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 - Somé, Athanase M.
AU - Millogo, Aida
AU - Ouédraogo, D. Florence
AU - Valéa, Innocent
AU - Sorgho, Hermann
AU - Tinto, Halidou
AU - van Hong, Nguyen
AU - Sitoe, Antonio
AU - Varo, Rosauro
AU - Bassat, Quique
AU - Cortés, Alfred
AU - Rosanas-Urgell, Anna
N1 - Funding Information: We are grateful to all the patients that participated in the studies. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO)/ Agencia Estatal de Investigación (AEI) (SAF2016-76190-R and PID2019-107232RB-I00 to A.C.), co-funded by the European Regional Development Fund (ERDF, European Union), and the Belgium Development Cooperation (DGD) under the Framework Agreement Program between DGD and ITM (FA3-III Vietnam, 2014–2016 & FA4 Burkina Faso, 2017-2021). The rosiglitazone adjuvant therapy trial for severe malaria was funded by the University Health Network (UHN), Toronto, Canada. ITM and ISGlobal were members of the TransGlobalHealth–Erasmus Mundus Joint Doctorate Programme, European Union (scholarship number 2016-1346 to H.P.P.). This research is part of ISGlobal's Program on the Molecular Mechanisms of Malaria, which is partially supported by the Fundación Ramón Areces. We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). Funding Information: We are grateful to all the patients that participated in the studies. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO)/ Agencia Estatal de Investigación (AEI) (SAF2016-76190-R and PID2019-107232RB-I00 to A.C.), co-funded by the European Regional Development Fund (ERDF, European Union), and the Belgium Development Cooperation (DGD) under the Framework Agreement Program between DGD and ITM (FA3-III Vietnam, 2014–2016 & FA4 Burkina Faso, 2017-2021). The rosiglitazone adjuvant therapy trial for severe malaria was funded by the University Health Network (UHN), Toronto, Canada. ITM and ISGlobal were members of the TransGlobalHealth–Erasmus Mundus Joint Doctorate Programme, European Union (scholarship number 2016-1346 to H.P.P.). This research is part of ISGlobal's Program on the Molecular Mechanisms of Malaria, which is partially supported by the Fundación Ramón Areces. We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). Publisher Copyright: © 2022 The Authors
PY - 2022/9/1
Y1 - 2022/9/1
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 investigated 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 stimulation of sexual conversion. Interpretation: We observed enhanced expression of SRBs after ART-based treatment in many patients, which suggests 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 circumstances this reduction may be attenuated by ART-enhanced sexual conversion. Funding: Spanish Agencia Estatal de Investigación (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobalHealth–Erasmus Mundus (European Union).
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 investigated 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 stimulation of sexual conversion. Interpretation: We observed enhanced expression of SRBs after ART-based treatment in many patients, which suggests 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 circumstances this reduction may be attenuated by ART-enhanced sexual conversion. Funding: Spanish Agencia Estatal de Investigación (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobalHealth–Erasmus Mundus (European Union).
KW - Artemisinin
KW - Malaria transmission
KW - Plasmodium falciparum
KW - Sexual conversion
KW - pfap2-g
UR - http://www.scopus.com/inward/record.url?scp=85135715320&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ebiom.2022.104198
DO - https://doi.org/10.1016/j.ebiom.2022.104198
M3 - Article
C2 - 35961203
SN - 2352-3964
VL - 83
JO - eBioMedicine
JF - eBioMedicine
M1 - 104198
ER -