TY - JOUR
T1 - Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients
AU - Portugaliza, Harvie P.
AU - Natama, H. Magloire
AU - Guetens, Pieter
AU - Rovira-Vallbona, Eduard
AU - Some, Athanase M.
AU - Millogo, Aida
AU - Ouedraogo, D. Florence
AU - Valea, Innocent
AU - Sorgho, Hermann
AU - Tinto, Halidou
AU - Nguyen Van Hong, null
AU - Sitoe, Antonio
AU - Varo, Rosauro
AU - Bassat, Quique
AU - Cortes, Alfred
AU - Rosanas-Urgell, Anna
N1 - FTX; DOAJ; (CC BY-NC-ND 4.0)
PY - 2022
Y1 - 2022
N2 - Background Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes.Methods The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total, n=109) collected before treatment and at 12 h intervals after treatment. As a secondary objective, we investi-gated factors that may influence the effect of treatment on sexual conversion rates.Findings In the majority of infections from the African cohorts, but not from Vietnam, we observed increased expression of pfap2-g and other SRBs after treatment. Estimated parasite age at the time of treatment was negatively correlated with the increase in pfap2-g transcript levels, suggesting that younger parasites are less susceptible to stim-ulation of sexual conversion.Interpretation We observed enhanced expression of SRBs after ART-based treatment in many patients, which sug-gests that in natural malaria infections sexual conversion rates can be altered by treatment. ART-based treatment reduces the potential of a treated individual to transmit the disease, but we hypothesise that under some circumstan-ces this reduction may be attenuated by ART-enhanced sexual conversion.Funding Spanish Agencia Estatal de Investigaci?on (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobal-Health-Erasmus Mundus (European Union).Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) eBioMedicine 104198 Published online https://doi.org/10.1016/j. ebiom.2022.104198
AB - Background Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes.Methods The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total, n=109) collected before treatment and at 12 h intervals after treatment. As a secondary objective, we investi-gated factors that may influence the effect of treatment on sexual conversion rates.Findings In the majority of infections from the African cohorts, but not from Vietnam, we observed increased expression of pfap2-g and other SRBs after treatment. Estimated parasite age at the time of treatment was negatively correlated with the increase in pfap2-g transcript levels, suggesting that younger parasites are less susceptible to stim-ulation of sexual conversion.Interpretation We observed enhanced expression of SRBs after ART-based treatment in many patients, which sug-gests that in natural malaria infections sexual conversion rates can be altered by treatment. ART-based treatment reduces the potential of a treated individual to transmit the disease, but we hypothesise that under some circumstan-ces this reduction may be attenuated by ART-enhanced sexual conversion.Funding Spanish Agencia Estatal de Investigaci?on (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobal-Health-Erasmus Mundus (European Union).Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) eBioMedicine 104198 Published online https://doi.org/10.1016/j. ebiom.2022.104198
KW - Plasmodium falciparum
KW - Sexual conversion
KW - Artemisinin
KW - Malaria transmission
KW - pfap2-g
KW - DIHYDROARTEMISININ-PIPERAQUINE
KW - ARTEMETHER-LUMEFANTRINE
KW - COMBINATION THERAPY
KW - GAMETOCYTE CARRIAGE
KW - ANTIMALARIAL-DRUGS
KW - TRANSMISSION
KW - RESISTANCE
KW - COMMITMENT
KW - REVEALS
KW - MECHANISMS
U2 - 10.1016/j.ebiom.2022.104198
DO - 10.1016/j.ebiom.2022.104198
M3 - A1: Web of Science-article
SN - 2352-3964
VL - 83
JO - EBioMedicine
JF - EBioMedicine
M1 - 104198
ER -