Dados do Trabalho

Título

Tracking molecular changes associated with P. falciparum chemoresistance in Amazonas state.

Introdução

Malaria is a public health problem worldwide. Despite the global efforts to malaria control, antimalarial drug resistance remains a great challenge. In 2009, our team identified firstly in Brazil a chloroquine (CQ) susceptible P. falciparum isolate from Amazonas state. This finding guided us to carry out a study for tracking molecular changes in P. falciparum parasites in this region.

Objetivo(s)

Investigate SNPs in genes associated with chemoresistance to CQ (pfcrt and pfmdr1), sulfadoxine-pyrimethamine (SP) (pfdhfr/pfdhps), and artemisinin (ART) (pfk13) in P. falciparum parasites.

Material e Métodos

Sixty-nine P. falciparum samples from Amazonas state (Manaus, São Gabriel da Cachoeira, Barcelos, Lábrea and Tefé) were collected from 2010 to 2021 in patients diagnosed at the Reference Research Center for Treatment and Diagnosis of Malaria (CPD-Mal/Fiocruz). These samples were subjected to PCR and DNA Sanger sequencing to identify mutations in pfdhfr (A16V/S, C50R, N51I, C59R, S108N, V140L, I164L), pfdhps (S436A/F/C, A437G, K540E, A581G and A613T/S), pfcrt (C72S, M74I, N75E/D, K76T), pfmdr1 (N86Y, E130K, Y184F, S1034C, N1042D, V1109I, D1246Y) and pfk13 genes.

Resultados e Conclusão

No mutations in the pfk13 gene were found. The CQ and SP resistant pfcrt and pfdhps/pfdhpr genotypes were predominant. But, three samples showed a CQ pfcrt sensitive-wild type genotype. The haplotypic multilocus analysis of these 3 samples showed 2 types: one from Manaus (2010) also pfdhps and pfmdr1 wild-type/sensitives (ACICNVI + SAKAA + NEYSNVD + CVMNK) while the other two (Manaus, 2017 and Barcelos, 2018) were also resistant to pfdhps and pfmdr1 (ACICNVI + SAGAA + NEFSNVY + CVMNK).
To date, in our casuist, no mutants were found for the artemisinin resistance marker (pfk13), reinforcing the absence of ART-resistant parasites. The accumulation of mutations in pfdhfr and pfdhps suggests the fixation of SP-resistant mutant alleles, while the presence of pfcrt and pfmdr1 wildtypes conjecture the fixation of CQ-sensitive parasites and the possibility of re-expansion of these parasites in Amazonas state.

Palavras-chave

P. falciparum; chemoresistance; malaria; pfcrt, pfk13, pfmdr1, pfdhps/pfdhpr.

Área

Eixo 06 | Protozooses