Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection

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....

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Autores principales:	Nicanor Obaldia, Elamaran Meibalan, Juliana M. Sa, Siyuan Ma, Martha A. Clark, Pedro Mejia, Roberto R. Moraes Barros, William Otero, Marcelo U. Ferreira, James R. Mitchell, Danny A. Milner, Curtis Huttenhower, Dyann F. Wirth, Manoj T. Duraisingh, Thomas E. Wellems, Matthias Marti
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Aotus real-time PCR Saimiri blood-stage parasites gametocytes immunohistochemistry Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cb06839074534f7b963b7dc61e34c995
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spelling	oai:doaj.org-article:cb06839074534f7b963b7dc61e34c9952021-11-15T16:00:26ZBone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection10.1128/mBio.00625-182150-7511https://doaj.org/article/cb06839074534f7b963b7dc61e34c9952018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00625-18https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Plasmodium vivax malaria continues to cause major public health burdens worldwide. Yet, significant knowledge gaps in the basic biology and epidemiology of P. vivax malaria remain, largely due to limited available tools for research and diagnostics. Here, we present a systematic examination of tissue sequestration during P. vivax infection. Studies of nonhuman primates and malaria patients revealed enrichment of developing sexual stages (gametocytes) and mature replicative stages (schizonts) in the bone marrow and liver, relative to those present in peripheral blood. Identification of the bone marrow as a major P. vivax tissue reservoir has important implications for parasite diagnosis and treatment.Nicanor ObaldiaElamaran MeibalanJuliana M. SaSiyuan MaMartha A. ClarkPedro MejiaRoberto R. Moraes BarrosWilliam OteroMarcelo U. FerreiraJames R. MitchellDanny A. MilnerCurtis HuttenhowerDyann F. WirthManoj T. DuraisinghThomas E. WellemsMatthias MartiAmerican Society for MicrobiologyarticleAotusreal-time PCRSaimiriblood-stage parasitesgametocytesimmunohistochemistryMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aotus real-time PCR Saimiri blood-stage parasites gametocytes immunohistochemistry Microbiology QR1-502
spellingShingle	Aotus real-time PCR Saimiri blood-stage parasites gametocytes immunohistochemistry Microbiology QR1-502 Nicanor Obaldia Elamaran Meibalan Juliana M. Sa Siyuan Ma Martha A. Clark Pedro Mejia Roberto R. Moraes Barros William Otero Marcelo U. Ferreira James R. Mitchell Danny A. Milner Curtis Huttenhower Dyann F. Wirth Manoj T. Duraisingh Thomas E. Wellems Matthias Marti Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection
description	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. IMPORTANCE Plasmodium vivax malaria continues to cause major public health burdens worldwide. Yet, significant knowledge gaps in the basic biology and epidemiology of P. vivax malaria remain, largely due to limited available tools for research and diagnostics. Here, we present a systematic examination of tissue sequestration during P. vivax infection. Studies of nonhuman primates and malaria patients revealed enrichment of developing sexual stages (gametocytes) and mature replicative stages (schizonts) in the bone marrow and liver, relative to those present in peripheral blood. Identification of the bone marrow as a major P. vivax tissue reservoir has important implications for parasite diagnosis and treatment.
format	article
author	Nicanor Obaldia Elamaran Meibalan Juliana M. Sa Siyuan Ma Martha A. Clark Pedro Mejia Roberto R. Moraes Barros William Otero Marcelo U. Ferreira James R. Mitchell Danny A. Milner Curtis Huttenhower Dyann F. Wirth Manoj T. Duraisingh Thomas E. Wellems Matthias Marti
author_facet	Nicanor Obaldia Elamaran Meibalan Juliana M. Sa Siyuan Ma Martha A. Clark Pedro Mejia Roberto R. Moraes Barros William Otero Marcelo U. Ferreira James R. Mitchell Danny A. Milner Curtis Huttenhower Dyann F. Wirth Manoj T. Duraisingh Thomas E. Wellems Matthias Marti
author_sort	Nicanor Obaldia
title	Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection
title_short	Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection
title_full	Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection
title_fullStr	Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection
title_full_unstemmed	Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection
title_sort	bone marrow is a major parasite reservoir in <named-content content-type="genus-species">plasmodium vivax</named-content> infection
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/cb06839074534f7b963b7dc61e34c995
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Bone Marrow Is a Major Parasite Reservoir in <named-content content-type="genus-species">Plasmodium vivax</named-content> Infection

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