Rapid decline in the susceptibility of Plasmodium falciparum to dihydroartemisinin-piperaquine in the south of Vietnam

Background Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub‑region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear. Methods In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up. Patients received the national recommended first‑line treatment dihydroartemisinin‑piperaquine for three days. Results Over the 5 years the proportion of patients with detectable parasitaemia on day 3 rose steadily from 38 to 57% (P andlt; 0.001). In Binh Phuoc province, the parasite clearance half‑life increased from 3.75 h in 2011 to 6.60 h in 2015 (P andlt; 0.001), while treatment failures rose from 0% in 2012 and 2013, to 7% in 2014 and 26% in 2015 (P andlt; 0.001). Recrudescence was associated with in vitro evidence of artemisinin and piperaquine resistance. In the treatment failures cases of 2015, all 14 parasite isolates carried the C580Y Pfkelch 13 gene, marker of artemisinin resistance and 93% (13/14) of them carried exoE415G mutations, markers of piperaquine resistance. Conclusions In the south of Vietnam recent emergence of piperaquine resistant P. falciparum strains has accelerated the reduced response to artemisinin and has led to treatment failure rates of up to 26% to dihydroartemisinin‑piperaquine, Vietnam’s current first‑line ACT. Alternative treatments are urgently needed

K13-propeller mutations in Plasmodium falciparum populations in malaria endemic regions of Vietnam from 2009 to 2016

The spread of artemisinin resistant P. falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACT) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant for Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT for P. falciparum The propeller domain gene of K13, a molecular marker of artemisinin resistance, was sequenced successfully in 1060 P. falciparum isolates collected at 3 malaria hotspots in Vietnam between 2009 and 2016. Eight K13 propeller mutations (Thr474Ile, Tyr493His, Arg539Thr, Ile543Thr, Pro553Leu, Val568Gly, Pro574Leu and Cys580Tyr) were found, including several that have been validated as artemisinin resistant markers. The prevalences of K13 mutations were 29% (222/767), 6% (11/188) and 43% (45/105) in in Binh Phuoc, Ninh Thuan and Gia Lai respectively. Cys580Tyr became the dominant genotype in recent years comprising 79.1% (34/43) of isolates in Binh Phuoc and 63% (17/27) in Gia Lai Province. K13 mutations were associated with reduced ring stage susceptibility to dihydroartemisinin (DHA) in-vitro and prolonged parasite clearance in-vivo. An analysis of haplotypes flanking K13 suggested the presence of multiple strains with Cys580Tyr, rather than a single strain expanding across the three sites

K13-propeller mutations in Plasmodium falciparum populations in malaria endemic regions of Vietnam from 2009 to 2016

The spread of artemisinin resistant P. falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACT) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant for Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT for P. falciparum The propeller domain gene of K13, a molecular marker of artemisinin resistance, was sequenced successfully in 1060 P. falciparum isolates collected at 3 malaria hotspots in Vietnam between 2009 and 2016. Eight K13 propeller mutations (Thr474Ile, Tyr493His, Arg539Thr, Ile543Thr, Pro553Leu, Val568Gly, Pro574Leu and Cys580Tyr) were found, including several that have been validated as artemisinin resistant markers. The prevalences of K13 mutations were 29% (222/767), 6% (11/188) and 43% (45/105) in in Binh Phuoc, Ninh Thuan and Gia Lai respectively. Cys580Tyr became the dominant genotype in recent years comprising 79.1% (34/43) of isolates in Binh Phuoc and 63% (17/27) in Gia Lai Province. K13 mutations were associated with reduced ring stage susceptibility to dihydroartemisinin (DHA) in-vitro and prolonged parasite clearance in-vivo. An analysis of haplotypes flanking K13 suggested the presence of multiple strains with Cys580Tyr, rather than a single strain expanding across the three sites

A multi centre randomized open label trial of chloroquine for the treatment of adults with SARS-CoV-2 infection in Vietnam

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/202

Porcine pancreatic α-amylase inhibitors from Euonymus laxiflorus Champ

[[abstract]]Twenty-six samples of indigenous medicinal plants were collected in Dak Lak Province of Vietnam and evaluated for α-amylase inhibitory activity. Of these samples, trunk bark extract from Euonymus laxiflorus Champ. (ELC extract) showed the greatest α-amylase inhibitory activity with the smallest 50 % inhibitory concentration (IC50) of 6.6 ± 0.6 µg/mL against porcine pancreatic α-amylase. This extract possessed strong inhibitory activity against human saliva α-amylase and slightly lower activity against Bacillus subtilis α-amylase, with IC50 values of 4.2 ± 0.2 and 27.8 ± 1.8 µg/mL, respectively. ELC extract was found to be strongly thermostable, retaining 72–100 % relative activity even after heating at 100 °C for 5 min to 2 h. This extract was also stable at various pH values. These results suggest that ELC extract may be a good candidate for treatment of non-insulin-dependent diabetes mellitus (NIDDM) and obesity.[[notice]]補正完