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Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania.
- Source :
-
Malaria journal [Malar J] 2018 Oct 17; Vol. 17 (1), pp. 369. Date of Electronic Publication: 2018 Oct 17. - Publication Year :
- 2018
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Abstract
- Background: Artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment of uncomplicated malaria in most malaria endemic countries, including Tanzania. Unfortunately, there have been reports of artemisinin resistance and ACT failure from South East Asia highlighting the need to monitor therapeutic efficacy of ACT in these countries as recommended by World Health Organization.<br />Methods: Open-label single arm studies in mainland Tanzania were conducted in nine sentinel sites in 2011, 2012 and 2015 to assess the efficacy and safety of artemether/lumefantrine (AL) and artesunate/amodiaquine (ASAQ) using 28 days follow-up and dihydroartemisinin/piperaquine (DHAPQ) using 42 days follow-up. Mutations in the propeller domain of the Plasmodium falciparum kelch 13 (k13) gene and amplification of the P. falciparum plasmepsin 2 (pm2) gene, associated with artemisinin and piperaquine (PQ) resistance, were also investigated.<br />Results: Of the 428 patients enrolled, 328 patients provided study endpoint. For AL, the PCR corrected per-protocol analysis showed adequate clinical and parasitological response (ACPR) of 90.3% (n = 28; 95% CI 74.2-98.0) in Kyela 2012, 95.7% (n = 22; 95% CI 78.1-99.0) in Chamwino, 100% in Muheza (n = 29; 95% CI 88.1-100), 100% in Nagaga (n = 39; 95% CI 91.0-100) and Kyela 2015 (n = 60; 95% CI 94.0-100). For ASAQ, PCR corrected ACPR of 98% (n = 49; 95% CI 89.4-99.9) and 100% (n = 25; 95% CI 86.3-100) were observed in 2011 in Ujiji and Kibaha, respectively. For DHAPQ, the ACPR was 100% (n = 71; 95% CI 94.9-100). Of the 235 samples with genetic interpretable results, only 7 (3%) had non-synonymous k13 mutations. None of these are candidate or validated markers of artemisinin resistance and all patients carrying these alleles cleared the parasites on day 3. Of the DHAPQ group, 10% (3/29) of the samples with interpretable results had pm2 multiple copies and none of them was associated with treatment failure.<br />Conclusion: All the tested ACT in mainland Tanzania were highly efficacious and none of validated k13 mutants associated with artemisinin resistance was observed. However, three isolates with multiple copy numbers of pm2 gene associated with PQ resistance among the limited samples tested successfully calls for further investigation. Trial registration Number ACTRN12615000159550. Registered 18th February 2015, https://www.anzctr.org.au/trial/MyTrial.aspx.
- Subjects :
- Adolescent
Amodiaquine adverse effects
Antimalarials adverse effects
Artemether, Lumefantrine Drug Combination adverse effects
Artemisinins adverse effects
Child
Child, Preschool
Drug Combinations
Female
Humans
Infant
Male
Plasmodium falciparum drug effects
Prospective Studies
Quinolines adverse effects
Tanzania
Amodiaquine therapeutic use
Antimalarials therapeutic use
Artemether, Lumefantrine Drug Combination therapeutic use
Artemisinins therapeutic use
Malaria, Falciparum prevention & control
Quinolines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2875
- Volume :
- 17
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Malaria journal
- Publication Type :
- Academic Journal
- Accession number :
- 30333022
- Full Text :
- https://doi.org/10.1186/s12936-018-2524-x