Plasmodium vivax Parasite Load Is Associated With Histopathology in Saimiri boliviensis With Findings Comparable to P vivax Pathogenesis in Humans

Abstract

Background Plasmodium vivax can cause severe malaria with multisystem organ dysfunction and death. Clinical reports suggest that parasite accumulation in tissues may contribute to pathogenesis and disease severity, but direct evidence is scarce. Methods We present quantitative parasitological and histopathological analyses of tissue sections from a cohort of naive, mostly splenectomized Saimiri boliviensis infected with P vivax to define the relationship of tissue parasite load and histopathology. Results The lung, liver, and kidney showed the most tissue injury, with pathological presentations similar to observations reported from autopsies. Parasite loads correlated with the degree of histopathologic changes in the lung and liver tissues. In contrast, kidney damage was not associated directly with parasite load but with the presence of hemozoin, an inflammatory parasite byproduct. Conclusions This analysis supports the use of the S boliviensis infection model for performing detailed histopathological studies to better understand and potentially design interventions to treat serious clinical manifestations caused by P vivax.

Plasmodium vivaxspleen-dependent genes encode antigens associated with cytoadhesion and clinical protection

“…One particular open question regards the conundrum of low peripheral blood parasitemia coincident with severe disease. Recent evidence indicates that this seeming discrepancy could be due to the adherent capacity and sequestration of iRBC parasite populations, outside the peripheral blood, and particularly in the spleen (6,(42)(43)(44)(45)(46), the bone marrow (47,48), and with a less degree of certainty, to other organs (3,6). Our data thus support a model (Fig.…”

Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

“…Strategies to overcoming this problem have been proposed but remain impractical due to a large initial and continuous investment of labor and infrastructure [41]. The success of short-term culture utilizing young reticulocytes from placental blood [40,42] and indefinite culture in Saimiri boliviensis and Aotus nancymae monkeys [43,44] shed lights on pathogenesis in humans and potential ligands for invasion [39,44], though several unanswered questions remain.…”

“…As P. vivax requires reticulocytes for growth [46][47][48][49], the general low proportion of reticulocytes (that make up only 1% of the total number of host erythrocytes) may explain low parasite loads in symptomatic patients [50][51][52] and a lack of observable schizonts in blood circulation [52,53]. Additionally, pathological analyses of S. boliviensis tissues showed that P. vivax infections also affect the lungs and kidneys, both of which had mononuclear infiltrates, higher macrophage levels, alveolar wall thickening, collagen deposition, and type II pneumocyte hyperplasia [44]. The level of tissue damage is parasite-load dependent and determined by the amount of bi-product, namely hemozoin, being produced [44].…”

“…Additionally, pathological analyses of S. boliviensis tissues showed that P. vivax infections also affect the lungs and kidneys, both of which had mononuclear infiltrates, higher macrophage levels, alveolar wall thickening, collagen deposition, and type II pneumocyte hyperplasia [44]. The level of tissue damage is parasite-load dependent and determined by the amount of bi-product, namely hemozoin, being produced [44]. These findings may imply a large number of asymptomatic P. vivax carriers in the general populations.…”

Functional genomics of simian malaria parasites and host–parasite interactions

“…Plasmodium vivax and P. falciparum can be studied in the small New World monkey hosts (e.g. see [79, 85–87]), albeit with limitations compared to macaque infections, due to the small size of New World monkeys, lower and resolving parasitemias, blood volume limitations, and the inability to acquire multiple bone marrow samples. Moreover, while some do, most strains that have been adapted to the blood of these animals will not productively infect mosquitoes and yield sporozoites (reviewed in [88]); similarly, most strains of P. falciparum adapted to long-term in vitro culture do not produce gametocytes that will productively infect mosquitoes, and there is no comparable in vitro culture system yet in place for P. vivax [89].…”