World Health Organization , 2020. World Malaria Report 2020: 20 Years of Global Progress and Challenges. Geneva, Switzerland: WHO. Available at: https://www.who.int/publications/i/item/9789240015791.
Santé Mdl , 2019. Annuaire des statistiques sanitaires. Cotonou, Benin: Santé Mdl, 144.
Haldar K , Bhattacharjee S , Safeukui I , 2018. Drug resistance in Plasmodium. Nat Rev Microbiol 16: 156–170.
World Health Organization , 2015. Guidelines for the Treatment of Malaria. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/guidelines-for-the-treatment-of-malaria-eng.pdf?sfvrsn=a0138b77_2. Accessed April 6, 2021.
World Health Organization , 2009. Methods for Surveillance of Antimalarial Drug Efficacy. Geneva, Switzerland: WHO. Available at: https://apps.who.int/iris/bitstream/handle/10665/44048/9789241597531_eng.pdf?sequence=1&isAllowed=y.
World Health Organization , 2015. Status Report on Artemisinin Resistance. Geneva, Switzerland: WHO. Available at: https://www.who.int/malaria/publications/atoz/status-rep-artemisinin-act-resistance-sept2015.pdf. Accessed April 6, 2021.
Santé Mdl , 2017. Directives Nationales de Prise en Charge des Cas de Paludisme. Cotonou, Benin: Paludisme PNdLcl, 6.
World Health Organization , 2011 .Global Plan for Artemisinin Resistance Containment. Geneva, Switzerland: WHO. Available at: https://www.who.int/malaria/publications/atoz/9789241500838/en/. Accessed August 10, 2020.
Ogouyèmi-Hounto A , Azandossessi C , Lawani S , Damien G , de Tove YSS , Remoue F , Gazard DK , 2016. Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. Malar J 15: 1–8.
Abuaku B , Duah N , Quaye L , Quashie N , Malm K , Bart-Plange C , Koram K , 2016. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana. Malar J 15: 6.
Ebenebe JC et al., 2018. Efficacy of artemisinin-based combination treatments of uncomplicated falciparum malaria in under-five-year-old Nigerian children ten years following adoption as first-line antimalarials. Am J Trop Med Hyg 99: 649–664.
Gansané A et al., 2021. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018. Malar J 20: 1–12.
Borre MB et al., 1991. Primary structure and localization of a conserved immunogenic Plasmodium falciparum glutamate rich protein (GLURP) expressed in both the preerythrocytic and erythrocytic stages of the vertebrate life cycle. Mol Biochem Parasitol 49: 119–131.
Fenton B , Clark JT , Khan CM , Robinson JV , Walliker D , Ridley R , Scaife JG , McBride JS , 1991. Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. Mol Cell Biol 11: 963–971.
Cattamanchi A , Kyabayinze D , Hubbard A , Rosenthal PJ , Dorsey G , 2003. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg 68: 133–139.
Daniels R , Hamilton EJ , Durfee K , Ndiaye D , Wirth DF , Hartl DL , Volkman SK , 2015. Methods to increase the sensitivity of high resolution melting single nucleotide polymorphism genotyping in malaria. J Vis Exp 105: 52839.
Vestergaard LS , Ringwald P , 2007. Responding to the challenge of antimalarial drug resistance by routine monitoring to update national malaria treatment policies. Am J Trop Med Hyg 77: 153–159.
Ogouyemi-Hounto A , Azandossessi C , Lawani S , Damien G , de Tove YS , Remoue F , Kinde Gazard D , 2016. Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. Malar J 15: 37.
Abuaku B , Duah N , Quaye L , Quashie N , Koram K , 2012. Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana. Malar J 11: 388.
Davlantes E et al., 2018. 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. Malar J 17: 144.
Plucinski MM et al., 2015. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uige Provinces, angola. Antimicrob Agents Chemother 59: 437–443.
Niare K et al., 2016. In vivo efficacy and parasite clearance of artesunate + sulfadoxine-pyrimethamine versus artemether-lumefantrine in Mali. Am J Trop Med Hyg 94: 634–639.
Talundzic E et al., 2018. Next-generation sequencing and bioinformatics protocol for malaria drug resistance marker surveillance. Antimicrob Agents Chemother 62: e02474-17.
de Laurent ZR , Chebon LJ , Ingasia LA , Akala HM , Andagalu B , Ochola-Oyier LI , Kamau E , 2018. Polymorphisms in the K13 gene in Plasmodium falciparum from different malaria transmission areas of Kenya. Am J Trop Med Hyg 98: 1360–1366.
Ljolje D et al., 2018. Prevalence of molecular markers of artemisinin and lumefantrine resistance among patients with uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2015. Malar J 17: 84.
Fancony C , Brito M , Gil JP , 2016. Plasmodium falciparum drug resistance in Angola. Malar J 15: 74.
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In 2005, artemether-lumefantrine (AL), an artemisinin-based combination therapy, was introduced as the first-line treatment of uncomplicated Plasmodium falciparum malaria in Benin. Per World Health Organization recommendations to monitor the efficacy of antimalarial treatment, we conducted a therapeutic efficacy study with AL for uncomplicated P. falciparum malaria in Bohicon and Kandi, Benin, from 2018 to 2019. Febrile patients aged 6 to 59 months with confirmed P. falciparum monoinfection received supervised doses of AL for 3 days. We monitored patients clinically and parasitologically on days 1, 2, 3, 7, 14, 21, and 28. A molecular analysis to detect mutations in the P. falciparum Kelch propeller gene (Pfk13) gene was carried out on day 0 samples. A total of 205 patients were included in the study. In Bohicon, the uncorrected adequate clinical and parasitological response (ACPR) proportion was 91.3% (95% confidence interval [CI]: 84.6–95.8%), whereas in Kandi this proportion was 96.7% (95% CI: 90.6–99.3%). Genotype-corrected ACPR proportions were 96.3% (95% CI: 90.9–99.0%) and 96.7% (95% CI: 90.6–99.3%) in Bohicon and Kandi, respectively. On day 3, 100% of patients in Bohicon and 98.9% of patients in Kandi had undetectable parasitemia. The C580Y mutation in the Pfk13 gene was not observed. AL remains effective for P. falciparum malaria in these two sites in Benin. Monitoring antimalarial efficacy and prevalence of molecular-resistance markers in Benin should be continued to allow for early detection of antimalarial resistance and to guide treatment policies.
Financial support: Funding for this study was partially provided by the U.S. Agency for International Development through the President’s Malaria Initiative.
Disclaimer: The funding sources for this study had no role in study design, data collection, analysis, or interpretation. The opinions expressed herein are those of the authors and do not necessarily reflect the views of the Benin National Malaria Control Program, U.S. Agency for International Development, or the Centers for Disease Control and Prevention.
Authors’ addresses: Augustin Kpemasse, Programme National de Lutte contre le Paludisme, Laboratory Service and Chemosensitivity, Cotonou, Benin, E-mail: kpemasseaugustin@yahoo.fr. Fortune Dagnon, USAID, Benin, Cotonou, E-mail: lecuredars@yahoo.fr. Ramani Saliou, Alexis Sacca Yarou Maye, Cyriaque Dossou Affoukou, Programme National de Lutte contre le Paludisme, MS, Cotonou, Benin, E-mails: ramani.saliou@yahoo.fr, yarou_alexis@yahoo.fr, and moiacdm@yahoo.fr. Alassane Zoulkaneri, Ministry of Health Benin, Kandi Health Center, Kandi, Benin, E-mail: alphazoul@yahoo.fr. Blaise Guézo-Mévo, Hopital de zone, Département de senté du Mono-Couffo, Comé, Benin, E-mail: guemebla@yahoo.fr. Leah F. Moriarty, Centers for Disease Control and Prevention Center for Global Health, Malaria Branch, Atlanta, GA, E-mail: wvp4@cdc.gov or lmoriarty@cdc.gov. Yaye D. Ndiaye, Awa Bineta Deme, and Daouda Ndiaye, Univerté Cheikh Anta Diop, Parasitologie-Mycologie, Dakar, Senegal, E-mails: ydndiaye@gmail.com, deme.awa@gmail.com, and dndiaye@hsph.harvard.edu. Mamane Nassirou Garba, Hospital DANTEC, Molecular Biology and Genomics Laboratory, Dakar, Senegal, E-mail: nassirou.garba@gmail.com. Aurore Ogouyemi Hounto, Programme National de Lutte contre le Paludisme, Directorate, Cotonou, Benin, E-mail: aurorefel@yahoo.fr.
World Health Organization , 2020. World Malaria Report 2020: 20 Years of Global Progress and Challenges. Geneva, Switzerland: WHO. Available at: https://www.who.int/publications/i/item/9789240015791.
Santé Mdl , 2019. Annuaire des statistiques sanitaires. Cotonou, Benin: Santé Mdl, 144.
Haldar K , Bhattacharjee S , Safeukui I , 2018. Drug resistance in Plasmodium. Nat Rev Microbiol 16: 156–170.
World Health Organization , 2015. Guidelines for the Treatment of Malaria. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/guidelines-for-the-treatment-of-malaria-eng.pdf?sfvrsn=a0138b77_2. Accessed April 6, 2021.
World Health Organization , 2009. Methods for Surveillance of Antimalarial Drug Efficacy. Geneva, Switzerland: WHO. Available at: https://apps.who.int/iris/bitstream/handle/10665/44048/9789241597531_eng.pdf?sequence=1&isAllowed=y.
World Health Organization , 2015. Status Report on Artemisinin Resistance. Geneva, Switzerland: WHO. Available at: https://www.who.int/malaria/publications/atoz/status-rep-artemisinin-act-resistance-sept2015.pdf. Accessed April 6, 2021.
Santé Mdl , 2017. Directives Nationales de Prise en Charge des Cas de Paludisme. Cotonou, Benin: Paludisme PNdLcl, 6.
World Health Organization , 2011 .Global Plan for Artemisinin Resistance Containment. Geneva, Switzerland: WHO. Available at: https://www.who.int/malaria/publications/atoz/9789241500838/en/. Accessed August 10, 2020.
Ogouyèmi-Hounto A , Azandossessi C , Lawani S , Damien G , de Tove YSS , Remoue F , Gazard DK , 2016. Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. Malar J 15: 1–8.
Abuaku B , Duah N , Quaye L , Quashie N , Malm K , Bart-Plange C , Koram K , 2016. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana. Malar J 15: 6.
Ebenebe JC et al., 2018. Efficacy of artemisinin-based combination treatments of uncomplicated falciparum malaria in under-five-year-old Nigerian children ten years following adoption as first-line antimalarials. Am J Trop Med Hyg 99: 649–664.
Gansané A et al., 2021. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018. Malar J 20: 1–12.
Borre MB et al., 1991. Primary structure and localization of a conserved immunogenic Plasmodium falciparum glutamate rich protein (GLURP) expressed in both the preerythrocytic and erythrocytic stages of the vertebrate life cycle. Mol Biochem Parasitol 49: 119–131.
Fenton B , Clark JT , Khan CM , Robinson JV , Walliker D , Ridley R , Scaife JG , McBride JS , 1991. Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. Mol Cell Biol 11: 963–971.
Cattamanchi A , Kyabayinze D , Hubbard A , Rosenthal PJ , Dorsey G , 2003. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg 68: 133–139.
Daniels R , Hamilton EJ , Durfee K , Ndiaye D , Wirth DF , Hartl DL , Volkman SK , 2015. Methods to increase the sensitivity of high resolution melting single nucleotide polymorphism genotyping in malaria. J Vis Exp 105: 52839.
Vestergaard LS , Ringwald P , 2007. Responding to the challenge of antimalarial drug resistance by routine monitoring to update national malaria treatment policies. Am J Trop Med Hyg 77: 153–159.
Ogouyemi-Hounto A , Azandossessi C , Lawani S , Damien G , de Tove YS , Remoue F , Kinde Gazard D , 2016. Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Benin. Malar J 15: 37.
Abuaku B , Duah N , Quaye L , Quashie N , Koram K , 2012. Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana. Malar J 11: 388.
Davlantes E et al., 2018. 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. Malar J 17: 144.
Plucinski MM et al., 2015. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uige Provinces, angola. Antimicrob Agents Chemother 59: 437–443.
Niare K et al., 2016. In vivo efficacy and parasite clearance of artesunate + sulfadoxine-pyrimethamine versus artemether-lumefantrine in Mali. Am J Trop Med Hyg 94: 634–639.
Talundzic E et al., 2018. Next-generation sequencing and bioinformatics protocol for malaria drug resistance marker surveillance. Antimicrob Agents Chemother 62: e02474-17.
de Laurent ZR , Chebon LJ , Ingasia LA , Akala HM , Andagalu B , Ochola-Oyier LI , Kamau E , 2018. Polymorphisms in the K13 gene in Plasmodium falciparum from different malaria transmission areas of Kenya. Am J Trop Med Hyg 98: 1360–1366.
Ljolje D et al., 2018. Prevalence of molecular markers of artemisinin and lumefantrine resistance among patients with uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2015. Malar J 17: 84.
Fancony C , Brito M , Gil JP , 2016. Plasmodium falciparum drug resistance in Angola. Malar J 15: 74.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1512 | 578 | 198 |
Full Text Views | 214 | 33 | 1 |
PDF Downloads | 156 | 13 | 1 |