HIV's Challenge to Measles Control

Scott et al. [1] have investigated an important and challenging aspect of the continuingly increasing efforts to reduce global measles-associated morbidity and mortality. What are the factors that may accelerate receptivity to attenuated measles virus vaccine by HIV-infected infants and thereby reduce their early susceptibility to “wild-type” measles virus? In early 2001, the American Red Cross initiated a program that developed a collaboration of the International Red Cross and Red Crescents, the World Health Organization, the United Nations Children's Fund, the United Nations Foundation, the Centers for Disease Control and Prevention, and, later, the Church of Latter Day Saints, the Canadian International Development Agency, and the Gates Foundation. As Rotary International had accepted the challenge of global polio eradication, the Red Cross chose to focus on measles. Before a vaccine was available, the World Health Organization estimated that nearly 8 million children died each year as a result of measles and its complications. Although a vaccine had been available for 38 years when the Red Cross program was launched in early 2001, it was estimated that there were still nearly 900,000 measles-associated deaths annually. The initial goal of this consortium, now identified as the Measles Initiative, or Measles Partnership, was to reduce measles-associated mortality by 50% by 2005 [2]. Indeed, the consortium exceeded their goal with the vaccination of >360 million children in sub-Saharan Africa from 2001 through 2005, resulting in a 60% reduction of deaths, to 345,000, from the previously calculated 873,000. In Africa, it is estimated that 506,000 deaths had been reduced to 126,000 [2]. In addition to measles vaccination, the campaigns of the consortium have provided polio vaccine, tetanus toxoid (to women of childbearing age), antihelminthics, vitamin A, oral rehydration solution, soap, and insecticide-treated bed nets. Their next expressed goal is a global 90% reduction in measles-associated mortality by 2010. Preliminary data suggest they may have already achieved an 85% reduction by the end of 2006 (E. Hoekstra, personal communication). Lurking in the background of these successes have been the issues studied by Scott et al. [1] regarding the optimal time of administration of measles vaccination for an initial response and, hopefully, prolonged effective protection against measles for HIV-infected infants and children. Results of studies of HIV infection among women at prenatal clinics in Africa reveal infection rates that range from 3% (in Democratic Republic of Congo) to 40% (in Swaziland) (C. Wilfert, personal communication). Scott et al. [1] revealed that, in Zambia, the levels of transplacentally acquired maternal antimeasles antibodies in HIV-infected infants were lower than those in HIV-seronegative infants and that such antibodies were catabolized more rapidly; thus, infants could be successfully immunized as early as 6 months of age instead of the usual 9–12 months of age. A corollary, of course, is that this same decrease in maternal antibody levels renders infants susceptible to “wild-type” measles virus, with a high risk of morbidity and mortality at an earlier age. Other studies have demonstrated that, after vaccination, there is a lower titer of measles virus neutralizing antibodies in HIV-infected children than in HIV-uninfected children, and these antibodies are detectable in a smaller percentage of HIV-infected children, compared with HIV-uninfected. Although the results of these antibody studies are worrisome, it is important to remember that determination of cell-mediated immunity may be more critical than determination of antibody levels to an evaluation of the containment of the replication of transmitted measles viruses. The solution to these problems could be earlier administration of measles vaccine to infants infected by or exposed to HIV intra partum or in utero. However, facilities to identify these early susceptibilities currently defy implementation in the regions where the problems exists. Screening of newborns routinely for antibody to HIV (or any other neonatal assay) is rarely available or feasible at this time. Another concern that has yet to be answered is whether immunocompromised, HIV-infected infants who receive measles vaccine may suffer any adverse events as a result of the possible persistence and later replication of the attenuated virus. To date, there have been no data indicating serious short-term or long-term complications among recipients of vaccine in the Measles Initiative, but the observations in these large-scale programs provide only short-term (⩽30-day) surveillance, whereas a vaccine virus-induced giant cell pneumonia or CNS pathologic characteristic might not manifest for many months or even years. However, in the United States and other more affluent nations, where widespread administration of measles vaccine has nearly eliminated natural infection, only 2 cases of such serious ill effects of vaccine have been observed and reported in HIV-infected individuals over the years, despite the vaccination of hundreds of millions of infants and children, several thousand of whom were infected with HIV. The Measles Initiative is now extending its focus to Southeast Asia, where measles remains a killer among children in India, Pakistan, and neighboring nations. India alone, with an annual birth cohort of 27 million, poses major challenges for the development and implementation of measles vaccination programs that aim to achieve 95% coverage. It is estimated that currently, only 59% of Indian children receive measles vaccine and that annually, nearly 160,000 deaths due to measles and its complications occur among Indian children. Less than 1% of the Indian population are said to be HIV infected; therefore, these statistics may be of somewhat less concern. However, the lessons learned in sub-Saharan Africa of program development and implementation will be critical to the anticipated initiation and conduct of nationwide measles vaccination in Southeast Asia. Potential conflicts of interest. S.L.K.: no conflicts.

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