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Governments, funders, and research bodies must take action to ensure that research is undertaken ethically during global health emergencies, says a new report from the Nuffield Council on Bioethics.
The facilitators of and barriers to antimicrobial use and misuse in Lalitpur, Nepal: a qualitative study.
BackgroundAntimicrobial resistance (AMR) is a pressing global health concern driven by inappropriate antibiotic use, which is in turn influenced by various social, systemic, and individual factors. This study, nested within FIND's AMR Diagnostic Use Accelerator clinical trial in Nepal, aimed to (i) explore the perspectives of patients, caregivers, and healthcare workers (HCWs) on antibiotic prescription adherence and (ii) assess the impact of a training and communication (T&C) intervention on adherence to antibiotic prescriptions.MethodsUsing qualitative, semi-structured interviews, pre-intervention and Day 7 follow-up components, and the Behaviour Change Wheel process, we investigated the facilitators of and barriers to the use and misuse of antibiotic prescriptions.ResultsResults of the study revealed that adherence to antibiotic prescriptions is influenced by a complex interplay of factors, including knowledge and understanding, forgetfulness, effective communication, expectations, beliefs and habits, attitudes and behaviours, convenience of purchasing, trust in medical effectiveness, and issues of child preferences. The T&C package was also shown to play a role in addressing specific barriers to treatment adherence.ConclusionsOverall, the results of this study provide a nuanced understanding of the challenges associated with antibiotic use and suggest that tailored interventions, informed by behaviour frameworks, can enhance prescription adherence, may be applicable in diverse settings and can contribute to the global effort to mitigate the rising threat of AMR.
Pathogen diversity and antimicrobial resistance transmission of Salmonella enterica serovars Typhi and Paratyphi A in Bangladesh, Nepal, and Malawi: a genomic epidemiological study.
BackgroundEnteric fever is a serious public health concern. The causative agents, Salmonella enterica serovars Typhi and Paratyphi A, frequently have antimicrobial resistance (AMR), leading to limited treatment options and poorer clinical outcomes. We investigated the genomic epidemiology, resistance mechanisms, and transmission dynamics of these pathogens at three urban sites in Africa and Asia.MethodsS Typhi and S Paratyphi A bacteria isolated from blood cultures of febrile children and adults at study sites in Dhaka (Bangladesh), Kathmandu (Nepal), and Blantyre (Malawi) during STRATAA surveillance were sequenced. Isolates were charactered in terms of their serotypes, genotypes (according to GenoTyphi and Paratype), molecular determinants of AMR, and population structure. We used phylogenomic analyses incorporating globally representative genomic data from previously published surveillance studies and ancestral state reconstruction to differentiate locally circulating from imported pathogen AMR variants. Clusters of sequences without any single-nucleotide variants in their core genome were identified and used to explore spatiotemporal patterns and transmission dynamics.FindingsWe sequenced 731 genomes from isolates obtained during surveillance across the three sites between Oct 1, 2016, and Aug 31, 2019 (24 months in Dhaka and Kathmandu and 34 months in Blantyre). S Paratyphi A was present in Dhaka and Kathmandu but not Blantyre. S Typhi genotype 4.3.1 (H58) was common in all sites, but with different dominant variants (4.3.1.1.EA1 in Blantyre, 4.3.1.1 in Dhaka, and 4.3.1.2 in Kathmandu). Multidrug resistance (ie, resistance to chloramphenicol, co-trimoxazole, and ampicillin) was common in Blantyre (138 [98%] of 141 cases) and Dhaka (143 [32%] of 452), but absent from Kathmandu. Quinolone-resistance mutations were common in Dhaka (451 [>99%] of 452) and Kathmandu (123 [89%] of 138), but not in Blantyre (three [2%] of 141). Azithromycin-resistance mutations in acrB were rare, appearing only in Dhaka (five [1%] of 452). Phylogenetic analyses showed that most cases derived from pre-existing, locally established pathogen variants; 702 (98%) of 713 drug-resistant infections resulted from local circulation of AMR variants, not imported variants or recent de novo emergence; and pathogen variants circulated across age groups. 479 (66%) of 731 cases clustered with others that were indistinguishable by point mutations; individual clusters included multiple age groups and persisted for up to 2·3 years, and AMR determinants were invariant within clusters.InterpretationEnteric fever was associated with locally established pathogen variants that circulate across age groups. AMR infections resulted from local transmission of resistant strains. These results form a baseline against which to monitor the impacts of control measures.FundingWellcome Trust, Bill & Melinda Gates Foundation, EU Horizon 2020, and UK National Institute for Health and Care Research.
Safety, pharmacokinetics, and potential neurological interactions of ivermectin, tafenoquine, and chloroquine in Rhesus macaques
ABSTRACT Ivermectin (IVM) could be used for malaria control as treated individuals are lethal to blood-feeding Anopheles , resulting in reduced transmission. Tafenoquine (TQ) is used to clear the liver reservoir of Plasmodium vivax and as a prophylactic treatment in high-risk populations. It has been suggested to use ivermectin and tafenoquine in combination, but the safety of these drugs in combination has not been evaluated. Early derivatives of 8-aminoquinolones (8-AQ) were neurotoxic, and ivermectin is an inhibitor of the P-glycoprotein (P-gp) blood brain barrier (BBB) transporter. Thus, there is concern that co-administration of these drugs could be neurotoxic. This study aimed to evaluate the safety and pharmacokinetic interaction of tafenoquine, ivermectin, and chloroquine (CQ) in Rhesus macaques. No clinical, biochemistry, or hematological outcomes of concern were observed. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was employed to assess potential neurological deficits following drug administration. Some impairment was observed with tafenoquine alone and in the same monkeys with subsequent co-administrations. Co-administration of chloroquine and tafenoquine resulted in increased plasma exposure to tafenoquine. Urine concentrations of the 5,6 orthoquinone TQ metabolite were increased with co-administration of tafenoquine and ivermectin. There was an increase in ivermectin plasma exposure when co-administered with chloroquine. No interaction of tafenoquine on ivermectin was observed in vitro . Chloroquine and trace levels of ivermectin, but not tafenoquine, were observed in the cerebrospinal fluid. The 3′′- O -demethyl ivermectin metabolite was observed in macaque plasma but not in urine or cerebrospinal fluid. Overall, the combination of ivermectin, tafenoquine, and chloroquine did not have clinical, neurological, or pharmacological interactions of concern in macaques; therefore, this combination could be considered for evaluation in human trials.
A retrospective investigation of the population structure and geospatial distribution of Salmonella Paratyphi A in Kathmandu, Nepal.
Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has increased in prevalence in recent decades in certain endemic regions in comparison to S. Typhi, the most prevalent cause of enteric fever. Despite this increase, data on the prevalence and molecular epidemiology of S. Paratyphi A remain generally scarce. Here, we analysed the whole genome sequences of 216 S. Paratyphi A isolates originating from Kathmandu, Nepal between 2005 and 2014, of which 200 were from patients with acute enteric fever and 16 from the gallbladder of people with suspected chronic carriage. By exploiting the recently developed genotyping framework for S. Paratyphi A (Paratype), we identified several genotypes circulating in Kathmandu. Notably, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and systematically replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced susceptibility to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes encoding the type 3 secretion systems. Finally, we show that person-to-person is likely the most common mode of transmission and chronic carriers seem to play a limited role in maintaining disease circulation.
Safety and immunogenicity of varied doses of R21/Matrix-M™ vaccine at three years follow-up: A phase 1b age de-escalation, dose-escalation trial in adults, children, and infants in Kilifi-Kenya.
BackgroundFalciparum malaria remains a global health problem. Two vaccines, based on the circumsporozoite antigen, are available. RTS, S/AS01 was recommended for use in 2021 following the advice of the World Health Organisation (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization and WHO Malaria Policy Advisory Group (MPAG). It has since been pre-qualified in 2022 by the WHO. R21 is similar to RTS, S/AS01, and recently licensed in Nigeria, Ghana and Burkina Faso following Phase 3 trial results.MethodsWe conducted a Phase 1b age de-escalation, dose escalation bridging study after a change in the manufacturing process for R21. We recruited healthy adults and children and used a three dose primary vaccination series with a booster dose at 1-2 years. Variable doses of R21 and adjuvant (Matrix-M ™) were administered at 10µgR21/50 µg Matrix-M™, 5µgR21/25µg Matrix-M™ and 5µgR21/50µg Matrix-M™ to 20 adults, 20 children, and 51 infants.ResultsSelf-limiting adverse events were reported relating to the injection site and mild systemic symptoms. Two serious adverse events were reported, neither linked to vaccination. High levels of IgG antibodies to the circumsporozoite antigen were induced, and geometric mean titres in infants, the target group, were 1.1 (0.9 to 1.3) EU/mL at day 0, 10175 (7724 to 13404) EU/mL at day 84 and (following a booster dose at day 421) 6792 (5310 to 8687) EU/mL at day 456.ConclusionR21/Matrix-M™ is safe, and immunogenic when given at varied doses with the peak immune response seen in infants 28 days after a three dose primary vaccination series given four weeks apart. Antibody responses were restored 28 days after a 4 th dose given one year post a three dose primary series in the young children and infants.RegistrationClinicaltrials.gov (NCT03580824; 9 th of July 2018; Pan African Clinical Trials Registry (PACTR202105682956280; 17 th May 2021).
Profiling IgG and IgA antibody responses during vaccination and infection in a high-risk gonorrhoea population
AbstractDevelopment of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, highly exposed individuals may develop immunity against re-infection with the same strain. Retrospective epidemiological studies have shown that vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provide a degree of cross-protection against Ng infection. We conducted a clinical trial (NCT04297436) of 4CMenB (Bexsero, GSK), a licensed Nm vaccine containing OMVs and recombinant antigens, comprising a single arm, open label study of two doses with 50 adults in coastal Kenya who have high exposure to Ng. Data from a Ng antigen microarray established that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 but had declined by 24 weeks. For most reactive OMV-derived antigens, the reverse was the case. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.
Nutritional supplementation in children with severe pneumonia in Uganda and Kenya (COAST-Nutrition): a phase 2 randomised controlled trial.
BackgroundSevere pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes.MethodsCOAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180.FindingsBetween 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was no significant difference in the composite endpoint (probabilistic index 0.49, 95% CI 0.45-0.53, p = 0.74). Respective 90-day mortality (13/420 3.1% vs 14/421 3.3%) and MUAC increment (0.54 (SD 0.85) vs 0.55 (SD 0.81)) were similar between arms. There was no difference in any anthropometric secondary endpoints to Day 28, 90 or 180 except skinfold thickness at Day 28 and Day 90 was greater in the RUTF arm. Serious adverse events were higher in the RUTF arm (n = 164 vs 108), mainly due to hospital readmission for acute illness (54/387 (14%) vs 37/375 (10%).InterpretationOur study suggested that nutritional supplementation with RUTF did not improve outcomes to 180 days in children with severe pneumonia.FundingThis trial is part of the EDCTP2 programme (grant number RIA-2016S-1636-COAST-Nutrition) supported by the European Union, and UK Joint Global Health Trials scheme: Medical Research Council, Department for International Development, Wellcome Trust (grant number MR/L004364/1, UK).
SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART)
Background Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission (<24hours). Lactic acidosis, largely due to impairment of the microcirculatory flow due to parasite sequestration, is a main risk factor for poor outcome. There are no adjuvant treatments for severe malaria that target this complication. Sevuparin, a heparin-like drug, binds to Plasmodium falciparum erythrocyte membrane protein blocking merozoite invasion, preventing cytoadherence and transiently de-sequestering infected erythrocytes. Leading to improved microcirculatory flow by reversing/preventing parasite sequestration. If given early during admission this could result in improvements in outcomes. Sevuparin has been shown to be safe and well tolerated in adults with only some mild transient effects on activated partial thromboplastin time (APTT) were reported, without clinical consequences. Methods A Phase I trial designed to provide data on safety, dosing, feasibility of sevuparin as an adjuvant therapy in Kenya and Zambian children with severe malaria complicated by lactic acidosis (> 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient’s APTT results using standard methods. Conclusions The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. Registration PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021)
Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine in adults in Kenya: a phase 1/2 single-blind, randomised controlled trial.
BackgroundThere are limited data on the immunogenicity of coronavirus disease 2019 (COVID-19) vaccines in African populations. Here we report the immunogenicity and safety of the ChAdOx1 nCoV-19 (AZD1222) vaccine from a phase 1/2 single-blind, randomised, controlled trial among adults in Kenya conducted as part of the early studies assessing vaccine performance in different geographical settings to inform Emergency Use Authorisation.MethodsWe recruited and randomly assigned (1:1) 400 healthy adults aged ≥18 years in Kenya to receive ChAdOx1 nCoV-19 or control rabies vaccine, each as a two-dose schedule with a 3-month interval. The co-primary outcomes were safety, and immunogenicity assessed using total IgG enzyme-linked immunosorbent assay (ELISA) against SARS-CoV-2 spike protein 28 days after the second vaccination.ResultsBetween 28 th October 2020 and 19 th August 2021, 400 participants were enrolled and assigned to receive ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Local and systemic adverse events were self-limiting and mild or moderate in nature. Three serious adverse events were reported but these were deemed unrelated to vaccination. The geometric mean anti-spike IgG titres 28 days after second dose vaccination were higher in the ChAdOx1 group (2773 ELISA units [EU], 95% CI 2447, 3142) than in the rabies vaccine group (61 EU, 95% CI 45, 81) and persisted over the 12 months follow-up. We did not identify any symptomatic infections or hospital admissions with respiratory illness and so vaccine efficacy against clinically apparent infection could not be measured. Vaccine efficacy against asymptomatic SARS-CoV-2 infection was 38.4% (95% CI -26.8%, 70.1%; p=0.188).ConclusionsThe safety, immunogenicity and efficacy against asymptomatic infection of ChAdOx1 nCoV-19 among Kenyan adults was similar to that observed elsewhere in the world, but efficacy against symptomatic infection or severe disease could not be measured in this cohort.Pan-african clinical trials registrationPACTR202005681895696 (11/05/2020).
Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.
BackgroundHydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use.Methods and findingsHealthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507.InterpretationIn this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs.Trial registrationClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.
Effects of the COVID-19 pandemic on hospital admissions and inpatient mortality in Kenya: a retrospective cohort study
Background The impact of COVID-19 in Africa remains poorly described. We examined hospitalisation trends for all medical causes, clinician-diagnosed pneumonia admissions, and inpatient mortality in Kenya two years before and across the first six waves of the pandemic. Methods We conducted a hospital-based observational study of patients admitted to 13 public referral facilities in Kenya from January 2018 to December 2022. The pre-COVID-19 population included admissions before 1st March 2020. Time series models, adjusted for seasonality and hospital, compared observed and predicted trends. To estimate the impact of the COVID-19 pandemic, we calculated incidence rate ratios (IRR) from negative binomial mixed-effects models. Results 357,631 patients were admitted across the 13 sites (range 15,354 to 67,241 per hospital). 45,349 patients (42.1%) were admitted to the adult medical wards. On the paediatric ward, 163,608 individuals (47.4%) were aged under five years and 36,227 individuals (10.5%) were aged five years and older. In comparison to the pre-pandemic period, hospitalisations reduced for adults (IRR 0.75, 95% CI 0.69–0.82) and paediatric cases (IRR 0.69, 95% CI 0.64–0.75). In-hospital deaths also declined for adults (IRR 0.83, 95% CI 0.77–0.89) and children (IRR 0.85, 95% CI 0.77–0.94). Adult pneumonia admissions increased (IRR 1.59, 95% CI 1.36–1.85), while paediatric cases decreased overall, (IRR 0.78, 95% CI 0.51–1.20), but became elevated in late 2021 compared to the pre-pandemic period. Conclusions The COVID-19 pandemic did not cause a surge in hospitalisations in Kenya. However, pneumonia admissions among adults (but not children) increased significantly, with peaks aligning with the pandemic waves. These findings underscore the importance of syndromic inpatient surveillance in detecting and monitoring outbreaks.
Field evaluation of a point-of-care triage test for active tuberculosis (TriageTB).
BackgroundTo improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability. The TriageTB diagnostic test study aims to assess the accuracy of diagnostic test candidates, as well as field-test, finalise the design and biomarker signature, and validate a point-of-care multi-biomarker test (MBT).MethodsThis observational diagnostic study will evaluate sensitivity and specificity of biomarker-based diagnostic candidates including the MBT and Xpert® TB Fingerstick cartridge compared with a gold-standard composite TB outcome classification defined by symptoms, sputum GeneXpert® Ultra, smear and culture, radiological features, response to TB therapy and presence of an alternative diagnosis. The study will be conducted in research sites in South Africa, Uganda, The Gambia and Vietnam which all have high TB prevalence. The two-phase design allows for finalisation of the MBT in Phase 1 in which candidate host proteins will be evaluated on stored serum from Asia, South Africa and South America and on fingerstick blood from 50 newly recruited participants per site. The MBT test will then be locked down and validated in Phase 2 on 250 participants per site.DiscussionBy targeting confirmatory TB testing to those with a positive triage test, 75% of negative GXPU may be avoided, thereby reducing diagnostic costs and patient losses during the care cascade. This study builds on previous biomarker research and aims to identify a point-of-care test meeting or exceeding the minimum World Health Organisation target product profile of a 90% sensitivity and 70% specificity. Streamlining TB testing by identifying individuals with a high likelihood of TB should improve TB resources use and, in so doing, improve TB care.Trial registrationNCT04232618 (clinicaltrials.gov) Date of registration: 16 January 2020.
Exploring attitudes to research involving human subjects among Vietnamese university students: establishing a prospective longitudinal mixed-methods student cohort at the University of Medicine and Pharmacy at Ho Chi Minh City.
Research capacity is increasing in low- and middle-income countries (LMICs), with progressive development in the range and complexity of studies being undertaken, often in collaboration with high-income country partners. Although senior local stakeholders are typically involved in ensuring that research is conducted according to accepted standards for ethical and scientific quality, to date there has been little exploration of the views of younger generations around the ethics of research involving human subjects. We present our protocol to establish a longitudinal mixed-methods student cohort at the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam, that is investigating students' views around the ethics of clinical and public-health oriented research. We use a synergistic approach involving initial deliberative engagement activities ( e.g. science cafes, debates) to inform participants about complex concepts, prior to formal quantitative and qualitative methods (surveys, focus group discussions and in-depth interviews) that are designed to explore the students' views in detail. We focus in particular on dengue research, i.e. research that addresses a locally relevant disease with which the students are likely familiar, and probe their thoughts on such themes as appropriate remuneration for research participants, involvement of vulnerable groups, use of human challenge trials in LMICs etc. A snapshot of the cohort and its activities after one year is also presented; among 429 active students, primarily from the Faculty of Medicine, the proportions of male and female students were similar, the majority were from southern or central Vietnam where dengue is endemic, and available data indicates the cohort to be representative of the expected spectrum of socioeconomic groups. The cohort provides a unique resource to investigate the views of young people on medical ethics, an important but hitherto underrepresented group in such discussions. Feedback indicates a clear interest in contributing thoughts and ideas to the development of clinical research in Vietnam.