In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome ...sequences of two SARS‐CoV‐2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human‐to‐human transmission of SARS‐CoV‐2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi‐morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.
Highlights
Transmission of SARS‐CoV‐2 is a global public health and clinical concern.
This report describes clinical features, virus isolation, and complete genome sequences from the first two SARS‐CoV‐2 infections in Vietnam.
Epidemiological and phylogenetic analysis suggested evidence of human‐to‐human transmission of SARS‐CoV‐2. Comparison of SARS‐CoV‐2 strains isolated from these two patients with those from Wuhan showed high similarities.
Nonsynonymous substitutions existed in the ORF1ab region of the viral sequence.
Compared with mild clinical and virological manifestations in the younger patient, the elderly suffered from pneumonia, prolonged viral shedding, and residual lung damage.
Antimicrobial resistance has emerged as a major concern in developing countries. The present study sought to define the pattern of antimicrobial resistance in ICU patients with ventilator-associated ...pneumonia.
Between November 2014 and September 2015, we enrolled 220 patients (average age ~ 71 yr) who were admitted to ICU in a major tertiary hospital in Ho Chi Minh City, Vietnam. Data concerning demographic characteristics and clinical history were collected from each patient. The Bauer-Kirby disk diffusion method was used to detect the antimicrobial susceptibility.
Antimicrobial resistance was commonly found in ceftriaxone (88%), ceftazidime (80%), ciprofloxacin (77%), cefepime (75%), levofloxacin (72%). Overall, the rate of antimicrobial resistance to any drug was 93% (n = 153/164), with the majority (87%) being resistant to at least 2 drugs. The three commonly isolated microorganisms were Acinetobacter (n = 75), Klebsiella (n = 39), and Pseudomonas aeruginosa (n = 29). Acinetobacter baumannii were virtually resistant to ceftazidime, ceftriaxone, piperacilin, imipenem, meropenem, ertapenem, ciprofloxacin and levofloxacin. High rates (>70%) of ceftriaxone and ceftazidime-resistant Klebsiella were also observed.
These data indicated that critically ill patients on ventilator in Vietnam were at disturbingly high risk of antimicrobial resistance. The data also imply that these Acinetobacter, Klebsiella, and Pseudomonas aeruginosa and multidrug resistance pose serious therapeutic problems in ICU patients. A concerted and systematic effort is required to rapidly identify high risk patients and to reduce the burden of antimicrobial resistance in developing countries.
The immune system maintains constant surveillance to prevent the infiltration of both endogenous and exogenous threats into host organisms. The process is regulated by effector immune cells that ...combat external pathogens and regulatory immune cells that inhibit excessive internal body inflammation, ultimately establishing a state of homeostasis within the body. Disruption to this process could lead to autoimmunity, which is often associated with the malfunction of both T cells and B cells with T cells playing a more major role. A number of therapeutic mediators for autoimmune diseases are available, from conventional disease-modifying drugs to biologic agents and small molecule inhibitors. Recently, ribosomally synthesized peptides, specifically cyclotides from plants are currently attracting more attention as potential autoimmune disease therapeutics due to their decreased toxicity compared to small molecules inhibitors as well as their remarkable stability against a number of factors. This review provides a concise overview of various cyclotides exhibiting immunomodulatory properties and their potential as therapeutic interventions for autoimmune diseases.
Cyclotides are plant peptides characterized with a head-to-tail cyclized backbone and three interlocking disulfide bonds, known as a cyclic cysteine knot. Despite the variations in cyclotides peptide ...sequences, this core structure is conserved, underlying their most useful feature: stability against thermal and chemical breakdown. Cyclotides are the only natural peptides known to date that are orally bioavailable and able to cross cell membranes. Cyclotides also display bioactivities that have been exploited and expanded to develop as potential therapeutic reagents for a wide range of conditions (e.g., HIV, inflammatory conditions, multiple sclerosis, etc.). As such, in vitro production of cyclotides is of the utmost importance since it could assist further research on this peptide class, specifically the structure–activity relationship and its mechanism of action. The information obtained could be utilized to assist drug development and optimization. Here, we discuss several strategies for the synthesis of cyclotides using both chemical and biological routes.
Article Note: Manh H. Dao and Hieu T. Nguyen contributed equally to this study and are joint first authors. CAPTION(S): Supplementary information. Byline: Guangxiang (George) Luo, Hinh Ly, Shou-Jiang ...Gao, Manh H. Dao, Hieu T. Nguyen, Thinh V. Nguyen, Anh H. Nguyen, Quang C. Luong, Nhung H. P. Vu, Hang T. T. Pham, Thao N. T. Nguyen, Dung H. Thach, Lo V. Nguyen, Luan V. Bui, Hang M. Nguyen, Loan K. T. Huynh, Long T. Nguyen, Thang M. Cao, Quang D. Pham, Thuong V. Nguyen, Lan T. Phan
Extracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including ...Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage.
In this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction, with thrombi observed later. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery.
HIT may jeopardize patient's care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.
Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B ...deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking.
In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile.
The risk of death at week 2 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 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group.
Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).
Greater levels of insect resistance and constraints on the use of current pesticides have recently led to increased crop losses in agricultural production. Further, the health and environmental ...impacts of pesticides now restrict their application. Biologics based on peptides are gaining popularity as efficient crop protection agents with low environmental toxicity. Cysteine-rich peptides (whether originated from venoms or plant defense substances) are chemically stable and effective as insecticides in agricultural applications. Cysteine-rich peptides fulfill the stability and efficacy requirements for commercial uses and provide an environmentally benign alternative to small-molecule insecticides. In this article, cysteine-rich insecticidal peptide classes identified from plants and venoms will be highlighted, focusing on their structural stability, bioactivity and production.
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•Peptide-based agents offer ecofriendly-potent alternatives to current chemical pesticides.•Cyclic peptides from plants (cyclotides) target insect cells by disrupting the membranes.•Cysteine-rich venom peptides target ion channels expressed in the nervous system.•We review the development of these two classes as insecticidal reagents over the past 5 years.
Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and ...mortality caused by RVA. From 2016 to 2021, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 2020. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 2021 were mapped using next-generation sequencing. From 2016 to 2021, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P8, G3P8 and G8P8. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019–2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2–99.9% and 99.1–99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.
•In Vietnam from 2016 to 2021, the G9 RVA genotype was the most frequently detected, followed by G3 (23.9%) and G8 (18.8%)•The circulating G3P8 genotypes were phylogenetically diverse with human and equine-like strains equally distributed.•The antigenic epitopes present on VP7 protein of G1, G3 and G9 strains differed considerably with vaccine strains.
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.
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.
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).
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.
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