The transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 02, 2020
- Source ID
- 10.1038/s41467-020-19988-z
Entities
People
- Anwar E. Ahmed
- Benjamin K. Abuaku
- Courage Kakaney
- Elizabeth Cudjoe
- Evans Obboh
- Festus K. Acquah
- James S. Mccarthy
- Jones A. Amponsah
- Kim C Williamson
- Linda E. Amoah
- Michelle C. Barbeau
- Ruth Ayanful-torgby
- Surendra K. Prajapati
- Zuleima Pava
Organizations
- Gates Foundation
- National Institute of Allergy and Infectious Diseases
- Uniformed Services University of the Health Sciences