Browsing by Author "Asingura, Bannet"
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Item In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion(BMC Complementary Medicine and Therapies, 2021) Olwenyi, Omalla A.; Asingura, Bannet; Naluyima, Prossy; Anywar, Godwin Upoki; Nalunga, Justine; Nakabuye, MariamIn Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups. A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.Item Training Needs for Emerging Infectious Diseases Research, Surveillance and Control in High-Risk and Resource-Constrained Settings: Findings and Recommendations for Uganda(ResearchSquare, 2022) Asingura, Bannet; Kiweewa, Francis; Kaawa-Mafigiri, David; Achabo, Sheila; Mimbe, Derrick; Okullo, Allen Eva; Eyu, Patricia; Nanyondo, Jauhara; Naluyima, Prossy; Kandole, Martha; Tindikahwa, Allan; Nalunga, Justine; Ssekitoleko, Mathias; Nakakeeto, Josephine; Nawatti, Jesca; Kibirige, Daniel; Nansalire, WinfredUganda 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.A qualitative study involving a desk review, 25 key informant interviews and a 1-day consultative workshop to review study findings.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.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.