Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam
Abstract Background Reduced artemisinin susceptibility and artemisinin-based combination therapy (ACT)-resistance against Plasmodium falciparum and chloroquine (CQ)-resistant P. vivax malaria has been reported in Vietnam. Two therapeutic efficacy studies were conducted in Thuan Bac District (Ninh Th...
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doaj-6dc02931545746e7a4b2eb560ea6a6282020-11-25T02:19:27ZengBMCMalaria Journal1475-28752019-01-0118111110.1186/s12936-019-2640-2Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central VietnamNguyen Chinh Phong0Marina Chavchich1Huynh Hong Quang2Nguyen Ngoc San3Geoffrey W. Birrell4Ilin Chuang5Nicholas J. Martin6Nguyen Duc Manh7Michael D. Edstein8Vietnam People’s Army Military Institute of Preventive MedicineAustralian Defence Force Malaria and Infectious Disease InstituteInstitute of Malariology, Parasitology and EntomologyVietnam People’s Army Military Institute of Preventive MedicineAustralian Defence Force Malaria and Infectious Disease InstituteNaval Medical Research CenterNaval Medical Research Unit-TWOVietnam People’s Army Military Institute of Preventive MedicineAustralian Defence Force Malaria and Infectious Disease InstituteAbstract Background Reduced artemisinin susceptibility and artemisinin-based combination therapy (ACT)-resistance against Plasmodium falciparum and chloroquine (CQ)-resistant P. vivax malaria has been reported in Vietnam. Two therapeutic efficacy studies were conducted in Thuan Bac District (Ninh Thuan Province, Vietnam) in 2015 and 2016 to determine the extent of reduced artemisinin susceptibility and ACT resistant falciparum malaria, and CQ-resistant vivax malaria were present. Methods Twenty-seven patients with falciparum malaria were randomized to receive artesunate alone (AS ~ 4 mg/kg/day) for 4 days followed by dihydroartemisinin (DHA) (2.2 mg/kg)–piperaquine (PPQ) (18 mg/kg) daily for 3 days or artemether (AM) (1.7 mg/kg)–lumefantrine (LUM) (12 mg/kg) twice daily for 3 days. Sixteen subjects with vivax malaria received CQ (total 25 mg/kg over 3 days). The therapeutic efficacy study for treating falciparum malaria was complemented with molecular analysis for artemisinin and piperaquine resistance, and in vitro drug susceptibility testing. Patient’s drug exposure following both falciparum and vivax treatment studies was determined. Results Twenty-five of 27 patients treated with the artemisinin regimens completed the 42-day follow-up period. None had parasites present on day 3 after commencing treatment with no incidence of recrudescence (100% curative rate). One patient on AS + DHA–PPQ was lost to follow-up and one patient had Plasmodium falciparum and Plasmodium vivax infection on day 0 by PCR. Of the vivax patients, 15 of 16 completed CQ treatment and two had a recurrence of vivax malaria on day 28, a failure rate of 13.3% (2/15). No mutations in the Pfkelch-13 gene for artemisinin resistance or exo-E415G gene polymorphism and amplification in plasmepsins 2 and 3 for piperaquine resistance were observed. In vitro testing of patient’s falciparum parasites indicated susceptibility (low IC50 nM values) to dihydroartemisinin, lumefantrine, piperaquine and pyronaridine. Patient’s drug exposure to artesunate and lumefantrine was comparable to published data, however, blood CQ concentrations were lower. Conclusions Clinical findings, molecular analysis and in vitro testing revealed that the falciparum parasites at Phuoc Chien Commune were artemisinin susceptible. The clinical failure rate of the 15 vivax patients who completed CQ treatment was 13%. Further studies are required to determine whether CQ-resistant vivax malaria is present at the commune.http://link.springer.com/article/10.1186/s12936-019-2640-2MalariaVietnamPlasmodium falciparumPlasmodium vivaxArtesunateArtemether |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nguyen Chinh Phong Marina Chavchich Huynh Hong Quang Nguyen Ngoc San Geoffrey W. Birrell Ilin Chuang Nicholas J. Martin Nguyen Duc Manh Michael D. Edstein |
spellingShingle |
Nguyen Chinh Phong Marina Chavchich Huynh Hong Quang Nguyen Ngoc San Geoffrey W. Birrell Ilin Chuang Nicholas J. Martin Nguyen Duc Manh Michael D. Edstein Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam Malaria Journal Malaria Vietnam Plasmodium falciparum Plasmodium vivax Artesunate Artemether |
author_facet |
Nguyen Chinh Phong Marina Chavchich Huynh Hong Quang Nguyen Ngoc San Geoffrey W. Birrell Ilin Chuang Nicholas J. Martin Nguyen Duc Manh Michael D. Edstein |
author_sort |
Nguyen Chinh Phong |
title |
Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam |
title_short |
Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam |
title_full |
Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam |
title_fullStr |
Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam |
title_full_unstemmed |
Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam |
title_sort |
susceptibility of plasmodium falciparum to artemisinins and plasmodium vivax to chloroquine in phuoc chien commune, ninh thuan province, south-central vietnam |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2019-01-01 |
description |
Abstract Background Reduced artemisinin susceptibility and artemisinin-based combination therapy (ACT)-resistance against Plasmodium falciparum and chloroquine (CQ)-resistant P. vivax malaria has been reported in Vietnam. Two therapeutic efficacy studies were conducted in Thuan Bac District (Ninh Thuan Province, Vietnam) in 2015 and 2016 to determine the extent of reduced artemisinin susceptibility and ACT resistant falciparum malaria, and CQ-resistant vivax malaria were present. Methods Twenty-seven patients with falciparum malaria were randomized to receive artesunate alone (AS ~ 4 mg/kg/day) for 4 days followed by dihydroartemisinin (DHA) (2.2 mg/kg)–piperaquine (PPQ) (18 mg/kg) daily for 3 days or artemether (AM) (1.7 mg/kg)–lumefantrine (LUM) (12 mg/kg) twice daily for 3 days. Sixteen subjects with vivax malaria received CQ (total 25 mg/kg over 3 days). The therapeutic efficacy study for treating falciparum malaria was complemented with molecular analysis for artemisinin and piperaquine resistance, and in vitro drug susceptibility testing. Patient’s drug exposure following both falciparum and vivax treatment studies was determined. Results Twenty-five of 27 patients treated with the artemisinin regimens completed the 42-day follow-up period. None had parasites present on day 3 after commencing treatment with no incidence of recrudescence (100% curative rate). One patient on AS + DHA–PPQ was lost to follow-up and one patient had Plasmodium falciparum and Plasmodium vivax infection on day 0 by PCR. Of the vivax patients, 15 of 16 completed CQ treatment and two had a recurrence of vivax malaria on day 28, a failure rate of 13.3% (2/15). No mutations in the Pfkelch-13 gene for artemisinin resistance or exo-E415G gene polymorphism and amplification in plasmepsins 2 and 3 for piperaquine resistance were observed. In vitro testing of patient’s falciparum parasites indicated susceptibility (low IC50 nM values) to dihydroartemisinin, lumefantrine, piperaquine and pyronaridine. Patient’s drug exposure to artesunate and lumefantrine was comparable to published data, however, blood CQ concentrations were lower. Conclusions Clinical findings, molecular analysis and in vitro testing revealed that the falciparum parasites at Phuoc Chien Commune were artemisinin susceptible. The clinical failure rate of the 15 vivax patients who completed CQ treatment was 13%. Further studies are required to determine whether CQ-resistant vivax malaria is present at the commune. |
topic |
Malaria Vietnam Plasmodium falciparum Plasmodium vivax Artesunate Artemether |
url |
http://link.springer.com/article/10.1186/s12936-019-2640-2 |
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