11 : The Resurgence of Malaria

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In the 20th century, there have been three major stages in the understanding of malaria: (i) a period of discovery, beginning in the late 19th century, which defined the parasite life cycle and identified the parasites that infect humans; (ii) a worldwide malaria eradication program, based on massive use of chloroquine (CQ) and dichlorodiphenyltrichloroethane (DDT), which began in the 1950s and continued for 20 years until it was acknowledged as a failure in the 1970s; and (iii) an era of active scientific investigation that began with development of the in vitro culture system for and permitted the application of advances in molecular biology, cell biology, and immunology to malaria in the 1980s and 1990s. This chapter begins by reviewing these three stages. It then examines the biologic and public health reasons that malaria remains a major problem in Southeast Asia, South America, and sub-Saharan Africa at a time when it has been possible to eradicate or control smallpox, polio, yellow fever, and guinea worm (dracunculiasis). The chapter concludes by examining the global impact of increasing resistance to antimalarials and by highlighting recent works which may permit the development of long-term strategies for successful malaria control. The resurgence of malaria is likely to continue for at least the next 3 to 5 years.

Citation: Tsai Y, Krogstad D. 1998. The Resurgence of Malaria, p 195-212. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 2. ASM Press, Washington, DC. doi: 10.1128/9781555816957.ch11
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Figure 1

Malaria parasite life cycle. Sporozoites released from the salivary gland of the female anopheles mosquito are injected under the skin when the mosquito bites a human (step 1). They then travel through the bloodstream to the liver and enter hepalocytes ( ). Within hepalocytes. parasites mature to tissue schizonts ( ). They are then released into the bloodstream as merozoites ( ) and produce symptomatic infection as they invade and destroy RBCs (6 to II). However, some parasites remain dormant in the liver as hypnozoites (2, dashed line from I to 3). These parasites (in infections) cause relapsing malaria when they mature and produce merozoites 6 to 11 months or more later. Once within the bloodstream, merozoites ( ) invade RBCs ( ), and mature to ring ( ), trophozoite ( ) and schizont ( ) asexual-stage parasites, Schizonts lyse their host RBCs as they complete their maturation and release the next generation of merozoites ( ), which then invade previously uninfected RBCs. Within RBCs, some parasites differentiate to sexual forms (male and female gametocytes) ( ). When gametocyles are taken up by a female anopheles mosquito, the male gametocyte loses its flagellum to produce male gametes which fertilize the female gamete ( ) to produce a zygote ( ). The zygote invades the gut of the mosquito ( ) and develops into an oocyst ( ). Mature oocysts produce sporozoites, which migrate to the salivary gland of the mosquito ( ) and repeat the cycle. The dashed line between 12 and 13 indicates that absence of the mosquito vector precludes natural (mosquito-borne) transmission via this cycle. Note, however, that the injection of infected blood bypasses this constraint and permits transmission among intravenous drug addicts and to persons who receive blood transfusions from infected donors. (Reproduced from reference 53a with permission from Williams and Wilkins.)

Citation: Tsai Y, Krogstad D. 1998. The Resurgence of Malaria, p 195-212. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 2. ASM Press, Washington, DC. doi: 10.1128/9781555816957.ch11
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Table 1

Criteria that favor disease eradication relative to malaria

Citation: Tsai Y, Krogstad D. 1998. The Resurgence of Malaria, p 195-212. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 2. ASM Press, Washington, DC. doi: 10.1128/9781555816957.ch11
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Table 2

Ligands and receptors involved in parasite entry and cytoadherence in humans

Citation: Tsai Y, Krogstad D. 1998. The Resurgence of Malaria, p 195-212. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 2. ASM Press, Washington, DC. doi: 10.1128/9781555816957.ch11
Generic image for table
Table 3

Global heterogeneity of malaria

Citation: Tsai Y, Krogstad D. 1998. The Resurgence of Malaria, p 195-212. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 2. ASM Press, Washington, DC. doi: 10.1128/9781555816957.ch11
Generic image for table
Table 4

Reasons for the resurgence of malaria

Citation: Tsai Y, Krogstad D. 1998. The Resurgence of Malaria, p 195-212. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 2. ASM Press, Washington, DC. doi: 10.1128/9781555816957.ch11

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