A phase I COVID-19 vaccine trial among SARS-CoV-2 seronegative and seropositive individuals in Uganda utilizing a self-amplifying RNA vaccine platform: Screening and enrollment experiences.

We report the screening and enrollment process for a phase I vaccine trial in Masaka, Uganda that investigated the safety and immunogenicity of a self-amplifying SARS-CoV-2 RNA vaccine amongst individuals with and without antibodies to SARS-CoV-2. Participant screening and enrollment were conducted between December 2021 and April 2022. Individuals were eligible if they were aged between 18 and 45 years, healthy, and never vaccinated against COVID-19. SARS-CoV-2 antibody status was determined using two point-of-care rapid tests, i.e. Multi G (MGFT3) and Standard Q (Standard Q COVID-19 IgM/IgG Plus). Data were entered and managed in OpenClinica. Analyses were performed and presented descriptively. A total of 212 individuals were screened and 43(20.3%) enrolled. The most common reasons for exclusion were ≥ grade 1 laboratory abnormalities (39, 18.4%), followed by discordant SARS-CoV-2 antibody results (23, 10.9%). While the first 38 participants were quickly enrolled over a period of 9 weeks, it took another 9 weeks to enroll the remaining five, as antibody negative participants became scarce during the surge of the Omicron variant. The SARS-CoV-2 antibody positivity rate was determined to be 60.8% and 84.4% in each half of the 18 months of screening respectively. The mean age (±Standard Deviation, SD) of screened and enrolled participants was 27.7 (±8.1) and 30.2 (±8.3) years respectively. We demonstrated that it is feasible to successfully screen and enroll participants for COVID-19 vaccine trials in Uganda in the time of a pandemic. Our experiences may be useful for investigators planning to undertake similar work in Africa.

Willingness to participate in COVID-19 vaccine trials; a survey among a population of healthcare workers in Uganda.

BACKGROUND: Healthcare workers (HCWs) are at high risk of acquiring SARS-CoV-2 and COVID-19 and may therefore be a suitable population for COVID-19 vaccine trials. We conducted a survey to evaluate willingness-to-participate in COVID-19 vaccine trials in a population of HCWs at three hospitals in Uganda. METHODS: The survey was conducted between September and November 2020. Using a standardised questionnaire, data were collected on socio-demographics, previous participation in health research, COVID-19 information sources, underlying health conditions, and willingness-to-participate in COVID-19 vaccine trials. Data were analysed descriptively and a binomial generalised linear model with a log link function used to investigate factors associated with unwillingness to participate. RESULTS: 657 HCWs (female, 63%) were enrolled with a mean age of 33 years (Standard Deviation, 10). Overall willingness-to-participate was 70.2%. Key motivating factors for participation were: hope of being protected against COVID-19 (81.1%), altruism (73.3%), and the opportunity to get health care (26.0%). Selected hypothetical trial attributes reduced willingness-to-participate as follows: weekly-quarterly study visits over a 12-month period (70.2%-63.2%, P = 0.026); provision of approximately 50ml of blood at each study visit (70.2%-63.2%, P = 0.026); risk of mild-moderate local adverse reactions (70.2%-60.3%, P<0.001); chance of receiving candidate vaccine or placebo (70.2%-56.9%, P<0.001); and delay of pregnancy [Overall, 70.2%-57.1% P<0.001); Female, 62.8%-48.4% (P = 0.002); Male, 82.5%-71.5% (P = 0.003)]. Collectively, these attributes reduced willingness-to-participate from [70.2%-42.2% (P<0.001) overall; 82.5%-58.1% (P<0.001) in men; 62.8%-32.6% (P<0.001) in women]. Among individuals that were unwilling to participate, the commonest barriers were concerns over vaccine safety (54.6%) and fear of catching SARS-CoV-2 (31.6%). Unwillingness to participate was associated with being female (aRR 1.97, CI 1.46-2.67, P<0.001) and having university or other higher-level education (aRR 1.52, CI 1.05-2.2, P = 0.026). CONCLUSIONS: Willingness-to-participate in COVID-19 vaccine trials among HCWs in Uganda is high but may be affected by vaccine trial requirements and concerns about the safety of candidate vaccines.

Knowledge, Attitudes, and Practices Regarding COVID-19 among Healthcare Workers in Uganda: A Cross-Sectional Survey.

Healthcare workers (HCWs) are at high risk of COVID-19. However, data on HCWs' knowledge, attitudes, and practices (KAP) toward COVID-19 are limited. Between September and November 2020, we conducted a questionnaire-based COVID-19 KAP survey among HCWs at three hospitals in Uganda. We used Bloom's cut-off of ≥80% to determine sufficient knowledge, good attitude, and good practice, and multivariate Poisson regression with robust variance for statistical analysis. Of 717 HCWs invited to participate, 657 (91.6%) agreed and were enrolled. The mean age (standard deviation) of enrollees was 33.2 (10.2) years; most were clinical HCWs (64.7%) and had advanced secondary school/other higher-level education (57.8%). Overall, 83.9% had sufficient knowledge, 78.4% had a positive attitude, and 37.0% had good practices toward COVID-19. Factors associated with KAP were: Knowledge: being a clinical HCW (aRR: 1.12; 95% CI: 1.02-1.23) and previous participation in health research (aRR: 1.10; 95% CI: 1.04-1.17); Attitude: age > 35 years (aRR: 0.88; 95% CI: 0.79-0.98); Practice: being a clinical HCW (aRR: 1.91; 95% CI: 1.41-2.59). HCWs in Uganda have good knowledge and positive attitude but poor practices towards COVID-19. Differences in COVID-19 KAP between clinical and non-clinical HCWs could affect uptake of COVID-19 interventions including vaccination.

Implementation of accelerated research: strategies for implementation as applied in a phase 1 Ad26.ZEBOV, MVA-BN-Filo two-dose Ebola vaccine clinical trial in Uganda.

BACKGROUND: The 2013-2016 Ebola epidemic in West Africa is the worst ever caused by Ebolaviruses with over 28,000 human cases and 11,325 deaths. The World Health Organisation (WHO) declared the epidemic a public health crisis that required accelerated development of novel interventions including vaccines. The Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit (MRC/UVRI & LSHTM Uganda Research Unit) was among the African research sites that implemented the VAC52150EBL1004 Ebola vaccine trial. OBJECTIVE: We report on the strategies utilised by the Unit and sponsor in ensuring expedited clinical trial approval and accelerated conduct. METHODS: Janssen Vaccines and Prevention B.V. conducted a phase 1 trial to evaluate the safety, tolerability, and immunogenicity of heterologous two-dose vaccination regimens using Ad26.ZEBOV and MVA-BN-Filo, in healthy adults in Africa. Accelerated implementation strategies are hereby presented. RESULTS: Strategies included: holding the African Vaccine Regulatory Forum (AVAREF) joint review meeting; expedited review by institutional ethics and country-specific regulatory bodies; competitive recruitment between sites; electronic data capture (EDC); frequent study monitoring schedule; involvement of a community advisory board (CAB); and utilization of a 'phased' study information-sharing approach in community engagement and participant recruitment. These strategies enabled the site to acquire approvals within 2 months and enrol 47 participants within a spurn of five. The same milestone is usually acquired in at least 1 year without accelerated implementation. CONCLUSION: The use of well-thought strategies by sponsors and research sites can enable the implementation of accelerated research. We recommend the use of similar strategies in other settings.

The role of community acceptance over time for costs of HIV and STI prevention interventions: analysis of the Masaka Intervention Trial, Uganda, 1996-1999.

OBJECTIVE: The objective of this study is to estimate the annual costs of information, education, and communication (IEC), both community- and school-based; strengthened public and private sexually transmitted infections treatment; condom social marketing (CSM); and voluntary counseling and testing (VCT) implemented in Masaka, Uganda, over 4 years, and to explore how unit costs change with varying population use/uptake. STUDY: Total economic provider's costs and intervention outputs were collected annually to estimate annual unit costs between 1996 and 1999. RESULTS: In early intervention years, uptake of all activities grew dramatically and continued to grow for public STI treatment, CSM, and VCT. Attendance at IEC performances started to drop in year 4. Unit costs dropped rapidly with increasing uptake of and participation in interventions. CONCLUSIONS: When implementing long-term community-based interventions, it is important to take into account that it takes time for communities to scale up their participation, since this can lead to large variations in unit costs.