Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance
Abstract Background Artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) are the currently recommended first-and second-line therapies for uncomplicated Plasmodium falciparum infections in Chad. This study assessed the efficacy of these artemisinin-based combinations, proportion of day 3...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-08-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-023-04644-w |
| _version_ | 1797577933028589568 |
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| author | Mahamat Souleymane Issa Marian Warsame Moussa Hassane Taisso Mahamat Issakha Diar Mahamat Saleh Kodbsse Boulotigam Honoré Djimrassengar Ali Haggar Issa Ousmane Abdelkader Manah Hassoumi Mbanga Djimadoum Cécile Doderer-Lang Jean Bosco Ndihiokubwayo Charlotte Rasmussen Didier Menard |
| author_facet | Mahamat Souleymane Issa Marian Warsame Moussa Hassane Taisso Mahamat Issakha Diar Mahamat Saleh Kodbsse Boulotigam Honoré Djimrassengar Ali Haggar Issa Ousmane Abdelkader Manah Hassoumi Mbanga Djimadoum Cécile Doderer-Lang Jean Bosco Ndihiokubwayo Charlotte Rasmussen Didier Menard |
| author_sort | Mahamat Souleymane Issa |
| collection | DOAJ |
| description | Abstract Background Artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) are the currently recommended first-and second-line therapies for uncomplicated Plasmodium falciparum infections in Chad. This study assessed the efficacy of these artemisinin-based combinations, proportion of day 3 positive patients, proportions of molecular markers associated with P. falciparum resistance to anti-malarial drugs and variable performance of HRP2-based malaria rapid diagnostic tests (RDTs). Methods A single-arm prospective study assessing the efficacy of AS–AQ and AL at three sites (Doba, Kelo and Koyom) was conducted between November 2020 to January 2021. Febrile children aged 6 to 59 months with confirmed uncomplicated P. falciparum infection were enrolled sequentially first to AS–AQ and then AL at each site and followed up for 28 days. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples collected on day 0 were analysed for mutations in pfkelch13, pfcrt, pfmdr-1, pfdhfr, pfdhps genes and deletions in pfhrp2/pfhrp3 genes. Results By the end of 28-day follow-up, per-protocol PCR corrected ACPR of 97.8% (CI 95% 88.2–100) in Kelo and 100% in Doba and Kayoma were observed among AL treated patients. For ASAQ, 100% ACPR was found in all sites. All, but one patient, did not have parasites detected on day 3. Out of the 215 day 0 samples, 96.7% showed pfkelch13 wild type allele. Seven isolates carried nonsynonymous mutations not known to be associated artemisinin partial resistance (ART-R). Most of samples had a pfcrt wild type allele (79% to 89%). The most prevalent pfmdr-1 allele detected was the single mutant 184F (51.2%). For pfdhfr and pfdhps mutations, the quintuple mutant allele N51I/C59R/S108N + G437A/540E responsible for SP treatment failures in adults and children was not detected. Single deletion in the pfhrp2 and pfhrp3 gene were detected in 10/215 (4.7%) and 2/215 (0.9%), respectively. Dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, were observed in 5/215 (2.3%) isolates. Conclusion The results of this study confirm that AS–AQ and AL treatments are highly efficacious in study areas in Chad. The absence of known pfkelch13 mutations in the study sites and the high parasite clearance rate at day 3 suggest the absence of ART-R. The absence of pfdhfr/pfdhps quintuple or sextuple (quintuple + 581G) mutant supports the continued use of SP for IPTp during pregnancy. The presence of parasites with dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, warrants the continued surveillance. Trial registration ACTRN12622001476729 |
| first_indexed | 2024-03-10T22:16:05Z |
| format | Article |
| id | doaj.art-1a7f662031194c6bba5c673b9379dc55 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-03-10T22:16:05Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-1a7f662031194c6bba5c673b9379dc552023-11-19T12:26:20ZengBMCMalaria Journal1475-28752023-08-0122111310.1186/s12936-023-04644-wTherapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillanceMahamat Souleymane Issa0Marian Warsame1Moussa Hassane Taisso Mahamat2Issakha Diar Mahamat Saleh3Kodbsse Boulotigam4Honoré Djimrassengar5Ali Haggar Issa6Ousmane Abdelkader7Manah Hassoumi8Mbanga Djimadoum9Cécile Doderer-Lang10Jean Bosco Ndihiokubwayo11Charlotte Rasmussen12Didier Menard13Chad National Malaria Control ProgrammeSchool of Public Health and Community Medicine, University of GothenburgFaculty of Science and Human Health, University of N’DjamenaChad National Malaria Control ProgrammeChad National Malaria Control ProgrammeWorld Health OrganizationEcole Nationale des Agents Sanitaires et Sociaux (ENASS)Ministry of Health, Public and Human SolidarityHôpital de l’Amitié Tchad-ChineFaculty of Science and Human Health, University of N’DjamenaInstitute of Parasitology and Tropical Diseases, UR7292 Dynamics of Host-Pathogen Interactions, Université de StrasbourgWorld Health OrganizationWorld Health OrganizationInstitute of Parasitology and Tropical Diseases, UR7292 Dynamics of Host-Pathogen Interactions, Université de StrasbourgAbstract Background Artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) are the currently recommended first-and second-line therapies for uncomplicated Plasmodium falciparum infections in Chad. This study assessed the efficacy of these artemisinin-based combinations, proportion of day 3 positive patients, proportions of molecular markers associated with P. falciparum resistance to anti-malarial drugs and variable performance of HRP2-based malaria rapid diagnostic tests (RDTs). Methods A single-arm prospective study assessing the efficacy of AS–AQ and AL at three sites (Doba, Kelo and Koyom) was conducted between November 2020 to January 2021. Febrile children aged 6 to 59 months with confirmed uncomplicated P. falciparum infection were enrolled sequentially first to AS–AQ and then AL at each site and followed up for 28 days. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples collected on day 0 were analysed for mutations in pfkelch13, pfcrt, pfmdr-1, pfdhfr, pfdhps genes and deletions in pfhrp2/pfhrp3 genes. Results By the end of 28-day follow-up, per-protocol PCR corrected ACPR of 97.8% (CI 95% 88.2–100) in Kelo and 100% in Doba and Kayoma were observed among AL treated patients. For ASAQ, 100% ACPR was found in all sites. All, but one patient, did not have parasites detected on day 3. Out of the 215 day 0 samples, 96.7% showed pfkelch13 wild type allele. Seven isolates carried nonsynonymous mutations not known to be associated artemisinin partial resistance (ART-R). Most of samples had a pfcrt wild type allele (79% to 89%). The most prevalent pfmdr-1 allele detected was the single mutant 184F (51.2%). For pfdhfr and pfdhps mutations, the quintuple mutant allele N51I/C59R/S108N + G437A/540E responsible for SP treatment failures in adults and children was not detected. Single deletion in the pfhrp2 and pfhrp3 gene were detected in 10/215 (4.7%) and 2/215 (0.9%), respectively. Dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, were observed in 5/215 (2.3%) isolates. Conclusion The results of this study confirm that AS–AQ and AL treatments are highly efficacious in study areas in Chad. The absence of known pfkelch13 mutations in the study sites and the high parasite clearance rate at day 3 suggest the absence of ART-R. The absence of pfdhfr/pfdhps quintuple or sextuple (quintuple + 581G) mutant supports the continued use of SP for IPTp during pregnancy. The presence of parasites with dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, warrants the continued surveillance. Trial registration ACTRN12622001476729https://doi.org/10.1186/s12936-023-04644-wMalariaPlasmodium falciparumArtesunate–amodiaquineArtemether–lumefantrineArtemisinin resistancepfKelch13 |
| spellingShingle | Mahamat Souleymane Issa Marian Warsame Moussa Hassane Taisso Mahamat Issakha Diar Mahamat Saleh Kodbsse Boulotigam Honoré Djimrassengar Ali Haggar Issa Ousmane Abdelkader Manah Hassoumi Mbanga Djimadoum Cécile Doderer-Lang Jean Bosco Ndihiokubwayo Charlotte Rasmussen Didier Menard Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance Malaria Journal Malaria Plasmodium falciparum Artesunate–amodiaquine Artemether–lumefantrine Artemisinin resistance pfKelch13 |
| title | Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance |
| title_full | Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance |
| title_fullStr | Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance |
| title_full_unstemmed | Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance |
| title_short | Therapeutic efficacy of artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance |
| title_sort | therapeutic efficacy of artesunate amodiaquine and artemether lumefantrine for the treatment of uncomplicated falciparum malaria in chad clinical and genetic surveillance |
| topic | Malaria Plasmodium falciparum Artesunate–amodiaquine Artemether–lumefantrine Artemisinin resistance pfKelch13 |
| url | https://doi.org/10.1186/s12936-023-04644-w |
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