindustrialized countries. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S136 - 9 The introduction of Haemophilus influenzae type b immunization into the United Kingdom: practical steps to assure success; Salisbury DM; Haemophilus influenzae type b (Hib) vaccine was introduced into the routine childhood immunization program in the UK in October, 1992 . The implementation was coordinated on a national basis, taking account of market research of the information needs of both the public and health professionals . Vaccine distribution arrangements were linked to the scheduling of children for immunization, which was implemented through a national computerized system of calling children for immunization . All children commencing immunization were called for three doses of Hib vaccine . Children < 1 year of age were called back for three doses of vaccine; children >1 but <4 years were called for one dose . No boosters were given . National coverage from the outset of the campaign exceeded 90%; it is now 95% and the incidence of invasive Hib infection has declined by >95% . Some of the lessons learned from the UK introduction may be of relevance to other countries presently considering the implementation of Hib immunization into their routine immunization programs. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S132 - 6 Epidemiology of Haemophilus influenzae type b disease and impact of Haemophilus influenzae type b conjugate vaccines in the United States and Canada; Wenger JD; Haemophilus influenzae type b (Hib) was the major cause of invasive bacterial disease in the United States and Canada before the introduction of Hib conjugate vaccines . Between 10000 and 20000 cases of Hib meningitis and other serious diseases occurred each year, leading to death in at least 3% of all patients and long term neurologic problems in up to 25% of survivors of meningitis . Introduction of Hib conjugate vaccines in Canada and the United States, first in children 18 months and older and later as a routine infant immunization, dramatically decreased the incidence of disease . By 1995 Hib disease levels had declined by more than 95% below preimmunization levels . The remarkably rapid reduction in disease incidence was partly because of the ability of the vaccine to reduce nasopharyngeal carriage of the organism, leading, when given widely, to reduced rates of exposure and infection even in those not immunized . Complete elimination of Hib disease in North America, however, will require achievement of relatively high coverage rates, especially in hard to reach populations where much of the remaining disease is occurring. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S126 - 32 Haemophilus influenzae type b disease and vaccination in Europe: lessons learned; Peltola H; OBJECTIVE: To scrutinize the experiences of those European countries that have played a central role in understanding the behavior of and vaccination for Haemophilus influenzae type b (Hib) diseases, to enlighten weaknesses and to explore whether lessons learned would benefit other countries in combating Hib . DESIGN: Epidemiologic and clinical data on Hib infections and vaccinations were analyzed, including all disease manifestations and all age groups . To improve reliability, sources that used active case finding were especially searched for . RESULTS: In the prevaccination era meningitis represented 40 to 70% of all classical Hib diseases . Epiglottitis was the second most common presentation, except in southern Europe (data not available from former socialist countries) . The overall incidence of meningitis and of all Hib disease combined for children ages 0 to 4 years was 23 and 41 per 100000, suggesting 9900 and 17800 cases per year, respectively . Including all age groups and entities, >20000 Hib cases occurred annually . Vaccination, accomplished with two or three primary doses and a late booster, has almost eliminated Hib disease in >10 countries, and >10000 cases per year are prevented . An age analysis of Hib meningitis suggests that strong early immunogenicity is not as imperative in Europe as in some other regions . The incidence of non-type b H . influenzae infections has not increased . CONCLUSIONS: With Hib epidemiology comparable with that in Europe, good protection is achieved by various conjugate vaccines also with two primary doses only . However, active research on the whole Hib issue should be a priority, especially in southern and eastern European countries. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S123 - 5 The Gambian Haemophilus influenzae type b vaccine trial: what does it tell us about the burden of Haemophilus influenzae type b disease? Mulholland EK, Adegbola RA. The true burden of disease caused by Haemophilus influenzae type b (Hib) remains a mystery in many parts of the developing world . The most frequent manifestations of Hib disease are pneumonia and meningitis . In developing countries where it has been studied, Hib has proved to be a major cause of infant meningitis, generally occurring with greater frequency, in younger infants and with a worse outcome than in industrialized countries in the prevaccine era . The burden of Hib pneumonia is more difficult to define . Studies from developing countries of pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of severe pneumonia . A Gambian study found Hib to be responsible for 7% of cases . However, a recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden of severe pneumonia . The same trial demonstrated a mild herd effect, so this figure may be an underestimate . The biases that lead to the underestimation of the contribution of Hib to the pneumonia burden also apply to estimates of the proportion of severe pneumonia caused by Streptococcus pneumoniae . Vaccine trials may reveal the true burden of that pathogen also. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S117 - 22 Haemophilus influenzae type b conjugate vaccines: a review of efficacy data; Heath PT; BACKGROUND: The development of a vaccine against Haemophilus influenzae type b (Hib) was stimulated by its recognition as a major pathogen of early childhood . The first vaccine to be developed was composed of the capsular polysaccharide of the organism, polyribosylribitol phosphate (PRP), and although effective in older children, it failed to protect those <2 years of age, the group with the highest burden of disease . The conjugation of PRP to protein led to a group of vaccines with enhanced immunogenicity and the ability to induce immunologic memory and thus the potential to protect in infancy . OBJECTIVES: To review the trials of Hib conjugate vaccines in which protective efficacy in infants has been assessed and the experience in countries in which Hib conjugate vaccines have been introduced into the routine infant immunization schedule . DISCUSSION: Each of the Hib conjugate vaccines {PRP-diphtheria toxoid conjugate (PRP-D), PRP conjugated to outer membrane protein of Neisseria meningitidis group B (PRP-OMP), PRP oligosaccharides conjugated to mutant diphtheria toxin CRM197, (HbOC) and PRP conjugated to tetanus toxoid (PRP-T)} has been subjected to prospective clinical trials and all have demonstrated high protective efficacy with one exception: that of the least immunogenic vaccine, PRP-D, when used in a Native American population with a high level of natural disease . The trials have used different populations and different schedules, which limits conclusions about relative efficacies . However, it seems likely that all the vaccines are capable of high efficacy in populations with low levels and late age of Hib disease . Three vaccines (PRP-D, PRP-OMP, PRP-T) have been tested in populations with high rates of disease and only PRP-D has been found lacking . As predicted by immunogenicity data, PRP-OMP affords efficacy after one dose, and PRP-T is efficacious with an accelerated schedule . Of more practical significance the effectiveness of these vaccines when introduced into populations has been uniformly impressive . CONCLUSIONS: Particularly where vaccine coverage is high, it is now likely that Hib disease can be eliminated using Hib conjugate vaccines in infancy. Pediatr Infect Dis J, 1998 Sep, 17(9 Suppl), S113 - 6 Haemophilus influenzae type b vaccines: history, choice and comparisons; Decker MD et al.; The conjugate Haemophilus influenzae type b (Hib) vaccines are safe and far more immunogenic among infants and young children than is the unconjugated H . influenzae type b polysaccharide . The vaccines differ in their immunogenicity when used for primary immunization of infants, and these differences appear to be predictive of efficacy, such that some vaccines might be more suitable than others in certain populations. Kansenshogaku Zasshi, 1998 Aug, 72(8), 781 - 7 {Risk factors for clinical prognosis in bacterial meningitis beyond the neonatal period}; Nagai K et al.; A retrospective clinical study of 64 cases with bacterial meningitis beyond the neonatal period in the department of pediatrics of St . Mary's Hospital (1985-1995) was conducted . Haemophilus influenzae (H . influenzae) (28 cases, 43.8%) and Streptococcus pneumoniae (S . pneumoniae) (23 cases, 35.9%) were common pathogens . The prognosis was classified into three groups; normal (42 cases, 65.6%), neurological sequelae (17 cases, 26.6%) and death (5 cases, 7.8%) . We analyzed the risk factors associated with their outcome . The body temperature at admission, platelet count, CSF examination (WBC, glucose, GOT, GPT) were prognostic factors . The prognosis of bacterial meningitis caused by S . pneumoniae was worse than those due to H . influenzae (p = 0.0347). An Med Interna, 1998 Aug, 15(8), 439 - 42 {Which are the vaccines that human immunodeficiency virus infected patients must receive?}; Valencia Ortega ME et al.; Patients with aids are at increased risk of opportunistic and non opportunistic infections . It is now known that the incidence can be reduced by prophylactic measures and/or the use of vaccines . HIV infection produces an elevated frequency of severe pneumococcal disease with a rate of bacteriemia caused by Streptococcus pneumoniae 150-300 fold greater than rates reported in non-HIV infected people . For this reason, pneumococcal vaccine should be administered as early as possible in the course of the infection . Besides, the antibody response may be significantly higher for asymptomatic persons . Acute hepatitis caused by hepatitis B virus is milder than in non HIV infected patients but chronic disease is more frequent . The prognosis is worse and there is higher risk for infecting another persons . Hepatitis B vaccine is indicated for all the patients with HIV and negative serology fo