Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania

Autor: Johannes B. Kataraihya, Renata Mandike, Mwaka A. Kakolwa, Deus S. Ishengoma, Didier Menard, Marian Warsame, Abdunoor M. Kabanywanyi, Celine I. Mandara, Zul Premji, Martha M. Lemnge, Erasmus Kamugisha, Billy Ngasala, Muhidin K. Mahende, Frank Chacky, Ritha Njau, Sigsbert Mkude
Přispěvatelé: Ifakara Health Institute [Dar-es-Salaam, Tanzania], National Institute for Medical Research [Tanzania] (NIMR), Muhimbili University of Health and Allied Sciences, Catholic University of Health and Allied Sciences [Tanzania], National Malaria Control Programme [Dar es Salaam, Tanzanie] (NMCP), World Health Organization Country Office [Dar es Salaam, Tanzanie], Aga Khan University Hospital (AKUH), Nairobi, University of Gothenburg (GU), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Menard, Didier
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
medicine.medical_treatment
Tanzania
chemistry.chemical_compound
0302 clinical medicine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Artemether
Prospective Studies
Artemisinin
Malaria
Falciparum
Child
Artemisinins
3. Good health
Drug Combinations
Infectious Diseases
Child
Preschool
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Quinolines
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Female
Safety
medicine.drug
medicine.medical_specialty
lcsh:Arctic medicine. Tropical medicine
Adolescent
Efficacy
lcsh:RC955-962
030106 microbiology
030231 tropical medicine
Plasmodium falciparum
Dihydroartemisinin
Amodiaquine
Lumefantrine
lcsh:Infectious and parasitic diseases
03 medical and health sciences
Antimalarials
Internal medicine
Piperaquine
parasitic diseases
medicine
Humans
lcsh:RC109-216
business.industry
Research
Artemether
Lumefantrine Drug Combination
Infant
Molecular markers
medicine.disease
Artemisinin-based combination therapy
Malaria
chemistry
Artesunate
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Parasitology
business
Zdroj: Malaria Journal
Malaria Journal, BioMed Central, 2018, 17, pp.369. ⟨10.1186/s12936-018-2524-x⟩
Malaria Journal, 2018, 17, pp.369. ⟨10.1186/s12936-018-2524-x⟩
Malaria Journal, Vol 17, Iss 1, Pp 1-10 (2018)
ISSN: 1475-2875
DOI: 10.1186/s12936-018-2524-x⟩
Popis: 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. 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. 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. 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
Databáze: OpenAIRE
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