Molecular Surveillance for Polymorphisms Associated with Artemisinin-Based Combination Therapy Resistance in Plasmodium falciparum Isolates Collected in the State of Roraima, Brazil

Abstract

Given that the C580Y polymorphism in the Plasmodium falciparum propeller domain of the kelch 13 gene (pfk13) was documented in Guyana, monitoring for mutations associated with antimalarial resistance was undertaken in neighboring Roraima state in Brazil. Polymorphisms in the pfmdr1 and pfk13 genes were investigated in 275 P. falciparum samples. No pfk13 mutations were observed. Triple mutants 184F, 1042D, and 1246Y were observed in 100% of the samples successfully sequenced for the pfmdr1 gene, with 20.1% of these having an additional mutation at codon 1034C. Among them, 2.5% of samples harbored two copies of the pfmdr1 gene. We found no evidence of the spread of C580Y parasites to Roraima state, Brazil. As previously observed, the 184F, 1042D, and 1246Y mutations in the pfmdr1 gene appear to be fixed in this region. Continued molecular surveillance is essential to detect any potential migration or local emergence of artemisinin-resistant mutation.

Malaria in Venezuela: changes in the complexity of infection reflects the increment in transmission intensity

“…Mutations linked to artemisinin delayed phenotype in Pfk13 were not found in the 88 isolates genotyped for this gene; a result consistent with a recent study on samples collected on Venezuelan migrants in Brazil [13]. This is an important finding since there is constant movement between Guyana, Brazil, and Venezuela as a result of the illegal exploitation of gold mines [6].…”

“…The increase in malaria cases in Venezuela, and the subsequent mass migration across international borders, is likely the most important event affecting the goal toward malaria elimination in Latin-America [5,13,35]. It is worth noting that the long-term impacts of the current situation in Venezuela, in the context of cross-border malaria, are still poorly understood.…”

“…Most reports focus on counting the number of imported cases [5,35]. Yet, data are being collected in other aspects, such as the prevalence of mutations linked to drug resistance in P. falciparum [12,13]. Here, baseline data on the circulating parasites found in Bolívar State in 2018, the epicentre of the current malaria epidemic affecting Venezuela, were described.…”

“…Regional connectivity may not only affect malaria in the region in terms of imported cases but also because the local epidemiology in the area has allowed for the independent emergence of P. falciparum mutations linked to anti-malarial drug resistance [6][7][8][9][10][11][12][13]. Thus, such emergent drug-resistant genotypes are at risk of spilling over the region.…”

Evidence of a Recent Bottleneck in Plasmodium falciparum Populations on the Honduran–Nicaraguan Border

“…The genetic diversity of Plasmodium spp. has been related to the ability of parasites to adapt adequately to their hosts through the selection of advantageous traits, such as antigenic variability that allows them to evade the immune response, as well as the emergence of mutations responsible for resistance to antimalarials [3][4][5][6][7]. Genetically diverse populations of Plasmodium are common in regions with high transmission patterns, such as sub-Saharan Africa and some Southeast Asian countries [8][9][10][11][12], but as the incidence of malaria declines, the parasite's genetic diversity is expected to decline as well [13,14].…”