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PUBLIC HEALTH New Vaccines Could Balance Global Burden of Disease In providing for the public's health, a program often depends as much on political will as scientific capability. Among infectious and parasitic diseases, for example, HIV/AIDS, tuberculosis, and malaria are the leading causes of death and disability in the world. There is increasing confidence in the scientific community that these diseases can be controlled by vaccination. But vaccines cannot reach the people who need them most without cooperation between wealthy nations with the resources to develop these vaccines and poor nations with the bulk of the patients. In a recent JAMA, Barry Bloom and colleagues describe the most promising approaches to developing vaccines against HIV, TB, and the malaria parasite, the leading causes of death and disability in the world among infectious and parasitic diseases. Photo by Steve Gilbert In two articles in the Feb. 7 Journal of the American Medical Association, HSPH dean Barry Bloom and colleagues describe the most promising approaches to vaccine development and encourage an international effort for testing and distribution. The JAMA issue, with contributions from many Harvard authors, explores opportunities for medical research in the 21st century. Modern Plagues Despite success against other pathogens, vaccines have little to show against the AIDS virus, TB bacterium, and malaria parasite, which kill more than 5 million people worldwide every year. TB incidence and death is boosted by the rise of multidrug-resistant strains and by immunosuppression caused by HIV. Malaria has found ways to compete more successfully, too. The disease-causing parasite Plasmodium falciparum has developed drug resistance, and its carrier, the Anopheles mosquito, has built up a resistance to insecticides. Aggravating the problem are the relocation of nonimmune refugees to regions where malaria is endemic and a population jump in the malarial zone south of the Sahara. "AIDS, TB, and malaria are more severe problems in poor countries than in affluent ones, and these diseases have not received an investment in research dollars commensurate with their importance," write Bloom; Norman Letvin, HMS professor of medicine at Beth Israel Deaconess; and Stephen Hoffman, of the Naval Medical Research Center, in a paper on vaccine prospects. It's hard to dismiss the numbers involved. Citing U.N. statistics, the authors say that 35.8 percent of the adult population in Botswana is infected with HIV, and in South Africa, the figure is 19.9 percent. These are just two of 16 countries with more than one tenth of their population aged 15 to 49 infected. "HIV can only be controlled worldwide by development of an effective vaccine," the authors say. Though TB and malaria cut narrower swaths, a vaccine offensive to reduce their incidence is similarly attractive. A primary strategy against HIV—to provoke multiple arms of the immune system—appears to be equally promising for the other two diseases. To-do List In the case of HIV, researchers have shown that during initial infection, CD8 cytotoxic T lymphocytes limit viral replication, keeping clinical disease at bay. Linked to replication control is the activity of HIV-specific CD4 T lymphocytes. According to the authors, an effective HIV vaccine should elicit both the virus-specific CD8s and CD4s. It would also be ideal to develop neutralizing antibodies to block infection. Vaccine strategies to achieve these functions are the subject of ongoing investigations. Other methods combine two different strategies to simultaneously prime and boost the immune system, such as stimulating a cytotoxic T cell response and augmenting it with a T cell growth factor. (See AIDS Vaccine, Focus, April 21, 2000.) Vaccines that provoke a cytotoxic T cell offensive and that may exploit complementary immune strategies might be used against TB and malaria as well as HIV. The authors believe that these scientific challenges can be met in the coming decades, but a worldwide commitment is needed. In a companion paper on the global burden of disease, Bloom, Catherine Michaud, of the Harvard Center for Population and Development Studies, and Christopher Murray, HSPH professor of international health economics at the center, argue that health care resources should be allocated more equitably across nations, which would help both rich and poor since disease is blind to national boundaries. They write: "An increase in investments by the United States and other developed nations on major causes of burden of diseases that disproportionately affect the poor worldwide—HIV, tuberculosis, and malaria—is justifiable both on humanitarian grounds and also in the enlightened self-interest of people in these developed countries." —Robert Neal