Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname

Abstract

In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum. We genotyped the PfK13 propeller domain of P. falciparum in 40 samples as well as other mutations proposed to be associated with artemisininresistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia, but we found fixed resistance mutations for chloroquine (CQ) and sulfadoxine-pyrimethamine. Additionally, the PfCRT C350R mutation, associated with reversal of CQ resistance and piperaquine-selective pressure, was present in 62% of the samples. Our results from neutral microsatellite data also confirmed a high parasite gene flow in the Guiana Shield. Although recruiting participants for therapeutic efficacy studies is challenging in areas where malaria endemicity is very low due to the low number of malaria cases reported, conducting these studies along with molecular surveillance remains essential for the monitoring of artemisinin-resistant alleles and for the characterization of the population structure of P. falciparum in areas targeted for malaria elimination.

Prevalence of mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, and association with ex vivo susceptibility to common anti-malarial drugs against African Plasmodium falciparum isolates

“…In contrast, the K76T mutation did not appear to be associated with in vitro reduced susceptibility to piperaquine (Table 3), confirming previous results [21,38]. Previous studies found several new mutations in pfcrt associated with piperaquine reduced susceptibility, like the mutations T93S, H97Y, C101F, F145I, M343L and G353V in Cambodian parasites [22,23,[25][26][27][28][29] and C350R in isolates from French Guiana [24] and Suriname [30]. However in studies on African P. falciparum samples, there was no report of identification of these mutations [39,40].…”

“…This mutation was not found in P. falciparum positively isolates after artemether-lumefantrine treatment. A different amino acid substitution on the locus 356 (I356L) was also found in isolates from Latin America [1,30], but this mutation was absent the present 602 African isolates. However, this mutation was not observed in isolates from Suriname [30].…”

“…Many other mutations were found in pfcrt but few were investigated for their association with anti-malarial drug resistance. The mutation I356T/L for instance is often found both on Asian or South-American parasites [30,31].…”

Malaria serology data from the Guiana shield: first insight in IgG antibody responses to Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae antigens in Suriname

“…An in vivo efficacy study in 2014 with artesunate further revealed that at least 17.9% of samples exhibited a parasite half-life ≥ 5 h [ 3 ]. Molecular characterizations of drug-associated markers of isolates from Suriname did not reveal noteworthy alterations in potential molecular markers in the pfATP6 [ 4 ], pfmdr1 [ 5 ] and K13 genes [ 6 ], but increased pfmdr1 copy numbers in P. falciparum isolates [ 7 ] have been observed. The possible emerging of resistance to artemisinin is further fueled with reported self-treatment and poor adherence by miners in remote areas.…”

Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015–2016

“…Declining e cacy of ACTs in Southeast Asia (e.g., Cambodia, Thailand) has led to heightened concern for the spread of resistant parasites to other malaria endemic countries [4,5] and the independent emergence of resistant mutants in other malaria endemic countries as was observed in Guyana [6] and Rwanda [7]. Thus, it is necessary to routinely monitor the therapeutic e cacy of ACTs.…”