Clinical implications of C6 complement component deficiency.

Background: Terminal complement component deficiencies are risk factors for neisserial infections. Objective: To review the clinical characteristics, the diagnosis and the management of patients with a terminal complement component deficiency. Methods: Pertinent articles were selected and reviewed in relation to a case presentation of C6 deficiency. Results: A case of a 56-year old patient with a history of meningitis, chronic rash, and C6 deficiency was presented, followed by discussion of clinical characteristics, diagnosis, and management of terminal complement component deficiencies. Clinical pearls and pitfalls were reviewed for the practicing allergist/immunologist and fellow-in-training. Conclusion: C6 deficiency is the most common terminal complement component deficiency and can present later in age with N. meningitidis infections. Patients can be screened for terminal complement component deficiency by checking CH50.

Risk factors for acquisition of meningococcal carriage in the African meningitis belt.

OBJECTIVE: To investigate potential risk factors for acquisition in seven countries of the meningitis belt. METHODS: Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions. RESULTS: Over the course of the study, acquisition was higher in: (i) 5-to 14-year olds, as compared with those 30 years or older (OR 3.6, 95% CI 1.4-9.9); (ii) smokers (OR 3.6, 95% CI 0.98-13); and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3-5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season (OR 3.7, 95% CI 2.0-6.7) and lower in those reporting antibiotic use (OR 0.17, 95% CI 0.03-0.56). CONCLUSIONS: Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt.

OBJECTIF: Investiguer les facteurs de risque potentiels d'acquisition dans sept pays de la ceinture de la méningite. MÉTHODES: Des ménages ont été suivis toutes les deux semaines pendant deux mois, puis tous les mois pendant quatre mois. Des prélèvements pharyngés sur écouvillons ont été collectés auprès de tous les membres disponibles du ménage à chaque visite et des questionnaires ont été remplis. Les risques d'acquisition sur l'ensemble de la période d'étude et pour chaque visite ont été analysés par une série de régressions logistiques. RÉSULTATS: Au cours de l'étude, l'acquisition a été plus élevée chez: (i) les 5-14 ans, par rapport à ceux âgés de 30 ans ou plus (OR = 3,6; IC95%: 1,4-9,9); (ii) les fumeurs (OR = 3,6; IC95%: 0,98-13); et (iii) les personnes exposées à la fumée de bois à la maison (OR = 2,6; IC95%: 1,3-5,6). Le risque d'acquisition d'une visite à l'autre était plus élevé chez les personnes signalant un mal de gorge pendant la saison sèche (OR = 3,7; IC95%: 2,0-6,7) et plus faible chez celles signalant une utilisation d'antibiotique (OR = 0,17; IC95%: 0,03-0,56). CONCLUSIONS: L'acquisition du portage du méningocoque a culminé chez les enfants d'âge scolaire. Les symptômes récents de maux de gorge pendant la saison sèche, mais pas pendant la saison des pluies, étaient associés à un risque d'acquisition plus élevé. Les infections des voies respiratoires supérieures pourraient être un facteur important d'épidémies dans la ceinture de la méningite.

Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?

Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.

Maternal and perinatal factors associated with subsequent meningococcal, Haemophilus or enteroviral meningitis in children: database study.

We used a database of 248 659 births, with follow-up to subsequent disease, in the Oxford record linkage archive (1979-1999) to study the influence of family, maternal, and perinatal factors on subsequent hospital admission for meningococcal, Haemophilus, and enteroviral meningitis in the children. In this summary, we report key findings that were significant in multivariate analysis. Meningococcal meningitis was significantly associated with maternal smoking [odds ratio (OR) 2·1, 95% confidence interval (CI) 1·2-3·7]. Haemophilus meningitis was associated with having older siblings (e.g. second child compared to first-born, OR 3·3, 95% CI 2·0-5·6). Enteroviral meningitis was associated with low birth weight (OR 2·2, 95% CI 1·3-3·6) and male sex (OR 1·7, 95% CI 1·2-2·3). The mothers of six of the 312 children with enteroviral meningitis had previously had enteroviral meningitis themselves. We concluded that several maternal characteristics influence the risk of these types of meningitis.

Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC / Development and maintenance of immunological memory after immunization against Neisseria meningitidis B with vaccine VA-MENGOC-BC

Neisseria meningitidis é uma das principais causas de meningite bacteriana e septicemia em todo o mundo, acometendo principalmente crianças menores de 4 anos. Atualmente, não existe uma vacina universal contra o meningococo B (MenB). A imunidade protetora contra o meningococo caracteriza-se pela presença e persistência de anticorpos bactericidas, porém pouco se sabe sobre os mecanismos de desenvolvimento desta memória sorológica. Avaliamos em modelo animal e em humanos, a geração e manutenção das células secretoras de anticorpos (ASC) e dos linfócitos B de memória (LBm) após vacinação contra MenB. Utilizamos como referência a vacina diftérica (dt ou DTP), considerada ter ótima eficácia em humanos. Para o estudo em modelo animal, grupos de 6 a 8 camundongos suíços, fêmeas, de 5 a 6 semanas, foram imunizados com 3 doses da vacina VA-MENGOC-BC ou DTP, via intramuscular, com intervalo de 2 semanas entre as doses. Aproximadamente 2, 4 ou 6 meses após a última dose, os animais receberam a dose reforço. A vacina anti-MenB induziu uma resposta primária de ASC maior que a resposta à dose reforço. Ao contrário, a resposta de ASC à vacina dT foi maior após o booster. A resposta de LBm anti-MenB permaneceu constante (média de 1%) ao longo de todo o estudo, mas a resposta ao toxóide diftérico (TD) foi maior após o booster (média de 1,9%) que após a imunização primária. A concentração de IgC, anticorpos bactericidas e opsonizantes contra MenB foi dose-dependente e foi reativada após a administração das doses reforços. Esses resultados sugerem que os LBm presentes no baço foram responsáveis pela forte resposta de anticorpos observada após a dose reforço. Para o TD, ambas ASC e LBm foram importantes na manutenção da memória sorológica. Para o estudo em humanos, seis voluntários foram imunizados com 3 doses da vacina VA-MENGOC-BC, via intramuscular, com intervalo de 6 a 7 semanas entre as doses. Seis meses após a imunização primária, os indivíduos receberam uma dose...

Neisseria meningitides is one of the leading causes of bacterial meningitis and septicemia worldwide, particularly in children less than four years old. Currently, there is no universal vaccine agoinst serogroup B meningococcus (MenB). Protective immunity against meningococcus is characterized by the presence and persistence of bactericidal antibody, but little is known about the mechanisms of development of the serological memory. In this study, we evaluated in animal model and in humans the generation and maintenance of antibody secreting cells (ASC) and memory B cell after vaccination against MenB. We used the diphtheria vaccine (dT or DTP) as a reference for efficacy in humans. Five to six-week old female Swiss mice in groups of 6 to 8 were immunized with three intramuscular injections of VA-MENGOC-BC or DTP vaccine 2 weeks apart. Approximately 2, 4 or 6 months after the last dose, mice received a booster injection of the vaccine. Vaccination against MenB induced a higher ASC primary response compared with the booster response. In contrast, ASC response to dT was higher after booster than after primary immuinization. Memory B-cell to MenB remained at constant levels (mean of 1%) during the whole study, but the response to diphtheria toxoid (TD) was higher after boosting (mean of 1.9%) when compared with the primary response. IgG, bactericidal and opsonic antibody concentrations to MenB was dose-dependent and was reactivated after booster doses. These data suggest that spleen memory B-cells were responsible for the strong boosting antibody response to MenB. For TD, both ASC and memory B-cell were important for maintenance of the serological memory. For the human study, six volunteers were immunized with three intramuscular injections of VA-MENGOC-BC 6 to 8 weeks apart. Six months after the last dose, subjects received a booster dose. Another group of volunteers (n=5) were immunized with a booster dose of dT vaccine. Three doses of vaccine...

[Safety and efficacy of vaccination in children after stem cell transplantation. Part 1]. / Bezpieczenstwo i skutecznosc szczepien ochronnych prowadzonych u dzieci po przeszczepieniu komórek krwiotwórczych. Doniesienie 1.

UNLABELLED: The aim of the study was the evaluation of safety and efficacy of vaccination in children after stem cell transplantation. PATIENTS AND METHODS: 21 patients, 1.4-22 (average 7.8) years old, 13 boys and 8 girls after autologous (11-52%) and allogeneic (10-48%) transplantation were included in the vaccination protocol. Indications for transplantation were: neoplastic disease--16, immunodeficiencies--3 and aplastic anaemia 2 cases. Time between transplantation and beginning of vaccination protocol was 0.8-4 (average 1.5) years. Vaccination protocol was constructed on the basis of the European Group for Blood and Marrow Transplantation indications. We have evaluated: (1) quality of recipient immune reconstitution and protection against common pathogens (2) immunogenicity of revaccination schedule; (3) safety of the vaccination programme. RESULTS: With the exception of one patient presenting with repeated fever, lymph node enlargement, muscle and joint pain, no important side effects were observed. Meningococcial meningitis developed in one patient who refused vaccination. The mean concentrations of antibodies in the plasma before and after vaccination were as follows: anti-diphteria (54; 2285), anti-tetanus (136; 3149) and anti-hepatitis B virus (anti-HBs: 24; 474) IU/ml. CONCLUSIONS: (1) Vaccination in patients after transplantation is efficient and well tolerated. (2) Significant increase of antibody level was detected. (3) Any delay in beginning the vaccination can result in life threatening complications.

Environmental exposures and invasive meningococcal disease: an evaluation of effects on varying time scales.

Invasive meningococcal disease (IMD) is an important cause of meningitis and bacteremia worldwide. Seasonal variation in IMD incidence has long been recognized, but mechanisms responsible for this phenomenon remain poorly understood. The authors sought to evaluate the effect of environmental factors on IMD risk in Philadelphia, Pennsylvania, a major urban center. Associations between monthly weather patterns and IMD incidence were evaluated using multivariable Poisson regression models controlling for seasonal oscillation. Short-term weather effects were identified using a case-crossover approach. Both study designs control for seasonal factors that might otherwise confound the relation between environment and IMD. Incidence displayed significant wintertime seasonality (for oscillation, P < 0.001), and Poisson regression identified elevated monthly risk with increasing relative humidity (per 1% increase, incidence rate ratio = 1.04, 95% confidence interval: 1.004, 1.08). Case-crossover methods identified an inverse relation between ultraviolet B radiation index 1-4 days prior to onset and disease risk (odds ratio = 0.54, 95% confidence interval: 0.34, 0.85). Extended periods of high humidity and acute changes in ambient ultraviolet B radiation predict IMD occurrence in Philadelphia. The latter effect may be due to decreased pathogen survival or virulence and may explain the wintertime seasonality of IMD in temperate regions of North America.

[Complement protein hereditary deficits during purulent meningitis: study of 61 adult Tunisian patients]. / Déficits héréditaires en protéines du complément au cours des méningites purulentes: étude de 61 patients adultes tunisiens et revue de la littérature.

Sixty one Tunisian adult patients with bacterial meningitis were screened for complement deficiency. Functional activity of the classical and the alternative pathways of complement (CH50 and AP50 respectively) were measured according to standard haemolytic procedures. Serum concentrations of C3 and C4 were determined by nephelometry. Late complement component (C5-C9) and properdin concentrations were assessed by double-ligand EISA. Complement deficiency was found in eight patients (13%): Seven had late complement component deficiency (three C7 deficiency, two C5 deficiency, one C6 deficiency and one C8 deficiency) and one had partial properdin deficiency. Patients with late complement component deficiency had a mean age of 24 years (range 17-32 years). All deficient patients had meningococcal meningitis. Recurrent meningitis was reported in half of the patients. Our findings demonstrated a high prevalence of complement deficiency in Tunisia suggesting that screening for hereditary complement deficiency should be performed in case of bacterial meningitides and meningococcal disease patients.

Influence of age and carriage status on salivary IgA to Neisseria meningitidis.

Asymptomatic carriage of Neisseria meningitidis is common (5-35% of individuals) while the incidence of invasive meningococcal disease is fairly low (<1-5 per 100,000 per annum in Europe). Naturally acquired protective immunity may account for this difference. In this study, we investigated the relationship between anti-meningococcal salivary IgA and age and carriage. We showed that salivary IgA to a range of meningococcal antigens increased successively with age with some specificity for commonly circulating serosubtypes. In a group of 258 students 37 (14%) of whom were carriers of N. meningitidis serogroup B, higher levels of specific IgA were associated with carriage. Stratified analysis revealed a positive relationship between smoking and specific anti- N. meningitidis IgA independent of current carriage, weighted odds ratio (OR) 4.1 (95% CI 1.1-18) and OR 3.8 (95% CI 0.96-16) for reference strains B:1:P1.14 and B:4:P1.5,4 respectively. These data implicate IgA as a factor in host defence from meningococcal invasion, although the precise mechanisms remain uncertain.

Human-like immune responses in CD46 transgenic mice.

Neisseria meningitidis is a major cause of sepsis and/or meningitis. These bacteria normally cause disease only in humans, however, mice expressing human CD46 are susceptible to meningococcal disease. To explain the sensitivity of CD46 transgenic mice to meningococci, we evaluated early immune responses. Stimulation of TNF, IL-6, and IL-10 was stronger in CD46 transgenic mice compared with nontransgenic mice, and resembled human responses. In CD46 transgenic mice, bacterial clearance in blood started at later time points, and neutrophil numbers in blood were lower compared with nontransgenic mice. Further, elevated levels of activated microglia cells and cyclooxygenase-2 were observed in brain of infected CD46 transgenic mice. Intraperitoneal administration of meningococci lead to increased levels of macrophages only in the i.p. cavity of CD46 transgenic mice. Most of the responses were impaired or absent using LPS-deficient meningococci, showing the importance of LPS in the early immune response to meningococcal infection. Taken together, these data demonstrate that responses in mice expressing human CD46 mimic human meningococcal disease in many aspects, and demonstrate novel important links between CD46 and the innate immune system.

Critério diagnóstico da doença meningocócica na Região Metropolitana de Campinas, São Paulo, Brasil / Meningococcal disease diagnostic criteria in Greater Metropolitan Campinas, São Paulo State, Brazil

Foi estudado o critério de confirmação etiológica: cultura, clínico, teste do Látex e contraimunoeletroforese, exame bacterioscópico e clínico/epidemiológico dos 568 casos notificados de doença meningocócica na Região Metropolitana de Campinas, São Paulo, Brasil, de 1993 a 2002. Foram analisadas as variáveis: forma clínica, idade, sexo, local de moradia e internação, época do ano de ocorrência, letalidade e sorogrupo da Neisseria meningitidis. Confirmaram-se, pela cultura, 68,7 por cento dos casos. A letalidade foi diferente de acordo com o critério de confirmação da doença. As formas clínicas: meningite sem meningococcemia (OR = 2,87; IC: 1,89-4,38) e a meningococcemia sem meningite (OR = 0,26; IC: 0,17-0,45) mostraram-se associadas com o critério cultura. Maior atenção à confirmação diagnóstica deve ser dada aos casos mais severos. A utilização do teste da reação em cadeia de polimerase pode ser útil para aumentar a capacidade da confirmação etiológica da doença meningocócica em casos de culturas negativas.

Inmunogenicidad inducida por la vacuna antimeningocócica VA-MENGOC-BC® contra la cepa de N. meningitidis ATCC C11 en adolescentes después de 12 años de vacunados / Immunogenecity induced by the VA-MENGOC-BC® antimeningococcal vaccine against the ATCC C11 N. meningitidis strain in adolescents 12 years after being vaccinated

Se estudió la respuesta de anticuerpos inducida por la vacuna antimeningocócica cubana VA-MENGOC-BC® contra la cepa ATCC C11 mediante Ensayo Bactericida del Suero y ELISA, a 184 adolescentes de un Politécnico de Ciego de Ávila, que habían sido inmunizados en campañas masivas 12 años antes. Se realizaron extracciones de sangre antes de aplicar la primera dosis (T0), 4 semanas después de esta (T1) y 4 semanas después de la segunda dosis (T2). Después de 12 años de la vacunación, 25 por ciento de los adolescentes presentó títulos bactericidas ≥ 1:8 frente a la cepa evaluada. Por ELISA, 78 por ciento mostró una concentración de anticuerpos superior al límite de detección contra el polisacárido capsular del meningococo C. Los porcentajes de seroconversión posterior a la primera dosis fueron 59 por Ensayo Bactericida del Suero y 82 por ELISA. No hubo diferencias significativas (p> 0,05) entre los resultados obtenidos después de la primera y segunda dosis por ambos ensayos. La reinmunización con 2 dosis de la vacuna no provocó hiporrespuesta frente a la cepa ATCC C11 en este grupo de edad

Risk factors for meningococcal meningitis in northern Ghana.

Meningococcal meningitis is a major cause of morbidity and mortality in the meningitis belt of sub-Saharan Africa where it occurs in epidemics every 8-12 years. Risk factors for the disease in this setting remain largely unknown. We carried out a case-control study to investigate possible risk factors among survivors of a meningitis epidemic occurring in 1997 in northern Ghana. A structured questionnaire on socio-economic factors, housing and household overcrowding, smoking and exposure to smoke and close contact with a case was administered to 505 of the survivors and 505 of age-, sex- and location-matched controls. Cooking in kitchens with firewood stoves (OR 9.00, CI 1.25-395) and sharing a bedroom with a case (OR 2.18 CI 1.43-3.4) were found to be risk factors for disease. Socio-economic factors, overcrowding, smoking and passive exposure to tobacco smoke were not found to be risk factors. Exposure to smoke from cooking fires or close contact with a case puts people at risk of contracting meningococcal meningitis. In the hot dry months, exposure to smoke from cooking fires should be minimized by encouraging alternatives to cooking over wood fires, or cooking outside. If wood-burning stoves cannot be avoided, kitchens should be made larger with improved ventilation. Meningitis cases should be nursed in well-ventilated rooms and the number of people sharing a room with a case kept at a minimum.

Tendencias en la etiología de la meningitis bacteriana aguda en niños chilenos período 1989-1998: impacto de la vacuna anti-H influenzae tipo b Hib / Etiology of acute bacterial meningitis in chilean children from 1989 to 1998: impact of anti H influenzae type b vaccine

Background: Acute bacterial meningitis still has a high mortality and rate of complications. Aim: To assess the impact of anti H influenzae vaccination on the epidemiology of acute bacterial meningitis in Chilean children. Material and methods: A retrospective study of hospital discharge records of patients with acute bacterial meningitis. Causative agents were studied globally, by hospital and by age group. The changes in etiology from 1989 to 1995 were also assessed. Between 1996 and 1998, only those patients with acute bacterial meningitis caused by H influenzae were recollected. Results: In the period prior to vaccination (1989-1995), 1000 cases were registered. The main causative agents were N meningitidis in 33.8 percent, H influenzas type b in 21.9 percent and S pneumoniae in 15.4 percent. The incidence of H influenzae decreased in the period from 36.4 to 9.9 percent (p<0.001) and the incidence of N meningitidis increased from 22.9 to 52.1 percent (p <0.001). The incidence of S pneumoniae did not change significantly. H influenzae predominated in children between 4 and 24 months of age and N meningitidis predominated in children over 25 months of age. In the period after the introduction of vaccination (1995-1998), there was a further decrease in the incidence of H influenzae from 10 to 2 percent (p <0.001). Until 1997, there was a considerable increase in the incidence of N meningitidis, specially in children over 25 months of age. It declined in 1998 to 38 percent. Conclusions: There was a reduction in the incidence of acute bacterial meningitis caused by H influenzae prior to the introduction of the vaccine against H influenzae type b. The decrease was more pronounced after the introduction of the vaccine

Meningitis por Nisseriea meningitis no tipificable. Reporte de un caso y revisión de la literatura / Meningitis by non-classified Neisseria meningitidis. A case report and review of the literature

La meningitis por Neisseria meningitidis (N. meningitidis) o meningococo es poco común en México, los casos son esporádicos, los serogrupos B y C son los más frecuentes. La tipificación en algunos casos es difícil de realizar. Los mecanismos de patogenicidad, los factores del hospedero que influyen en la presentación clínica, en el pronóstico y la respuesta al tratamiento son analizados en esta revisión que presentamos a propósito de un caso clínico esporádico, tratado satisfactoriamente en el Hospital Central Militar, en el que se identificó N. meningitidis no tipificable.

Marijuana use and social networks in a community outbreak of meningococcal disease.

BACKGROUND: We examined the role of social networks and marijuana smoking in a community outbreak of infections due to Neisseria meningitidis. METHODS: We interviewed all patients and their contacts. Isolates were tested by pulsed field electrophoresis and multilocus enzyme electrophoresis. RESULTS: Nine cases of meningococcal disease occurred in the outbreak; isolates from seven cases with positive cultures were identical. Multiple overlapping social networks were found for case-patients and their contacts. All case-patients were linked by the marijuana-related activities of their contacts. CONCLUSION: Investigation of social networks and marijuana exposure might help identify close contacts of patients with meningococcal disease and help prevent secondary infections.

Gene expression and production of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), IL-8, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and gamma interferon-inducible protein 10 by human neutrophils stimulated with group B meningococcal outer membrane vesicles.

Accumulation of polymorphonuclear neutrophils (PMN) into the subarachnoidal space is one of the hallmarks of Neisseria meningitidis infection. In this study, we evaluated the ability of outer membrane vesicles (OMV) from N. meningitidis B to stimulate cytokine production by neutrophils. We found that PMN stimulated in vitro by OMV produce proinflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-8, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-1beta. A considerable induction of gamma interferon (IFN-gamma)-inducible protein 10 (IP-10) mRNA transcripts, as well as extracellular IP-10 release, was also observed when neutrophils were stimulated by OMV in combination with IFN-gamma. Furthermore, PMN stimulated by OMV in the presence of IFN-gamma demonstrated an enhanced capacity to release TNF-alpha, IL-1beta, IL-8, and MIP-1beta compared to stimulation with OMV alone. In line with its downregulatory effects on neutrophil-derived proinflammatory cytokines, IL-10 potently inhibited TNF-alpha, IL-1beta, IL-8, and MIP-1beta production triggered by OMV. Finally, a neutralizing anti-TNF-alpha monoclonal antibody (MAb) did not influence the release of IL-8 and MIP-1beta induced by OMV, therefore excluding a role for endogenous TNF-alpha in mediating the induction of chemokine release by OMV. In contrast, the ability of lipopolysaccharide from N. meningitidis B to induce the production of IL-8 and MIP-1beta was significantly inhibited by anti-TNF-alpha MAb. Our results establish that, in response to OMV, neutrophils produce a proinflammatory profile of cytokines and chemokines which may not only play a role in the pathogenesis of meningitis but may also contribute to the development of protective immunity to serogroup B meningococci.