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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2014
|
| _version_ | 1797065438778097664 |
|---|---|
| author | Chotivanich, K Tripura, R Das, D Yi, P Day, N Pukrittayakamee, S Chuor, C Socheat, D Dondorp, A White, N |
| author_facet | Chotivanich, K Tripura, R Das, D Yi, P Day, N Pukrittayakamee, S Chuor, C Socheat, D Dondorp, A White, N |
| author_sort | Chotivanich, K |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-06T21:28:40Z |
| format | Journal article |
| id | oxford-uuid:43f0c688-e389-4d55-a362-20182e8293fd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:28:40Z |
| publishDate | 2014 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:43f0c688-e389-4d55-a362-20182e8293fd2022-03-26T14:58:36ZLaboratory detection of artemisinin-resistant Plasmodium falciparum.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:43f0c688-e389-4d55-a362-20182e8293fdEnglishSymplectic Elements at OxfordAmerican Society for Microbiology2014Chotivanich, KTripura, RDas, DYi, PDay, NPukrittayakamee, SChuor, CSocheat, DDondorp, AWhite, NConventional 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. |
| spellingShingle | Chotivanich, K Tripura, R Das, D Yi, P Day, N Pukrittayakamee, S Chuor, C Socheat, D Dondorp, A White, N Laboratory detection of artemisinin-resistant Plasmodium falciparum. |
| title | 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_short | Laboratory detection of artemisinin-resistant Plasmodium falciparum. |
| title_sort | laboratory detection of artemisinin resistant plasmodium falciparum |
| work_keys_str_mv | AT chotivanichk laboratorydetectionofartemisininresistantplasmodiumfalciparum AT tripurar laboratorydetectionofartemisininresistantplasmodiumfalciparum AT dasd laboratorydetectionofartemisininresistantplasmodiumfalciparum AT yip laboratorydetectionofartemisininresistantplasmodiumfalciparum AT dayn laboratorydetectionofartemisininresistantplasmodiumfalciparum AT pukrittayakamees laboratorydetectionofartemisininresistantplasmodiumfalciparum AT chuorc laboratorydetectionofartemisininresistantplasmodiumfalciparum AT socheatd laboratorydetectionofartemisininresistantplasmodiumfalciparum AT dondorpa laboratorydetectionofartemisininresistantplasmodiumfalciparum AT whiten laboratorydetectionofartemisininresistantplasmodiumfalciparum |