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

Clinical Features of Dengue in a Large Vietnamese Cohort: Intrinsically Lower Platelet Counts and Greater Risk for Bleeding in Adults than Children

Dengue is a common and potentially serious viral illness. Complications include plasma leakage from small blood vessels causing shock and dysfunction of the systems that control blood clotting, resulting in bleeding. The disease used to affect children predominantly, but in recent years, the number of adult patients has been increasing. As there is limited data describing the patterns of complications by age, we performed this study to compare clinical and laboratory features, management, and outcomes of the disease for over 1,500 children and adults with confirmed dengue recruited at the same time at a single hospital in the Southern Vietnam. We found that plasma leakage and shock were more common and severe in children than adults, while bleeding and organ dysfunction were more frequent in adults. Adults had lower platelet counts throughout the illness course as well as at a follow-up visit several weeks after recovery. Platelets are a crucial element in controlling bleeding, and the intrinsically lower counts in adults compared to children may contribute to the greater risk for bleeding in this patient group. Knowledge about differences in the patterns of dengue-related complications between children and adults should help clinicians to diagnose and treat patients more effectively

The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam : a study protocol for an open single-arm interventional trial [awaiting peer review]

Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018

COVID-19 Social Science and Public Engagement Action Research in Vietnam, Indonesia and Nepal (SPEAR): Protocol for a mixed methods study exploring the experiences and impacts of COVID-19 for healthcare workers and vulnerable communities

Background: When the novel coronavirus – SARS-CoV-2 – started to spread globally, there was a call for social and behavioral scientists to conduct research to explore the wider socio-cultural contexts of coronavirus disease 2019 (COVID-19), to understand vulnerabilities, as well as to increase engagement within communities to facilitate adoption of public health measures. In this manuscript, we describe the protocol for a study conducted in Indonesia, Nepal, and Vietnam. In the study, we explore how the COVID-19 pandemic is affecting individuals and their communities. We focus on the wider health and economic impacts of COVID-19, in particular emerging and increased burden on mental health, as well as new or deepened vulnerabilities in the communities. The introduction of vaccines has added another layer of complexity and highlights differences in acceptance and inequalities around access.  Methods: We use mixed methods, combining survey methods and social media surveillance to gain a picture of the general situation within each country, with in-depth qualitative methods to gain a deeper understanding of issues, coupled with a synergistic engagement component. We also include an exploration of the role of social media in revealing or driving perceptions of the pandemic more broadly. Participants include health workers and members of communities from 13 sites across the three countries. Data collection is spread across two phases. Phase 1 is concerned with exploring lived experiences, impacts on working lives and livelihoods, mental health and coping strategies. Phase 2 is concerned with acceptance of COVID-19 vaccines, factors that increase and reduce acceptance, and factors that influence access. Conclusions: We will disseminate findings in multiple ways including short reports and policy briefs, articles in peer-reviewed journals, and digital diaries will be edited into short films and uploaded onto social media sites.</ns3:p

A matrix approach to tropical marine ecosystem service assessments in South east Asia

Ecosystem service assessments are increasingly used to support natural resource management, but there is a bias in their application towards terrestrial systems and higher income countries. Tropical marine applications are particularly scarce, especially in SE Asia. Given the growing coastal population and expansion in blue economy sectors in SE Asia, evidence to support effective marine planning, such as ecosystem service assessments, is urgently needed. Data deficiencies for marine systems, especially (but not only) in lower income countries is a significant obstacle for ecosystem service assessments. To overcome this, we develop an ecosystem service potential matrix which combines evidence taken from an extensive literature review together with expert opinion. The matrix includes both natural and modified habitats as the service providing units. The ecosystem service potential for habitats are scored at the macro level (e.g. mangrove) due to insufficient evidence to score micro-habitats (e.g. fringe, basin or riverine mangroves). The majority of evidence is available for biogenic habitats (mangroves, coral reefs and seagrass meadows) with comparatively little for sedimentary habitats. While provisioning, regulating and cultural services are scored, published evidence is more readily available for provisioning and regulating services. Confidence scores, indicating the uncertainty in the ecosystem service potential scores are included in the matrix. To our knowledge this is the first attempt to systematically capture the provision of ecosystem services from tropical marine habitats. Although initially developed for four marine biosphere reserves and protected areas in SE Asia, the generic nature of the evidence included suggests that the matrix constitutes a valuable baseline for marine ecosystem service assessments within SE Asia and provides a robust foundation for development in future work

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Molecular Genetics, Clinical Characteristics, and Treatment Outcomes of K(ATP)-Channel Neonatal Diabetes Mellitus in Vietnam National Children's Hospital

BACKGROUND: Neonatal diabetes mellitus (NDM) is defined as insulin-requiring persistent hyperglycemia occurring within the first 6 months of life, which can result from mutations in at least 25 different genes. Activating heterozygous mutations in genes encoding either of the subunits of the ATP-sensitive K(+) channel (K(ATP) channel; KCNJ11 or ABCC8) of the pancreatic beta cell are the most common cause of permanent NDM and the second most common cause of transient NDM. Patients with NDM caused by K(ATP) channel mutations are sensitive to sulfonylurea (SU) treatment; therefore, their clinical management can be improved by replacing insulin with oral agents. PATIENTS AND METHODS: Seventy patients were diagnosed with NDM between May 2008 and May 2021 at Vietnam National Children's Hospital, and molecular genetic testing for all genes known to cause NDM was performed at the Exeter Genomic Laboratory, UK. Patients with ABCC8 or KCNJ11 mutations were transferred from insulin to oral SU. Clinical characteristics, molecular genetics, and annual data relating to glycemic control, SU dose, severe hypoglycemia, and side effects were collected. The main outcomes of interest were SU dose, SU failure (defined as permanent reintroduction of daily insulin), and glycemic control (HbA1c). RESULTS: Fifty-four of 70 patients (77%) with NDM harbored a genetic mutation and of these; 27 (50%) had activating heterozygous mutations in ABCC8 or KCNJ11. A total of 21 pathogenic mutations were identified in the 27 patients, including 13 mutations in ABCC8 and 8 mutations in KCNJ11. Overall, 51% had low birth weight (below 3rd percentile), 23 (85%) were diagnosed before 3 months of age, and 23 (85%) presented with diabetic ketoacidosis. At diagnosis, clinical and biochemical findings (mean ± SD) were pH 7.16 ± 0.16; HCO3- , 7.9 ± 7.4 mmol/L; BE, -17.9 ± 9.1 mmol/L; HbA1C, 7.98% ± 2.93%; blood glucose, 36.2 ± 12.3 mmol/L; and C-peptide median, 0.09 (range, 0-1.61 nmol/l). Twenty-six patients were successfully transferred from insulin to SU therapy. In the remaining case, remission of diabetes occurred prior to transfer. Glycemic control on SU treatment was better than on insulin treatment: HbA1c and blood glucose level decreased from 7.58% ± 4.63% and 19.04 ± 14.09 mmol/L when treated with insulin to 5.8 ± 0.94% and 6.87 ± 3.46 mmol/L when treated with SU, respectively. CONCLUSIONS: This is the first case series of NDM patients with ABCC8/KCNJ11 mutations reported in Vietnam. SU is safe in the short term for these patients and more effective than insulin therapy, consistent with all studies to date. This is relevant for populations where access to and cost of insulin are problematic, reinforcing the importance of genetic testing for NDM.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted version, submitted versio

DNA barcoding of Vietnamese bent-toed geckos (Squamata: Gekkonidae: Cyrtodactylus) and the description of a new species

Nguyen, Sang Ngoc, Yang, Jun-Xiao, Le, Thanh-Ngan Thi, Nguyen, Luan Thanh, Orlov, Nikolai L., Hoang, Chung Van, Nguyen, Truong Quang, Jin, Jie-Qiong, Rao, Ding-Qi, Hoang, Thao Ngoc, Che, Jing, Murphy, Robert W., Zhang, Ya-Ping (2014): DNA barcoding of Vietnamese bent-toed geckos (Squamata: Gekkonidae: Cyrtodactylus) and the description of a new species. Zootaxa 3784 (1), DOI: 10.11646/zootaxa.3784.1.

Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection.

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P &lt; 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease