Pfcrt mutant haplotypes may not correspond with chloroquine resistance
Introduction: Chloroquine resistance in Plasmodium falciparum is associated with mutations in pfcrt and pfmdr1 genes. The frequency distribution of pfcrt K76T and pfmdr1 N86Y mutations and their association with chloroquine susceptibility was studied in an endemic area along the Indo-Bangladesh bord...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Journal of Infection in Developing Countries
2014-06-01
|
| Series: | Journal of Infection in Developing Countries |
| Subjects: | |
| Online Access: | https://jidc.org/index.php/journal/article/view/3398 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850035633777541120 |
|---|---|
| author | Diganta Goswami Sunil Dhiman Bipul Rabha Dinesh Kumar Indra Baruah Dhirendra Kumar Sharma Vijay Veer |
| author_facet | Diganta Goswami Sunil Dhiman Bipul Rabha Dinesh Kumar Indra Baruah Dhirendra Kumar Sharma Vijay Veer |
| author_sort | Diganta Goswami |
| collection | DOAJ |
| description | Introduction: Chloroquine resistance in Plasmodium falciparum is associated with mutations in pfcrt and pfmdr1 genes. The frequency distribution of pfcrt K76T and pfmdr1 N86Y mutations and their association with chloroquine susceptibility was studied in an endemic area along the Indo-Bangladesh border.
Methodology: A single-arm prospective study of clinical and parasitological responses in P. falciparum malaria patients to chloroquine was conducted in vivo. PCR-RFLP assay was used to detect pfcrt K76T and pfmdr1 N86Y mutations in P. falciparum. The PCR products of pfcrt gene were sequenced, translated and aligned for haplotyping.
Results: Out of 63 cases, 44 (69.8%) responded adequately to chloroquine treatment. Pfcrt K76T mutation was recorded in 100% of the treatment failure cases, whereas pfmdr1 N86Y mutation was found in 52.6% of the cases only. Early treatment failure (84.2%) occurred more frequently than late treatment failure (15.8%). Kaplan–Meier survival analysis showed that the probability estimate for treatment success after 7 and 15 days was 0.84 (95% CI = 0.72-0.92) and 0.70 (95% CI = 0.57-0.80), respectively. Sequence analysis of 72 to 76 pfcrt gene codons revealed the presence of two mutant (CVMNT, CVIET) and two wild (CVMNK, CVIEK) haplotypes. The mutant CVIET haplotype was predominantly distributed (42.1%).
Conclusions: The presence of mutations in pfcrt K76T and pfmdr1 N86Y genes is not sufficient to explain the therapeutic efficacy of chloroquine to P. falciparum. Study suggests that pfcrt K76T mutant haplotypes are widely distributed and are spreading diligently, which needs to be taken into account in devising an antimalarial policy.
|
| format | Article |
| id | doaj-art-7fc882f5c6fe4106b9ffa4e3c3fcfd19 |
| institution | DOAJ |
| issn | 1972-2680 |
| language | English |
| publishDate | 2014-06-01 |
| publisher | The Journal of Infection in Developing Countries |
| record_format | Article |
| series | Journal of Infection in Developing Countries |
| spelling | doaj-art-7fc882f5c6fe4106b9ffa4e3c3fcfd192025-08-20T02:57:25ZengThe Journal of Infection in Developing CountriesJournal of Infection in Developing Countries1972-26802014-06-0180610.3855/jidc.3398Pfcrt mutant haplotypes may not correspond with chloroquine resistanceDiganta Goswami0Sunil Dhiman1Bipul Rabha2Dinesh Kumar3Indra Baruah4Dhirendra Kumar Sharma5Vijay Veer6Defence Research Laboratory, Tezpur, Assam, IndiaDefence Research Laboratory, Tezpur, Assam, IndiaDefence Research Laboratory, Tezpur, Assam, IndiaDefence Research Laboratory, Tezpur, Assam, IndiaDefence Research Laboratory, Tezpur, Assam, IndiaGauhati University, Guwahati, Assam, IndiaDefence Research Laboratory, Tezpur, Assam, IndiaIntroduction: Chloroquine resistance in Plasmodium falciparum is associated with mutations in pfcrt and pfmdr1 genes. The frequency distribution of pfcrt K76T and pfmdr1 N86Y mutations and their association with chloroquine susceptibility was studied in an endemic area along the Indo-Bangladesh border. Methodology: A single-arm prospective study of clinical and parasitological responses in P. falciparum malaria patients to chloroquine was conducted in vivo. PCR-RFLP assay was used to detect pfcrt K76T and pfmdr1 N86Y mutations in P. falciparum. The PCR products of pfcrt gene were sequenced, translated and aligned for haplotyping. Results: Out of 63 cases, 44 (69.8%) responded adequately to chloroquine treatment. Pfcrt K76T mutation was recorded in 100% of the treatment failure cases, whereas pfmdr1 N86Y mutation was found in 52.6% of the cases only. Early treatment failure (84.2%) occurred more frequently than late treatment failure (15.8%). Kaplan–Meier survival analysis showed that the probability estimate for treatment success after 7 and 15 days was 0.84 (95% CI = 0.72-0.92) and 0.70 (95% CI = 0.57-0.80), respectively. Sequence analysis of 72 to 76 pfcrt gene codons revealed the presence of two mutant (CVMNT, CVIET) and two wild (CVMNK, CVIEK) haplotypes. The mutant CVIET haplotype was predominantly distributed (42.1%). Conclusions: The presence of mutations in pfcrt K76T and pfmdr1 N86Y genes is not sufficient to explain the therapeutic efficacy of chloroquine to P. falciparum. Study suggests that pfcrt K76T mutant haplotypes are widely distributed and are spreading diligently, which needs to be taken into account in devising an antimalarial policy. https://jidc.org/index.php/journal/article/view/3398Chloroquinepfcrtpfmdr1resistancehaplotype |
| spellingShingle | Diganta Goswami Sunil Dhiman Bipul Rabha Dinesh Kumar Indra Baruah Dhirendra Kumar Sharma Vijay Veer Pfcrt mutant haplotypes may not correspond with chloroquine resistance Journal of Infection in Developing Countries Chloroquine pfcrt pfmdr1 resistance haplotype |
| title | Pfcrt mutant haplotypes may not correspond with chloroquine resistance |
| title_full | Pfcrt mutant haplotypes may not correspond with chloroquine resistance |
| title_fullStr | Pfcrt mutant haplotypes may not correspond with chloroquine resistance |
| title_full_unstemmed | Pfcrt mutant haplotypes may not correspond with chloroquine resistance |
| title_short | Pfcrt mutant haplotypes may not correspond with chloroquine resistance |
| title_sort | pfcrt mutant haplotypes may not correspond with chloroquine resistance |
| topic | Chloroquine pfcrt pfmdr1 resistance haplotype |
| url | https://jidc.org/index.php/journal/article/view/3398 |
| work_keys_str_mv | AT digantagoswami pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance AT sunildhiman pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance AT bipulrabha pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance AT dineshkumar pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance AT indrabaruah pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance AT dhirendrakumarsharma pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance AT vijayveer pfcrtmutanthaplotypesmaynotcorrespondwithchloroquineresistance |