Spatial analysis of pneumococcal meningitis in São Paulo in the pre- and post-immunization era

ABSTRACT OBJECTIVE To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005-2009) and post-vaccination (2011-2013) periods and its associations with socioeconomic variables and vaccination coverage. METHODS The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions. RESULTS From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination - one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002-1.052). CONCLUSIONS Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.

Meningitis neumocócica en Cantabria (España) en la era de las vacunas conjugadas antineumocócicas (2001-2015) / Pneumococcal meningitis in Cantabria (Spain) in the pneumococcal conjugate vaccine era (2001-2015)

Objetivo. Analizar las características de la meningitis neumocócica en < 14 años tras la comercialización de vacunas antineumocócicas conjugadas en nuestra comunidad. Métodos. Estudio retrospectivo de los casos de meningitis neumocócica en el que se analizaron dos períodos: pre vacuna antineumocócica trecevalente (VNC13v) (2001-2010) y post-VNC13v (2010-2015). Se recogieron datos demográficos y clínicos de los pacientes y datos microbiológicos. Resultados. Se diagnosticaron 18 casos. La incidencia media pre-VNC13v fue de 2,3/100 000, y disminuyó a 0,5/100 000 tras la VNC13v. Los serotipos más frecuentemente identificados fueron 6A y 10A (pre-VNC13v); 6B y 15B (post-VNC13v, solo dos casos). Trece de dieciocho pacientes ingresaron en la Unidad de Cuidados Intensivos. Todos los casos fueron tratados con cefotaxima y recibieron dexametasona 14/18. Seis pacientes sobrevivieron con secuelas y uno falleció. Conclusión. Se observa un importante descenso en la incidencia de meningitis neumocócica desde la comercialización de la VNC13v, por lo que cabe esperar que tras su introducción sistemática se produzca un descenso aún mayor.

Objective. To analyze the characteristics of pneumococcal meningitis in children < 14 years old following the market introduction of pneumococcal conjugate vaccines in our community. Methods. Retrospective study of pneumococcal meningitis cases with a two-period analysis: pre-13-valent pneumococcal conjugate vaccine (PCV13) (2001-2010) and post-PCV13 (2010-2015). Patient demographic and clinical data, and microbiological data were collected. Results. Eighteen cases were diagnosed. The mean incidence in the pre-PCV13 period was 2.3/100 000, which reduced to 0.5/100 000 after the PCV13 introduction. The most commonly identified serotypes were 6A and 10A (pre-PCV13); 6B and 15B (post-PCV13, only 2 cases). Out of 18 patients, 13 were admitted to the intensive care unit. All cases were treated with cefotaxime, and 14/18 received dexamethasone. Six patients survived with sequelae, and 1 died. Conclusion. A major reduction has been observed in the incidence of pneumococcal meningitis since the introduction of the PCV13 to the market, so an even greater reduction is expected following its systematic introduction.

Características epidemiológicas, clínicas y bacteriológicas de meningitis neumocócica en pacientes pediátricos de Lima, Perú / Epidemiologic, clinical and bacteriologic characteristics of pneumococcal meningitis in pediatric patients from Lima, Peru

RESUMEN Objetivos. Describir las características clínicas, letalidad, susceptibilidad antibiótica y distribución de serotipos de meningitis neumocócica en pacientes pediátricos de Lima, Perú. Materiales y Métodos. Serie de casos de meningitis neumocócica en niños menores de 16 años. Los datos fueron obtenidos de dos estudios multicéntricos prospectivos, de vigilancia pasiva de enfermedad neumocócica invasiva realizados en Lima-Perú desde los años 2006 al 2008, y del 2009 al 2011. Resultados. Reportamos 44 episodios de meningitis neumocócica; 68,2% fueron en niños menores de 2 años. La tasa de letalidad fue 32,6; y 92,9% de los casos letales ocurrieron en niños menores de dos años (p<0,05). La desnutrición estuvo asociada a los casos letales (p<0,05). El 64,3% de los casos fatales murieron dentro de los 2 primeros días. El 41,9% de los cultivos con neumococo fueron resistentes a la penicilina, 23,3% mostró resistencia intermedia a ceftriaxona (ninguno mostró resistencia completa) y 9,3% mostró resistencia a cloranfenicol. Los serotipos más frecuentes fueron 6B, 14, 19F y 23F, los cuales constituyeron el 68,3% de todas las cepas; 84,1% de las cepas encontradas están incluidas en los serotipos de la vacuna 13 valente. Conclusiones. La meningitis neumocócica continúa siendo una enfermedad letal, especialmente en niños menores de 2 años. Dado que aproximadamente dos tercios de los casos letales fallecen en las primeras 48 h, es crítico un diagnóstico y tratamiento oportuno, así como asegurar el cumplimiento de la inmunización con la vacuna neumocócica.

ABSTRACT Objectives. To describe the clinical characteristics, lethality, antibiotic susceptibility, and serotype distribution of pneumococcal meningitis in pediatric patients in Lima, Peru. Materials and Methods. A case series of pneumococcal meningitis in children less than 16 years of age from two prospective, multicenter, passive surveillance studies of invasive pneumococcal diseases held in Lima-Peru from 2006 to 2008 and 2009 to 2011. Results. We report 44 pneumococcal meningitis episodes; 68.2% of them were in children less than 2 years old. The overall case fatality rate was 32.6%; 92.9% of fatal cases were in children less than 2 years of age (p<0.05). Malnutrition was associated with fatal cases (p<0.05). 64.3% of fatal cases died within the first two days. 41.9% of pneumococcal isolates were resistant to penicillin, 23.3% were intermediate resistant to ceftriaxone (none were highly resistant) and 9.3% were resistant to chloramphenicol. The most common serotypes were 6B, 14, 19F and 23F, which accounted for 68.3% of all strains; 84.1% of strains were PCV13 serotypes. Conclusions. Pneumococcal meningitis continues to be a lethal disease, especially in children less than 2 years of age. Since almost two third of lethal cases lead to death within the first 48 hours, prompt diagnosis and management is critical, as well as assurance of immunization with pneumococcal vaccine.

Caracterización de pacientes fallecidos por enfermedad neumocóccica invasiva en la poblacion infantil de Bogotá, Colombia / Characterization of patients who died of invasive pneumococcal disease in the child population of Bogota, Colombia

Introducción: El Streptococcus pneumoniae (S. pneumoniae), también denominado neumococo, es una de las principales bacterias asociadas a mortalidad en menores de 2 años, con una incidencia de morbimortalidad variable de acuerdo a la demografía y exposición a factores protectores o de riesgo. Objetivo: Caracterizar los pacientes fallecidos por enfermedad neumocóccica invasiva (ENI) entre el 2008-2014 en la población infantil de 8 instituciones de salud en Bogotá, Colombia. Pacientes y método: Estudio observacional descriptivo tipo serie de casos, en pacientes fallecidos por ENI, mayores de 28 días hasta los 18 años, en 8 instituciones de tercer nivel de atención en Bogotá, Colombia. Periodo del estudio del 1 de enero de 2008 al 15 de enero de 2014. Tamaño de la muestra: 239 pacientes. Resultados: Se revisaron 239 casos registrados de ENI, presentando una mortalidad del 7,5% (n = 18). La edad promedio de los pacientes que fallecieron fue de 43,7 meses, con un rango de edad entre 2 y 176 meses (14 años); el 66% de los casos era de sexo masculino. Se identificaron serotipos en 8 pacientes, encontrando: 6A, 6B, 10A, 14, 18C, 23B, 23F, 35B. La presentación clínica más frecuente de los casos de mortalidad fue meningitis con el 33% (6 casos), seguida por bacteriemia sin foco en el 28% (5 casos) y neumonía con el 27% (5 casos). Se presentaron situaciones clínicas combinadas como neumonía y meningitis en el 11% (2 casos). Dos de los pacientes tenían factores de riesgo para ENI claramente documentados (asplenia y enfermedad respiratoria crónica). Conclusiones: La mortalidad por ENI es especialmente alta en los menores de 2 años y en pacientes de sexo masculino, especialmente cuando presenta foco meníngeo (44%). La serotipificación no fue posible en todos los pacientes fallecidos, ya que no se envió la cepa aislada al Instituto Nacional de Salud. Se requiere una vigilancia continua y sistemática para evaluar el impacto de la vacunación y las posibles modificaciones en el patrón de presentación de la enfermedad.

Introduction: Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus, is one of the main bacteria associated with mortality in children under 2 years of age, with a morbidity and mortality incidence that varies according to demographics and exposure to risk, or protective factors. Objective: To describe the child mortality due to invasive pneumococcal disease (IPD) between 2008 -2014 (6 years), in 8 Medical Centres in Bogotá, Colombia. Patients and method: Descriptive observational case series of patients who died of IPD, aged 28 days to 18 years, in 8 tertiary care institutions in Bogota, Colombia. The study period was from 1 January 2008 to 15 January 2014. Sample size: 239 patients. Results: A total of 239 registered cases of IPD were reviewed, showing a mortality of 8% (n 18). The mean age of patients that died was 43.7 months, with an age range from 2 to 176 months (14 years), with 66% of the cases being male. Serotypes were identified in 8 patients, finding: 6A, 6B, 10A, 14, 18C, 23B, 23F, and 35B. The most common clinical presentation of the cases was meningitis with mortality of 33% (6 cases), followed by bacteraemia without focus in 28% (5 cases), and pneumonia with 27% (5 cases). Combined clinical situations were presented, such as pneumonia and meningitis in 11% (2 cases). Two of the patients had clearly documented risk factors for IPD (asplenia and chronic respiratory disease). Conclusions: IPD mortality is particularly high in children under 2 years in male patients, especially when presented with a meningeal focus (44%). Serotyping was not possible in all patients who died, since no strain isolated was sent to the National Institute of Health. Continuous and systematic vigilance is required to evaluate the impact of vaccination and possible changes in the pattern of presentation of disease.

Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil

Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3–42); 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n = 64, 78.1%), bacteraemic pneumococcal pneumonia (n = 12, 14.6%) and bacteraemia (n = 6, 7.3%) were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n = 12, 14.6%) was the most common, followed by 23F (n = 10, 12.2%), 12F (n = 8, 9.8%), 18 C (n = 5, 6.1%) and 6B (n = 5, 6.1%). Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6%) of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil / Impacto de la vacuna neumocócica conjugada 10-valente en la meningitis neumocócica en niños de hasta dos años de edad en Brasil / Impacto da vacina pneumocócica conjugada 10-valente na meningite pneumocócica em crianças com até dois anos de idade no Brasil

The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009) and post-vaccination (2011-2012) periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.

El objetivo de este estudio fue analizar el impacto de la vacunación contra el Streptococcus pneumoniae en la morbilidad y mortalidad de la meningitis neumocócica en niños ≤ 2 años en Brasil, 2007-2012. Se trata de un estudio descriptivo ecológico que analiza los datos del Sistema de Información Enfermedades de Notificación Obligatoria en Brasil. El período previo (2007-2009) y posterior a la vacunación (2011-2012) fueron examinados para comparar las tasas de incidencia y mortalidad. 1.311 casos de meningitis neumocócica con 430 muertes se registraron durante el período de estudio. Hubo una disminución de la incidencia de 3,70 casos por 100.000 habitantes en 2007, a 1,84/100.000 en 2012, mientras que la tasa de mortalidad cayó 1,30 a 0,40 óbitos/100.000, se produjeron reducciones del 50% y 69%, respectivamente, con mayores impactos identificados entre los niños de 6-11 meses de edad. Los resultados indican una reducción en la morbilidad y mortalidad por meningitis neumocócica dos años después de la introducción de la vacuna conjugada antineumocócica 10-valente, lo que sugiere su eficacia.

O objetivo deste trabalho foi analisar o impacto da vacinação contra o Streptococcus pneumoniae na morbidade e mortalidade por meningite pneumocócica em crianças ≤ 2 anos, no Brasil, entre 2007-2012. Este é um estudo descritivo com análise ecológica, utilizando dados do Sistema de Informação de Agravos de Notificação. Foram definidos os períodos pré-vacinal (2007-2009) e pós-vacinal (2011-2012) para comparar as taxas de incidência e mortalidade. Foram identificados 1.311 casos e 430 óbitos no período do estudo. A taxa de incidência diminuiu de 3,70/100.000 no ano de 2007 para 1,84/100.000 em 2012, e a mortalidade reduziu de 1,30/100.000 para 0,40/100.000, o que significa uma redução de 50% e 69%, respectivamente, com maior impacto identificado na faixa etária de 6 a 11 meses. Os resultados indicam uma diminuição nos indicadores de morbidade e mortalidade de meningite pneumocócica, observados dois anos após a introdução da vacina pneumocócica conjugada 10-valente, sugerindo sua efetividade.

Meningitis neumocócica: experiencia de 12 años en un hospital pediátrico, previa a la inmunización universal con vacuna conjugada / Pneumococcal meningitis: A 12 year experience in a children's hospital prior to the universal immunization with a conjugate vaccine

Introducción. La meningitis por Streptococcus pneumoniae provoca frecuentemente elevada morbimortalidad. El objetivo del presente estudio fue identificar las características epidemiológicas y clínicas, la susceptibilidad antibiótica y la evolución de los niños con meningitis por neumococo antes de la introducción de la vacuna en Argentina. Métodos. Se incluyeron pacientes menores de 18 años internados en el Hospital J. P. Garrahan entre 1999 y 2010. Se revisaron los registros del laboratorio de microbiología y las historias clínicas de los niños. Resultados. Se identificaron 111 niños con meningitis por S. pneumoniae. En el período 1999-2002, hubo 40 casos, 35 en 2003-2006 y 36 en 2007-2010. La media de edad fue 7 meses (r: 1-191). Eran inmunocompetentes 104 pacientes (94%). Solo 20 pacientes (18%) tenían enfermedad de base. La presentación clínica más frecuente fue el compromiso neurológico en 80 pacientes (75%) y la sepsis en 59 pacientes (53%). Requirieron admisión en terapia intensiva 49 pacientes (44%). Otro foco clínico de infección estuvo presente en 24 pacientes (22%); en la mitad de ellos, neumonía. El cultivo de líquido cefalorraquídeo fue positivo en 103 pacientes (93%) y los hemocultivos en 88 pacientes (79%). Se identificó resistencia a la penicilina en 15% de los casos y en el 5% resistencia a cefotaxima. La resistencia antibiótica disminuyó a lo largo de los años. Presentaron complicaciones 56 pacientes (50%), y 11 pacientes (10%) fallecieron por la infección. Conclusión. La resistencia de S. pneumoniae a los antimicrobianos disminuyó a lo largo de los años. Es importante mantener la vigilancia epidemiológica para evaluar el impacto de la vacunación en Argentina

Introduction. Pneumococcal meningitis is caused by Streptococcus pneumoniae and has high morbidity and mortality rates. The objective of this study was to identify the epidemiological and clinical characteristics, antibiotic sensitivity and evolution of pneumococcal meningitis in children prior to the introduction of the vaccine in Argentina. Methods. Patients younger than 18 years old hospitalized at Hospital J. P. Garrahan between 1999 and 2010 were included. Children's microbiology lab records and case records were reviewed. Results. One hundred and eleven children with S. pneumoniae meningitis were identified. Forty cases were found in the 1999-2002 period, 35 in the 2003-2006 period, and 36 in the 2007- 2010 period. The mean age was 7 months old (range: 1-191). One hundred and four patients were immunocompetent (94%). Only 20 patients (18%) had an underlying disease. The most commonly observed clinical presentation was neurological involvement in 80 patients (75%), and sepsis in 59 (53%). Forty-nine patients (44%) had to be admitted to the ICU. A second clinical source of infection was identified in 24 patients (22%); half of these cases corresponded to pneumonia. Positive findings were observed in the cerebrospinal fluid culture of 103 patients (93%) and in the blood culture of 88 (79%). Resistance to penicillin was identified in 15% of cases, while 5% showed resistance to cefotaxime. Antibiotic resistance was reduced over the years. Complications occurred in 56 patients (50%), and 11 (10%) died because of the infection. Conclusion. Antimicrobial resistance by S. pneumoniae was reduced over time. It is important to maintain epidemiological surveillance to assess the impact of immunization in Argentina.

Meningitis neumocócica en niños menores de 15 años: Dieciséis años de vigilancia epidemiológica en Misiones, Argentina / Pneumococcal meningitis in children under 15 years of age in Misiones (Argentina): Sixteen year's epidemiological surveillance

Se presentan en este trabajo los resultados de 16 años de vigilancia epidemiológica de meningitis neumocócica llevada a cabo en el Hospital Provincial de Pediatría de Misiones (Argentina), antes de la introducción de la vacuna conjugada al calendario nacional. En el período que va de enero de 1994 a diciembre de 2009 se diagnosticaron 167 casos de meningitis por Streptococcus pneumoniae en niños (1 mes-15 años). La tasa de ataque cada 100 000 niños varió entre 19,2 (1997) y 4,3 (2009), con una media de 10,6 y una tendencia en disminución (y = ""0,689x + 16,52). Esto fue a expensas del grupo de niños entre 1 y 11 meses (94/167, 56 %), en el que disminuyó de 146,6 a 34,8 casos cada 100 000 niños. El 30,7 % de los aislamientos (46/150) fueron resistentes a penicilina y el 16,7 % (25/150) no sensibles a cefotaxima. La resistencia a β-lactámicos se incrementó a partir de 1997 y comenzó a disminuir en 2005. Se detectaron 19 serotipos, predominó el 14 (32 %; 40/125). El 84,8 % de los aislamientos quedaron circunscriptos a nueve serotipos: 14, 5, 1, 7F, 18C, 6B, 9N, 9V y 4. La cobertura teórica en los niños < 2 años y > 2 años fue de 84,1 % (74/88) y 83,8 % (31/37) con la vacuna 10-valente, y de 89,8 % (79/88) y 83,8 % (31/37) con la vacuna 13-valente, respectivamente. La resistencia a penicilina estuvo circunscripta a 8 serotipos (14, 6B, 6A, 9V, 4, 23B, 1 y 19A), y la no sensibilidad a cefotaxima a 3 serotipos (14, 9V y 1), el más importante fue en ambos casos el serotipo 14. Este estudio permitirá evaluar el impacto de la implementación de las vacunas conjugadas en nuestra zona.

We report the results of pneumococcal meningitis surveillance conducted at the Provincial Pediatric Hospital of Posadas, Misiones (Argentina), before the conjugate vaccine was introduced into the national vaccination schedule. Between January 1994 and December 2009, 167 cases of Streptococcus pneumoniae meningitis were diagnosed in children aged 1 month to 15 years. The attack rate/100,000 children ranged from 19.2 (1997) to 4.3 (2009), with a mean of 10.6 and a tendency to decrease (y=""0.689x+16.52). The number of cases per 100,000 children decreased from 146.6 to 34.8 and particularly involved the group of children aged 1 to 11 months (94/167, 56%). Thirty point seven percent (30.7%) (46/150) of the isolates were resistant to penicillin whereas 16.7% (25/150) were non-susceptible to cefotaxime. β-lactam resistance increased as from 1997 and began to decline in 2005. Nineteen serotypes were detected; type 14 was predominant and accounted for 32% (40/125). Eighty four point eight percent (84.8%) of the isolates were circumscribed to nine serotypes: 14, 5, 1, 7F, 18C, 6B, 9N, 9V and 4. Theoretical coverage for patients aged <2 years and >2 years was 84.1% (74/88) and 83.8% (31/37) for the 10-valent vaccine and 89.8 % (79/88) and 83.8% (31/37) for the 13-valent vaccine respectively. Penicillin resistance was restricted to 8 serotypes (14, 6B, 6A, 9V, 4, 23B, 19A1) and nonsusceptibility to cefotaxime was circumscribed to 3 serotypes (14, 9V and 1). This study will allow to evaluate the impact of the implementation of conjugate vaccines on our area.

Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines / Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas

A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA) y con infecciones invasivas (INV) en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar incorporarla al calendario nacional de vacunación para niños menores de 2 años en la Argentina.

Caracterização molecular de sorotipos não-vacinais de Streptococcus pneumoniae isolados de pacientes com meningite em Salvador, antes e após a implementação da vacina conjugada PCV-10 / Molecular characterization of non-vaccine serotypes of Streptococcus pneumoniae isolates from meningitis patients in Salvador, before and after implementation of the conjugate vaccine PCV-10

O advento das vacinas pneumocócicas conjugadas veio contribuir de forma decisiva para a redução da incidência dos casos de doença invasiva por S. pneumoniae em vários países do mundo. Em contrapartida, tem-se verificado um aumento de casos decorrentes de sorotipos não vacinais, que escapam da vacina e reduzem o seu efeito a partir da expansão de clones pré-existentes com consequente substituição de sorotipos e/ou do fenômeno de troca capsular (capsular switching). No Brasil, a vacina conjugada 10-valente (PCV10) foi introduzida no calendário nacional de imunização a partir de 2010. Este estudo teve como objetivo caracterizar através de técnicas fenotípicas e moleculares os sorotipos não-vacinais (SNVT) de S.pneumoniae, isolados de pacientes com meningite nos períodos anterior (janeiro/2008 - junho/2010) e posterior (julho/2010 - dezembro/2012) à implementação da vacina pneumocócica conjugada 10-valente (PCV10), na cidade de Salvador, Bahia. Os isolados de S. pneumoniae foram identificados através de métodos microbiológicos clássicos e a determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a oito antimicrobianos foi realizada através da técnica de microdiluição em caldo e a caracterização genotípica por intermédio das técnicas de PFGE e MLST...

The licensure and subsequent widespread use of pneumococcal conjugate vaccines have contributed for the reduction in the overall incidence of invasive pneumococcal disease worldwide. However, the emergence of Streptococcus pneumoniae nonvaccine serotypes (SNVT), which escape from the vaccine by the expansion of pre-existing clones following serotype replacement and/or by capsular switching is a matter of concern. In 2010, Brazil introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into its routine National Immunization Program. Our aim was to characterize the phenotypic and genotypic profile of S. pneumoniae non-vacine serotypes (SNVT) isolated from patients with meningitis before (January 2008 – June 2010) and after (July 2010 – December 2012) the introduction of PCV10 in Salvador, Bahia. The pneumococcal isolates were identified by classical microbiological methods and submitted to capsular deduction by multiplex-PCR and/or Quellung reaction. The antimicrobial susceptibility was performed the broth microdilution method. The genotypic profile was assessed by PFGE and MLST...

Custos hospitalares da meningite causada por Streptococcus pneumoniae na cidade de São José dos Campos, São Paulo, Brasil / Hospital costs related to streptococcal meningitis among children in São José dos Campos, São Paulo State, Brazil

O conhecimento dos custos hospitalares é de grande importância para os processos de tomada de decisão em saúde pública. O objetivo deste estudo foi estimar os custos hospitalares diretos relacionados à meningite pneumocócica em crianças com até 13 anos (inclusive), na cidade de São José dos Campos, São Paulo, Brasil, de janeiro de 1999 a dezembro de 2008. Foram obtidos dados de prontuários médicos. O cálculo foi realizado pelo método misto de mensuração das quantidades dos itens de custos e atribuição de valor aos itens consumidos (micro-costing e gross-costing). Os valores monetários referem-se a novembro de 2009, sendo expressos em reais. A análise das frequências e médias foi realizada pelo programa Epi Info versão 3.5.1. Foram notificados 41 casos. Os custos hospitalares diretos variaram de R$ 1.277,90 a R$ 19.887,56 (média = R$ 5.666,43), ou seja, 10 a 20 vezes maiores que o custo médio de internações pago pelo SUS. Os custos dos honorários profissionais foram os mais relevantes, seguidos pelos custos dos medicamentos, procedimentos, materiais e exames laboratoriais.

Knowledge of hospital costs is highly important for public health decision-making. This study aimed to estimate direct hospital costs related to pneumococcal meningitis in children 13 years or younger in the city of São José dos Campos, São Paulo State, Brazil, from January 1999 to December 2008. Data were obtained from medical records. Hospital costs were calculated according to the mixed method for measurement of quantities of items with identified costs and value attribution to items consumed (micro-costing and gross-costing). All costs were calculated according to monetary values for November 2009 and in Brazilian currency (Real). Epi Info 3.5.1 was used for frequencies and means analysis. Forty-one cases were reported. Direct hospital costs varied from R$ 1,277.90 to R$ 19,887.56 (mean = R$ 5,666.43), or 10 to 20 times the mean cost of hospitalization for other diseases. Hospital staff labor was the highest cost, followed by medication, procedures, supplies, and lab tests.

Invasive pneumococcal diseases among hospitalized children in Lima, Peru / Enfermedades neumocócicas invasoras en niños hospitalizados en Lima, Perú

OBJECTIVE: To determine the epidemiology of invasive pneumococcal disease (IPD) and the antibiotic susceptibility and serotype distribution of S. pneumoniae in pediatric patients in Lima, Peru. METHODS: A 2-year, multicenter, passive surveillance study conducted from May 2006- April 2008 in 11 public hospitals and five private laboratories in Lima, Peru, in patients less than 16 years of age with sterile site cultures yielding S. pneumoniae. Antibiotic susceptibility was performed by Etest® (AB Biodisk, Solna, Switzerland). Strains were serotyped by the Quellung reaction. RESULTS: In all, 101 IPD episodes were studied, 68.3 percent of which were among children less than 24 months of age. Diagnoses were: pneumonia (47.5 percent), meningitis (38.6 percent), and sepsis (7.9 percent). The overall case fatality rate was 22.0 percent; case fatality rate in meningitis was 32.4 percent. While 80.0 percent of fatal cases were in those less than 24 months of age, only 50.7 percent of non-fatal cases (P < 0.05) were in this age group. Resistance rates were high for trimethoprim/ sulfamethoxazole (76.2 percent), erythromycin (24.8 percent), and penicillin (22.8 percent). The most common serotypes were 14, 6B, 19F, 23F, and 5, which accounted for 69.7 percent of all strains and 87.0 percent of penicillin non-susceptible strains. CONCLUSIONS: IPD in hospitalized children in Lima is associated with high antimicrobial resistance levels and elevated case fatality rate, especially in young children. This baseline data will be useful for evaluating the effects of vaccine introduction.

OBJETIVO: Determinar la epidemiología de la enfermedad neumocócica invasora y la sensibilidad a los antibióticos y la distribución de los serotipos de S. pneumoniae en pacientes pediátricos en Lima, Perú. MÉTODOS: Estudio multicéntrico de vigilancia pasiva durante dos años, entre mayo del 2006 y abril del 2008, en 11 hospitales públicos y 5 consultorios privados de Lima, en pacientes menores de 16 años con cultivos de sitios estériles positivos para S. pneumoniae. Se determinó la sensibilidad a los antibióticos mediante Etest® (AB Biodisk, Solna, Suiza). Se serotipificaron las cepas mediante la reacción de Quellung. RESULTADOS: En total, se estudiaron 101 episodios de enfermedad neumocócica invasora, 68,3 por ciento de ellos en niños menores de 24 meses, con los siguientes diagnósticos: neumonía (47,5 por ciento), meningitis (38,6 por ciento) y septicemia (7,9 por ciento). La tasa de letalidad general fue de 22,0 por ciento y la tasa de letalidad por meningitis de 32,4 por ciento. Si bien 80,0 por ciento de los casos mortales ocurrió en menores de 24 meses, solo 50,7 por ciento de los casos no mortales (P < 0,05) ocurrió en este grupo de edad. Las tasas de resistencia fueron elevadas para trimetoprima-sulfametoxazol (76,2 por ciento), eritromicina (24,8 por ciento) y penicilina (22,8 por ciento). Los serotipos más comunes, 14, 6B, 19F, 23F y 5, representaron 69,7 por ciento de todas las cepas, y 87,0 por ciento de las cepas no sensibles a la penicilina. CONCLUSIONES: La enfermedad neumocócica invasora en niños hospitalizados en Lima se asocia con altos niveles de resistencia a los antimicrobianos y una tasa de letalidad elevada, especialmente en niños pequeños. Estos datos iniciales serán útiles para evaluar los efectos de la introducción de las vacunas.

Impacto de la enfermedad por Streptococcus pneumoniae en población adulta mayor en Bogotá, Colombia, 2008 / The impact of pneumococcal disease on adults living in Bogota, Colombia, 2008

Objetivo Estimar el impacto de la enfermedad por Streptococcus pneumoniae en la población mayor de 60 años en Bogotá D.C. Colombia. Métodos Se realizó un estudio de impacto de enfermedad por neumococo combinando una búsqueda sistemática de literatura con el análisis de fuentes de datos rutinarios de mortalidad, consultas y hospitalizaciones debidas neumonías y meningitis en adultos mayores de 60 años. Resultados Se estimó para 2008 en la población bogotana mayor de 60 años la ocurrencia de 6 585 neumonías por todos los agentes, 689 debidas a Streptococcus pneumoniae, y 73 meningitis, 12 producidas por neumococo. El total de muertes por neumonías se estimó en 1 910, 82 atribuibles al neumococo, y de las 40 muertes por meningitis, 7 habrían ocurrido en casos de meningitis neumocócicas. Conclusiones El impacto de la enfermedad debida a neumococo en población mayor de 60 años en Bogotá justifica la consideración de estrategias específicas de prevención tales como la vacunación.

Objective Estimating the impact of pneumococcal disease amongst adults living in Bogota, Colombia Methods The impact of pneumococcal disease was studied by combining a systematic literature search with analysing routine sources regarding mortality, consultation and hospitalisation dates due to pneumonia and meningitis. Results The occurrence of 6,585 cases of pneumonia by all germs was estimated for 2008 in the adult population aged over 60, 689 cases being due to Streptococcus pneumonia, and 73 cases of meningitis, plus 12 cases caused by pneumococcus. The total of deaths from pneumonia was estimated to be 1,910 cases (82 due to pneumonia) and 40 deaths occurred from meningitis (7 of these cases being due to pneumococcal meningitis). Conclusiones The impact of pneumococcal disease in adults aged over 60 in Bogota (only taking into account cases of meningitis and pneumonia with blood and CSF isolates) justifies considering specific prevention strategies such as vaccination.

Establishment of population-based surveillance for invasive pneumococcal disease in Bangalore, India.

Background :Invasive pneumococcal disease (IPD) is vaccine-preventable but few data on the incidence of PD exist for Indian children. Aims: To assess the feasibility of implementing prospective, population-based surveillance for PD among children less than five years of age. Settings and Design :Hospitals and health agencies, Bangalore, India. Retrospective review and analysis of hospitalization records as well as public health and demographic data. Material and Methods : Records for 2006 hospitalizations for pneumococcal disease-associated syndromes (meningitis, pneumonia and sepsis) were identified at three pediatric referral hospitals (Indira Gandhi Institute of Child Health, Kempegowda Institute of Child Health and Vani Vilas Hospital) in Bangalore using International Classification of Diseases, 9th revision codes. Hospital microbiology laboratory records were assessed to ensure capacity for identifying S. pneumoniae. Population data were identified from national census and polio surveillance data. Results : The Bangalore city southern zone includes 33 wards occupying 51 Km 2 with 150,945 children between 0-5 years of age served by three referral pediatric hospitals. From January--December 2006, records of these three hospitals showed 2,219 hospitalizations of children less than five years of age (967 pneumonia, 768 sepsis, and 484 meningitis) with PD-associated diagnoses (southern zone area incidence: 0.15/100,000 PD-associated hospitalizations, less than five years of age). There were 178 deaths in children less than five years of age, of which 87 were attributable to sepsis, 56 to pneumonia and 35 to meningitis. Conclusion : Our analysis suggests that the PD-associated disease burden in Bangalore is high and local institutions have capacity for population-based surveillance. In a prospective study, systematic attention to potential barriers in identifying children with pneumococcal infections will improve estimation of IPD incidence in India.

Acute bacterial meningitis in adults: an analysis of 95 cases from Saudi Arabia

To study the clinical features, laboratory profiles, treatment especially door-to-antibiotic time and outcome in adult patients admitted with acute bacterial meningitis in a tertiary care hospital. Neurology and medical department, King Abdul Aziz Hospital and Oncology Center, Jeddah, Saudi Arabia. Retrospective analysis of 95 consecutive cases of acute bacterial meningitis in adults admitted during study period from January 2000 till June 2005. Clinical and laboratory features, treatment and outcome were analyzed. Total of 95 patients were identified. There were 78[82%] males and 17[18%] females. The mean age was 30 years with range from 14 to 74. Out of the 95 patients, 52[54.7%] cases had meningitis caused by Neisseria meningitides and 16 [16.8%] by Streptococcus pneumoniae. There was one case of meningitis caused by Klebsiella and E. coli each. Latex agglutination [bacterial antigen detection] test was positive in 72 [75%] cases, Gram stain in 40 [42%], and CSF culture in 27 [28.4%]. Triad of fever, headache and neck stiffness or altered conscious level was seen in only 52% of cases. Sixty-five [68%] cases belonged to an African ethnic background and a low socio-economic class. Unfavorable outcome was seen in 19 [20%]. Overall mortality was 6.3% [6 out 95 cases]. Mortality was more with pneumococcal meningitis 12.5% [2out of the 16 cases] compared with meningococcal meningitis 4% [2 out of 52 cases]. Patients, who died, were admitted in deep coma [Glasgow coma scale below 8]. Acute bacterial meningitis remained common and life threatening infection in the community. Neisseria meningitides and Streptococcus pneumoniae are the two most common pathogens for bacterial meningitis in immuno-competent adults. An African ethnic background, poor socioeconomic class and overcrowding were the main predisposing factors. Triad of fever, headache and neck stiffness or altered mental status was seen in about half of the cases

Evaluating the costs of pneumococcal disease in selected Latin American countries

OBJECTIVES: To estimate the costs of pneumococcal disease in Brazil, Chile and Uruguay, to describe how these costs vary between different patient groups, and to discuss factors that affect these cost variations. METHODS: The cost of pneumococcal disease was estimated from the health care perspective. For each country, baseline cost estimates were primarily developed using health resources information from patient-level data and facility-specific cost data. A regression model was constructed separately for four types of pneumococcal diseases. The skewness-kurtosis test and the Cook-Weisberg test were performed to test the normality of the residuals and the heteroscedasticity, respectively. RESULTS: The treatment of pneumococcal meningitis generated up to US$ 5 435 per child. The treatment costs of pneumococcal pneumonia were lower, ranging from US$ 372 per child to US$ 3 483 per child. Treatment of acute otitis media cost between US$ 20 per child and US$ 217 per child. The main source of treatment costs variations was level of service provided and country in which costs were incurred. However, the tendency of costs to change with these variables was not statistically significant at the 5 percent level for most pneumococcal disease models. CONCLUSIONS: Pneumococcal disease resulted in significant economic burden to selected health care systems in Latin America. The patterns of treatment cost of pneumococcal disease showed a great deal of variation.

OBJETIVOS: Estimar los costos de la enfermedad neumocócica en Brasil, Chile y Uruguay, describir cómo varían estos costos entre diferentes grupos de pacientes y discutir los factores que influyen en las variaciones de estos costos. MÉTODOS: El costo de la enfermedad neumocócica se estimó desde la perspectiva de la atención sanitaria. Inicialmente se establecieron estimados de referencia de los costos para cada país a partir de la información de los recursos sanitarios empleados, según los datos de cada paciente y los costos específicos de cada institución. Se construyeron modelos de regresión por separado para cuatro tipos de enfermedad neumocócica. Se realizaron las pruebas de asimetría-curtosis y de Cook-Weisberg para comprobar la normalidad de los residuos y la heterocedasticidad, respectivamente. RESULTADOS: El costo del tratamiento de la meningitis neumocócica fue de US$ 5 435 por cada niño, mientras el de la neumonía neumocócica fue menor, entre US$ 372 y US$ 3 483 por niño. El costo del tratamiento de la otitis media aguda fue de US$ 20 a US$ 217 por niño. La principal fuente de variación en los costos de tratamiento fue el nivel de servicio brindado y el país en que se generaron los costos. No obstante, la tendencia de los costos a variar no fue estadísticamente significativa (P > 0,05) en la mayoría de los modelos de la enfermedad neumocócica. CONCLUSIONES: La enfermedad neumocócica constituye una notable carga económica para los sistemas de salud seleccionados de América Latina. Los patrones del costo de tratamiento de la enfermedad neumocócica mostraron una gran variación.

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.

Manejo hospitalario de la meningoencefalitis bacteriana por S. Neumoniae / Hospital management of bacterial meningoencephalitis due to S. pneumoniae

La actitud terapéutica ante la meningitis bacteriana (MEB) es uno de los retos más importantes a los que se enfrenta el pediatra, pues de su oportuno y adecuado manejo depende el pronóstico. Los cambios en la epidemiología de los síndromes neurológicos infecciosos bacterianos observados en Cuba a partir del año 2000, promovieron la implementación de modificaciones al régimen terapéutico antibiótico convencional. En este artículo, sin olvidar que el tratamiento ideal es el preventivo, se expone una revisión actualizada del manejo hospitalario de las MEB por S.pneumoniae, que incluye: adopción de medidas generales, instauración temprana de acciones dirigidas a atenuar los efectos perjudiciales de la respuesta inflamatoria sistémica, conducta específica contra el agente (antibioticoterapia) y finalmente la identificación precoz e inicio de la rehabilitación de secuelas. Se hace énfasis en las modificaciones al esquema antibiótico adoptadas recientemente por la Comisión Nacional de SNI. Se exponen consideraciones sobre la introducción de la vancomicina en esquema antimicrobiano de las MEB por S.pneumoniae.

Emergência de streptococcus pneumoniae resistente à penicilina em Salvador, Bahia: um estudo epidemiológico e molecular / Emergence of penicilin-resistant Strpetococcus pneumoniae in Salvador, Bahia: a molecular epidemiology study

As infecções pelo S. pneumoniae persitem como uma das principais causas de morbimortalidade, apesar da disponibilidade de antibioticoperatia apropriada. Em 1995, foi implantado uma rede de vigilância para identificar pneumococos não susceptível à penicilina em dois diferentes grupos populacionais: 1) pacientes com meningite pneumocócica e 2) indivíduos saudáveis na comunidade. No período de dezembro de 1995 a agosto de 2002, o Hospital Couto Maia atendeu 477 pacientes com meningite penumocócica identificados através da cultura de liquor positiva para S. pneumoniae, 453 (95 por cento) tiveram os isolados caracterizados quanto à susceptibilidade e sorotipagem. Cepas não susceptíveis à penicilina (CIM 0,1 - 1,0 ug/ml) foram isoladas em 59 (13 por cento) indivíduos com meningite pneumocócica. Os sorotipos mais prevalentes foram 14 (14 por cento ), 3 (10 por cento), 19 F (8 por cento), 6B (8 por cento), 6A (7 por cento, 23 f (6 por cento), 4 (5 por cento), 18C (5 por cento) e 8 (4 por cento), sendo que reduzida sensibilidade à penicilina foi associada aos sorogrupos 14 (38), 6 ((), 23 (7) e 19 (5). A provável taxa de cobertura da vacina heptavalente conjugada foi de 70 por cento entre pacientes < 5 anos e 91 entre aqueles com isolados não susceptíveis à penicilina. Tipagem de cepas pela reação de polimerase em cadeia (PCR) do elemento repetitivo - BOX A, demonstrou que os isolados de sorotipo 14 não susceptíveis à penicilina tinham um padrão clonal relacionado e quando comparados com isolados de outras cidades brasieliras tiveram um padrão similar. O segundo grupo populacional foram residentes de 39 domicílios selecionados randomicamente em uma comunidade urbana. Neste grupo, a colonização nasofaringeana foi investigada em 262 indivíduos ( ...) Em contraste com o estudo de cepas causadoras de minigite, pneumococos não susceptíveis à penicilina tinham um padrão distinto, nãor elacionado. Em contraste com o estudo de cepas causadoras de meningite, pneumococos não suceptíveis à penicilina associados com colonização não parecem esr clonais. Além do mais, uma limitada proporção destas cepas é de sorotipos representados na vacina heptavalente conjugada.

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