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Haemophilus influenzae type B (HiB)

Haemophilus influenzae type b, or Hib, is a bacterium estimated to be responsible for some three million serious illnesses and an estimated 386 000 deaths per year, chiefly through meningitis and pneumonia. Almost all victims are children under the age of five, with those between four and 18 months of age especially vulnerable.

In developing countries, where the vast majority of Hib deaths occur, pneumonia accounts for a larger number of deaths than meningitis. However, Hib meningitis is also a serious problem in such countries with mortality rates several times higher than seen in developed countries; it leaves 15 to 35% of survivors with permanent disabilities such as mental retardation or deafness. Contrary to what the name Haemophilus influenzae suggests, the bacterium does not cause influenza.

The Hib dilemma

Hib is preventable — highly effective vaccines have been available since the early 1990s. Yet hundreds of thousands of children die year after year from Hib disease.

The two major obstacles to prevention of Hib disease are a shortage of information and a shortage of money. The information shortage is largely due to the difficulty of diagnosing Hib disease — it claims most of its victims without ever being recognized. In addition, Hib vaccine is more expensive than classic childhood vaccines — at the price offered to the world's lower income nations in 2005, it costs roughly seven times the total cost of vaccines against measles, polio, tuberculosis, diphtheria, tetanus, and pertussis.

Those two factors put many developing countries in a difficult situation. They want evidence of the extent and damage done by Hib before deciding whether to add a more costly vaccine to their infant immunization programmes. Developing countries may also need external funding assistance if they decide to provide vaccination against Hib.

The World Health Organization (WHO), recognizing these obstacles, recommends Hib vaccine "where resources permit its use and the burden of disease is established". Recent efforts by WHO and other international health organizations have included programmes to help countries determine the true disease burden posed by Hib and to help them devise ways to afford the vaccine.

Hib burden and vaccination in industrialized countries

Industrialized countries, with sophisticated health-surveillance systems, became aware of the threat posed by Hib as much as 50 years ago. Before immunization programmes began in the early 1990s, Hib was demonstrated to be the leading cause of childhood bacterial meningitis in nearly all countries in which appropriate studies were performed, including Australia, Canada, Finland, the Netherlands, Sweden and the United States of America. (The rate of Hib-caused pneumonia in developed countries was not clear, although it was considered to occur less often than meningitis — the opposite of the situation in the developing world). Systematic vaccination has now virtually eliminated Hib disease in industrialized nations.

Current vaccine coverage

Eighty-nine countries offered infant immunization against Hib by the end of 2004, with two of those countries providing it in parts of their territories. Ninety-two percent of the populations of developed countries was vaccinated against Hib as of 2003. The vaccination coverage was 42% for developing countries, and 8% for least-developed countries (the majority of which are in sub-Saharan Africa). The incidence of Hib in Southeast Asia has been a matter of debate, and vaccine use there is very low. Malaysia, the first Asian country to introduce the vaccine, began a regular Hib vaccination programme in 2002.

A hidden disease

Hib is commonly found in the noses and throats of healthy individuals living in regions where vaccination is not carried out. Almost all unvaccinated children are exposed to Hib by age five. The bacterium is spread by exhaled droplets. Occasionally, Hib can invade the bloodstream and cause infection and disease in other parts of the body, including the meninges (membranes enveloping the brain and spinal cord) leading to meningitis, and the lungs, causing pneumonia.

Unlike measles, polio or diphtheria, Hib does not cause a specific illness with which it, alone, can be identified. The most deadly forms of Hib infection include pneumonia and meningitis, but those diseases can have other causes, and can look the same whether caused by Hib or some other agent. More rarely, Hib is responsible for other life-threatening complications in young children, such as septic arthritis, an inflammation of the joints, and septicaemia, or blood poisoning, both of which also can have other causes. And it may lead to epiglottitis (a life-threatening inflammation of the flexible cartilage that covers the gap in the vocal cords during swallowing).

Doctors who are treating cases of childhood pneumonia or meningitis tend to respond quickly with antibiotics in an effort to save lives. To confirm a case of Hib, however, samples must be taken from an ill person — a blood specimen in the case of pneumonia, and a spinal-fluid specimen by lumbar puncture in the case of meningitis — and the bacteria must then be isolated from those specimens in a laboratory. That is a challenge even for sophisticated laboratories. In developing countries, such tests may not be made at all, or laboratories may fail to carry them out correctly, or Hib's presence may be masked because antibiotics were given before the samples were taken.

The hidden nature of Hib means its impact is often underestimated. Studies have shown a lack of awareness of Hib among medical professionals in some developing countries, or have shown that they associate Hib only with meningitis — when in fact Hib pneumonia occurs five times as frequently in such countries. In 2004, the Global Alliance for Vaccines and Immunization (GAVI) contended that the Hib disease burden is "not well understood."

Tools for assessing the incidence of Hib

Large, population-based disease burden studies showed rates of Hib meningitis at 20 to 60 cases per 100 000 children under five years of age in the United States (before immunization began); at 40 to 60 cases per 100 000 in sub-Saharan Africa; and at 10 to 40 per 100 000 in Latin America and Western Europe.

Most studies from Asia and Eastern Europe showed much lower rates — fewer than ten cases per 100 000. But studies based on the introduction of Hib vaccine into populations in Lombok, Indonesia, and Dhaka, Bangladesh, led a WHO panel of experts to conclude in 2004 that "in both studies, Hib meningitis incidence was greater than that which could be measured through surveillance for laboratory-confirmed cases." Meningitis statistics tend to be used in Hib surveys rather than pneumonia statistics because Hib meningitis is much more likely to be correctly diagnosed.

Vaccine-introduction studies have recently been found to be an effective method for estimating the burden of Hib disease. In these studies, Hib vaccine is administered to a population and the subsequent declines in meningitis and/or pneumonia cases are compared with the numbers of cases from before vaccination. Such studies have been carried out in Chile, Colombia, The Gambia, Indonesia, Uruguay and other countries. In the Gambia, the annual incidence of meningitis fell from more than 200 per 100 000 to 21 per 100 000 in 12 months, and the disease has now virtually disappeared. In Colombia, cases of acute bacterial meningitis fell by 40% in a year.

A "Rapid Assessment Tool" has been developed by WHO and the United States Centers for Disease Control and Prevention (CDC) to allow countries to make estimates of the extent of Hib disease by studying past hospital records, childhood mortality rates, or pneumonia mortality rates. This tool has worked well in many regions, but in order to adjust for differences in diagnostic patterns of Hib disease in Eastern Europe and Asia, WHO is now considering adapting or revising this tool for use in these parts of the world.


Treatment of Hib is through an intensive, sustained course of antibiotics, but this is not always accessible to poor populations in developing countries.

Resistance of Hib to several of the more inexpensive but effective antibiotics is a growing cause of concern and provides additional impetus for expanding vaccine coverage.

Vaccination regime and cost

Hib conjugate vaccines, given by intramuscular injection, are highly effective and have almost no side effects. Three doses are usually administered in infancy, starting at around age six weeks. In some countries, a booster dose is also offered between 12 and 18 months of age, although this might not be necessary in countries where Hib disease incidence is high in infancy, such as African or Latin American countries. Increasingly, Hib is administered as part of combination vaccines which can also include protection against diphtheria, tetanus, pertussis, and hepatitis B.

Hib vaccines, as provided to developing countries, currently cost around US$ 7 per child for the recommended three doses. (By contrast, full courses of each of six standard vaccines given to children in developing countries — against measles, polio, diphtheria, pertussis, tetanus, and tuberculosis — cost about US$ 1.)

Steps towards affordability

GAVI has unveiled a strategy to expand the coverage of Hib vaccines in the world's 75 poorest nations, focusing on external funding followed by a shift to financial sustainability within these countries after five years, most likely through shared arrangements between governments and long-term donors. In May 2005, GAVI awarded the Hib Initiative to a consortium including Johns Hopkins University (JHU), London School of Hygiene & Tropical Medicine (LSHTM), CDC and WHO. The Hib Initiative will provide countries with research and technical assistance to address and clarify the opportunity of introducing Hib vaccine.

What WHO is doing

In 1998, WHO noted that: "Wherever thorough studies have been performed, Hib has been shown to be an important cause of childhood meningitis and a major cause of bacterial pneumonia in children. In view of the demonstrated safety and efficacy of the Hib conjugate vaccines, Hib vaccine should be included, as appropriate to national capacities and priorities, in routine infant immunization programmes. In geographical regions where the burden of Hib disease is unclear, efforts should be made to evaluate the magnitude of this problem."

WHO is an active participant in the GAVI Hib Initiative that will assist countries in deciding if Hib vaccine introduction is a public health priority, and, if so, how to introduce the vaccine in a sustainable fashion.

The Global Immunization Vision and Strategy (GIVS), developed by WHO, UNICEF, and partners, has among its aims "strengthening the current immunization system so that it can maximally deliver currently available vaccines as well as under-utilized vaccines," including Hib. The GIVS also incorporates the GAVI goal of "50% of the poorest countries with high disease burdens and adequate delivery systems will have introduced Hib vaccine by 2005".

Sources: US Department of Health; The World Health Organization

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