Plasmodium vivax malaria: tissue burden and disease severity in Saimiri bolviensis model

Background: Plasmodium vivax is responsible for over 40% of malaria cases outside of Africa and causes a wide spectrum of clinical manifestations ranging from mild to lethal disease. In humans, organ damage may occur as a result of a variety of factors, including inflammatory processes. Plasmodium vivax has not been implicated in deep vascular tissue sequestration like P. falciparum, but modeling, experimental, and case studies point to potential ‘concealment’ of P. vivax parasites in organs such that they are removed from the peripheral blood circulation. We utilized a nonhuman primate model to investigate the effect of P. vivax parasites on different organs, and identified inflammatory processes that were associated with P. vivax-mediated pathology. Black-caped squirrel monkeys (Saimiri boliviensis) are susceptible to P. vivax infection, and have been used historically to obtain parasite source material and for vaccine studies. Using this monkey model to study short-term acute clinical blood-stage infections with P. vivax, we describe significant pathology, quantify apparent parasite tissue preferences, and make associations with immunopathogenesis. Materials and Methods: Seven splenectomized and one intact S. boliviensis monkeys were inoculated with P. vivax Brazil VII strain infected red blood cells, and allowed to reach parasitemias of at least 1%, after which they were euthanized with standardized approved protocols for the maximum collection of parasite material for systems biology projects and the analysis of organ pathology. Hematoxylin and eosin stained tissues from major organ systems were assessed. Parasitized red blood cells, pigmented monocytes, and free hemozoin were quantified for comparison between tissues, and associated with the noted pathology. Results and Conclusions: Parasites associated with pathology were observed and classified in the organ tissues of all monkeys. Organ damage was associated with inflammatory processes, with significant immune infiltrate composed predominantly of mononuclear cells, namely in the kidneys, lungs, meninges, and liver. Saimiri boliviensis infected with P. vivax suffer similar pathologies comparable to humans and they are a valuable model for immune response and pathogenesis studies. This is the most comprehensive study to date of acute P. vivax infections and tissues using a nonhuman primate model.