Causes, Epidemiology, Manifestations, and Diagnosis
Four species of the genus Plasmodium cause malarial infections in humans: P. falciparum, P. vivax, P. ovale, and P. malariae. Virtually all deaths are caused by falciparum malaria. Human infection begins when the malaria vector, a female anopheline mosquito, inoculates plasmodial sporozoites from its salivary gland into humans during a blood meal. The sporozoites mature in the liver and are released into the bloodstream as merozoites. These invade red blood cells, causing malaria fevers. Some forms of the parasites (gametocytes) are ingested by anopheline mosquitoes during feeding and develop into sporozoites, restarting the cycle.
P. falciparum predominates in Haiti, Papua New Guinea, and Sub-Saharan Africa, while P. vivax is more common in Central America and the Indian subcontinent and causes more than 80 million clinical episodes of illness yearly (Mendis and others 2001). The prevalence of these two species is approximately equal in the Indian subcontinent, eastern Asia, Oceania, and South America. P. malariae is found in most endemic areas, especially throughout Sub-Saharan Africa, but is much less common than the other species. P. ovale is unusual outside Africa, and where it is found accounts for less than 1 percent of isolates.
While more than 40 anophelines can transmit malaria, the most effective are those such as Anopheles gambiae, which are long-lived, occur in high densities in tropical climates, breed readily, and bite humans in preference to other animals. The entomological inoculation rate (EIR)—that is, the number of sporozoite-positive mosquito bites per person per year—is the most useful measure of malarial transmission and varies from less than 1 in some parts of Latin America and Southeast Asia to more than 300 in parts of tropical Africa.
The epidemiology of malaria may vary considerably within relatively small geographic areas. In tropical Africa or coastal Papua New Guinea, with P. falciparum transmission, more than one human bite per infected mosquito can occur per day and people are infected repeatedly throughout their lives. In such areas, morbidity and mortality during early childhood are considerable. For survivors, some immunity against disease develops in these areas, and by adulthood, most malarial infections are asymptomatic. This situation, with frequent, intense, year-round transmission, is termed stable malaria. In areas where transmission is low, erratic, or focal, full protective immunity is not acquired and symptomatic disease may occur at all ages. This situation is termed unstable malaria. An epidemic or complex emergency can develop when changes in environmental, economic, or social conditions occur, such as heavy rains following drought or migrations of refugees or workers from a nonmalarious to an endemic region. A breakdown in malaria control and prevention services intensifies epidemic conditions. Epidemics occur most often in areas with unstable malaria, such as Ethiopia, northern India, Madagascar, Sri Lanka, and southern Africa. Many other African countries situated in the Sahelian and Sub-Saharan areas are susceptible to epidemics (Djimde and others 2004; Worrall, Rietveld, and Delacollette 2004). Public health specialists have only recently begun to appreciate the considerable contribution of urban malaria, with up to 28 percent of the burden in Africa occurring in rapidly growing urban centers (Keiser and others 2004).
The determinants of malaria and of risk factors for patients and communities relate to intrinsic (human, parasite, and vector) and extrinsic (environmental, control, and socioeconomic) factors (figure 21.1)(Breman 2001). Both humoral and cellular immunity are necessary for protection.
[Figure
21.1]
Anemia may be quite common among young children living in areas with stable transmission, particularly where the parasite is resistant to chloroquine, sulfadoxine-pyrimethamine (SP), or other drugs. Correctly and promptly treated, uncomplicated falciparum malaria has a mortality rate of approximately 0.1 percent (Sudre and others 1992). Once vital organ dysfunction occurs or the proportion of erythrocytes infected increases to more than 3 percent, mortality rises steeply. Coma is a characteristic and ominous feature of falciparum malaria, and despite treatment it is associated with death rates of some 20 percent among adults and 15 percent among children. Convulsions, usually generalized and often repeated, occur in up to 50 percent of children with cerebral malaria (CM) (Mung'Ala-Odera, Snow, and Newton 2004). Whereas less than 3 percent of adults suffer neurological sequelae, roughly 10 to 15 percent of children surviving CM—especially those with hypoglycemia, severe malarial anemia (SMA), repeated seizures, and deep coma—have some residual neurological deficit when they regain consciousness. Protein-calorie under-nutrition and micronutrient deficiencies, particularly zinc and vitamin A, contribute substantially to the malaria burden (Caulfield, Richard, and Black 2004).
In areas with intense and stable transmission, falciparum malaria in primigravid and secundigravid women is associated with low birthweight (average reduction of about 170 grams) and consequently with increased infant and childhood mortality (Steketee and others 2001). HIV infection predisposes all pregnant women to more frequent and severe malaria, and the reverse may also be true (Ter Kuile and others 2004). P. vivax malaria in pregnancy is also associated with a reduction in birthweight (average reduction of some 100 grams), and this effect is greater in multigravid than in primigravid women (Nosten and others 1999).
The confirmatory diagnosis of clinical malaria rests on the microscopic demonstration of asexual forms of the parasite in stained peripheral blood smears. Newer diagnostic tests using antigen and nucleic acid detection methods are being evaluated. These tests are promising, but their limitations in relation to species sensitivity (except for P. falciparum), parasite quantitation, field feasibility, and costs necessitate further development and evaluation (Warhurst and Williams 2004).
