Immunoprophylaxis

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Shortly after the recognition of sulfonamide-resistant meningococci, and the obvious implications for prevention of secondary cases through chemoprophylaxis, efforts to develop immunogenic vaccines against the major meningo-coccal serogroups intensified.132 While immunity is variable following vaccination, no current commercially available meningococcal polysaccharide vaccine is immunogenic in children under 24 months of age and therefore chemopro-phylaxis is a primary strategy in day-care centers. Conjugate vaccines are urgently needed (see later discussion). Large-scale studies have clearly documented the immunogenicity and protective efficacy of vaccines against serogroups A and C meningococci. The use of these vaccines in developing countries has markedly increased in recent years, as discussed in the following sections.

immunization has never been recommended with these vaccines135-138 and their primary use has been in emergency campaigns.139

For maximum efficacy, emergency mass immunization of populations at risk requires early recognition of the outbreak and rapid mobilization of immunization. Thus, markers of outbreaks are critically needed at the local level quickly. Moore and colleagues140 evaluated the pattern of meningococcal epidemics in Burkina Faso and found that 2 consecutive weeks of 15 cases per 100,000 population was a good early predictor of a major outbreak and could be used to trigger immunization. As shown in Figure 25-9, mass immunization of a population in Nairobi, Kenya, prevented a large number of cases, but many more cases could have been prevented if immunization had been started earlier. This concept has now been integrated into an emergency response plan by the World Health Organization (WHO), which outlines necessary steps to accurately identify and respond to outbreaks.139 Even with accurate detection and rapid response, however, it is estimated that only about 60% of outbreak-related cases can be prevented by this strategy. Prevention of additional cases, and ultimate prevention of outbreaks altogether, require more effective vaccines.

Following the example provided by the H. influenzae type b conjugate vaccines, preparations of serogroup A, C, or W-135 polysaccharide chemically conjugated to proteins have been evaluated in clinical trials.141-144 Conceptually, the conjugated product will perform as a T cell dependent antigen, which induces larger immune responses in infants, primes immuno-logic memory, and can lead to booster responses with subsequent doses. The introduction of similar conjugated vaccines into routine immunization programs in Africa appears to be the only effective way to prevent future epidemics. Indeed, this approach has already proven feasible. Chemoprophylaxis is impractical in resource-limited settings (e.g., the sub-Saharan meningitis belt) to control meningococcal disease. The first major worldwide epidemic of serogroup W-135 disease followed the hajj (the annual pilgrimage of Muslims to Mecca) in 2000 and spread throughout areas of Africa (e.g., Burkina Faso) and Europe through 2002. A conjugate vaccine, developed and deployed rapidly against serogroups A, W-135, and C produced a dramatic decline in cases during 2003 to 2004.

The meningococcal vaccine project, a collaboration of the WHO, CHI/Path, and the Gates Foundation, with a new manufacturer (the Serum Institute of India) is on target to produce a cheap (approximately 40i/dose) serogroup A meningococcal conjugate vaccine by 2009. The goal is to target high-risk groups, ages 1 to 29 years, in 18 countries, a total population of approximately 270 million.

Serogroup A

Gotschlich and coworkers133 conclusively demonstrated the protective activity of bactericidal antibody against capsular polysaccharide. Serogroup A polysaccharide vaccines seem to be immunogenic in older children and adults, but are unreliable in children less than 2 years of age. In addition, protection from a single dose is limited to less than 3 years in children who receive the vaccine between the ages of 1 and 4 years.27,134 In older children, efficacy declines slowly over 3 years but long-term duration has not been studied. Thus, routine infant

Serogroup C

The serogroup C polysaccharide vaccine shares many of the characteristics of the serogroup A polysaccharide vaccine (in the United States, the only licensed meningococcal vaccine is a combination of serogroups A, C, Y, and W-135 antigens, but monovalent A, monovalent C, and bivalent A-C are available in other areas). Again, the serogroup C vaccine is not effective in children less than 2 years of age.129 In addition, 7 to 10 days is required following immunization to reach appreciable antibody levels, so rapid immunization is essential to maximize

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