Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017
Abstract Background The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malari...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12936-018-2290-9 |
| _version_ | 1819144473745031168 |
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| author | Elizabeth Davlantes Pedro Rafael Dimbu Carolina Miguel Ferreira Maria Florinda Joao Dilunvuidi Pode Jacinto Félix Edgar Sanhangala Benjamin Nieto Andrade Samaly dos Santos Souza Eldin Talundzic Venkatachalam Udhayakumar Chantelle Owens Eliane Mbounga Lubbe Wiesner Eric S. Halsey José Franco Martins Filomeno Fortes Mateusz M. Plucinski |
| author_facet | Elizabeth Davlantes Pedro Rafael Dimbu Carolina Miguel Ferreira Maria Florinda Joao Dilunvuidi Pode Jacinto Félix Edgar Sanhangala Benjamin Nieto Andrade Samaly dos Santos Souza Eldin Talundzic Venkatachalam Udhayakumar Chantelle Owens Eliane Mbounga Lubbe Wiesner Eric S. Halsey José Franco Martins Filomeno Fortes Mateusz M. Plucinski |
| author_sort | Elizabeth Davlantes |
| collection | DOAJ |
| description | Abstract Background The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications’ therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces. Methods Enrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance. Results Of 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91–100%, 95% confidence interval) in Zaire and 97% (93–100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97–100%) in Benguela and 93% (88–99%) in Zaire. The corrected efficacy of DP was 100% (96–100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure. Conclusions AL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola. |
| first_indexed | 2024-12-22T12:42:42Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-22T12:42:42Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-5241e180a982495f90f7637969afe22d2022-12-21T18:25:23ZengBMCMalaria Journal1475-28752018-04-0117111110.1186/s12936-018-2290-9Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017Elizabeth Davlantes0Pedro Rafael Dimbu1Carolina Miguel Ferreira2Maria Florinda Joao3Dilunvuidi Pode4Jacinto Félix5Edgar Sanhangala6Benjamin Nieto Andrade7Samaly dos Santos Souza8Eldin Talundzic9Venkatachalam Udhayakumar10Chantelle Owens11Eliane Mbounga12Lubbe Wiesner13Eric S. Halsey14José Franco Martins15Filomeno Fortes16Mateusz M. Plucinski17Epidemic Intelligence Service, United States Centers for Disease Control and PreventionNational Malaria Control Programme, Ministry of HealthPSI AngolaNational Malaria Control Programme, Ministry of HealthField Epidemiology Training Programme, Ministry of HealthField Epidemiology Training Programme, Ministry of HealthField Epidemiology Training Programme, Ministry of HealthPSI AngolaMalaria Branch, Centers for Disease Control and PreventionMalaria Branch, Centers for Disease Control and PreventionMalaria Branch, Centers for Disease Control and PreventionMalaria Branch, Centers for Disease Control and PreventionUnited States President’s Malaria Initiative, United States Agency for International DevelopmentDivision of Clinical Pharmacology, University of Cape TownMalaria Branch, Centers for Disease Control and PreventionNational Malaria Control Programme, Ministry of HealthNational Malaria Control Programme, Ministry of HealthMalaria Branch, Centers for Disease Control and PreventionAbstract Background The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications’ therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces. Methods Enrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance. Results Of 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91–100%, 95% confidence interval) in Zaire and 97% (93–100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97–100%) in Benguela and 93% (88–99%) in Zaire. The corrected efficacy of DP was 100% (96–100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure. Conclusions AL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola.http://link.springer.com/article/10.1186/s12936-018-2290-9Antimalarial resistanceArtemether–lumefantrineArtesunate–amodiaquineDihydroartemisinin–piperaquinepfK13pfmdr1 |
| spellingShingle | Elizabeth Davlantes Pedro Rafael Dimbu Carolina Miguel Ferreira Maria Florinda Joao Dilunvuidi Pode Jacinto Félix Edgar Sanhangala Benjamin Nieto Andrade Samaly dos Santos Souza Eldin Talundzic Venkatachalam Udhayakumar Chantelle Owens Eliane Mbounga Lubbe Wiesner Eric S. Halsey José Franco Martins Filomeno Fortes Mateusz M. Plucinski Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017 Malaria Journal Antimalarial resistance Artemether–lumefantrine Artesunate–amodiaquine Dihydroartemisinin–piperaquine pfK13 pfmdr1 |
| title | Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017 |
| title_full | Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017 |
| title_fullStr | Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017 |
| title_full_unstemmed | Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017 |
| title_short | Efficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017 |
| title_sort | efficacy and safety of artemether lumefantrine artesunate amodiaquine and dihydroartemisinin piperaquine for the treatment of uncomplicated plasmodium falciparum malaria in three provinces in angola 2017 |
| topic | Antimalarial resistance Artemether–lumefantrine Artesunate–amodiaquine Dihydroartemisinin–piperaquine pfK13 pfmdr1 |
| url | http://link.springer.com/article/10.1186/s12936-018-2290-9 |
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