Pentavalent DTP vaccine

Abstract

Hemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis among infants and young children and the second leading cause of bacterial pneumonia deaths among children under 5 y. The overall case-fatality rate for Hib meningitis is 20–29%, and nearly 30% of surviving children suffer from major disabilities, while all invasive Hib disease (including meningitis) has a case fatality rate of 16% in India. Using the estimates from the Hib study, ~215,000 new cases of Hib pneumonia occur yearly in Indian children under the age of 5 y and result in over 61,000 deaths. This level of mortality is because of poor access to health services and poor health-seeking behavior by population, lack of laboratory infrastructure, and difficulty to diagnosis Hib disease among affected children. Disease burden is difficult to calculate. Even for those affected children who do reach healthcare facilities, the lack of quality health services and increasing prevalence of antibiotic-resistance makes treatment difficult for these children. Even in countries that have poor immunization coverage, indirect benefits of the Hib vaccine have been reported due to the herd effect. The Hib vaccine thus should be effective in India where Universal Immunization Programme (UIP) coverage is poor.

Following the World Health Organization (WHO) recommendation that Hib-containing Pentavalent DTP vaccine (a combination vaccine that protects against five killer diseases: diphtheria, pertussis, tetanus, hepatitis B [hepB] and Hib) should be administered to every child in the world, the Government of India asked the National Technical Advisory Group on Immunization (NTAGI) to study the need for HepB and Hib vaccines in the Indian population. The India Ministry of Health and Family Welfare introduced Pentavalent DTP vaccines in the UIP with the aim of reducing the burden of Hib-related morbidity and mortality.

Keywords: :

• meningitis
• pneumonia
• mortality
• disabilities
• vaccine

Pentavalent vaccine: Need to be incorporated in the vaccination program of India

In India, Hemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis among infants and young children and the second leading cause of bacterial pneumonia deaths among children under 5 y.¹ The overall case-fatality rate for Hib meningitis is 20–29% and nearly 30% of surviving children suffer from major disabilities, while all invasive Hib disease have a case fatality rate of 16% in India.^2-5

Hib pneumonia and meningitis in India may be more prevalent than previously thought. A large percentage of Indian children are at high risk of contracting Hib disease due to increasing antibiotic resistance as well as limited access to healthcare facilities. Watt et al. estimated the 2000 annual burden in India at ~2.4–3.0 million cases and 72,000 deaths in children under age five due to invasive Hib disease (which includes pneumonia and meningitis),^6,7 which accounted for ~4% of all deaths below 5 y of age.⁶ The incidence of pneumonia far exceeds that of meningitis, while the latter has a higher case-fatality rate. In 2008, Rudan et al. estimated that in India 43 million new cases of clinical pneumonia in children under age five occur each year and result in ~400,000 deaths.⁸ Using the estimates from the Hib study, ~215,000 new cases of Hib pneumonia occur annually in Indian children under age five and result in over 61,000 deaths.⁸

In India, poor access to health services and poor health-seeking behavior result in many affected children never being correctly diagnosed or receiving appropriate treatment.⁹ Due to lack of laboratory infrastructure, it is very difficult to diagnose Hib disease in affected children and to calculate disease burden. Even for those affected children who do reach facilities, the lack of quality services and increasing prevalence of antibiotic resistance make treatment difficult.^10,11

The global burden of Hib disease is substantial but vaccine-preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease mortality.¹² The 150 countries that have introduced Hib vaccine have reported a dramatic decline in the incidence of invasive disease and death. Hib vaccines were rapidly introduced in North America and western Europe, but only slowly in developing countries⁸ because of high cost, concerns about program sustainability, limited vaccine supply, and uncertainty about Hib disease burden.¹² Hib vaccine has nearly eliminated Hib disease in all developed and developing countries where it has been introduced (Uganda,¹³ Kenya,¹⁴); however, Hib disease continues to occur in countries that do not use Hib vaccines widely. It should be noted that all available Hib vaccines are Hib conjugate vaccines, in which the Hib capsular polysaccharide (CPs) is covalently linked (conjugated) to a carrier protein. This conjugation to protein enables the Hib CPs, which is non-immunogenic in very young children, to be immunogenic. Hib conjugate vaccines have been licensed for more than 20 y.

Morris and colleagues in a systematic review of the effectiveness of Hib vaccine demonstrated that Hib vaccines were highly effective in reducing the incidence of invasive Hib disease, with similar effectiveness seen across geographical regions and different levels of socioeconomic development.¹⁵

Even in countries with poor immunization coverage, indirect benefits of the vaccine have been reported due to the herd immunity effect. For instance, data from Gambia have shown the benefits of herd immunity even when vaccine coverage has been < 60%.¹⁶ The vaccine thus should be effective in India where UIP coverage is poor. After the WHO recommendation that pentavalent vaccine be administered to every child in the world, the Government of India asked the NTAGI to study the need for HepB and Hib vaccines in the Indian population. The NTAGI recommended to the Government of India in 2008 that Hib vaccine should be introduced in all states as early as feasible and under the UIP,⁷ and that since the poor are at most risk, it is imperative to incorporate this vaccine into routine immunization.

On the basis of these recommendations, the India Ministry of Health and Family Welfare in 2009 introduced Hib-containing Pentavalent DTP vaccines in the UIP with the aim of reducing the burden of Hib -related diseases.¹⁷ The decision was supported by the GAVI (Global Alliance for Vaccines and Immunizations), who in 2009 decided to provide funding of $165 million to the Government of India to support the introduction of Pentavalent vaccine.¹⁸ The vaccine was to be introduced in a phased manner. In the first phase, the vaccine would roll out in 10 states of India with the goal of vaccinating ~18 million infants.

Strategy for introduction of Pentavalent vaccine

Government of India has introduced Hib as Pentavalent vaccine combined with DTP and HepB, available in liquid form in 10-dose vials. The use of this combination formulation has certain clear programmatic advantages. First, the number of injections per completed schedule will be fewer, consequently requiring fewer syringes and generating less potentially hazardous sharps waste. Cold-chain space will be saved given that one vial of Pentavalent vaccine replaces three vials of individual vaccines. Pentavalent vaccine has been recommended for all infants and will be given in a 3-dose schedule. The first dose is given at 6 weeks of age or older, followed by dose-2 after a gap of at least 4 weeks, and dose-3 also after a gap of at least 4 weeks. The vaccine is offered to all children younger than 1 y of age; the booster dose is not recommended in UIP in India.^7,19

To ease program implementation, Government of India policy states that Pentavalent vaccine will be given to a progressive birth cohort whereby all children who present for their first dose of DTP (DTP1) will be provided their first dose of Pentavalent vaccine. Infants who had initiated their schedule of DTP + HepB will complete the DPT and HepB vaccine schedule. In addition, monovalent HepB vaccine will continue to be used for the at-birth-dose, and DTP vaccines will continue to be used for booster doses at 16–24 mo and 5–6 y of age.^7,19

The vaccine can be given in combination with DTP and HepB, thus not requiring a separate injection. Kerala and Tamil Nadu states (from December 2011) and Haryana state (from December 2012) have introduced Pentavalent vaccine into their UIP schedule.

The Government of India should introduce Pentavalent vaccine in the UIP of all the states as soon as possible.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.