Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study

Abstract Background Strengthening malaria control and expediting progress toward elimination requires targeting gametocytes to interrupt transmission. Artemisinin-based combination therapy (ACT) effectively clears Plasmodium falciparum asexual parasites and immature gametocytes but has a limited imp...

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Main Authors: Kassahun Habtamu, Hallelujah Getachew, Ashenafi Abossie, Assalif Demissew, Arega Tsegaye, Teshome Degefa, Daibin Zhong, Xiaoming Wang, Ming-Chieh Lee, Guofa Zhou, Solomon Kibret, Christopher L. King, James W. Kazura, Beyene Petros, Delenasaw Yewhalaw, Guiyun Yan
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Malaria Journal
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Online Access:https://doi.org/10.1186/s12936-025-05279-9
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author Kassahun Habtamu
Hallelujah Getachew
Ashenafi Abossie
Assalif Demissew
Arega Tsegaye
Teshome Degefa
Daibin Zhong
Xiaoming Wang
Ming-Chieh Lee
Guofa Zhou
Solomon Kibret
Christopher L. King
James W. Kazura
Beyene Petros
Delenasaw Yewhalaw
Guiyun Yan
author_facet Kassahun Habtamu
Hallelujah Getachew
Ashenafi Abossie
Assalif Demissew
Arega Tsegaye
Teshome Degefa
Daibin Zhong
Xiaoming Wang
Ming-Chieh Lee
Guofa Zhou
Solomon Kibret
Christopher L. King
James W. Kazura
Beyene Petros
Delenasaw Yewhalaw
Guiyun Yan
author_sort Kassahun Habtamu
collection DOAJ
description Abstract Background Strengthening malaria control and expediting progress toward elimination requires targeting gametocytes to interrupt transmission. Artemisinin-based combination therapy (ACT) effectively clears Plasmodium falciparum asexual parasites and immature gametocytes but has a limited impact on mature gametocytes, which mosquitoes ingest during a blood meal. To address this gap, the World Health Organization recommends adding a single low dose of primaquine (PQ) to ACT regimens. This study assessed the efficacy of a single low-dose PQ for P. falciparum gametocyte clearance and evaluated mosquito infectiousness in Ethiopia. Methods A prospective cohort study was conducted using passive case detection to enrol individuals with uncomplicated P. falciparum malaria at six health facilities. Participants were treated with either ACT alone or ACT plus 0.25 mg/kg single-dose PQ (ACT + PQ) and followed for 28 days with weekly visits. Blood smears for parasite counts, filter paper samples for DNA isolation, and whole blood for RNA preservation were collected on days 0, 7, 14, 21, and 28. On day 7, venous blood was obtained for membrane feeding assays using the Hemotek® system to assess mosquito infection. Logistic regression analysed mosquito infection predictors, while gametocyte prevalence was compared between treatment arms using χ2 or Fisher’s exact tests. Results Of 304 screened patients, 192 were enroled, with a median age of 23 (IQR 17–30) years; 65.7% were male. Post-treatment, 11 human-to-mosquito transmission cases were identified on day 7. Participants receiving ACT + SLD-PQ were significantly less likely to be infectious on day 7 (OR 0.12, 95% CI 0.02–0.57, p = 0.008) and had a significantly reduced prevalence of gametocytes (OR 0.22, 95% CI 0.06–0.83, p = 0.026) compared to those receiving ACT alone. Conclusion A single course of low-dose primaquine (PQ) given with ACT significantly decreases the prevalence of gametocytaemia. Furthermore, membrane-feeding assays show that this combination also considerably lowers mosquito infection, confirming existing knowledge and emphasizing the promise of low-dose PQ as a successful transmission-blocking strategy in managing malaria.
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spelling doaj-art-a463315e2c64455e969ca3a845836dab2025-08-20T02:51:27ZengBMCMalaria Journal1475-28752025-03-0124111310.1186/s12936-025-05279-9Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort studyKassahun Habtamu0Hallelujah Getachew1Ashenafi Abossie2Assalif Demissew3Arega Tsegaye4Teshome Degefa5Daibin Zhong6Xiaoming Wang7Ming-Chieh Lee8Guofa Zhou9Solomon Kibret10Christopher L. King11James W. Kazura12Beyene Petros13Delenasaw Yewhalaw14Guiyun Yan15Department of Microbial, Cellular and Molecular Biology, Addis Ababa UniversityDepartment of Medical Laboratory Sciences, Arbaminch College of Health SciencesDepartment of Medical Laboratory Sciences, College of Medicine and Health Sciences, Arba Minch UniversityDepartment of Medical Laboratory Sciences, College of Medicine and Health Sciences, Ambo UniversityCollege of Natural Science, Department of Biology, Jimma UniversitySchool of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma UniversityProgram in Public Health, University of California at IrvineProgram in Public Health, University of California at IrvineProgram in Public Health, University of California at IrvineProgram in Public Health, University of California at IrvineWest Valley Mosquito and Vector Control DistrictCenter for Global Health and Diseases, School of Medicine, Case Western Reserve UniversityCenter for Global Health and Diseases, School of Medicine, Case Western Reserve UniversityDepartment of Microbial, Cellular and Molecular Biology, Addis Ababa UniversitySchool of Medical Laboratory Sciences, Faculty of Health Sciences, Jimma UniversityProgram in Public Health, University of California at IrvineAbstract Background Strengthening malaria control and expediting progress toward elimination requires targeting gametocytes to interrupt transmission. Artemisinin-based combination therapy (ACT) effectively clears Plasmodium falciparum asexual parasites and immature gametocytes but has a limited impact on mature gametocytes, which mosquitoes ingest during a blood meal. To address this gap, the World Health Organization recommends adding a single low dose of primaquine (PQ) to ACT regimens. This study assessed the efficacy of a single low-dose PQ for P. falciparum gametocyte clearance and evaluated mosquito infectiousness in Ethiopia. Methods A prospective cohort study was conducted using passive case detection to enrol individuals with uncomplicated P. falciparum malaria at six health facilities. Participants were treated with either ACT alone or ACT plus 0.25 mg/kg single-dose PQ (ACT + PQ) and followed for 28 days with weekly visits. Blood smears for parasite counts, filter paper samples for DNA isolation, and whole blood for RNA preservation were collected on days 0, 7, 14, 21, and 28. On day 7, venous blood was obtained for membrane feeding assays using the Hemotek® system to assess mosquito infection. Logistic regression analysed mosquito infection predictors, while gametocyte prevalence was compared between treatment arms using χ2 or Fisher’s exact tests. Results Of 304 screened patients, 192 were enroled, with a median age of 23 (IQR 17–30) years; 65.7% were male. Post-treatment, 11 human-to-mosquito transmission cases were identified on day 7. Participants receiving ACT + SLD-PQ were significantly less likely to be infectious on day 7 (OR 0.12, 95% CI 0.02–0.57, p = 0.008) and had a significantly reduced prevalence of gametocytes (OR 0.22, 95% CI 0.06–0.83, p = 0.026) compared to those receiving ACT alone. Conclusion A single course of low-dose primaquine (PQ) given with ACT significantly decreases the prevalence of gametocytaemia. Furthermore, membrane-feeding assays show that this combination also considerably lowers mosquito infection, confirming existing knowledge and emphasizing the promise of low-dose PQ as a successful transmission-blocking strategy in managing malaria.https://doi.org/10.1186/s12936-025-05279-9Artemisinin combination therapySingle low dose primaquineMembrane feeding assaysGametocytesPlasmodium falciparumEthiopia
spellingShingle Kassahun Habtamu
Hallelujah Getachew
Ashenafi Abossie
Assalif Demissew
Arega Tsegaye
Teshome Degefa
Daibin Zhong
Xiaoming Wang
Ming-Chieh Lee
Guofa Zhou
Solomon Kibret
Christopher L. King
James W. Kazura
Beyene Petros
Delenasaw Yewhalaw
Guiyun Yan
Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study
Malaria Journal
Artemisinin combination therapy
Single low dose primaquine
Membrane feeding assays
Gametocytes
Plasmodium falciparum
Ethiopia
title Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study
title_full Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study
title_fullStr Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study
title_full_unstemmed Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study
title_short Post-treatment transmissibility of Plasmodium falciparum infections: an observational cohort study
title_sort post treatment transmissibility of plasmodium falciparum infections an observational cohort study
topic Artemisinin combination therapy
Single low dose primaquine
Membrane feeding assays
Gametocytes
Plasmodium falciparum
Ethiopia
url https://doi.org/10.1186/s12936-025-05279-9
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