The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data
Background: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/155078 |
| Acceso en línea: | https://hdl.handle.net/2445/155078 |
| Access Level: | acceso abierto |
| Palabra clave: | Plasmodium falciparum Malària Malaria |
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The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient dataBretscher, Michael T.Dahal, PrabinGriffin, Jamie T.Stepniewska, KasiaBassat Orellana, QuiqueBaudin, ElisabethAlessandro, Umberto d'Djimde, Abdoulaye A.Dorsey, GrantEspié, EmmanuelleFofana, BakaryGonzález, RaquelJuma, ElizabethKarema, CorineLasry, EstrellaLell, BertrandLima, NinesMenéndez, ClaraMombo-Ngoma, GhyslainMoreira, ClarissaNikiema, FredericOuédraogo, Jean B.Staedke, Sarah G.Tinto, HalidouValea, InnocentYeka, AdokeGhani, Azra C.Guerin, Philippe J.Okell, Lucy C.Plasmodium falciparumMalàriaPlasmodium falciparumMalariaBackground: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. Methods: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. Results: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7–15.7) for AL and 15.2 days (95% CI 12.8–18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7–18.6 days for AL and 10.2–18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. Conclusion: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.BioMed Central2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/155078Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1186/s12916-020-1494-3BMC Medicine, 2020, vol. 18http://dx.doi.org/10.1186/s12916-020-1494-3cc-by (c) Bretscher et al., 2020http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1550782026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| title |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| spellingShingle |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data Bretscher, Michael T. Plasmodium falciparum Malària Plasmodium falciparum Malaria |
| title_short |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| title_full |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| title_fullStr |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| title_full_unstemmed |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| title_sort |
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data |
| dc.creator.none.fl_str_mv |
Bretscher, Michael T. Dahal, Prabin Griffin, Jamie T. Stepniewska, Kasia Bassat Orellana, Quique Baudin, Elisabeth Alessandro, Umberto d' Djimde, Abdoulaye A. Dorsey, Grant Espié, Emmanuelle Fofana, Bakary González, Raquel Juma, Elizabeth Karema, Corine Lasry, Estrella Lell, Bertrand Lima, Nines Menéndez, Clara Mombo-Ngoma, Ghyslain Moreira, Clarissa Nikiema, Frederic Ouédraogo, Jean B. Staedke, Sarah G. Tinto, Halidou Valea, Innocent Yeka, Adoke Ghani, Azra C. Guerin, Philippe J. Okell, Lucy C. |
| author |
Bretscher, Michael T. |
| author_facet |
Bretscher, Michael T. Dahal, Prabin Griffin, Jamie T. Stepniewska, Kasia Bassat Orellana, Quique Baudin, Elisabeth Alessandro, Umberto d' Djimde, Abdoulaye A. Dorsey, Grant Espié, Emmanuelle Fofana, Bakary González, Raquel Juma, Elizabeth Karema, Corine Lasry, Estrella Lell, Bertrand Lima, Nines Menéndez, Clara Mombo-Ngoma, Ghyslain Moreira, Clarissa Nikiema, Frederic Ouédraogo, Jean B. Staedke, Sarah G. Tinto, Halidou Valea, Innocent Yeka, Adoke Ghani, Azra C. Guerin, Philippe J. Okell, Lucy C. |
| author_role |
author |
| author2 |
Dahal, Prabin Griffin, Jamie T. Stepniewska, Kasia Bassat Orellana, Quique Baudin, Elisabeth Alessandro, Umberto d' Djimde, Abdoulaye A. Dorsey, Grant Espié, Emmanuelle Fofana, Bakary González, Raquel Juma, Elizabeth Karema, Corine Lasry, Estrella Lell, Bertrand Lima, Nines Menéndez, Clara Mombo-Ngoma, Ghyslain Moreira, Clarissa Nikiema, Frederic Ouédraogo, Jean B. Staedke, Sarah G. Tinto, Halidou Valea, Innocent Yeka, Adoke Ghani, Azra C. Guerin, Philippe J. Okell, Lucy C. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Plasmodium falciparum Malària Plasmodium falciparum Malaria |
| topic |
Plasmodium falciparum Malària Plasmodium falciparum Malaria |
| description |
Background: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. Methods: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. Results: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7–15.7) for AL and 15.2 days (95% CI 12.8–18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7–18.6 days for AL and 10.2–18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. Conclusion: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
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https://hdl.handle.net/2445/155078 |
| url |
https://hdl.handle.net/2445/155078 |
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Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1186/s12916-020-1494-3 BMC Medicine, 2020, vol. 18 http://dx.doi.org/10.1186/s12916-020-1494-3 |
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cc-by (c) Bretscher et al., 2020 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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cc-by (c) Bretscher et al., 2020 http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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BioMed Central |
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BioMed Central |
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Articles publicats en revistes (ISGlobal) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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