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4.1). Thus, schizogony does not occur (Telford et al., 1993). The erythrocyte membrane is
damaged, with perforations, protrusions and inclusions, as the merozoites leave the cell, ultimately resulting in hemolysis (Sun et al.,
1983). Because there is no synchronous schizogony, as with Plasmodium species, massive hemolysis does not occur.
Mechanisms of Injury
There are three identified mechanisms by which infection with Babesia species causes injury to the host: hemolysis and resultant anemia; increased cytoadherence of erythrocytes within the vasculature; and the release of harmful mediators. In studies of hamsters infected with B. microti, intravascular and extravascular hemolysis ensues, often resulting in profound anemia (Lykins et al., 1975; Cullen and Levine, 1987; Dao and Eberhard, 1996; Wozniak et al., 1996). In a morphological study of erythrocytes from an asplenic human infected with B. microti, extensive damage to erythrocyte membranes was observed (Sun et al., 1983). Such damage could theoretically result in intravascular hemolysis, as well as retention in the spleen of the deformed and potentially more rigid erythrocytes, resulting in clearance of infected erythrocytes, as is thought to occur in malaria (Looareesuwan et al., 1987). It has been suggested that antierythrocyte membrane antibodies are produced during Babesia infection and that the resultant anemia might be due to a humoral mechanism (Adachi et al, 1992, 1994).
Vascular lesions characterized by the accumulation of erythrocytes within blood vessels as a result of Babesia infection have been described by some but not all investigators. The brains of B. boris-infected cattle were found to contain capillaries packed with erythrocytes. The erythrocytes contained knob-like projections which formed the point of attachment to endothelial cells, in a manner reminiscent of the attachment of erythrocytes to endothelial cells in cerebral malaria (Aikawa et al., 1992). Earlier studies had demonstrated the isolation and characterization of a cryofibrinogen complex in the plasma of B. boris-infected cattle. It was postulated that the complex facilitated the sludging of erythrocytes within visceral blood vessels (Goodger et al., 1978). A newly identified strain of Babesia, strain WA-1, recently isolated from a patient in Washington State, was noted to cause profound intravascular stasis within several organs in infected hamsters (Dao and Eberhard, 1996). Aggregates of inflammatory cells occluded blood vessels. Thrombosis and coagulation necrosis were described. In contrast, no vascular lesions were detected in hamsters in the same and other
PRINCIPLES AND PRACTICE OF CLINICAL PARASITOLOGY
studies infected with B. microti (Cullen and Levine, 1987; Wozniak et al., 1996). In summary, it appears that host injury in Babesia infection might be mediated through vascular occlusion, perhaps via mechanisms similar to those observed in malaria.
Host soluble mediators have been implicated in the injury resulting from Babesia infection. Clark postulated that endotoxin was involved in injury and death during babesiosis and acute malaria (Clark, 1978). He noted that babesiosis has effects similar to ‘endotoxin shock’. Since these studies have been performed, it has become clear that much of endotoxin shock is mediated by the release of cytokines (Dinarello et al.,
1993). It is possible that Babesia also elicits the production of cytokines by host cells and that cytokines might be responsible for some of the observed injury, in much the same manner as postulated for malaria (Harpaz et al., 1992; Urquhart, 1994). Other potential mediators of injury in Babesia infection have been postulated, including oxygen-derived free radicals (Clark et al, 1986).
The encounter between Babesia organisms and the host results in several immune responses. The finding of potentially protective immune responses against Babesia has led to a search for a suitable vaccine, particularly against B. bovis.
Immunoglobulin production is induced during Babesia infection. There is a non-specific B cell response after infection, resulting in a marked polyclonal hypergammaglobulinemia, in humans acutely infected with B. microti (Benach et al., 1982). Additionally, specific antibody production directed against Babesia antigens has been well documented. An early indication of antibody production was the demonstration of passive protection of mice from B. rodhaini infection with immune serum (Abdalla et al., 1978; Meeusen et al., 1984). After experimental infection of calves with B. bigemina, specific IgG and IgM appeared at 7 days. Whereas IgM titers declined by 4 weeks after infection, IgG titers remained elevated after 7 weeks (O’Donoghue
et al., 1985). In studies of hamsters infected with
B. microti, specific antibody was detected 2 weeks after infection. The peak antibody response was correlated temporally with a fall in parasitema (Hu et al., 1996).