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Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101139802 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2875 (Electronic) Linking ISSN: 14752875 NLM ISO Abbreviation: Malar J Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2002-
    • Subject Terms:
      Antimalarials*/pharmacology ; Antimalarials*/therapeutic use ; Malaria, Falciparum*/epidemiology; Humans ; Sulfadoxine/pharmacology ; Sulfadoxine/therapeutic use ; Pyrimethamine/pharmacology ; Pyrimethamine/therapeutic use ; Plasmodium falciparum ; Chloroquine/pharmacology ; Chloroquine/therapeutic use ; Colombia ; Artemether/therapeutic use ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Drug Combinations ; Drug Resistance/genetics ; Polymorphism, Genetic ; Codon
    • Abstract:
      Background: Resistance to anti-malarial drugs is associated with polymorphisms in target genes and surveillance for these molecular markers is important to detect the emergence of mutations associated with drug resistance and signal recovering sensitivity to anti-malarials previously used.
      Methods: The presence of polymorphisms in genes associated with Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated by Sanger sequencing, in 85 P. falciparum day of enrollment samples from a therapeutic efficacy study of artemether-lumefantrine conducted in 2018-2019 in Quibdo, Colombia. Samples were genotyped to assess mutations in pfcrt (codons 72-76), pfdhfr (codons 51, 59, 108, and 164), and pfdhps genes (codons 436, 437, 540, and 581). Further, the genetic diversity of infections using seven neutral microsatellites (NMSs) (C2M34, C3M69, Poly α, TA1, TA109, 2490, and PfPK2) was assessed.
      Results: All isolates carried mutant alleles for pfcrt (K76T and N75E), and for pfdhfr (N51I and S108N), while for pfdhps, mutations were observed only for codon A437G (32/73, 43.8%). Fifty samples (58.8%) showed a complete neutral microsatellites (NMS) profile. The low mean number of alleles (2 ± 0.57) per locus and mean expected heterozygosity (0.17 ± 0.03) showed a reduced genetic diversity. NMS multilocus genotypes (MMG) were built and nine MMG were identified.
      Conclusions: Overall, these findings confirm the fixation of chloroquine and pyrimethamine-resistant alleles already described in the literature, implying that these drugs are not currently appropriate for use in Colombia. In contrast, mutations in the pfdhps gene were only observed at codon 437, an indication that full resistance to sulfadoxine has not been achieved in Choco. MMGs found matched the clonal lineage E variant 1 previously reported in northwestern Colombia.
      (© 2022. The Author(s).)
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    • Contributed Indexing:
      Keywords: Chloroquine; Colombia; Molecular markers; Neutral microsatellites; Plasmodium falciparum; Sulfadoxine-pyrimethamine
    • Accession Number:
      37338-39-9 (fanasil, pyrimethamine drug combination)
      88463U4SM5 (Sulfadoxine)
      Z3614QOX8W (Pyrimethamine)
      0 (Antimalarials)
      886U3H6UFF (Chloroquine)
      C7D6T3H22J (Artemether)
      0 (Artemether, Lumefantrine Drug Combination)
      0 (Drug Combinations)
      0 (Codon)
    • Publication Date:
      Date Created: 20221029 Date Completed: 20221101 Latest Revision: 20221101
    • Publication Date:
      20240105
    • Accession Number:
      PMC9617338
    • Accession Number:
      10.1186/s12936-022-04328-x
    • Accession Number:
      36307852