Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study
In: ISSN: 1549-1277, 2021
Online
academicJournal
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International audience ; Background A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax . The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P . vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. Methods and findings We examined spleen tissue in 22 mostly untreated individuals naturally exposed to P . vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from individuals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or sample size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P . vivax , 13 P . falciparum , and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P . vivax -infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P ...
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Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study
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| Autor/in / Beteiligte Person: | Kho, Steven ; Qotrunnada, Labibah ; Leonardo, Leo ; Andries, Benediktus ; Wardani, Putu, A. I. ; Fricot, Aurelie ; Henry, Benoit ; Hardy, David ; Margyaningsih, Nur, I. ; Apriyanti, Dwi ; Puspitasari, Agatha, M. ; Prayoga, Pak ; Trianty, Leily ; Kenangalem, Enny ; Chretien, Fabrice ; Brousse, Valentine ; Safeukui, Innocent ; del Portillo, Hernando, A. ; Fernandez-Becerra, Carmen ; Meibalan, Elamaran ; Marti, Matthias ; Price, Ric, N. ; Woodberry, Tonia ; Ndour, Papa, A. ; Russell, Bruce, M. ; Yeo, Tsin, W. ; Minigo, Gabriela ; Noviyanti, Rintis ; Poespoprodjo, Jeanne, R. ; Siregar, Nurjati, C. ; Buffet, Pierre, A. ; Anstey, Nicholas, M. ; Global and Tropical Health Division Rocklands, Australia ; Menzies School of Health Research Australia ; Charles Darwin University Australia -Charles Darwin University Australia ; Eijkman Institute for Molecular Biology Jakarta ; Papuan Health and Community Development Foundation Timika, Papua Indonesia ; Rumah Sakit Umum Daerah Kabupaten Mimika Timika, Papua, Indonesia ; Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)) ; Institut National de la Transfusion Sanguine Paris (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes Guadeloupe -Université des Antilles (UA)-Université Paris Cité (UPCité) ; Neuropathologie expérimentale / Experimental neuropathology ; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité) ; University of Notre Dame Indiana (UND) ; Instituto de Salud Global - Institute For Global Health Barcelona (ISGlobal) ; Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP) ; Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies (ICREA) ; Harvard School of Public Health ; Brigham & Women’s Hospital Boston (BWH) ; Harvard Medical School Boston (HMS) ; University of Glasgow ; University of Oxford ; Mahidol University Bangkok ; University of Otago Dunedin, Nouvelle-Zélande ; Universitas Gadjah Mada ; Universitas Indonesia (UI ) ; 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. ; We thank patients and relatives of patients in Indonesia and France for their participation and support, staff in the laboratory and operating theatre at RSUD hospital and French hospitals, Dr Daniel Lampah and Dr Freis Candrawati for clinical input, Dr Gregory Jouvion, Dr Sarah Auburn and Dr Jutta Marfurt for methodological and intellectual advice, Dr Grennady Wirjanata, Ms Aisah Resti Amelia and Mrs Magali Tichit for laboratory assistance, and Prof Yati Soenarto for facilitating the study. We are grateful to colleagues at the Timika Research Facility for their support. |
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| Zeitschrift: | ISSN: 1549-1277, 2021 |
| Veröffentlichung: | HAL CCSD ; Public Library of Science, 2021 |
| Medientyp: | academicJournal |
| DOI: | 10.1371/journal.pmed.1003632 |
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