ArticlesRandomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants
Introduction
Invasive disease due to Haemophilus influenzae type b (Hib) remains a major problem in developing countries, where the epidemiology of the disease differs from that seen in industrialised countries in several important respects. In developing countries, the incidence of Hib disease is greater than in industrialised countries, and the disease occurs in younger children, with most cases occurring before 12 months of age and almost half before the age of 6 months.1, 2 The clinical pattern of disease also differs; in developing countries, pneumonia is commoner than meningitis, whereas epiglottitis is not seen.3 The outcome of Hib meningitis in developing countries is poor. In sub-Saharan Africa, 20–40% of patients who reach health-care facilities die from the disease and neurological sequelae occur in a significant proportion of survivors.2 Nasopharyngeal carriage of Hib is commoner and occurs in younger children in developing than in industrialised countries.4, 5, 6
Protein-polysaccharide conjugate vaccines against Hib have been highly effective in reducing Hib disease and carriage in industrialised countries.7, 8 Although, before the present study, no randomised double-blind efficacy study of the Hib polysaccharide-tetanus protein conjugate vaccine (PRP-T) had been done, the vaccine was effective in preventing Hib meningitis in British infants in an open study.9 Two randomised trials of other Hib conjugate vaccines in American communities whose living conditions resemble those of developing countries produced differing results. Hib polysaccharide-Neisseria meningitidis group B outer membrane protein complex conjugate vaccine (PRP-OMPC) proved effective in Navajo Indians,10 whereas Hib polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) did not in Alaskan natives.11
Before this study, no efficacy studies of any Hib vaccines had been done in developing countries, although an effectiveness study was done in Santiago, Chile, where PRP-T was shown to prevent invasive Hib disease.12 However, the epidemiology of Hib disease in Santiago is more similar to that in the USA than to that in poorer developing countries. For example, the proportions of cases of Hib disease in infants younger than 12 months in Chile, the USA (before vaccination), and The Gambia were 60%, 51%, and 84%, respectively.13, 14 Furthermore, no studies have evaluated the efficacy of vaccination against Hib pneumonia, which is probably the most common manifestation of invasive Hib disease in developing countries. The study reported here was designed to assess the efficacy of an Hib conjugate given to infants in a poor developing country for the prevention of pneumonia and other invasive disease due to Hib. As selection of pneumonia cases for investigation is subjective, a double-blind study design was used.
Section snippets
Methods
The study was done in the Western Region of The Gambia, an area where the epidemiology of Hib disease has been well studied and where most cases of invasive Hib disease are likely to reach medical attention.14, 15 During the 3 years before the study, the incidence of invasive Hib disease in children under age 12 months living in the study area was estimated to be 274 per 100 000 children each year.15 The study area, which is populated by about half of the one million people who live in The
Results
Between March 8, 1993, and Oct 1, 1995, 42 848 infants were enrolled into the study, of whom 21 490 received the PRP-T mixed with DTP and 21 358 received DTP alone (figure). Study vaccines were available until March 1, 1996, for partly vaccinated children who presented for later doses. Of the 42 848 children enrolled, 40 366 (94%) received a second dose of vaccine and 35 713 (83%) received all three doses. The median ages of administration for doses one, two, and three were 11 weeks, 18 weeks,
Discussion
Murray and Lopez estimated that over 200 000 cases of Hib meningitis occur in the developing world every year.23 The mortality and morbidity amongst those who get medical attention is substantial; a significant proportion die without getting any medical attention. Our study showed that PRP-T Hib conjugate vaccine was highly effective in preventing pneumonia and meningitis due to Hib after three doses given in infancy, and offered 75% protection from the time the first dose was given. As has
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