ArticleAntimicrobial agents and chemotherapy2010
In vitro activities of quinine and other antimalarials and pfnhe polymorphisms in Plasmodium isolates from Kenya.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 42 citations in OpenAlex.
- Limited ability of Plasmodium falciparum pfcrt, pfmdr1, and pfnhe1 polymorphisms to predict quinine in vitro sensitivity or clinical effectiveness in Uganda.Antimicrobial agents and chemotherapy · 2011Trial
- Article
- Analysis of Plasmodium falciparum NaBMC infectious diseases · 2019Article
- Screening of a library of traditional Chinese medicines to identify anti-malarial compounds and extracts.Malaria journal · 2018Article
- Amodiaquine resistance inWellcome open research · 2017Article
- Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network.The American journal of tropical medicine and hygiene · 2015Review
- Prevalence of Plasmodium falciparum anti-malarial resistance-associated polymorphisms in pfcrt, pfmdr1 and pfnhe1 in Muheza, Tanzania, prior to introduction of artemisinin combination therapy.Malaria journal · 2015Observational
- The MSPDBL2 codon 591 polymorphism is associated with lumefantrine in vitro drug responses in Plasmodium falciparum isolates from Kilifi, Kenya.Antimicrobial agents and chemotherapy · 2015Article
- Reduced in vitro doxycycline susceptibility in plasmodium falciparum field isolates from Kenya is associated with PfTetQ KYNNNN sequence polymorphism.Antimicrobial agents and chemotherapy · 2014Article
- Polymorphisms in Pfmdr1, Pfcrt, and Pfnhe1 genes are associated with reduced in vitro activities of quinine in Plasmodium falciparum isolates from western Kenya.Antimicrobial agents and chemotherapy · 2014Article
- A HECT ubiquitin-protein ligase as a novel candidate gene for altered quinine and quinidine responses in Plasmodium falciparum.PLoS genetics · 2014Article
- Challenges of drug-resistant malaria.Parasite (Paris, France) · 2014Review
- A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.PloS one · 2014Article
- Global analysis of Plasmodium falciparum Na(+)/H(+) exchanger (pfnhe-1) allele polymorphism and its usefulness as a marker of in vitro resistance to quinine.International journal for parasitology. Drugs and drug resistance · 2013Review
- Repeat polymorphisms in the low-complexity regions of Plasmodium falciparum ABC transporters and associations with in vitro antimalarial responses.Antimicrobial agents and chemotherapy · 2013Article
- The interplay between drug resistance and fitness in malaria parasites.Molecular microbiology · 2013Review
- In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger transporter (Pfnhe-1) gene in 393 isolates from Dakar, Senegal.Malaria journal · 2013Article
- Quinine treatment selects the pfnhe-1 ms4760-1 polymorphism in Malian patients with Falciparum malaria.The Journal of infectious diseases · 2013Article
- Plasmodium falciparum Na+/H+ exchanger (pfnhe-1) genetic polymorphism in Indian Ocean malaria-endemic areas.The American journal of tropical medicine and hygiene · 2013Article
- In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon.BMC infectious diseases · 2012Article
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
Resistance to the amino alcohol quinine has been associated with polymorphisms in pfnhe, a sodium hydrogen exchanger. We investigated the role of this gene in quinine resistance in vitro in isolates from Kenya. We analyzed pfnhe whole-gene polymorphisms, using capillary sequencing, and pfcrt at codon 76 (pfcrt-76) and pfmdr1 at codon 86 (pfmdr1-86), using PCR-enzyme restriction methodology, in 29 isolates from Kilifi, Kenya, for association with the in vitro activities of quinine and 2 amino alcohols, mefloquine and halofantrine. In vitro activity was assessed as the drug concentration that inhibits 50% of parasite growth (IC50). The median IC50s of quinine, halofantrine, and mefloquine were 92, 22, and 18 nM, respectively. The presence of 2 DNNND repeats in microsatellite ms4760 of pfnhe was associated with reduced susceptibility to quinine (60 versus 227 nM for 1 and 2 repeats, respectively; P<0.05), while 3 repeats were associated with restoration of susceptibility. The decrease in susceptibility conferred by the 2 DNNND repeats was more pronounced in parasites harboring the pfmdr1-86 mutation. No association was found between susceptibility to quinine and the pfcrt-76 mutation or between susceptibility to mefloquine or halofantrine and the pfnhe gene and the pfcrt-76 and pfmdr1-86 mutations. Using previously published data on the in vitro activities of chloroquine, lumefantrine, piperaquine, and dihydroartemisinin, we investigated the association of their activities with pfnhe polymorphism. With the exception of a modulation of the activity of lumefantrine by a mutation at position 1437, pfnhe did not modulate their activities. Two DNNND repeats combined with the pfmdr1-86 mutation could be used as an indicator of reduced susceptibility to quinine.
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