Pregnant women with chronic hepatitis B virus infection at the assessment of tenofovir disoproxil fumarate prescription: Baseline characteristics of a prospective cohort study in Vietnam.

Objectives: We aimed to determine epidemiological characteristics and serologic markers among chronically hepatitis B virus (HBV)-infected pregnant women during the assessment of tenofovir disoproxil fumarate (TDF) prescription in Vietnam. Methods: We consecutively recruited 375 pregnant women with chronic HBV (cHBV) infection at week 25±2 of pregnancy, at which time they were assessed for TDF use as pre-prophylaxis and/or pre-treatment at the Hospital for Tropical Diseases in southern Vietnam during December 2019-April 2021. Demographic characteristics, serological biomarkers, and prenatal liver ultrasounds were obtained through interviews and reviews of medical records. Results: The median age of pregnant women was 29 years (interquartile range: 26-32). More than half of pregnant women (208/375; 55.5%) started TDF for prevention of mother-to-child transmission of HBV and/or treatment of chronic hepatitis B (CHB). Among the pregnant women initiating TDF, 96.1% (198/206) tested positive for hepatitis B e antigen, and 21.6% (45/208) had quantitative hepatitis B surface antigen (qHBsAg) ≤104 IU/mL. A relatively strong correlation between qHBsAg and HBV deoxyribonucleic acid (DNA) (r = 0.81; 95% CI: 0.76-0.85) was observed in pregnant women starting TDF. Conclusions: Our results demonstrate the high need for TDF prescription for prevention and/or treatment purposes in pregnant women with cHBV infection. Pregnant women with qHBsAg levels ≤104 IU/mL may prioritize HBV DNA testing over qHBsAg to decide on TDF prescription.

Multidimensional Analysis of the Mother-to-child Transmission Risk Factors in Chronic Hepatitis B Virus Infection in Pregnant Women in Vietnam.

Background: Hepatitis B virus (HBV) infection remains a major public health problem. The interaction between HBV and the host inflammatory response is an important factor contributing to liver damage and disease development. We investigate of the correlation between peripheral blood cell levels, HBV DNA, and the risk of transmission to the baby in pregnant women infected with hepatitis B. Methods: A multidimensional analysis was performed on data collected from 60 Vietnamese pregnant women and their babies (cord blood). Results: Taking the risk ratio test results of cord blood HBsAg as a positive probability, the boundary of maternal PBMC concentration is 8.03x106 cells/ml (with negative correlation) and for CBMCs is 6.64x106 cells/ml (with positive correlation). That means that HBsAg positivity in the blood may be related to the increasing of CBMCs and the diminution of maternal PBMCs. When the maternal viral load is higher than 5x107 copies/ml, the risk of being HBsAg-positive in cord blood is 123% (RR=2.23 [1.48,3.36]); when the viral load is lower than this baseline, the risk is decreased by 55% (RR=0.45 [0.30,0.67]) (p<0.001). Conclusions: With several steps of the analysis, this study found maternal peripheral blood cell levels and cord blood positively cor-related in pregnant women with a load lower than 5x107 copies of HBV DNA/ml. The study's results suggest that the role of PBMCs and HBV DNA in vertical infection is essential.

Learning meaningful latent space representations for patient risk stratification: Model development and validation for dengue and other acute febrile illness.

Background: Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented. Methods: We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications. Results: The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman, 0.830; Procrustes, 0.301; GMM 0.321). Conclusion: This study demonstrates that when adequately configured, autoencoders can produce two-dimensional representations of a complex dataset that conserve the distance relationship between points. The output visualisation groups patients with clinically relevant features closely together and inherently supports user interpretability. Work is underway to incorporate these findings into an electronic clinical decision support system to guide individual patient management.

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

The compensatory reserve index predicts recurrent shock in patients with severe dengue.

BACKGROUND: Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU. METHODS: We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data. RESULTS: One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively). CONCLUSION: CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue.

Multifunctional nanocarriers of Fe3O4@PLA-PEG/curcumin for MRI, magnetic hyperthermia and drug delivery.

Background: Despite medicinal advances, cancer is still a big problem requiring better diagnostic and treatment tools. Magnetic nanoparticle (MNP)-based nanosystems for multiple-purpose applications were developed for these unmet needs. Methods: This study fabricated novel trifunctional MNPs of Fe3O4@PLA-PEG for drug release, MRI and magnetic fluid hyperthermia. Result: The MNPs provided a significant loading of curcumin (∼11%) with controllable release ability, a high specific absorption rate of 82.2 W/g and significantly increased transverse relaxivity (r2 = 364.75 mM-1 s-1). The in vivo study confirmed that the MNPs enhanced MRI contrast in tumor observation and low-field magnetic fluid hyperthermia could effectively reduce the tumor size in mice bearing sarcoma 180. Conclusion: The nanocarrier has potential for drug release, cancer treatment monitoring and therapy.

In this study, the authors designed and fabricated novel magnetic trifunctional nanoparticles of Fe₃O₄@PLA-PEG. The 8.5 nm Fe₃O₄ core was covered with the polymeric matrix of PLA-PEG to encapsulate an anticancer agent of curcumin at a content of about 11%. Curcumin release from the nanoparticles (NPs) could be controlled by applying a remote alternating magnetic field. The NPs enhanced MRI contrast, which allowed the authors to better distinguish the tumor and surroundings in MR images, which would help monitor treatment. The heat that NPs generated when applied to a field at low intensity could effectively reduce the tumor size in mice bearing sarcoma 180. The nanocarrier, therefore, has potential for cancer treatment monitoring and drug release conjuvant with magnetic hyperthermia therapy.

Clinical prognostic models for severe dengue: a systematic review protocol.

Background: Dengue is a common mosquito-borne, with high morbidity rates recorded in the annual. Dengue contributes to a major disease burden in many tropical countries. This demonstrates the urgent need in developing effective approaches to identify severe cases early. For this purpose, many multivariable prognostic models using multiple prognostic variables were developed to predict the risk of progression to severe outcomes. The aim of the planned systematic review is to identify and describe the existing clinical multivariable prognostic models for severe dengue as well as examine the possibility of combining them. These findings will suggest directions for further research of this field. Methods: This protocol has followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta - Analyses Protocol (PRISMA-P). We will conduct a comprehensive search of Pubmed, Embase, and Web of Science. Eligibility criteria include being published in peer-review journals, focusing on human subjects and developing the multivariable prognostic model for severe dengue, without any restriction on language, location and period of publication, and study design. The reference list will be captured and removed from duplications. We will use the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to extract data and Prediction study risk of bias assessment tool (PROBAST) to assess the study quality. Discussion: This systematic review will describe the existing prediction models, summarize the current status of prognostic research on dengue, and report the possibility to combine the models to optimize the power of each paradigm. PROSPERO registration: CRD42018102907.

Anatomical Characteristics of Thalamus-Cortical Sensory Tract in the Human Brain Using Diffusion Tensor Tractography at 3.0 Tesla Scanner.

BACKGROUND: Our knowledge about characteristics of the thalamocortical tract (THT) according to the cerebral origin is still few of studies about this structure on Vietnamese. AIM: Here, we aim to characterise the morphology of the thalamocortical tract in the human brain using diffusion tensor tractography (DTT) at 3.0 tesla scanner. METHODS: Fifty healthy subjects have enrolled in this study. Reconstructed images of the thalamocortical tract in the human brain were built using DTT at 3.0 tesla scanner. RESULTS: The median length of the right thalamocortical tract was 130.64 mm, and the left THT was 123.14 mm, and an average of two sides was 126.34 mm. The difference between the two sides was statically significance (p < 0.001). The median fibre number of the right THT was 401.50, and the left THT was 315.00, and an average of two sides was 365.50. There was a diverse branch of THT: two branches (5%); three branches (25%); four branches (42%); five branches (16%); six branches (12%); in which branched contralateral for the right was 50%, and for the left was 50%. CONCLUSION: Using the DTI and 3D image reconstruction techniques allow to build the image of sensory THT intuitively and accurately, which helps to identify the morphological characteristic of the thalamocortical tract of healthy people without invasive effects.

Factors associated with a low prevalence of exclusive breastfeeding during hospital stay in urban and semi-rural areas of southern Vietnam.

BACKGROUND: There is a paucity of data regarding risk factors associated with suboptimal breastfeeding practices in urbanized areas of low-middle income countries (LMICs). METHODS: Through a large prospective birth cohort, which enrolled 6706 infants in Vietnam between 2009 and 2013, we investigated the practice of exclusive breastfeeding during hospital stay in urban and semi-rural populations and aimed to identify factors associated with suboptimal breastfeeding practices. Univariate and multivariable logistic regression were performed to determine factors associated with not exclusive breastfeeding during hospital stay. RESULTS: Of 6076 mothers, 33% (2187) breastfed their infant exclusively before hospital discharge; 9% (364/4248) in urban and 74% (1823/2458) in semi-rural areas. Exclusive breastfeeding up to 4 months was recorded in 15% (959/6210) of participants; this declined to < 1% (56/6093) at 6 months. Delivery by Caesarean section (Odds Ratio [OR] 0.07; 95% Confidence Interval [CI] 0.04, 0.11 and OR 0.05; 95% CI 0.03, 0.08) and neonatal complications (OR 0.2; 95% CI 0.07, 0.47 and OR 0.25; 95% CI 0.14, 0.46) were common and highly significant risk factors associated with a lack of exclusive breastfeeding during hospital stay in urban and semi-rural settings, respectively. CONCLUSIONS: To our knowledge, this is the first large-scale investigation aimed at identifying factors associated with exclusive breastfeeding during hospital stay in Vietnam. Breastfeeding promotion strategies should prioritize common risk factors in hospital, such as Caesarean section and neonatal complications, and other location specific factors associated with socioeconomics.

Methods to discriminate primary from secondary dengue during acute symptomatic infection.

BACKGROUND: Dengue virus infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic infection through to severe dengue. Although prior infection with another viral serotype, i.e. secondary dengue, is known to be an important factor influencing disease severity, current methods to determine primary versus secondary immune status during the acute illness do not consider the rapidly evolving immune response, and their accuracy has rarely been evaluated against an independent gold standard. METHODS: Two hundred and ninety-three confirmed dengue patients were classified as experiencing primary, secondary or indeterminate infections using plaque reduction neutralisation tests performed 6 months after resolution of the acute illness. We developed and validated regression models to differentiate primary from secondary dengue on multiple acute illness days, using Panbio Indirect IgG and in-house capture IgG and IgM ELISA measurements performed on over 1000 serial samples obtained during acute illness. RESULTS: Cut-offs derived for the various parameters demonstrated progressive change (positively or negatively) by day of illness. Using these time varying cut-offs it was possible to determine whether an infection was primary or secondary on single specimens, with acceptable performance. The model using Panbio Indirect IgG responses and including an interaction with illness day showed the best performance throughout, although with some decline in performance later in infection. Models based on in-house capture IgG levels, and the IgM/IgG ratio, also performed well, though conversely performance improved later in infection. CONCLUSIONS: For all assays, the best fitting models estimated a different cut-off value for different days of illness, confirming how rapidly the immune response changes during acute dengue. The optimal choice of assay will vary depending on circumstance. Although the Panbio Indirect IgG model performs best early on, the IgM/IgG capture ratio may be preferred later in the illness course.

Excess body weight and age associated with the carriage of fluoroquinolone and third-generation cephalosporin resistance genes in commensal Escherichia coli from a cohort of urban Vietnamese children.

PURPOSE: Antimicrobial-resistant bacterial infections in low- and middle-income countries (LMICs) are a well-established global health issue. We aimed to assess the prevalence of and epidemiological factors associated with the carriage of ciprofloxacin- and ceftriaxone-resistant Escherichia coli and associated resistance genes in a cohort of 498 healthy children residing in urban Vietnam. METHODOLOGY: We cultured rectal swabs onto MacConkey agar supplemented with resistant concentrations of ciprofloxacin and ceftriaxone. Additionally, we screened meta-E. coli populations by conventional PCR to detect plasmid-mediated quinolone resistance (PMQR)- and extended-spectrum ß-lactamase (ESBL)-encoding genes. We measured the associations between phenotypic/genotypic resistance and demographic characteristics using logistic regression.Results/Key findings. Ciprofloxacin- and ceftriaxone-resistant E. coli were cultured from the faecal samples of 67.7 % (337/498) and 80.3 % (400/498) of children, respectively. The prevalence of any associated resistance marker in the individual samples was 86.7 % (432/498) for PMQR genes and 90.6 % (451/498) for ß-lactamase genes. Overweight children were significantly more likely to carry qnr genes than children with lower weight-for-height z-scores [odds ratios (OR): 1.24; 95 % confidence interval (CI): 10.5-1.48 for each unit increase in weight for height; P=0.01]. Additionally, younger children were significantly more likely to carry ESBL CTX-M genes than older children (OR: 0.97, 95 % CI: 0.94-0.99 for each additional year, P=0.01). CONCLUSION: The carriage of genotypic and phenotypic antimicrobial resistance is highly prevalent among E. coli in healthy children in the community in Vietnam. Future investigations on the carriage of antimicrobial resistant organisms in LMICs should focus on the progression of carriage from birth and structure of the microbiome in obesity.

Quantifying antimicrobial access and usage for paediatric diarrhoeal disease in an urban community setting in Asia.

Objectives: Antimicrobial-resistant infections are a major global health issue. Ease of antimicrobial access in developing countries is proposed to be a key driver of the antimicrobial resistance (AMR) epidemic despite a lack of community antimicrobial usage data. Methods: Using a mixed-methods approach (geospatial mapping, simulated clients, healthcare utilization, longitudinal cohort) we assessed antimicrobial access in the community and quantified antimicrobial usage for childhood diarrhoea in an urban Vietnamese setting. Results: The study area had a pharmacy density of 15.7 pharmacies/km2 (a pharmacy for every 1316 people). Using a simulated client method at pharmacies within the area, we found that 8% (3/37) and 22% (8/37) of outlets sold antimicrobials for paediatric watery and mucoid diarrhoea, respectively. However, despite ease of pharmacy access, the majority of caregivers would choose to take their child to a healthcare facility, with 81% (319/396) and 88% (347/396) of responders selecting a specialized hospital as one of their top three preferences when seeking treatment for watery and mucoid diarrhoea, respectively. We calculated that at least 19% (2688/14427) of diarrhoea episodes in those aged 1 to <5 years would receive an antimicrobial annually; however, antimicrobial usage was almost 10 times greater in hospitals than in the community. Conclusions: Our data question the impact of community antimicrobial usage on AMR and highlight the need for better education and guidelines for all professionals with the authority to prescribe antimicrobials.

Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial.

BACKGROUND: Over the last 15 years, hand, foot, and mouth disease (HFMD) has emerged as a major public health burden across the Asia-Pacific region. A small proportion of HFMD patients, typically those infected with enterovirus 71 (EV71), develop brainstem encephalitis with autonomic nervous system (ANS) dysregulation and may progress rapidly to cardiopulmonary failure and death. Although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a number of children still deteriorate despite this treatment. Magnesium sulfate (MgSO4) is a cheap, safe, and readily available medication that is effective in managing tetanus-associated ANS dysregulation and has shown promise when used empirically in EV71-confirmed severe HFMD cases. METHODS/DESIGN: We describe the protocol for a randomized, placebo-controlled, double-blind trial of intravenous MgSO4 in Vietnamese children diagnosed clinically with HFMD plus ANS dysregulation with systemic hypertension. A loading dose of MgSO4 or identical placebo is given over 20 min followed by a maintenance infusion for 72 h according to response, aiming for Mg levels two to three times the normal level in the treatment arm. The primary endpoint is a composite of disease progression within 72 h defined as follows: development of pre-specified blood pressure criteria necessitating the addition of milrinone, the need for ventilation, shock, or death. Secondary endpoints comprise these parameters singly, plus other clinical endpoints including the following: requirement for other inotropic agents; duration of hospitalization; presence of neurological sequelae at discharge in survivors; and neurodevelopmental status assessed 6 months after discharge. The number and severity of adverse events observed in the two treatment arms will also be compared. Based on preliminary data from a case series, and allowing for some losses, 190 patients (95 in each arm) will allow detection of a 50 % reduction in disease progression with 90 % power at a two-sided 5 % significance level. DISCUSSION: Given the large numbers of HFMD cases currently being seen in hospitals in Asia, if MgSO4 is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications, this finding would be important to pediatric care throughout the region. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 August 2013).

Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy. METHODS: Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms. RESULTS: Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures. CONCLUSIONS: We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.Chinese Clinical Trials Registration. ISRCTN03147572.

Corticosteroids for dengue - why don't they work?

BACKGROUND: Dysregulated immune responses may contribute to the clinical complications that occur in some patients with dengue. FINDINGS: In Vietnamese pediatric dengue cases randomized to early prednisolone therapy, 81 gene-transcripts (0.2% of the 47,231 evaluated) were differentially abundant in whole-blood between high-dose (2 mg/kg) prednisolone and placebo-treated patients two days after commencing therapy. Prominent among the 81 transcripts were those associated with T and NK cell cytolytic functions. Additionally, prednisolone therapy was not associated with changes in plasma cytokine levels. CONCLUSION: The inability of prednisolone treatment to markedly attenuate the host immune response is instructive for planning future therapeutic strategies for dengue.