In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018
Abstract Background Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-021-03922-9 |
| _version_ | 1818368004340056064 |
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| author | Abel Nhama Lídia Nhamússua Eusébio Macete Quique Bassat Crizolgo Salvador Sónia Enosse Baltazar Candrinho Eva Carvalho Arsénio Nhacolo Arlindo Chidimatembue Abuchahama Saifodine Rose Zulliger Naomi Lucchi Samaly S. Svigel Leah F. Moriarty Eric S. Halsey Alfredo Mayor Pedro Aide |
| author_facet | Abel Nhama Lídia Nhamússua Eusébio Macete Quique Bassat Crizolgo Salvador Sónia Enosse Baltazar Candrinho Eva Carvalho Arsénio Nhacolo Arlindo Chidimatembue Abuchahama Saifodine Rose Zulliger Naomi Lucchi Samaly S. Svigel Leah F. Moriarty Eric S. Halsey Alfredo Mayor Pedro Aide |
| author_sort | Abel Nhama |
| collection | DOAJ |
| description | Abstract Background Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS–AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results Totals of 368 and 273 patients were enrolled in the AL and AS–AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS–AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS–AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3–89.2%) for AL and 98.8% (95% CI 96.7–99.8%) for AS–AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6–99.2%) for AL and 99.6% (95% CI 97.9–100%) for AS–AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS–AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion Both AL and AS–AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov: NCT04370977 |
| first_indexed | 2024-12-13T23:01:03Z |
| format | Article |
| id | doaj.art-d7fcf41e715d4331a632b40ce0e89937 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-13T23:01:03Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-d7fcf41e715d4331a632b40ce0e899372022-12-21T23:28:23ZengBMCMalaria Journal1475-28752021-10-0120111210.1186/s12936-021-03922-9In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018Abel Nhama0Lídia Nhamússua1Eusébio Macete2Quique Bassat3Crizolgo Salvador4Sónia Enosse5Baltazar Candrinho6Eva Carvalho7Arsénio Nhacolo8Arlindo Chidimatembue9Abuchahama Saifodine10Rose Zulliger11Naomi Lucchi12Samaly S. Svigel13Leah F. Moriarty14Eric S. Halsey15Alfredo Mayor16Pedro Aide17Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Instituto Nacional de Saúde (INS), Ministério da SaúdeInstituto Nacional de Saúde (INS), Ministério da SaúdePrograma Nacional de Controlo da Malária, Ministério da SaúdeWorld Health Organization, WHO Country Office MaputoCentro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)United States President’s Malaria Initiative, United States Agency for International DevelopmentUnited States President’s Malaria Initiative, 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 PreventionMalaria Branch, Centers for Disease Control and PreventionCentro de Investigação em Saúde de Manhiça (CISM)Centro de Investigação em Saúde de Manhiça (CISM)Abstract Background Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS–AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results Totals of 368 and 273 patients were enrolled in the AL and AS–AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS–AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS–AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3–89.2%) for AL and 98.8% (95% CI 96.7–99.8%) for AS–AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6–99.2%) for AL and 99.6% (95% CI 97.9–100%) for AS–AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS–AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion Both AL and AS–AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov: NCT04370977https://doi.org/10.1186/s12936-021-03922-9EfficacyArtemether–lumefantrineArtesunate–amodiaquineUncomplicated malariaChildrenMozambique |
| spellingShingle | Abel Nhama Lídia Nhamússua Eusébio Macete Quique Bassat Crizolgo Salvador Sónia Enosse Baltazar Candrinho Eva Carvalho Arsénio Nhacolo Arlindo Chidimatembue Abuchahama Saifodine Rose Zulliger Naomi Lucchi Samaly S. Svigel Leah F. Moriarty Eric S. Halsey Alfredo Mayor Pedro Aide In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018 Malaria Journal Efficacy Artemether–lumefantrine Artesunate–amodiaquine Uncomplicated malaria Children Mozambique |
| title | In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018 |
| title_full | In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018 |
| title_fullStr | In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018 |
| title_full_unstemmed | In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018 |
| title_short | In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018 |
| title_sort | in vivo efficacy and safety of artemether lumefantrine and amodiaquine artesunate for uncomplicated plasmodium falciparum malaria in mozambique 2018 |
| topic | Efficacy Artemether–lumefantrine Artesunate–amodiaquine Uncomplicated malaria Children Mozambique |
| url | https://doi.org/10.1186/s12936-021-03922-9 |
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