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)

Visible light-induced switching of soft matter materials properties based on thioindigo photoswitches

Thioindigos are visible light responsive photoswitches with excellent spatial control over the conformational change between their trans- and cis- isomers. However, they possess limited solubility in all conventional organic solvents and polymers, hindering their application in soft matter materials. Herein, we introduce a strategy for the covalent insertion of thioindigo units into polymer main chains, enabling thioindigos to function within crosslinked polymeric hydrogels. We overcome their solubility issue by developing a thioindigo bismethacrylate linker able to undergo radical initiated thiol-ene reaction for step-growth polymerization, generating indigo-containing polymers. The optimal wavelength for the reversible trans-/cis- isomerisation of thioindigo was elucidated by constructing a detailed photochemical action plot of their switching efficiencies at a wide range of monochromatic wavelengths. Critically, indigo-containing polymers display significant photoswitching of the materials’ optical and physical properties in organic solvents and water. Furthermore, the photoswitching of thioindigo within crosslinked structures enables visible light induced modulation of the hydrogel stiffness. Both the thioindigo-containing hydrogels and photoswitching processes are non-toxic to cells, thus offering opportunities for advanced applications in soft matter materials and biology-related research

Triple Combination of Amantadine, Ribavirin, and Oseltamivir Is Highly Active and Synergistic against Drug Resistant Influenza Virus Strains In Vitro

The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1) has prompted the World Health Organization to declare the first pandemic of the 21st century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors) occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine), and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI). To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD) regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05), including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of approved influenza antivirals, and thus may represent a highly active antiviral therapy for seasonal and pandemic influenza

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

Depressive Symptoms at HIV Testing and Two-Year All-Cause Mortality Among Men Who Inject Drugs in Vietnam

People who inject drugs (PWID) with HIV experience an elevated risk of death. A potentially important determinant of survival is the high burden of depression. This study examined the relationship of depressive symptoms at HIV testing with 2-year all-cause mortality among newly diagnosed HIV-positive PWID in Vietnam. At HIV testing, 141 PWID (42%) experienced severe depressive symptoms, and over the 2 years following diagnosis, 82 PWID (24%) died. Controlling for potential confounders, the 2-year risk of death among those with depressive symptoms was 9.7% (95% CI − 1.2, 20.6%) higher than the risk among those without depressive symptoms. This increased risk of mortality for PWID with depressive symptoms was relatively consistent throughout the 2-year period: at 6, 12, and 18 months, the risk difference was 12.6% (5.5–19.7%), 13.9% (4.6–23.2%), and 11.0% (0.9–21.1%), respectively. HIV diagnosis may provide an important opportunity for depression screening and treatment, subsequently improving survival in this key population. Trial registry: ClinicalTrials.gov NCT01689545

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

Climate Services For Infectious Disease Control: A Nexus Between Public Health Preparedness And Sustainable Development, Lessons Learned From Long-Term Multi-Site Time-Series Analysis Of Dengue Fever In Vietnam

BACKGROUND: Climate services provide valuable information for making actionable, data-driven decisions to protect public health in a myriad of manners. There is mounting global evidence of the looming threat climate change poses to human health, including the variability and intensity of infectious disease outbreaks in Vietnam and other low-resource and developing areas. In light of the Sustainable Development Goals, this study aimed to examine the utility of spatial and time-series analysis, to inform public health preparedness strategies for sustainable urban development, in terms of dengue epidemiology, surveillance, control, and early warnings. SUBJECTS AND METHODS: Nearly 40 years of spatial and temporal (times-series) dataset of meteorological records, including rainfall, temperature, and humidity (among others) which can be predictors of dengue were assembled for all provinces of Vietnam. This dataset was associated with case data reported to General Department of Preventive Medicine, Ministry of Health of Vietnam, during the same period. Time series of climate and disease variables were analyzed for trend and changing pattern over time. The time-series statistical analysis method sought to identify spatial (when possible) and temporal trend, seasonality, cyclical pattern of disease, and to discover anomalous outbreak events, which departed from expected epidemiological pattern, and corresponding meteorological phenomena, such as El Nino Southern Oscillation (ENSO). RESULTS: Analysis yielded largely converged findings with other locations in South East Asia for larger outbreak years and events such as ENSO. Seasonality, trend, and cycle in many provinces were persistent throughout the dataset, indicating strong potential for climate services to be used in dengue early warnings. CONCLUSION: Public health practitioners, having adequate tools for dengue control available, must plan and budget vector control and patient treatment efforts well in advance of large scale dengue epidemics to curb such events with overall morbidity and mortality. Urban and sustainable development in Vietnam might benefit from evidence linking climate change and ill-health events spatially and temporally in future planning. Long term analysis of dengue case data and meteorological records, provided a cases study evidence for emerging opportunities that on how refined climate services, could contribute to protection of public health. Keywords: dengue, Vietnam, climate change, time-series analysis, climate servic