Crit Care Med, 2005 Jan, 33(1), 224 - 225 Prognostic value of procalcitonin in children with meningococcal sepsis; Carrol ED et al.; OBJECTIVE:: To compare procalcitonin, lactate, and C-reactive protein as prognostic markers in children with meningococcal septic shock . DESIGN:: Prospective observational study . SETTING:: Alder Hey Children's Hospital, Liverpool, UK . PATIENTS:: Children admitted to our hospital during a 16-month period with a diagnosis of meningococcal sepsis . RESULTS:: Plasma procalcitonin at admission was significantly higher in children with septic shock (median, 73.80 vs . 16.44 ng/mL), those requiring ventilation (median, 47.02 vs . 12.00 ng/mL), and those with a duration of hospital stay >10 days (median, 131.35 vs . 19.26 ng/mL) . Both procalcitonin and lactate reliably discriminated between those children with septic shock (area under the curve {AUC} = 0.85 and 0.84, respectively) and durations of hospital stay exceeding 10 days (AUC = 0.87 and 0.79, respectively) and those without, but C-reactive protein did not . Procalcitonin alone reliably discriminated between those children requiring ventilation and those who did not (AUC = 0.72) . CONCLUSION:: Procalcitonin is a reliable prognostic marker of septic shock, requirement for ventilation, and prolonged hospital stay in children with meningococcal sepsis and performs better than lactate and C-reactive protein. Clin Diagn Lab Immunol, 2005 Jan, 12(1), 152 - 6 Serological Specificities of Murine Hybridoma Monoclonal Antibodies against Neisseria meningitidis Serogroups B, C, Y, and W135 and Evaluation of Their Usefulness as Serogrouping Reagents by Indirect Whole-Cell Enzyme-Linked Immunosorbent Assay; Tsang RS et al.; Murine hybridoma monoclonal antibodies (MAbs) were produced against the capsular antigens of serogroups B, C, Y, and W135 meningococci . Each serogroup-specific MAb reacted with the extracted capsular polysaccharide from its homologous serogroup only and did not react with capsules from the other three serogroups . The application of these MAbs for serogroup identification of meningococci was demonstrated by their abilities to correctly identify 183 clinical isolates of 185 meningococci recovered from individual invasive meningococcal disease (IMD) patients during routine surveillance in 2002 . The remaining two meningococci were identified by PCR grouping as C in one case and Y in another, but neither isolate was positive by bacterial agglutination using rabbit antisera or by enzyme-linked immunosorbent assay using MAbs . The specificities of the anti-Y and anti-W135 MAbs were further assessed by tests with 37 serogroup W135 and 106 serogroup Y meningococci recovered from IMD cases during 1999 to 2001 and 2003 . All 143 meningococci except one serogroup Y isolate were correctly identified by positive reactions with the corresponding MAbs that identified their homologous serogroups . The single serogroup Y isolate was received as nonagglutinable and tested as negative with both rabbit anti-Y antiserum and anti-Y MAb but was positive for the serogroup Y-specific siaD gene . The advantage of using MAbs for serogrouping of meningococci is discussed. Srp Arh Celok Lek, 2001 May-Jun, 129 Suppl 1, 42 - 6 {Results of intensive therapy of meningococcal septicaemia in children}; Plastic surgery management in pediatric meningococcal-induced purpura fulminans; Division of Plastic Surgery, Baylor College of Medicine, Scurlock Tower, 6560 Fannin, Suite 800, Houston, TX 77030, USAPurpura fulminans associated with meningococcemia is a devastating disease in children . The tissue loss can be extensive and difficult to determine at the outset . The authors suggest a strategy to manage these wounds with the goal of preserving as much tissue and function as possible . At the present time, conservative therapy to the wounds appears to be the best course in the initial, critical phase, as long as no active local purulence is found . Debridement or amputation is performed when the nonviable tissue margins are delineated . Temporary coverage with allograft may be required; definitive coverage is accomplished when the local tissue perfusion has recovered . Future revisions are often necessary to improve these children's quality of life. Acta Med Port, 2004 Jan-Feb, 17(1), 49 - 53 Epub 2004 Feb 27. {Acceptance of the new conjugate vaccines . Meningococcal and pneumococcal vaccines.}; De Queiros L et al.; The new conjugate vaccines against group C meningococcal infection and pneumococcal infection were introduced in Portugal in 2001 . In 2001/2002, the media published several alarming news on meningococcal disease and there was an increased demand of those vaccines, not included in the Portuguese National Vaccination Programme . In order to assess the coverage with these new vaccines against Neisseria meningitidis and Streptococcus pneumoniae, we conducted a descriptive study of the cohort born in 1999, using a convenience sample, from eight health centres in the North of Portugal . Data was collected from the vaccination records of 1877 children born in 1999: 37.2% had received the group C meningococcal conjugate vaccine and 33.3% the pneumococcal conjugate vaccine, while 21,2% had received both . Most vaccinations with pneumococcal conjugate vaccine were performed after 23 months of age, above the recommended age range . The biggest number of group C meningococcal conjugate vaccines given in a month, was recorded in February of 2002, when the maximum number of reported cases of meningococcal disease was also observed . Correlation of both distributions over time was very high (R(2>)=0.95) . In February 2002 the number of pneumococcal conjugate vaccine doses given rose again, after having been decreasing since October 2001 . This study suggested research hypothesis for the future. Pediatr Crit Care Med, 2005 Jan, 6(1), 39 - 43 Short-term psychiatric adjustment of children and their parents following meningococcal disease; Shears D et al.; OBJECTIVE: To assess short-term changes in child and parent psychiatric status following meningococcal disease . DESIGN: Prospective cohort study; 3-month follow-up using parent, teacher, and child questionnaires . SETTING: Hospital admissions to three pediatric intensive care units and 19 general pediatric wards . PATIENTS: Sixty children aged 3-6 yrs, 60 mothers, and 45 fathers . INTERVENTIONS: We administered measures of illness severity (Glasgow Meningococcal Septicaemia Prognostic Score, days in hospital) and psychiatric morbidity (Strengths and Difficulties Questionnaires, parent and teacher versions; Impact of Event scales; General Health Questionnaire-28) . MEASUREMENTS AND MAIN RESULTS: In children admitted to pediatric intensive care units, parental reports at 3-month follow-up showed a significant increase in emotional and hyperactivity symptoms and in related impairment; symptoms of posttraumatic stress disorder were present in four of 26 (15%) children >8 yrs old . Regarding the parents, 26 of 60 (43%) mothers in the total sample had questionnaire scores indicative of high risk for psychiatric disorder and 22 of 58 (48%) for posttraumatic stress disorder . In fathers there was high risk for psychiatric disorder in 11 of 45 (24%) and for posttraumatic stress disorder in 8 of 43 (19%) . Severity of the child's physical condition on admission was significantly associated with hyperactivity and conduct symptoms at follow-up . Length of hospital admission was associated with psychiatric symptoms in the child and posttraumatic stress disorder symptoms in parents . There were also significant associations between psychiatric symptoms in children and parents . CONCLUSIONS: Admission of children to pediatric intensive care units for meningococcal disease is associated with an increase in and high levels of psychiatric and posttraumatic stress disorder symptoms in children and parents . Length of admission is associated with psychiatric symptoms in children and posttraumatic stress disorder symptoms in parents . Pediatric follow-up should explore psychiatric as well as physical sequelae in children and parents. Pediatr Crit Care Med, 2005 Jan, 6(1), 9 - 13 Early application of generic mortality risk scores in presumed meningococcal disease; Festa MS et al.; OBJECTIVE: Mortality from meningococcal disease typically occurs within 24 hrs of intensive care unit (ICU) admission . An early, accurate mortality-risk tool may aid in trial design for novel therapies . We assessed the performance of two generic scores that assign mortality risk within 1 hr of ICU admission: the Preintensive Care Pediatric Risk of Mortality (Pre-ICU PRISM) and Pediatric Index of Mortality (PIM) . DESIGN: Prospective, observational study over 21 months . SETTING: Two tertiary pediatric ICUs accepting referrals from southeast England . PATIENTS: Patients were 165 consecutive children with meningococcal disease . Ages ranged from 0.1 to 17 yrs (median 2.3 yrs) . INTERVENTIONS: None . MEASUREMENTS AND MAIN RESULTS: PIM demonstrated greater sensibility, with complete data collected in 93% of cases, compared with 35% for the pre-ICU PRISM . Both scores discriminated well . The area under the receiver operating characteristic curve was 0.90 (95% confidence interval, 0.81-1.00) for PIM and 0.94 (95% confidence interval, 0.88-0.98) for Pre-ICU PRISM; this did not change when applied to the subgroup of patients with complete data . Both scores calibrated poorly, overestimating mortality in the medium-risk strata (and also in the high-risk stratum in the case of Pre-ICU PRISM) . When used as a stratification tool for a hypothetical trial (60% reduction in mortality, 80% power), the scores allowed for a reduction in study size by 50% (PIM) and 43% (pre-ICU PRISM) . CONCLUSIONS: Pre-ICU PRISM and PIM both discriminate well but calibrate poorly when applied to a cohort of children with meningococcal sepsis . Both scores provide an effective means of stratification for clinical trial purposes . The main advantage for PIM appears to be ease of data collection. J Clin Microbiol, 2005 Jan, 43(1), 144 - 9 Interlaboratory comparison of PCR-based identification and genogrouping of Neisseria meningitidis; Taha MK et al.; Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries . Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci . The remaining laboratory was located in Burkina Faso . Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA) . The PCR-based nonculture method for the detection of N . meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively . Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC) . The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7% . Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR . The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs. J Reconstr Microsurg, 2004 Nov, 20(8), 605 - 9 Thoracodorsal artery perforator (TAP) flap reconstruction of a soft-tissue defect of the knee following below-knee amputation; Fortin AJ et al.; Soft-tissue coverage of lower extremity defects with thin, sensate, mobile, and durable soft tissue is challenging . Reconstructive options are further limited in the setting of a below-knee amputation . The authors present the first report of an innervated thoracodorsal artery perforator (TAP) flap for coverage of an anterior knee soft-tissue defect in a patient with bilateral below-knee amputations following disseminated meningococcemia . The soft-tissue defect measured 11 x 17 cm2 centered over the patella, and the TAP flap provided adequate pedicle length, with optimal soft-tissue thickness and pliability with the potential for innervation and minimal donor-site morbidity . Six months postoperatively, the patient is ambulating well with prostheses fitted over her well-healed, stable, knee coverage. Lancet Infect Dis, 2005 Jan, 5(1), 21 - 30 Meningococcal polysaccharide-protein conjugate vaccines; Snape MD et al.; It is now 5 years since the UK became the first country to introduce the serogroup C meningococcal polysaccharide-protein conjugate vaccines (MenC) into its routine immunisation schedule . This article reviews the global use of MenC with particular reference to the range of immunisation strategies used internationally . To date, concerns that MenC may result in an increase in meningococcal disease due to non-C serogroups have not been realised . The vaccine has proved to be highly safe and effective; however, concerns have arisen regarding the duration of vaccine effectiveness . Although booster doses of MenC may potentially extend the duration of protection offered by the vaccine, there are, as yet, no studies assessing this option . Clinical trials are underway to assess new combination conjugate vaccines (containing A, C, Y, and W polysaccharides), and it is probable that these more broadly protective vaccines will become available in the near future. Lancet Infect Dis . 2005 Jan;5(1):14. Meningitis threat addressed on the web; Larkin M; "Look out for meningitis symptoms this winter", urge officials of Health Protection Scotland (HPS; ) . HPS consultant epidemiologist Jim McMenamin noted in a communication that, whereas the meningitis C vaccine has been "extremely successful" in reducing cases, "we continue to see different strains of meningitis that we have no vaccine for," such as serogroup B infection () . HPS officials advised GPs and hospital doctors to use their local and national reference laboratories to rapidly identify the strains of meningococcal bacteria they find, so that appropriate antibiotics can be administered . The threat is not, of course, limited to the UK, with vaccines for some meningococcal strains still a way off . Meanwhile, infectious-disease professionals and their patients can keep abreast of news and information about meningitis by consulting the following sites. Vaccine, 2005 Jan 11, 23(8), 977 - 83 Naturally-acquired immunity to Neisseria meningitidis group A; Amir J et al.; Group A meningococcal disease is epidemic in Sudan, less common in Uganda, a country bordering the "meningitis belt," and rare in North America . The basis of naturally-acquired group A immunity is unknown but in North America protection has been attributed to a high prevalence of serum anticapsular antibodies elicited by cross-reacting bacteria . We measured group A anticapsular antibody concentrations and bactericidal titers in sera from 236 adults (47 from the Sudan obtained at the height of a group A epidemic, 57 from Uganda, and 132 from North America) . Anticapsular antibody concentrations were higher in Sudanese sera than in North American or Ugandan sera (geometric mean of 31.5 versus 5.4 and 5.3mug/ml, respectively, P < 0.0001) . Bactericidal titers of >/=1:4 (presumed to be a protective titer when measured with human complement) were detected in 66% of Sudanese sera as compared with 27 and 23%, respectively, of North American and Ugandan sera (P < 0.0001) . Bactericidal activity was inhibited by group A polysaccharide in 58% of the Sudanese bactericidal sera as compared to 17 and 6% of North America and Ugandan bactericidal sera (P < 0.0005) . Approximately 50% of non-bactericidal Sudanese sera had high IgA anticapsular antibody concentrations, which were rare in bactericidal Sudanese sera . Thus, serum anticapsular antibodies and bactericidal activity are prevalent in Sudanese exposed to a group A epidemic . Cross-reacting group A anticapsular antibodies are prevalent in North American and Ugandan sera, but bactericidal activity is infrequent and when present is largely directed at non-capsular antigens. Curr Opin Crit Care, 2004 Dec, 10(6), 442 - 8 Vasopressin in the ICU; Holmes CL et al.; PURPOSE OF THE REVIEW: Vasopressin is one of the most important endogenously released stress hormones during shock . In this review, studies published in the past year that add to our understanding of the use of vasopressin in the ICU are discussed . RECENT FINDINGS: Endogenous vasopressin levels are inappropriately low in adults with severe sepsis but not in children with meningococcal septic shock . Vasopressin but not norepinephrine improved renal blood flow and oxygen delivery and prolonged survival in animal models of septic shock . In human vasodilatory shock, the combination of low-dose vasopressin and norepinephrine was found to be safe and effective . In humans, vasopressin can cause gastrointestinal hypoperfusion and ischemic skin lesions . In hypodynamic animal models of sepsis vasopressin compromised oxygen delivery and decreased systemic and gut blood flow.High-dose bolus vasopressin appeared promising in animal studies of hemorrhagic shock and cardiopulmonary arrest and in a large, randomized clinical trial of vasopressin versus epinephrine in human cardiopulmonary arrest with asystole . However, poor neurologic outcomes raised controversy in introducing vasopressin into CPR guidelines . SUMMARY: There is growing evidence that vasopressin infusion in septic shock is safe and effective . Several studies published this year support the hypothesis that vasopressin should be used as a continuous low-dose infusion (between 0.01 and 0.04 U/min in adults) and not titrated as a single vasopressor agent . However, multiple studies highlight the clinical equipoise that exists regarding the use of vasopressin in vasodilatory shock . Guidelines on management of septic shock recommend "cautious use of vasopressin pending further studies." Med Trop (Mars), 2004, 64(4), 363 - 6 {Pharyngeal carriage of Neisseria meningitidis in a school of Niamey, Niger}; Djibo S et al.; This study of pharyngeal carriage of Neisseria meningitidis in a school in Niamey, Nigeria was carried out to confirm the feasibility of evaluating the impact of conjugate vaccine on the meningococcal carriage . All 90 pupils attending the school were examined during the dry season in February 1998 . All children had been vaccinated using polysaccharide A/C in 1996 . Samples were collected from the soft palate and immediately seeded on selective medium . After incubation at 37 degrees C for 24 hours, suspicious colonies were re-seeded on Miller-Hinton medium . Identification of N . meningitidis was based on standard biochemical criteria, agglutination grouping and DNA fingerprinting . Seven carriers of N . meningitidis X:NT:P1.5 were found . One of these carriers also presented a strain of N . meningitis A:4:P1.9 . The high prevalence of serogroup X strains coincided with an outbreak of meningitis involving the same sub-type and sequence-type in Niamey. Gesundheitswesen, 2004 Dec, 66(12), 790 - 5 {Public health management in invasive meningococcal diseases.}; Ehrhard I et al.; At the 54 (th) Scientific Congress of the German Professional Association of Public Health Service Physicians and Dentists in Marburg on 6th May 2004 the working group on meningococci (Arbeitsgemeinschaft Meningokokken, AGMK) organised the international workshop "Public Health Management of invasive Meningococcal Disease" . In recent years significant changes in the epidemiology of meningococcal disease took place in Europe: In some countries and regions the number of disease caused by meningococci serogroup C has increased significantly . In the Netherlands this increase led to the introduction of an immunisation programme with conjugated meningococcal vaccines targeting children aged 1 up to 18 years . In Switzerland a peak in the number of reported meningococcal group C cases could be observed in some regions . Therefore, a regional vaccination programme has been introduced . Nevertheless, compared with Germany, the indications for vaccination against meningococci in Switzerland are more extensive . In the workshop, Professor Ulrich Vogel and Dr . Ingrid Ehrhard presented the epidemiological situation in Germany and the recommended prophylaxis regimen against meningococci. Cad Saude Publica, 2004 Nov-Dec, 20(6), 1531 - 7 Epub 2004 Dec 08. {Meningococcal disease diagnostic criteria in Greater Metropolitan Campinas, Sao Paulo State, Brazil.}; Donalisio MR et al.; The aim of this article is to evaluate confirmatory criteria: culture, latex agglutination, counter immunoelectrophoresis, microscopic examination, and clinical/epidemiological criteria for cases of meningococcal disease reported in Greater Metropolitan Campinas, Sao Paulo State, Brazil, from 1993 to 2002 (568 cases) . The following variables were also studied: clinical features, gender, age, city, hospital, case fatality, seasonality, and Neisseria meningitidis serogroup . Culture as a confirmatory criterion was the dependent variable in univariate analysis . The mean proportion of confirmatory criterion by culture was 68.7% . Clinical features of meningococcal disease - meningitis without septicemia (OR = 2.87; CI: 1.89-4.38) and septicemia without meningitis (OR = 0.26; CI: 0.17-0.45) - were associated with confirmation by culture . Case fatality rates were different among all diagnostic criteria . More attention should be given to etiological diagnostic confirmation in more severe cases . Diagnostic methods such as PCR may improve etiological confirmation of meningococcal disease in cases with negative cultures. Ann Acad Med Singapore, 2004 Nov, 33(6), 758 - 62 Oropharyngeal carriage and penicillin resistance of Neisseria meningitidis in primary school children in Manisa, Turkey; Gazi H et al.; INTRODUCTION: To determine the oropharyngeal carriage rates and serogroups of Neisseria meningitidis in primary school children in Manisa, Turkey as well as the prevalence and penicillin resistance of N . meningitidis . MATERIALS AND METHODS: Throat swabs obtained from 1128 children were cultured and recovered organisms were tested by disk diffusion method and the E-test for antimicrobial susceptibilities . RESULTS: The carriage rate of N . meningitidis in our region was 6.2% (71 strains) and the serogroups identified were serogroups A (28.1%), B (22.5%), C (35.2%), D (2.8%) and W-135 (11.2%) . Penicillin resistance was found in 16 strains (22.5%), while beta-lactamase activity was found in none . CONCLUSIONS: The carriage rate of N . meningitidis and serogroups are similar to the rates reported in other countries . Continued surveillance of meningococci for antimicrobial resistance will allow early detection of changes in susceptibility patterns that might affect recommendations for chemoprophylaxis as well as for treatment. Eur J Clin Microbiol Infect Dis, 2004 Oct, 23(10), 776 - 9 Invasive meningococcal disease presenting as Henoch-Schonlein purpura; Tsolia MN et al.; Henoch-Schonlein purpura (HSP) is an acute systemic form of vasculitis that has been associated with a number of viral and bacterial infections . Described here are the cases of two children with invasive meningococcal disease who presented with clinical and laboratory findings typical of HSP . Meningococcal infection may have been the trigger for the manifestation of HSP in these patients. Vaccine, 2005 Jan 4, 23(7), 932 - 9 Immunization of mice with Neisseria meningitidis serogroup B genomic expression libraries elicits functional antibodies and reduces the level of bacteremia in an infant rat infection model; Yero CD et al.; The feasibility of expression library immunization against the pathogenic bacterium Neisseria meningitidis was studied . A genomic library of N . meningitidis serogroup B strain CU385, containing 6000 individual clones, was constructed and divided into 10 sublibraries . Immunization of BALB/c mice with plasmid DNA from six sublibraries induced a humoral response, with recognition of several meningococcal proteins by Western blot . Three of these sublibraries elicited bactericidal antibodies against the homologous strain, and sera from mice immunized with one of these sublibraries reduced significantly the number of viable bacteria in blood of infant rats challenged with N . meningitidis . In addition, after DNA immunization, mice were boosted intraperitoneally with 5 x 10(2) colony forming units of strain CU385 . Mice immunized with nine of the 10 libraries developed bactericidal antibodies 1 week after the boost and controls did not, demonstrating the priming capacity and specificity of our immunization strategy . Our study demonstrates, for the first time, that genomic immunization offers a novel approach for screening possible vaccine candidates against N . meningitidis. Pediatr Infect Dis J, 2004 Oct, 23(10), 969 - 70 W135 meningococcal pericarditis: report of two cases and review of the literature; El Bashir H et al.; Pericarditis is a rare but recognized complication of meningococcal disease . After the 2000 and 2001 hajj in Saudi Arabia, a worldwide outbreak of meningococcal W135:2a:P1.2,5 (epidemic strain) was reported including the United Kingdom . Cases of meningococcal disease occurred in pilgrims and their household contacts; and community spread occurred among non-Muslims . Between July 2001 and January 2002, 2 children with pericarditis associated with W135 meningococcal disease were admitted to our hospital in east London. J Microbiol Immunol Infect, 2004 Dec, 37(6), 371 - 4 Use of universal polymerase chain reaction assay and endonuclease digestion for rapid detection of Neisseria meningitides; Lin HW et al.; Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in children . Early diagnosis and empiric antibiotic treatment have led to a reduction in morbidity and mortality . The value of the traditional gold standard diagnostic tests, blood culture and cerebrospinal fluid (CSF) culture, has been adversely affected by preadmission use of parenteral penicillin and fewer lumbar punctures . We report a case of N . meningitidis in a 19-year-old male who was admitted after suffering from progressive severe headache, and intermittent high fever for 2 days . Gram stain and culture of CSF, and culture of throat swab were negative . However, N . meningitidis was detected by polymerase chain reaction (PCR) with a universal primer set and endonuclease digestion . This report indicated that the PCR method may be an alternative method for the rapid diagnosis of meningococcal meningitis. Pediatr Infect Dis J, 2004 Dec, 23(12 Suppl), S293 - 8 The strategy to control New Zealand's epidemic of group B meningococcal disease; O'Hallahan J et al.; BACKGROUND: In New Zealand today, babies of Pacific ethnicity born in South Auckland have a 1-in-48 chance of contracting meningococcal disease by the time they are 5 years of age . METHODS: The New Zealand government, Chiron Vaccines and the University of Auckland have collaborated to develop and investigate a group B meningococcal vaccine to allow a mass-immunization program to control a prolonged and intense epidemic . Within 3 years, a strain-specific meningococcal outer membrane vesicle vaccine has been developed, and overlapping clinical trials have been undertaken; a report was submitted for regulatory approval within 2 years . An important aspect of the project's strategy was to apply, with physicochemical data, the results of the New Zealand outer membrane vesicle vaccine trials to the parent vaccine produced and evaluated by the Norwegian National Institute of Public Health . Immunogenicity results for the New Zealand vaccine are promising, with the vaccine showing a reactogenicity profile similar to that of the parent vaccine . CONCLUSIONS: Controlling the epidemic depends on delivering an effective vaccine to the individuals at greatest risk, ie, mainly Maori and Pacific populations that previous health programs have struggled to reach . Participation of and partnership with these communities in public health decision-making and vaccine delivery will be critical to a successful immunization program. Pediatr Infect Dis J, 2004 Dec, 23(12 Suppl), S285 - 92 Meningococcal vaccines; Danzig L; BACKGROUND: The 5 major pathogenic serogroups of the Gram-negative encapsulated bacterium Neisseria meningitidis are A, B, C, Y, and W135 . In the 1960s, vaccines consisting of purified capsular polysaccharide antigens were developed against serogroups A, C, Y, and W135 . These vaccines were highly effective among adults but were not efficacious among infants and young children . Capsular polysaccharide-protein conjugate vaccines were subsequently developed . METHODS: The development of second-generation capsular polysaccharide glycoconjugate vaccines that are effective among infants and children is reviewed . The approaches for development of a broadly protective serogroup B vaccine, including attempts toward optimization of outer membrane vesicle vaccines and identification of conserved antigens, are discussed . CONCLUSIONS: Monovalent serogroup C conjugate vaccines have been successful in reducing the burden of serogroup C meningococcal disease among infants, older children, and adults in the United Kingdom and Canada . Tetravalent serogroup A/C/W/Y conjugate vaccines are in late stage development . The use of serogroup B capsular polysaccharide as the basis for a vaccine for prevention of serogroup B meningococcal disease has proved problematic . The recent sequencing of the serogroup B genome led to the identification of additional, genome-derived, neisserial antigens, through a process called "reverse vaccinology." Pediatr Infect Dis J, 2004 Dec, 23(12 Suppl), S280 - 4 Meningococcal C vaccines: the Canadian experience; De Wals P; BACKGROUND: Several outbreaks caused by virulent strains of serogroup C Neisseria meningitidis were observed in several Canadian provinces in the early 1990s . In an attempt to control these outbreaks, local immunization programs, with polysaccharide vaccines, directed at school age children and adolescents were initiated . In Quebec, however, the incidence of serogroup C meningococcal disease remained high among unvaccinated groups, and clusters appeared in previously unaffected areas . As a result, a 1-dose immunization campaign was initiated, targeting all 1.9 million people between 6 months and 20 years of age for vaccination with the polysaccharide vaccine . This campaign was effective in controlling the epidemic, but there was no evidence of vaccine effectiveness among children <2 years of age and protection was short-lived among older individuals . A second series of serogroup C meningococcal disease outbreaks were observed in several Canadian provinces from 1999 to 2001, and a mass immunization campaign with glycoconjugate vaccines against serogroup C meningococcal disease was implemented in the autumn of 2001 . METHODS: Evaluation of the effects of the glycoconjugate vaccination campaign was made with data on confirmed cases of serogroup C disease reported to the regional health authorities between January 1, 2001, and December 31, 2002 . A cost effectiveness analysis of different glycoconjugate vaccine immunization strategies was also performed . CONCLUSIONS: The 1999-2001 glycoconjugate vaccine mass immunization campaign was effective in reducing disease incidence among vaccinated and unvaccinated individuals . Results of the cost effectiveness study indicated that the most effective long term control strategy was a routine, 3-dose, infant vaccination program but the most cost-effective strategy was a routine 1-dose vaccination program in the setting of an acute outbreak. Pediatr Infect Dis J, 2004 Dec, 23(12 Suppl), S274 - 9 Global epidemiology of meningococcal disease and vaccine efficacy; Pollard AJ; BACKGROUND: Control of meningococcal infection has a high priority in many industrialized nations, because of the high mortality rates associated with invasive infection, the public health effects of disease outbreaks, and the position of Neisseria meningitidis as a leading infectious cause of death in childhood . Throughout the past 200 years, epidemics of meningococcal infection have been noted in Europe, Africa, Asia, the United States, and New Zealand . The proportions of cases caused by the 5 predominant capsular types (A, B, C, Y, and W135) associated with the disease vary among different regions and within specific geographic areas with time . Comprehensive disease control can be achieved only with the use of vaccines that target all of these disease-causing serogroups . METHODS: Routine immunization with a new generation of conjugate vaccines against serogroup C meningococci in the United Kingdom since 1999 has had a major effect on serogroup C disease in the region . The success of the vaccine involves 2 mechanisms, ie, (1) direct protective effects for vaccinated individuals through induction of bactericidal antibodies and (2) reductions in nasopharyngeal carriage of the organism and consequent generation of herd immunity through reductions in transmission to unimmunized individuals . CONCLUSIONS: Ongoing development of tetravalent A, C, Y, and W135 conjugate vaccines raises the hope that disease caused by these serogroups can be controlled in the near future . However, development of effective strategies to control serogroup B meningococcal disease is still needed for comprehensive control of meningococcal disease. Anal Chem, 2004 Dec 15, 76(24), 7387 - 90 LC/MS characterization of meningococcal depolymerized polysaccharide group C reducing endgroup and internal repeating unit; Cai X et al.; Hydrogen peroxide has been used to cleave the native Neisseria meningiditis polysaccharide (PS) from mega-Dalton molecular weight to a smaller size (approximately 20 kDa) depolymerized polysaccharide . The polysaccharide was examined after partial peroxide depolymerization to verify the presence of the carboxyl group at position 1 and the intactness of the internal sialic acid repeating units . The reducing end group of meningococcal polysaccharide type C was also examined after derivatization by L-tyrosine hydrazide . Partial peroxide depolymerization did not result in loss of the position 1 carboxyl group at the reducing end of the polysaccharide . In addition, no loss of structural integrity was noted for the internal sialic repeat units. J Infect Dis, 2005 Jan 1, 191(1), 33 - 9 Epub 2004 Nov 29. Neisseria meningitidis serogroup W-135 carriage among US travelers to the 2001 Hajj; Dull PM et al.; In 2000, a large international outbreak of meningococcal disease caused by Neisseria meningitidis serogroup W-135 was identified among pilgrims returning from the Hajj in Saudi Arabia . To assess ongoing risk, we evaluated N . meningitidis carriage among US travelers to the 2001 Hajj . Of 25 N . meningitidis isolates obtained, 15 (60%) were nongroupable and 8 (32%) were serogroup W-135 when tested by standard slide-agglutination techniques . Two additional nongroupable isolates were characterized as serogroup W-135 when tested by polymerase chain reaction . Nine of 10 serogroup W-135 isolates were indistinguishable from the Hajj-2000 clone . None of the departing, but 9 (1.3%) of the returning, pilgrims carried serogroup W-135 (P=.01); all carriers reported previous vaccination . Carriage of N . meningitidis serogroup W-135 increased significantly in pilgrims returning from the Hajj . Although the risk of disease to pilgrims appears to be low, the risk of spread to others of this pathogenic strain remains a concern. Euro Surveill . 2004 Nov 01;9(11) {Epub ahead of print} Surveillance of invasive meningococcal disease in the Czech Republic; Kriz P; Routine notification of invasive meningococcal disease has a long tradition in the Czech Republic, mortality data are available from 1921 and morbidity data from 1943 . The collection of Neisseria meningitidis strains kept in the NRL for Meningococcal Infections in Prague dates from 1970 onwards, and represents more than 3500 strains isolated from invasive disease and their contacts, from healthy carriers and from respiratory infection . Analysis of these strains showed that the Czech meningococcal population is different from that seen in western Europe . In 1993, the incidence serogroup C meningococcal disease increased and was associated with the emergence of the hypervirulent complex Neisseria meningitidis C, ST-11, ET-15/37, and caused an increase in the incidence of invasive meningococcal disease which peaked in 1995 (2.2/100 000) . A vaccination strategy targeting the part of the population at highest risk of invasive meningococcal disease was adopted in the country. Voen Med Zh, 2004 Oct, 325(10), 49 - 59, 96 {The meningococcal infection on Navy: modern clinical-and-epidemiological aspects} {Meningococcal disease} Dittmann S. Arbeitsgemeinschaft Meningokokken des Deutschen Grunen Kreuzes e.V . sd.internat.immun.consult@t-online.de Due to a high complication and case fatality rate, meningococcal diseases are important health problems both in tropical countries experiencing severe epidemics as well as in countries of moderate climate zones . Worldwide N . meningitidis of sero-groups A, B, and C are predominant and to a lesser extent serogroups W (135) and Y play a role, whereas in Europe more than 90 % of meningococcal diseases are caused by serogroups B and C of N . meningitidis . In Germany and other developed countries the majority of cases occur in very young children and adolescents . Since many years, meningococcal polysaccharide vaccines against diseases due to N.meningitidis serogroup A, C, Y and W (135) are commercially available . Unfortunately, a vaccine against diseases caused by N . meningitidis serogroup B is still under development . The recently developed and licensed conjugated meningococcal vaccines against N . meningitidis serogroup C are also protective against disease in very young children . Eight countries in Western Europe as well as Australia have already established country-wide immunization programs for children and adolescents . Within only 2 to 3 years, well managed programs have achieved far-reaching control of meningococcal C disease in UK and the Netherlands . In Germany, the Advisory Committee on Immunization (STIKO recommends immunization for selected risk groups . The current increase of the percentage of meningococcal C diseases to 28 - 30 % gives reason for further discussion regarding immunization strategies . How-ever, the STIKO expressively declares, that in addition to the recommendation for risk groups, the physician can use all vaccines licensed in Germany without any restriction . It is his/her responsibility to advice the patients regarding immunization possibilities against the life-threatening meningococcal disease, particularly if cases are occurring. Commun Dis Intell, 2004, 28(3), 345 - 7 An outbreak of meningococcal disease in a secondary school--implications for public health practice; Miles TA et al.; This report describes briefly the management of three cases of meningococcal disease which all occurred within one week at a secondary school on the Central Coast of New South Wales in late winter 2003 . The Central Coast health area has a population of approximately 300,000 . Between 10 and 15 cases of meningococcal disease are notified to the Central Coast Public Health Unit each year . The three cases all presented to Gosford Hospital, Cases 1 and 2, both in Year 9, on Thursday 14 August 2003 and Case 3 in Year 8 on Friday 15 August 2003. Commun Dis Intell, 2004, 28(3), 324 - 38 Surveillance of adverse events following immunisation: Australia 2002 to 2003; Lawrence G et al.; Reports of suspected adverse events following immunisation (AEFI) are reviewed by the Adverse Drug Reactions Advisory Committee and collated in a central database . We analysed AEFI records for vaccines administered during October 2002 to December 2003, and assessed AEFI reporting trends for 2000 to 2003 . AEFI reporting rates were calculated using denominator data from the Australian Childhood Immunisation Register and the annual national influenza vaccination coverage survey . A total of 1,744 AEFI records were analysed for October 2002 to December 2003 . The majority described non-serious events; 9 per cent (n=149) described AEFIs defined as 'serious' . Four deaths were reported but none were causally related to immunisation . Dose-based AEFI reporting rates were 2.1 per 100,000 doses of influenza vaccine for adults aged 40 years or over and 19.8 per 100,000 doses of scheduled vaccines for children aged <7 years . The most frequently reported individual AEFI was injection site reaction in children after a fourth or fifth dose of an acellular pertussis-containing vaccine (54 and 98 reports per 100,000 doses respectively) . The most frequently suspected vaccine was meningococcal C conjugate vaccine (34% of reports-mostly injection site reactions, gastrointestinal symptoms and headaches) . The average annual reporting rate was 7.0 per 100,000 population, the highest to date . The increase in the AEFI reporting rate was due to a greater number of children becoming eligible to receive a fourth or fifth consecutive dose of acellular pertussis vaccine and the introduction of the meningococcal C vaccination program in January 2003 for those aged 1-19 years . The low reporting rate of serious AEFIs demonstrates the high level of safety of vaccines in Australia. J Leukoc Biol . 2004 Nov 29; {Epub ahead of print} Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages; Jack DL et al.; Deficiency of mannose-binding lectin (MBL) is probably the most common human immunodeficiency and is associated with an increased risk of mucosally acquired infections including meningococcal disease . Tissue macrophages are an important component of mucosal defense, and so we determined the effect of MBL on uptake of meningococci by human monocyte-derived macrophages . Opsonization with MBL significantly increased the capture and doubled the amount of internalization of Neisseria meningitidis . Inhibition of f-actin polymerization indicated that MBL exerted this effect by a dose-dependent acceleration of uptake into phagosomes, which was maximal within the normal physiological concentration of MBL (1.5 microg/ml) and was independent of scavenger receptors . MBL accelerated the acquisition and subsequent loss of the early endosome marker, early endosomal antigen-1, and enhanced the acquisition of the late endosomal marker, lysosome-associated membrane protein-1 . MBL reduced the survival of meningococci within macrophages by more than half, despite the increased uptake of organisms, and significantly reduced the number of viable extracellular bacteria by 80% . We conclude that MBL is a dependent opsonin . able to accelerate microbial uptake and killing . These results suggest that MBL could modify disease susceptibility by modulating macrophage interactions with mucosal organisms at the site of initial acquisition. Braz J Infect Dis, 2004 Aug, 8(4), 328 - 30 Epub 2004 Aug. Deficiency of the eighth component of complement associated with recurrent meningococcal meningitis: case report and literature review; Rosa DD et al.; The authors report a case of deficiency of the eighth component of complement in a young adult with a history of three episodes of meningitis; one of them proved to be meningococcal . The literature was reviewed and meningitis due to Neisseria meningitidis strains causing disease in complement-deficient and complement-sufficient patients was demonstrated . Meningococcal disease may be the first manifestation of complement deficiency; screening for complement function must be considered for those with invasive meningococcal disease, with posterior evaluation of the components of the terminal pathway of complement. Sante, 2004 Jul-Sep, 14(3), 153 - 9 {Meningococcal meningitis epidemics in Benin}; Fourn L et al.; Epidemics of meningococcal meningitis are common in several African countries, including Benin . In northern Benin, part of the "meningitis belt", incidence has been increasing over the past decade, and lethality is high . The A and C serogroups are the primary causal agents . Recently, the appearance of the W135 strain in bordering countries induced considerable fear and necessitated more rigorous epidemiological surveillance in the north . Little epidemiologic information on the course and trends of these epidemics is available . The goal of this article is to describe the pattern of these outbreaks in two northern districts -- Atacora and Donga -- based on a retrospective collection and analysis of data from 16 health centres over the four-year period of 1998 through 2001 . Crude incidence rates increased from 85 to 567 per 100,000 in Atacora and 71 to 619 per 100,000 in Donga . The fatality rate is higher in Donga (3.1%) than Atacora (2.7%) . The epidemic pattern is bimodal in Atacora and unimodal in Donga, although they appear to have a common source . Comparison of the trends in the two districts indicated no significant differences (p>0.05) . The authors suggest that epidemiological data be collected and updated routinely, that vaccination against the A and C serogroups be reinforced while awaiting a vaccine against W135, and that epidemiological surveillance be intensified, in Donga and especially along the border area between Atacora and Togo. JAMA, 2004 Nov 24, 292(20), 2491 - 4 Effectiveness of a mass immunization campaign using serogroup C meningococcal conjugate vaccine; De Wals P et al.; CONTEXT: Meningococcal polysaccharide vaccines are of limited effectiveness . New protein-polysaccharide conjugate vaccines have yet to be evaluated in field conditions . OBJECTIVE: To assess the effectiveness of a serogroup C conjugate meningococcal vaccine in an outbreak setting . DESIGN, SETTING, AND PARTICIPANTS: Population-based observational study of cases of invasive serogroup C meningococcal disease from 1996 through 2002 in Quebec identified from the provincial registry of notifiable diseases and from the provincial reference laboratory . In 2001, a mass immunization campaign with a conjugate vaccine was conducted to control an emerging epidemic . The number of vaccinated individuals was extracted from meningococcal immunization registries . MAIN OUTCOME MEASURES: Incidence of invasive meningococcal disease before and 1 year after the campaign in vaccinated and unvaccinated individuals . RESULTS: Vaccination coverage of those 2 months to 20 years was 82.1% . After the campaign, the number of cases of serogroup C disease decreased from 58 in 2001 to 27 in 2002, and the incidence from 7.8 per million to 3.6 per million . Vaccine effectiveness was found to be 96.8% (95% confidence interval, 75.0%-99.9%) . There was no observed increase in the incidence of the other serogroups . CONCLUSION: The new conjugate vaccine was effective in controlling an emerging epidemic of serogroup C meningococcal disease, as well as providing short-term protection across a wide age range. J Immunol, 2004 Dec 1, 173(11), 6921 - 7 Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex; Bossi F et al.; The infrequent occurrence of septic shock in patients with inherited deficiencies of the terminal complement components experiencing meningococcal disease led us to suspect that the terminal complement complex is involved in vascular leakage . To this end, the permeabilizing effect of the cytolytically inactive soluble terminal complement complex (SC5b-9) was tested in a Transwell system measuring the amount of fluorescein-labeled BSA (FITC-BSA) leaked through a monolayer of endothelial cells . The complex caused increased permeability to FITC-BSA after 15 min as opposed to the prompt response to bradykinin (BK) . The effect of SC5b-9 was partially reduced by HOE-140 or CV-3988, two selective antagonists of BK B2 and platelet-activating factor receptors, respectively, and was completely neutralized by the mixture of the two antagonists . Also, DX-88, a specific inhibitor of kallikrein, partially inhibited the activity of SC5b-9 . The permeabilizing factor(s) released after 30 min of incubation of endothelial cells with SC5b-9 caused a prompt leakage of albumin like BK . Intravital microscopy confirmed both the extravasation of circulating FITC-BSA across mesenteric microvessels 15 min after topical application of SC5b-9 and the complete neutralization by the mixture of HOE-140 and CV-3988 . SC5b-9 induced opening of interendothelial junctions in mesenteric endothelium documented by transmission electron microscopy. J Chromatogr B Analyt Technol Biomed Life Sci, 2004 Dec 25, 813(1-2), 103 - 12 Quantification of residual EDU (N-ethyl-N'-(dimethylaminopropyl) carbodiimide (EDC) hydrolyzed urea derivative) and other residual by LC-MS/MS; Lei QP et al.; An LC-MS/MS method for determination of the break down product of N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) urea derivative, EDU, has been developed and validated for monitoring the residual coupling reagents . Results indicate that the method exhibits suitable specificity, sensitivity, precision, linearity and accuracy for quantification of residual EDU in the presence of meningococcal polysaccharide-diphtheria toxoid conjugate vaccine and other vaccine matrix compounds . The assay has been validated for a detection range of 10-100 ng/mL and then successfully transferred to quality control (QC) lab . This same method has also been applied to the determination of residual diaminohexane (DAH) in the presence of EDU . LC-MS/MS has proven to be useful as a quick and sensitive approach for simultaneous determination of multiple residual compounds in glycoconjugate vaccine samples. Immunology, 2004 Dec, 113(4), 518 - 23 Complement component C7 deficiency in two Spanish families; Barroso S et al.; Different genetic mutations have been described in complement component C7 deficiency, a molecular defect clinically associated with an increased susceptibility to neisserial recurrent infections . In this work we report the genetic basis of C7 deficiency in two different Spanish families (family 1 and family 2) . In family 1, of Gypsy ethnical background, exon-specific polymerase chain reaction and sequencing revealed a not previously described single base deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father, leading to a stop codon that causes the premature truncation of the C7 protein (K416 X 419) . Additionally, the patient and her mother displayed a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in a change of amino acid (G357R) . This mutation was firstly described in individuals of Moroccan Sephardic Jewish ancestry and has been also reported among Spaniards . In family 2, another novel mutation was found in homozygosity in two siblings; a two base-pair deletion of nucleotides 1922 and 1923 in exon 14 leading to the generation of a downstream stop codon causing the truncation of the C7 protein product (S620 X 630) . Our results provide more evidence for the heterogeneous molecular basis of C7 deficiency as well as for the subsequent susceptibility to meningococcal disease, since different families carry different molecular defects . On the other hand, certain C7 defects appear to be prevalent in individuals from certain populations or living in defined geographical areas. Zh Mikrobiol Epidemiol Immunobiol, 2004 Sep-Oct, (5), 71 - 5 {Humoral immune response in animals after the oral administration of group C meningococcal whole-culture preparation} {Characterization of the foci of meningococcal infection in closed groups of males} {No authors listed} A total of 257 foci of meningococcal infection in groups of servicemen were selectively examined in 1982-2002 . From these groups 353 patients with generalized forms of the disease underwent hospitalization . Most of the foci had a single infection, the proportion of foci with 10-40 patients was 82.6% . The meningococcal infection rate among humans in the foci was 25-37%, group A meningococci playing the leading role . In the structure of meningococcal infection generalized forms of infection constituted 16%, localized forms constituted 25% and inapparent forms (carriers)--59% . The formation of the morbidity structure was influenced by the type of the focus (with a single or multiple infection) and the character of morbidity for many years (during epidemic or at the period between epidemics) . No absolute dependence of the level of meningococcal carrier state in the groups of servicemen on the appearance of the generalized forms of meningococcal infection was noted . Thus, both during epidemic and at the period between epidemics the population of meningococci, heterogeneous in its serological structure and differing in its clinical and epidemiological importance, constantly circulated with the leading role played by group A meningococci. Emerg Med Serv, 2004 Oct, 33(10), 120 - 2; discussion 123-7 Case conference: EMS response to meningococcal meningitis; Whisman K et al.; This article presents timelines for two emergency medical incidents in which an atypical, unsafe scene was detected and managed by paramedics . Both incidents involved patients who were correctly diagnosed with meningococcal meningitis and meningococcemia (septic shock) by the paramedics on scene . A case review is presented in moderated format to discuss meningococcal disease and to present several points about scene safety in the setting of an infectious disease emergency, management principles for occupational exposures, and the local emergency management approach to a potential public health emergency in a municipality that does not have its own health department or health officer. Clin Diagn Lab Immunol, 2004 Nov, 11(6), 1100 - 4 Effects of prior polysaccharide vaccination on magnitude, duration, and quality of immune responses to and safety profile of a meningococcal serogroup C tetanus toxoid conjugate vaccination in adults; Southern J et al.; Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide . We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naive adults and prior MACP vaccinees . Laboratory staff (n = 113) were recruited; 73 were naive to meningococcal vaccination, and 40 had previously received > or =1 dose of MACP vaccine . Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later . At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of > or =8 or > or =128 were similar (P > 0.46); >94% of subjects achieved titers of > or =128 at 1 month . However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naive (1,757; 95% confidence interval {95% CI}, 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001) . Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months . Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study . MCC-TT was well tolerated, with similar safety profiles in the two groups . Pain in the arm and headache were the most frequently reported events following vaccination . The study shows that MCC-TT is safe and immunogenic in naive and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower. Mol Biol Evol . 2004 Nov 10; {Epub ahead of print} The Influence of Mutation, Recombination, Population History, and Selection on Patterns of Genetic Diversity in Neisseria meningitidis; Jolley KA et al.; Patterns of genetic diversity within populations of human pathogens, shaped by the ecology of host-microbe interactions, contain important information about the epidemiological history of infectious disease . Exploiting this information, however, requires a systematic approach that distinguishes the genetic signal generated by epidemiological processes from the effects of other forces, such as recombination, mutation and population history . Here, a variety of quantitative techniques were employed to investigate multilocus sequence information from isolate collections of Neisseria meningitidis, a major cause of meningitis and septicemia world wide . This allowed quantitative evaluation of alternative explanations for the observed population structure . A coalescent based approach was employed to estimate the rate of mutation, the rate of recombination, and the size distribution of recombination fragments from samples from disease-associated and carried meningococci obtained in the Czech Republic in 1993, and a global collection of disease-associated isolates collected globally from 1937-1996 . The parameter estimates were used to reject a model in which genetic structure arose by chance in small populations and analysis of molecular variation showed that geographically restricted gene flow was unlikely to be the cause of the genetic structure . The genetic differentiation between disease and carriage isolate collections indicated that, while certain genotypes were over represented among the disease isolate collections (the 'hyperinvasive' lineages), disease-associated and carried meningococci exhibited remarkably little differentiation at the level of individual nucleotide polymorphisms . In combination, these results indicated the repeated action of natural selection on meningococcal populations, possibly arising from the coevolutionary dynamic of host-pathogen interactions. J Trop Pediatr, 2004 Dec, 50(6), 372 - 4 An uncommon presentation: chronic meningococcaemia associated with cholestatic hepatitis in a Turkish child; Totan M et al.; Chronic meningococcaemia is a very rare clinical manifestation of invasive infection by Neisseria meningitidis . A 9-year-old girl was admitted to our clinic with complaints of fever, headache, arthralgia, and maculopapular rash . The diagnosis was made by the growth of Neisseria meningitidis in the blood cultures . Four days after admission, liver function tests were increased and were compatible with cholestatic hepatitis . Thereafter, the patient was successfully treated and symptoms were completely resolved . To our knowledge, there have been no previous reports of Neisseria meningitidis causing cholestatic hepatitis . Herein, we present an unusual child patient with chronic meningococcaemia associated with cholestatic hepatitis. Arch Intern Med, 2004 Nov 8, 164(20), 2206 - 16 Cigarette smoking and infection; Arcavi L et al.; BACKGROUND: Infectious diseases may rival cancer, heart disease, and chronic lung disease as sources of morbidity and mortality from smoking . We reviewed mechanisms by which smoking increases the risk of infection and the epidemiology of smoking-related infection, and delineated implications of this increased risk of infection among cigarette smokers . METHODS: The MEDLINE database was searched for articles on the mechanisms and epidemiology of smoking-related infectious diseases . English-language articles and selected cross-references were included . RESULTS: Mechanisms by which smoking increases the risk of infections include structural changes in the respiratory tract and a decrease in immune response . Cigarette smoking is a substantial risk factor for important bacterial and viral infections . For example, smokers incur a 2- to 4-fold increased risk of invasive pneumococcal disease . Influenza risk is severalfold higher and is much more severe in smokers than nonsmokers . Perhaps the greatest public health impact of smoking on infection is the increased risk of tuberculosis, a particular problem in underdeveloped countries where smoking rates are increasing rapidly . CONCLUSIONS: The clinical implications of our findings include emphasizing the importance of smoking cessation as part of the therapeutic plan for people with serious infectious diseases or periodontitis, and individuals who have positive results of tuberculin skin tests . Controlling exposure to secondhand cigarette smoke in children is important to reduce the risks of meningococcal disease and otitis media, and in adults to reduce the risk of influenza and meningococcal disease . Other recommendations include pneumococcal and influenza vaccine in all smokers and acyclovir treatment for varicella in smokers. Ned Tijdschr Geneeskd, 2004 Oct 16, 148(42), 2072 - 6 {Television watching and some eating habits of 6-14-year-old children in Amsterdam, the Netherlands; a cross-sectional study}; Renders CM et al.; OBJECTIVE: To describe the time spent by children between the ages of 6-14 years watching television during a weekday and to examine associated factors . DESIGN: Cross-sectional questionnaire study . METHOD: Data were collected during a vaccination campaign against meningococci C in Amsterdam in September 2002 . From a sample of 2910 parents of 6-14-year-old children 1775 agreed to participate in the study . Socio-demographic characteristics and data on television viewing the previous day, the presence of a television in the child's bedroom and on eating habits were collected by short interviews . RESULTS: In total 1587 children were included in the analyses, 805 boys and 782 girls . In total 40.1% of the boys and 36.5% of the girls had watched television for > or = 2 h during the previous day . Among the children < or = 10 years 28.7% had a television in their bedroom, among children > 10 years this was 45.7% . Age (> 10 years), ethnicity (notably Surinam origin) and having a television in the bedroom was related to spending more time watching television . Having parents with a high socioeconomic status (SES) was associated with less television viewing than having parents with a lower SES . Children who had not eaten fresh fruit or who had visited a snackbar the previous day had been watching television for > or = 2 h more often than children who had eaten fresh fruit (p < 0.001) or who had not visited a snackbar (p < 0.05) . CONCLUSION: Children spent a lot of time watching television . In view of the relation between television viewing and overweight this is an alarming development . Possibilities for the prevention of overweight by reducing television viewing must be investigated. Indian J Pediatr, 2004 Oct, 71(10), 909 - 13 Management of meningococcemia; Singh J et al.; Meningococcemia causes substantial morbidity and mortality worldwide, usually in the term of fulminant disease . This paper reviews the background, pathophysiology, clinical manifestations, and treatment of this entity, along with prevention measures and public health issues to be considered . The authors present updated information on breakthroughs in the understanding of genetic predisposition to invasive disease . The status of adjunctive treatment modalities such as monoclonal antibodies and activated protein C, and progress in conjugate vaccine development and implementation are also addressed. Vaccine, 2004 Dec 9, 23(4), 470 - 9 Economic evaluation of meningococcal serogroup C conjugate vaccination programmes in The Netherlands and its impact on decision-making; Welte R et al.; The cost-effectiveness of one time vaccination of all persons aged 14 months to 18 years (catch-up programme) and of routine childhood immunisation at either ages 2 + 3 + 4 months, 5 + 6 months, or 14 months with a meningococcal C conjugate vaccine was estimated for The Netherlands, from a societal and a health care payer perspective . A decision analysis cohort model was employed (time horizon 77 years), direct and indirect costs (friction cost method) were considered and future costs and effects were discounted at 4% . The results showed that all vaccination options yield a substantial health gain and that the catch-up programme and routine vaccination at 14 months render favourable cost-effectiveness ratios: between about 13,200 and 17,700 per life year gained for the catch-up programme and between about 2200 and 2400 per life year gained for routine childhood vaccination at 14 months, depending on the perspective . In comparison to vaccination at 14 months, routine childhood vaccination during the first year of life is much less cost-effective: each additional life year gained costs approximately 147,000 (2 + 3 + 4 months) or 102,000 (5 + 6 months), from both perspectives . Additionally, inclusion of the likely herd immunity effect of the catch-up programme increases these incremental cost-effectiveness ratios . These results played a major role in the decision to add meningococcal C vaccination to the routine childhood immunisation schedule at 14 months and to implement a catch-up vaccination programme in The Netherlands in 2002. Vaccine, 2004 Dec 9, 23(4), 444 - 9 Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination; Bertley FM et al.; Early or low dose antigen exposure can prime the immune system for subsequent responses; the so-called "prime-boost" effect . In the context of a Sudanese measles vaccine trial, we assessed whether or not such early exposure could influence the response to revaccination . Children received either Connaught high titer vaccine (CN: n = 53; 10(4.7)pfu) or meningococcal A + C vaccine as a placebo (MEN: n = 58) at 5 months of age . At 9 months of age, all received standard titer Schwarz vaccine (SCH: 10(3.9)pfu) . Neutralizing antibodies were measured before initial vaccination and at 9 months of age (plaque reduction neutralization assay (PRN)) and again at 5 years of age (syncytium inhibition assay (SIA)) . Lymphoproliferative responses to measles virus (MV) antigens were evaluated at 5 years of age . Eleven of the 53 CN-SCH children (21%) had sub-protective neutralizing antibody titers prior to revaccination (log PRN 1.5 +/- 0.03 versus 2.9 +/- 0.07 in the remaining 42 children; P < 0.004) . Maternal antibody titers at the time of initial vaccination in these 11 were high (PRN 2.44 +/- 0.12 versus 1.9 +/- 0.04; P < 0.0001) . At 5 years of age, neutralizing antibodies were comparable in the 11 CN-SCH poor responders (log SIA 2.1 +/- 0.09), the remaining CN-SCH children (2.2 +/- 0.06) and the MEN-SCH group vaccinated only once at 9 months of age (2.25 +/- 0.06) . In contrast, 7/11 of the CN-SCH poor responders (64%) had stimulation indices (SI) > 3 in response to MV antigens at 5 years of age (SI 3.1 +/- 0.6) compared with only 14% in the remaining children of the CN-SCH group (2.0 +/- 0.3; P = 0.05) and 8% in the MEN-SCH group (1.4 +/- 0.2; P < 0.0003) . These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination. J Clin Microbiol, 2004 Nov, 42(11), 5146 - 53 Distribution of serogroups and genotypes among disease-associated and carried isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway; Yazdankhah SP et al.; The distribution of serogroups and multilocus sequence types (STs) in collections of disease-associated and carried meningococci from the period 1991 to 2000 in three European countries (the Czech Republic, Greece, and Norway) was investigated . A total of 314 patient isolates and 353 isolates from asymptomatic carriers were characterized . The frequency distributions of serogroups and clone complexes differed among countries and between disease and carrier isolate collections . Highly significant differentiation was seen at each housekeeping locus . A marked positive association of serogroup C with disease was evidenced . The ST-11 complex was strongly positively associated with disease; associations for other clone complexes were weaker . The genetic diversity of the clone complexes differed . A single ST dominated the ST-11 clone complex, while the ST-41/44 complex exhibited greater levels of diversity . These data robustly demonstrated differences in the distribution of meningococcal genotypes in disease and carrier isolates and among countries . Further, they indicated that differences in genotype diversity and pathogenicity exist between meningococcal clone complexes. Cell Microbiol, 2004 Dec, 6(12), 1153 - 66 Interaction of Neisseria meningitidis with human brain microvascular endothelial cells: role of MAP- and tyrosine kinases in invasion and inflammatory cytokine release; Sokolova O et al.; Neisseria meningitidis traversal across the blood-cerebrospinal fluid barrier is an essential step in the pathogenesis of bacterial meningitis . We have previously shown that invasion of human brain microvascular endothelial cells (HBMEC) by meningococci is mediated by bacterial outer membrane protein Opc that binds fibronectin, thereby anchoring the bacterium to the integrin alpha 5 beta 1-receptor on the endothelial cell surface . However, subsequent signal transduction mechanisms essential for or regulated by N . meningitidis adhesion and invasion, or HBMEC responses to N . meningitidis are unknown . In this report we investigated the role of c-Jun N-terminal kinases 1 and 2 (JNK1 and JNK2), p38 mitogen-activated (MAP) kinase and protein tyrosine kinases in endothelial-N . meningitidis interaction . Binding of meningococci to HBMEC phosphorylated and activated JNK1 and JNK2 and p38 MAPK as well as their direct substrates c-Jun and MAP kinase activated kinase-2 (MAPKAPK-2), respectively . Non-invasive meningococcal strains lacking opc gene (opc mutants and sequence type 11 complex meningococci) still activated p38 MAPK, however, failed to activate JNK . Inhibition of JNK1 and JNK2 significantly reduced internalization of N . meningitidis by HBMEC without affecting its adherence . Blocking the endothelial integrin alpha 5 beta 1 also decreased N . meningitidis-induced JNK activation in HBMEC . These findings indicate the crucial role of JNK signalling pathway in N . meningitidis invasion in HBMEC . In contrast, p38 MAPK pathway was important for the control of interleukin-6 (IL-6) and IL-8 release by HBMEC . Genistein, a protein tyrosine kinase inhibitor, decreased both invasion of N . meningitidis into HBMEC and IL-6 and IL-8 release, indicating that protein tyrosine kinases, which link signals from integrins to intracellular signalling pathways are essential for both bacterial internalization and cytokine secretion by HBMEC. J Biol Chem . 2004 Nov 2; {Epub ahead of print} The Neisseria meningitidis outer membrane lipoprotein FrpD binds the RTX protein FrpC; Prochazkova K et al.; At conditions of low iron availability, Neisseria meningitidis produces a family of FrpC-like, type I-secreted RTX proteins of unknown role in meningococcal lifestyle . It is shown here that starvation for iron induces also production of FrpD, the other protein expressed from a gene located immediately upstream of the frpC gene in a predicted iron-regulated frpDC operon . We found that FrpD is highly conserved in a set of meningococcal strains representative of all serogroups and does not exhibit any similarity to known sequences of other organisms . Subcellular localization and {3H}-palmitic acid labeling in E . coli revealed that FrpD is synthesized with a type II signal peptide for export across the cytoplasmic membrane and is, upon processing to a lipoprotein, sorted to the outer bacterial membrane . Furthermore, the biological function of FrpD appears to be linked to that of the RTX protein FrpC, since FrpD was found to bind the amino-proximal portion of FrpC (first 300 residues) with very high affinity (apparent Kd ~0.2 nM) . These results suggest that FrpD represents an rtx loci-encoded accessory lipoprotein that could be involved in anchoring of the secreted RTX protein to the outer bacterial membrane. Salud Publica Mex, 2004 Sep-Oct, 46(5), 438 - 50 {Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives}; Almeida-Gonzalez L et al.; Bacterial meningitis constitutes a significant global public health problem . In particular, Neisseria meningitidis continues to be a public health problem among human populations in both developed and developing countries . Meningococcal infection is present as an endemic and an epidemic disease . Meningococcal disease is manifested not only as meningitis, but also as meningococcemia . The latter is usually fulminant . The global persistence of N . meningitidis is due to the significant number of carriers and the dynamics of transmission and disease . Approximately 500 million people worldwide are carriers of the bacterium in their nasopharynx . Multiple factors have been identified that predispose to the transmissibility of N . meningitidis, including active or passive inhalation tobacco smoking, upper viral respiratory tract infections, drought seasons, and overcrowding . These factors explain the frequent occurrence of outbreaks in military barracks, schools, prisons, and dormitories . Some of the determinants of invasiveness of the bacteria include nasopharyngeal mucosal damage in colonized individuals, virulence of the strains, absence of bactericidal antibodies, and deficiencies of the complement system . During both endemic and epidemic scenarios of meningococcal disease, control measures should include treating the cases with appropriate antimicrobial therapy (penicillin, ceftriaxone, or chloramphenicol); providing chemoprophylactic drugs to contacts (rifampin or ciprofloxacin), and close observation of contacts . Nevertheless, the key to effective control and prevention of meningococcal disease is immunoprophylaxis . Available vaccines include the polysaccharide monovalent, bivalent (serogroups A, C), or tetravalent (A, C, Y, W-135 serogroups) vaccines; conjugate vaccine (serogroup C); and the combined vaccine with outer membrane proteins and polysaccharide (serogroups B, C) . Due to a recent increase in case reporting of serogroup C N . meningitidis in Mexico, we have developed a national response strategy that includes availability of vaccines and medications for chemoprophylaxis . This review aims at providing health care workers with updated information regarding the epidemiological, clinical, and preventive aspects of meningococcal disease . The English version of this paper is available at: http://www.insp.mx/salud/index.html. Przegl Epidemiol, 2004, 58(2), 241 - 51 {Bacterial meningitis caused by Neisseria meningitidis . Prophylactic measures}; Magdzik W; Meningitis caused by Neisseria meningitidis is one of the most frequent and most serious, with fatal rate between few up to 20% . Majority of cases are caused by Neisseria meningitidis of serological groups A, B, C, as well as Y and W 135 . Vaccination is the most effective prophylactic measure against meningococcal meningitidis . Polysaccharide, not conjugated vaccines against Neisseria meningitidis serological groups A, C, W 135, Y effective for children over 2 years old, adolescents and adults as well as vaccine against serogroup C conjugated with protein carrier, effective for children over 2 months of life, adolescents and adults are used . Conjugated vaccine against serological group C was used in 1998/1999 in Great Britain in the mass vaccination of infants in 2, 3, 4 months of life, children and adolescents up to 17 . In Poland as well as in other European countries serological group B is an etiological factor of majority of cases caused by Neisseria meningitidis . Intensive studies are performed in the field on effective, safety, cheap vaccine against all serological groups of Neisseria meningitidis. Immunobiology, 2004, 209(3), 265 - 76 Preferential use of lambda light chains is associated with defective mouse antibody responses to the capsular polysaccharide of Neisseria meningitidis group B; Colino J et al.; The capsular polysaccharide of Neisseria meningitidis group B (CpsB) is a very poor immunogen in mammals; this has been considered to be due to the induction of tolerance to cross-reactive host glycoconjugates . It has hampered the development of an effective vaccine against this meningococcal group for many years . Syngeneic populations have a similar tolerogenic background . Thus, we used the variability in ability to mount CpsB-specific immunoglobulin (Ig) responses of individuals from these populations to reveal underlying mechanisms to tolerance contributing to the poor immunogenicity of CpsB . Here we analyze by ELISA, the individual CpsB-specific Ig response of BALB/c and other syngeneic mice to immunization with intact bacteria, using the distribution of light chains as a direct indicator of the repertoire dynamics of the response . Although approximately 96% of anti-CpsB Ig bear kappa-light chains, BALB/c mouse populations were heterogeneous in the light chain composition of their individual anti-CpsB Ig responses . The proportion of kappa and lambda-light chains used for anti-CpsB Ig was a private characteristic that remained relatively constant, for each individual, through repetitive immunizations regardless of the bacterial stimuli size . Despite the prevalence of individual use of kappa-light chains, 5% of BALB/c mice showed restricted usage of lambda-light chains in their CpsB-specific Ig responses, and an additional 11% use them significantly . The preferential use of lambda-light chains in these mice was strongly associated with defective IgM, and absent or barely detectable IgG anti-CpsB responses even after repetitive bacterial immunization . We conclude that differences in the private repertoire of specific Ig also contribute to mouse unresponsiveness to CpsB. Med Clin (Barc), 2004 Oct 16, 123(13), 486 - 9 {Meningococcal disease in Catalonia, Spain (1990-1997)}; Carmona G et al.; BACKGROUND AND OBJECTIVE: We aimed to study the behavior of meningococcal disease in Catalonia during the period 1990-1997, identifying the possible epidemic periods . MATERIAL AND METHOD: All cases reported to the notifiable disease system which fulfilled the criteria of confirmed or suspected cases during this period were analyzed . RESULTS: The global incidence rate was 4.8/100,000 . The incidence rate for serogroup B was 1.9/100,000 and for serogroup C 0.8/100,000 . The disease incidence tended to diminish slightly during the study period, with a constant annual growth of 0.11/100,000 . The increased incidence of serogroup C cases in 1996-1997 was associated with an increased incidence in the 10-19 years age group . CONCLUSIONS: Globally, in the 1990-1997 period, the disease incidence tended to diminish slightly . During the last two years, an increased incidence was observed, mostly due to the increase in the number of serogroup C cases . This fact was associated with a change in the age pattern of cases, which increased in the 10-19 years age group, as observed in other countries and coinciding with epidemic periods or greater meningococcal activity. N Engl J Med, 2004 Oct 28, 351(18), 1849 - 59 Clinical features and prognostic factors in adults with bacterial meningitis; van de Beek D et al.; BACKGROUND: We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis . METHODS: From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively evaluated . All patients underwent a neurologic examination on admission and at discharge, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score of 1 to 4 points at discharge) or favorable (a score of 5) . Predictors of an unfavorable outcome were identified through logistic-regression analysis . RESULTS: We evaluated 696 episodes of community-acquired acute bacterial meningitis . The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent) . The classic triad of fever, neck stiffness, and a change in mental status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status . On admission, 14 percent of patients were comatose and 33 percent had focal neurologic abnormalities . The overall mortality rate was 21 percent . The mortality rate was higher among patients with pneumococcal meningitis than among those with meningococcal meningitis (30 percent vs . 7 percent, P<0.001) . The outcome was unfavorable in 34 percent of episodes . Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimentation rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count . CONCLUSIONS: In adults presenting with community-acquired acute bacterial meningitis, the sensitivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status . The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S . pneumoniae . Commun Dis Intell, 2003, 27(4), 520 - 3 Using the national guidelines to manage a meningococcal group C outbreak in a Brisbane boarding school--some discretionary judgements are needed; Davison RP et al.; The management of an organisational outbreak of meningococcal disease using the national Guidelines for the early clinical and public health management of meningococcal disease in Australia (the Guidelines), could be considered a relatively straightforward task . Nevertheless, discretional judgements are often still required by the outbreak control team, as no guidelines can fully cover every eventuality . The greatest challenges generated by this outbreak did not result from the magnitude of the intervention, but from the difficulties in defining the margins of the intervention in the face of heightened community and professional concern . Also Public Health decisions and communication strategies needed to be responsive to these concerns. Emerg Infect Dis, 2004 Oct, 10(10), 1812 - 5 Disease susceptibility to ST11 complex meningococci bearing serogroup C or W135 polysaccharide capsules, North America; Pollard AJ et al.; Clusters of meningococcal disease caused by a hyperinvasive lineage of Neisseria meningitidis, the ST11 complex, bearing a serogroup C polysaccharide capsule, have been prominent in Europe and North America since the early 1990s . This situation has led to expensive public health measures for outbreak control and, finally, to the introduction of a serogroup C glyconjugate vaccine into the primary immunization schedule in the United Kingdom and elsewhere . ST11 complex meningococci may also express serogroup W135 polysaccharide capsules . We investigated the level of population immunity to this hyperinvasive clone in association with the appearance of outbreaks of meningococcal disease in southern British Columbia . We found that most adults and almost all children were apparently susceptible to infection with ST11 complex meningococci bearing both C and W135 polysaccharide capsules, which suggests that a vaccine program directed against only serogroup C meningococci may be insufficient to prevent hyperinvasive ST11 disease. Infect Immun, 2004 Nov, 72(11), 6511 - 8 Expression of heterologous antigens in commensal Neisseria spp.: preservation of conformational epitopes with vaccine potential; O'dwyer CA et al.; Commensal neisseriae share with Neisseria meningitidis (meningococcus) a tendency towards overproduction of the bacterial outer envelope, leading to the formation and release during growth of outer membrane vesicles (OMVs) . OMVs from both meningococci and commensal neisseriae have shown promise as vaccines to protect against meningococcal disease . We report here the successful expression at high levels of heterologous proteins in commensal neisseriae and the display, in its native conformation, of one meningococcal outer membrane protein vaccine candidate, NspA, in OMVs prepared from such a recombinant Neisseria flavescens strain . These NspA-containing OMVs conferred protection against otherwise lethal intraperitoneal challenge of mice with N . meningitidis serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen . This development promises to facilitate the design of novel vaccines containing membrane protein antigens that are otherwise difficult to present in native conformation that provide cross-protective efficacy in the prevention of meningococcal disease. Infect Immun, 2004 Nov, 72(11), 6503 - 10 Development of immunity to serogroup B meningococci during carriage of Neisseria meningitidis in a cohort of university students; Jordens JZ et al.; Understanding the basis of protective immunity is a key requirement for the development of an effective vaccine against infection with Neisseria meningitidis of serogroup B . We have conducted a longitudinal study into the dynamics of meningococcal acquisition and carriage in first-year university students . The detection of carriage of serogroup B meningococci correlated with an increase in detection of serum bactericidal activity (SBA) against both colonizing and heterologous serogroup B strains . Once induced, SBA remained high throughout the study . Although students showed increases in antibodies reactive with capsular polysaccharide and lipopolysaccharide (LPS), these antibody responses were transitory, and their decline was not accompanied by a corresponding decline in SBA . In contrast, there was a significant correlation between the presence of antibodies to the PorA outer membrane protein and SBA against both homologous and heterologous strains . SBA induced by a PorA-negative mutant confirmed the contribution of PorA to heterologous activity . Increases in SBA against a range of serogroup B strains were also observed in students in whom no meningococcal carriage was detected . This heterologous protection could not be associated with the presence of antibodies reacting with capsule, LPS, PorA, PorB, Rmp, Opa, Opc, or pilin, demonstrating that other, as yet unidentified, antigens contribute to the development of immunity to serogroup B meningococci . Identification of such antigens with the ability to induce an effective cross-reactive bactericidal response to a range of strains would be a major step in the production of a universally effective vaccine against infections caused by serogroup B meningococci. Arch Dis Child, 2004 Nov, 89(11), 1064 - 8 The incidence and mortality for meningococcal disease associated with area deprivation: an ecological study of hospital episode statistics; Heyderman RS et al.; AIMS: To determine whether incidence, mortality, and case fatality for meningococcal disease (MD) differs by area deprivation, and if this has changed over time . METHODS: The population of children aged less than 5 years with MD was analysed as quintiles of area deprivation scores over two time periods, 1995-99 and 1991-94 . Annual age standardised rates were calculated and the association between incidence, mortality, and area deprivation quintiles assessed using Poisson regression and the risk ratios determined . Case fatality was calculated from the odds ratio of mortality by area deprivation score for the two time periods . RESULTS: There were 10,524 cases of MD and 441 deaths (4.2%) . Incidence rates were higher for 1995-99 (45.4 per 100,000) compared to 1991-94 (27.4 per 100,000) . Mortality rates remained stable over time, indicating a decline in risk of death of around 40% . The incidence rates for the most deprived quintile were around twice those for the most affluent quintile, but this gradient declined over time . A threefold gradient was seen for mortality rates across the top and bottom quintiles, which was constant over time . The odds of mortality did not show a linear pattern, with mortality being lowest in the first and highest in the second and fifth area deprivation quintiles . CONCLUSIONS: These data show that MD incidence and mortality are socially patterned . The determinants of case fatality are more complex and require further investigation. Emerg Infect Dis, 2004 Sep, 10(9), 1621 - 6 Space-time cluster analysis of invasive meningococcal disease; Hoebe CJ et al.; Clusters are recognized when meningococcal cases of the same phenotypic strain (markers: serogroup, serotype, and subtype) occur in spatial and temporal proximity . The incidence of such clusters was compared to the incidence that would be expected by chance by using space-time nearest-neighbor analysis of 4,887 confirmed invasive meningococcal cases identified in the 9-year surveillance period 1993-2001 in the Netherlands . Clustering beyond chance only occurred among the closest neighboring cases (comparable to secondary cases) and was small (3.1%, 95% confidence interval 2.1%-4.1%). Mil Med, 2004 Sep, 169(9), 684 - 6 Suspected meningococcal meningitis on an aircraft carrier; Farr W et al.; A suspected case of meningococcal meningitis was diagnosed in a 24-year-old sailor onboard an aircraft carrier at sea in 2003 . He was immediately confined to the ship's hospital ward under respiratory isolation precautions and was treated with intravenously administered antibiotics . His illness resolved without sequelae . A total of 99 close contacts from the ship were identified and given antibiotic prophylaxis, with directly observed therapy . British public health authorities were contacted to trace and treat persons identified as close contacts during a port call a few days before presentation . Managing a communicable disease such as meningococcal meningitis in the austere shipboard environment represents a unique challenge to military medical personnel . Successful management is possible through prompt treatment, respiratory isolation, and open communication between primary health care providers and public health officials . The identification of shipboard close contacts and other infection control procedures used by the ship's medical department are reviewed. Saudi Med J, 2004 Oct, 25(10), 1410 - 3 Changes in epidemiological pattern of Meningococcal disease in Saudi Arabia . Does it constitute a new challenge for prevention and control? Al-Mazrou YY, Al-Jeffri MH, Abdalla MN, Elgizouli SA, Mishskas AA. OBJECTIVE: Meningococcal meningitis epidemics, which occurred in the Kingdom of Saudi Arabia (KSA) coincided with Hajj and Umra seasons; the 2 major pilgrims to Muslims . In many countries, the disease showed major changes of its epidemiological determinants, in particular to age and prevailing serogroup . This study was conducted to determine the epidemiological trend of meningococcal meningitis disease in KSA . METHODS: All confirmed meningococcal meningitis cases reported in KSA during the period from January 1999 to December 2002 were studied retrospectively . Confirmation of cases was based on isolation of the causative organism from cerebrospinal fluid (CSF) or blood culture or detection of antigen in the CSF . Personal, clinical and laboratory results were analyzed using Epi info version 6 software . Categorical data were tested using chi2 test . RESULTS: A total of 729 cases were reported, 304 cases (42%) were among people coming from abroad for Hajj or Umra and 425 (58%) were among local population . Nearly half of the later (48%) were reported at the 2 holy areas of Makkah and Madinah, KSA . Thirty-nine percent of cases were children aged <2 years and 58% were <5 years of age . Proportion of cases affected with serogroup W135 increased over time (up to 95%) and significantly affected children aged <5 years (p<0.001) . CONCLUSION: Continuous monitoring of epidemiological determinants is essential to guide vaccination policy. Int J Med Microbiol, 2004 Sep, 294(2-3), 75 - 82 Genetic lineages and their traits in Neisseria meningitidis; Vogel U et al.; Neisseria meningitidis is a model organism for the study of bacterial population biology, for genome sequencing and pathogenicity research . In the recent years, our group has identified a variety of markers for hypervirulent lineages of meningococci, which in part could be validated for typing purposes . Furthermore, carrier strain collections of meningococci and N . lactamica were studied by multilocus sequence typing, and elucidated the impressive genetic variability of those species . Characterisation of meningococcal carrier strains allowed to define the capsule null locus (cnl) of meningococci, which frequently occurs among carrier isolates and renders strains constitutively unencapsulated . This finding poses the question about the yet unclear role of the meningococcal polysaccharide capsule in transmission and carriage . O-acetylation of the meningococcal polysaccharides is another variably expressed trait in meningococci . We identified the genes responsible for O-acetylation of the serogroup C, W-135 and Y capsules, and provided the genetic basis for understanding the variability of O-acetylation patterns in meningococci . The oatC and oatWY genes proved to be the first genes identified to be responsible for O-acetylation of polysialic acid. Am J Clin Pathol, 2004 Nov, 122(5), 754 - 64 Pathogenesis and diagnosis of human meningococcal disease using immunohistochemical and PCR assays; Guarner J et al.; Neisseria meningitidis remains the leading cause of fatal sepsis . Cultures may not be available in fulminant fatal cases . An immunohistochemical assay for N meningitidis was applied to formalin-fixed samples from 14 patients with meningococcal disease . Histopathologic findings in 12 fatal cases included interstitial pneumonitis, hemorrhagic adrenal glands, myocarditis, meningitis, and thrombi in the glomeruli and choroid plexus . Meningeal inflammation was observed in 6 patients . Skin biopsies of 2 surviving patients showed leukocytoclastic vasculitis and cellulitis . By using immunohistochemical analysis, meningococci and granular meningococcal antigens were observed inside monocytes, neutrophils, and endothelial cells or extracellularly . By using real-time polymerase chain reaction (PCR) on formalin-fixed tissue samples, meningococcal serogroup determination was possible in 11 of 14 cases (8 serogroup C, 2 Y, and 1 B) . Diagnosis and serogrouping of N meningitidis can be performed using immunohistochemical analysis and PCR on formalin-fixed tissue samples . Immunohistochemical analysis determined the distribution of meningococci and meningococcal antigens in tissue samples, allowing better insights into N meningitidis pathogenesis. Mol Microbiol, 2004 Nov, 54(3), 731 - 41 Modulation of the mtrCDE-encoded efflux pump gene complex of Neisseria meningitidis due to a Correia element insertion sequence; Rouquette-Loughlin CE et al.; The mtr (multiple transferable resistance) gene complex in Neisseria gonorrhoeae encodes an energy-dependent efflux pump system that is responsible for export of anti-bacterial hydrophobic agents . Expression of the mtrCDE operon in gonococci is negatively regulated by the MtrR protein . Hydrophobic agent resistance mediated by the mtr system is also inducible, which results from an AraC-like protein termed MtrA . In this work, we identified and characterized a pump similar to the gonococcal mtr system in various strains of Neisseria meningitidis . Unlike the situation with gonococci, the mtr system in meningococci is not subject to the MtrR or MtrA regulatory schemes . An analysis of the promoter region of the mtrCDE operon in a panel of meningococcal strains revealed the presence of one or two classes of insertion sequence elements . A 155-159 bp insertion sequence element known as the Correia element, previously identified elsewhere in the gonococcal and meningococcal genomes, was present in the mtrCDE promoter region of all meningococcal strains tested . In addition to the Correia element, a minority of strains had a tandemly linked, intact copy of IS1301 . As described previously, a binding site for the integration host factor (IHF) was present at the centre of the Correia element upstream of mtrCDE genes . IHF was found to bind specifically to this site and deletion of the IHF binding site enhanced mtrC transcription . We also identified a post-transcriptional regulation of the mtrCDE transcript by cleavage in the inverted repeat of the Correia element, as previously described by Mazzone et al . {Gene278: 211-222 (2001)} and De Gregorio et al . {Biochim Biophys Acta 1576: 39-44 (2002)}for other Correia element . We conclude that the mtr efflux system in meningococci is subject to transcriptional regulation by IHF and post-transcriptional regulation by cleavage in the inverted repeat of the Correia element. Mol Immunol, 2005 Jan, 42(1), 105 - 11 C5 complement deficiency in a Spanish family . Molecular characterization of the double mutation responsible for the defect; Delgado-Cervino E et al.; The complement C5 deficiency is a recessive autosomal defect associated with recurrent infectious episodes, generally caused by Gram-negative micro-organisms . To date, only two mutations responsible for C5 deficiency have been characterized, both in heterozygosis . In this paper, we evaluate by immunochemical methods the C5 deficiency in a six-member family, in which one member suffered from meningococcal sepsis and several pneumonia episodes; and a second one with two bacterial meningitis episodes and frequent tonsillitis, pneumonia and herpetic episodes . We also characterize the molecular basis of this deficiency . No C5 protein was found in the serum from three of the children . They were found to be homozygous for a double mutation in the exon 40 of the C5 gene . The parents and the other children have half-normal levels of C5, and they were heterozygotes for the double mutation . This mutation modifies the reading frame, leading to a premature stop codon, and the resulting protein lacks 50 amino acids . As a result, homozygotes and heterozygotes have a total or a partial C5 deficiency respectively . This is the first report of a whole molecular characterization of C5 deficiency. Expert Rev Anti Infect Ther, 2003 Dec, 1(4), 589 - 96 Host response to Neisseria meningitidis lacking lipopolysaccharides; Brandtzaeg P; Plasma levels of lipopolysaccharides are closely associated with disease manifestations and outcomes in meningococcal infections . The knockout mutant lpxA-Neisseria meningitidis completely lacking lipopolysaccharides has made it possible to study the contribution of nonlipopolysaccharide molecules in the bacterial cell wall to the host's response . The lpxA-N . meningitidis requires 10- to 100-fold higher concentrations of bacteria to elicit the same level of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and -6) as the wild type parent strain . It activates human mononuclear peripheral blood cells through CD14 and Toll-like receptor-2 receptor complex whereas the wild type strain activates these cells through the CD14-Toll-like receptor-4-MD2 pathway . Dendritic cells are hardly activated by the lpxA-N . meningitidis . It is as efficient as the wild type strain in activating complement . The lpxA-N . meningitidis expresses pili but does not adhere or invade mucosal cells normally . The defensin-mediated adhesion of lpxA-N . meningitidis to the respiratory epithelial cells is severely reduced as compared with the wild-type strain. Zh Mikrobiol Epidemiol Immunobiol, 2004 Jul-Aug, (4), 35 - 40 {Antigenic activity of oral whole-culture meningococcal preparation, serogroup B}; Delay in reporting meningococcal disease to public health departments; Health Protection Unit NE London, London . elizabeth.sheridan@doctors.org.uk Prompt reporting of meningococcal disease improves the management of contacts . We looked at cases from five major local hospitals over a two-year period to ascertain the time taken to report and reasons for delays . Over 80% of cases were reported in the first 24 hours . Transfer to another unit was a frequent reason for a report being delayed . Nearly half the delayed cases were reported by the microbiology laboratory rather than the clinical team . We stress the need to emphasise timely reporting in the training of frontline medical staff, and the need to designate an individual in accident and emergency as responsible for reporting cases. N Z Med J . 2004 Aug 20;117(1200):1 p preceding U1027. Proceedings of the Meningococcal Vaccine Strategy World Health Organization satellite meeting, 10 March 2004, Auckland, New Zealand; Sexton K et al.; From 1991 to the end of 2003 there have been 5293 cases and 216 deaths from meningococcal disease in New Zealand . On 10 March 2004, the New Zealand Ministry of Health hosted a special meeting to release the first results of the clinical trial in 16 to 24 month olds of a new vaccine (MeNZB), which has been tailor-made to provide protection against the New Zealand epidemic strain . These proceedings summarise the key points from the meeting presentations and highlight some of the important issues considered in the subsequent discussion . In the toddler age-group trial, 75% of the MeNZB recipients exhibited a four-fold or greater rise in serum bactericidal antibodies after three doses of MeNZB--compared with 4% of the control vaccine recipients . Local reactions to MeNZB and the control vaccine were common, especially injection site tenderness . These data, along with data from New Zealand clinical trials in four other age groups and efficacy and safety data from the Norwegian parent vaccine, were used to support the application for a licence to use MeNZB in a proposed mass immunisation programme for 0-19 year olds . During the immunisation programme, a comprehensive safety monitoring programme will be in place to monitor for any adverse reactions following MeNZB immunisation . This will include real-time hospital-based monitoring in the regions first to roll out the vaccine. Mol Biotechnol, 2004 Oct, 28(2), 139 - 45 Genotypic characterization of Neisseria meningitidis using Pyrosequencing; Diggle MA et al.; Pyrosequencing involves the synthesis of single-stranded deoxyribonucleic acid leading to rapid and accurate analysis of nucleotide sequences . This article describes the development of typing assays for the characterization of Neisseria meningitidis using Pyrosequencing . This involved developing methods for the nucleotide sequence analysis of important variable regions contained on a major capsule gene and on outer membrane protein genes that are used for grouping, typing, and subtyping meningococci . To achieve this, primers were designed for amplification of three genes, siaD, porB, and porA from the four main serogroups B, C, Y, and W135 . To facilitate throughput and reproducibility, the method was also automated . Data from 717 isolates have shown that Pyrosequencing can be used for the single nucleotide polymorphism and sequence-analysis characterization of meningococci. Braz J Infect Dis, 2004 Jun, 8(3), 241 - 8 Epub 2004 Sep 29. Three decades of meningococcal disease in the state of Santa Catarina, Brazil; Puricelli RC et al.; Consolidation of data on meningococcal disease surveillance for the state of Santa Catarina, Brazil, has provided new insight about the evolution of this disease during the period of 1971-2000 . A descriptive epidemiological study, based on retrospective analysis of all cases of meningococcal disease notified in the state of Santa Catarina, linked the surveillance data from the Secretary of the State of Health, magnetic tape records and the data from the national surveillance of diseases of obligatory notification . Following World Health Organization guidelines, cumulative incidence exceeding five cases per 100,000 inhabitants was considered indicative of an epidemic . Official population data from the Fundacao Instituto Brasileiro de Geografia e Estatistica were used for the incidence denominator . During the 1971-2000 period, 7,893 cases and 1,354 deaths caused by meningococcal disease were reported . This corresponds to a mean of 263 cases and 45 deaths per year, with a mean incidence of 6.4 cases per 100,000 inhabitants and a fatality rate of 17.2% . Three distinct epidemiological periods were identified, two of which can be considered epidemic . Two of three distinct epidemiological periods were characterized by an epidemic of meningococcal disease, covering 20 of the 30 years analyzed . Identification of the epidemics and preventive actions, such as vaccination and health education, contributed to the reduction of morbidity and mortality due to this disease. N Z Med J . 2004 Aug 20;117(1200):U1016. Prevention of group B meningococcal disease by vaccination: a difficult task; Thomas M; New Zealand has embarked on an immunisation program to reduce the incidence of disease caused by serogroup B Neisseria meningitidis . Similar immunisation programs in Norway and South America have shown good efficacy in older vaccinees (ie, persons receiving vaccinations), but variable efficacy in younger vaccinees . Protective efficacy correlates well with the ability of the vaccine to stimulate a fourfold rise in serum bactericidal antibodies . Unfortunately, second and third doses of serogroup B N . meningitidis vaccines do not boost serum bactericidal antibody titres to very high levels; consequently protective efficacy wanes within a few years of immunisation . The overall outcome of the immunisation program will reflect both the immunogenicity of the vaccine and the uptake of the vaccine by the target population . The especially high incidence of meningococcal disease in Pacific and Maori children means that particular efforts will need to be made to reach these groups. N Z Med J . 2004 Aug 20;117(1200):U1015. The New Zealand Meningococcal Vaccine Strategy: a tailor-made vaccine to combat a devastating epidemic; Sexton K et al.; The New Zealand Meningococcal Vaccine Strategy aims to end the devastating 14-year epidemic of B:4:P1.7b,4 group B meningococcal disease in New Zealand through a mass immunisation programme to all under 20 year olds using a tailor-made vaccine (MeNZB) . This paper describes the scientific rationale, development, and key components of the New Zealand Meningococcal Vaccine Strategy . A summary of the efficacy and safety data of existing outer membrane vesicle group B meningococcal vaccines is included as these data critically support the Strategy. An Pediatr (Barc), 2004 Sep, 61(3), 261 - 5 {Recombinant human activated protein C in the treatment of children with meningococcal purpura fulminans}; Martinon-Torres F et al.; Meningococcal purpura fulminans (MPF) produces high mortality and morbidity, despite appropriate standard therapy . Administration of recombinant human activated protein C (rhAPC) has been successfully applied in adults with MPF and pediatric studies are under way . We report three pediatric patients with MPF treated with rhAPC as compassionate therapy . In two of these patients, positive clinical and laboratory effects were observed and both children achieved full recovery . The remaining patient died after 36 hours from refractory multiorgan failure . No rhAPC-related adverse effects were detected . The reported cases highlight the usefulness of rhAPC in children with MPF at least as a rescue compassionate treatment . Further clinical trials are needed to better delineate its efficacy and administration schedule in children. BMC Fam Pract . 2004 Oct 06;5(1):21. An unusual case of chronic meningitis; Boos C et al.; BACKGROUND: Chronic meningitis is defined as symptoms and signs of meningeal inflammation and persisting cerebrospinal fluid abnormalities such as elevated protein level and pleocytosis for at least one month . CASE PRESENTATION: A 62-year-old woman, of unremarkable past medical history, was admitted to hospital for investigation of a four-week history of vomiting, malaise an associated hyponatraemia . She had a low-grade pyrexia with normal inflammatory markers . A CT brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of the right frontal cortex but with no evidence of meningeal enhancement . Due to increasing confusion and patient clinical deterioration a lumbar puncture was performed at 17 days post admission . This revealed gram-negative coccobacilli in the CSF, which was identified as Neisseria meningitidis group B . The patient made a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for meningococcal meningitis . CONCLUSIONS: 1) Chronic bacterial meningitis may present highly atypically, particularly in the older adult . 2) There may be an absent or reduced febrile response, without a rise in inflammatory markers, despite a very unwell patient . 3) Early lumbar puncture is to be encouraged as it is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate antibiotic therapy can still lead to a good outcome. Arch Phys Med Rehabil, 2004 Oct, 85(10), 1711 - 7 Energy expenditure and gait characteristics of a bilateral amputee walking with C-leg prostheses compared with stubby and conventional articulating prostheses; Perry J et al.; OBJECTIVE: To compare energy cost and stride characteristics during walking with 3 different types of prostheses in a person with bilateral knee disarticulations . DESIGN: Single-case study . Setting Pathokinesiology laboratory . PARTICIPANT: A subject with bilateral knee disarticulations and bilateral transradial amputations secondary to meningococcemia with purpura fulminans . INTERVENTIONS: Not applicable . MAIN OUTCOME MEASURES: Energy cost, stride characteristics, and motion analysis . RESULTS: When wearing the C-Leg prostheses, the subject walked the farthest and fastest, with an overall lower rate of oxygen consumption and oxygen cost compared with walking with either of the other prostheses . Gait analysis while the patient was wearing the C-Leg prostheses revealed premature hip extension, absence of knee flexion during loading response, and a rate of swing in the referent range . CONCLUSIONS: Walking in a C-leg was the most efficient method of ambulation for our subject. Pediatr Ann, 2004 Sep, 33(9), 590 - 5 Rates of Neisseria meningitidis increasing in young adults; Gaur S et al.; The burden of meningococcal disease has remained unchanged in the United States for the past 4 decades . The currently available meningococcal vaccine is safe and effective, however, due to immunogenic limitations inherent to polysaccharide vaccines, it has been available only for high-risk populations older than 2 . Incorporation of a more immunogenic and effective conjugated vaccine into the routine immunization schedule offers an opportunity to substantially affect the incidence of meningococcal disease . The routine use of a meningococcal conjugate vaccine in the United States will save lives and prevent significant morbidity in children and young adults. Commun Dis Intell, 2004, 28(2), 194 - 206 Annual report of the Australian Meningococcal Surveillance Programme, 2003; Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people et al.; National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145 . robertm3@chw.edu.au This report complements the Vaccine Preventable Diseases and Vaccination Coverage reports produced biannually since 2000 by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases in association with the Australian Institute of Health and Welfare . It integrates the available sources of routinely collected data relevant to the current status of vaccine preventable diseases and vaccine coverage in Aboriginal and Torres Strait Islander people in Australia . It aims to better inform Indigenous communities, Indigenous health care providers and planners of immunisation services of the current status and future needs for vaccine prevention in Indigenous people . The data presented here demonstrate that vaccination programs have had a significant impact on the health of Aboriginal and Torres Strait Islander people . Several areas are highlighted for further development of vaccination policy recommendations, in particular high rates of preventable hepatitis A and B, influenza and pneumococcal disease . Areas where more research is needed include means to more accurately monitor vaccination status, the applicability of meningococcal serogroup B vaccines when available, and effective ways of increasing vaccination coverage and timeliness of vaccination . Such issues need to be considered and implemented in full cooperation with Aboriginal and Torres Strait Islander people. An Pediatr (Barc), 2004 Oct, 61(4), 305 - 13 {Meningococcal sepsis in pediatrics . Parameters associated with poor outcome}; Blanco Quiros A et al.; BACKGROUND: Mortality due to meningococcal sepsis continues to be extremely high . Patients with a poor prognosis require aggressive therapy and should be identified early . OBJECTIVE: To investigate the clinical and biological factors associated with poor outcome . PATIENTS AND METHOD: Seventy-one children aged 2 months to 13 years with meningococcal s