(February 2006) Haemophilus influenzae type B (Hib) is a bacterium that causes severe pneumonia, meningitis, and other life-threatening conditions in children under age 5. The World Health Organization (WHO) estimates that Hib disease annually causes an estimated 3 million cases of serious illness and 400,000 deaths, most commonly from pneumonia.1 Children often carry Hib bacteria in the nose and throat without showing any signs of illness, and spread the bacteria to others through close contact, coughing, or sneezing.

A safe and effective vaccine to prevent Hib disease has been available for over 15 years. In more developed countries, where this vaccine is routinely used, Hib disease has been virtually eliminated. Similar results have been seen in less developed countries where the Hib vaccine has been introduced in routine childhood immunizations, such as The Gambia (see Figure 1).2


Figure 1
The Gambia Hib Vaccine Program Resulted in Virtual Disease Elimination

Gambia Hib Vaccine Program Resulted in Virtual Disease Elimination

Source: R.A. Adegbola et al., "Elimination of Haemophilus Influenzae Type B (Hib) Disease from The Gambia after the Introduction of Routine Immunization with a Hib Conjugate Vaccine: A Prospective Study," Lancet 366 (2005): 144-50.


But despite the availability of financing for Hib vaccination through the Global Alliance for Vaccines and Immunization (GAVI)—and despite evidence that the vaccine is safe and effective—most countries eligible for GAVI funding have not introduced the vaccine, largely because of information gaps, leaving almost three-quarters of the world's children at risk for Hib disease (see Figure 2).3


Figure 2
Global Status of Countries Using Hib Vaccine in Their National Immunization System, 2004

Global Status of Countries Using Hib Vaccine in Their </b><b>National Immunization System, 2004

Source: World Health Organization (WHO).


To reduce or eliminate this risk to children, a number of new initiatives have been targeted at decisionmakers.

Implications of Hib Disease

If diagnosed early enough, children with Hib-related illnesses can recover. However, most children with these illnesses—particularly those with meningitis and pneumonia—require hospitalization, which may be difficult in many developing countries that have limited access to hospitals or health care facilities.

And treating Hib-related illnesses in hospitals is often challenging because many children arrive for care in the late stage of their illness, and there are an increasing number of antibiotic-resistant infections associated with Hib. Resistant infections typically require more expensive antibiotics, which are not often available to poor children. (See "Antimicrobial Resistance Jeopardizes Medical Advancement")

Death rates for Hib meningitis patients hospitalized in developing countries are between 20 percent and 60 percent—several times higher than the death rates in more developed countries.4 For children who survive Hib meningitis, up to one-third may suffer lifelong disability—including deafness, mental retardation, paralysis, and learning disabilities.

In developing countries, the future for children with lifelong disabilities can be dim. The emotional and financial toll on families can be enormous. And if a child dies after hospitalization, the family may be left with bills that force them to cover the debt or seek loans at high interest rates, thus contributing to a household's downward spiral of poverty.

Challenges to Widespread Implementation of the Hib Vaccine

Detection. Uncertainty about the prevalence of Hib disease and the potential impact of the vaccine is the major obstacle to Hib vaccine decisions. Hib can be difficult to detect for a variety of reasons:

  • It is a fragile organism sensitive to the environment, and many developing country laboratories do not utilize the procedures needed to identify Hib.
  • Limited access to health care can also interfere with detection of Hib. In poorer regions of the world, children with Hib might never reach a hospital where they can be diagnosed and treated.
  • Inappropriate antibiotic use is widespread in some countries, and treatment with antibiotics prior to diagnosis makes it much more difficult to detect Hib.

Even when data are available, the prevalence of the most common form of Hib disease—pneumonia—remains underestimated. There are no sensitive diagnostic tests for Hib pneumonia, and at present, the only way to fully assess the burden of Hib pneumonia is to use the Hib vaccine as an assessment tool.

Vaccine impact (otherwise known as "vaccine probe") studies use mathematical modeling techniques to give an indirect estimate of disease prevalence: These techniques calculate how many cases of pneumonia, for example, were prevented following the administration of Hib vaccine. Although these studies are the best way to estimate the true burden of disease, they are not feasible to conduct in every country because of difficulty and expense.

Nonetheless, some vaccine impact studies have shown that Hib vaccine can significantly reduce disease burden. For instance, vaccine probe studies from The Gambia and Chile have shown that the vaccine reduced severe pneumonia in these countries by 21 percent and 22 percent, respectively.5 This indirect way of measuring disease burden has also demonstrated a higher prevalence of Hib disease than previously estimated using routine diagnostic tests. In many parts of the developing world, vaccine probe studies may be needed in select areas to help clarify the true disease burden.

Awareness. Full introduction of the Hib vaccine into national immunization programs faces several challenges. Challenges in detection and research limit awareness about Hib in some countries. When doctors, parents, and government officials are not aware that Hib is causing disease, they have little motivation to add Hib vaccine to a national immunization schedule. A concerted effort is needed to share information and experiences.

Supply and Cost. Even with strong data, uncertainties over vaccine supply and sustainable financing may also delay decisions regarding the introduction of Hib vaccine. The high cost of the vaccine is an important consideration in most low-income countries. While most countries are interested in combination vaccines, which can easily be integrated into existing programs, the addition of the Hib component alone can cost more than the entire cost of a routine vaccination program.

The current price for a combination vaccine that includes Hib has risen over the past several years to US $3.60 a dose for countries eligible for financing from GAVI, a public-private partnership that includes governments, vaccine manufacturers, nongovernmental organizations, research institutes, United Nations organizations, the World Bank, and the Bill & Melinda Gates Foundation. Currently, there is only one supplier of the preferred combination vaccine (known as DTP-Hep B-Hib), although additional suppliers and presentations of the vaccine are expected to be available soon.

New Initiatives

The significance of vaccines to the prevention of childhood mortality and disability has prompted significant international attention. GAVI has spearheaded the International Financing Facility for Immunization (IFFIm), a new vaccine-financing mechanism that will ensure a consistent and reliable supply of vaccine funding worldwide until 2015.6 Other initiatives include advance purchase contracts and additional financing options that address cost concerns in developing countries.

And the Hib Initiative, a global consortium of academic and public health experts, has received a $37 million grant from GAVI to help expedite evidence-based decisionmaking regarding the use of the Hib vaccine. The Hib Initiative provides a much-needed focus on national-level decisions about vaccination through:

  • Strategic coordination among partners and donors to ensure all parties understand the urgency of addressing Hib;
  • Support for studies to measure disease burden and the impact of financial decisions in saving lives; and
  • Rapid information dissemination of research results to decisionmakers.7

The GAVI $37 million grant supports a four-year project that will focus on two sets of countries where the disease burden is clear: those that have already introduced the vaccine (such as Kenya and Ghana) but need further support for decisions regarding continued use; and those (such as Tanzania) that have yet to make the decision to introduce the vaccine but where regional Hib disease burden is clear.8

Where the disease burden is unclear, the Hib Initiative is collaborating with governments and researchers to further define the scope of the disease. One example of such a project is a collaboration among the Indian government and local researchers in three sites to define the burden of Hib disease in India. It is expected that this project will help support decisions on Hib vaccination programs throughout South Asia.

"We are looking forward to really making a difference in the poorer countries," says Dr. Rana Hajjeh, project director for the initiative. "With additional focus on Hib and added expertise that our team will provide, countries will be able to expedite decisions about routine use of Hib vaccine based on evidence. These decisions in turn can have an almost immediate impact on saving children's lives and reducing suffering."


Lois Privor-Dumm is director of communications strategy for the Hib Initiative at the Johns Hopkins University Bloomberg School of Public Health.


References

  1. World Health Organization (WHO), "Vaccines and Biologicals," accessed online at www.who.int/vaccines, on Nov. 3, 2005. Haemophilus influenzae is not related to influenza.
  2. R.A. Adegbola et al., "Elimination of Haemophilus Influenzae Type B (Hib) Disease from The Gambia after the Introduction of Routine Immunization with a Hib Conjugate Vaccine: A Prospective Study," Lancet 366 (2005): 144-50.
  3. The three-quarters figure is calculated based on UN Population Division 2002 national population estimates and Hib vaccine usage by country as of November 2004 from the WHO IVB database.
  4. H.A. Bijlmer, "World-wide Epidemiology of Haemophilus influenzae Meningitis: Industrialized versus Non-industrialized Countries," Vaccine 9, Supplement (1991): S5-9.
  5. For the Gambian study, see Kim Mulholland et al., "Randomised Trial of Haemophilus Influenzae Type-b Tetanus Protein Conjugate Vaccine for Prevention of Pneumonia and Meningitis in Gambian Infants," Lancet 349, no. 9060 (1997): 1191-97. For the Chilean study, see Orin S. Levine et al., "Defining the Burden of Pneumonia in Children Preventable by Vaccination Against Haemophilus Influenzae Type B," Pediatric Infectious Diseases Journal 18, no. 12 (1999): 1060-64.
  6. FFIm raises funds by borrowing against a $4 billion long-term, legally binding commitment from the U.K., France, Italy, Spain, Sweden, and Norway. These monies will also be used to extend funding for countries already receiving GAVI funds for Hib vaccine, but these countries will be required to develop a plan for an increasing portion of country contributions until the vaccine price reaches a target of US $1.85 in 2015. Should the price of vaccine still be higher than that amount by 2015, GAVI will bear the additional risk.
  7. Further information on the Hib Initiative can be found at www.HibAction.org.
  8. John V. Bennett et al., "Vaccines and Biologicals: Haemophilus Influenzae Type B (Hib) Meningitis in the Pre-vaccine Era: A Global Review of Incidence, Age Distributions, and Case-fatality Rates" (Geneva: WHO, 2002), accessed online at www.who.int/vaccines-documents, on Jan. 20, 2006.