Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial
Background: Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown. Methods: A randomized, controlled trial of CQ vs artesunate-mefloquine (AS...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/83425 http://hdl.handle.net/10220/41420 |
| _version_ | 1826129478789627904 |
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| author | Grigg, Matthew J. William, Timothy Menon, Jayaram Barber, Bridget E. Wilkes, Christopher S. Rajahram, Giri S. Edstein, Michael D. Auburn, Sarah Price, Ric N. Yeo, Tsin W. Yeo, Tsin Wen Anstey, Nicholas M. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Grigg, Matthew J. William, Timothy Menon, Jayaram Barber, Bridget E. Wilkes, Christopher S. Rajahram, Giri S. Edstein, Michael D. Auburn, Sarah Price, Ric N. Yeo, Tsin W. Yeo, Tsin Wen Anstey, Nicholas M. |
| author_sort | Grigg, Matthew J. |
| collection | NTU |
| description | Background: Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown. Methods: A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan–Meier analysis. Results: From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8–75.6) after CQ and 0% (95% CI, 0–.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5–9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P = .001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5–9.3; P = .005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60–.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment. Conclusions: High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected. |
| first_indexed | 2024-10-01T07:41:16Z |
| format | Journal Article |
| id | ntu-10356/83425 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:41:16Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/834252022-02-16T16:30:10Z Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial Grigg, Matthew J. William, Timothy Menon, Jayaram Barber, Bridget E. Wilkes, Christopher S. Rajahram, Giri S. Edstein, Michael D. Auburn, Sarah Price, Ric N. Yeo, Tsin W. Yeo, Tsin Wen Anstey, Nicholas M. Lee Kong Chian School of Medicine (LKCMedicine) Plasmodium vivax Malaria Background: Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown. Methods: A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan–Meier analysis. Results: From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8–75.6) after CQ and 0% (95% CI, 0–.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5–9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P = .001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5–9.3; P = .005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60–.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment. Conclusions: High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected. Published version 2016-09-06T04:24:09Z 2019-12-06T15:22:17Z 2016-09-06T04:24:09Z 2019-12-06T15:22:17Z 2016 Journal Article Grigg, M. J., William, T., Menon, J., Barber, B. E., Wilkes, C. S., Rajahram, G. S., et al. (2016). Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial. Clinical Infectious Diseases, 62(11), 1403-1411. 1058-4838 https://hdl.handle.net/10356/83425 http://hdl.handle.net/10220/41420 10.1093/cid/ciw121 27107287 en Clinical Infectious Diseases © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 9 p. application/pdf |
| spellingShingle | Plasmodium vivax Malaria Grigg, Matthew J. William, Timothy Menon, Jayaram Barber, Bridget E. Wilkes, Christopher S. Rajahram, Giri S. Edstein, Michael D. Auburn, Sarah Price, Ric N. Yeo, Tsin W. Yeo, Tsin Wen Anstey, Nicholas M. Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial |
| title | Efficacy of Artesunate-mefloquine for Chloroquine-resistant
Plasmodium vivax
Malaria in Malaysia: An Open-label, Randomized, Controlled Trial |
| title_full | Efficacy of Artesunate-mefloquine for Chloroquine-resistant
Plasmodium vivax
Malaria in Malaysia: An Open-label, Randomized, Controlled Trial |
| title_fullStr | Efficacy of Artesunate-mefloquine for Chloroquine-resistant
Plasmodium vivax
Malaria in Malaysia: An Open-label, Randomized, Controlled Trial |
| title_full_unstemmed | Efficacy of Artesunate-mefloquine for Chloroquine-resistant
Plasmodium vivax
Malaria in Malaysia: An Open-label, Randomized, Controlled Trial |
| title_short | Efficacy of Artesunate-mefloquine for Chloroquine-resistant
Plasmodium vivax
Malaria in Malaysia: An Open-label, Randomized, Controlled Trial |
| title_sort | efficacy of artesunate mefloquine for chloroquine resistant plasmodium vivax malaria in malaysia an open label randomized controlled trial |
| topic | Plasmodium vivax Malaria |
| url | https://hdl.handle.net/10356/83425 http://hdl.handle.net/10220/41420 |
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