Browsing by Author "Bbuye, Mudarshiru"
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Item Association of circulating serum free bioavailable and total vitamin D with cathelicidin levels among active TB patients and household contacts(Research Square, 2022) Acen, Ester Lilian; Worodria, William; Kateete, David Patrick; Olum, Ronald; Joloba, Moses L.; Akintola, Ashraf; Bbuye, Mudarshiru; Biraro Andia, IreneThe free hormone hypothesis postulates that the estimation of free circulating 25(OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D levels because it is the fraction involved in biological activities. Studies have shown that cathelicidin inhibits the growth of Mycobacterium Tuberculosis in a vitamin D-dependent manner and therefore adequate vitamin D is required for its expression. The aim of the study was to determine the association between serum-free and bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI and individuals with no TB infection. This was a cross sectional study and free and bioavailable vitamin D and LL-37 levels were measured. 95 specimens were further selected to estimate total vitamin D levels. The median free and bioavailable vitamin D levels of study participants were 3.8 ng/mL. The median LL-37 levels were 318.8 ng/mL. The mean total vitamin D levels were 18.9 ng/mL. Significantly weak inverse associations were found and vitamin D is involved in the regulation of LL-37 expression and low vitamin D levels can alter this relationship. Background Vitamin D deficiency is a prominent risk factor for TB disease worldwide (1–5). Vitamin D can be obtained in two forms, D2 is obtained through diet and D3 is obtained through skin biosynthesis (6). Its main circulating active metabolite 1, 25(OH)D is involved in regulation of antimicrobial activity and therefore important in TB therapy (7). So far, total vitamin D or 25(OH)D has been considered a better index for determining vitamin D status due to its longer half-life (6, 8–11). However, the free hormone hypothesis postulates that the estimation of free circulating 25(OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D levels because it is the fraction involved in biological activities (10, 12–14). Bioavailable 25(OH)D is used to represent free vitamin D and the 10–15% fraction is loosely bound to albumin (8, 15). About 85–90% of total 25(OH)D is bound to VDBP and 10–15% is loosely bound to albumin and a small fraction remains unbound (13, 16). Free 25(OH)D is increased and readily available to cells when DBP levels are at low concentrations Previous studies report that changes in DBP levels and 25(OH)D binding affinity can lead to higher levels of free 25(OH)D, even in the absence of total vitamin D levels (17, 18). According to the Endocrine Society, total vitamin D status is classified into three groups: <20 ng/mL deficient, 21–29 ng/mL deficient, and > 30 ng/mL optimal; or sufficient amounts (19). In vitro and in vivo studies have shown that LL-37 inhibits the growth of MTB in a vitamin D-dependent manner (20, 21). Accordingly, studies have reported that adequate levels of 25(OH)D are required for expression of LL-37(22, 23). According to our systematic review, six studies reported that vitamin D regulates LL-37 expression and that vitamin D deficiency alters this function (24). Because the free fraction of vitamin D, which enters cells to cause biological effects, has not been studied with the LL-37 molecule, we hypothesize that there is no relationship between free and bioavailable vitamin D and total vitamin D with the LL-37 levels among the ATB patients, LTBI and individuals with no TB infection. This study aimed to determine the association between serum-free and bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI and individuals with no TB infection.Item Evaluation of circulating serum cathelicidin levels as a potential biomarker to discriminate between active and latent tuberculosis in Uganda(PloS one, 2022) Acen, Ester Lilian; Kateete, David Patrick; Worodria, William; Olum, Ronald; Joloba, Moses L.; Bbuye, Mudarshiru; Biraro, Irene AndiaTuberculosis remains a major public health problem worldwide accounting for 1.4 million deaths annually. LL-37 is an effector molecule involved in immunity with both antimicrobial and immunomodulatory properties. The purpose of this study was to compare LL-37 circulatory levels among participants with active and latent tuberculosis and to determine its ability to discriminate between the two infectious states. Methods A cross-sectional study was performed among 56 active tuberculosis patients, 49 latent tuberculosis individuals, and 43 individuals without tuberculosis infection. The enzymelinked immunosorbent assay was used to assess LL-37 levels. Data analysis was performed using STATA software and Graph pad Prism version 8. Mann-Whitney U test was used for correlation between variables with two categories and the Kruskal-Wallis test for three or more categories. Results The study had more female participants than males, with similar median ages across the three groups, 29.5, 25.0, and 23.0 years respectively. Active tuberculosis patients had significantly higher LL-37 levels compared to those with latent tuberculosis and without tuberculosis. The median/interquartile ranges were 318.8 ng/ml (157.9–547.1), 242.2 ng/ml (136.2–579.3), 170.9 ng/ml (129.3–228.3); p = 0.002 respectively. Higher LL-37 was found in the male participant with median/interquartile range, 424.8 ng/ml (226.2–666.8) compared to the females 237.7 ng/ml (129.6–466.6); p = 0.045. LL-37 had better discriminatory potential between active tuberculosis and no tuberculosis (AUC = 0.71, sensitivity 71.4% specificity = 69.8%) than with latent tuberculosis (AUC = 0.55, sensitivity = 71.4%, specificity = 44.9%). There was moderate differentiation between latent tuberculosis and no tuberculosis (AUC = 0.63, sensitivity = 44.9% specificity = 90.7%). Conclusion Significantly higher LL-37 levels were observed among active tuberculosis patients than those without tuberculosis infection and were, therefore able to discriminate between active tuberculosis and other tuberculosis infectious states, especially with no tuberculosis. Further assessment of this biomarker as a screening tool to exclude tuberculosis is required.Item Perceptions of Adolescents and Health Workers Towards Adolescents’ TB Diagnosis in Central Uganda: A Cross-Sectional Qualitative Study(Risk Management and Healthcare Policy, 2021) Muttamba, Winters; Bbuye, Mudarshiru; Baruch Baluku, Joseph; Kyaligonza, Stephen; Nalunjogi, Joanitah; Kimuli, Ivan; Kirenga, BrucePrompt diagnosis of TB among adolescents may reduce transmission and improve individual outcomes. However, TB diagnosis in adolescents is challenging. This study sought to understand challenges to adolescent TB diagnosis. We conducted qualitative focus group discussions (FGDs) to explore adolescents’ and health workers’ perspectives on challenges to TB diagnosis among adolescents seeking care at four secondary health care facilities in Uganda. Eight FGDs were conducted: four with 32 adolescents consulting for medical care and four with 34 health workers involved in TB care.Item Risk perception and usage of non-occupational post-exposure prophylaxis among fisherfolk in Ggulwe parish on the shores of Lake Victoria in central Uganda(Frontiers Media S.A., 2023-11) Bahikire, Daraus; Nanyingi, Miisa; Atuhairwe, Christine; Matama, Catherine; Ninsiima, Lesley Rose; Bbuye, MudarshiruAbstract BackgroundThe use of non-occupational post-exposure prophylaxis (nPEP) to prevent HIV acquisition among those exposed as an approach to HIV prevention has expanded in Uganda. Although there are increased efforts to avail nPEP services among most at-risk populations, the usage of nPEP medicines remains low. Therefore, this study examined the risk perception and usage of non-occupational post-exposure prophylaxis (nPEP) among fisherfolk in the Ggulwe fishing parish, Bussi sub-county, Wakiso district.MethodsA cross-sectional study among adults was carried out from October 2020 to January 2021 in Ggulwe parish, Bussi sub-county, Wakiso district, to examine the usage of nPEP and factors influencing the usage. Data were collected using semi-structured questionnaires, and key informants' interviews were conducted among healthcare providers and the local leadership. The quantitative data were summarized using bivariate and multivariate logistic regression, while the qualitative data were analyzed thematically to enrich the quantitative results.ResultsOverall, 248 fisherfolk encountered an event that required the use of nPEP, and of these, 55/248 (22.2%) were able to use nPEP to prevent them from acquiring HIV. The usage of nPEP among adults in the Bussi sub-county, Wakiso district, was associated with not knowing that HIV can be prevented using nPEP medicines (AOR:0.1, 95% CI 0.03–0.36, p < 0.001), lack of knowledge of the existence of nPEP (AOR: 0.3, 95% CI 0.13–0.76, p = 0.01), the perception that nPEP can effectively prevent HIV infection after exposure (AOR 0.0586, 95% CI: 0.0177–0.1944, p < 0.001), and the community's opinion affecting the willingness to take nPEP (AOR 0.1924, 95% CI: 0.0380–0.9727, p = 0.0462).ConclusionThe usage of nPEP among fisherfolk was low (22.2%). The low usage of nPEP was associated with a lack of knowledge and awareness about nPEP. This effort to improve the usage of nPEP should include community sensitization and HIV infection prevention using nPEP to raise awareness about HIV infection exposures and the risk of HIV infection during non-occupational exposures.Item 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 AndiaType 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.