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Chapter 50 : Malaria: Clinical and Epidemiological Aspects
Category: Immunology; Clinical Microbiology
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The cycle of invasion, multiplication, and reinvasion takes place over 48 hours for P. falciparum, P. vivax, and P. ovale; 72 hours for P. malariae; and 24 hours for P. knowlesi. Although some degree of anemia resulting from hemolysis of infected red blood cells is an expected consequence of symptomatic malaria infections, the pathogenesis of severe malarial anemia, seen most commonly in P. falciparum disease, and also present withP. vivax, is multifactorial. Malaria during pregnancy also carries a risk of adverse birth outcomes such as spontaneous abortion, stillbirth, and premature birth or intrauterine growth restriction, both of which contribute to low birth weight, which is the single most important indicator of infant mortality. With the recent call for malaria elimination, more tools, including vaccines, can be anticipated in the near future. Host genetic factors that play important roles in malaria risk and epidemiology are summarized in this chapter. The new goal of using vaccines for malaria elimination places an increased emphasis on vaccines that would completely prevent infection and thus transmission by targeting the pre-erythrocytic stages of the parasite life cycle or block transmission directly by generating immunity against the sexual and mosquito stages. Most malaria vaccines are based on recombinant versions of antigenic targets from specific stages of the parasite life cycle, although DNA vaccines and viral vector expression approaches have been used with limited success to date. The most advanced malaria vaccine is based on the circum sporozoite protein that coats the surface of the infectious sporozoites.
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Scanning electron micrographs showing a normal uninfected erythrocyte (top), a Plasmodium falciparum trophozoite-infected erythrocyte with knobs expressing cytoadherent P. falciparum erythrocyte membrane protein-1 (center), and abnormally large and widely separated knobs on a similarly parasitized erythrocyte from an individual with hemoglobin AC, which is associated with protection from severe malaria (bottom). Reprinted by kind permission from the author and Macmillan Publishers Ltd.: Nature 435:1119, copyright 2005.
Schematic representation of infection, disease, and death rates by transmission intensity. Protective immunity to malaria is acquired more rapidly in high and moderate transmission areas than in low transmission areas, and disease patterns also vary with transmission intensity. (A) In high transmission areas (entomological inoculation rate [EIR] >100 infected mosquito bites per person per year), the incidence of uncomplicated malaria falls rapidly after childhood despite the high prevalence of asymptomatic parasitemia. Severe anemia occurs in the youngest children, while cerebral malaria is less common and occurs in slightly older children, reflecting the contribution of acquired immunity to pathogenesis of this syndrome. (B) In areas of low but stable transmission (EIR = 1-10), the incidence of uncomplicated malaria declines later and more slowly than in higher transmission settings, and the prevalence of asymptomatic parasitemia also declines with age. Severe anemia and cerebral malaria are equally common, with cerebral malaria again occurring in slightly older children. (C) In areas of unstable or epidemic malaria transmission (e.g., EIR < 1 and R0 < 1), asymptomatic infection rates are low, but people of all ages remain susceptible to both uncomplicated and severe disease. Severe anemia remains limited mainly to young children but the risk of cerebral malaria extends into adulthood and is compounded by risk of multiorgan disease in adults. Adapted from Immunological Reviews ( Struik & Riley, 2004 ) with kind permission of the author and John Wiley & Sons, Inc.
Age distribution of hospital admissions with severe malaria and case-fatality rate at various altitudes in Tanzania, showing concentration of severe disease in younger age groups in lowaltitude areas with higher malaria transmission and relatively stronger and more rapidly acquired natural immunity. At higher altitudes, there is less malaria transmission, less immunity, and an extension of disease risk into older age groups. Adapted with kind permission of the author and the publisher from the Journal of the American Medical Association, 2005, 293:1465. Copyright © 2005 American Medical Association. All rights reserved.