title: Plasmodium falciparum transmission stages accumulate in the human bone marrow.
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 reentering 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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Joice
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Nilsson
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, P. O. Box 30096, Chichiri, Blantyre 3, Malawi. Liverpool School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, UK.
authors.forename: Jacqui
authors.initials: J
authors.lastname: Montgomery
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Selasi
authors.initials: S
authors.lastname: Dankwa
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Egan
authors.affiliation: Department of Biology, Loyola University, 1032 West Sheridan Road, Chicago, IL 60660, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Morahan
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre 3, Malawi. College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Karl B
authors.initials: KB
authors.lastname: Seydel
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanita, Viale Regina Elena n. 299, 00191 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Bertuccini
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanita, Viale Regina Elena n. 299, 00191 Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Alano
authors.affiliation: Department of Biology, Loyola University, 1032 West Sheridan Road, Chicago, IL 60660, USA.
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre 3, Malawi. College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre 3, Malawi. Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Milner
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. mmarti@hsph.harvard.edu.
authors.forename: Matthias
authors.initials: M
authors.lastname: Marti
mesh_terms: D001853:Bone Marrow / Q000469:parasitology* / Q000473:pathology; D002648:Child; D006413:Hematopoietic System / Q000469:parasitology / Q000473:pathology; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000635:transmission*; D010963:Plasmodium falciparum / Q000254:growth & development*