Global Hib vaccination: reasons to cheer and fear
Authors: Stephen R C Howie
Journal: The Lancet Global Health (2016)

Conjugate Haemophilus influenzae type b (Hib) vaccination is one of the major global health achievements of the past three or four decades. H influenzae type b is a key cause of disease and death in unvaccinated populations, and that burden falls most severely on young children. Those of us at medical schools in developed countries in the late 1980s learned about H influenzae type b disease but rarely saw it in practice, such was the effectiveness of the conjugate vaccine introduced in those settings in the 1990s. At that time the disease's principal impact was to be seen in low-income countries, which would not use the vaccine for years. More than 90% of countries now routinely provide conjugate Hib vaccine to their children, a proportion that was achieved through an impressive global public health push. However, the world is divided on the dosing schedule used: the vast majority of developed countries give a booster dose at age 12–23 months, whereas most low-income countries do not. WHO policy is a three-dose primary series in infancy with no booster, and vaccine funding for low-income countries follows this recommendation. For health agencies and experts in the field, the question of whether low-income countries should have a booster dose is one that is not going away. Therefore, the report in The Lancet Global Health by Laura Hammitt and colleagues,1Hammitt LL Crane RJ Karani A et al.Eff ect of Haemophilus infl uenzae type b vaccination without a booster dose on invasive H infl uenzae type b disease, nasopharyngeal carriage, and population immunity in Kilifi, Kenya: a 15-year regional surveillance study.Lancet Glob Health. 2016; (published online Feb 4.)http://dx.doi.org/10.1016/S2214-109X(15)00316-2Google Scholar who have assessed Hib vaccine effectiveness, nasopharyngeal carriage, and population immunity in Kenya, is important. The investigators report that the introduction in 2001 of routine conjugate Hib vaccination with a three-dose primary series without a booster resulted in a major and sustained reduction in invasive Hib disease in the Kilifi district of Kenya over 13 years. This adds to earlier evidence of sustained long-term control of disease with the same schedule in The Gambia, the first country in Africa to introduce the vaccine in 1997.2Howie S Oluwalana C Secka O et al.The effectiveness of conjugate haemophilus influenzae type b vaccine in The Gambia 14 years after introduction.Clin Infect Dis. 2013; 57: 1527-1534Crossref PubMed Scopus (25) Google Scholar So why should we worry that the vaccine will stop working, or stop working so well, without a booster? There are both empirical and theoretical reasons to worry. Good long-term control has not occurred in all countries that have started with a three-dose primary series alone. The UK introduced Hib vaccine in 1993 and was one of the few developed countries not to schedule a booster dose from the outset. Control was excellent initially3Ladhani S Slack MP Heys M White J Ramsay ME Fall in Haemophilus influenzae serotype b (Hib) disease following implementation of a booster campaign.Arch Dis Child. 2008; 93: 665-669Crossref PubMed Scopus (72) Google Scholar and H influenzae type b carriage in the upper respiratory tract was eliminated,4McVernon J Howard AJ Slack MP Ramsay ME Long-term impact of vaccination on Haemophilus influenzae type b (Hib) carriage in the United Kingdom.Epidemiol Infect. 2004; 132: 765-767Crossref PubMed Scopus (61) Google Scholar but after several years a resurgence of disease prompted the introduction of a booster dose in 2003, which was associated with a return to good control.3Ladhani S Slack MP Heys M White J Ramsay ME Fall in Haemophilus influenzae serotype b (Hib) disease following implementation of a booster campaign.Arch Dis Child. 2008; 93: 665-669Crossref PubMed Scopus (72) Google Scholar This resurgence in disease was concerning, and Ireland seemed to have a similar experience to the UK.5Fitzgerald M Canny M O'Flanagan D Vaccination catch-up campaign in response to recent increase in Hib infection in Ireland.Euro Surveill. 2005; 10: E050929.2PubMed Google Scholar Another, theoretical, reason to worry is that immunity of vaccinated children to H influenzae type b infection could wane over the years (by contrast with earlier generations whose immunity was based on exposure to the pathogen itself). In this state of lowered immunity, this vaccinated group might form a new reservoir of Hib carriage and disease (typically mild disease) and expose young children to greater risk of disease, typically severe. This kind of dynamic contributes to resurgences in another disease, pertussis. Clearly, a booster dose might help to avert this. Mexico introduced a booster in 2007 in the face of evidence of waning immunity in children.6Rodriguez RS Mascarenas C Conde-Glez CJ et al.Serological protection induced by Haemophilus influenzae type B conjugate vaccine in Mexican children: is a booster dose of the vaccine needed?.Clin Vaccine Immunol. 2010; 17: 1639-1641Crossref PubMed Scopus (8) Google Scholar The evidence from Kenya for sustained immunity in older children and the absence of a H influenzae type b reservoir in that group partly allays concerns about waning immunity with long-term use of Hib vaccine, but not completely. Different contexts have varying factors at play, and the Hib vaccine has not been in use in enough low-income countries for long enough to be sure that no pitfalls await. Indeed, Mackenzie and colleagues7Mackenzie GA Ikumapayi UN Scott S et al.Increased disease due to Haemophilus influenzae type b: population-based surveillance in eastern Gambia, 2008–2013.Pediatr Infect Dis J. 2015; 34: e107-e112Crossref PubMed Scopus (13) Google Scholar reported a resurgence of disease in The Gambia beyond 14 years of vaccine use. So what can be done? It is tempting to recommend a unified global policy of a booster dose and be done with it. This solution will not suffice though because of constrained budgets, competing priorities, complicated logistics, and, crucially, a lack of evidence for its necessity. But doing nothing is not an option. Countries must first be vigilant with disease surveillance—they will not know if they have a problem unless disease burden is measured, a principle that clearly applies not just to H influenzae type b disease. Second, the dynamics of H influenzae type b control and resurgence must be better understood in varying contexts to avoid countries being caught unprepared by resurgent disease. The world has enough challenges without letting this disease get a second hold on countries that have already taken actions against it. I declare no competing interests. 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 studyIn 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. Full-Text PDF Open Access