Association between Polymorphisms in the Pf mdr6 Gene and Ex Vivo Susceptibility to Quinine in Plasmodium falciparum Parasites from Dakar, Senegal

Abstract

Polymorphisms and the overexpression of transporter genes, especially of the ATP-binding cassette superfamily, have been involved in antimalarial drug resistance. The objective of this study was to use 77 Senegalese Plasmodium falciparum isolates to evaluate the association between the number of Asn residues in the polymorphic microsatellite region of the Plasmodium falciparum multidrug resistance 6 gene (Pfmdr6) and the ex vivo susceptibility to antimalarials. A significant association was observed between the presence of 7 or 9 Asn repeats and reduced susceptibility to quinine.

Absence of a High Level of Duplication of the Plasmepsin II Gene in Africa

“…A wide range of the PPQ responses was already observed in several studies, regardless of the methodology used. PPQ IC 50 s, assessed by a 72 h incubation with atmospheric generators for capnophilic bacteria and HRP2 ELISA in isolates from Dakar in 2013 to 2014 and 2013 to 2015, ranged from 2.5 to 168 nM and 3.9 to 241.9 nM, respectively (17,18). The distribution of PPQ IC 50 from 313 isolates obtained between 2008 and 2012 from patients hospitalized in France for imported malaria and assessed by a 42-h isotopic test ranged from 9.8 to 217.3 nM (19).…”

“…After collection from patients, the storage temperature of the samples was controlled by sensor. Additionally, Senegalese isolates, which were assessed immediately, presented the same wide range of in vitro responses (17,18). One isolate had a reduced susceptibility to PPQ (IC 50 , Ͼ135 nM) (19).…”

Are k13 and plasmepsin II genes, involved in Plasmodium falciparum resistance to artemisinin derivatives and piperaquine in Southeast Asia, reliable to monitor resistance surveillance in Africa?

“…Additionally, mutations on pfmdr1 genes were shown to be correlated with in vitro reduced susceptibility to artemisinin derivatives [40–42]. The involvement of polymorphisms in potential genes was evaluated, such as pfubp - 1 encoding the P. falciparum ubiquitin specific protease 1 [43–45], the gene encoding the RING E3 protein ubiquitin ligase [46, 47], pfap2mu encoding the P. falciparum adaptor protein complex 2 mu subunit [44, 48], pfmdr5 encoding the P. falciparum multidrug resistance 5 protein [49] or pfmdr6 encoding the P. falciparum multidrug resistance 6 protein [49–51]. Only mutations pfap2mu S160N and pfubp1 E1525D/Q were found in cases of African imported P. falciparum malaria with clinical failure with ACT [25].…”

Malaria, tuberculosis and HIV: what's new? Contribution of the Institut Hospitalo-Universitaire Méditerranée Infection in updated data

“…The IHU-Méditerranée Infection participates in identification, development and/or validation of new molecular resistance markers to doxycycline ( pfmdt and pftetQ ) [59] , [60] , [61] , [62] , quinine ( pfnhe-1 ) [63] , artemisinin ( pfK13 ) [64] , [65] , [66] , [67] , [68] and quinolines ( pfmdr1, pfmdr2, pfmdr5, pfmdr6, etc.) [69] , [70] , [71] , [72] .…”