Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda.
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 microsatel...
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| Format: | Article |
| Language: | English |
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Springer Nature
2025
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| Online Access: | http://hdl.handle.net/20.500.12493/2874 |
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| author | Mwesigwa, Alex Golumbeanu, Monica Jones, Sam Cantoreggi, L. Sara Musinguzi, Benson Nankabirwa, I. Joaniter Bikaitwoha, Everd Maniple Kalyango, N. Joan Karamagi, Charles Plucinski, Mateusz Nsobya, L. Samuel Nsanzabana, Christian Byakika-Kibwika, Pauline |
| author_facet | Mwesigwa, Alex Golumbeanu, Monica Jones, Sam Cantoreggi, L. Sara Musinguzi, Benson Nankabirwa, I. Joaniter Bikaitwoha, Everd Maniple Kalyango, N. Joan Karamagi, Charles Plucinski, Mateusz Nsobya, L. Samuel Nsanzabana, Christian Byakika-Kibwika, Pauline |
| author_sort | Mwesigwa, Alex |
| collection | KAB-DR |
| description | 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 |
| format | Article |
| id | oai:idr.kab.ac.ug:20.500.12493-2874 |
| institution | KAB-DR |
| language | English |
| publishDate | 2025 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oai:idr.kab.ac.ug:20.500.12493-28742025-02-06T11:35:38Z Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda. Mwesigwa, Alex Golumbeanu, Monica Jones, Sam Cantoreggi, L. Sara Musinguzi, Benson Nankabirwa, I. Joaniter Bikaitwoha, Everd Maniple Kalyango, N. Joan Karamagi, Charles Plucinski, Mateusz Nsobya, L. Samuel Nsanzabana, Christian Byakika-Kibwika, Pauline Plasmodium falciparum Recrudescence Reinfection microsatellites msp-1 msp-2 antimalarial drug 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 Kabale University EDCTP3 The Infectious Diseases Institute (IDI) The Government of Uganda through the Makerere University Research and Innovation Fund (Mak-RIF PhD grants). 2025-02-06T08:12:04Z 2025-02-06T08:12:04Z 2025 Article Mwesigwa, A., Golumbeanu, M., Jones, S., Cantoreggi, S. L., Musinguzi, B., Nankabirwa, J. I., Bikaitwoha, E. M., Kalyango, J. N., Karamagi, C., Plucinski, M., Nsobya, S. L., Nsanzabana, C., & Byakika-Kibwika, P. (2025). Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda. Springer Nature, 15, 4375. ht t p s : / / d o i . o r g / 1 0 . 1 0 3 8 / s 4 1 5 9 8 - 0 2 5 - 8 8 8 9 2 - 7 . https://doi.org/10.1038/s41598-025-88892-7 http://hdl.handle.net/20.500.12493/2874 en Attribution-NonCommercial-NoDerivs 3.0 United States http://creativecommons.org/licenses/by-nc-nd/3.0/us/ application/pdf Springer Nature |
| spellingShingle | Plasmodium falciparum Recrudescence Reinfection microsatellites msp-1 msp-2 antimalarial drug Mwesigwa, Alex Golumbeanu, Monica Jones, Sam Cantoreggi, L. Sara Musinguzi, Benson Nankabirwa, I. Joaniter Bikaitwoha, Everd Maniple Kalyango, N. Joan Karamagi, Charles Plucinski, Mateusz Nsobya, L. Samuel Nsanzabana, Christian Byakika-Kibwika, Pauline Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda. |
| 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 antimalarial drug |
| url | http://hdl.handle.net/20.500.12493/2874 |
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