Background Introduction of antiretroviral therapy (ART) has been associated with a decline in HIV-related mortality, though HIV remains a leading cause of death in sub-Saharan Africa. We describe all-cause mortality and its predictors in people living with HIV (PLWH) in the African Cohort Study (AFRICOS). Methods AFRICOS enrolls participants with or without HIV at 12 sites in Kenya, Uganda, Tanzania, and Nigeria. Evaluations every six months include socio-behavioral questionnaires, medical history, physical examination, and laboratory tests. Mortality data are collected from medical records and survivor interviews. Multivariable Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for factors associated with mortality. Results From 2013 through 2020, 2724 PLWH completed at least one follow-up visit or experienced death. Of these 58.4% were females, 25.8% were aged ≥ 50 years, and 98.3% were ART-experienced. We observed 11.42 deaths per 1000 person-years (95%CI: 9.53-13.68) with causes ascertained in 54% of participants. Deaths were caused by malignancy (28.1%), infections (29.7%), and other non-HIV related conditions. Predictors of mortality included CD4 ≤ 350 cells/µl (aHR 2.01 [CI: 1.31-3.08]), a log10copies/mL increase of viral load (1.36 [1.22-1.51]), recent fever (1.85[1.22-2.81]), body mass index <18.5 kg/m 2 (2.20 [1.44-3.38]), clinical depression (2.42 [1.40-4.18]), WHO stage III (2.18 [1.31-3.61]), a g/dL increase in hemoglobin (0.79 [0.72-0.85]) and every year on ART (0.67 [0.56-0.81]). Conclusions The mortality rate was low in this cohort of mostly virally suppressed PLWH. Patterns of deaths and identified predictors suggest multiple targets for interventions to reduce mortality.
Clinical vaccine development and regulatory approval generally occurs in a linear, sequential manner: Phase 1: safety, immunogenicity; Phase 2: immunogenicity, safety, dose ranging, and preliminary efficacy; Phase 3: definitive efficacy, safety, lot consistency; and following regulatory approval, Phase 4: post-marketing safety and effectiveness. For candidate filovirus vaccines, where correlates of protection have not been identified, and phase 2 and 3 efficacy of disease prevention trials untenable, large and/or protracted, each trial may span decades, with full licensure expected only after several decades of development. Given the urgent unmet need for new Marburg virus and Ebola Sudan virus vaccines, the Sabin Vaccine Institute hosted a key stakeholder virtual meeting in May 2021 to explore the possibility of licensure by use of an “animal rule-like” licensure process, based on a risk/benefit assessment specific to regional needs and informed by epidemiology. This may be appropriate for diseases where there are no or limited treatment options, and those prone to sporadic outbreaks with high rates of transmission, morbidity, and mortality. The discussion focused on two contexts: licensure within the Ugandan regulatory environment, a high burden country where Ebola vaccine trials are ongoing, and licensure by the United States FDA—a well-resourced regulatory agency.
Introduction: Infectious diseases and neglected tropical diseases continue to be a major challenge in resource limited settings, causing significant morbidity and mortality. Although vaccines are a key biomedical prevention tool, resource limited settings often lack the infrastructure, regulatory frameworks, and skilled human resource to conduct vaccine clinical trials. To address this gap, the Makerere University Walter Reed Project (MUWRP) was established and has contributed to vaccine research in Uganda and globally. Methods: This was achieved through training a strong vaccine clinical trial workforce; development of requisite clinical trial infrastructure for research activities and management of investigational products; conducting phase I-III vaccine trials and contribution to national ethical and regulatory frameworks that protect participants. Results: As of 2022, MUWRP had successfully conducted and completed five phase I/II HIV vaccine clinical trials, five for Ebola and Marburg, while one phase I/II Schistosomiasis and one phase III COVID-19 vaccine clinical trial are ongoing. Discussion: The completed vaccine trials provided critical scientific knowledge on the safety and immunogenicity of investigational products which informed the design of better vaccines for diseases of global health importance. Conclusion: Academia, through establishment of appropriate partnerships can contribute to the identification of solutions to complex public health challenges. Keywords: Vaccines; community participation; developing countries.
Background Uganda is prone to Emerging Infectious Diseases (EIDs) which can cause serious epidemics and pandemics. Uganda’s capacity for EID research, surveillance and control is improving but still low partly due to inadequate highly knowledgeable and skilled human and animal health workers. To inform the design of training programs that can address Uganda’s health workforce capacity gaps, we conducted a training needs assessment. Methods A qualitative study involving a desk review, 25 key informant interviews and a 1-day consultative workshop to review study findings. Results The majority of infectious disease research, surveillance and control in Uganda focuses on HIV/AIDS, Tuberculosis, Malaria and viral hemorrhagic fevers e.g., Ebola and Marburg. Health workforce capacity for surveillance and control is robust compared to many other resource-constrained settings but research capacity and output are relatively low, especially for EIDs. Public and private tertiary institutions in Uganda predominantly offer training in primary health care and population studies through problem-based learning, community-based education and services, and Blended Learning (BL). There are several training programs in advanced clinical and epidemiological sciences, but few opportunities in biomedical sciences (e.g. virology, immunology, bioinformatics and predictive modeling), social sciences, One Health and leadership. To address the gaps, the following interventions were recommended: 1) advanced graduate and/or post-graduate training in basic biomedical sciences; 2) short-term training for continuous knowledge and skills development in multidisciplinary/One Health approaches; and 3) pedagogy and mentorship through BL, networking and experiential training programs that effectively leverage North-South collaborations. Training and mentorship should be achieved by (a) conducting most of the in-person didactic and experiential training at Southern tertiary and research institutions, (b) utilizing electronic-learning for didactic training and mentor-mentee interactions with subject-matter experts at Northern institutions, and (c) well-orchestrated placements at Northern institutions for hands-on experience using the latest advances in science and technology. Conclusion Inadequate health workforce capacity for EID research was identified as a priority gap that requires long and short-term multidisciplinary training interventions. Efficiently leveraging North-South collaborations for e-learning, short-term placements and mentorship will enable Uganda to remain abreast with latest advances in science and technology for EID research, surveillance and control.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.