Elsevier

The Lancet

Volume 366, Issue 9480, 9–15 July 2005, Pages 144-150
The Lancet

Articles
Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study

https://doi.org/10.1016/S0140-6736(05)66788-8Get rights and content

Summary

Background

Routine immunisation of infants in The Gambia with a Haemophilus influenzae type b (Hib) polysaccharide-tetanus toxoid conjugate vaccine began in May, 1997. We investigated the effectiveness of the vaccine when delivered through the expanded programme on immunisation and the effect of national immunisation on incidence of Hib disease.

Methods

Surveillance for Hib disease was maintained in the western half of The Gambia using standard methods with an emphasis on meningitis. We estimated vaccine efficacy using the case control method, and vaccine coverage and population denominators for incidence rates using a cluster sample survey. Prevalence of Hib carriage in a sample of 1–2-year old children attending health centres for vaccination was ascertained with oropharyngeal swabs plated onto antiserum agar.

Findings

Between May, 1997, and April, 2002, a total of 5984 children were examined for possible Hib infections. 49 children had Hib disease, 36 of whom had meningitis. The annual incidence rates of Hib meningitis before any use of the vaccine (1990–93) dropped from over 200 per 100 000 children aged younger than 1 year to none per 100 000 in 2002, and from 60 to no cases per 100 000 in children younger than 5 years. The prevalence of Hib carriage decreased from 12% to 0·25% (p<0·0001). Two doses of vaccine were needed for direct protection from Hib disease (vaccine efficacy 94%, 95% CI 62–99). Since most children received a protective dose after the age of greatest disease risk, indirect effects were important in reducing disease incidence.

Interpretation

The Gambian Hib immunisation programme reduced the occurrence of Hib disease despite irregular vaccine supply. The effect of the programme in The Gambia has important implications for the introduction of the vaccine into routine immunisation programmes of other developing countries.

Introduction

Before the widespread use of conjugate vaccines for Haemophilus influenzae type b (Hib), this organism was the most common cause of severe invasive childhood infections in developed countries.1 The introduction of routine vaccination in developed countries has led to substantial declines in the incidence of Hib disease.2, 3 However, routine use of these vaccines in less developed countries has been delayed until recently4, 5 because there was little information available about the burden of Hib disease and because the high price of conjugate vaccines made them unaffordable.6

Studies undertaken in The Gambia before the Hib conjugate vaccine was investigated showed that the epidemiology of Hib disease was different from that seen in more developed countries. Overall incidence was higher, infections occurred in children of younger ages, and pneumonia was more prevalent and related to a worse outcome in The Gambia than in more developed countries.7, 8 The case fatality rate of Hib meningitis was 30%,9 sequelae were common, and less than half of patients recovered fully from Hib disease.10 However, epiglottitis was not reported in The Gambia or any other developing countries.11

A successful trial of a Hib conjugate vaccine was undertaken in 42 000 infants in The Gambia during 1993 to 1995.12 The vaccine used was a Hib polysaccharide-tetanus toxoid conjugate (PRP-T; Act-Hib, supplied by Pasteur Mérieux, Lyon, France). The vaccine showed 95% efficacy against culture-confirmed invasive Hib disease, 21% efficacy against radiologically defined pneumonia with definite alveolar consolidation, and 60% protection against carriage in the second year of life.12, 13 However, reports of vaccine efficacy under optimum trial conditions do not guarantee that a vaccine will be effective in routine use. This possible situation is especially relevant in developing countries where suboptimum storage and transport conditions can reduce vaccine efficacy. Indirect effects (herd immunity) can make vaccination more effective than suggested by an individually randomised efficacy trial. Additionally, national immunisation could change the epidemiology of Hib disease in developing countries, leading to the emergence of epiglottitis.

Routine immunisation of Gambian infants with PRP-T vaccine was introduced on May 1, 1997, via the Gambia's national expanded programme on immunisation (EPI). The Gambia's EPI is one of the most successful immunisation programmes in Africa. Staff at health centres throughout the country administer standard EPI vaccines (BCG, diphtheria-tetanus-pertussis [DTP], polio, measles, hepatitis B, yellow fever). DTP vaccinations are scheduled to be given at 2 months, 3 months, and 4 months of age although, in practice, they are usually given later. Vaccine coverage is assessed regularly by use of the cluster survey technique, recommended by WHO.14 The coverage of DTP3 has been more than 85% since 1990. The vaccine was supplied as part of a donation agreement between Pasteur Mérieux (now Sanofi Pasteur MSD), the vaccine manufacturers, and the Gambia Government, mediated by UNICEF. Since 2002, supply of Hib vaccine has continued with support from the Global Alliance for Vaccines and Immunization (GAVI).

We aimed to determine the effectiveness of PRP-T vaccine in preventing Hib meningitis among Gambian children when delivered through The Gambia's EPI since 1997. We also sought to estimate the contribution of indirect effects, associated with reduced throat carriage of Hib in the second year of life, to the reduction of disease incidence. Finally, we endeavoured to document any unusual or late presentations of Hib disease occurring in children who received vaccination in early infancy during the efficacy trial.

Section snippets

Study population

Surveillance for Hib disease was restricted to the western region of The Gambia. This region includes rural, urban, and rapidly growing periurban areas, with a total population in 2003 of 836 000—60% of the total population of the country (Ndow ASM, Department of Central Statistics, Banjul, The Gambia, unpublished, 2004).

We enrolled children in the present study if they had been investigated as possible cases of Hib disease and if they were younger than 6 years. Children from the previous

Results

Introduction of Hib vaccine into the routine EPI immunisation schedule was implemented on May 1, 1997. Health centre staff were trained to record DTP and Hib vaccinations on the standard health card; children born after May 1, 1997, were issued with a modified health card that explicitly outlined Hib vaccination. Routine immunisation with Hib and DTP was interrupted from time to time because of a meningitis vaccination campaign (July to August, 1997) and irregular supplies of vaccine (figure 1).

Discussion

After the introduction of routine Hib immunisation, the annual incidence rate of meningitis in infants in The Gambia dropped sharply from over 200 per 100 000 to 21 per 100 000 in the first 2 years of vaccination.5 The incidence declined further to 0 per 100 000 in the fifth year after the introduction of routine immunisation. This reduction was achieved despite difficulties with a regular supply of vaccine. No cases of Hib disease have been identified in the western region since 2002.

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