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Purpose: CD4+ T-lymphocytopenia is a risk for tuberculosis (TB) infection, reactivation and severe disease. We sought to determine the prevalence and predictors of CD4 T-lymphocytopenia among HIV-negative patients with bacteriologically confirmed TB in Uganda. Patients and Methods: Eligible participants were adult HIV-negative patients with bacteriologically confirmed TB at the National TB Treatment Centre in Uganda. CD4+ and CD8+ T-lymphocyte counts were determined by flow cytometry. We defined CD4+ T-lymphocytopenia as a CD4+ T-lymphocyte count of <418 cells/mm 3 as per the population estimate for Ugandans. We performed logistic regression analysis to determine predictors of CD4+ T-lymphocytopenia. Results: We enrolled 216 participants whose mean age (standard deviation (±SD)) was 32.5 (±12.1) years, of whom 146 (67.6%) were males. The prevalence of CD4+ T-lymphocytopenia was 25% (54/216) (95% confidence interval (CI): 19.6-31.2%). Patients with anaemia (adjusted odds ratio (aOR): 3.83, 95% CI: 1.59-9.23, p = 0.003), weight loss (aOR: 3.61, 95% CI: 1.07-12.23, p = 0.039) and a low CD8+ T-cell count (aOR: 6.10, 95% CI: 2.68-13.89, p < 0.001) were more likely to have CD4+ T-lymphocytopenia while those with monocytosis (aOR: 0.35, 95% CI: 0.14-0.89, p = 0.028) were less likely to have CD4+ T-lymphocytopenia. Conclusion: There was a high prevalence of CD4+ T-lymphocytopenia among HIVnegative TB patients. Patients with weight loss, anaemia and a low CD8+ count were more likely to have CD4+ T-lymphocytopenia while those with monocytosis were less likely to have CD4+ lymphocytopenia. The findings suggest that CD4+ lymphocytopenia is indicative of severe disease and globally impaired cell-mediated immune responses against TB.

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. HIV and tuberculosis (TB) interact at an epidemiological, clinical, cellular, and molecular level to create a coepidemic 1. In 2018, HIV contributed 251,000 of the 1.2 million TB deaths while TB was the leading cause of death among HIV positive individuals 2,3. Notwithstanding, an estimated 3 million TB cases were missed in 2018 and only 79% of HIV-positive individuals knew their HIV status 2,3. To increase the detection of TB and HIV, it is important to target high risk and vulnerable populations through active community based screening strategies 4-6. Slum dwellers have a higher risk for HIV, TB and HIV/TB co-infection than the national averages 7,8. However, slum dwellers are less likely to utilise health services for HIV and TB diagnosis and have a low level of knowledge regarding prevention strategies for either disease 9,10. The low utilisation is partly attributed to the perceived poor quality of services at public facilities and thus high risk groups are not covered by facility based screening strategies 11,12. Within slum settlements, bars and social drinking places carry the highest risk for TB transmission than other social gathering places such as churches, clinics, hospitals, taxis, community halls, schools, and supermarkets 13-16. As such, bars and social alcohol drinking groups are avenues for TB transmission to bar customers, employees and neighbours, and they propagate outbreaks from an index case 17-21. Moreover, alcohol consumption is an established risk factor for tuberculosis in a dose dependent fashion, and exacerbates TB infection by blunting CD4 and CD8 T-lymphocyte cellular responses 22,23 .

Background. Rifampicin resistance (RR) is associated with mortality among tuberculosis (TB) patients coinfected with HIV. We compared the prevalence of RR among TB patients with and without HIV coinfection at the National Tuberculosis Treatment Center (NTTC) in Uganda, a TB/HIV high burdened country. We further determined associations of RR among TB/HIV-coinfected patients. Methods. In this secondary analysis, we included adult (≥18 years) bacteriologically confirmed TB patients that were enrolled in a cross-sectional study at the NTTC in Uganda between August 2017 and March 2018. TB, RR, and bacillary load were confirmed by the Xpert® MTB/RIF assay in the primary study. A very low bacillary load was defined as a cycle threshold value of >28. We compared the prevalence of RR among TB patients with and without HIV coinfection using Pearson’s chi-square test. We performed logistic regression analysis to determine associations of RR among TB/HIV-coinfected patients. Results. Of the 303 patients, 182 (60.1%) were male, 111 (36.6%) had TB/HIV coinfection, and the median (interquartile range) age was 31 (25-39) years. RR was found among 58 (19.1%) patients. The prevalence of RR was 32.4% (36/111) (95% confidence interval (CI): 24-42) among TB/HIV-coinfected patients compared to 11.5% (22/192) (95% CI: 7–17) among HIV-negative TB patients (p<0.001). Among TB/HIV-coinfected patients, those with RR were more likely to be rural residents (adjusted odds ratio (aOR): 5.24, 95% CI: 1.51–18.21, p=0.009) and have a very low bacillary load (aOR: 13.52, 95% CI: 3.15–58.08, p<0.001). Conclusion. There was a high prevalence of RR among TB/HIV-coinfected patients. RR was associated with rural residence and having a very low bacillary load among TB/HIV-coinfected patients. The findings highlight a need for universal access to drug susceptibility testing among TB/HIV-coinfected patients, especially in rural settings.

Background There is need for simple, cost effective and widely available point of care tests for low level health facilities in developing countries to screen for drug resistant tuberculosis (TB) after bacteriological confirmation of TB by smear microscopy. We evaluated the sensitivity and specificity of the mean corpuscular volume (MCV) and CD4/CD8 ratio in discriminating between rifampicin resistant (RR-TB) and rifampicin sensitive (RS-TB) tuberculosis. Methods We performed a secondary analysis of data from a cross sectional study that enrolled adult participants with bacteriologically confirmed pulmonary TB at a national tuberculosis treatment center in Uganda. Blood samples were tested for CD4 and CD8 cell counts, HIV serology and a full hemogram. Rifampicin sensitivity and the bacillary load grade were determined by Xpert MTB/RIF®. Fifty-five participants that had RR-TB (cases) were matched with 110 participants that had RS-TB (controls) for age, sex and HIV status in a ratio of 1:2 respectively. Sensitivity (Se), specificity (Sp), area under curve (AUC) analysis and determination of optimal cut-offs were performed using receiver operating characteristic curves. Results Cases differed from controls with respect to residence (p = 0.031), bacillary load grade (p < 0.010) and MCV (p = 0.021). The Se, Sp and AUC of the MCV (cut-off of > 74.6 femtolitres (fl)) were 88.9%, 34% and 0.607 (p = 0.021) respectively for RR-TB. Among HIV positive participants, the respective Se, Sp and AUC of the MCV for RR-TB (cut-off of > 72.5 fl) were 97.2%, 22.2% and 0.608 (p = 0.061). The respective Se, Sp and AUC of the CD4/CD8 ratio (cut-off of > 0.40) were 67.3%, 50.0% and 0.559 (p = 0.199) on the overall and 54.1%, 71.6% and 0.628 (p = 0.024) among the HIV positive participants for RR-TB. Conclusion The MCV had a high sensitivity but very low specificity for RR-TB. The CD4/CD8 ratio had a low sensitivity and specificity for RR-TB among HIV positive individuals. The utility of either test is low due to low diagnostic accuracy.

If we are to break new grounds in TB research, we need to have a complete understanding of what is occurring at the site of infection in humans. Postmortem studies give us an opportunity compare involved and uninvolved tissues, in diseased and non-diseased tissues within the same individual. We examined the feasibility of carrying out a postmortem study in Mulago and Kiruddu National Referral Hospitals in Uganda, to determine whether we could use immune cells collected postmortem for immunological studies. We report that we can consent the Next-of-Kin, perform postmortem procedures and process tissues within 8 hours. Immune cells remain viable and functional up to 14 hours after death. We found subtle differences in T cell subsets within TB groups. Depletion of CD4 CD69+CD103+ depletion in lungs and BAL which is associated with HIV whereas CD8 CD69+CD103- depletion in BAL was associated with TB. Our data show overall changes Tissue Resident Memory T cells within, and between, TB-infected and TB-uninfected human lungs.