Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India
Abstract Background Artesunate plus sulfadoxine–pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associate...
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BMC
2020-08-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-020-03274-w |
| _version_ | 1818112716889391104 |
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| author | Ashish Pathak Andreas Mårtensson Sudhir Gawariker Ashish Sharma Vishal Diwan Manju Purohit Johan Ursing |
| author_facet | Ashish Pathak Andreas Mårtensson Sudhir Gawariker Ashish Sharma Vishal Diwan Manju Purohit Johan Ursing |
| author_sort | Ashish Pathak |
| collection | DOAJ |
| description | Abstract Background Artesunate plus sulfadoxine–pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015–2016 after 3–4 years of ASP use, are reported. Methods Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16–185, pfdhps 436–632 and K13 407–689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism. Results Sulfadoxine–pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively. Conclusion The frequency of P. falciparum with reduced susceptibility to sulfadoxine–pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use. |
| first_indexed | 2024-12-11T03:23:22Z |
| format | Article |
| id | doaj.art-c943624b91744d7896737b70c0b76143 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-11T03:23:22Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
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| series | Malaria Journal |
| spelling | doaj.art-c943624b91744d7896737b70c0b761432022-12-22T01:22:35ZengBMCMalaria Journal1475-28752020-08-011911710.1186/s12936-020-03274-wStable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, IndiaAshish Pathak0Andreas Mårtensson1Sudhir Gawariker2Ashish Sharma3Vishal Diwan4Manju Purohit5Johan Ursing6Department of Pediatrics, R D Gardi Medical CollegeDepartment of Women and Children’s Health, International Maternal and Child Health Unit, Uppsala UniversityDepartment of Medicine, R D Gardi Medical CollegeDepartment of Medicine, R D Gardi Medical CollegeDepartment of Women and Children’s Health, International Maternal and Child Health Unit, Uppsala UniversityGlobal Health–Health Systems and Policy: Medicines, Focusing Antibiotics, Department of Global Public Health, Karolinska InstitutetDepartment of Infectious Diseases, Danderyd HospitalAbstract Background Artesunate plus sulfadoxine–pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015–2016 after 3–4 years of ASP use, are reported. Methods Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16–185, pfdhps 436–632 and K13 407–689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism. Results Sulfadoxine–pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively. Conclusion The frequency of P. falciparum with reduced susceptibility to sulfadoxine–pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.http://link.springer.com/article/10.1186/s12936-020-03274-wPlasmodium falciparumArtesunate sulfadoxine pyrimethamineChloroquineResistancepfcrtpfmdr1 |
| spellingShingle | Ashish Pathak Andreas Mårtensson Sudhir Gawariker Ashish Sharma Vishal Diwan Manju Purohit Johan Ursing Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India Malaria Journal Plasmodium falciparum Artesunate sulfadoxine pyrimethamine Chloroquine Resistance pfcrt pfmdr1 |
| title | Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India |
| title_full | Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India |
| title_fullStr | Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India |
| title_full_unstemmed | Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India |
| title_short | Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India |
| title_sort | stable high frequencies of sulfadoxine pyrimethamine resistance associated mutations and absence of k13 mutations in plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine pyrimethamine in ujjain madhya pradesh india |
| topic | Plasmodium falciparum Artesunate sulfadoxine pyrimethamine Chloroquine Resistance pfcrt pfmdr1 |
| url | http://link.springer.com/article/10.1186/s12936-020-03274-w |
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