Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine
Abstract Background A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Niger...
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-019-2977-6 |
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| author | Moses N. Ikegbunam Charles N. Nkonganyi Bolaji N. Thomas Charles O. Esimone Thirumalaisamy P. Velavan Olusola Ojurongbe |
| author_facet | Moses N. Ikegbunam Charles N. Nkonganyi Bolaji N. Thomas Charles O. Esimone Thirumalaisamy P. Velavan Olusola Ojurongbe |
| author_sort | Moses N. Ikegbunam |
| collection | DOAJ |
| description | Abstract Background A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria. Methods Filter-paper blood samples were collected from 725 non-febrile individuals, comprising 250 children (≤ 12 years), 250 pregnant women and 225 other adults, between October 2014 and February 2015 in Nnewi town, Southeast Nigeria. Nested PCR followed by direct sequencing was employed for the genotyping of Pfcrt and Pfmdr1 genes. Results A total of 103 parasites-positive samples were recovered, comprising of 48 (19.20%) among children, 20 (20.00%) among pregnant women and 35 (15.50%) among other adults cohort. The frequency of the mutant genotype of Pfcrt 76T, 75E and 74I was 94.50% each. Parasite isolates from children had a frequency of 100% for mutant alleles in all Pfcrt codons while isolates from pregnant women and other adults had a frequency of 91% each in all codons. Haplotype distribution of pfcrt gene were 5.45, 0.00 and 76.37% for CVMNK, SVMNT and CVIET, respectively. For Pfmdr1 gene, the frequency of 86Y, 184F and 1246Y mutant alleles were 8.54, 29.27 and 3.66%, respectively. Amongst the Pfmdr1 haplotypes analysed, NFD had the highest frequency of 24.4%, followed by YFD at 6.10%. NYF and NYY occurred the least (1.20%). Conclusion The high level of Pfcrt mutations is suggestive of a sustained CQ pressure on P. falciparum isolates in the study area, despite the change of first line treatment from CQ to artemisinin combination therapy for 11 years. A new strategy to ensure the complete withdrawal of CQ from the country is recommended. |
| first_indexed | 2024-12-12T02:14:00Z |
| format | Article |
| id | doaj.art-1b30c501f62749fe90b28ebd4cd6e91b |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-12T02:14:00Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-1b30c501f62749fe90b28ebd4cd6e91b2022-12-22T00:41:50ZengBMCMalaria Journal1475-28752019-10-011811710.1186/s12936-019-2977-6Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquineMoses N. Ikegbunam0Charles N. Nkonganyi1Bolaji N. Thomas2Charles O. Esimone3Thirumalaisamy P. Velavan4Olusola Ojurongbe5Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe UniversityInstitute of Tropical Medicine, University of TübingenDepartment of Biomedical Sciences, College of Health Sciences and Technology, Rochester Institute of TechnologyDepartment of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe UniversityInstitute of Tropical Medicine, University of TübingenDepartment of Medical Microbiology and Parasitology, Ladoke Akintola University of TechnologyAbstract Background A reversal of chloroquine (CQ) resistance following a period of withdrawal has raised the possibility of its re-introduction. This study evaluated the current prevalence of Pfcrt and Pfmdr1 alleles in Plasmodium falciparum isolates, 11 years after CQ withdrawal in Southeast Nigeria. Methods Filter-paper blood samples were collected from 725 non-febrile individuals, comprising 250 children (≤ 12 years), 250 pregnant women and 225 other adults, between October 2014 and February 2015 in Nnewi town, Southeast Nigeria. Nested PCR followed by direct sequencing was employed for the genotyping of Pfcrt and Pfmdr1 genes. Results A total of 103 parasites-positive samples were recovered, comprising of 48 (19.20%) among children, 20 (20.00%) among pregnant women and 35 (15.50%) among other adults cohort. The frequency of the mutant genotype of Pfcrt 76T, 75E and 74I was 94.50% each. Parasite isolates from children had a frequency of 100% for mutant alleles in all Pfcrt codons while isolates from pregnant women and other adults had a frequency of 91% each in all codons. Haplotype distribution of pfcrt gene were 5.45, 0.00 and 76.37% for CVMNK, SVMNT and CVIET, respectively. For Pfmdr1 gene, the frequency of 86Y, 184F and 1246Y mutant alleles were 8.54, 29.27 and 3.66%, respectively. Amongst the Pfmdr1 haplotypes analysed, NFD had the highest frequency of 24.4%, followed by YFD at 6.10%. NYF and NYY occurred the least (1.20%). Conclusion The high level of Pfcrt mutations is suggestive of a sustained CQ pressure on P. falciparum isolates in the study area, despite the change of first line treatment from CQ to artemisinin combination therapy for 11 years. A new strategy to ensure the complete withdrawal of CQ from the country is recommended.http://link.springer.com/article/10.1186/s12936-019-2977-6Plasmodium falciparumDrug resistanceChloroquinePfmdr1Pfcrt |
| spellingShingle | Moses N. Ikegbunam Charles N. Nkonganyi Bolaji N. Thomas Charles O. Esimone Thirumalaisamy P. Velavan Olusola Ojurongbe Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine Malaria Journal Plasmodium falciparum Drug resistance Chloroquine Pfmdr1 Pfcrt |
| title | Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine |
| title_full | Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine |
| title_fullStr | Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine |
| title_full_unstemmed | Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine |
| title_short | Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine |
| title_sort | analysis of plasmodium falciparum pfcrt and pfmdr1 genes in parasite isolates from asymptomatic individuals in southeast nigeria 11 years after withdrawal of chloroquine |
| topic | Plasmodium falciparum Drug resistance Chloroquine Pfmdr1 Pfcrt |
| url | http://link.springer.com/article/10.1186/s12936-019-2977-6 |
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