Plasmodium falciparum transmission stages accumulate in the human bone marrow

Regina Joice; Sandra K. Nilsson; Jacqui Montgomery; Selasi Dankwa; Elizabeth Egan; Belinda Morahan; Karl B. Seydel; Lucia Bertuccini; Pietro Alano; Kim C. Williamson; Manoj T. Duraisingh; Terrie E. Taylor; Danny A. Milner; Matthias Marti

doi:10.1126/scitranslmed.3008882

Plasmodium falciparum transmission stages accumulate in the human bone marrow

Regina Joice, Sandra K. Nilsson, Jacqui Montgomery, Selasi Dankwa, Elizabeth Egan, Belinda Morahan, Karl B. Seydel, Lucia Bertuccini, Pietro Alano, Kim C. Williamson, Manoj T. Duraisingh, Terrie E. Taylor, Danny A. Milner, Matthias Marti^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

226 Scopus citations

Abstract

Transmission of Plasmodium falciparum malaria parasites requires formation and development of gametocytes, yet all but the most mature of these sexual parasite forms are absent from the blood circulation. We performed a systematic organ survey in pediatric cases of fatal malaria to characterize the spatial dynamics of gametocyte development in the human host. Histological studies revealed a niche in the extravascular space of the human bone marrow where gametocytes formed in erythroid precursor cells and underwent development before re-entering the circulation. Accumulation of gametocytes in the hematopoietic system of human bone marrow did not rely on cytoadherence to the vasculature as does sequestration of asexual-stage parasites. This suggests a different mechanism for the sequestration of gametocytes that could potentially be exploited to block malaria transmission.

Original language	English
Article number	244re5
Journal	Science Translational Medicine
Volume	6
Issue number	244
DOIs	https://doi.org/10.1126/scitranslmed.3008882
State	Published - 6 Jul 2014
Externally published	Yes

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10.1126/scitranslmed.3008882

Cite this

Joice, R., Nilsson, S. K., Montgomery, J., Dankwa, S., Egan, E., Morahan, B., Seydel, K. B., Bertuccini, L., Alano, P., Williamson, K. C., Duraisingh, M. T., Taylor, T. E., Milner, D. A., & Marti, M. (2014). Plasmodium falciparum transmission stages accumulate in the human bone marrow. Science Translational Medicine, 6(244), Article 244re5. https://doi.org/10.1126/scitranslmed.3008882

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abstract = "Transmission of Plasmodium falciparum malaria parasites requires formation and development of gametocytes, yet all but the most mature of these sexual parasite forms are absent from the blood circulation. We performed a systematic organ survey in pediatric cases of fatal malaria to characterize the spatial dynamics of gametocyte development in the human host. Histological studies revealed a niche in the extravascular space of the human bone marrow where gametocytes formed in erythroid precursor cells and underwent development before re-entering the circulation. Accumulation of gametocytes in the hematopoietic system of human bone marrow did not rely on cytoadherence to the vasculature as does sequestration of asexual-stage parasites. This suggests a different mechanism for the sequestration of gametocytes that could potentially be exploited to block malaria transmission.",

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T1 - Plasmodium falciparum transmission stages accumulate in the human bone marrow

AU - Joice, Regina

AU - Nilsson, Sandra K.

AU - Montgomery, Jacqui

AU - Dankwa, Selasi

AU - Egan, Elizabeth

AU - Morahan, Belinda

AU - Seydel, Karl B.

AU - Bertuccini, Lucia

AU - Alano, Pietro

AU - Williamson, Kim C.

AU - Duraisingh, Manoj T.

AU - Taylor, Terrie E.

AU - Milner, Danny A.

AU - Marti, Matthias

PY - 2014/7/6

Y1 - 2014/7/6

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AB - Transmission of Plasmodium falciparum malaria parasites requires formation and development of gametocytes, yet all but the most mature of these sexual parasite forms are absent from the blood circulation. We performed a systematic organ survey in pediatric cases of fatal malaria to characterize the spatial dynamics of gametocyte development in the human host. Histological studies revealed a niche in the extravascular space of the human bone marrow where gametocytes formed in erythroid precursor cells and underwent development before re-entering the circulation. Accumulation of gametocytes in the hematopoietic system of human bone marrow did not rely on cytoadherence to the vasculature as does sequestration of asexual-stage parasites. This suggests a different mechanism for the sequestration of gametocytes that could potentially be exploited to block malaria transmission.

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