Infectious disease remains one of the biggest killers in developingcountries. Two of them account for an enormous toll: Elevenmillion people live with tuberculosis (TB), and almost 250 millioncases of malaria—and roughly a million deaths among children—were reported in 2008; a staggering assault on human-kind. The 33 million people who live with HIV/AIDS are frequently co-infected with TB and/or malaria, and co-infection increases the overall risk of mortality and morbidity from all three diseases. Once, we aspired to find "magic bullet" solutions to these plaguesusing vaccines or drugs, but we have learned that there are no cure-all or simple solutions. These pathogens have complexrepertoires of genetic resources that permit them to constantlyreinvent themselves and escape the pressures applied by infection-control measures. To curb these elusive targets, we, too, need a large repertoire of tools.
In this special issue of Science, two pairs of Reviews investigatethe variety of cell, molecular, and epidemiological researchstrategies currently being used to understand and control malaria and TB. Kappe et al. (p. 862) describe aspects of the basic biology of malaria infection and how understanding it might someday contribute to the ambitious goal of eradication. Mackinnon and Marsh (p. 866) focus on the constantly shifting selective pressures acting on the most lethal form of the malaria parasite, Plasmodium falciparum. Russell et al. (p. 852) explore the basic biology of Mycobacterium tuberculosis, the infectious agentresponsible for TB, and highlight the gaps in knowledge that hamper the ability to successfully treat the disease. Dye and Williams (p. 856) explore the population dynamics of TB at a time when, despite much success in providing effective therapy, disease burden remains enormous and highly drug-resistant strains are emerging.
The News section focuses exclusively on malaria, chronicling the remarkable successes in malaria control in Africa in the past few years and the huge remaining challenges (p. 842). These gains are in jeopardy, however, from resistance to artemisinin-based combination therapies, the gold standard of malaria treatment, which is emerging on the Thai-Cambodian border sooner than anyone expected (p. 844). Another piece examines how the research agenda has changed since Bill and Melinda Gates uttered the "E" word, eradication, in October 2007 (p. 843). High on this new agenda are transmission-blocking vaccines that can neutralize a mosquito's ability to pass on the disease (p. 847). Also, since the Gateses'call, a number of countries that have malaria relatively under control have declared their intent to eliminate the disease within their borders, a challenge whose difficulties and costs should not be underestimated (p. 849). The island of Hispaniola, which Haiti and the Dominican Republic uneasily share, provides a striking example (p. 850).
In a related Editorial, Bloom discusses the need for the United States to continue its investment in the Global Fund to Fight AIDS, Tuberculosis, and Malaria. In the end, it will be careful, well-funded R&D, combined with political will and strong health care systems, that will help to lessen the impact of these terrible diseases of poverty.
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