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.
Highlights
Malaria is spread by the transmission of sexual stage parasites, called gametocytes
To better understand the early stages of sexual differentiation in vivo and to develop molecular markers for gc-rings, this study examines the transcriptomes of uncomplicated malaria patients that had either high (H)-gametocyte-conversion rate (GCR) or low (L)-GCR in the ex vivo assay
An aliquot of blood was preserved for RNA isolation, and the rest was cultured ex vivo for 8 days in the presence of N-acetyl glucosamine to block asexual growth and allow GCR quantification
Summary
Malaria is spread by the transmission of sexual stage parasites, called gametocytes. with Plasmodium falciparum, gametocytes can only be detected in peripheral blood when they are mature and transmissible to a mosquito, which complicates control efforts. Circulation of stage V gametocytes in a patient’s peripheral blood only happens ~8–12 days after sexual commitment[6] and currently serves as the only diagnostic stage for transmission potential This delay in gametocyte detection after the initial commitment to sexual differentiation makes it difficult to evaluate factors influencing the production of gc-rings in vivo as well as for early diagnosis and treatment of gametocytes before a person is infectious. To better understand the early stages of sexual differentiation in vivo and to develop molecular markers for gc-rings, this study examines the transcriptomes of uncomplicated malaria patients that had either high (H)-gametocyte-conversion rate (GCR) or low (L)-GCR in the ex vivo assay. We suggest gcring biomarkers are important tools to predict gametocyte production in submicroscopic to symptomatic infections ~8–12 days prior to circulation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
