Causes of Pediatric Meningitis in Botswana: Results From a 16-Year National Meningitis Audit.

BACKGROUND: Central nervous system infections are an important cause of childhood morbidity and mortality in high HIV-prevalence settings of Africa. We evaluated the epidemiology of pediatric meningitis in Botswana during the rollout of antiretroviral therapy, pneumococcal conjugate vaccine and Haemophilus influenzae type B (HiB) vaccine. METHODS: We performed a cross-sectional study of children (<15 years old) evaluated for meningitis by cerebrospinal fluid (CSF) examination from 2000 to 2015, with complete national records for 2013-2014. Clinical and laboratory characteristics of microbiologically confirmed and culture-negative meningitis were described and incidence of Streptococcus pneumoniae, H. influenzae and cryptococcal meningitis was estimated for 2013-2014. RESULTS: A total of 6796 unique cases were identified. Median age was 1 year [interquartile range 0-3]; 10.4% (435/4186) of children with available HIV-related records were known HIV-infected. Overall, 30.4% (2067/6796) had abnormal CSF findings (positive microbiologic testing or CSF pleocytosis). Ten percent (651/6796) had a confirmed microbiologic diagnosis; including 26.9% (175/651) Cryptococcus, 18.9% (123/651) S. pneumoniae, 20.3% (132/651) H. influenzae and 1.1% (7/651) Mycobacterium tuberculosis. During 2013-2014, national cryptococcal meningitis incidence was 1.3 cases per 100,000 person-years (95% confidence interval, 0.8-2.1) and pneumococcal meningitis incidence 0.7 per 100,000 person-years (95% confidence interval, 0.3-1.3), with no HiB meningitis diagnosed. CONCLUSIONS: Following HiB vaccination, a marked decline in microbiologically confirmed cases of H. influenzae meningitis occurred. Cryptococcal meningitis remains the most common confirmed etiology, demonstrating gaps in prevention-of-mother-to-child transmission and early HIV diagnosis. The high proportion of abnormal CSF samples with no microbiologic diagnosis highlights limitation in available diagnostics.

Meningitis por Haemophilus influenzae b: ¿estamos ante una reemergencia? 24 años de experiencia en un hospital pediátrico / Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital

Introducción. Haemophilus influenzae b era la principal causa de meningitis bacteriana en menores de 5 años. Después de la introducción de la vacuna al calendario (1998), se observó un descenso significativo de la incidencia, pero, en los últimos años, hubo un aumento. Los objetivos de este estudio fueron describir las características y analizar la curva epidémica de los casos de meningitis por Haemophilus influenzae b (MHib) comparando los períodos pre- y posvacunación. Material y métodos. Estudio de series temporales. Se incluyeron todos los pacientes internados por MHib en el Hospital de Niños "R. Gutiérrez" (enero de 1992-mayo de 2016). Se compararon las tasas de hospitalización antes (prevacunación) y después (posvacunación) de la introducción de la vacuna. Se dividió la etapa posvacunación en tres períodos similares. Resultados. Fueron admitidos 85 pacientes con MHib (73,3% prevacunación). Las características clínicas y sociodemográficas de los casos en ambos períodos no mostraron diferencias. Prevacunación: 10,5 casos/año; y posvacunación: 0,7 casos/año. A partir de 2014, se observó un aumento. Tasa de letalidad: 4,8% (todos prevacunación). Datos posvacunación (n= 15): 40% del esquema primario completo, 40% del esquema atrasado para la edad. Reducción global de la tasa hospitalaria de MHib de 89,8% (IC 95%: -82,79-93,96%; p < 0,001) en el período posvacunación. Al analizar los diferentes períodos posvacunación, se observa una caída en la reducción a lo largo del tiempo. Conclusiones. Se observó una disminución muy importante de las hospitalizaciones por MHib pos introducción de la vacuna, pero, en los últimos años, se evidenció un aumento de estos casos sin modificaciones en las características de los pacientes.

Introduction. Haemophilus influenzae type B (Hib) used to be the main cause of bacterial meningitis in children younger than 5 years old. Following the introduction of the Hib vaccine in the immunization schedule (1998), its incidence reduced significantly but it has increased over the last years. The objectives of this study included describing the characteristics and analyzing the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing the pre- and postimmunization periods. Material and methods. Time-series study. All patients hospitalized with Hib meningitis at Hospital de Niños "R. Gutiérrez" (January 1992-May 2016). Hospitalization rates were compared before (pre-immunization) and after (post-immunization) the introduction of the Hib vaccine. The post-immunization period was divided into three similar periods. Results. Eighty-five patients with Hib meningitis were admitted (73.3% in the pre-immunization period). No differences were observed in relation to the clinical and sociodemographic characteristics of cases in both periods. Pre-immunization: 10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n= 15): 40% had completed their primary immunization schedule, 40% were delayed on the immunization schedule for their age. Overall reduction in the hospital rate of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in the post-immunization period. The analysis of the different post-immunization periods shows a decline in reduction over time. Conclusions. A very significant reduction in hospitalizations due to Hib meningitis was observed after the Hib vaccine was introduced; however, over the past years, the number of cases has increased although no changes have been observed in patient characteristics.

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.

Incidência de meningite por Haemophilus influenzae no RS 1999-2010: impacto da cobertura vacinal / Incidence of meningitis caused by Haemophilus influenzae in the state of Rio Grande do Sul 1999-2010: impact of vaccination campaign

O objetivo deste artigo é analisar e verificar a situação epidemiológica das meningites causadas pelo agente Haemophilus influenzae tipo b nos últimos 10 anos no Rio Grande do Sul. Estudo retrospectivo, descritivo, utilizando o sistema de dados de notificação de meningites, e cobertura vacinal, armazenados em base on line Tabnet - Tabulação de dados Epidemiológicos - CEVS/SES/RS, abrangendo o período de 1999 a 2010. Foram utilizados casos notificados e confirmados, tendo como critério de seleção o ano de inicio dos sintomas, idade, diagnostico e evolução. Foi analisado o Estado do Rio Grande do Sul, representado por 19 coordenadorias de saúde. Comparações entre proporções foram avaliadas pelo teste de z. No RS foram notificados 3043 casos confirmados de meningite bacteriana, sendo 6,77% dos casos causados por H. influenzae. O coeficiente de incidência da meningite por H. influenzae, sem considerar faixa etária, caiu significativamente (95,6%) após 1999, assim como a mortalidade. Crianças menores de um ano continuam sendo as mais acometidas (52%), não havendo alteração na letalidade. Os resultados apresentados revelaram um impacto positivo das estratégias de vacinação contra Hib no Estado do Rio Grande do Sul nos últimos dez anos.

This article seeks to analyze and update the epidemiological situation of meningitis caused by Haemophilus influenzae type b in the past 10 years in the state of Rio Grande do Sul (RS). It is a retrospective, descriptive study, which used the data notification system of meningitis and vaccination campaign coverage, stored in the Epidemiological TABNET online database, for the period from 1999 to 2010. Cases notified and confirmed were used and the selection criteria were the year when the symptoms were detected, age, diagnosis, and evolution. Nineteen health centers in the state of Rio Grande do Sul were analyzed. The z-test was used to evaluate comparisons between the proportions. In the period studied, 3043 confirmed cases of bacterial meningitis were reported, of which 6.77% were caused by H. influenzae. The incidence and mortality rates of meningitis caused by H. influenzae, without taking age group into consideration, fell significantly (95.6%) after 1999. Children under one year old continue to be the most affected (52%), there being no change in lethality. The results presented revealed a positive impact of Hib vaccination strategies in the state of Rio Grande do Sul over the past ten years.

Long-term mortality in children diagnosed with Haemophilus influenzae meningitis: a Danish nationwide cohort study.

BACKGROUND: The long-term mortality in children diagnosed with Haemophilus influenzae meningitis is poorly documented. METHODS: We performed a nationwide, population-based cohort study including all Danish children diagnosed at the age between 0 and <5 years with H. influenzae meningitis from 1977 through 1996 and who were alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. For each H. influenzae meningitis patient, 6 age- and gender-matched population controls were indentified. We constructed Kaplan-Meier survival curves and used Cox regression analysis to estimate mortality rate ratios (MRR) and analyze causes of death. The risk of inpatient admission and of requiring hospital outpatient services during follow-up was calculated. RESULTS: We identified 1242 H. influenzae meningitis patients and 7452 population controls, with a median follow-up time of 21.3 years. The MRR for patients with H. influenzae meningitis was 1.08 (95% confidence interval, 0.57-2.05), adjusted MRR was 0.97 (95% confidence interval, 0.50-1.89). No increased mortality due to infections, respiratory diseases, or cancer was observed. The overall risk of inpatient admission and of requiring hospital outpatient services for the H. influenzae meningitis patients was increased the first 15 years of follow-up, mainly due to the nervous system diseases and ear diseases, thereafter the risk decreased to that of the population controls. CONCLUSIONS: In a developed country, children younger than 5 years surviving the acute phase of H. influenzae meningitis have no increased long-term mortality and only moderately increased morbidity.

Situação epidemiológica das meningites por haemophilus influenzae b na Direção Regional de Piracicaba - São Paulo / Epidemiological profile of Haemophilus influenzae b meningitis in Regional Health Board of Piracicaba - São Paulo - Brazil / Situación epidemiológica de las meningitis por Haemophilus influenzae b en la Dirección Regional de Piracicaba - São Paulo - Brasil

O presente estudo objetivou caracterizar a população acometida por meningites por Hib em relação às variáveis demográficas e relativas ao processo saúde-doença, no período de 1992 a 2001, na DIR de Piracicaba, SP, Brasil. Os dados foram coletados a partir de fichas de notificação compulsória, sendo sistematizados através do Programa SINAN. Observou-se que ocorreu um pico de incidência da doença em 1994, e um pico de óbitos em 1999, anteriores à introdução da vacina. Os mais acometidos foram crianças menores de 5 anos, do sexo masculino, confirmando dados de literatura. A maioria dos pacientes foi atendida em unidades hospitalares públicas de Piracicaba e Limeira, referências para as comunidades desses municípios, concretizando um dos princípios do Sistema Único de Saúde (SUS): a regionalização. A introdução da vacina promoveu redução dos casos em cerca de 73 por cento, o que corrobora a sua importância e impele à necessidade de estimular a adesão à vacinação.

The objective of the present study was to characterize the population affected by Hib meningitis from 1992 to 2001, in the Regional Health Board of Piracicaba (São Paulo-Brazil) in terms of variables regarding demographics and the health-disease process. Data were collected from disease notification reports, and arranged using the SINAN Data Program . It was observed there was a peak in the incidence of meningitis in 1994 and a peak of deaths in 1999, before the vaccine had been introduced. The most affected group were male children under the age of 5 years, which is in agreement with literature. Most patients received care at public hospitals in the municipalities of Piracicaba and Limeira, which are references for the community of the entire region, which puts into effect one of the axes of the Health System of Brazil (SUS): regionalization. The introduction of the vaccine reduced incidence in about 73 percent, which corroborates its importance and shows that is necessary to encourage adherence to vaccination.

El presente estudio objetivó caracterizar la población afectada por meningitis causada por Hib en relación a las variables demográficas y relativas al proceso salud-enfermedad, en el período de 1992 a 2001 en la DIR de Piracicaba, SP, Brasil. Los datos fueron recolectados a partir de fichas de notificación obligatorias, las cuales fueron sistematizadas a través del programa SINAN. Se observó que ocurrió un pico de incidencia de la enfermedad en 1994 y un pico de fallecimientos en 1999, con antelación a la introducción de la vacuna. Los más afectados fueron niños menores de 5 años, de sexo masculino, confirmando datos de la bibliografía. La mayoría de los pacientes fue atendida en unidades hospitalarias públicas de Piracicaba y Limeira, referenciales para las comunidades de tales municipios, concretando uno de los principios del Sistema Único de Salud (SUS): su regionalización. La introducción de la vacuna promovió la reducción de casos en cerca del 73 por ciento, lo que corrobora su importancia e impulsa la necesidad de estimular la adhesión a la vacunación.

Impact of Haemophilus influenzae type b conjugate vaccine on bacterial meningitis in the Dominican Republic / Impacto de la vacuna conjugada contra Haemophilus influenzae tipo b sobre la meningitis bacteriana en la República Dominicana

OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib) vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children < 5 years of age were identified from admission records of the main pediatric hospital in Santo Domingo during 1998-2004. Laboratory criteria were used to classify meningitis cases with probable bacterial etiology; confirmed cases had positive bacterial culture or antigen detection in cerebrospinal fluid. Cumulative incidence rates of confirmed and probable bacterial meningitis were calculated for children living in the National District. Confirmed cases of Hib meningitis were enrolled in a case-control study with age- and neighborhood-matched control children to calculate vaccine effectiveness. RESULTS: Before vaccine introduction, annual rates of meningitis with probable bacterial etiology were 49 cases per 100 000 children < 5 years old; Hib accounted for 60 percent of confirmed bacterial cases. During 2002-2004, after vaccine introduction, annual rates of probable bacterial meningitis were 65 percent lower at 16 cases per 100 000, and Hib accounted for 26 percent of confirmed cases. Rates of Hib meningitis and probable bacterial meningitis with no determined etiology declined by 13 and 17 cases per 100 000, respectively. CONCLUSIONS: Introduction of Hib vaccine substantially reduced the incidence of confirmed and probable bacterial meningitis in the Dominican Republic. The estimated impact of Hib vaccination was twice as great when non-culture-confirmed disease was included.

OBJETIVOS: El uso generalizado de la vacuna contra Haemophilus influenzae tipo b (Hib) ha permitido reducir radicalmente la carga de enfermedad por Hib en las Américas. Pocos estudios han evaluado el impacto de la vacunación contra Hib sobre los casos no confirmados mediante cultivo. En este estudio se analizaron las tendencias en el número de casos probables de meningitis bacteriana antes y después de la introducción de la vacuna contra Hib en la República Dominicana y se estimó la eficacia de la vacuna contra la meningitis. MÉTODOS: Se identificaron los casos de meningitis en niños menores de 5 años a partir de los registros de ingreso del principal hospital pediátrico de Santo Domingo entre 1998 y 2004. Los casos de meningitis con probable etiología bacteriana se clasificaron según criterios de laboratorio; los casos confirmados contaban con cultivo bacteriano positivo o detección de antígenos específicos en el líquido cefalorraquídeo. Se calcularon las tasas de incidencia acumulada de casos confirmados y probables de meningitis en los niños que vivían en el Distrito Nacional. Los casos confirmados de meningitis por Hib se incorporaron a un estudio de casos y controles -pareados según la edad y el barrio de residencia- para calcular la eficacia de la vacuna. RESULTADOS: Antes de la introducción de la vacuna, la tasa anual de meningitis de posible etiología bacteriana era de 49 casos por 100 000 niños menores de 5 años; de los casos confirmados de origen bacteriano, 60 por ciento fue por Hib. En el período 2002-2004, después de la introducción de la vacuna, la tasa anual de meningitis de posible etiología bacteriana fue de 16 casos por 100 000, es decir 65 por ciento más baja, y 26 por ciento de los casos confirmados correspondieron a Hib. Las tasas de meningitis por Hib y de posible origen bacteriano de etiología desconocida se redujeron en 13 y 17 casos por 100 000, respectivamente. CONCLUSIONES: La introducción de la vacuna...

Impact of the Haemophilus influenzae type b vaccination program on HIB meningitis in Brazil

This study aimed to evaluate the impact of vaccination against Haemophilus influenzae type b (HIB) in Brazil on the morbidity, mortality, and case fatality of HIB meningitis, using the Ministry of Health database and population data from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística - IBGE). Impact was evaluated through a time series analysis (1983-2002), using regression forecasting (RF) by dividing the time series into two periods: (a) historical (1983-1998) and (b) validation (1999-2002). Impact of the vaccination was positive, although more significant for incidence and mortality than for case fatality rates.

A proposta deste trabalho foi avaliar o impacto da vacinação contra Haemophilus influenzae tipo b (HIB) no Brasil sobre a morbi-mortalidade e a letalidade das meningites por HIB, a partir de base de dados fornecida pelo Ministério da Saúde e as estimativas populacionais provenientes do Instituto Brasileiro de Geografia e Estatística (IBGE). Para a avaliação do impacto utilizou-se análise de tendência temporal (1983-2002), aplicando-se a técnica RF (regression forecasting), dividindo-se a série em dois períodos: (a) período histórico (1983-1998) e (b) período de estimação (1999-2002). O impacto da vacinação foi positivo, embora tenha se revelado mais expressivo sobre a morbi-mortalidade que sobre a letalidade.

[Two cases of meningitis caused by the same Haemophilus influenzae type B strain in a nursery at a 3-month interval].

We present 2 cases of meningitis caused by the same Haemophilus influenzae type b (Hib) strain in a nursery at a 3-month interval. Causative agents isolated showed good susceptibility to beta-lactams and both patients recovered without any sequelae. Survey culture at each occurrence of meningitis showed 10 asymptomatic nasopharyngeal carriers. Oral rifampin was administrated to all staff and infants, but 2 carriers were found a month later from chemoprophylaxis. Pulsed-field gel electrophoresis analysis showed that the two strains isolated from meningitis patients and 12 from asymptomatic carriers were apparently identical. When systemic Hib infection occurs in a nursery, other infants may be at high risk for secondary disease. It is difficult, however, to eliminate Hib carriage by chemoprophylaxis, indicating that Hib vaccination to prevent systemic Hib infection is necessary in Japan.

The impact of routine infant immunization with Haemophilus influenzae type b conjugate vaccine in Malawi, a country with high human immunodeficiency virus prevalence.

Malawi has extreme poverty and a high-human immunodeficiency virus (HIV) prevalence. Following Haemophilus influenzae type b (Hib) conjugate vaccine introduction during 2002, we evaluated vaccine impact by reviewing hospital surveillance data for acute bacterial meningitis in Blantyre district among children age 1-59 months admitted during 1997-2005. Documented annual Hib meningitis incidence rates decreased from 20-40/100,000 to near zero among both rural and urban residents despite no change in pneumococcal meningitis incidence rates. Before vaccine introduction, an average of 10 children/year had Hib meningitis and HIV infection compared to 2/year during 2003-2004 and none during 2005. Vaccine effectiveness was high following two or more doses of vaccine. The most urgent future need is for a sustainable routine infant immunization program, including a less expensive vaccine that preferably is delivered in a multivalent form.

Meningitis Agudas en Córdoba, Colombia 2002 - 2004 / Acute meningitis in Córdoba, Colombia (2002-2004)

Objetivo: Establecer las características epidemiológicas y microbiológicas de las meningitis agudas del departamento de Córdoba. Métodos: Se realizó un estudio descriptivo de vigilancia epidemiológica en el Hospital San Jerónimo de Montería. Se tomaron todos los casos de meningitis, presentados (junio 2002 - junio 2004), las pruebas de laboratorio incluyeron: citoquímico, prueba de látex, tinción de Gram y cultivo. Resultados: Se analizaron 503 muestras de liquido cefalorraquídeo, confirmados por cultivo 57 (11,3 por ciento) casos y 85 (16,8 por ciento) casos probables. Se presentaron 63 aislamientos distribuidos así: 17 bacilos Gram negativos no fermentadores (26,9 por ciento), 16 Streptococcus pneumoniae (25,4 por ciento), 7 Enterobacterias (1 por ciento), 5 Criptococcus neoformans (8 por ciento), 4 Neisseria meningitidis serotipo B (6,3 por ciento), 3 S. viridans (4,8 por ciento), 2 Streptococcus grupo B (3,2 por ciento), 2 Haemophilus influenzae tipo B (3,2 por ciento), 2 S. aureus (3,2 por ciento), 2 Staphylococcus coagulasa negativos (3,2 por ciento), 2 Enterococcus (3,2 por ciento) y 1 Candida albicans (1,6 por ciento). Los serotipos de S. Pneumoniae fueron: 5 (n=4), 23F (n=3), 14 (n=2), 18C (n=2), 18A (n=1), 17F (n=1), 1 (n=1). Conclusión: El estudio permitió determinar los aspectos epidemiológicos y microbiológicos hasta ahora desconocidos de las meningitis agudas en el departamento de Córdoba. Streptococcus pneumoniae (25,4 por ciento) fue el principal agente causal de meningitis, los aspectos epidemiológicos establecidos confirman la necesidad de fortalecer e implantar medidas para el control y vigilancia de las meningitis en Córdoba.

Impact of specific medical interventions on reducing the prevalence of mental retardation.

OBJECTIVE: To explore the impact of medical interventions on reducing the prevalence of mental retardation (MR) in the United States over the last 50 years. DESIGN: We reviewed the medical literature and other data from 1950 to 2000 to construct estimates of the general and condition-specific prevalence of MR in the United States over time. We further explored the existing literature to document historically important influences on condition-specific prevalence, including the year that an effective intervention was introduced, the likelihood of success of the intervention, and the availability of such interventions nationwide. Specific conditions included congenital syphilis, Rh hemolytic disease of the newborn, measles, Haemophilus influenzae type B meningitis, congenital hypothyroidism, phenylketonuria, and congenital rubella syndrome. SETTING: Twentieth-century North America. PARTICIPANTS: Children with MR or 1 of the 7 specific conditions listed earlier. MAIN OUTCOME MEASURES: Case-specific and general prevalence of MR from 1950 to 2000. RESULTS: The prevalence of MR caused by a number of specific medical conditions has decreased sharply over the last 50 years. However, the incidence of each of these conditions is relatively low, and cases of MR due to these conditions represent, at most, 16.5% of the total number of cases of MR in 1950. CONCLUSION: Although specific medical interventions have prevented thousands of cases of MR, their contribution to the overall prevalence of MR is relatively small.

Impacto de la vacuna conjugada en la incidencia de meningitis por Haemophilus influenzae en el Distrito Federal de Brasil: resultados de tres años de seguimiento / Impact of anti-Hib conjugate vaccine on the incidence of Haemophilus influenzae meningitis in Brazil's Federal District: results of a three-year follow-up

INTRODUCCION: Haemophilus influenzae del serotipo b (Hib) es todavía un importante agente causal de procesos infecciosos. Su variante encapsulada es la causa de formas invasoras de enfermedad. En algunas poblaciones aborígenes, la incidencia de enfermedades causadas por Hib es mayor de 400 por 100 000 niños menores de 5 años. En los decenios de 1970 y 1980, tras la identificación de anticuerpos protectores contra la cápsula de Hib, se desarrollaron vacunas contra este microorganismo. OBJETIVO: Estimar el impacto que ha tenido desde su introducción, en marzo de 1998, la vacunación contra Hib en el Distrito Federal de Brasil. MÉTODO: Con los datos de base poblacional del Sistema de Vigilancia de la Secretaría de Salud del Distrito Federal de Brasil, se compararon las tasas de incidencia de meningitis correspondientes a los tres años anteriores y posteriores a la introducción de la vacuna. Se compararon también los cambios en su tendencia. RESULTADOS: Al comparar los dos períodos se advierte una reducción de aproximadamente 90 por ciento en la incidencia de meningitis por Hib, cambio que no ocurre en el caso de las meningitis ocasionadas por otros agentes bacterianos. Se registró un aumento proporcional de los casos entre los niños de 6 meses de edad y menores, debido a la reducción de la incidencia entre los mayores de esa edad. CONCLUSION: La introducción de la vacuna conjugada en el Distrito Federal de Brasil redujo de 168 por 100 000 (1995-1997) a 15 por 100 000 (1999-2001) la incidencia de meningitis por Hib entre niños de 7 a 35 meses. Esto representa una reducción de 91,1%.

Occurrence of Haemophilus influenzae strains in three Brazilian states since the introduction of a conjugate Haemophilus influenzae type b vaccine.

Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib) conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi) isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54), Santa Catarina (South, N = 19), and Rio de Janeiro (Southeast, N = 156). The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.

Occurrence of Haemophilus influenzae strains in three Brazilian states since the introduction of a conjugate Haemophilus influenzae type b vaccine

Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib) conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi) isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54), Santa Catarina (South, N = 19), and Rio de Janeiro (Southeast, N = 156). The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.

Meningites por Haemophilus influenzae b após a implantaçäo da vacina específica / Occurrence of Haemophylus influenzae b meningitis after the implementation of a mass vaccination program

OBJETIVO: Avaliar a incidência de meningite por Hib antes e após a introduçäo da vacinaçäo de rotina contra esse agente no Rio Grande do Sul em 1999. MÉTODOS: Este estudo retrospectivo representa todos os dados sobre meningites por Hib investigados pela Coordenaçäo do Controle de Doenças Transmissíveis Agudas (CCDTA - sistema de vigilância) da Secretaria da Saúde do Rio Grande do Sul entre 1995 e 2001. Todos os dados foram analisados usando o teste de qui-quadrado, com p < 0,05 sendo considerado estatisticamente significativo. RESULTADOS: A diminuiçäo dos casos de meningites por Hib esteve associada com a realizaçäo da vacinaçäo em larga escala contra Hib na infância. De 1995 a 2001, a incidência das meningites por Hib diminuiu 89 por cento: de 1,35 casos/100.000 habitantes em 1995 para 0,15 casos/100.000 em 2001 (p < 0,01), especialmente em crianças menores de um ano (p < 0,005). No mesmo período, a letalidade das meningites por Hib diminuiu de 17,8 por cento para 6,7 por cento (p < 0,01). CONCLUSÕES: A introduçäo do programa de vacinaçäo contra Hib resultou na quase eliminaçäo das meningites por Hib no Rio Grande do Sul. Esses achados reforçam a necessidade de manter a vacinaçäo apropriada na infância, com a investigaçäo completa e a comunicaçäo dos casos meningites por Hib

Meningitis and pneumonia in Guatemalan children: the importance of Haemophilus influenzae type b and Streptococcus pneumoniae

OBJECTIVE: To determine the epidemiology of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae invasive infections in hospitalized Guatemalan children. This is an important issue since Hib vaccine has not been incorporated into the routine immunization program in Guatemala and information from hospital records in 1995 indicated a low incidence of Hib and S. pneumoniae as causes of meningitis and invasive infections. METHODS: Children who were hospitalized in Guatemala City with clinical signs compatible with bacterial infections were evaluated for evidence of Hib or S. pneumoniae infection. Normally sterile body fluids were cultured, and antigen detection was performed on cerebrospinal fluid (CSF) and pleural fluid. RESULTS: Of 1 203 children 1-59 months of age hospitalized over a 28-month period, 725 of them (60.3 percent) had a primary diagnosis of pneumonia, 357 (29.7 percent) of meningitis, 60 (5.0 percent) of cellulitis, and 61 (5.1 percent) of sepsis and other conditions. Hib was identified in 20.0 percent of children with meningitis and S. pneumoniae in 12.9 percent. The average annual incidence of Hib meningitis was 13.8 cases per 100 000 children under 5 years of age, and 32.4 percent of meningitides caused by Hib and 58.7 percent of S. pneumoniae meningitides occurred prior to 6 months of age. Case fatality rates were 14.1 percent, 37.0 percent, and 18.0 percent, respectively, for children with Hib, S. pneumoniae, and culture-negative and antigen-negative meningitis. Prior antibiotic therapy was common and was associated with significant reductions in CSF-culture-positive results for children with other evidence of Hib or S. pneumoniae meningitis. CONCLUSIONS: Improvements in case detection, culture methods, and latex agglutination for antigen detection in CSF resulted in identification of Hib and S. pneumoniae as important causes of severe disease in Guatemalan children. Using a cutoff of > 10 white blood cells per cubic millimeter in CSF would improve the sensitivity for detection of bacterial meningitis and help estimate the burden of bacterial meningitis in Guatemala and other developing countries.

National Surveillance System and Hib meningitis incidence in Italy.

In 1994, the Italian Ministry of Health implemented a National Surveillance System to obtain data on the incidence of bacterial meningitis and its causative agents, including Haemophilus influenzae type b (Hib). As a consequence, case reporting of Hib meningitis is increasing year by year; in 1996, there were 126 notifications, of which 73% were in children under 2 years of age. Although underreporting still exists, parallel prospective or retrospective epidemiological surveys conducted in some Italian Regions allowed for partial correction of the incidence of Hib meningitis (up to 18.5/100,000 population in 1994).

Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. The Israeli Pediatric Bacteremia and Meningitis Group.

An ongoing nationwide prospective surveillance program for invasive H. influenzae b (Hib) disease in Israel enabled us to study the effectiveness of a national infant Hib immunization program, which included all infants born since January 1994. The vaccine used was Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis b (PRP-OMPC). For the cohort born during the 3 years since January 1994, the vaccine effectiveness was 94.9% for all invasive Hib diseases and 96.6% for meningitis. The efficacy in fully immunized subjects was 98.7 and 99.5%, respectively. A herd immunity effect could be observed, since a reduction in cases also occurred among infants too young to be immunized. No increase in invasive cases caused by S. pneumoniae and N. meningitidis was observed during the study period. This is the first report outside North America and Western Europe that demonstrates a nationwide extensive reduction of invasive Hib disease within a short time of the introduction of Hib conjugate vaccines to the infant immunization program.

Molecular epidemiology of Haemophilus influenzae type B isolates from Uruguay

A informaçäo disponível sobre a epidemiologia molecular e as interrelaçöes genéticas dos Haemophilus influenzae serotipo b (Hib) recuperados de pacientes que vivem na América do Sul é escassa. Quarenta e três cepas isoladas de pacientes com doença invasiva no Uruguai entre 1987 e 1992 foram caracterizadas por genótipo enzimático multilocus e por subtipo de proteína de membrana externa (outer membrana protein: OMP). As análises de OMP identificaram 3 dos subtipos conhecidos, incluindo 3L (70 por cento), 2L (18 por cento) e 18L(2 por cento). Também se encontrou dois padröes, näo descritos anteriormente, relacionados à famílias dos subtipos L e U, cada um representando 5 por cento dos organismos. Quatro tipos electroforéticos de enzimas multilocus foram identificados, incluindo ET 12,5 (67,3 por cento), 12,8 (23,3 por cento), 12,7 (4,7 por cento), e um ET 12.5/3L foi responsável por 63 por cento de todos os isolamentos, e causou 83 por cento dos casos de meningite mas somente 55 por cento dos episódios de pneumonia e septicemia. Em geral, a frequência da ocorrência de subclones Hib no Uruguai foi igual à registrada em vários países da Europa