Women are particularly susceptible to malaria during first and second pregnancies, even though they may have developed immunity over years of residence in endemic areas. Plasmodium falciparum-infected red blood cells (IRBCs) were obtained from human placentas. These IRBCs bound to purified chondroitin sulfate A (CSA) but not to other extracellular matrix proteins or to other known IRBC receptors. IRBCs from nonpregnant donors did not bind to CSA. Placental IRBCs adhered to sections of fresh-frozen human placenta with an anatomic distribution similar to that of naturally infected placentas, and this adhesion was competitively inhibited by purified CSA. Thus, adhesion to CSA appears to select for a subpopulation of parasites that causes maternal malaria.

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There are still approximately 500 million cases of malaria and 1 million deaths from malaria each year. Yet recently, malaria incidence has been dramatically reduced in some parts of Africa by increasing deployment of antimosquito measures and new artemisinin-containing treatments, prompting renewed calls for global eradication. However, treatment and mosquito control currently depend on too few compounds and thus are vulnerable to the emergence of compound-resistant parasites and mosquitoes. As discussed in this Review, new drugs, vaccines, and insecticides, as well as improved surveillance methods, are research priorities. Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions.

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