TY - JOUR
T1 - Monitoring of efficacy, tolerability and safety of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon
T2 - an open-label clinical trial
AU - Adegbite, Bayode R
AU - Edoa, Jean R
AU - Honkpehedji, Yabo J
AU - Zinsou, Frejus J
AU - Dejon-Agobe, Jean C
AU - Mbong-Ngwese, Mirabeau
AU - Lotola-Mougueni, Fabrice
AU - Koehne, Erik
AU - Lalremruata, Albert
AU - Kreidenweiss, Andrea
AU - Nguyen, The T
AU - Kun, Jutta
AU - Agnandji, Selidji T
AU - Lell, Bertrand
AU - Safiou, Abdou R
AU - Obone Atome, Fridia A
AU - Mombo-Ngoma, Ghyslain
AU - Ramharter, Michael
AU - Velavan, Thirumalaisamy P
AU - Mordmüller, Benjamin
AU - Kremsner, Peter G
AU - Adegnika, Ayola A
PY - 2019/12/16
Y1 - 2019/12/16
N2 - Background: Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. Methods: A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of antimalarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. Results: Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. Conclusion: This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True
AB - Background: Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon. Methods: A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of antimalarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened. Results: Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment. Conclusion: This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True
KW - Amodiaquine/therapeutic use
KW - Antimalarials/therapeutic use
KW - Artemether, Lumefantrine Drug Combination/therapeutic use
KW - Artemisinins/therapeutic use
KW - Child
KW - Child, Preschool
KW - Drug Combinations
KW - Drug Monitoring/statistics & numerical data
KW - Female
KW - Gabon
KW - Humans
KW - Infant
KW - Malaria, Falciparum/drug therapy
KW - Male
KW - Plasmodium falciparum/drug effects
KW - Protozoan Proteins/genetics
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85076715128&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31842893
U2 - https://doi.org/10.1186/s12936-019-3015-4
DO - https://doi.org/10.1186/s12936-019-3015-4
M3 - Article
C2 - 31842893
SN - 1475-2875
VL - 18
JO - Malaria journal
JF - Malaria journal
IS - 1
M1 - 424
ER -