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in the host-cell chemokine receptor CCR5, which reduces the risk of acquiring HIV infection after exposure (Sullivan et al., 2001). As another example, certain major histocompatibility complex class I molecules have been shown to reduce the risk of dying from HIV infection (Kaslow et al., 1996; Gao et al., 2001). Likewise, several different mutations or polymorphic systems influence the susceptibility to or likelihood of death from meningococcal infection (Read et al., 2000; Nadel et al., 1996; Westendorp et al., 1997). Numerous other examples exist of genetic associations with diseases, including cancers and chronic diseases, and the list is growing rapidly (Hill, 2001; Topcu et al., 2002; Chen et al., 2002a; Calhoun et al., 2002; Helminen et al., 2001; Pain et al., 2001).
Host susceptibility to infection is aggravated by malnutrition. A strong and consistent relationship has been found between childhood malnutrition and increased risk of death from diarrhea, acute respiratory infection, and possibly malaria (Rice et al., 2000). Conversely, infectious processes, especially those associated with diarrhea, drive malnutrition in young children (Mata, 1992; Mata et al., 1977), so that diarrheal illness is both a cause and an effect of malnutrition (Guerrant et al., 1992; Wierzba et al., 2001; Lima et al., 1992). Clinically, malnutrition is characterized by inadequate intake of protein, energy, and micronutrients and by frequent infections or disease (WHO, 2002d). Malnutrition has been associated with 50 percent of all deaths among children worldwide (Rice et al., 2000). In 2000, an estimated 150 million of the world’s children under age 5 were malnourished on the basis of low weight for age (WHO, 2002d). More than two-thirds (70 percent) of these children were in Asia, especially southern Asia. The number of malnourished children living in Africa—26 percent of the world’s malnourished children—has risen as a result of population growth in the region, as well as natural disasters, wars, civil disturbances, and population displacement (WHO, 2000b).
Malnutrition diminishes host resistance to infection through a number of mechanisms. Virtually all bodily processes and physical barriers that keep infectious agents from invading the host are affected. These include the skin, mucous membranes, gastric acidity, absorptive capacity, intestinal flora, cell-mediated immunity, phagocyte function, and cytokine production (Chandra, 1997; Levander, 1997). Although multiple-nutrient deficiencies are much more common than single-nutrient deficiencies, lack of even one vitamin or mineral (e.g., zinc; selenium; iron; copper; vitamins A, C, E, B-6, and folic acid) can impair the immune response. For example, vitamin A deficiency significantly increases the risk of severe illness and death from common childhood infections, such as diarrheal disease and