Publication:
Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study

Issued Date

2021-05-01

Resource Type

Article

ISSN

15491676
15491277

DOI

10.1371/journal.pmed.1003632

Other identifier(s)

2-s2.0-85106956605

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS Medicine. Vol.18, No.5 (2021)

Suggested Citation

Steven Kho, Labibah Qotrunnada, Leo Leonardo, Benediktus Andries, Putu A.I. Wardani, Aurelie Fricot, Benoit Henry, David Hardy, Nur I. Margyaningsih, Dwi Apriyanti, Agatha M. Puspitasari, Pak Prayoga, Leily Trianty, Enny Kenangalem, Fabrice Chretien, Valentine Brousse, Innocent Safeukui, Hernando A. del Portillo, Carmen Fernandez-Becerra, Elamaran Meibalan, Matthias Marti, Ric N. Price, Tonia Woodberry, Papa A. Ndour, Bruce M. Russell, Tsin W. Yeo, Gabriela Minigo, Rintis Noviyanti, Jeanne R. Poespoprodjo, Nurjati C. Siregar, Pierre A. Buffet, Nicholas M. Anstey Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study. PLoS Medicine. Vol.18, No.5 (2021). doi:10.1371/journal.pmed.1003632 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/78222

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Title

Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study

Author(s)

Steven Kho
 Labibah Qotrunnada
 Leo Leonardo
 Benediktus Andries
 Putu A.I. Wardani
 Aurelie Fricot
 Benoit Henry
 David Hardy
 Nur I. Margyaningsih
 Dwi Apriyanti
 Agatha M. Puspitasari
 Pak Prayoga
 Leily Trianty
 Enny Kenangalem
 Fabrice Chretien
 Valentine Brousse
 Innocent Safeukui
 Hernando A. del Portillo
 Carmen Fernandez-Becerra
 Elamaran Meibalan
 Matthias Marti
 Ric N. Price
 Tonia Woodberry
 Papa A. Ndour
 Bruce M. Russell
 Tsin W. Yeo
 Gabriela Minigo
 Rintis Noviyanti
 Jeanne R. Poespoprodjo
 Nurjati C. Siregar
 Pierre A. Buffet
 Nicholas M. Anstey

Other Contributor(s)

Faculty of Tropical Medicine, Mahidol University
 Université Paris Cité
 Instituto de Salud Global de Barcelona
 Eijkman Institute for Molecular Biology
 Universitas Gadjah Mada
 Universitas Indonesia
 Institució Catalana de Recerca i Estudis Avançats
 Harvard T.H. Chan School of Public Health
 Menzies School of Health Research
 University of Notre Dame
 University of Otago
 Brigham and Women's Hospital
 Nuffield Department of Medicine
 Institut Pasteur, Paris
 University of Glasgow
 Germans Trias i Pujol Research Institute
 Rumah Sakit Umum Daerah Kabupaten Mimika
 Papuan Health and Community Development Foundation

Abstract

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. vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P. vivax- than in P. falciparum-infected spleens. Histological analyses revealed 96% of P. vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted. Conclusions Immature CD71+ reticulocytes and splenic P. vivax-infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P. vivax infection. Findings provide insight into P. vivax-specific adaptions that have evolved to maximise survival and replication in the spleen.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/78222

Collections

Scopus 2021