Browsing by Author "Nabwana, Martin"

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    Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1–Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda
    (JBMR plus, 2021) Matovu, Flavia Kiweewa; Nabwana, Martin; Kiwanuka, Noah; Scholes, Delia; Isingel, Esther; Nolan, Monica L; Fowler, Mary G; Musoke, Philippa; Pettifor, John M; Brown, Todd T; Beksinska, Mags E
    Most studies evaluating BMD in human immunodeficiency virus (HIV)-infected populations have focused on antiretroviral therapy (ART)-experienced patients. In this study, the association between HIV-1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV-1–infected women in a resource-limited setting was assessed before long-term exposure to ART. The data were then compared with that of the 2005–2008 United States National Health and Nutrition Examination Survey data for non-Hispanic White and Black women. Women aged 18–35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV-1 status and DMPA use: (i) HIV-1–infected current DMPA users, (ii) HIV-1–infected previous DMPA users, (iii) HIV-1–infected nonhormonal-contraceptive users, and (iv) HIV-uninfected nonhormonal-contraceptive users. All HIV-1– infected women reported being ART-naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV-1 and/or DMPA and BMD Z-scores. Baseline data were analyzed for 452 HIV-1–infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV-1– uninfected nonhormonal-contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12-48]. A higher proportion of HIV-1–infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z-score ≤−2 at any of the three sites) compared with agematched HIV-1–uninfected women (2.9%). HIV-1 infection and DMPA use were independently associated with significantly lower mean BMD Z-scores at all sites, with the greatest difference being among HIV-1–infected current DMPA users (5.6%–8.0%) versus uninfected nonhormonal users. Compared with non-Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV-1–infected women in resource-limited settings.
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    Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda
    (BMC Cardiovascular Disorders, 2022) Baruch Baluku, Joseph; Nabwana, Martin; Nalunjogi, Joanitah; Muttamba, Winters; Mubangizi, Ivan; Nakiyingi, Lydia; Ssengooba, Willy; Olum, Ronald; Bongomin, Felix; Andia-Biraro, Irene; Worodria, William
    Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. Methods In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. Results Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4–69.1), hypertension (40.6%; 33.8–47.9), central obesity (39.3%; 32.9–46.1), smoking (36.3%; 30.1–43.1), high BMI (8.0%; 5.0–12.8) and DM (6.5%; 3.7–11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06–1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14– 3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21–0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00–1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00–1.06). Conclusion There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.
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    Cigarette Smoking is Associated with an Increase in Blood Monocytes in People with Tuberculosis: a cross-sectional study.
    (Medicine, 2022) Baluku, Joseph Baruch; Nabwana, Martin; Kansiime, Grace; Nuwagira, Edwin
    The effect of smoking on immune responses in people with tuberculosis (TB) is not well elucidated. We aimed to compare peripheral blood counts of CD4+ and CD87 + T-lymphocytes, monocytes, and neutrophils and the CD4:CD8 ratio in TB patients with and without history of cigarette smoking. We further determined factors associated with current smoking. Participants with TB were consecutively enrolled in a cross-sectional study at a national TB treatment center in Uganda in 2018. We compared cell counts and the CD4:CD8 ratio using the median test among never smokers, past smokers (>6 months ago) and current smokers (≤6 months). Factors associated with current smoking were determined using logistic regression. A post hoc analysis for factors associated with an increase in the monocytes was also performed. Of 363 participants, there were 258 (71.1%) never smokers, 50 (13.8%) past smokers, and 55 (15.2%) current smokers. Most current smokers (49.1%) had a high sputum mycobacterial load. They also had the lowest body mass index and the highest axillary temperature. The median (interquartile range [IQR]) monocyte count among current smokers was 815 (540–1425) cells/mm3 and was significantly higher than that among past smokers (610 (350–900) cells/mm3, P = .017) and never smokers (560 [400–800] cells/mm3, P = .001). The monocyte counts positively correlated with the number of cigarettes smoked per day among current smokers (R = 0.43, P = .006). Current smokers also had higher neutrophil and CD4+ T-cell counts than never smokers. In a multivariable logistic regression model, an increase in the monocyte count was associated with current cigarette smoking (adjusted odds ratio [aOR] = 4.82, 95% confidence interval 1.61–14.39, P = .005). Similarly, current cigarette smoking was independently associated with an increase in the monocyte count (aOR = 1.80, 95% CI 1.39–2.32, P < .001). Cigarette smoking is associated with an increase in the blood monocytes in people with TB in a dose- and time-dependent manner. Further, current smoking is associated with an increase in neutrophils and CD4+ T-lymphocytes. The findings suggest that current smokers have systemic inflammation that is not necessarily beneficial to TB control in TB patients.
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    Prevalence of Intestinal Helminth Coinfection in Drug-Resistant Tuberculosis in Uganda
    (Open Forum Infectious Diseases, 2022) Baluku, Joseph Baruch; Nakazibwe, Bridget; Wasswa, Amir; Naloka, Joshua; Ntambi, Samuel; Waiswa, Damalie; Okwir, Mark; Nabwana, Martin; Bongomin, Felix; Katuramu, Richard; Nuwagira, Edwin; Ntabadde, Kauthrah; Katongole, Paul; Senyimba, Catherine; Andia-Biraro, Irene
    Although a third of people with tuberculosis (TB) are estimated to be coinfected with helminths, the prevalence is largely unknown among people with drug-resistant TB (DR-TB). We determined the prevalence of helminth coinfection among people with DR-TB in Uganda. In a multicenter, cross-sectional study, eligible Ugandan adults with confirmed DR-TB were consecutively enrolled between July to December 2021 at 4 treatment centers. Sociodemographic data were collected using a questionnaire. Participants underwent anthropometric and blood pressure measurements, and blood samples were evaluated for random blood glucose, glycated hemoglobin, nonfasting lipid profile, human immunodeficiency virus (HIV) infection, and a complete blood count. Fresh stool samples were evaluated for adult worms, eggs, and larvae using direct microscopy after Kato-Katz concentration techniques. Of 212 participants, 156 (73.6%) were male, 118 (55.7%) had HIV, and 3 (2.8%) had malaria coinfection. The prevalence of intestinal helminth coinfection was 4.7% (10/212) (95% confidence interval, 2.6%–8.6%). The frequency of helminth infections was Ancylostoma duodenale (n = 4), Schistosoma mansoni (n = 2), Enterobius vermicularis (n = 2), Ascaris lumbricoides (n = 1), and Trichuris trichiura (n = 1). The prevalence of helminth coinfection was low among people with DR-TB. More studies are needed to determine the clinical relevance of helminth/DR-TB coinfection.
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    Quantitative expression of estrogen, progesterone and human epidermal growth factor receptor-2 and their correlation with immunohistochemistry in breast cancer at Uganda Cancer Institute
    (Public Library of Science, 2025-01) Wannume, Henry; Niyonzima, Nixon; Kalungi, Sam; Okuni, Julius Boniface; Okecha, Tonny; Kakungulu, Edward; Kiwuwa, Steven Mpungu; Waiswa, Geoffrey; Kadhumbula, Sylvester; Namayanja, Monica; Nabwana, Martin; Orem, Jackson
    The detection of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human epidermal growth factor receptor 2 (HER-2) is important for the stratification of breast cancer and the selection of therapeutic modalities. This study aimed to determine the quantitative expression of ER, PR and HER-2 using Immunohistochemistry and their correlation with quantitative baseline Ct values measured using Quantitative Polymerase Chain Reaction (PCR). This study also assessed the use of fresh breast tissue biopsies preserved in RNAlater solution in the quantitative detection of these receptors using PCR technique. The study evaluated 20 matched formalin fixed paraffin embedded and RNAlater preserved samples for ER, PR, and HER-2 using IHC and quantitative PCR technique. One portion of the breast tissue biopsy was fixed immediately in 10% neutral buffered formalin and another was preserved in RNAlater. After the histological confirmation of breast cancer by the H&E technique, formalin fixed paraffin embedded tissues (FFPE)—positive cases were matched with their corresponding RNAlater samples for IHC and qPCR. The extracted RNA was quantified using Nanodrop technology, resulting into complementary DNA. ER and PR using IHC were expressed in 60% (n = 12) of the study samples and were negative in 40% (n = 8) of samples. HER-2 was negative in 70% (n = 14) of study samples, 25% (n = 5) positive, and 5% (n = 1) equivocal. With the quantitative expression of ER, PR, and HER-2 being reported in the IHC triple—negative breast cancer cases. The mean Ct values for the hormonal receptors correlated with what has been previously studied with ER at 19.631, PR at 25.410 and HER-2 at 25.695. There was no statistically significant difference between the mean Ct values of RNAlater and FFPE with their P-values being 0.9919, 0.0896 and < 0.0001 for ER, PR, and HER-2 respectively. P-values; 0.9919 and 0.0896 for ER and PR respectively being greater than 0.05 it’s a borderline significance although HER-2 had a statistical significance. With a concordance in the detection of these breast cancer hormonal receptors, qPCR can be used in our setting considering the delays that may be associated in following the samples through IHC processing.
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    A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda
    (BioMed Central, 2024-05) Okello, Clement D; Orem, Jackson; Nabwana, Martin; Kiwanuka, Noah; Shih, Andrew W; Heddle, Nancy; Mayanja-Kizza, Harriet
    Abstract BACKGROUNDMortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting.METHODSAn open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality.RESULTSThere were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality.CONCLUSIONSThe study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed.TRIAL REGISTRATIONPan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023. MEDLINE - Academic
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    Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study
    (Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, 2021) Baluku, Joseph Baruch; Nakazibwe, Bridget; Naloka, Joshua; Nabwana, Martin; Mwanja, Sarah; Mulwana, Rose; Sempiira, Mike; Nassozi, Sylvia; Babirye, Febronius; Namugenyi, Carol; Ntambi, Samuel; Namiiro, Sharon; Bongomin, Felix; Katuramu, Richard; Andia-Biraro, Irene; Worodria, William
    Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR – TB). This study aimed at determining the treatment outcomes of DR – TB patients with poor prognostic indicators in Uganda. We reviewed treatment records of DR – TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR – TB, a treatment outcome in 2014–2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co-infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, cigarette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluoroquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. Of 1122 DR – TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0–45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39–0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12–0.26, p < 0.001) and severe anaemia (OR: 0.09, 95% CI 0.05–0.17, p < 0.001) and previous exposure to SLDs (OR: 0.19, 95% CI 0.08–0.48, p < 0.001) predicted lower odds of treatment success while the number of poor prognostic indicators (HR: 1.62, 95% CI 1.30–2.01, p < 0.001), for every additional poor prognostic indicator) predicted mortality. Among DR – TB patients with multiple poor prognostic indicators, mortality was the most frequent unsuccessful outcomes. Every additional poor prognostic indicator increased the risk of mortality while anaemia and previous exposure to SLDs were associated with lower odds of treatment success. The management of anaemia among DR – TB patients needs to be evaluated by prospective studies. DR – TB programs should also optimise DR – TB treatment the first time it is initiated.