Dataset Information

In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.

ABSTRACT: By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam.From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS) (2mg/kg/day versus 4 mg/kg/day for three days) followed by dihydroartemisinin-piperaquine (DHA-PPQ) and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time.166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2.72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4%) and late clinical failure occurred in one (2%) of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR) rates in the three groups were 94%, 100%, and 100% (p=0.04).This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but slower clearance in comparison with historical data from Vietnam. Further studies to determine whether this represents the emergence of artemisinin resistance in this area are needed. Currently, the therapeutic response to DHA-PPQ remains satisfactory in southern Vietnam.NTC01165372.

SUBMITTER: Hien TT

PROVIDER: S-EPMC3504531 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.

Hien Tran Tinh TT Thuy-Nhien Nguyen Thanh NT Phu Nguyen Hoan NH Boni Maciej F MF Thanh Ngo Viet NV Nha-Ca Nguyen Thuy NT Thai Le Hong le H Thai Cao Quang CQ Toi Pham Van PV Thuan Phung Duc PD Long Le Thanh le T Dong Le Thanh le T Merson Laura L Dolecek Christiane C Stepniewska Kasia K Ringwald Pascal P White Nicholas J NJ Farrar Jeremy J Wolbers Marcel M

Malaria journal 20121026

<h4>Background</h4>By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasito ...[more]

PMID: 23101492

Similar Datasets

Project description: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.

Project description:The naturally acquired microbiota of Anopheles can influence vector's susceptibility to Plasmodium and its capacity to transmit them. Microbiota modification is a new challenge to limit disease transmission but it still needs advanced knowledges on bacterial community in Anopheles, especially in wild and infected specimens from diverse origin and species. Bacterial culture and 16S rRNA gene-PCR associated to Temporal Temperature Gradient Electrophoresis (TTGE) were applied to explore the bacterial diversity in the abdomen of 100 wild specimens (eight Anopheles species) collected in the Binh Phuoc Province, Vietnam. Culture and PCR-TTGE were complementary. The bacterial richness of the mosquito collection encompassed 105 genera belonging to seven phyla, mostly Proteobacteria, Firmicutes, and Actinobacteria. Staphylococcus, Clostridium, and Bacillus in Firmicutes were the most prevalent genera. However, Proteobacteria represented by 57 genera was the most diversified phylum in Anopheles microbiota. The high overall of Anopheles-associated bacteria is confirmed with, to our knowledge, 51 genera described for the first time in Anopheles microbiota. However, the diversity per specimen was low with average diversity index and the average Shannon-Wiener score (H) of 4.843 and 5.569, respectively. The most represented bacterial genera were present in <30% of the specimens. Consequently, the core microbiota share by Anopheles from Binh Phuoc was very narrow, suggesting that Anopheles microbiota was greatly influenced by local environments. The repertory of bacterial genera in two specimens of An. dirus and An. pampanai naturally infected by Plasmodium vivax was also described as preliminary results. Finally, this study completed the repertory of bacteria associated to wild Anopheles. Anopheles associated-bacteria appeared specimen-dependent rather than mosquitoe species- or group-dependent. Their origin and the existence of Anopheles-specific bacterial taxa are discussed.

Project description:BackgroundPlasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries.MethodsA non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days) was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia), parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope), and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels.ResultsThe median (range) parasite clearance half-life and time were 4.8 (2.1-9.7) and 60 (24-96) hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours) in approximately 1/3 of infections. Fourteen of 52 participants (26.9%) had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics.ConclusionsA subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread to this location from its site of origin in western Cambodia. Resistance containment efforts are underway in Myanmar.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12610000896077.

Project description:BACKGROUND: Human malaria is still a burden in Dak Nong and Binh Phuoc Provinces in south-central Vietnam that border Cambodia. Several Anopheles species that transmit human malarial Plasmodium may also transmit Wuchereria bancrofti, the nematode that causes Bancroftian lymphatic filariasis. The objective of this study was to investigate the role of Anopheles species in the transmission of these two pathogens in the two highly malaria endemic provinces of Vietnam. METHODS: Anopheles mosquitoes were collected in Dak Nong and Binh Phuoc Provinces in November and December of 2010 and 2011. Human landing catches, paired collections on human and buffalo, and resting captures were made with mouth aspirators. Collections were also made with light traps. Morphological and PCR-based methods were used to identify the species. Real-time PCR was used to detect Plasmodium species and W. bancrofti in individual mosquitoes. RESULTS: Twenty-four Anopheles species were identified among 797 captured mosquitoes. Anopheles dirus was found in both provinces and was the predominant species in Binh Phuoc Province; An. maculatus was the most prevalent species in Dak Nong Province. Anopheles minimus was collected only in Binh Phuoc Province. Some specimens of An. minimus and An. pampanai were misidentified based on morphology. Four specimens of An. scanloni were identified, and this is the first report of this species of the Dirus Complex in Vietnam. Two females, one An. dirus and one An. pampanai, collected in Binh Phuoc Province were infected with P. vivax, for an overall infection rate of 0.41% (2/486): 0.28% for An. dirus (1/361) and 20% for An. pampanai (1/5). No mosquitoes were found to be infected with P. falciparum, P. knowlesi or W. bancrofti in either province. CONCLUSION: A diversity of Anopheles species occurs in Dak Nong and Binh Phuoc Provinces of Vietnam, several of which are considered to be actual and potential vectors of malarial protozoa and microfilariae. It is highly likely that two of the species, An. dirus and An. pampanai, are active in malaria transmission based on the detection of P. vivax in females of these species. This is the first report of An. scanloni in Vietnam.

Project description:BackgroundArtemisinin-based combination therapies (ACTs) have significantly contributed to reduce Plasmodium falciparum malaria burden in Vietnam, but their efficacy is challenged by treatment failure of dihydroartemisinin/piperaquine ACT in Southern provinces.ObjectivesTo assess the efficacy of dihydroartemisinin/piperaquine for uncomplicated P. falciparum malaria in Gia Lai, Central Vietnam, and determine parasite resistance to artemisinin (ClinicalTrials.gov identifier NCT02604966).MethodsSixty patients received either dihydroartemisinin/piperaquine (4 mg/kg/day, 3 days; n = 33) or artesunate monotherapy (4 mg/kg/day, 3 days; n = 27) followed by dihydroartemisinin/piperaquine (AS + DHA/PPQ). Clinical phenotypes were determined during a 42 day follow-up and analysed together with ex vivo susceptibility to antimalarials and molecular markers of drug resistance.ResultsDay 3 positivity rate was significantly higher in the AS + DHA/PPQ arm compared with dihydroartemisinin/piperaquine (70.4% versus 39.4%, P = 0.016). Parasite clearance time was 95.2 h (AS + DHA/PPQ) versus 71.9 h (dihydroartemisinin/piperaquine, P = 0.063) and parasite clearance half-life was 7.4 h (AS + DHA/PPQ) versus 7.0 h (dihydroartemisinin/piperaquine, P = 0.140). Adequate clinical and parasitological response at Day 42 was 100% in both arms. By RT-qPCR, 36% (19/53) patients remained positive until Day 7. No recurrences were detected. kelch13 artemisinin resistance mutations were found in 87% (39/45) of isolates and 50% (20/40) were KEL1/C580Y. The piperaquine resistance marker plasmepsin-2 was duplicated in 10.4% (5/48). Isolates from Day 3-positive patients (n = 18) had higher ex vivo survival rates to artemisinin compounds (P < 0.048) and prevalence of kelch13 mutations (P = 0.005) than Day 3-negative patients (n = 5). The WHO definition of artemisinin resistance was fulfilled in 60% (24/40) of cases.ConclusionsAlthough dihydroartemisinin/piperaquine remained effective to treat P. falciparum, the high Day 3 positivity rate and prevalence of KEL1 strains calls for continuous monitoring of dihydroartemisinin/piperaquine efficacy in Central Vietnam.

Dataset Information

In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.

Publications

In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets