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Therapeutic efficac...
Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Chad: clinical and genetic surveillance
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Issa, M. S. (författare)
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- Warsame, Marian (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Institute of Medicine, School of Public Health and Community Medicine
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Mahamat, M. H. T. (författare)
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Saleh, I. D. M. (författare)
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Boulotigam, K. (författare)
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Djimrassengar, H. (författare)
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Issa, A. H. (författare)
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Abdelkader, O. (författare)
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Hassoumi, M. (författare)
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Djimadoum, M. (författare)
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Doderer-Lang, C. (författare)
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Ndihiokubwayo, J. B. (författare)
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Rasmussen, C. (författare)
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Menard, D. (författare)
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Malaria Journal. ; 22:1
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BackgroundArtesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) are the currently recommended first-and second-line therapies for uncomplicated Plasmodium falciparum infections in Chad. This study assessed the efficacy of these artemisinin-based combinations, proportion of day 3 positive patients, proportions of molecular markers associated with P. falciparum resistance to anti-malarial drugs and variable performance of HRP2-based malaria rapid diagnostic tests (RDTs).MethodsA single-arm prospective study assessing the efficacy of AS-AQ and AL at three sites (Doba, Kelo and Koyom) was conducted between November 2020 to January 2021. Febrile children aged 6 to 59 months with confirmed uncomplicated P. falciparum infection were enrolled sequentially first to AS-AQ and then AL at each site and followed up for 28 days. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples collected on day 0 were analysed for mutations in pfkelch13, pfcrt, pfmdr-1, pfdhfr, pfdhps genes and deletions in pfhrp2/pfhrp3 genes.ResultsBy the end of 28-day follow-up, per-protocol PCR corrected ACPR of 97.8% (CI 95% 88.2-100) in Kelo and 100% in Doba and Kayoma were observed among AL treated patients. For ASAQ, 100% ACPR was found in all sites. All, but one patient, did not have parasites detected on day 3. Out of the 215 day 0 samples, 96.7% showed pfkelch13 wild type allele. Seven isolates carried nonsynonymous mutations not known to be associated artemisinin partial resistance (ART-R). Most of samples had a pfcrt wild type allele (79% to 89%). The most prevalent pfmdr-1 allele detected was the single mutant 184F (51.2%). For pfdhfr and pfdhps mutations, the quintuple mutant allele N51I/C59R/S108N + G437A/540E responsible for SP treatment failures in adults and children was not detected. Single deletion in the pfhrp2 and pfhrp3 gene were detected in 10/215 (4.7%) and 2/215 (0.9%), respectively. Dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, were observed in 5/215 (2.3%) isolates.ConclusionThe results of this study confirm that AS-AQ and AL treatments are highly efficacious in study areas in Chad. The absence of known pfkelch13 mutations in the study sites and the high parasite clearance rate at day 3 suggest the absence of ART-R. The absence of pfdhfr/pfdhps quintuple or sextuple (quintuple + 581G) mutant supports the continued use of SP for IPTp during pregnancy. The presence of parasites with dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, warrants the continued surveillance.Trial registration ACTRN12622001476729ConclusionThe results of this study confirm that AS-AQ and AL treatments are highly efficacious in study areas in Chad. The absence of known pfkelch13 mutations in the study sites and the high parasite clearance rate at day 3 suggest the absence of ART-R. The absence of pfdhfr/pfdhps quintuple or sextuple (quintuple + 581G) mutant supports the continued use of SP for IPTp during pregnancy. The presence of parasites with dual pfhrp2/pfhrp3 deletions, potentially threatening the efficacy of HRP2-based RDTs, warrants the continued surveillance.Trial registration ACTRN12622001476729
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Malaria
- Plasmodium falciparum
- Artesunate-amodiaquine
- Artemether-lumefantrine
- Artemisinin resistance
- pfKelch13
- Pfcrt
- Pfmdr-1
- Pfdhfr
- Pfdhps
- Pfhrp-2 deletion
- HRP2-based RDT
- Chad
- sulfadoxine-pyrimethamine resistance
- histidine-rich protein-2
- plasmodium-falciparum
- dihydropteroate synthase
- artemisinin resistance
- molecular markers
- mutations
- Infectious Diseases
- Parasitology
- Tropical Medicine
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Issa, M. S.
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Warsame, Marian
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Mahamat, M. H. T ...
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Saleh, I. D. M.
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Boulotigam, K.
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Djimrassengar, H ...
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visa fler...
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Issa, A. H.
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Abdelkader, O.
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Hassoumi, M.
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Djimadoum, M.
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Doderer-Lang, C.
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Ndihiokubwayo, J ...
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Rasmussen, C.
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Menard, D.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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- Malaria Journal
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Göteborgs universitet