Impact of treatment and re-treatment with artemether-lumefantrine and artesunate-amodiaquine on selection of Plasmodium falciparum multidrug resistance gene-1 polymorphisms in the Democratic Republic of Congo and Uganda.

Autor: Baraka V; National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania.; Global Health Institute, University of Antwerp, Antwerp, Belgium., Mavoko HM; Global Health Institute, University of Antwerp, Antwerp, Belgium.; Département de Médecine Tropicale, Faculté de Médecine, Université de Kinshasa, Kinshasa, Democratic Republic of Congo., Nabasumba C; Global Health Institute, University of Antwerp, Antwerp, Belgium.; Epicentre Mbarara Research Base, Mbarara, Uganda., Francis F; National Institute for Medical Research, Tanga Centre, Tanga, United Republic of Tanzania., Lutumba P; Département de Médecine Tropicale, Faculté de Médecine, Université de Kinshasa, Kinshasa, Democratic Republic of Congo., Alifrangis M; Centre for Medical Parasitology at the Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; Department of Infectious Diseases, National University Hospital (Rigshospitalet), Copenhagen, Denmark., Van Geertruyden JP; Global Health Institute, University of Antwerp, Antwerp, Belgium.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Feb 01; Vol. 13 (2), pp. e0191922. Date of Electronic Publication: 2018 Feb 01 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0191922
Abstrakt: Background: The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings.
Methods: P. falciparum positive samples were collected from children aged 12-59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays.
Results: The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre-RCT, RCT and post-RCT phases in both AL and ASAQ treatment arms. Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure (RR = 0.34, 95% CI:0.11-1.05, p = 0.04) while no evidence for D1246 allele (RR = 1.02; 95% CI: 0.42-2.47, p = 1.0). Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms.
Conclusion: We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs. These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections. Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje