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We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.

Abstract Background Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. Methods We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. Results Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28–90, and IgG titers plateaued between day 90–360. During the BA.1/BA.2 wave (February–March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. Conclusions mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.

Objectives: We studied the immunogenicity after primary and booster vaccinations of the Abdala COVID-19 vaccine, a receptor-binding domain protein subunit vaccine, in Vietnamese people by determining the level of neutralization and cross-neutralization activities against the ancestral SARS-CoV-2 and its variants and SARS-CoV-1. Methods: We performed a prospective observational study, enrolling adults aged 19-59 years in Dong Thap province, southern Vietnam, and collected blood samples from baseline until 4 weeks after the booster dose. We measured anti-nucleocapsid, anti-spike, and neutralizing antibodies against SARS-CoV-2 and assessed the cross-neutralization against 14 SARS-CoV-2 variants and SARS-CoV-1. Complementary antibody data came from Vietnamese health care workers fully vaccinated with ChAdOx1-S. Results: After primary vaccination, anti-spike antibody and neutralizing antibodies were detectable in 98.4% and 87% of 251 study participants, respectively, with neutralizing antibody titers similar to that induced by ChAdOx1-S vaccine. Antibody responses after a homologous (Abdala COVID-19) or heterologous (messenger RNA BNT162b2) booster could neutralize 14 SARS-CoV-2 variants (including Omicron) and SARS-CoV-1. Conclusions: Abdala COVID-19 vaccine is immunogenic in Vietnamese people. Enhanced antibody response after a booster dose could cross-neutralize 14 SARS-CoV-2 variants and SARS-CoV-1. Our results have added to the growing body of knowledge about the contribution of protein subunit vaccine platforms to pandemic control.

Abstract Hand foot and mouth disease (HFMD) is caused by a variety of enteroviruses, and occurs in large outbreaks in which a small proportion of children deteriorate rapidly with cardiopulmonary failure. Determining which children are likely to deteriorate is difficult and health systems may become overloaded during outbreaks as many children require hospitalization for monitoring. Heart rate variability (HRV) may help distinguish those with more severe diseases but requires simple scalable methods to collect ECG data. We carried out a prospective observational study to examine the feasibility of using wearable devices to measure HRV in 142 children admitted with HFMD at a children’s hospital in Vietnam. ECG data were collected in all children. HRV indices calculated were lower in those with enterovirus A71 associated HFMD compared to those with other viral pathogens. HRV analysis collected from wearable devices is feasible in a low and middle income country (LMIC) and may help classify disease severity in HFMD.

Abstract Background Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of a gold standard. Current microbiological tests lack sensitivity and clinical diagnostic approaches are subjective. We therefore built a diagnostic model that can be used before microbiological test results are known. Methods We included 659 individuals aged $$\ge 16$$ ≥ 16 years with suspected brain infections from a prospective observational study conducted in Vietnam. We fitted a logistic regression diagnostic model for TBM status, with unknown values estimated via a latent class model on three mycobacterial tests: Ziehl–Neelsen smear, Mycobacterial culture, and GeneXpert. We additionally re-evaluated mycobacterial test performance, estimated individual mycobacillary burden, and quantified the reduction in TBM risk after confirmatory tests were negative. We also fitted a simplified model and developed a scoring table for early screening. All models were compared and validated internally. Results Participants with HIV, miliary TB, long symptom duration, and high cerebrospinal fluid (CSF) lymphocyte count were more likely to have TBM. HIV and higher CSF protein were associated with higher mycobacillary burden. In the simplified model, HIV infection, clinical symptoms with long duration, and clinical or radiological evidence of extra-neural TB were associated with TBM At the cutpoints based on Youden’s Index, the sensitivity and specificity in diagnosing TBM for our full and simplified models were 86.0% and 79.0%, and 88.0% and 75.0% respectively. Conclusion Our diagnostic model shows reliable performance and can be developed as a decision assistant for clinicians to detect patients at high risk of TBM. Summary Diagnosis of tuberculous meningitis is hampered by the lack of gold standard. We developed a diagnostic model using latent class analysis, combining confirmatory test results and risk factors. Models were accurate, well-calibrated, and can support both clinical practice and research.

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

Digital transformation in the management of training activities is an indispensable and mandatory requirement when universities undertake digital transformation. The digital transformation in training activities brings about changes in the modes of conducting educational procedures which also necessitate corresponding changes in management. This article presents the research findings on the digital transformation in the management of training activities at universities in the current context.

Developing digital infrastructure and promoting the application of digital technology in the management of training institutions is currently an urgent issue for universities associated with the trend of digital transformation in the field of education and training towards building a smart university. Vinh University, with more than 1,000 officials, annually pays an average of more than 2,500 travel documents in many different fields of work. The manual issuance and approval process is a waste of time and resources, has posed the problem of applying digital technology in online travel document management, improving management efficiency. This article presents the results of research and application of the online travel document management system, one of the digital technology application solutions of Vinh University.

A strong and effective COVID-19 and future pandemic responses rely on global efforts to carry out surveillance of infections and emerging SARS-CoV-2 variants and to act accordingly in real time. Many countries in Southeast Asia lack capacity to determine the potential threat of new variants, or other emerging infections. Funded by Wellcome, the Southeast Asia initiative to combat SARS-CoV-2 variants (SEACOVARIANTS) consortium aims to develop and apply a multidisciplinary research platform in Southeast Asia (SEA) for rapid assessment of the biological significance of SARS-CoV-2 variants, thereby informing coordinated local, regional and global responses to the COVID-19 pandemic. Our proposal is delivered by the Vietnam and Thailand Wellcome Africa Asia Programmes, bringing together a multidisciplinary team in Indonesia, Thailand and Vietnam with partners in Singapore, the UK and the USA. Herein we outline five work packages to deliver strengthened regional scientific capacity that can be rapidly deployed for future outbreak responses.

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013–2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions.

Mpox was diagnosed in 2 women returning to Vietnam from the United Arab Emirates. The monkeypox viruses belonged to an emerging sublineage, A.2.1, distinct from B.1, which is responsible for the ongoing multicountry outbreak. Women could contribute to mpox transmission, and enhanced genomic surveillance is needed to clarify pathogen evolution.

Abstract Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system. The clinical syndrome of autonomic nervous system dysfunction (ANSD) seen in severe tetanus is characterized principally by changes in heart rate and blood pressure which have been linked to increased circulating catecholamines. Previous studies have described varying relationships between catecholamines and signs of ANSD in tetanus, but are limited by confounders and assays used. In this study, we aimed to perform detailed characterization of the relationship between catecholamines (adrenaline and noradrenaline), cardiovascular parameters (heart rate and blood pressure) and clinical outcomes (ANSD, mechanical ventilation required, and length of intensive care unit stay) in adults with tetanus, as well as examine whether intrathecal antitoxin administration affected subsequent catecholamine excretion. Noradrenaline and adrenaline were measured by ELISA from 24-h urine collections taken on day 5 of hospitalization in 272 patients enrolled in a 2 × 2 factorial-blinded randomized controlled trial in a Vietnamese hospital. Catecholamine results measured from 263 patients were available for analysis. After adjustment for potential confounders (i.e., age, sex, intervention treatment, and medications), there were indications of non-linear relationships between urinary catecholamines and heart rate. Adrenaline and noradrenaline were associated with subsequent development of ANSD, and length of ICU stay.

The IT-based management of training activities at universities has many inadequacies. According to the facilitation of comprehensive IT system application under digital transformation in education sector with the aim of smart-university driven model application, this paper provides a systematic view of a smart university, and analyses some issues related to IT-based training management, which supports Vietnamese universities to integrate smart-university driven management systems.

Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments.

[Purpose] This study analyzes the inequalities of ethnic minority children to adapt to online education. This is also a challenge to the whole education system in Vietnam before the 4th COVID-19 outbreak is considered to have a serious impact on the economy and society of Vietnam. [Methodology/Approach/Design] A case study is conducted in a cross-sectional form with 50 high school students and 10 teachers of the boarding ethnic minority school in Nam Pu district, Dien Bien province of Vietnam. Questions were conducted for students, teachers, and school administrators. [Findings] The lack of WiFi catchers such as laptops, tablets, and smartphones along with poor infrastructure are the main factors affecting the effectiveness of online learning. [Practical Implications] Equality in education is the sustainable development goal adopted by the United Nations in 2015. Geographical differences and economic conditions are factors that directly impact the effectiveness of students' online learning in the context of COVID-19 19. The Government of Vietnam should have an effective financial policy to provide connectivity for poor students, reducing the gap in access to general education services for online classes that are ethnic minorities.

Alcohol beverages have been widely consumed in several parts of the world. In this study, volatile organic compounds in alcoholic beverages including acetaldehyde, ethyl acetate, methanol, and higher ethanol were investigated and evaluated using a headspace gas chromatograph equipped with a mass spectrometer. This study evaluated the suitability of the chromatographic system, linearity, limit of detection, and limit of quantification, accuracy, and precision of the single and simultaneous determination of acetaldehyde, ethyl acetate, and methanol in thousand folds of ethanol. Results showed that the acetaldehyde concentration in local beer samples and local manual product liqueur samples ranged from 4.65 to 13.22 mg/L and from 5.55 to 75.96 mg/L, respectively, but in local industrial product liqueur samples, acetaldehyde was not detected. Methanol was only detected in a few local beer samples and locally manually produced liqueur samples within low concentrations. Ethyl acetate was only detected in all local beer samples, but it was not present in local industrial product liqueur samples.

In this study, the complex of difluoroboron, curcumin (BF2-Cur), has been synthesized and characterized via the combination of Boron trifluoride-diethyl etherate ((C2H5)2OBF3) and curcumin. However, the new dissociation constants, pKa1 and pKa2 of the BF2-Cur complex, have been indicted by the values of 8.44 ± 0.16 and 9.76 ± 0.13, respectively. On the other hand, the reagent was also used to determine As(III) in aqueous solutions by UV–Vis spectrophotometry. As a result, the method was validated for accuracy, precision, linearity, and sensitivity, and the linear range was from 1.0 to 25.0 µmol/L, with the linear regression, A = 0.0027 C + 0.0106, correlation coefficient R2 = 0.9969. Besides, the limit of detection (LOD) and limit of quantification (LOQ) were determined as 0.83 and 2.10 µmol/L, respectively. Thus, the developed method is successfully used for quantitative analysis of total arsenic in wastewater by reducing As(V) to As(III), then determining As(III) with high accuracy results.

Encephalitis is a major cause of morbidity and mortality worldwide. The clinical syndrome of encephalitis consists of altered mental status, seizures, neurologic signs, and is often accompanied by fever, headache, nausea, and vomiting. The encephalitis in children has been known that more common than in adult, with the incidence rate of infants was 3.9 times higher than that of people 20-44 years of age. The reported incidence of hospitalization attributed to paediatric encephalitis ranged from 3 to 13 admissions per 100,000 children per year with the overall mortality ranging from 0 to 7%. There are however more than 100 pathogens that can cause encephalitis and accurate diagnosis is challenging. Over 50% of patients with encephalitis are left undiagnosed despite extensive laboratory investigations. Furthermore, recent studies in high-income settings have suggested autoimmune encephalitis has now surpassed infectious aetiologies, mainly due to increased awareness and diagnostic capacity, which further challenges routine diagnosis and clinical management, especially in developing countries. There are limited contemporary data on the causes of encephalitis in children in Vietnam. Improving our knowledge of the causative agents of encephalitis in this resource-constrained setting remains critical to informing case management, resource distribution and vaccination strategy. Therefore, we conduct a prospective observational study to characterise the clinical, microbiological, and epidemiological features of encephalitis in a major children’s hospital in southern Vietnam. Admission clinical samples will be collected alongside meta clinical data and from each study participants. A combination of classical assays (serology and PCR) and metagenomic next-generation sequencing will used to identify the causative agents. Undiagnosed patients with clinical presentations compatible with autoimmune encephalitis will then be tested for common forms of the disease. Finally, using direct- and indirect costs, we will estimate the economic burden of hospitalization and seven days post hospital discharge of paediatric encephalitis in our setting.

Abstract Background Tetanus remains common in many low- and middle-income countries, but as critical care services improve, mortality from tetanus is improving. Nevertheless, patients develop severe syndromes associated with autonomic nervous system disturbance (ANSD) and the requirement for mechanical ventilation (MV). Understanding factors associated with worse outcome in such settings is important to direct interventions. In this study, we investigate risk factors for disease severity and long-term physical outcome in adults with tetanus admitted to a Vietnamese intensive care unit. Methods Clinical and demographic variables were collected prospectively from 180 adults with tetanus. Physical function component scores (PCS), calculated from Short Form Health Survey (SF-36), were assessed in 79 patients at hospital discharge, 3 and 6 months post discharge. Results Age, temperature, heart rate, lower peripheral oxygen saturation (SpO2) and shorter time from first symptom to admission were associated with MV (OR 1.03 [ 95% confidence interval (CI) 1.00, 1.05], p = 0.04; OR 2.10 [95% CI 1.03, 4.60], p = 0.04; OR 1.04 [ 95% CI 1.01, 1.07], p = 0.02); OR 0.80 [95% CI 0.66, 0.94], p = 0.02 and OR 0.65 [95% CI 0.52, 0.79, p

We tested pre-pandemic (2015–-2019) plasma samples from 148 Vietnamese children and 100 Vietnamese adults at high risk of zoonotic infections for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive. The data thus demonstrated no evidence of prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam. No pre-existing cross-reactivity might explain Vietnam success of COVID-19 control.

Antibody response against nucleocapsid and spike proteins of SARS-CoV-2 in 11 persons with mild or asymptomatic infection rapidly increased after infection. At weeks 18–30 after diagnosis, all remained seropositive but spike protein–targeting antibody titers declined. These data may be useful for vaccine development.

We report a superspreading event of severe acute respiratory syndrome coronavirus 2 infection initiated at a bar in Vietnam with evidence of symptomatic and asymptomatic transmission, based on ministry of health reports, patient interviews, and whole-genome sequence analysis. Crowds in enclosed indoor settings with poor ventilation may be considered at high risk for transmission.

Central nervous system (CNS) infection is a serious neurologic condition, although the etiology remains unknown in >50% of patients. We used metagenomic next-generation sequencing to detect viruses in 204 cerebrospinal fluid (CSF) samples from patients with acute CNS infection who were enrolled from Vietnam hospitals during 2012–2016. We detected 8 viral species in 107/204 (52.4%) of CSF samples. After virus-specific PCR confirmation, the detection rate was lowered to 30/204 (14.7%). Enteroviruses were the most common viruses detected (n = 23), followed by hepatitis B virus (3), HIV (2), molluscum contagiosum virus (1), and gemycircularvirus (1). Analysis of enterovirus sequences revealed the predominance of echovirus 30 (9). Phylogenetically, the echovirus 30 strains belonged to genogroup V and VIIb. Our results expanded knowledge about the clinical burden of enterovirus in Vietnam and underscore the challenges of identifying a plausible viral pathogen in CSF of patients with CNS infections.

Hand, foot and mouth disease (HFMD) is an emerging infection with pandemic potential. Knowledge of neutralizing antibody responses among its pathogens is essential to inform vaccine development and epidemiologic research. We used 120 paired-plasma samples collected at enrollment and >7 days after the onset of illness from HFMD patients infected with enterovirus A71 (EV-A71), coxsackievirus A (CVA) 6, CVA10, and CVA16 to study cross neutralization. For homotypic viruses, seropositivity increased from

In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.

ABSTRACT: Background: Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited. Methods: We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing. Findings: Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.002). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms. Interpretation: Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals. Funding: Wellcome and NIH/NIAID

Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies.Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis.Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96–31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases.Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2–3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.

We investigated enterovirus A71–associated hand, foot and mouth disease in Vietnam and found that, after replacing subgenogroup C4 in 2013, B5 remained the leading cause of this disease. In contrast with previous observations, this switch did not result in an explosive outbreak, and B5 evolution was driven by negative selection.

Among soil pollutants, lead (Pb) is one of the toxic metal pollutants widely used in many industrial processes and occurs as a contaminant in environment. In this study, a field experiment was carried out to investigate the accumulation of lead from soil contaminated by this metal ion on the biomass of some vegetables, including spinach, lettuce, carrots, and potatoes. The results showed that lead was cumulative metal. Besides, the level of lead accumulation in soil of the studied vegetables decreased in the order of tubers of carrots, tubers of potato, spinach root, lettuce root, stems and leaves of spinach, stem and leaves of carrot, stems and leaves of potato, and stem and leaves of lettuce, respectively. Our investigations demonstrate the effect of copper and zinc micronutrient elements which play an important role in the growth and development of plants, on the accumulation of lead from contaminated soil of the studied vegetables. The obtained results showed that high concentration of copper and zinc in soil cause competition with lead in the process of absorption and accumulation in the plant. Specifically, copper and zinc showed the inhibition effect on the uptake and accumulation of lead by these plants.

Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011-2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. We report the results of a hospital-based study conducted during 2015-2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015-2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017-early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Our data have provided significant insights into important aspects of HFMD over four years (2015-2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD.

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 31/03/2020

Hand foot and mouth disease (HFMD) and tetanus are serious infectious diseases in low- and middle-income countries. Tetanus, in particular, has a high mortality rate and its treatment is resource-demanding. Furthermore, HFMD often affects a large number of infants and young children. As a result, its treatment consumes enormous healthcare resources, especially when outbreaks occur. Autonomic nervous system dysfunction (ANSD) is the main cause of death for both HFMD and tetanus patients. However, early detection of ANSD is a difficult and challenging problem. The authors aim to provide a proof-of-principle to detect the ANSD level automatically by applying machine learning techniques to physiological patient data, such as electrocardiogram waveforms, which can be collected using low-cost wearable sensors. Efficient features are extracted that encode variations in the waveforms in the time and frequency domains. The proposed approach is validated on multiple datasets of HFMD and tetanus patients in Vietnam. Results show that encouraging performance is achieved. Moreover, the proposed features are simple, more generalisable and outperformed the standard heart rate variability analysis. The proposed approach would facilitate both the diagnosis and treatment of infectious diseases in low- and middle-income countries, and thereby improve patient care.

BackgroundDiseases caused by human enteroviruses (EVs) are a major global public health problem. Thus, the effective diagnosis of all human EVs infections and the monitoring of epidemiological and ecological dynamic changes are urgently needed.MethodsBased on two comprehensive virological surveillance systems of hand, foot and mouth disease (HFMD), real-time PCR and nested RT-PCR (RT-snPCR) methods based on the enteroviral VP1, VP4-VP2 and VP4 regions were designed to directly detect all human EVs serotypes in clinical specimens.ResultsThe results showed that the proposed serotyping strategy exhibit very high diagnostic efficiency (Study 1: 99.9%; Study 2: 89.5%), and the variance between the study was due to inclusion of the specific Coxsackie virus A6 (CVA6) real-time RT-PCR and VP4 RT-snPCR in Study 1 but not Study 2. Furthermore, only throat swabs were collected and analyzed in Study 2, whereas in Study 1, if a specific EV serotype was not identified in the primary stool sample, other sample types (rectal swab and throat swab) were further tested where available. During the study period from 2013 to 2018, CVA6 became one of the main HFMD causative agents, whereas the level of enterovirus A71 (EV-A71) declined in 2017.ConclusionThe findings of this study demonstrate the appropriate application of PCR methods and the combination of biological sample types that are useful for etiological studies and propose a molecular strategy for the direct detection of human EVs in clinical specimens associated with HFMD.

We report human pegivirus 2 (HPgV-2) infection in Vietnam. We detected HPgV-2 in some patients with hepatitis C virus/HIV co-infection but not in patients with HIV or hepatitis A, B, or C virus infection, nor in healthy controls. HPgV-2 strains in Vietnam are phylogenetically related to global strains.

Hand, foot and mouth disease (HFMD) is a major public health issue in Asia and has global pandemic potential. Coxsackievirus A6 (CV-A6) was detected in 514/2,230 (23%) of HFMD patients admitted to 3 major hospitals in southern Vietnam during 2011–2015. Of these patients, 93 (18%) had severe HFMD. Phylogenetic analysis of 98 genome sequences revealed they belonged to cluster A and had been circulating in Vietnam for 2 years before emergence. CV-A6 movement among localities within Vietnam occurred frequently, whereas viral movement across international borders appeared rare. Skyline plots identified fluctuations in the relative genetic diversity of CV-A6 corresponding to large CV-A6–associated HFMD outbreaks worldwide. These data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies.

Abstract Background Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. Methods Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing. Results Samples from patients with CNS infection (51 children – 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children – 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown. Conclusion We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response.

Abstract Background Central nervous system (CNS) infections are an important cause of childhood morbidity and mortality. The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia. Methods We did a one year prospective study of children hospitalised with suspected CNS infection at Angkor Hospital for Children, Siem Reap. Cerebrospinal fluid specimens (CSF) samples underwent culture, multiplex PCR and serological analysis to identify a range of bacterial and viral pathogens. Viral metagenomics was performed on a subset of pathogen negative specimens. Results Between 1st October 2014 and 30th September 2015, 284 analysable patients were enrolled. The median patient age was 2.6 years; 62.0% were aged

Abstract Background Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities. Methods We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children. Results The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged

Redondoviridae is a recently discovered DNA virus family consisting of two species, vientovirus and brisavirus. Here we used PCR amplification and sequencing to characterize redondoviruses in nasal/throat swabs collected longitudinally from a cohort of 58 individuals working with animals in Vietnam. We additionally analyzed samples from animals to which redondovirus DNA-positive participants were exposed. Redondoviruses were detected in approximately 60% of study participants, including 33% (30/91) of samples collected during episodes of acute respiratory disease and in 50% (29/58) of baseline samples (with no respiratory symptoms). Vientovirus (73%; 24/33) was detected more frequently in samples than brisaviruses (27%; 9/33). In the 23 participants with at least 2 redondovirus-positive samples among their longitudinal samples, 10 (43.5%) had identical redondovirus replication-gene sequences detected (sampling duration: 35–132 days). We found no identical redondovirus replication genes in samples from different participants, and no redondoviruses were detected in 53 pooled nasal/throat swabs collected from domestic animals. Phylogenetic analysis described no large-scale geographical clustering between viruses from Vietnam, the US, Spain, and China, indicating that redondoviruses are highly genetically diverse and have a wide geographical distribution. Collectively, our study provides novel insights into the Redondoviridae family in humans, describing a high prevalence, potentially associated with chronic shedding in the respiratory tract with lack of evidence of zoonotic transmission from close animal contacts. The tropism and potential pathogenicity of this viral family remain to be determined.

The ongoing coronavirus disease 2019 (COVID-19) pandemic emphasizes the need to actively study the virome of unexplained respiratory diseases. We performed viral metagenomic next-generation sequencing (mNGS) analysis of 91 nasal-throat swabs from individuals working with animals and with acute respiratory diseases. Fifteen virus RT-PCR-positive samples were included as controls, while the other 76 samples were RT-PCR negative for a wide panel of respiratory pathogens. Eukaryotic viruses detected by mNGS were then screened by PCR (using primers based on mNGS-derived contigs) in all samples to compare viral detection by mNGS versus PCR and assess the utility of mNGS in routine diagnostics. mNGS identified expected human rhinoviruses, enteroviruses, influenza A virus, coronavirus OC43, and respiratory syncytial virus (RSV) A in 13 of 15 (86.7%) positive control samples. Additionally, rotavirus, torque teno virus, human papillomavirus, human betaherpesvirus 7, cyclovirus, vientovirus, gemycircularvirus, and statovirus were identified through mNGS. Notably, complete genomes of novel cyclovirus, gemycircularvirus, and statovirus were genetically characterized. Using PCR screening, the novel cyclovirus was additionally detected in 5 and the novel gemycircularvirus in 12 of the remaining samples included for mNGS analysis. Our studies therefore provide pioneering data of the virome of acute-respiratory diseases from individuals at risk of zoonotic infections. The mNGS protocol/pipeline applied here is sensitive for the detection of a variety of viruses, including novel ones. More frequent detections of the novel viruses by PCR than by mNGS on the same samples suggests that PCR remains the most sensitive diagnostic test for viruses whose genomes are known. The detection of novel viruses expands our understanding of the respiratory virome of animal-exposed humans and warrant further studies.

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016

Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.

Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, viral pathogens were detected in a total count of 270/294 (91.8%, 95% CI 88.1-94.7) by the Luminex among reference assays, whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.

New complexes of 5,11,17,23-tetra[(2-ethyl acetoethoxyphenyl)(azo)phenyl]calix[4]arene (TEAC) with Pb(II) and Cr(III) were prepared in basic solution with a mixture of MeOH and H2O as solvent. The ratio of TEAC and metal ion in complexes was found to be 1 : 1 under investigated condition. The complex formation constants (based on Benesi-Hildebrand method) for TEAC-Pb(II) and TEAC-Cr(III) were 4.03 × 104 and 1.2 × 104, respectively. Additionally, the molar extinction coefficients were 5 × 104 and 1.42 × 104 for TEAC-Pb(II) and TEAC-Cr(III), respectively. The H-Point Standard Addition Method (HPSAM) has been applied for simultaneous determination of complexes formation of Cr(III)/Pb(II) and TEAC with concentration from 2 : 1 to 1 : 20 (w/w). The proposed method was successfully utilized to invest lead and chromium contents in plating wastewater samples. The results for several analyzed samples were found to be in satisfied agreement with those acquired by using the inductively coupled plasma mass spectrometry (ICP-MS) technique.

Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management.Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses. Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%).Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the majority of morbidity/mortality amongst patients with a confirmed/probable diagnosis is preventable by adequate vaccination/treatment, and are therefore of public health significance.

ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus. IMPORTANCE Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology frequently remains unknown, which hampers development of therapeutic or preventive strategies. Hence, identification of novel pathogens is essential and is facilitated by current next-generation sequencing-based methods. Using such technology, we identified and characterized the full genome of a novel cyclovirus in cerebrospinal fluid (CSF) specimens from two Vietnamese patients with CNS infections of unknown etiology, which was subsequently detected in none of 122 CSF specimens from patients with noninfectious neurological disorders but 4% of 642 CSF specimens from Vietnamese patients with suspected or confirmed CNS infections. Similar detection rates in feces from healthy children suggested food-borne or orofecal transmission routes, while frequent detection in feces from Vietnamese pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further studies are needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

BACKGROUND:Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children hospitalised in Siem Reap province, Cambodia. METHODS AND FINDINGS:A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12(th) 2009 and October 12(th) 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8-6.4) years, with 850 (69%) episodes in children