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.

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.

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...

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.

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