In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso
Abstract Background Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether–lumefantrine (AL) and artesunate–amodiaqu...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-019-3089-z |
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| author | Moussa Lingani Léa Nadège Bonkian Isidore Yerbanga Adama Kazienga Innocent Valéa Hermann Sorgho Jean Bosco Ouédraogo Petronella Francisca Mens Henk D. F. H. Schallig Raffaella Ravinetto Umberto d’Alessandro Halidou Tinto |
| author_facet | Moussa Lingani Léa Nadège Bonkian Isidore Yerbanga Adama Kazienga Innocent Valéa Hermann Sorgho Jean Bosco Ouédraogo Petronella Francisca Mens Henk D. F. H. Schallig Raffaella Ravinetto Umberto d’Alessandro Halidou Tinto |
| author_sort | Moussa Lingani |
| collection | DOAJ |
| description | Abstract Background Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. Methods In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. Results Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). Conclusion These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1 |
| first_indexed | 2024-12-14T15:16:52Z |
| format | Article |
| id | doaj.art-a0a9b3bb0842490595761c4ebe67af4b |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-14T15:16:52Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-a0a9b3bb0842490595761c4ebe67af4b2022-12-21T22:56:17ZengBMCMalaria Journal1475-28752020-01-0119111310.1186/s12936-019-3089-zIn vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina FasoMoussa Lingani0Léa Nadège Bonkian1Isidore Yerbanga2Adama Kazienga3Innocent Valéa4Hermann Sorgho5Jean Bosco Ouédraogo6Petronella Francisca Mens7Henk D. F. H. Schallig8Raffaella Ravinetto9Umberto d’Alessandro10Halidou Tinto11Institut de Recherche en Sciences de la Santé/Direction Régionale du Centre Ouest (IRSS/DRCO)Unité de Recherche sur le Paludisme et Maladies Tropicales NégligéesUnité de Recherche Clinique de Nanoro (URCN)Unité de Recherche Clinique de Nanoro (URCN)Institut de Recherche en Sciences de la Santé/Direction Régionale du Centre Ouest (IRSS/DRCO)Institut de Recherche en Sciences de la Santé/Direction Régionale du Centre Ouest (IRSS/DRCO)Institut de Recherche en Sciences de la Santé/Direction Régionale du Centre Ouest (IRSS/DRCO)Department of Medical Microbiology, Experimental Parasitology Unit, Amsterdam University Medical Centres, Academic Medical Centre at the University of AmsterdamDepartment of Medical Microbiology, Experimental Parasitology Unit, Amsterdam University Medical Centres, Academic Medical Centre at the University of AmsterdamPublic Health Department, Institute of Tropical MedicineMedical Research Council Unit, The Gambia, Disease Control & Elimination ThemeInstitut de Recherche en Sciences de la Santé/Direction Régionale du Centre Ouest (IRSS/DRCO)Abstract Background Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. Methods In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. Results Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). Conclusion These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1https://doi.org/10.1186/s12936-019-3089-zArtemisinin-based combination therapyIn vivo/ex vivoEfficacySafetyUncomplicated malariaPaediatric |
| spellingShingle | Moussa Lingani Léa Nadège Bonkian Isidore Yerbanga Adama Kazienga Innocent Valéa Hermann Sorgho Jean Bosco Ouédraogo Petronella Francisca Mens Henk D. F. H. Schallig Raffaella Ravinetto Umberto d’Alessandro Halidou Tinto In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso Malaria Journal Artemisinin-based combination therapy In vivo/ex vivo Efficacy Safety Uncomplicated malaria Paediatric |
| title | In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso |
| title_full | In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso |
| title_fullStr | In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso |
| title_full_unstemmed | In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso |
| title_short | In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso |
| title_sort | in vivo ex vivo efficacy of artemether lumefantrine and artesunate amodiaquine as first line treatment for uncomplicated falciparum malaria in children an open label randomized controlled trial in burkina faso |
| topic | Artemisinin-based combination therapy In vivo/ex vivo Efficacy Safety Uncomplicated malaria Paediatric |
| url | https://doi.org/10.1186/s12936-019-3089-z |
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