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Prior to implementation of Haemophilus influenzae type b (Hib)-conjugate vaccination programs in the 1990s, Hib was the commonest cause of bacterial meningitis in children aged <5 years. While the burden of all Hib disease has significantly decreased in the post-vaccination era, Hib still accounted for >29,000 deaths worldwide in children aged <5 years in 2015. We reviewed literature data on the most widely used Hib vaccines and vaccination strategies which led to the global prevention and control of Hib disease and aim to highlight important factors for continued disease control and elimination in the future. More than 90% of countries worldwide have implemented Hib-conjugate vaccination in their national immunization programs. Vaccines containing Hib polyribosylribitol phosphate (PRP) conjugated with tetanus toxoid (Hib-TT) are the most commonly used. Neisseria meningitidis outer membrane protein complex of PRP (Hib-OMP) is also used. Although the kinetics of the immune response varies with Hib vaccine and schedule used, high control of Hib disease was observed in all settings/scenarios. Further improving global Hib vaccination coverage may result in disease elimination. What is the context? Haemophilus influenzae is causing a variety of diseases, from otitis media and sinusitis to invasive disease (e.g. meningitis and pneumonia). H. influenzae type b (Hib) was the most common cause of bacterial meningitis in children <5 years of age, and especially among <2-year-olds. Even with appropriate treatment, up to 40% of children with bacterial meningitis can suffer permanent disabilities and up to 5% will die. The development of vaccines to protect against Hib disease has started in the late 1970s and has culminated with the licensure of 4 Hib conjugate vaccines, of which 2 are currently widely used. What is new? In this review, we gathered evidence on the different Hib vaccines and vaccination strategies that have contributed to the global prevention and control of Hib disease. The review indicates: the incidence of Hib disease has decreased considerably due to the introduction of Hib vaccines in national immunization programs worldwide. However, Hib disease is not yet completely eradicated. the vaccines currently used offer protection against Hib over long periods of time. carriage of the pathogen by healthy individuals seem to be less frequent, but data are still needed to fully evaluate the impact of vaccination. other H. influenzae types are now more frequent. Why is this important? Despite the huge success of Hib vaccination, continuous surveillance is needed to anticipate potential re-emergences and devise the best strategies for prevention and control of disease. Hib vaccination should be considered in the few countries who have not yet implemented it, to decrease associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Introduction: The development of diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b (Hib) conjugate vaccine combinations culminated with hexavalent vaccines, the largest, most complex vaccine combinations in the immunization calendar. Hexavalent vaccines are used widely in Europe and are co-administered with multiple other recommended vaccines. Hib immunogenicity may reduce when combined with acellular pertussis antigens, or in some co-administrations. We reviewed the epidemiology of H. influenzae disease in Europe aiming to evaluate the current level of Hib control and indirectly assess the effectiveness against Hib of GSK’s hexavalent vaccine in 10 countries where it is/has been used almost exclusively. Areas covered: We reviewed surveillance data from the European Union Invasive Bacterial Infections Surveillance Network and the European Surveillance System database from 1999–2014 and extracted case and incidence/notification rates (per 100,000 population) of invasive H. influenzae disease. We included age and serotype/strains distribution among countries in the European Union/European Economic Area region that reported to the European Centre for Disease Prevention and Control surveillance system. Expert commentary: The impact of Hib vaccination in Europe is sustained, testifying to continued effectiveness against invasive Hib disease after the implementation of hexavalent vaccines into immunization programs, which, since 2006, has been almost exclusively GSK´s hexavalent DTPa-HBV-IPV/Hib vaccine.

Introduction: The development of diphtheria-tetanus-acellular pertussis-Haemophilus influenzaetype b (Hib) conjugate vaccine combinations culminated with hexavalent vaccines, the largest, most complex vaccine combinations in the immunization calendar. Hexavalent vaccines are used widely in Europe and are co-administered with multiple other recommended vaccines. Hib immunogenicity may reduce when combined with acellular pertussis antigens, or in some co-administrations. We reviewed the epidemiology ofH. influenzaedisease in Europe aiming to evaluate the current level of Hib control and indirectly assess the effectiveness against Hib of GSK’s hexavalent vaccine in 10 countries where it is/has been used almost exclusively. Areas covered: We reviewed surveillance data from the European Union Invasive Bacterial Infections Surveillance Network and the European Surveillance System database from 1999–2014 and extracted case and incidence/notification rates (per 100,000 population) of invasiveH. influenzaedisease. We included age and serotype/strains distribution among countries in the European Union/European Economic Area region that reported to the European Centre for Disease Prevention and Control surveillance system. Expert commentary: The impact of Hib vaccination in Europe is sustained, testifying to continued effectiveness against invasive Hib disease after the implementation of hexavalent vaccines into immunization programs, which, since 2006, has been almost exclusively GSK´s hexavalent DTPa-HBV-IPV/Hib vaccine. [ABSTRACT FROM PUBLISHER]

Fourteen years after the first introduction of conjugate Haemophilus influenzae type b vaccine in The Gambia, effective disease control was maintained, with associated low carriage and high seroprotection. Continued surveillance must determine if protection wanes and a booster dose is needed.Background. The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction.Methods. Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to <2 years, Hib antibody levels in children aged <5 years, and Hib vaccine coverage and timing in children aged 1 to <2 years.Results. The incidence of Hib meningitis remained low (averaging 1.3 per 100 000 children aged <5 years annually), as did the Hib oropharyngeal carriage rate (0.9%). Hib antibody levels were protective in >99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1–2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively.Conclusions. Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries. [ABSTRACT FROM AUTHOR]

Abstract: Invasive Hib disease, which remains a major cause of childhood mortality and morbidity in most of the developing world, was eliminated in The Gambia by 2002 following the introduction of conjugate Hib vaccine in 1997. Formal disease surveillance was stopped in 2002 but five cases (including three of meningitis) were detected non-systematically between July 2005 and April 2006. This equates to an incidence of 3 per 100,000 annually for meningitis, a likely underestimate. The age distribution of cases (median 15 months, range 0–36 months) was older than previously seen and there were examples of apparent vaccine failure, but the cause for this re-emergence is not clear. No evidence was found of the emergence of a hypervirulent strain. The re-establishment of continuing surveillance is required to answer the questions raised by this report, and is particularly important in settings like The Gambia, where a booster dose is not given, to determine long-term effects of national immunisation with Hib vaccine. [Copyright &y& Elsevier]

Hib vaccine is the 8th vaccine knocking at the door to be included in the EPI the world over. However there are some controversies that need to be addressed, especially when it comes to use of this vaccine in India. It is difficult to culture Hib unless one uses sheep blood enriched media for culture. There is a lack of good community based data on Hib burden in India. This makes many feel that Hib is rare in India. However this is not true. There are many studies that have looked at this closely. Hib is a common cause of meningitis and pneumonitis in children less than 5 years old in India. There is wide spread problem of multi-drug resistance by Hib in India. Mortality of meningitis is as high as 100% if third generation cephalosporins are not used in time. Of the survivors of meningitis, 60% develop long-term sequelae. Hib vaccine is very effective and can lead to 99% reduction with mass vaccination in just 2-3 years. It is also a very safe vaccine. Of the conjugated vaccines available in India all are equally effective and safe and there is nothing to choose one over the other. There is a need to give a booster dose at 15-18 months of age. Even UK, which never gave the booster dose, is seriously thinking of changing their practice and give a booster dose. Lastly the combination vaccines of Hib with IPV, DPwT/DPaT, and Hepatitis B are safe and effective and should be encouraged to improve the compliance. The use of Hib vaccine is recommended in India, for those who can afford the vaccine. [ABSTRACT FROM AUTHOR]