The CIPAZ study protocol: an open label randomised controlled trial of azithromycin versus ciprofloxacin for the treatment of children hospitalised with dysentery in Ho Chi Minh City, Vietnam

Background: Diarrhoeal disease remains a common cause of illness and death in children <5 years of age. Faecal-oral infection by Shigella spp. causing bacillary dysentery is a leading cause of moderate-to-severe diarrhoea, particularly in low and middle-income countries. In Southeast Asia, S. sonnei predominates and infections are frequently resistant to first-line treatment with the fluoroquinolone, ciprofloxacin. While resistance to all antimicrobials is increasing, there may be theoretical and clinical benefits to prioritizing treatment of bacillary dysentery with the azalide, azithromycin. In this study we aim to measure the efficacy of treatment with azithromycin compared with ciprofloxacin, the current standard of care, for the treatment of children with bacillary dysentery. Methods and analysis: We will perform a multicentre, open-label, randomized controlled trial of two therapeutic options for the antimicrobial treatment of children hospitalised with dysentery. Children (6–60 months of age) presenting with symptoms and signs of dysentery at Children’s Hospital 2 in Ho Chi Minh City will be randomised (1:1) to treatment with either oral ciprofloxacin (15mg/kg/twice daily for 3 days, standard-of-care) or oral azithromycin (10mg/kg/daily for 3 days). The primary endpoint will be the proportion of treatment failure (defined by clinical and microbiological parameters) by day 28 (+3 days) and will be compared between study arms by logistic regression modelling using treatment allocation as the main variable. Ethics and dissemination: The study protocol (version 1.2 dated 27th December 2018) has been approved by the Oxford Tropical Research Ethics Committee (47–18) and the ethical review boards of Children's Hospital 2 (1341/NĐ2-CĐT). The study has also been approved by the Vietnamese Ministry of Health (5044/QĐ-BYT). Trial registration: Clinicaltrials.gov: NCT03854929 (February 26th 2019)

Antibacterial hydrogel containing Piper betle L. extract for acne treatment, an ex vivo investigation

The current treatments of acne vulgaris and acne-like disorders such as gram-negative folliculitis possess lots of unwanted side effects. Thus, alternative approach of utilizing natural plant extracts, specifically Piper betle L., have gained much attention. To this end, this work developed, characterized, and ex vivo evaluated novel antibiotics hydrogels containing P. betle L. leaf extract for acne treatment. Firstly, the design of experiments (DoE) D-optimal method was successfully developed, optimized, and validated, to investigate the relationship between P. betle L. extraction conditions and the extract properties. Secondly, the best extract was encapsulated in the hydrogel formulations composed of carbopol 940, propylene glycol, and cocamidopropyl betaine. Finally, the hydrogel was ex vivo determined its antibacterial activity on bacteria isolated from 15 patient acne samples. The optimal extraction condition being an extraction solvent/plant weight ratio of 4.034:1, an extraction time of 2.147 h, and a water extract volume of 91.4 mL. This condition yielded an extract total phenolic content of 3.337±0.034 g GAE/g, and minimum inhibitory concentrations of 32 µg/mL and 128 µg/mL on Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922, respectively. The hydrogel possessed suitable properties for a topical medication, including a viscosity of 6800 cps, a pH of 7.0, and a good foaming ability, at both 10°C, 25°C, and 40°C. The hydrogel showed higher antibacterial activity than the positive controls in both gram-positive and gram-negative bacteria. Conclusively, the hydrogel could become a potential pharmaceutical product for acne treatment

On the Out of Distribution Robustness of Foundation Models in Medical Image Segmentation

Constructing a robust model that can effectively generalize to test samples under distribution shifts remains a significant challenge in the field of medical imaging. The foundational models for vision and language, pre-trained on extensive sets of natural image and text data, have emerged as a promising approach. It showcases impressive learning abilities across different tasks with the need for only a limited amount of annotated samples. While numerous techniques have focused on developing better fine-tuning strategies to adapt these models for specific domains, we instead examine their robustness to domain shifts in the medical image segmentation task. To this end, we compare the generalization performance to unseen domains of various pre-trained models after being fine-tuned on the same in-distribution dataset and show that foundation-based models enjoy better robustness than other architectures. From here, we further developed a new Bayesian uncertainty estimation for frozen models and used them as an indicator to characterize the model's performance on out-of-distribution (OOD) data, proving particularly beneficial for real-world applications. Our experiments not only reveal the limitations of current indicators like accuracy on the line or agreement on the line commonly used in natural image applications but also emphasize the promise of the introduced Bayesian uncertainty. Specifically, lower uncertainty predictions usually tend to higher out-of-distribution (OOD) performance.Comment: Advances in Neural Information Processing Systems (NeurIPS) 2023, Workshop on robustness of zero/few-shot learning in foundation model

Mapping for engagement: setting up a community based participatory research project to reach underserved communities at risk for Hepatitis C in Ho Chi Minh City, Vietnam

Background: Approximately 1. 07 million people in Vietnam are infected with hepatitis C virus (HCV). To address this epidemic, the South East Asian Research Collaborative in Hepatitis (SEARCH) launched a 600-patient cohort study and two clinical trials, both investigating shortened treatment strategies for chronic HCV infection with direct-acting antiviral drugs. We conducted ethnographic research with a subset of trial participants and found that the majority were aware of HCV infection and its implications and were motivated to seek treatment. However, people who inject drugs (PWID), and other groups at risk for HCV were under-represented, although injecting drug use is associated with high rates of HCV. Material and Methods: We designed a community-based participatory research (CBPR) study to engage in dialogues surrounding HCV and other community-prioritized health issues with underserved groups at risk for HCV in Ho Chi Minh City. The project consists of three phases: situation analysis, CBPR implementation, and dissemination. In this paper, we describe the results of the first phase (i.e., the situation analysis) in which we conducted desk research and organized stakeholder mapping meetings with representatives from local non-government and community-based organizations where we used participatory research methods to identify and analyze key stakeholders working with underserved populations. Results: Twenty six institutions or groups working with the key underserved populations were identified. Insights about the challenges and dynamics of underserved communities were also gathered. Two working groups made up of representatives from the NGO and CBO level were formed. Discussion: Using the information provided by local key stakeholders to shape the project has helped us to build solid relationships, give the groups a sense of ownership from the early stages, and made the project more context specific. These steps are not only important preliminary steps for participatory studies but also for other research that takes place within the communities

Adapting to climate-change-induced drought stress for improving water management in Southeast Vietnam

In Southeast Vietnam, droughts have become more frequent, causing significant damage and impacting the region’s socio-economic development. Water shortages frequently affect the industrial and agricultural sectors in the area. This study aims to calculate the water balance and the resilience of existing water resource allocations in the La Nga-Luy River basin based on two scenarios: (1) business-as-usual and (2) following a sustainable development approach. The MIKE NAM and MIKE HYDRO BASIN models were used for Rainfall-Runoff (R-R) and water balance modelling, respectively, and the Keetch-Byram Drought Index (KBDI) was used to estimate the magnitude of droughts. The results identified areas within the Nga-Luy River basin where abnormally dry and moderate drought conditions are common and subbasins, i.e., in the Southeast and Northeast, where severe and extreme droughts often prevail. It is also shown that the water demand for the irrigation of the Winter-Spring and Summer-Autumn crop life cycles could be fully met under abnormally dry conditions. This decreases to 85–100% during moderate droughts, however. In contrast, 65% and 45–50% of the water demand for irrigation is met for the Winter-Spring and Summer-Autumn crop life cycles, respectively, during severe and extreme droughts. Furthermore, this study demonstrates that the water demand for irrigation could still be met 100% and 75–80% of the time during moderate, extreme, and severe droughts, respectively, through increased water use efficiency. This study could help managers rationally regulate water to meet the agricultural sector’s needs in the region and reduce the damage and costs caused by droughts

The impact of environmental and climatic variation on the spatiotemporal trends of hospitalized pediatric diarrhea in Ho Chi Minh City, Vietnam.

It is predicted that the integration of climate-based early warning systems into existing action plans will facilitate the timely provision of interventions to diarrheal disease epidemics in resource-poor settings. Diarrhea remains a considerable public health problem in Ho Chi Minh City (HCMC), Vietnam and we aimed to quantify variation in the impact of environmental conditions on diarrheal disease risk across the city. Using all inpatient diarrheal admissions data from three large hospitals within HCMC, we developed a mixed effects regression model to differentiate district-level variation in risk due to environmental conditions from the overarching seasonality of diarrheal disease hospitalization in HCMC. We identified considerable spatial heterogeneity in the risk of all-cause diarrhea across districts of HCMC with low elevation and differential responses to flooding, air temperature, and humidity driving further spatial heterogeneity in diarrheal disease risk. The incorporation of these results into predictive forecasting algorithms will provide a powerful resource to aid diarrheal disease prevention and control practices in HCMC and other similar settings

Genotyping and antibiotic resistance of thermophilic Campylobacter isolated from chicken and pig meat in Vietnam

Background Campylobacter species are recognized as the most common cause of foodborne bacterial gastroenteritis in humans. In this study nine Campylobacter strains isolated from chicken meat and pork in Hanoi, Vietnam, were characterized using molecular methods and tested for antibiotic resistance. Results The nine isolates (eight C. jejuni and one C. coli) were identified by multiplex PCR, and tested for the presence or absence of 29 gene loci associated with virulence, lipooligosaccharide (LOS) biosynthesis and further functions. flaA typing, multilocus sequence typing and microarray assay investigation showed a high degree of genetic diversity among these isolates. In all isolates motility genes (flaA, flaB, flhA, fliM), colonization associated genes (cadF, docB), toxin production genes (cdtA, cdtB, secD, secF), and the LOS biosynthesis gene pglB were detected. Eight gene loci (fliY, virB11, Cje1278, Cj1434c, Cj1138, Cj1438c, Cj1440c, Cj1136) could not be detected by PCR. A differing presence of the gene loci ciaB (22.2 %), Cje1280 (77.8 %), docC (66.7 %), and cgtB (55.6 %) was found. iamA, cdtC, and the type 6 secretion system were present in all C. jejuni isolates but not in C. coli. flaA typing resulted in five different genotypes within C. jejuni, MLST classified the isolates into seven sequence types (ST-5155, ST-6736, ST-2837, ST-4395, ST-5799, ST-4099 and ST-860). The microarray assay analysis showed a high genetic diversity within Vietnamese Campylobacter isolates which resulted in eight different types for C. jejuni. Antibiotic susceptibility profiles showed that all isolates were sensitive to gentamicin and most isolates (88.8 %) were sensitive to chloramphenicol, erythromycin and streptomycin. Resistance rates to nalidixic acid, tetracycline and ciprofloxacin were 88.9, 77.8 and 66.7 %, respectively. Conclusions To the best of our knowledge, this study is the first report that shows high genetic diversity and remarkable antibiotic resistance of Campylobacter strains isolated from meat in Vietnam which can be considered of high public health significance. These preliminary data show that large scale screenings are justified to assess the relevance of Campylobacter infections on human health in Vietnam

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired

Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB).Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18–85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety.Results: People with UHC had higher odds of depression (OR = 2.11; p &lt; 0.001) and anxiety (OR = 2.86; p &lt; 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p &lt; 0.001); and were significantly lower for those had UHC and interacted with “unchanged/more” physical activity (p &lt; 0.001), or “unchanged/more” drinking (p &lt; 0.001 for only anxiety), or “unchanged/healthier” eating (p &lt; 0.001), and high PB score (p &lt; 0.001), as compared to those without UHC and without S-COVID-19-S, “never/stopped/less” physical activity, drinking, “less healthy” eating, and low PB score, respectively.Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors