Abstract

Malaria is spread by the transmission of sexual stage parasites, called gametocytes. However, with Plasmodium falciparum, gametocytes can only be detected in peripheral blood when they are mature and transmissible to a mosquito, which complicates control efforts. Here, we identify the set of genes overexpressed in patient blood samples with high levels of gametocyte-committed ring stage parasites. Expression of all 18 genes is regulated by transcription factor AP2-G, which is required for gametocytogenesis. We select three genes, not expressed in mature gametocytes, to develop as biomarkers. All three biomarkers we validate in vitro using 6 different parasite lines and develop an algorithm that predicts gametocyte production in ex vivo samples and volunteer infection studies. The biomarkers are also sensitive enough to monitor gametocyte production in asymptomatic P. falciparum carriers allowing early detection and treatment of infectious reservoirs, as well as the in vivo analysis of factors that modulate sexual conversion.

Malaria gametocytes are sexual-stage parasites transmitted from mammalian host’s blood back to their insect vector. Here, Prajapati et al. identify gametocyte-committed ring-stage biomarkers allowing to forecast malaria transmission potential.

Details

Title
The transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential
Author
Prajapati, Surendra K. 1   VIAFID ORCID Logo  ; Ayanful-Torgby, Ruth 2 ; Pava, Zuleima 3 ; Barbeau, Michelle C. 4 ; Acquah, Festus K. 2 ; Cudjoe, Elizabeth 2 ; Kakaney, Courage 2 ; Amponsah, Jones A. 2 ; Obboh, Evans 5 ; Ahmed, Anwar E. 6 ; Abuaku, Benjamin K. 2 ; McCarthy, James S. 3 ; Amoah, Linda E. 2 ; Williamson, Kim C. 1   VIAFID ORCID Logo 

1  Uniformed Services University of the Health Sciences, Department of Microbiology and Immunology, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525) 
2  University of Ghana, Noguchi Memorial Institute for Medical Research, Accra, Ghana (GRID:grid.8652.9) (ISNI:0000 0004 1937 1485) 
3  QIMR Berghofer Medical Research Institute, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
4  Uniformed Services University of the Health Sciences, Department of Microbiology and Immunology, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); University of Virginia, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
5  University of Cape Coast, Cape Coast, Ghana (GRID:grid.413081.f) (ISNI:0000 0001 2322 8567) 
6  Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-19988-z
ProQuest document ID
2473276687
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020. corrected publication 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.