Therapeutic efficacy and tolerability of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Niger, 2020.
P. falciparum
Artemether–lumefantrine
Efficacy
Niger
Resistance
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
13 May 2024
13 May 2024
Historique:
received:
10
01
2024
accepted:
12
04
2024
medline:
14
5
2024
pubmed:
14
5
2024
entrez:
13
5
2024
Statut:
epublish
Résumé
Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether-lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger. A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000-200,000 asexual parasites/μL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan-Meier curve assessed parasite clearance. A total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4-101.0%), 92.2% (85.0-98.5%) and 97.1% (93.1-101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance. The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations. Trial registration NCT05070520, October 7, 2021.
Sections du résumé
BACKGROUND
BACKGROUND
Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether-lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger.
METHODS
METHODS
A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000-200,000 asexual parasites/μL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan-Meier curve assessed parasite clearance.
RESULTS
RESULTS
A total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4-101.0%), 92.2% (85.0-98.5%) and 97.1% (93.1-101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance.
CONCLUSION
CONCLUSIONS
The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations. Trial registration NCT05070520, October 7, 2021.
Identifiants
pubmed: 38741101
doi: 10.1186/s12936-024-04945-8
pii: 10.1186/s12936-024-04945-8
doi:
Substances chimiques
Artemether, Lumefantrine Drug Combination
0
Antimalarials
0
Banques de données
ClinicalTrials.gov
['NCT05070520']
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
144Informations de copyright
© 2024. The Author(s).
Références
MSP-PNLP. Plan stratégique de lutte contre le paludisme au Niger 2017–2021. Niamey: MSP-PNLP; 2016.
Doudou MH, Mahamadou A, Ouba I, Lazoumar R, Boubacar B, Arzika I, et al. A refined estimate of the malaria burden in Niger. Malar J. 2012;11:89.
doi: 10.1186/1475-2875-11-89
pubmed: 22453027
pmcid: 3342108
WHO. Traitement du paludisme. Geneva: World Health Organization. https://www.who.int/fr/teams/global-malaria-programme/case-management/treatment . Accessed 31 Oct 2022.
MSP_PNLP. Manuel de prise en charge du paludisme au Niger. Niamey: MSP_PNLP; 2020.
Fairhurst RM, Nayyar GML, Breman JG, Hallett R, Vennerstrom JL, Duong S, et al. Artemisinin-resistant malaria: research challenges, opportunities, and public health implications. Am J Trop Med Hyg. 2012;87:231–41.
doi: 10.4269/ajtmh.2012.12-0025
pubmed: 22855752
pmcid: 3414557
Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana SI, Yamauchi M, et al. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med. 2021;385:1163–71.
doi: 10.1056/NEJMoa2101746
pubmed: 34551228
Tacoli C, Gai PP, Bayingana C, Sifft K, Geus D, Ndoli J, et al. Artemisinin resistance-associated K13 polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010–2015. Am J Trop Med Hyg. 2016;95:1090–3.
doi: 10.4269/ajtmh.16-0483
pubmed: 27573632
pmcid: 5094222
WHO. Evaluation et surveillance de l'efficacité des antipaludiques pour le traitement du paludisme à Plasmodium falciparum non compliqué. Geneva: World Health Organization; 2004. https://apps.who.int/iris/bitstream/handle/10665/68595/WHO_HTM_RBM_2003.50_fre.pdf?sequence=1&isAllowed=y . Accessed 1 Nov 2022.
Ibrahima I. Étude de l’efficacité thérapeutique et de la tolérance de l’artéméther–luméfantrine et de l’artésunate–amodiaquine au Niger. Bull Société Pathol Exot. 2020;113:17–23.
doi: 10.3166/bspe-2020-0120
Grandesso F, Guindo O, Woi Messe L, Makarimi R, Traore A, Dama S, et al. Efficacy of artesunate–amodiaquine, dihydroartemisinin–piperaquine and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger. Malar J. 2018;17:52.
doi: 10.1186/s12936-018-2200-1
pubmed: 29370844
pmcid: 5785863
Adamou S, Mahamadou B, Maman D, Maazou A, Adehossi E, Halidou M, et al. Efficacité et tolérance de l’association artémether luméfantrine dans le traitement du paludisme simple à Plasmodium falciparum au Niger. J Rech Sci Université de Lomé. 2012;14:79–84.
Laminou IM, Lamine MM, Mahamadou B, Ascofaré OM, Dieye A. Polymorphism of pfk13-propeller in Niger: detection of novel mutations. J Adv Med Med Res. 2017;22:1–5.
doi: 10.9734/JAMMR/2017/34192
Laminou IM, Arzika I, Lamine MM, Mahamadou B. Detection of Plasmodium falciparum K13 propeller A569G mutation after artesunate-amodiaquine treatment failure in Niger. J Adv Biol Biotechnol. 2018;18:1–8.
doi: 10.9734/JABB/2018/42872
Issa I, Lamine MM, Hubert V, Ilagouma A, Adehossi E, Mahamadou A, et al. Prevalence of mutations in the Pfdhfr, Pfdhps, and Pfmdr1 genes of malarial parasites isolated from symptomatic patients in Dogondoutchi, Niger. Trop Med Infect Dis. 2022;7:155.
doi: 10.3390/tropicalmed7080155
pubmed: 36006247
pmcid: 9413624
Beshir KB, Muwanguzi J, Nader J, Mansukhani R, Traore A, Gamougam K, et al. Prevalence of Plasmodium falciparum haplotypes associated with resistance to sulfadoxine–pyrimethamine and amodiaquine before and after upscaling of seasonal malaria chemoprevention in seven African countries: a genomic surveillance study. Lancet Infect Dis. 2023;23:361–70.
doi: 10.1016/S1473-3099(22)00593-X
pubmed: 36328000
Ibrahim ML, Steenkeste N, Khim N, Adam HH, Konaté L, Coppée JY, et al. Field-based evidence of fast and global increase of Plasmodium falciparum drug-resistance by DNA-microarrays and PCR/RFLP in Niger. Malar J. 2009;8:32.
doi: 10.1186/1475-2875-8-32
pubmed: 19236701
pmcid: 2654903
Viriyakosol S, Siripoon N, Petcharapirat C, Petcharapirat P, Jarra W, Thaithong S, et al. Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bull World Health Organ. 1995;73:85–95.
pubmed: 7704931
pmcid: 2486592
Ibrahim A, Mahamane ML, Aboubacar M, Halima Z, Ibrahim ML: Polymorphisme msp1_2_CAMES SANTE.pdf. not a suitable reference—please add link and other details
Ménard D, Khim N, Beghain J, Adegnika AA, Shafiul-Alam M, Amodu O, et al. A worldwide map of Plasmodium falciparum K13-propeller polymorphisms. N Engl J Med. 2016;374:2453–64.
doi: 10.1056/NEJMoa1513137
pubmed: 27332904
pmcid: 4955562
Diarra Y, Koné O, Sangaré L, Doumbia L, Haidara DBB, Diallo M, et al. Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015–2016. Malar J. 2021;20:235.
doi: 10.1186/s12936-021-03760-9
pubmed: 34034754
pmcid: 8146210
Kpemasse A, Dagnon F, Saliou R, Yarou Maye AS, Affoukou CD, Zoulkaneri A, et al. Efficacy of artemether-lumefantrine for the treatment of Plasmodium falciparum malaria in Bohicon and Kandi, Republic of Benin, 2018–2019. Am J Trop Med Hyg. 2021;105:670–6.
doi: 10.4269/ajtmh.21-0086
pubmed: 34255739
pmcid: 8592339
Diallo MA, Yade MS, Ndiaye YD, Diallo I, Diongue K, Sy SA, et al. Efficacy and safety of artemisinin-based combination therapy and the implications of Pfkelch13 and Pfcoronin molecular markers in treatment failure in Senegal. Sci Rep. 2020;10:8907.
doi: 10.1038/s41598-020-65553-5
pubmed: 32483161
pmcid: 7264303
Toure OA, Assi SB, Kiki-Barro PMC, Yavo W, Abba T, Tiacoh LN, et al. Efficacy and safety of artesuante-amodiaquine and artemether lumefantrine, the first line malaria treatment in six sentinel’s sites of Côte d’Ivoire. West Africa Ann Parasitol. 2020;66:561–71.
pubmed: 33789028
OMS Niger_Rapport activités 2020.pdf. https://www.afro.who.int/sites/default/files/2021-04/OMS%20Niger_Rapport%20activit%C3%A9s%202020.pdf . Accessed 31 Oct 2022.
WHO. Chimioprévention du paludisme saisonnier par administration de sulfadoxine-pyriméthamine et d’amodiaquine aux enfants: guide de terrain. Geneva: World Health Organization. http://www.who.int/malaria/publications/atoz/9789241504737/fr/