Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum
Conventional 48-h in vitro susceptibility tests have low sensitivity in identifying artemisinin-resistant Plasmodium falciparum, defined phenotypically by low in vivo parasite clearance rates. We hypothesized originally that this discrepancy was explained by a loss of ring-stage susceptibility and s...
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American Society for Microbiology
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068498/ |
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pubmed-4068498 |
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pubmed-40684982014-07-17 Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum Chotivanich, Kesinee Tripura, Rupam Das, Debashish Yi, Poravuth Day, Nicholas P. J. Pukrittayakamee, Sasithon Chuor, Char Meng Socheat, Duong Dondorp, Arjen M. White, Nicholas J. Susceptibility Conventional 48-h in vitro susceptibility tests have low sensitivity in identifying artemisinin-resistant Plasmodium falciparum, defined phenotypically by low in vivo parasite clearance rates. We hypothesized originally that this discrepancy was explained by a loss of ring-stage susceptibility and so developed a simple field-adapted 24-h trophozoite maturation inhibition (TMI) assay focusing on the ring stage and compared it to the standard 48-h schizont maturation inhibition (WHO) test. In Pailin, western Cambodia, where artemisinin-resistant P. falciparum is prevalent, the TMI test mean (95% confidence interval) 50% inhibitory concentration (IC50) for artesunate was 6.8 (5.2 to 8.3) ng/ml compared with 1.5 (1.2 to 1.8) ng/ml for the standard 48-h WHO test (P = 0.001). TMI IC50s correlated significantly with the in vivo responses to artesunate (parasite clearance time [r = 0.44, P = 0.001] and parasite clearance half-life [r = 0.46, P = 0.001]), whereas the standard 48-h test values did not. On continuous culture of two resistant isolates, the artemisinin-resistant phenotype was lost after 6 weeks (IC50s fell from 10 and 12 ng/ml to 2.7 and 3 ng/ml, respectively). Slow parasite clearance in falciparum malaria in western Cambodia results from reduced ring-stage susceptibility. American Society for Microbiology 2014-06 /pmc/articles/PMC4068498/ /pubmed/24663013 http://dx.doi.org/10.1128/AAC.01924-13 Text en Copyright © 2014 Chotivanich et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) . |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Chotivanich, Kesinee Tripura, Rupam Das, Debashish Yi, Poravuth Day, Nicholas P. J. Pukrittayakamee, Sasithon Chuor, Char Meng Socheat, Duong Dondorp, Arjen M. White, Nicholas J. |
| spellingShingle |
Chotivanich, Kesinee Tripura, Rupam Das, Debashish Yi, Poravuth Day, Nicholas P. J. Pukrittayakamee, Sasithon Chuor, Char Meng Socheat, Duong Dondorp, Arjen M. White, Nicholas J. Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum |
| author_facet |
Chotivanich, Kesinee Tripura, Rupam Das, Debashish Yi, Poravuth Day, Nicholas P. J. Pukrittayakamee, Sasithon Chuor, Char Meng Socheat, Duong Dondorp, Arjen M. White, Nicholas J. |
| author_sort |
Chotivanich, Kesinee |
| title |
Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum |
| title_short |
Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum |
| title_full |
Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum |
| title_fullStr |
Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum |
| title_full_unstemmed |
Laboratory Detection of Artemisinin-Resistant Plasmodium falciparum |
| title_sort |
laboratory detection of artemisinin-resistant plasmodium falciparum |
| description |
Conventional 48-h in vitro susceptibility tests have low sensitivity in identifying artemisinin-resistant Plasmodium falciparum, defined phenotypically by low in vivo parasite clearance rates. We hypothesized originally that this discrepancy was explained by a loss of ring-stage susceptibility and so developed a simple field-adapted 24-h trophozoite maturation inhibition (TMI) assay focusing on the ring stage and compared it to the standard 48-h schizont maturation inhibition (WHO) test. In Pailin, western Cambodia, where artemisinin-resistant P. falciparum is prevalent, the TMI test mean (95% confidence interval) 50% inhibitory concentration (IC50) for artesunate was 6.8 (5.2 to 8.3) ng/ml compared with 1.5 (1.2 to 1.8) ng/ml for the standard 48-h WHO test (P = 0.001). TMI IC50s correlated significantly with the in vivo responses to artesunate (parasite clearance time [r = 0.44, P = 0.001] and parasite clearance half-life [r = 0.46, P = 0.001]), whereas the standard 48-h test values did not. On continuous culture of two resistant isolates, the artemisinin-resistant phenotype was lost after 6 weeks (IC50s fell from 10 and 12 ng/ml to 2.7 and 3 ng/ml, respectively). Slow parasite clearance in falciparum malaria in western Cambodia results from reduced ring-stage susceptibility. |
| publisher |
American Society for Microbiology |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068498/ |
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1612105312781729792 |