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

Simple item page
dc.contributor.authorDavlantes, Elizabeth
dc.contributor.authorDimbu, Pedro R
dc.contributor.authorFerreira, Carolina M
dc.contributor.authorFlorinda Joao, Maria
dc.contributor.authorPode, Dilunvuidi
dc.contributor.authorFélix, Jacinto
dc.contributor.authorSanhangala, Edgar
dc.contributor.authorAndrade, Benjamin N
dc.contributor.authordos Santos Souza, Samaly
dc.contributor.authorTalundzic, Eldin
dc.contributor.authorUdhayakumar, Venkatachalam
dc.contributor.authorOwens, Chantelle
dc.contributor.authorMbounga, Eliane
dc.contributor.authorWiesner, Lubbe
dc.contributor.authorHalsey, Eric S
dc.contributor.authorMartins, José F
dc.contributor.authorFortes, Filomeno
dc.contributor.authorPlucinski, Mateusz M
dc.date.accessioned2018-05-07T14:51:38Z
dc.date.available2018-05-07T14:51:38Z
dc.date.issued2018-04-03
dc.date.updated2018-04-09T15:15:04Z
dc.description.abstractBackground 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.
dc.identifier.apacitationDavlantes, E., Dimbu, P. R., Ferreira, C. M., Florinda Joao, M., Pode, D., Félix, J., ... Plucinski, M. M. (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. <i>Malaria Journal</i>, http://hdl.handle.net/11427/28001en_ZA
dc.identifier.chicagocitationDavlantes, Elizabeth, Pedro R Dimbu, Carolina M Ferreira, Maria Florinda Joao, Dilunvuidi Pode, Jacinto Félix, Edgar Sanhangala, et al "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." <i>Malaria Journal</i> (2018) http://hdl.handle.net/11427/28001en_ZA
dc.identifier.citationDavlantes, E., Dimbu, P. R., Ferreira, C. M., Joao, M. F., Pode, D., Félix, J., ... & Udhayakumar, V. (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. Malaria journal, 17(1), 144.
dc.identifier.ris TY - Journal Article AU - Davlantes, Elizabeth AU - Dimbu, Pedro R AU - Ferreira, Carolina M AU - Florinda Joao, Maria AU - Pode, Dilunvuidi AU - Félix, Jacinto AU - Sanhangala, Edgar AU - Andrade, Benjamin N AU - dos Santos Souza, Samaly AU - Talundzic, Eldin AU - Udhayakumar, Venkatachalam AU - Owens, Chantelle AU - Mbounga, Eliane AU - Wiesner, Lubbe AU - Halsey, Eric S AU - Martins, José F AU - Fortes, Filomeno AU - Plucinski, Mateusz M AB - 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. DA - 2018-04-03 DB - OpenUCT DP - University of Cape Town J1 - Malaria Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - 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 TI - 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 UR - http://hdl.handle.net/11427/28001 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12936-018-2290-9
dc.identifier.urihttp://hdl.handle.net/11427/28001
dc.identifier.vancouvercitationDavlantes E, Dimbu PR, Ferreira CM, Florinda Joao M, Pode D, Félix J, et al. 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. 2018; http://hdl.handle.net/11427/28001.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDivision of Chemical Pathologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s)
dc.sourceMalaria Journal
dc.source.urihttps://malariajournal.biomedcentral.com/
dc.subject.otherAntimalarial resistance
dc.subject.otherArtemether–lumefantrine
dc.subject.otherArtesunate–amodiaquine
dc.subject.otherDihydroartemisinin–piperaquine
dc.subject.otherpfK13
dc.subject.otherpfmdr1
dc.subject.otherpfcrt
dc.subject.otherpfpm2
dc.titleEfficacy and safety of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
12936_2018_Article_2290.pdf
Size:
1.01 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.72 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles