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. 2019 Aug 28;18(1):293.
doi: 10.1186/s12936-019-2919-3.

Low polymorphisms in pfact, pfugt and pfcarl genes in African Plasmodium falciparum isolates and absence of association with susceptibility to common anti-malarial drugs

Francis Tsombeng Foguim  1   2   3 , Marie Gladys Robert  1   2   3 , Mamadou Wagué Gueye  4 , Mathieu Gendrot  1   2   3 , Silman Diawara  4 , Joel Mosnier  1   2   3   5 , Rémy Amalvict  1   2   3   5 , Nicolas Benoit  1   2   3   5 , Raymond Bercion  6 , Bécaye Fall  4 , Marylin Madamet  1   2   3   5 , Bruno Pradines  7   8   9   10   11 ; French National Reference Centre for Imported Malaria Study Group
Collaborators, Affiliations

Low polymorphisms in pfact, pfugt and pfcarl genes in African Plasmodium falciparum isolates and absence of association with susceptibility to common anti-malarial drugs

Francis Tsombeng Foguim et al. Malar J. .

Abstract

Background: Resistance to all available anti-malarial drugs has emerged and spread including artemisinin derivatives and their partner drugs. Several genes involved in artemisinin and partner drugs resistance, such as pfcrt, pfmdr1, pfK13 or pfpm2, have been identified. However, these genes do not properly explain anti-malarial drug resistance, and more particularly clinical failures observed in Africa. Mutations in genes encoding for Plasmodium falciparum proteins, such as P. falciparum Acetyl-CoA transporter (PfACT), P. falciparum UDP-galactose transporter (PfUGT) and P. falciparum cyclic amine resistance locus (PfCARL) have recently been associated to resistance to imidazolopiperazines and other unrelated drugs.

Methods: Mutations on pfugt, pfact and pfcarl were characterized on 86 isolates collected in Dakar, Senegal and 173 samples collected from patients hospitalized in France after a travel in African countries from 2015 and 2016 to assess their potential association with ex vivo susceptibility to chloroquine, quinine, lumefantrine, monodesethylamodiaquine, mefloquine, dihydroartemisinin, artesunate, doxycycline, pyronaridine and piperaquine.

Results: No mutations were found on the genes pfugt and pfact. None of the pfcarl described mutations were identified in these samples from Africa. The K784N mutation was found in one sample and the K734M mutation was identified on 7.9% of all samples for pfcarl. The only significant differences in ex vivo susceptibility according to the K734M mutation were observed for pyronaridine for African isolates from imported malaria and for doxycycline for Senegalese parasites.

Conclusion: No evidence was found of involvement of these genes in reduced susceptibility to standard anti-malarial drugs in African P. falciparum isolates.

Keywords: Anti-malarial drug; In vitro; Malaria; Molecular marker; PfACT; PfCARL; PfUGT; Plasmodium falciparum; Resistance.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Geographical repartition and isolate number per country of the Plasmodium falciparum isolates collected between 2015 and 2016 from patients hospitalized in France with imported malaria from Africa
Fig. 2
Fig. 2
Dot plot of the IC50 total distribution of each Senegalese Plasmodium falciparum isolate assessed ex vivo for chloroquine (CQ), quinine (QN), monodesethylamodiaquine (DQ), mefloquine (MQ), lumefantrine (LMF), piperaquine (PPQ), pyronaridine (PND), dihydroartemisinin (DHA), artesunate (AS) and doxycycline (DOX). The red line represents the in vitro threshold of reduced susceptibility
Fig. 3
Fig. 3
Dot plot of the IC50 total distribution of each Plasmodium falciparum isolate from imported malaria to France assessed ex vivo for chloroquine (CQ), quinine (QN), monodesethylamodiaquine (DQ), mefloquine (MQ), lumefantrine (LMF), piperaquine (PPQ), pyronaridine (PND), dihydroartemisinin (DHA), artesunate (AS) and doxycycline (DOX). The red line represents the in vitro threshold of reduced susceptibility
See this image and copyright information in PMC

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