16 research outputs found

    The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam : a study protocol for an open single-arm interventional trial [awaiting peer review]

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    Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018

    SHORT REPORT: \u3ci\u3eIN VIVO\u3c/i\u3e SENSITIVITY OF \u3ci\u3ePLASMODIUM FALCIPARUM\u3c/i\u3e TO HALOFANTRINE IN SOUTHERN CENTRAL VIETNAM

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    Drug-resistant Plasmodium falciparum is present in Vietnam. We assessed the in vivo sensitivity of P. falciparum to halofantrine in two villages in the southern part of central Vietnam. Halofantrine (8 mg/kg × 3 doses) was administered to 37 patients with either P. falciparum (n = 32) or mixed P. falciparum/P. vivax malaria (n = 5). End points were parasite sensitivity or resistance (RI/RII/RIII) determined by parasite clearance, persistence, or recurrence during 28 days of follow-up. By day 28, 31 (93.9%) of 33 (95% confidence interval = 79.8−99.2%) patients were sensitive. Two patients had recurrent P. falciparum parasitemia on days 14 and 21. Halofantrine effectively treated uncomplicated P. falciparum malaria in these Vietnamese patients

    ASSESSING DRUG SENSITIVITY OF \u3ci\u3ePLASMODIUM VIVAX\u3c/i\u3e TO HALOFANTRINE OR CHOROQUINE IN SOUTHERN, CENTRAL VIETNAM USING AN EXTENDED 28-DAY \u3ci\u3eIN VIVO\u3c/i\u3e TEST AND POLYMERASE CHAIN REACTION GENOTYPING

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    Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1–100) chloroquine and 21/24 (87.5%) (95% CI 67.6–97.3) halofantrine-treated patients were sensitive. Three halofantrine recipients had initial clearance but subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias diiumffered, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and halofantrine. Genotyping was useful for differentiating the recurrent vivax parasitemias

    Inhibitory Antibodies Specific for the 19-Kilodalton Fragment of Merozoite Surface Protein 1 Do Not Correlate with Delayed Appearance of Infection with Plasmodium falciparum in Semi-Immune Individuals in Vietnam ▿

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    Inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein 1 (MSP119) are a significant component of inhibitory responses in individuals immune to malaria. Nevertheless, conflicting results have been obtained in determining whether this antibody specificity correlates with protection in residents of areas where malaria is endemic. In this study, we examined sera collected from a population of semi-immune individuals living in an area of Vietnam with meso-endemicity during a 6-month period. We used two Plasmodium falciparum parasite lines that express either endogenous MSP119 or the homologous region from Plasmodium yoelii to measure the MSP119-specific inhibitory activity. We showed that (i) the level of MSP119-specific inhibitory antibodies was not associated with a delay in P. falciparum infection, (ii) MSP119-specific inhibitory antibodies declined significantly during the convalescent period after infection, and (iii) there was no significant correlation between the MSP119-specific inhibitory antibodies and the total antibodies measured by enzyme-linked immunosorbent assay. These results have implications for understanding naturally acquired immunity to malaria and for the development and evaluation of MSP119-based vaccines

    A trial of Itraconazole or Amphotericin B HIV-associated talaromycosis

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    Background Talaromyces marneffei infection is a major cause of HIV-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate but it has significant side effects, high cost and limited availability. Itraconazole is orally available, better- tolerated and widely-used in place of amphotericin; however, these two strategies have not been compared in clinical trials. Methods In this open-label non-inferiority trial, we randomly assigned 440 HIV-infected adults with microscopy- or culture-confirmed talaromycosis between October 2012 and December 2015 across Vietnam to receive amphotericin 0.7 mg/kg/day (N=219) or itraconazole 400 mg/kg/day (N=221) for two weeks, followed by itraconazole maintenance therapy in all patients. The primary outcome was mortality by two weeks. Secondary outcomes included mortality by week 24, time to clinical resolution, early fungicidal activity, disease relapse, immune reconstitution inflammatory syndrome (IRIS), and tolerability. Results Mortality by two weeks was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.7 percentage points; non-inferiority P<0.0001); however, mortality risks by week 24 were 11.3% and 21.0%, respectively (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6 percentage points; P=0.006). Amphotericin was associated with significantly faster clinical resolution and fungal clearance, and lower rates of relapse and immune reconstitution inflammatory syndrome (IRIS). Patients on amphotericin experienced more infusion reactions, renal failure, hypokalemia, hypomagnesaemia, and anemia. Conclusions Amphotericin is superior to itraconazole as initial therapy for talaromycosis in terms of six-month mortality, clinical response, and fungicidal activity

    Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units

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    Background Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. Methods Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08: 00 a.m. on the survey day were included. Results Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/ 3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). Conclusion A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts

    Reclamation of beneficial bioactivities of herbal antioxidant condensed tannin extracted from Euonymus laxiflorus

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    [[abstract]]Natural condensed tannins (CT) have received great interest due to their vast beneficial bioactivities. Recently, Euonymus laxiflorus, an edible medicinal herb collected in the Central Highlands of Vietnam, was newly recognized as a natural source rich in antioxidant CT. The aim of this study is to scale up extraction and investigate various novel bioactivities of the isolated CT. The screening of the parts used rich in CT, such as heartwood, trunk bark, branch, and the leaves of EL, indicated that the EL trunk bark (ELTB) has the highest CT content. E. laxiflorus CT (ELCT) was extracted with high-level scale from ELTB via several techniques and then was qualified by NMR spectra and HPLC finger printing. A condensed tannin ELBT-3.1.d was isolated and showed its high molecular weight of ≥ 10 kDa and various in vitro bioactivities. ELBT-3.1.d demonstrated high antioxidant capacity (IC50 = 6.11 µg/mL), and potent enzymes inhibition targets in anti-diabetes, especially showing novel potential inhibition against human salivary α-amylase with IC50 value of 3.01 µg/mL. ELBT-3.1.d displayed no anti-NO effect but did show moderate to effective anticancer activities against A549, MCF-7, HepG2, and WiDr. Notably, condensed tannin ELBT-3.1.d displayed no toxicity to normal cells and a novel potential prebiotic effect on Lactobacillus paracasei BCRC14023 and Lactobacillus rhamnosus BCRC16000. In the animal test, ELCT demonstrated significant effect on reducing plasma glucose in mice at the doses of 50–100 mg/kg BW. The current study contributes to enrich the novel bioactivities of ELCT which may be suggested as functional food or drugs due to processing numerous beneficial bioactivities.[[sponsorship]]MOST[[notice]]補正完
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