Haemophilus influenzae type b infections are preventable everywhere
Authors: Mark C Steinhoff
Journal: The Lancet (1997)

The virtual elimination by vaccine of invasive Haemophilus influenzae type b (Hib) disease in industrial countries is a modern public health triumph. Early vaccines, consisting of the Hib polysaccharide capsule, were shown to be effective in the prevention of invasive disease in older children in Finland in 1974. Conjugate Hib vaccines consisting of protein combined with polysaccharide had better immunogenicity in young infants and were shown to be highly effective. During the 1990s widespread use of conjugate Hib vaccines has virtually eliminated Hib disease from North America, northern Europe, Australia, and New Zealand.1Ward JH influenzae vaccines.in: Plotkin SA Mortimer Jr, EA Vaccines. 2nd ed. WB Saunders Co, Philadelphia1994: 337-386Google Scholar, 2Robbins JB Schneerson R Anderson P Smith DH Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines.JAMA. 1996; 276: 1181-1185Crossref PubMed Scopus (145) Google Scholar Until recently the burden of Hib disease was not well defined in many developing regions, and it was not clear whether Hib vaccines would be effective in these regions.3Keusch GT Should Haemophilus influenzae type b conjugate vaccine be introduced into EPI?.Lancet. 1992; 339: 802-803Abstract PubMed Scopus (4) Google Scholar, 4Steinhoff MC Developing and deploying pneumococcal and haemophilus vaccines.Lancet. 1993; 342: 630-631Abstract PubMed Scopus (27) Google Scholar This issue of The Lancet carries two reports on the use of Hib vaccine, each of which confirms previous data and has notable implications. The evaluation of Hib vaccine introduction in the UK confirms the previously reported high effectiveness of this vaccine. As shown in Scandinavia, these data suggest that a booster dose after the first year of life may not be necessary for effectiveness in well-immunised populations. The analyses conducted after the introduction of the vaccine provide an example of the imaginative use of surveillance data to assess vaccine effectiveness. The prospective randomised efficacy trial from The Gambia shows that an Hib conjugate vaccine has an efficacy of more than 90% against Hib meningitis in a developing-country setting, similar to reports from North America, Europe,2Robbins JB Schneerson R Anderson P Smith DH Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines.JAMA. 1996; 276: 1181-1185Crossref PubMed Scopus (145) Google Scholar and Chile.5Lagos R Horwitz I Toro J et al.Large scale, postlicensure, selective vaccination of Chilean infants with PRP-T conjugate vaccine: practicality and effectiveness in preventing invasive Haemophilus influenzae type b infections.Pediatr Infect Dis J. 1996; 15: 216-222Crossref PubMed Scopus (107) Google Scholar A secondary analysis of data from the Gambian study shows an additional substantial effect against severe radiographically proven pneumonia. Although there are wide confidence limits on the estimated effect, these data extend and confirm earlier studies on the aetiology of pneumonia, which were known to underestimate Hib disease.6Funkhouser A Steinhoff MC Ward J H influenzae disease and immunization in developing countries.Rev Infect Dis. 1991; 13: S542-S554Crossref PubMed Scopus (75) Google Scholar In The Gambia bacterial pneumonia is far more common than bacterial meningitis. In the fully vaccinated cohort, 11 cases of meningitis and 38 cases of radiographic pneumonia were prevented, which suggests that the overall effect on pneumonia and meningitis is 4·5-fold greater than the effect on meningitis alone. This unexpected “bonus” for regions with higher rates of bacterial pneumonia is a case for not delaying the introduction of routine Hib vaccination in developing regions as Mulholland and colleagues emphasise. Because of the high efficacy of conjugate Hib vaccines in every environment in which they have been tested, and their very low rate of adverse events, WHO and the Children's Vaccine Initiative (CVI), are currently considering supply and delivery issues, before recommending its widespread use in Expanded Programs of Immunization (EPI). A recent meeting on Hib in Asia showed that Hib was the commonest cause of childhood bacterial meningitis in India and Thailand, but some Asian regions reported low levels of Hib disease.7Proceedings of International Seminar on Hib in Asia meeting, WHO, AMP. Indonesia, Dec 1996.Google Scholar Careful studies are needed to determine whether prior antibiotic therapy or bacterial and/or human host factors may account for the apparently low rates of Hib disease reported in some Asian societies. A separate issue is how to provide a new highly effective vaccine in the existing EPI system. In common with other newly developed vaccines, (including existing hepatitis B, and hepatitis A vaccines, and imminent pneumococcal conjugate vaccines, as well as respiratory syncytial virus, shigella, and typhoid vaccines), Hib vaccines are currently more expensive to produce than those already in the EPI. WHO, CVI, and others are exploring approaches to reducing the cost of these vaccines for non-industrialised countries. A recent meeting in Bellagio outlined approaches towards improving the availability of Hib and other vaccines.8Bellagio conference. Global availability of new vaccines. Rockefeller Foundation, Feb 1997.Google Scholar Hib disease is not mentioned in many textbooks of tropical medicine, yet now it must be considered a preventable illness in many tropical populations. Indeed, bacterial meningitis (most of which is due to Hib, pneumococcus, and meningococcus) could be targeted as a preventable illness if vaccines against these three organisms were added to EPI programmes.9Wright PF Approaches to prevention of acute bacterial meningitis in developing countries.Bull World Health Organ. 1989; 67: 479-486PubMed Google Scholar In many regions bacterial meningitis is under appreciated and not reported. The surveillance and reporting of bacterial meningitis should be given higher priority, since this syndrome soon will be vaccine preventable. Improved surveillance for childhood bacterial meningitis might usefully be added to current programmes for enhancing the surveillance of poliomyelitis. Although the impetus for development of Hib vaccines was prevention of the devastation caused by Hib meningitis in the industrialised countries, the vaccines will have an enlarged role in less developed countries in preventing Hib meningitis and pneumonia. Additionally, the success of Hib vaccines can accelerate the consideration of how new and more expensive vaccines can be made available to populations with limited resources. Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infantsPRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis. Full-Text PDF Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without boosterA high degree of efficacy has been observed with PRP-T vaccine given as a three-dose schedule in infancy and with HbOC as a single dose in older children. Efficacy of PRP-T appears to be enhanced by carrier priming. Although with increasing age there was a small decline in efficacy of PRP-T, Hib disease is now close to being eliminated in the UK, and we suggest that a booster is not necessary in the second year of life. Full-Text PDF