Malaria, a disease caused mainly by the parasites Plasmodium falciparum and Plasmodium vivax, (P. vivax) is associated with over 400,000 deaths each year. Previously, the spleen was assumed to mostly play a role in parasite destruction, as it eliminates malaria parasites after antimalarial treatment. A study published in the open access journal PLOS Medicine by Steven Kho and Nicholas Anstey at Menzies School of Health Research, Australia, and international colleagues, suggests that in chronic P. vivax infections, malaria parasites survive and replicate via a previously undetected lifecycle within the spleen.
A large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human subjects infected with Plasmodium vivax (P. vivax). However, the mechanisms underlying this intense reaction are unknown. To better understand the accumulation of malaria parasites in the spleen, researchers examined the spleen tissue in twenty-two individuals naturally exposed to P. vivax and P. falciparum undergoing splenectomy in Papua, Indonesia between 2015-2017. The authors then analysed the density of infection, parasites and immature red blood cells, as well as their distribution throughout the spleen.
The researchers found that the human spleen is a reservoir for immature red blood cells that are targeted by P. vivax for invasion, and that the examined spleens contained a substantial hidden biomass of malaria parasites, with densities hundreds to thousands of times higher than in circulating peripheral blood, suggesting an undetectable endosplenic lifecycle in asymptomatic P. vivax infections. The study had several limitations, such as the small sample size and asymptomatic status of all individuals included in the study. Future research should include acute, symptomatic malaria cases.
According to the authors, "Our findings provide a major contribution to the understanding of malaria biology and pathology and provide insight into P. vivax specific adaptations that have evolved to maximise survival and replication in the spleen".
Peer reviewed; Observational study; Humans
In your coverage please use this URL to provide access to the freely available paper: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003632
Funding: This work was supported by the Australian National Health and Medical Research Council (Program Grant #1037304, Fellowships to NA [#1042072 and #1135820], and 'Improving Health Outcomes in the Tropical North (HOTNORTH): A multidisciplinary collaboration [#1131932], and the Australian Centre of Research Excellence in Malaria Elimination), the Paris Ile-de-France Region under « DIM Thérapie génique » and « DIM Maladies Infectieuses » initiatives (awarded to PAB and BH), the French Institut National de la Santé Et de la Recherche Médicale (INSERM), the University of Paris, the Laboratory of excellence GREx, the Bill and Melinda Gates Foundation (BMGF OPP1123683), and the « Sauver la Vie Foundation » (to PAB), the Wellcome Trust (Grant #099875 awarded to JRP and Senior Fellowship in Clinical Science awarded to RNP [#200909]), an Australian Government Postgraduate Award Scholarship and OzEMalaR Travel award (awarded to SK), a Royal Society Wolfson Research Merit award (awarded to MM), the Singapore National Medical Research Council (award to TWY [CSA INV 15nov007]), and the Australian Department of Foreign Affairs and Trade. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Kho S, Qotrunnada L, Leonardo L, Andries B, Wardani PAI, Fricot A, et al. (2021) Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study. PLoS Med 18(5): e1003632. https://doi.org/10.1371/journal.pmed.1003632