Bone marrow is a major parasite reservoir in Plasmodium vivax infection

Obaldia III, N. et al. (2018) Bone marrow is a major parasite reservoir in Plasmodium vivax infection. mBio, 9(3), e00625-18. (doi:10.1128/mBio.00625-18) (PMID:29739900)

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Abstract

Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of P. vivax stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of P. vivax and Plasmodium falciparum blood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP (Aotus sp.). Histological analyses of P. vivax parasites in organs of 13 infected NHP (Aotus and Saimiri species) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Obaldia, Dr Nicanor and Marti, Professor Matthias
Authors: Obaldia III, N., Meibalan, E., Sa, J. M., Ma, S., Clark, M., Mejia, P., Moraes Barros, R. R., Otero, W., Otero, W., Ferreira, M. U., Mitchell, J. R., Milner, D. A., Huttenhower, C., Wirth, D. F., Duraisingh, M. T., Wellems, T. E., and Marti, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN:2150-7511
ISSN (Online):2150-7511
Published Online:08 May 2018

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/Z & AIII - PARASITOLOGY