Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries

doi:10.1016/j.vaccine.2011.10.101

Vaccine

Volume 30, Issue 2, 5 January 2012, Pages 486-492

https://doi.org/10.1016/j.vaccine.2011.10.101 Get rights and content

Abstract

To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used.

Highlights

► We analyzed Hib meningitis rates in four South American countries using Hib vaccine. ► Hib vaccination schedules included 3 doses and a booster dose in two countries. ► Vaccination reduced Hib meningitis incidence to low levels. ► Low incidence rates were maintained in countries with and without a booster dose.

Introduction

Haemophilus influenzae type b (Hib) remains an important cause of bacterial meningitis and pneumonia among children, especially in countries that have yet to introduce highly effective conjugate vaccines [1]. The World Health Organization (WHO) recommends that all countries introduce Hib conjugate vaccine into their routine infant immunization programs [2]. Hib vaccines are commonly given as a three-dose primary series at the same time as diphtheria-tetanus-pertussis (DTP) vaccination, and several combination vaccines are available [3]. Hib conjugate vaccine has been shown to be highly effective in preventing invasive Hib disease after a three-dose primary series [4], [5], [6]. However, resurgence of invasive Hib disease several years after introduction of a three-dose, accelerated (2, 3 and 4 months of age) Hib vaccination schedule in the United Kingdom raised concerns about the need for a booster dose for maintaining long-term immunity [7]. While national immunization programs in many industrialized countries administer a booster dose of Hib vaccine between 12 and 18 months of age, WHO's 2006 position paper on Hib vaccines noted that additional data were required to determine the need for booster doses in developing countries [2]. To provide additional data from developing countries, WHO requested an analysis of trends in Hib disease incidence in countries in the Americas Region that included Hib vaccination in their routine infant immunization schedule with and without a booster dose.

In 2006, all countries and territories except Haiti in the Americas Region had included Hib vaccination in their national immunization programs [8]. Among 19 Latin American countries with routine Hib vaccination, most provided a three-dose series of Hib vaccine without a booster, while 5 countries (Argentina, Mexico, Panama, Uruguay and Venezuela) provided a booster dose at 15–18 months of age [9]. The impact of vaccination on cases of Hib meningitis has been shown using surveillance data from several Latin American countries [8], [10], [11], [12]. To evaluate potential impact of use of a booster dose, we used surveillance data to compare trends in Hib meningitis incidence among children <5 years in four countries, two of which had a three dose immunization schedule with no booster (Chile and Colombia) and two of which had a three dose primary immunization schedule with a booster dose in the second year of life (Argentina and Uruguay). Surveys of nasopharyngeal carriage were conducted among children in Argentina and Colombia to compare prevalence of Hib colonization several years after introduction of Hib conjugate vaccines.

Section snippets

Study design

In 2002, the World Health Organization commissioned a multi-country evaluation to compare trends in Hib meningitis in Latin American countries using a three-dose primary immunization schedule for Hib vaccination with and without a booster dose in the second year of life. A multi-country protocol (“Propuesta para una evaluación sistemática del impacto de los programas de vacunación contra H. influenzae tipo b (Hib) en países Latinoamericanos” [in Spanish, available from the authors]) was

Surveillance for Hib meningitis

Data provided by the four countries showed wide variation in Hib meningitis incidence among children <5 years during the pre-vaccine period, from 47.5 to 4.9 cases per 100,000 among children <1 year and 7.0 to 0.5 cases per 100,000 among 1–4 years (Table 2). Hib meningitis rates prior to vaccine introduction were highest in surveillance areas in Chile and Uruguay and lowest in Colombia. In Chile, Hib meningitis incidence among children <1 and 1–4 years in 1993 through 1995 was lower than during

Discussion

Analysis of meningitis surveillance data from four Latin American countries showed significant reductions in Hib meningitis incidence through 6–10 years following vaccine introduction, whether or not a booster dose was given in the second year of life. In two countries without a booster dose, Colombia and Chile, high coverage with three vaccine doses sustained low incidence rates among children <5 years at least 6–9 years after vaccination. There have been no reports of increasing incidence of

Acknowledgments

The authors are indebted to surveillance officers and laboratory staff in all four countries for contributions to surveillance for Hib meningitis and data collection, to the surveillance departments of the Ministries of Health and national reference laboratories for providing the data for this analysis, and to the many individuals who contributed to this work, including Gloria Muzzio, Matías Fingermann, Adriana Barrios, Maria Cristina Salvay, Gustavo Ferrer, Claudia Roseto, Osvaldo Rico, María

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Cited by (14)

Haemophilus influenzae Type b Vaccines
2017, Plotkin's Vaccines
Effect of Haemophilus influenzae type b vaccination without a booster dose on invasive H influenzae type b disease, nasopharyngeal carriage, and population immunity in Kilifi, Kenya: A 15-year regional surveillance study
2016, The Lancet Global Health
Citation Excerpt :
As in The Gambia, our study occurred in a setting with high vaccine coverage: in the KHDSS, coverage with three doses of the Hib vaccine was 91% in children aged 12 months in 2002, 88% in children aged 9–23 months in 2004, 95% in children aged 12 months in 2007, and 93% in 2013 in those aged 12–23 months resident in the KHDSS since birth who had vaccine cards available (Scott JAG, unpublished).19,20 Additional evidence of sustained disease control in the absence of a booster dose is provided by data from South America, where the incidence of H influenzae type b meningitis 6–10 years after vaccination introduction was similar in four countries, two of which used a booster dose and two of which did not.21 By contrast, evidence of waning immunity has prompted three countries—the UK, Mexico, and South Africa—to add a booster dose of Hib vaccine, after they initially recommended only a primary series.
Haemophilus influenzae type b (Hib) conjugate vaccine, delivered as a three-dose series without a booster, was introduced into the childhood vaccination programme in Kenya in 2001. The duration of protection and need for a booster dose are unknown. We aimed to assess vaccine effectiveness, the impact of the vaccine on nasopharyngeal carriage, and population immunity after introduction of conjugate Hib vaccine in infancy without a booster dose in Kenya.
This study took place in the Kilifi Health and Demographic Surveillance System (KHDSS), an area of Kenya that has been monitored for vital events and migration every 4 months since 2000. We analysed sterile site cultures for H influenzae type b from children (aged ≤12 years) admitted to the Kilifi County Hospital (KCH) from Jan 1, 2000, through to Dec 31, 2014. We determined the prevalence of nasopharyngeal carriage by undertaking cross-sectional surveys in random samples of KHDSS residents (of all ages) once every year from 2009 to 2012, and measured Hib antibody concentrations in five cross-sectional samples of children (aged ≤12 years) within the KHDSS (in 1998, 2000, 2004–05, 2007, and 2009). We calculated incidence rate ratios between the prevaccine era (2000–01) and the routine-use era (2004–14) and defined vaccine effectiveness as 1 minus the incidence rate ratio, expressed as a percentage.
40 482 children younger than 13 years resident in KHDSS were admitted to KCH between 2000 and 2014, 38 206 (94%) of whom had their blood cultured. The incidence of invasive H influenzae type b disease in children younger than 5 years declined from 62·6 (95% CI 46·0–83·3) per 100 000 in 2000–01 to 4·5 (2·5–7·5) per 100 000 in 2004–14, giving a vaccine effectiveness of 93% (95% CI 87–96). In the final 5 years of observation (2010–14), only one case of invasive H influenzae type b disease was detected in a child younger than 5 years. Nasopharyngeal H influenzae type b carriage was detected in one (0·2%) of 623 children younger than 5 years between 2009 and 2012. In the 2009 serosurvey, 92 (79%; 95% CI 70–86) of 117 children aged 4–35 months had long-term protective antibody concentrations.
In this region of Kenya, use of a three-dose primary series of Hib vaccine without a booster dose has resulted in a significant and sustained reduction in invasive H influenzae type b disease. The prevalence of nasopharyngeal carriage is low and the profile of Hib antibodies suggests that protection wanes only after the age at greatest risk of disease. Although continued surveillance is important to determine whether effective control persists, these findings suggest that a booster dose is not currently required in Kenya.
Gavi, the Vaccine Alliance, Wellcome Trust, European Society for Paediatric Infectious Diseases, and National Institute for Health Research.
Invasive Haemophilus influenzae isolates in children younger than 5 years: Distribution of serotypes and antimicrobial sensitivity, SIREVA II, Colombia 2002-2013
2015, Infectio
Analizar del 2002 al 2013 los datos de la vigilancia de los serotipos y sensibilidad antimicrobiana de los aislamientos invasivos de Haemophilus influenzae (H. influenzae) en niños menores de 60 meses.
Se analizaron los datos demográficos, fuente y enfermedad asociada de los aislamientos invasivos de H. influenzae recibidos entre 2002 y 2013. Todos los aislamientos habían sido confirmados bacteriológicamente, tenían el dato del serotipo, el cual fue determinado por el método de aglutinación en lámina y PCR y los patrones de sensibilidad antimicrobiana por concentración inhibitoria mínima a ampicilina, SXT, cloranfenicol, cefuroxima y ceftriaxona. El análisis se realizó por periodos de 3 años.
Por enfermedad invasiva el 50,5% eran de pacientes con meningitis, 23,5% de neumonías, 19,5% de sepsis y bacteriemia, 2,0% de otros y 4,5% sin dato. Por procedencia se recibieron de Bogotá y Antioquia 55 aislamientos de cada uno, de Risaralda 24, de Valle 15, de Santander 11 y 40 de 14 departamentos. El serotipo predominante fue el Hib (40,5%), seguido de HiNT (38,0%), Hia (17,5%), Hid (2,0%), Hif (1,5%) y Hie (0,5%). Del total de los aislamientos, 12,0% eran resistentes a ampicilina; 16,5% a SXT; 1,0% a cloranfenicol y 0,5% a ceftriaxona. Todos los aislamientos fueron sensibles a cefuroxima y a rifampicina.
La vigilancia por el laboratorio es una vigilancia pasiva voluntaria pero, no obstante el número reducido de aislamientos, permite determinar que Hib continúa circulando en esta población y que hay otros serotipos de H. influenzae que causan enfermedad invasiva. Por tanto es necesario mantener y fortalecer la vigilancia de este patógeno.
To analyze 2002-2013 surveillance data on the serotypes and antimicrobial sensitivity of invasive Haemophilus influenzae (H. influenzae) isolates in children younger than 60 months.
We analyzed the demographic data, source and associated diseases of invasive HI isolates from cases recorded from 2002-2013. All isolates had been bacteriologically confirmed and had data on their serotype, which was determined by the slide agglutination method and polymerase chain reaction. The antimicrobial sensitivity patterns were determined by minimum inhibitory concentration of ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, cefuroxime and ceftriaxone. The analysis was conducted in 3-year periods.
According to invasive disease, 50.5% of patients had meningitis, 23.5% had pneumonia, 19.5% had sepsis and bacteremia, 2.0% had other diseases and 4.5% lacked data. By origin, 55 isolates each were received from Bogota and Antioquia, 24 were from Risaralda, 15 were from Valle, 11 were from Santander and 40 came from 14 departments. The predominant serotype was Hib (40.5%), followed by HiNT (38.0%), Hia (17.5%), Hid (2.0%), Hif (1.5%) and Hie (0.5%). Of the total isolates, 12.0% were resistant to ampicillin; 16.5% to trimethoprim-sulfamethoxazole, 1.0% to chloramphenicol and 0.5% to ceftriaxone. All isolates were sensitive to cefuroxime and rifampicin.
Laboratory surveillance is a voluntary passive surveillance; however, the low number of isolates helped determine that Hib continues to circulate in this population and that there are other H. influenzae serotypes that cause invasive disease. Therefore, surveillance of this pathogen needs to be maintained and reinforced.
Surveillance of Haemophilus influenzae serotypes in Argentina from 2005 to 2010 during the Haemophilus influenzae type b conjugate vaccine era
2013, Revista Argentina de Microbiologia
La introducción de la vacuna contra Haemophilus influenzae tipo b en los programas de inmunización de muchos países produjo una reducción marcada en la incidencia de en-fermedad invasiva causada por este serotipo y en su portación y un incremento de otros tipos capsulares y de aislamientos no capsulados. Se estudiaron 313 aislamientos de H. influenzae recuperados de sitio estéril, provenientes de pacientes pediátricos y adul-tos con enfermedad invasiva atendidos en 90 hospitales de la Red Nacional de Laborato-rios para Meningitis e Infecciones Respiratorias Agudas Bacterianas durante el período 2005–2010. Las patologías más frecuentes fueron neumonía, 40,3 % (n = 126), meningitis, 30,0 % (n = 94) y bacteriemia, 26,5 % (n = 83). En los pacientes pediátricos (n = 279), la mayor frecuencia de aislamientos correspondió a menores de 2 años, 74,5 % (n = 208). Con respecto a la distribución de tipos, el 61,3 %, correspondió a H. influenzae no capsu-lados (n = 192); el 20,1 % al b (n = 63); 11,2 % al a (n = 35); 4,8 % al f y 2,6 % a otros. En meningitis predominaron H. influenzae capsulados mientras que en neumonía y bacterie-mia resultaron dominantes los tipos no capsulados. Se determinó el biotipo en 306 aislamientos. Todos los aislamientos de tipo a correspondieron al biotipo II; el 66,7 % de los tipo b pertenecieron al biotipo I. Mediante las técnicas de aglutinación en lámina y PCR se estudiaron 220 aislamientos; la concordancia entre ambas fue de 0,982 (IC: 0,92–1,00). En el último año se encontró un aumento significativo del tipo b, lo cual indi-ca la importancia de mantener la vigilancia clínica y laboratorial de la enfermedad inva-siva por H. influenzae.
The introduction of the Haemophilus influenzae type b vaccine in the immunization programs of many countries has greatly reduced this invasive disease and the carriage caused by this serotype, also increasing other capsular types and non-capsular isolations. There were 313 isolations of H. influenzae under study, which were recovered from a sterile site coming from pediatric and adult patients carrying the invasive disease. Patients were treated at 90 different hospitals belonging to the Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas (National Lab Network for Meningitis and Acute Bacterial Respiratory Infections) from 2005 to 2010 for the following disorders: pneumonia, 40.3% (n = 126), meningitis, 30.0% (n = 94) and bacteremia, 26.5% (n = 83). In pediatric patients (n = 279), the highest frequency of isolations corresponded to children under the age of 2 years, 74.5% (n = 208). Regarding type distribution, 61.3% corresponded to non-capsular H. influenzae (n = 192), 20.1% to type b (n = 63), 11.2% to type a (n = 35), 4.8% to type f, and 2.6% to other types. Capsular H. influenzae was predominant in meningitis whereas non-capsular H. influenzae in pneumonia and bacteremia. The biotype was determined in 306 isolations. The totality (100%) of type a (n = 35) was biotype II whereas 66.7% of type b (n = 63) was biotype I. Slide agglutination and PCR tests were used in 220 isolations. There was a match of 0.982 (IC: 0.92-1.00) between them. During the last year, there was a great increase in type b, showing the importance of clinical and laboratory-based surveillance of the invasive disease caused by H. influenzae.
Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia
2013, Vaccine
Citation Excerpt :
According to Census population data Bogota has a population of 7.363.782 people, including 357.200 children <2 years of age, accounting for 13.9% of children under two years of the country. A total of 246 NP samples from children between 12 and 18 months of age were taken during the period before the introduction of PCV7, as part of a study on the impact of the Haemophilus influenzae type b vaccination carried out in several Latin American countries [15]. In the post PCV7 introduction, 197 NP samples were recovered from healthy children of 12 to 18 months of age, which were vaccinated with two or three doses.
In Bogotá, the Heptavalent Conjugate Vaccine (PCV7) was introduced into childhood immunization schedule since 2009. The aim of this study was to assess the changes in serotype distribution and penicillin susceptibility of Streptococcus pneumoniae isolates recovered from nasopharyngeal samples and invasive disease among children living in Bogotá, before and after PCV7 introduction.
Nasopharyngeal swabs were collected from healthy children aged between 12 and 18 months of age before (years 2005–2006) and after (2011) PCV7 introduction. Identification of S. pneumoniae was performed by multiplex PCR. Serotype was determined by PCR and Quellung reaction. Susceptibility to penicillin, ceftriaxone, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline and erythromycin was evaluated. In addition, distribution of serotypes and antimicrobial susceptibility before and after vaccine introduction among invasive isolates recovered from children ≤2 years old living in Bogotá was analyzed.
Prevalence of pneumococcal nasopharyngeal carriage declined from 55.7% (137/246) in unvaccinated to 44.2% (87/197) (p = 0.01) in vaccinated children. The proportion of children carrying PCV7 serotypes decreased from 23.6% (58/246) to 7.6% (15/197) (p < 0.001). The decrease was counterbalanced by an increase in the proportion of non-PCV7 serotypes. The most prevalent among emerging serotypes were 15A, 15B, 15 C, 11A and 35B. Among IPD isolates, PCV7 serotypes decreased from 69.1% (235/340) in 2005/2009 to 38.0% (32/84) in 2010/2011 (p < 0.001). The increase of non-PCV7 serotypes was significant. Resistance to penicillin among invasive isolates recovered from meningitis decreased from 41.1% (30/73) in the pre-vaccine period to 14.2% (2/14) in post-vaccine period (p = 0.02).
A decrease in the prevalence of pneumococcal nasopharyngeal carriage following the introduction of PCV7 vaccine, have been overshadowed by an important surge in the prevalence of non-PCV7 serotypes. Systematic surveillance combining nasopharyngeal carriage surveys and IPD detection could help in evaluating the impact of conjugate vaccines.
Invasive haemophilus influenzae infections after 3 decades of hib protein conjugate vaccine use
2021, Clinical Microbiology Reviews

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Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries

Abstract

Highlights

Introduction

Section snippets

Study design

Surveillance for Hib meningitis

Discussion

Acknowledgments

Lancet

Lancet

Vaccine

Lancet

Lancet

Lancet

Lancet

Vaccine

Vaccine

Vaccine

WHO position paper on Haemophilus influenzae type b conjugate vaccines

Wkly Epidemiol Rec

Efficacy of Haemophilus influenzae type b vaccination of children: a meta-analysis

Eur J Clin Microbiol Infect Dis

Conjugate vaccines for preventing Haemophilus influenzae type B infections

Cochrane Database Syst Rev

Haemophilus influenzae type b conjugate vaccines

Immunology

Progress in vaccination against Haemophilus influenzae type b in the Americas

PLoS Med

Rapid assessment of the impact of Haemophilus influenzae vaccine serotype b in Colombia. Public Health Laboratories

Rev Panam Salud Publica