Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018
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. M...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-022-04328-x |
| _version_ | 1811335372667355136 |
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| author | Angela Patricia Guerra Mario Javier Olivera Liliana Jazmín Cortés Stella M. Chenet Alexandre Macedo de Oliveira Naomi W. Lucchi |
| author_facet | Angela Patricia Guerra Mario Javier Olivera Liliana Jazmín Cortés Stella M. Chenet Alexandre Macedo de Oliveira Naomi W. Lucchi |
| author_sort | Angela Patricia Guerra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:23:09Z |
| format | Article |
| id | doaj.art-6169c05e95c24cf2968bdd61706848f7 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-13T17:23:09Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-6169c05e95c24cf2968bdd61706848f72022-12-22T02:37:54ZengBMCMalaria Journal1475-28752022-10-012111810.1186/s12936-022-04328-xMolecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018Angela Patricia Guerra0Mario Javier Olivera1Liliana Jazmín Cortés2Stella M. Chenet3Alexandre Macedo de Oliveira4Naomi W. Lucchi5Grupo de Parasitología, Instituto Nacional de SaludGrupo de Parasitología, Instituto Nacional de SaludGrupo de Parasitología, Instituto Nacional de SaludInstituto de Investigaciones en Ciencias Biomédicas, Universidad Ricardo PalmaMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and PreventionMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and PreventionAbstract 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.https://doi.org/10.1186/s12936-022-04328-xColombiaMolecular markersChloroquineSulfadoxine-pyrimethamineNeutral microsatellitesPlasmodium falciparum |
| spellingShingle | Angela Patricia Guerra Mario Javier Olivera Liliana Jazmín Cortés Stella M. Chenet Alexandre Macedo de Oliveira Naomi W. Lucchi Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018 Malaria Journal Colombia Molecular markers Chloroquine Sulfadoxine-pyrimethamine Neutral microsatellites Plasmodium falciparum |
| title | Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018 |
| title_full | Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018 |
| title_fullStr | Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018 |
| title_full_unstemmed | Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018 |
| title_short | Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018 |
| title_sort | molecular surveillance for anti malarial drug resistance and genetic diversity of plasmodium falciparum after chloroquine and sulfadoxine pyrimethamine withdrawal in quibdo colombia 2018 |
| topic | Colombia Molecular markers Chloroquine Sulfadoxine-pyrimethamine Neutral microsatellites Plasmodium falciparum |
| url | https://doi.org/10.1186/s12936-022-04328-x |
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