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Joseph Baruch Baluku,1,2 Sharon Namiiro,2 Martin Nabwana,3 Winters Muttamba,2 Bruce Kirenga2 1Division of Pulmonology, Kiruddu National Referral Hospital, Kampala, Uganda; 2Research and Innovation Department, Makerere University Lung Institute, Kampala, Uganda; 3Quality Management Division, Makerere University – Johns Hopkins University Research Collaboration, Kampala, UgandaCorrespondence: Joseph Baruch BalukuKiruddu National Referral Hospital, Kampala, UgandaTel +256706327972Email bbjoe18@gmail.comBackground: Undernutrition is associated with unfavourable treatment outcomes among people with drug-resistant tuberculosis (DRTB). Factors influencing the treatment outcomes among undernourished people with DRTB are not well characterised. The aim of this study was to determine factors associated with treatment success among undernourished people with DRTB in Uganda.Methods: We analysed data from a retrospective cohort of people with DRTB from 16 treatment sites in Uganda. We included participants with a pre-treatment body mass index (BMI) of < 18.5 kilograms/meters2 (kg/m2). Participants were categorised as having mild (BMI of 18.5– 17 kg/m2), moderate (BMI of 16.9– 16.0 kg/m2) or severe (BMI of < 16.0 kg/m2) undernutrition. We performed logistic regression analysis to determine factors associated with treatment success.Results: Among 473 people with DRTB, 276 (58.4%) were undernourished (BMI < 18.5 Kg/m2) and were included in the study. Of these, 92 (33.3%) had mild, 69 (25.0%) had moderate and 115 (41.7%) had severe undernutrition. The overall treatment success rate (TSR) for the undernourished was 71.4% (n = 197). Although the TSR was similar among participants with mild (71.7%), moderate (78.3%) and severe (67.0%) undernutrition (p = 0.258), all treatment failure cases (n =6) were among participants with severe undernutrition (p = 0.010). Cigarette smoking (odds ratio (OR) = 0.19, 95% CI 0.07– 0.47, p < 0.001), urban residence (OR = 0.31, 95% CI 0.14– 0.70, p = 0.005) and moderate (OR = 0.14, 95% CI 0.06– 0.35, p < 0.001) and severe anaemia (OR = 0.06, 95% CI 0.01– 0.29, p = 0.001) were associated with lower odds of treatment success.Conclusion: Most undernourished people with DRTB have severe undernutrition. Smoking and anaemia are modifiable factors which upon appropriate intervention could improve treatment success. The effect of urban residence on the TSR needs to be evaluated further.Keywords: MDR TB, undernutrition, malnutrition, drug resistant, tuberculosis, anaemia

Introduction: In-hospital mortality rates for tuberculosis (TB) patients are high within the first seven days of admission. This study sought to identify predictors of early inpatient mortality and assess the performance of a predictive score for early mortality in a Ugandan tertiary hospital., Materials and Methods: A case-control study was conducted at Kiruddu National Referral Hospital in Kampala, Uganda. Cases included patients admitted with TB who died within seven days of admission, while controls survived beyond this period. Logistic regression was utilized to identify early mortality predictors. The performance of an adapted predictive score ( PROS score) was evaluated, assigning scores based on the following criteria: P ulse rate >100 beats/min (1 point), R espiratory rate >20 breaths/min (2 points), O xygen saturation <92 % (4 points), and S ystolic blood pressure <90 mmHg (2 points)., Results: Of 602 hospitalized TB patients, 187 (31.0 %) died during admission. Among these, 78 (41.7 %) died within seven days. Wasting (adjusted odds ratio [aOR] = 5.76, 95 % confidence interval [CI] 2.12-15.63, p = 0.001) and respiratory rate >20 breaths/min (aOR = 2.89, 95 % CI 1.19-7.00, p = 0.019) predicted early mortality. PROS score of ≥1 demonstrated a sensitivity of 87.8 % and negative predictive value of 90.0 %. The ultimate TB treatment success rate of all hospitalized patients (n = 599) was 47.4 % with 275 (45.9 %) dying during TB treatment., Conclusion: Early and long term mortality rates among hospitalized TB patients are high. Wasting and tachypnea predict early inpatient mortality. The PROS score could be useful in ruling out low-risk patients in low-resource settings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objectives: To determine the incidence of mortality and its predictors among pulmonary tuberculosis (PTB) survivors treated at a rural Ugandan tertiary hospital., Methods: We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the World Health Organisation's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1000 population, crude all-cause mortality rate per 1000 person-years, and median years of potential life lost for deceased individuals. Using Cox proportional hazard models, we investigated predictors of mortality., Results: Of 334 PTB survivors enrolled, 38 (11.4%) had died. The cumulative incidence of all-cause mortality was 113.7 per 1000 population, and the crude all-cause mortality rate was 28.5 per 1000 person-years. The median years of potential life lost for deceased individuals was 23.8 years (IQR: 9.6-32.8). Hospitalization (adjusted hazard ratio (aHR): 4.3, 95% CI: 1.1-16.6) and unemployment (aHR: 7.04, 95% CI: 1.5-31.6) at TB treatment initiation predicted mortality., Conclusion: PTB survivors experience post high mortality rates after TB cure. Survivors who were hospitalized and unemployed at treatment initiation were more likely to die after cure. Social protection measures and long-term follow-up of previously hospitalized patients could improve the long-term survival of TB survivors., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) demonstrate good diagnostic accuracy in distinguishing lung cancer patients from healthy individuals, primarily in HIV-negative populations. We determined the sensitivity (Se), specificity (Sp), and area under the curve (AUC) of the NLR and PLR in discriminating between people living with HIV (PLWH) with and without lung cancer., Methods: This is a comparative analysis of secondary data. Cases were PLWH with lung cancer from a retrospective cohort treated at the Uganda Cancer Institute. Controls were unmatched PLWH without lung cancer who were randomly selected from three HIV clinics in Uganda. Se, Sp, and AUC analysis and determination of optimal cutoffs were performed using receiver operating characteristic (ROC) curves., Results: Of 115 PLWH (18 cases and 97 controls), 83 (72.2%) were female, 110 (95.7) were on ART, and the median (IQR) age was 46 (38-51) years. The median (IQR) NLR was higher among cases than controls (3.53 (3.14-7.71) vs. 0.92 (0.67-1.09), p   < 0.001). Similarly, the PLR was higher among cases than controls (237.5 (177.8-361.6) vs. 123.6 (100.6-155.4), p =0.001). At a cutoff of 2.44, the respective Se, Sp, and AUC of the NLR were 87.5% (95% CI: 61.7%-98.4%), 100% (95% CI: 96.2%-100%), and 0.94 (95% CI: 0.85-1.00, p   < 0.001). Similarly, the respective Se, Sp, and AUC for the PLR were 75% (95% CI: 47.6%-92.7%), 87.2% (95% CI: 78.8%-93.2%), and 0.81 (95% CI: 0.70-0.93, p   < 0.001) at a cutoff of 196.3., Conclusion: The NLR and PLR discriminated PLWH with and without lung cancer and could be useful in PLWH with respiratory symptoms in whom lung cancer can easily be misdiagnosed as other lung pathology., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Joseph Baruch Baluku et al.)

Objective: To compare cytogenetic abnormalities among people living with HIV (PLWH) with and without previous exposure to Mycobacterium tuberculosis (Mtb) (both latent tuberculosis infection [LTBI] and active tuberculosis [TB])., Methods: Adult PLWH (≥18 years) were randomly selected at three HIV clinics in Uganda. Previous active TB was confirmed in the clinics' TB records. LTBI was defined as a positive QuantiFERON-TB Gold Plus assay. Participants' buccal mucosal exfoliated cells were examined (per 2000 cells) using the buccal micronucleus assay for chromosomal aberrations (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal differentiated cells and basal cell frequency) and/or cell death (condensed chromatin, karyorrhexis, pyknotic and karyolytic cells)., Results: Among 97 PLWH, 42 (43.3%) had exposure to Mtb;16 had previous successfully treated active TB and 26 had LTBI. PLWH with exposure to Mtb had a higher median number of normal differentiated cells (1806.5 [1757.0 - 1842.0] vs. 1784.0 [1732.0 - 1843.0], p = 0.031) and fewer karyorrhectic cells (12.0 [9.0 - 29.0] vs. 18.0 [11.0 - 30.0], p = 0.048) than those without. PLWH with LTBI had fewer karyorrhectic cells than those without (11.5 [8.0 - 29.0] vs. 18.0 [11 - 30], p = 0.006)., Conclusion: We hypothesized that previous exposure to Mtb is associated with cytogenetic damage among PLWH. We found that exposure to Mtb is associated with more normal differentiated cells and less frequent karyorrhexis (a feature of apoptosis). It is unclear whether this increases the propensity for tumorigenesis., Competing Interests: Declaration of Competing Interest The authors declare no relevant conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: There are few reports on lung cancer among people with HIV (PWH) in Sub-Saharan Africa. In this report, we describe a cohort of PWH and lung cancer at the Uganda Cancer Institute., Methods: This retrospective cohort of PWH and lung cancer was managed at the Uganda Cancer Institute between 2008 and 2018. Sociodemographic and clinical data were abstracted from the patient charts. The median survival from diagnosis to death, loss-to-follow up or 31st December 2018, was estimated., Results: There were 18 people with HIV and lung cancer. The median (interquartile range, IQR) age was 49.5 (38.8-56.0) years, 11 (61.1%) were women and 5 (27.8%) were smokers. Of the 18 PWH, 13 (72.2%) were on antiretroviral therapy and the median (IQR) CD4 count (n = 13) was 380 (243.5-595) cells per mm 3 . Difficulty in breathing (88.9%), chest pain (78.6%, n = 11), cough (76.5%, n = 17) and weight loss (72.2%) were the commonest symptoms while pleural effusions were observed in 12 (66.7%). In this cohort, 8 (44.4%) were presumptively treated for tuberculosis before the diagnosis of lung cancer. Seven (38.9%) had an Eastern Cooperative Oncology Group performance status of 3. Non-small cell lung cancer was the predominant histological type observed in 17 (94.4%) of whom 14 (82.4%) had adenocarcinoma. Majority of PWH had stage IV disease (88.9%). The median (IQR) survival was 3.3 (1.1-13.2) months and all were either dead (72.2%) or lost-to-follow up (27.8%) at five years from diagnosis., Conclusion: People with HIV and lung cancer in Uganda report low rates of smoking, present with advanced disease and post very poor survival rates. There is need for biomarkers for early detection of lung cancer in HIV., (© 2022. The Author(s).)

Information on microbiota dynamics in pulmonary tuberculosis (TB) in Africa is scarce. Here, we sequenced sputa from 120 treatment-naïve TB patients in Uganda, and investigated changes in microbiota of 30 patients with treatment-response follow-up samples. Overall, HIV-status and anti-TB treatment were associated with microbial structural and abundance changes. The predominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria and Actinobacteria, accounting for nearly 95% of the sputum microbiota composition; the predominant genera across time were Prevotella, Streptococcus, Veillonella, Haemophilus, Neisseria, Alloprevotella, Porphyromonas, Fusobacterium, Gemella, and Rothia. Treatment-response follow-up at month 2 was characterized by a reduction in abundance of Mycobacterium and Fretibacterium, and an increase in Ruminococcus and Peptococcus; month 5 was characterized by a reduction in Tannerella and Fusobacterium, and an increase in members of the family Neisseriaceae. The microbiota core comprised of 44 genera that were stable during treatment. Hierarchical clustering of this core's abundance distinctly separated baseline (month 0) samples from treatment follow-up samples (months 2/5). We also observed a reduction in microbial diversity with 9.1% (CI 6-14%) of the structural variation attributed to HIV-status and anti-TB treatment. Our findings show discernible microbiota signals associated with treatment with potential to inform anti-TB treatment response monitoring., (© 2021. The Author(s).)

The study aim was to determine the association of a one United States dollar (USD) dollar incentive and tuberculosis (TB) treatment outcomes among people with TB receiving treatment at a rural hospital in Uganda under programmatic settings. We conducted a quasi-experiment in which people with TB were randomised (1:1 ratio) to receive either a one USD incentive at months 0, 2, 5 and 6 (Dollar arm) or routine care (Routine arm). A second control group (Retrospective controls) consisted of participants who had a treatment outcome in the preceding 6 months. Treatment outcomes were compared between the intervention and control groups using Pearson's chi-square and Fisher's exact tests. The association between the incentive and treatment outcomes was determined using Poisson regression analysis with robust variances. Between November 2018 and October 2019, we enrolled 180 participants (60 in the Dollar arm and 120 in the Control group). TB cure (33.3% vs. 20.8%, p = 0.068) and treatment success (70.0% vs. 59.2% p = 0.156) were higher in the Dollar arm than the Control group, while loss-to-follow-up was lower in the Dollar arm (10.0% vs. 20.8% p = 0.070). Participants in the Dollar arm were more likely to be cured (adjusted incidence rate ratio (aIRR): 1.59, 95% CI 1.04-2.44, p = 0.032) and less likely to be lost to follow-up (aIRR: 0.44, 95% CI 0.20-0.96, p = 0.040). A one-dollar incentive was associated with higher TB cure and lower loss-to-follow-up among people with TB in rural Uganda., (© 2021. The Author(s).)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2021 The Author(s).)

Individuals found at bars in slums have several risk factors for HIV and tuberculosis (TB). To determine the prevalence of HIV and TB among individuals found at bars in slums of Kampala, Uganda, we enrolled adults found at bars that provided written informed consent. Individuals with alcohol intoxication were excluded. We performed HIV testing using immunochromatographic antibody tests (Alere Determine HIV-1/2 and Chembio HIV 1/2 STAT-PAK). TB was confirmed using the Xpert MTB/RIF Ultra assay, performed on single spot sputum samples. We enrolled 272 participants from 42 bars in 5 slums. The prevalence of HIV and TB was 11.4% (95% CI 8.1-15.8) and 15 (95% CI 6-39) per 1,000 population respectively. Predictors of HIV were female sex (aOR 5.87, 95% CI 2.05-16.83), current cigarette smoking (aOR 3.23, 95% CI 1.02-10.26), history of TB treatment (aOR 10.19, 95% CI 3.17-32.82) and CAGE scores of 2-3 (aOR 3.90, 95% CI 1.11-13.70) and 4 (aOR 4.77, 95% CI 1.07-21.35). The prevalence of HIV and TB was twice and four times the national averages respectively. These findings highlight the need for concurrent programmatic screening for both HIV and TB among high risk populations in slums.