Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda
Abstract Antimalarial therapeutic efficacy studies are vital for monitoring drug efficacy in malaria-endemic regions. The WHO recommends genotyping polymorphic markers including msp-1, msp-2, and glurp for distinguishing recrudescences from reinfections. Recently, WHO proposed replacing glurp with m...
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Nature Portfolio
2025-02-01
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Online Access: | https://doi.org/10.1038/s41598-025-88892-7 |
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author | Alex Mwesigwa Monica Golumbeanu Sam Jones Sara L. Cantoreggi Benson Musinguzi Joaniter I. Nankabirwa Everd Maniple Bikaitwoha Joan N Kalyango Charles Karamagi Mateusz Plucinski Samuel L. Nsobya Christian Nsanzabana Pauline Byakika-Kibwika |
author_facet | Alex Mwesigwa Monica Golumbeanu Sam Jones Sara L. Cantoreggi Benson Musinguzi Joaniter I. Nankabirwa Everd Maniple Bikaitwoha Joan N Kalyango Charles Karamagi Mateusz Plucinski Samuel L. Nsobya Christian Nsanzabana Pauline Byakika-Kibwika |
author_sort | Alex Mwesigwa |
collection | DOAJ |
description | Abstract Antimalarial therapeutic efficacy studies are vital for monitoring drug efficacy in malaria-endemic regions. The WHO recommends genotyping polymorphic markers including msp-1, msp-2, and glurp for distinguishing recrudescences from reinfections. Recently, WHO proposed replacing glurp with microsatellites (Poly-α, PfPK2, TA1). However, suitable combinations with msp-1 and msp-2, as well as the performance of different algorithms for classifying recrudescence, have not been systematically assessed. This study investigated various microsatellites alongside msp-1 and msp-2 for molecular correction and compared different genotyping algorithms across three sites in Uganda. Microsatellites 313, Poly-α, and 383 exhibited the highest diversity, while PfPK2 and Poly-α revealed elevated multiplicity of infection (MOI) across all sites. The 3/3 match-counting algorithm classified significantly fewer recrudescences than both the ≥ 2/3 and Bayesian algorithms at probability cutoffs of ≥ 0.7 and ≥ 0.8 (P < 0.05). The msp-1/msp-2/2490 combination identified more recrudescences using the ≥ 2/3 and 3/3 algorithms in the artemether-lumefantrine (AL) treatment arm, while msp-1/msp-2/glurp combination classified more cases of recrudescence using the ≥ 2/3 in the dihydroartemisinin-piperaquine (DP) arm. Microsatellites PfPK2 and Poly-α, potentially sensitive to detecting minority clones, are promising replacements for glurp. Discrepancies in recrudescence classification between match-counting and Bayesian algorithms highlight the need for standardized PCR correction practices. |
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institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2025-02-01 |
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spelling | doaj-art-8a030f6293744b90a932be2f305c95742025-02-09T12:32:02ZengNature PortfolioScientific Reports2045-23222025-02-0115111010.1038/s41598-025-88892-7Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in UgandaAlex Mwesigwa0Monica Golumbeanu1Sam Jones2Sara L. Cantoreggi3Benson Musinguzi4Joaniter I. Nankabirwa5Everd Maniple Bikaitwoha6Joan N Kalyango7Charles Karamagi8Mateusz Plucinski9Samuel L. Nsobya10Christian Nsanzabana11Pauline Byakika-Kibwika12Clinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere UniversitySwiss Tropical and Public Health InstituteMMV Medicines for Malaria VentureSwiss Tropical and Public Health InstituteDepartent of Medical Laboratory Science, Faculty of Health Sciences, Muni UniversityClinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere UniversityDepartment of Community Health, School of Medicine, Kabale UniversityClinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere UniversityClinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere UniversityU.S. President’s Malaria Initiative, Centers for Disease Control and PreventionInfectious Diseases Research Collaboration, College of Health Sciences, Makerere UniversitySwiss Tropical and Public Health InstituteMbarara University of Science and TechnologyAbstract Antimalarial therapeutic efficacy studies are vital for monitoring drug efficacy in malaria-endemic regions. The WHO recommends genotyping polymorphic markers including msp-1, msp-2, and glurp for distinguishing recrudescences from reinfections. Recently, WHO proposed replacing glurp with microsatellites (Poly-α, PfPK2, TA1). However, suitable combinations with msp-1 and msp-2, as well as the performance of different algorithms for classifying recrudescence, have not been systematically assessed. This study investigated various microsatellites alongside msp-1 and msp-2 for molecular correction and compared different genotyping algorithms across three sites in Uganda. Microsatellites 313, Poly-α, and 383 exhibited the highest diversity, while PfPK2 and Poly-α revealed elevated multiplicity of infection (MOI) across all sites. The 3/3 match-counting algorithm classified significantly fewer recrudescences than both the ≥ 2/3 and Bayesian algorithms at probability cutoffs of ≥ 0.7 and ≥ 0.8 (P < 0.05). The msp-1/msp-2/2490 combination identified more recrudescences using the ≥ 2/3 and 3/3 algorithms in the artemether-lumefantrine (AL) treatment arm, while msp-1/msp-2/glurp combination classified more cases of recrudescence using the ≥ 2/3 in the dihydroartemisinin-piperaquine (DP) arm. Microsatellites PfPK2 and Poly-α, potentially sensitive to detecting minority clones, are promising replacements for glurp. Discrepancies in recrudescence classification between match-counting and Bayesian algorithms highlight the need for standardized PCR correction practices.https://doi.org/10.1038/s41598-025-88892-7Plasmodium falciparumRecrudescenceReinfectionMicrosatellitesmsp-1msp-2 |
spellingShingle | Alex Mwesigwa Monica Golumbeanu Sam Jones Sara L. Cantoreggi Benson Musinguzi Joaniter I. Nankabirwa Everd Maniple Bikaitwoha Joan N Kalyango Charles Karamagi Mateusz Plucinski Samuel L. Nsobya Christian Nsanzabana Pauline Byakika-Kibwika Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda Scientific Reports Plasmodium falciparum Recrudescence Reinfection Microsatellites msp-1 msp-2 |
title | Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda |
title_full | Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda |
title_fullStr | Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda |
title_full_unstemmed | Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda |
title_short | Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda |
title_sort | assessment of different genotyping markers and algorithms for distinguishing plasmodium falciparum recrudescence from reinfection in uganda |
topic | Plasmodium falciparum Recrudescence Reinfection Microsatellites msp-1 msp-2 |
url | https://doi.org/10.1038/s41598-025-88892-7 |
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