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Essays > Malaria (October 19, 1999 by Pat Heyman)
Robb had ended the letter: Now little Karen is smitten. Sarah and I are desperate. The course of the sickness is insidious. First a ghastly fever for half a day, then a recovery, then a more severe recurrence of the fever in two or three days. The cycle is repeated again and again, each attack worse than before. They’ve bled the child but we don’t hope for much. The coolies are dying after the third attack. And Karen is so very weak. God help us, I think Karen’s lost. –Tai-Pan, James Clavell (1966)
Three factors affect the pathology malaria: 1) parasitemia (parasites
in the blood); 2) destruction of erythrocytes; 3) defense response of
the host against the infection (Aikawa, 1980). The first event is the
parasitic invasion of erythrocytes. The parasites enter the red blood
cells and become part of a vacuole within the cell cytoplasm. There, they
digest the cell’s hemoglobin and replicate; the merozoites acquire their
characteristic hemozosin pigment here—most likely a byproduct of hemoglobinolysis
(Wernsdorfer, 1980). The erythrocyte may become as large as 3 mm before
lysis.
The next event is hemolysis. Erythrocytes are destroyed by both the Plasmodia and by the host’s own immune system. It is this stage that is thought to cause the pathology behind the paroxysm. They are very closely correlated with the levels of merozoites in the blood. (It is thought that the sporozoite phase of Plasmodium does not produce significant clinical changes. Some individuals with natural immunity may destroy sporozoites before they reach hepatocytes, but most of the time, no reaction takes place.)
It was once thought that since the ascending fevers of malaria (sometimes called paroxysms) follow the release of merozoites into the bloodstream, it was thought that the merozoites produced a toxin that affected the body’s metabolism. But no toxin was ever found. It is now believed that the paroxysms are caused by an allergic-anaphylactic reaction to the merozoites and bits of erythrocytic debris. The exact mechanism is unknown, and studies are inconclusive, but generally, a decrease in granulocytes is observed. There may be either a leukopenia or a leukocytosis, but leukocytosis will always be accompanied by a proportional increase in monocytes.
The magnitude of fever is directly proportional the numbers of circulating merozoites. The concentration varies widely from individual to individual, but generally speaking, a concentration of 100 merozoites per cubic millimeter is required to produce a fever of 100° F (Russell, 1963). Thus each cycle of erythrocytic schizogony brings the fever a little higher. The length of time required to produce the paroxysm (incubation) and the severity of the paroxysm depends on the length of schizogony and number of merozoites produced by each cycle. P. malariae sporulates every 72 hours versus P. vivax’s 48 hours. One schizont can produce approximately 2000 in P. malariae, 10,000 in P. vivax, and 30,000 in P. falciparum (Wernsdorfer, 1980).
The third stage is the body’s response to the parasites. This stage is poorly understood. The host’s immune system eventually consumes the merozoites, and the paroxysm comes under control. Physiological adaptations occur over time, allowing individuals with repeated infections to experience higher levels of parasitemia without symptoms. Indeed, some doctors believe that those living in endemic areas should only be treated until symptoms have disappeared, since the tolerance to merozoite presence increases with exposure over time (Garrett, 1994).
Etiology
Pathogenesis
Morphology
Clinical Manifestations