Case 17--141-150 10/26/04 1:52 PM Page 141

17--Case 17--141-150 10/26/04 1:52 PM Page 141 CASE 17 Preventing Hib Disease in Chile and the Gambia Geographic Areas: Chile and the Gambia Health Condition: Researchers in Chile estimated that the incidence of Hib disease in Santiago during the late 1980s was 32 per 100,000 infants under 6 months of age, and 63 per 100,000 in infants aged 6 to 11 months. The proportion of children who died after contracting the disease was relatively high at 16 percent. In the Gambia, just over 200 children per 100,000 developed Hib meningitis in 1990. Global Importance of the Health Condition Today: Worldwide, Hib disease is the leading cause of bacterial meningitis in children under 5, and the second most common cause of bacterial pneumonia deaths in this age group. It kills an estimated 450,000 children every year and causes some 2 million cases of disease. Intervention or Program: Chile’s Ministry of Health introduced the Hib vaccine into the routine immunization program for babies in 1996. The Gambia began administering the vaccine routinely as part of the national immunization program in 1997. Cost and Cost-Effectiveness: The government of Chile has paid $3.39 million for the combined DTP-Hib vaccine, a figure that represents nearly 23 percent of the total immunization budget and 0.7 percent of the government health expenditure. In Chile, the price per dose is $3, and the government saves an estimated $78 for each case of Hib prevented. Aventis Pas- teur’s donation of the vaccines in The Gambia helped make the immunizations possible there, and financial support from the Global Alliance for Vaccines and Immunization has helped sustain the program through 2008. Impact: The incidence of Hib meningitis in Chile fell by 91 percent and that of pneumonia and other forms of Hib disease fell by 80 percent. The number of children developing Hib meningitis in The Gambia dropped almost tenfold, from 200 per 100,000 to 21 per 100,000 in the 12-month period after the start of routine immunization. In the last two years of the study, there were just two cases. Although it is a major cause of bacterial meningitis tis is particularly lethal, killing 20 to 40 percent of and pneumonia in young children worldwide (Ben- the children who get it and leaving as many as half nett et al. 2002), the microbe Haemophilus influen- of the survivors with some lasting impairment, such zae type b (Hib) has avoided the notoriety of other as deafness or mental retardation. major killers. Yet researchers have estimated that it is In principle, most of this disease and suffering is responsible for the deaths of some 450,000 people avoidable. Since the late 1980s, highly effective vac- worldwide, and at least 2 million cases of disease, cines against Hib have been licensed (see box 17.1). each year (Peltola 2000, WHO 2002). Hib meningi- Their impact in the industrialized countries, where they are widely available, has been dramatic. For ex- ample, in the United States, within four years of the The first draft of this case was prepared by Phyllida Brown. PREVENTING HIB DISEASE 141 17--Case 17--141-150 10/26/04 1:52 PM Page 142 that Hib vaccines have merely dented the global bur- Box 17.1 Conjugate vaccines den of this disease, reducing the estimated number of cases per year by less than 40,000 (Peltola 2000). Until the late 1980s the only available Hib vaccines were based on the polysaccharide, or sug- ary, capsule of the bacterium. These vaccines Basics of Hib protected older children and adults but not young infants, who were at greatest risk of infec- The vast majority of Hib infections are in children tion, because their immune systems did not re- under the age of 5. The age group at greatest risk spond well to the vaccines. The new generation of Hib meningitis globally is babies aged 6 to 11 months. In this group, the estimated annual inci- of conjugate vaccines contain two components: dence is 67 per 100,000 (Bennett et al. 2002). After the Hib polysaccharide capsule and, attached age 2, the risk of contracting Hib meningitis drops to it, a “carrier” protein antigen such as tetanus sharply. Overall, among children under 5, 23 per toxoid. This antigen stimulates a strong T-cell re- 100,000 develop Hib meningitis each year. lated immune response from the infant immune Infection patterns differ around the world; in system. Several Hib conjugate vaccines have sub-Saharan Africa the number of new cases in been licensed, including combinations with DTP infants up to 11 months old is around 200 for and DTP plus hepatitis B. every 100,000 infants, compared with some 60 per 100,000 in the Americas. Europe and Asia appear to have lower rates. Within each region, certain popula- tions appear to have exceptionally high risks of Hib initial licensing of conjugate vaccines in December infection, including Navajo Indians and Alaskan In- 1987, the number of young children diagnosed with dians in the United States and Australian Aborigines. Hib disease fell by 71 percent, with up to 16,000 On average, 14 percent of the children who de- cases of the disease prevented in 1991 alone (Adams velop Hib meningitis will die, a measure known as et al. 1993). Similarly, in the United Kingdom and the case fatality rate (Bennett et al. 2002).1 However, Finland, Hib immunization resulted in as steep or this global average for Hib meningitis masks sharp even steeper declines in the incidence of the disease differences between wealthy and poor countries in (Slack et al. 1998; Peltola, Kilpi, and Anttila 1992). children’s chances of surviving the disease. In industri- For most low- and middle-income countries, the alized countries, the case fatality rate is just 3.2 per- relatively high cost of Hib vaccines (up to $7.50 for cent, because virtually all children who develop three doses, compared with just a few cents for the meningitis have access to emergency and adequate basic vaccines such as diphtheria-tetanus-pertussis, medical treatment. In developing countries overall, or DTP) has kept them beyond reach (personal com- the case fatality rate is more than five times greater, at munication with S. Jarrett, UNICEF supply divi- about 17 percent. In sub-Saharan Africa, where a high sion, 2003). But, even with this cost, one study for proportion of children lack access to specialized med- the former Children’s Vaccine Initiative estimated ical treatment, more than one in four affected chil- that the Hib vaccine could be delivered as part of dren will die, a case fatality rate of about 28 percent routine immunization in sub-Saharan Africa for just (Bennett et al. 2002). For every child who develops $21 to $22 per life year saved (Miller and McCann Hib meningitis in a given year, researchers estimate, 2000). This makes it highly attractive to govern- about five children will develop Hib pneumonia, ments, given that anything costing less than $25 per life year saved is considered an excellent “buy.” How- ever, developing-country governments have been un- 1. This is similar to the overall case fatality rate for severe acute able to take advantage of the potential investment, respiratory syndrome (SARS), which the WHO (2003) estimates and because of this, one recent assessment concluded to be 15 percent. 142 MILLIONS SAVED 17--Case 17--141-150 10/26/04 1:52 PM Page 143 making it the most common reason for death among formation about the extent of the disease in Chile. those infected with this microbe. The researchers analyzed clinical and laboratory The long-term impact on survivors of the dis- records between 1985 and 1987 at all seven govern- ease is rarely taken into account in assessments of the ment hospitals in the Santiago area. They matched social and economic costs of Hib. In The Gambia, these data with census records to estimate the inci- only 55 percent of meningitis survivors fully recover; dence of Hib in the Santiago population of children the rest may experience learning disabilities, neuro- under 5, which was estimated at 500,000 at that logical problems, deafness, and other major health time. During the study period they identified 343 and social problems (Adegbola et al. 1999). And cases of laboratory-confirmed Hib disease, including treatment for Hib disease is becoming more compli- 242 cases of meningitis; the remainder were other cated with the spread of antibiotic-resistant strains of forms of invasive Hib disease—that is, Hib pneumo- the microbe. nia, Hib bacteremia, and other severe forms of the All figures are approximate, because Hib pneu- disease. The peak age for infection was between 6 monia is relatively difficult to diagnose. Usually doc- and 11 months, with the risk rapidly reducing after tors do not establish exactly which microbes are re- infants passed their first birthday. sponsible for a child’s pneumonia before treating it. At first glance, the figures suggested that the For this reason, also, case fatality rates for Hib pneu- incidence of Hib was only about half as high as in monia are more difficult to document than rates for infants in the United States at the same time. How- Hib meningitis. ever, there were strong reasons to believe that the Researchers base their estimates of the incidence figures underestimated the true extent of Hib disease of Hib pneumonia on what proportion of all pneu- in Chile. Dr. Rosanna Lagos, a pediatrician at the monia cases are prevented when Hib vaccines are Center for Vaccine Development in Santiago and an given.

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