Epidemiology of Streptococcus suis infection in Viet Nam

Human Streptococcus suis infection is an emerging zoonotic disease in Southeast Asian countries. It can seriously threaten human heath causing both outbreaks with high morbidity and mortality and endemic disease. It can also have a major negative impact on the economically important pig industry across the region. The aims of this thesis were to understand the epidemiology of human S. suis infection in Viet Nam, focusing on the incidence rate, seasonality and risk factors for infection with S. suis. I conducted a prospective surveillance of central nervous system (CNS) infections in twelve provinces of Viet Nam including the Central, the Highlands and the south of the country. I was able to demonstrate that S. suis was an endemic disease across southern Viet Nam, and responsible for 49% of adult purulent bacterial meningitis. The incidence rate was 0.57 per 100,000 adult person-years (95% CI, 0.47-0.70) and infection had a case fatality rate of 8%. S. suis meningitis tended to predominantly occur in the hottest months of the year in central Viet Nam, but this seasonal pattern was not documented in the south of the country. A case control study demonstrated that occupational exposure to pigs or pork was a significant risk factor for S. suis infection. I was also able to identify novel and important risk factors for S. suis disease among the Vietnamese population. Eating fresh blood and undercooked pig products (OR1 = 2.22; 95%CI = [1.15-4.28] and OR2 = 4.44; 95%CI = [2.15-9.15]) and exposures of people with skin injuries to pigs or pork (OR = 7.48; 95% CI = [1.97-28.44] and OR2 = 15.96; 95%CI = [2.97-85.72]), were significant risk factors. These risk factors can be addressed in health education programs targeted at individuals and communities at risk, focusing on skin protection for those in direct contact with pigs or pork and avoiding eating fresh blood and undercooked pig products. In addition, we were unable to detect S. suis serotype 2 DNA from the throat and rectal swab samples of 1523 healthy persons and non-S. suis infected patients, including those with exposure to pigs and pork meat. Hence I was not able to demonstrate human carriage of S. suis serotype 2 in the Vietnamese population

BoMb-OT: On Batch of Mini-batches Optimal Transport

Mini-batch optimal transport (m-OT) has been successfully used in practical applications that involve probability measures with intractable density, or probability measures with a very high number of supports. The m-OT solves several sparser optimal transport problems and then returns the average of their costs and transportation plans. Despite its scalability advantage, the m-OT does not consider the relationship between mini-batches which leads to undesirable estimation. Moreover, the m-OT does not approximate a proper metric between probability measures since the identity property is not satisfied. To address these problems, we propose a novel mini-batching scheme for optimal transport, named Batch of Mini-batches Optimal Transport (BoMb-OT), that finds the optimal coupling between mini-batches and it can be seen as an approximation to a well-defined distance on the space of probability measures. Furthermore, we show that the m-OT is a limit of the entropic regularized version of the BoMb-OT when the regularized parameter goes to infinity. Finally, we carry out extensive experiments to show that the BoMb-OT can estimate a better transportation plan between two original measures than the m-OT. It leads to a favorable performance of the BoMb-OT in the matching and color transfer tasks. Furthermore, we observe that the BoMb-OT also provides a better objective loss than the m-OT for doing approximate Bayesian computation, estimating parameters of interest in parametric generative models, and learning non-parametric generative models with gradient flow.Comment: 36 pages, 20 figure

A novel diagnostic model for tuberculous meningitis using Bayesian latent class analysis

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 ≥ 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

The Virome of Acute Respiratory Diseases in Individuals at Risk of Zoonotic Infections

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

The Virome of Acute Respiratory Diseases in Individuals at Risk of Zoonotic Infections

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.Peer reviewe

Viral Metagenomic Analysis of Cerebrospinal Fluid from Patients with Acute Central Nervous System Infections of Unknown Origin, Vietnam.

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

The management of Staphylococcus aureus bacteremia in the United Kingdom and Vietnam: a multi-centre evaluation.

Background: Staphylococcus aureus bacteremia is a common and serious infection worldwide and although treatment guidelines exist, there is little consensus on optimal management. In this study we assessed the variation in management and adherence to treatment guidelines of S. aureus bacteremia. Methodology/Principal Findings: We prospectively recorded baseline clinical characteristics, management, and in-hospital outcome of all adults with S. aureus bacteremia treated consecutively over one year in eight centres in the United Kingdom, three in Vietnam and one in Nepal. 630 adults were treated for S. aureus bacteremia: 549 in the UK (21% methicillin-resistant), 80 in Vietnam (19% methicillin-resistant) and 1 in Nepal. In the UK, 41% had a removable infection focus (50% intravenous catheter-related), compared to 12% in Vietnam. Significantly (p50% of treatment with oral antibiotics alone (25% versus 4%). UK centres varied significantly (p50% of treatment (range 12-40%), in those treated for longer than 28 days (range 13-54%), and in those given combination therapy (range 14-94%). 24% died during admission: older age, time in hospital before bacteremia, and an unidentified infection focus were independent predictors of in-hospital death (p<0.001). Conclusions/Significance: The management of S. aureus bacteremia varies widely between the UK and Vietnam and between centres in the UK with little adherence to published guidelines. Controlled trials defining optimal therapy are urgently required

Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam.

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

THÀNH PHẦN HÓA HỌC VÀ HOẠT TÍNH CHỐNG OXY HÓA CỦA CÁC DỊCH CHIẾT TỪ HOA XUYẾN CHI (Bidens pilosa)

Bidens pilosa is used in traditional medicine in Vietnam. The antioxidant potential of the ethanol extract and fractions from the flowers of Bidens pilosa was evaluated through DPPH and ABTS radical scavenging and the total antioxidant capacity method. The ethyl acetate fraction exhibits the highest activity with the lowest IC50 value (IC50 = 31.54 μg·mL–1 and IC50 = 35.33 μg·mL–1 for DPPH and ABTS radical scavenging capacity), and the total antioxidant capacity was 85.05 ± 0.28 mg GA·g–1. The composition of Bidens pilosa flowers: the total phenolic, total flavonoid, polysaccharides, and triterpenoid, was examined by using the colorimetric method, and their quantities are equivalent to 59.35 ± 0.83 mg GAE·g–1, 42.35 ± 1.50 mg QE·g–1, 4.44 ± 0.02%, and 32.88 ± 0.66 mg acid oleanolic·g–1, respectively. Specifically, the polysaccharide and total triterpenoid content of Bidens pilosa flowers was reported for the first time.Xuyến chi đã được sử dụng trong các bài thuốc cổ truyền Việt Nam. Khả năng chống oxy hóa của cao toàn phần và các cao phân đoạn từ hoa cây Xuyến chi được đánh giá thông qua ba mô hình: tổng khả năng chống oxy hoá, khả năng bắt gốc tự do DPPH và khả năng bắt gốc ABTS. Kết quả cho thấy cao ethyl acetate có khả năng chống oxy hóa tốt nhất với IC50 nhỏ nhất (IC50 = 31,54 μg·mL–1 và           IC50 = 35,33 μg·mL–1 tương ứng với khả năng bắt gốc DPPH và ABTS) và hàm lượng các chất chống oxy hóa cao nhất (85,05 ± 0,28 mg·g–1 acid gallic). Hàm lượng các hợp chất có hoạt tính sinh học (tổng các hợp chất phenol, tổng flavonoid, tổng triterpenoid và polysaccharide) trong dịch chiết hoa cây Xuyến chi được xác định bằng phương pháp trắc quang. Hàm lượng tổng các hợp chất phenol và flavonoid là 59,35 ± 0,83 mg GAE·g–1 và 42,35 ± 1,50 mg QE·g–1; hàm lượng polysacharide và triterpenoid là 4,44 ± 0,02% và 32,88 ± 0,66 mg acid oleanolic·g–1. Lần đầu tiên, tổng hàm lượng triterpenoid và polysacharide trong hoa Xuyến chi được công bố