Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies
<p>Abstract</p> <p>Background</p> <p>Confirmation of artemisinin-delayed parasite clearance in <it>Plasmodium falciparum</it> along the Thai-Myanmar border has inspired a global response to contain and monitor drug resistance to avert the disastrous conseque...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-09-01
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| Series: | Malaria Journal |
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| Online Access: | http://www.malariajournal.com/content/11/1/333 |
| _version_ | 1818859115455184896 |
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| author | Brown Tyler Smith Linda S Oo Eh Kalu Shawng Kum Lee Thomas J Sullivan David Beyrer Chris Richards Adam K |
| author_facet | Brown Tyler Smith Linda S Oo Eh Kalu Shawng Kum Lee Thomas J Sullivan David Beyrer Chris Richards Adam K |
| author_sort | Brown Tyler |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Confirmation of artemisinin-delayed parasite clearance in <it>Plasmodium falciparum</it> along the Thai-Myanmar border has inspired a global response to contain and monitor drug resistance to avert the disastrous consequences of a potential spread to Africa. However, resistance data from Myanmar are sparse, particularly from high-risk areas where limited health services and decades of displacement create conditions for resistance to spread. Subclinical infections may represent an important reservoir for resistance genes that confer a fitness disadvantage relative to wild-type alleles. This study estimates the prevalence of resistance genotypes in three previously unstudied remote populations in Myanmar and tests the <it>a priori</it> hypothesis that resistance gene prevalence would be higher among isolates collected from subclinical infections than isolates collected from febrile clinical patients. A systematic review of resistance studies is provided for context.</p> <p>Methods</p> <p>Community health workers in Karen and Kachin States and an area spanning the Indo-Myanmar border collected dried blood spots from 988 febrile clinical patients and 4,591 villagers with subclinical infection participating in routine prevalence surveys. Samples positive for <it>P. falciparum</it> 18 s ribosomal RNA by real-time PCR were genotyped for <it>P. falciparum</it> multidrug resistance protein (<it>pfmdr1)</it> copy number and the <it>pfcrt</it> K76T polymorphism using multiplex real-time PCR.</p> <p>Results</p> <p><it>Pfmdr1</it> copy number increase and the <it>pfcrt</it> K76 polymorphism were determined for 173 and 269 isolates, respectively. Mean <it>pfmdr1</it> copy number was 1.2 (range: 0.7 to 3.7). <it>Pfmdr1</it> copy number increase was present in 17.5%, 9.6% and 11.1% of isolates from Karen and Kachin States and the Indo-Myanmar border, respectively. <it>Pfmdr1</it> amplification was more prevalent in subclinical isolates (20.3%) than clinical isolates (6.4%, odds ratio 3.7, 95% confidence interval 1.1 - 12.5). P<it>fcrt</it> K76T prevalence ranged from 90-100%.</p> <p>Conclusions</p> <p>Community health workers can contribute to molecular surveillance of drug resistance in remote areas of Myanmar. Marginal and displaced populations under-represented among previous resistance investigations can and should be included in resistance surveillance efforts, particularly once genetic markers of artemisinin-delayed parasite clearance are identified. Subclinical infections may contribute to the epidemiology of drug resistance, but determination of gene amplification from desiccated filter samples requires further validation when DNA concentration is low.</p> |
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| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-19T09:07:03Z |
| publishDate | 2012-09-01 |
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| spelling | doaj.art-7bfd4218e577433e98e3a17ef3b310fd2022-12-21T20:28:19ZengBMCMalaria Journal1475-28752012-09-0111133310.1186/1475-2875-11-333Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studiesBrown TylerSmith Linda SOo Eh KaluShawng KumLee Thomas JSullivan DavidBeyrer ChrisRichards Adam K<p>Abstract</p> <p>Background</p> <p>Confirmation of artemisinin-delayed parasite clearance in <it>Plasmodium falciparum</it> along the Thai-Myanmar border has inspired a global response to contain and monitor drug resistance to avert the disastrous consequences of a potential spread to Africa. However, resistance data from Myanmar are sparse, particularly from high-risk areas where limited health services and decades of displacement create conditions for resistance to spread. Subclinical infections may represent an important reservoir for resistance genes that confer a fitness disadvantage relative to wild-type alleles. This study estimates the prevalence of resistance genotypes in three previously unstudied remote populations in Myanmar and tests the <it>a priori</it> hypothesis that resistance gene prevalence would be higher among isolates collected from subclinical infections than isolates collected from febrile clinical patients. A systematic review of resistance studies is provided for context.</p> <p>Methods</p> <p>Community health workers in Karen and Kachin States and an area spanning the Indo-Myanmar border collected dried blood spots from 988 febrile clinical patients and 4,591 villagers with subclinical infection participating in routine prevalence surveys. Samples positive for <it>P. falciparum</it> 18 s ribosomal RNA by real-time PCR were genotyped for <it>P. falciparum</it> multidrug resistance protein (<it>pfmdr1)</it> copy number and the <it>pfcrt</it> K76T polymorphism using multiplex real-time PCR.</p> <p>Results</p> <p><it>Pfmdr1</it> copy number increase and the <it>pfcrt</it> K76 polymorphism were determined for 173 and 269 isolates, respectively. Mean <it>pfmdr1</it> copy number was 1.2 (range: 0.7 to 3.7). <it>Pfmdr1</it> copy number increase was present in 17.5%, 9.6% and 11.1% of isolates from Karen and Kachin States and the Indo-Myanmar border, respectively. <it>Pfmdr1</it> amplification was more prevalent in subclinical isolates (20.3%) than clinical isolates (6.4%, odds ratio 3.7, 95% confidence interval 1.1 - 12.5). P<it>fcrt</it> K76T prevalence ranged from 90-100%.</p> <p>Conclusions</p> <p>Community health workers can contribute to molecular surveillance of drug resistance in remote areas of Myanmar. Marginal and displaced populations under-represented among previous resistance investigations can and should be included in resistance surveillance efforts, particularly once genetic markers of artemisinin-delayed parasite clearance are identified. Subclinical infections may contribute to the epidemiology of drug resistance, but determination of gene amplification from desiccated filter samples requires further validation when DNA concentration is low.</p>http://www.malariajournal.com/content/11/1/333MalariaPlasmodium falciparumArtemisinin resistanceGeneticSubclinical infectionConflictMyanmar |
| spellingShingle | Brown Tyler Smith Linda S Oo Eh Kalu Shawng Kum Lee Thomas J Sullivan David Beyrer Chris Richards Adam K Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies Malaria Journal Malaria Plasmodium falciparum Artemisinin resistance Genetic Subclinical infection Conflict Myanmar |
| title | Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies |
| title_full | Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies |
| title_fullStr | Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies |
| title_full_unstemmed | Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies |
| title_short | Molecular surveillance for drug-resistant <it>Plasmodium falciparum</it> in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies |
| title_sort | molecular surveillance for drug resistant it plasmodium falciparum it in clinical and subclinical populations from three border regions of burma myanmar cross sectional data and a systematic review of resistance studies |
| topic | Malaria Plasmodium falciparum Artemisinin resistance Genetic Subclinical infection Conflict Myanmar |
| url | http://www.malariajournal.com/content/11/1/333 |
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