Browsing by Author "Nabatanzi, Rose"

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    Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial
    (Tropical medicine & international health, 2015) Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D.; Kamya, Moses R.; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet
    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery.A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported.Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.
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    CCR5 promoter variants among Ugandan HIV-1 elite and viremic controllers: a laboratory ฀ based cross ฀ sectional study
    (Research Square, 2020) Nyiro, Brian; Amanya, Sharon B.; Nabatanzi, Rose; Bayiyana, Alice; Kalazane, Linda I.; Waswa, Francis; Nabulime, Eva; Karara, Daniel; Kabali, Joel; Mboowa, Gerald; Kayongo, Alex; Kateete, David P.; Nankya, Immaculate
    Mechanisms for HIV control among HIV-1 elite and viremic-controllers are not fully understood. In Uganda, Studies have reported individuals who without Antiretroviral therapy have the inherent ability to control HIV progression to AIDS for a period of greater than 5 years. However, reasons for this phenotype are not understood. The study objective was to determine the distribution of CCR5 co-receptor on CD4+ T-cells and its associated promoter variants among HIV-1 elite and viremic-controllers. Methods We isolated CD4+T-cells from PBMCs using EasySep CD4+ T-cell negative selection kit, and stimulated them with anti-CD3 and anti-CD28 for 48 hours. To quantify CCR5 expression, we performed immune-phenotyping using flow cytometry. CCR5 promoter polymorphisms were determined through sanger sequencing. The Kruskal–Wallis and the Mann-Whitney test were used to compare differences in the percentages of CCR5+ CD4+ T-cells and the differences in CCR5 densities on CD4+ T-cells respectively. p values < 0.05 were considered significant. Results The percentage of CCR5+CD4+ T-cells was higher among the non-controllers compared to the controllers although, the difference was not statistically significant; elite and viremic-controllers (p=0.9173), viremic and non-controllers (0.0702), elite and non-controllers (0.6010). Of significance was the CCR5 densities on CD4+ T-cells, which were significantly higher among non-controllers relative to the controllers; elite and viremic-controllers (p=3048), viremic and non43 controllers (P=0.0312), elite and non-controllers (P=0.0210)
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    High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
    (BMC infectious diseases, 2011) Nakanjako, Damalie; Ssewanyana, Isaac; Mayanja-Kizza, Harriet; Kiragga, Agnes; Manabe, Yukari C.; Nabatanzi, Rose; Kamya, Moses R.; Cao, Huyen
    Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
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    Schistosoma mansoni Infection: A Major Contributor of Reduced Effective T Helper Responses against Plasmodium falciparum and Schistosoma mansoni Co-Infection in ex vivo: A Cross-Sectional Study to Assess Th1, Th2 & Th17 Immune Responses
    (Open Journal of Immunology, 2017) Candia, Rowel; Nabatanzi, Rose; Olobo, Joseph; Auma, Ann; Asiimwe, Benon; Mbabazi, Olive; Bayiyana, Alice; Enzaru, Annet; Tukahebwa, Edridah
    Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vaccine and chemotherapeutic efficacy. Schistosoma mansoni and Plasmodium falciparum are co-endemic in Uganda and are the leading parasitic causes of public health problems across sub-Saharan Africa. Objectives: The overall aim was therefore, to elucidate the impact of S. mansoni infection on protective T helper immune responses on P. falciparum and S. mansoni co-infection. Methodology: This study evaluated the T helper immune responses in individuals with independent S. mansoni infection, independent P. falciparum infection, co-infection and non-infection in school attending children in a co-endemic area along Lake Victoria shores, Uganda. Immune responses were categorized into Th1, Th2, and Th17 based on unique cytokine(s) produced by the T helper subpopulation in ex vivo. Kato Katz thick smears and circulating cathodic antigen tests were performed for S. mansoni screening, whereas thick and thin blood smear techniques were performed for P. falciparum screening. Results: We observed an up regulated Th1 T helper subpopulation in independent P. falciparum infections compared to the uninfected group. Suboptimal T helper immune responses were detected in independent S. mansoni infections characterized by significantly down regulated Th1 (Z = -1.425, p = 0.0313) response in comparison to the non-infected group. Suboptimal T helper immune responses were also recorded in the co-infected individuals characterized by significantly down regulated Th1 (Z = -3.260, p = 0.0273) and Th2 (Z = -1.180, p = 0.0078) responses compared to independent P. falciparum. Conclusions: S. mansoni infection is a major contributor of a reduced effective T helper immune response against P. falciparum in P. falciparum and S. mansoni co-infection.
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    Translational Research in Uganda: Linking Basic Science to Bedside Medicine in a Resource Limited Setting
    (Journal of translational medicine, 2021) Kwizera, Richard; Mande, Emmanuel; Omali, Denis; Okurut, Samuel; Nabweyambo, Sheila; Nabatanzi, Rose; Nakanjako, Damalie; Meya, David B.
    Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research. In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development. Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care.
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    Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda
    (Frontiers in immunology, 2021) Ssekamatte, Phillip; Nakibuule, Marjorie; Nabatanzi, Rose; Egesa, Moses; Musubika, Carol; Bbuye, Mudarshiru; Hepworth, Matthew R.; Biraro, Irene Andia
    Type 2 diabetes mellitus (T2DM) is a major risk factor for the acquisition of latent tuberculosis (TB) infection (LTBI) and development of active tuberculosis (ATB), although the immunological basis for this susceptibility remains poorly characterised. Innate lymphoid cells (ILCs) immune responses to TB infection in T2DM comorbidity is anticipated to be reduced. We compared ILC responses (frequency and cytokine production) among adult patients with LTBI and T2DM to patients (13) with LTBI only (14), T2DM only (10) and healthy controls (11). Using flow cytometry, ILC phenotypes were categorised based on (Lin−CD127+CD161+) markers into three types: ILC1 (Lin−CD127+CD161+CRTH2-CD117−); ILC2 (Lin−CD127+CD161+CRTH2+) and ILC3 (Lin−CD127+CD161+CRTH2−NKp44+/−CD117+). ILC responses were determined using cytokine production by measuring percentage expression of interferon-gamma (IFN-γ) for ILC1, interleukin (IL)-13 for ILC2, and IL-22 for ILC3. Glycaemic control among T2DM patients was measured using glycated haemoglobin (HbA1c) levels. Data were analysed using FlowJo version 10.7.1, and GraphPad Prism version 8.3. Compared to healthy controls, patients with LTBI and T2DM had reduced frequencies of ILC2 and ILC3 respectively (median (IQR): 0.01 (0.005-0.04) and 0.002 (IQR; 0.002-0.007) and not ILC1 (0.04 (0.02-0.09) as expected. They also had increased production of IFN-γ [median (IQR): 17.1 (5.6-24.9)], but decreased production of IL-13 [19.6 (12.3-35.1)]. We however found that patients with T2DM had lower ILC cytokine responses in general but more marked for IL-22 production (median (IQR): IFN-γ 9.3 (4.8-22.6); IL-13 22.2 (14.7-39.7); IL-22 0.7 (IQR; 0.1-2.1) p-value 0.02), which highlights the immune suppression status of T2DM. We also found that poor glycaemic control altered ILC immune responses. This study demonstrates that LTBI and T2DM, and T2DM were associated with slight alterations of ILC immune responses. Poor T2DM control also slightly altered these ILC immune responses. Further studies are required to assess if these responses recover after treatment of either TB or T2DM.