Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan
Abstract Background K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-021-03715-0 |
| _version_ | 1818339499759894528 |
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| author | Najia Karim Ghanchi Bushra Qurashi Hadiqa Raees Mohammad Asim Beg |
| author_facet | Najia Karim Ghanchi Bushra Qurashi Hadiqa Raees Mohammad Asim Beg |
| author_sort | Najia Karim Ghanchi |
| collection | DOAJ |
| description | Abstract Background K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan. Methods Two hundred and forty-nine samples were collected from patients with microscopy confirmed P. falciparum malaria attending Aga Khan University Hospital during September 2015-April 2018. DNA was isolated using the whole blood protocol for the QIAmp DNA Blood Kit. The k13 propeller gene (k13) was amplified using nested PCR. Double-strand sequencing of PCR products was performed using Sanger sequencing methodology. Sequences were analysed with MEGA 6 and Bio edit software to identify specific SNP combinations. Results All isolates analysed for k13 propeller allele were observed as wild-type in samples collected post implementation of ACT in Pakistan. C580Y, A675V, Y493H and R539T variants associated with reduced susceptibility to artemisinin-based combination therapy (ACT) were not found. Low frequency of M476I and C469Y polymorphisms was found, which is significantly associated with artemisinin resistance. Conclusion Low frequencies of both nonsynonymous and synonymous polymorphisms were observed in P. falciparum isolates circulating in Southern Pakistan. The absence of known molecular markers of artemisinin resistance in this region is favourable for anti-malarial efficacy of ACT. Surveillance of anti-malarial drug resistance to detect its emergence and spread need to be strengthened in Pakistan. |
| first_indexed | 2024-12-13T15:27:59Z |
| format | Article |
| id | doaj.art-3cb9d2299b5746738aaf65a16960ab9a |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-13T15:27:59Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-3cb9d2299b5746738aaf65a16960ab9a2022-12-21T23:40:17ZengBMCMalaria Journal1475-28752021-04-012011610.1186/s12936-021-03715-0Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern PakistanNajia Karim Ghanchi0Bushra Qurashi1Hadiqa Raees2Mohammad Asim Beg3Section of Microbiology, Department of Pathology and Laboratory Medicine, Aga Khan UniversitySection of Microbiology, Department of Pathology and Laboratory Medicine, Aga Khan UniversityCRM, Aga Khan UniversitySection of Microbiology, Department of Pathology and Laboratory Medicine, Aga Khan UniversityAbstract Background K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan. Methods Two hundred and forty-nine samples were collected from patients with microscopy confirmed P. falciparum malaria attending Aga Khan University Hospital during September 2015-April 2018. DNA was isolated using the whole blood protocol for the QIAmp DNA Blood Kit. The k13 propeller gene (k13) was amplified using nested PCR. Double-strand sequencing of PCR products was performed using Sanger sequencing methodology. Sequences were analysed with MEGA 6 and Bio edit software to identify specific SNP combinations. Results All isolates analysed for k13 propeller allele were observed as wild-type in samples collected post implementation of ACT in Pakistan. C580Y, A675V, Y493H and R539T variants associated with reduced susceptibility to artemisinin-based combination therapy (ACT) were not found. Low frequency of M476I and C469Y polymorphisms was found, which is significantly associated with artemisinin resistance. Conclusion Low frequencies of both nonsynonymous and synonymous polymorphisms were observed in P. falciparum isolates circulating in Southern Pakistan. The absence of known molecular markers of artemisinin resistance in this region is favourable for anti-malarial efficacy of ACT. Surveillance of anti-malarial drug resistance to detect its emergence and spread need to be strengthened in Pakistan.https://doi.org/10.1186/s12936-021-03715-0ArtemisininPlasmodium falciparumPakistanDrug resistance |
| spellingShingle | Najia Karim Ghanchi Bushra Qurashi Hadiqa Raees Mohammad Asim Beg Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan Malaria Journal Artemisinin Plasmodium falciparum Pakistan Drug resistance |
| title | Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan |
| title_full | Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan |
| title_fullStr | Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan |
| title_full_unstemmed | Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan |
| title_short | Molecular surveillance of drug resistance: Plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in Kelch protein propeller (K13) domain from Southern Pakistan |
| title_sort | molecular surveillance of drug resistance plasmodium falciparum artemisinin resistance single nucleotide polymorphisms in kelch protein propeller k13 domain from southern pakistan |
| topic | Artemisinin Plasmodium falciparum Pakistan Drug resistance |
| url | https://doi.org/10.1186/s12936-021-03715-0 |
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