Pulmonary Tuberculosis In Kampala Research Articles

The socioeconomic burden of pediatric tuberculosis and role of child-sensitive social protection

BackgroundHouseholds of children with tuberculosis (TB) experience financial and social hardships, but TB-specific social protection initiatives primarily focus on adults.MethodsWe conducted a single-arm, pilot study of multi-component supportive benefits for children with pulmonary TB in Kampala, Uganda. At diagnosis, participants received in-kind coverage of direct medical costs, a cash transfer, and patient navigation. Caregivers were surveyed before diagnosis and 2 months into TB treatment on social and financial challenges related to their child’s illness, including estimated costs, loss of income and dissaving practices.ResultsWe included 368 children from 321 households. Pre-diagnosis, 80.1% of caregivers reported that their child’s illness negatively impacted household finances, 44.1% of caregivers missed work, and 24% engaged in dissaving practices. Catastrophic costs (> 20% annual income) were experienced by 18.4% (95% CI 13.7–24.0) of households. School disruption was common (25.6%), and 28% of caregivers were concerned their child was falling behind in development. Two months post-diagnosis, 12 households (4.8%) reported being negatively affected by their child’s TB disease (difference -75.2%, 95% CI -81.2 to -69.2, p < 0.001), with limited ongoing loss of income (1.6%) or dissavings practices (0.8%). Catastrophic costs occurred in one household (0.4%) at 2 months post-diagnosis.ConclusionsHouseholds face financial and social challenges prior to a child’s TB diagnosis, and child-sensitive social protection support may mitigate ongoing burden.

Low treatment success rate among previously treated persons with drug-susceptible pulmonary tuberculosis in Kampala, Uganda

RationaleIn 2017, the treatment regimen for previously treated persons with tuberculosis (TB) changed to a shorter regimen that lasts six months and consists of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. Few studies have examined treatment success rate (TSR) among previously treated persons with TB including the associated factors. ObjectiveTo determine TSR and the associated factors among previously treated persons with bacteriologically confirmed pulmonary TB on a six-month treatment regimen in Kampala, Uganda. MethodsWe retrieved data (January 2012 and December 2021) across six TB clinics in the Kampala Metropolitan area for all previously treated persons with bacteriologically confirmed pulmonary TB. TSR was defined as cure or treatment completion. Frequencies and percentages for categorical data, and the mean and standard deviation for numerical data were computed. Multivariable modified Poisson regression analysis was performed to identify factors associated with TSR, reported as adjusted risk ratio (aRR) with a 95% confidence interval (CI). Measurements and main resultsWe enrolled 230 participants with a mean age of 34.8±10.6 years. TSR was 52.2% and was associated with Mycobacterium tuberculosis (MTB) sputum smear load of ≥2+ (1–10 or >10 Acid Fast Bacilli (AFB)/Field) (aRR = 0.51; 95% CI, 0.38–0.68), TB/human immunodeficiency virus (HIV) (aRR = 0.67; 95% CI, 0.51–0.88) or unknown HIV serostatus (aRR = 0.42; 95% CI, 0.26–0.68), and digital community-based directly observed therapy short-course (DOTS) (aRR = 0.42; 95% CI, 0.20–0.88). ConclusionsThe TSR among previously treated persons with bacteriologically confirmed pulmonary TB on a six-month treatment regimen is suboptimal. TSR is less likely for people with TB/HIV co-infection or unknown HIV serostatus, high MTB sputum smear load, and on digital community-based DOTs. We recommend strengthening of TB/HIV collaborative activities and people with TB with high MTB sputum smear load should receive targeted treatment support, and the contextual barriers to digital community DOTS should be addressed.

The transition to Xpert MTB/RIF ultra: diagnostic accuracy for pulmonary tuberculosis in Kampala, Uganda

BackgroundThe World Health Organization (WHO) has endorsed the next-generation Xpert MTB/RIF Ultra (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda.MethodsWe sampled adults referred for Xpert testing at two hospitals and a health center over a 12-month period. We enrolled adults with positive Xpert and a random 1:1 sample with negative Xpert results. Expectorated sputum was collected for Ultra, and for solid and liquid culture testing for Xpert-negative patients. We measured sensitivity and specificity of Ultra overall and by HIV status, prior history of TB, and hospitalization, in reference to Xpert and culture results. We also assessed how classification of results in the new “trace” category affects Ultra accuracy.ResultsAmong 698 participants included, 211 (30%) were HIV-positive and 336 (48%) had TB. The sensitivity of Ultra was 90.5% (95% CI 86.8–93.4) and specificity was 98.1% (95% CI 96.1–99.2). There were no significant differences in sensitivity and specificity by HIV status, prior history of TB or hospitalization. Xpert and Ultra results were concordant in 670 (96%) participants, with Ultra having a small reduction in specificity (difference 1.9, 95% CI 0.2 to 3.6, p=0.01). When “trace” results were considered positive for all patients, sensitivity increased by 2.1% (95% CI 0.3 to 3.9, p=0.01) without a significant reduction in specificity (− 0.8, 95% CI − 0.3 to 2.0, p=0.08).ConclusionsAfter 1 year of implementation, Ultra had similar performance to Xpert. Considering “trace” results to be positive in all patients increased case detection without significant loss of specificity. Longitudinal studies are needed to compare the benefit of greater diagnoses to the cost of overtreatment.

A Prospective Evaluation of Xpert MTB/RIF Ultra for Childhood Pulmonary Tuberculosis in Uganda

Xpert MTB/RIF Ultra (Xpert Ultra) has improved the sensitivity to detect pulmonary tuberculosis (TB) in adults. However, there have been limited prospective evaluations of its diagnostic accuracy in children. We enrolled children undergoing assessment for pulmonary TB in Kampala, Uganda, over a 12-month period. Children received a complete TB evaluation and were classified as Confirmed, Unconfirmed, or Unlikely TB. We calculated the sensitivity and specificity of Xpert Ultra among children with Confirmed vs Unlikely TB. We also determined the diagnostic accuracy with clinical, microbiological, and extended microbiological reference standards (MRSs). Of the 213 children included, 23 (10.8%) had Confirmed TB, 88 (41.3%) had Unconfirmed TB, and 102 (47.9%) had Unlikely TB. The median age was 3.9 years, 13% were HIV-positive, and 61.5% were underweight. Xpert Ultra sensitivity was 69.6% (95% confidence interval [CI]: 47.1-86.8) among children with Confirmed TB and decreased to 23.4% (95% CI: 15.9-32.4) with the clinical reference standard. Specificity was 100% (95% CI: 96.4-100) among children with Unlikely TB and decreased to 94.7% (95% CI: 90.5-97.4) with a MRS. Sensitivity was 52.9% (95% CI: 35.1-70.2) and specificity 95.5% (95% CI: 91.4-98.1) with the extended MRS. Of the 26 positive Xpert Ultra results, 6 (23.1%) were "Trace-positive," with most (5/6) occurring in children with Unconfirmed TB. Xpert Ultra is a useful tool for diagnosing pulmonary TB in children, but there remains a need for more sensitive tests to detect culture-negative TB.

Evaluation of multi-antigen serological screening for active tuberculosis among people living with HIV.

Better triage tests for screening tuberculosis (TB) disease are needed for people living with HIV (PLHIV). We performed the first evaluation of a previously-validated 8-antigen serological panel to screen PLHIV for pulmonary TB in Kampala, Uganda. We selected a random 1:1 sample with and without TB (defined by sputum culture) from a cohort of PLHIV initiating antiretroviral therapy. We used a multiplex microbead immunoassay and an ensemble machine learning classifier to determine the area under the receiver operating characteristic curve (AUC) for Ag85A, Ag85B, Ag85C, Rv0934-P38, Rv3881, Rv3841-BfrB, Rv3873, and Rv2878c. We then assessed the performance with the addition of four TB-specific antigens ESAT-6, CFP-10, Rv1980-MPT64, and Rv2031-HSPX, and every antigen combination. Of 262 participants (median CD4 cell-count 152 cells/μL [IQR 65–279]), 138 (53%) had culture-confirmed TB. The 8-antigen panel had an AUC of 0.53 (95% CI 0.40–0.66), and the additional 4 antigens did not improve performance (AUC 0.51, 95% CI 0.39–0.64). When sensitivity was restricted to ≥90% for the 8- and 12-antigen panel, specificity was 2.2% (95% CI 0–17.7%) and 8.1% (95% CI 0–23.9%), respectively. A three-antigen combination (Rv0934-P38, Ag85A, and Rv2031-HSPX) outperformed both panels, with an AUC of 0.60 (95% CI 0.48–0.73), 90% sensitivity (95% CI 78.2–96.7%) and 29.7% specificity (95% CI 15.9–47%). The multi-antigen panels did not achieve the target accuracy for a TB triage test among PLHIV. We identified a new combination that improved performance for TB screening in an HIV-positive sample compared to an existing serological panel in Uganda, and suggests an approach to identify novel antigen combinations specifically for screening TB in PLHIV.

Evaluation of in-house PCR for diagnosis of smear-negative pulmonary tuberculosis in Kampala, Uganda

BackgroundNucleic acid amplification tests (NAATs) have offered hope for rapid diagnosis of tuberculosis (TB). However, their efficiency with smear-negative samples has not been widely studied in low income settings. Here, we evaluated in-house PCR assay for diagnosis of smear-negative TB using Lowenstein-Jensen (LJ) culture as the baseline test. Two hundred and five pulmonary TB (PTB) suspects with smear-negative sputum samples, admitted on a short stay emergency ward at Mulago Hospital in Kampala, Uganda, were enrolled. Two smear-negative sputum samples were obtained from each PTB suspect and processed simultaneously for identification of MTBC using in-house PCR and LJ culture.ResultsSeventy two PTB suspects (35%, 72/205) were LJ culture positive while 128 (62.4%, 128/205) were PCR-positive. The sensitivity and specificity of in-house PCR for diagnosis of smear-negative PTB were 75% (95% CI 62.6-85.0) and 35.9% (95% CI 27.2-45.3), respectively. The positive and negative predictive values were 39% (95% CI 30.4-48.2) and 72.4% (95% CI 59.1-83.3), respectively, while the positive and negative likelihood ratios were 1.17 (95% CI 0.96-1.42) and 0.70 (95% CI 0.43-1.14), respectively. One hundred and seventeen LJ culture-negative suspects (75 PCR-positive and 42 PCR-negative) were enrolled for follow-up at 2 months. Of the PCR-positive suspects, 45 (60%, 45/75) were still alive, of whom 29 (64.4%, 29/45) returned for the follow-up visit; 15 (20%, 15/75) suspects died while another 15 (20%, 15/75) were lost to follow-up. Of the 42 PCR-negative suspects, 22 (52.4%, 22/42) were still alive, of whom 16 (72.7%, 16/22) returned for follow-up; 11 (26.2%, 11/42) died while nine (21.4%, 9/42) were lost to follow-up. Overall, more PCR-positive suspects were diagnosed with PTB during follow-up visits but the difference was not statistically significant (27.6%, 8/29 vs. 25%, 4/16, p = 0.9239). Furthermore, mortality was higher for the PCR-negative suspects but the difference was also not statistically significant (26.2% vs. 20% p = 0.7094).ConclusionIn-house PCR correlates poorly with LJ culture for diagnosis of smear-negative PTB. Therefore, in-house PCR may not be adopted as an alternative to LJ culture.

Long delays and missed opportunities in diagnosing smear-positive pulmonary tuberculosis in Kampala, Uganda: a cross-sectional study.

BackgroundEarly detection and treatment of tuberculosis cases are the hallmark of successful tuberculosis control. We conducted a cross-sectional study at public primary health facilities in Kampala city, Uganda to quantify diagnostic delay among pulmonary tuberculosis (PTB) patients, assess associated factors, and describe trajectories of patients' health care seeking.Methodology/Principal FindingsSemi-structured interviews with new smear-positive PTB patients (≥15 years) registered for treatment. Between April 2007 and April 2008, 253 patients were studied. The median total delay was 8 weeks (IQR 4–12), median patient delay was 4 weeks (inter-quartile range [IQR] 1–8) and median health service delay was 4 weeks (IQR 2–8). Long total delay (>14 weeks) was observed for 61/253 (24.1%) of patients, long health service delay (>6 weeks) for 71/242 (29.3%) and long patient delay (>8 weeks) for 47/242 (19.4%). Patients who knew that TB was curable were less likely to have long total delay (adjusted Odds Ratio [aOR] 0.28; 95%CI 0.11–0.73) and long patient delay (aOR 0.36; 95%CI 0.13–0.97). Being female (aOR 1.98; 95%CI 1.06–3.71), staying for more than 5 years at current residence (aOR 2.24 95%CI 1.18–4.27) and having been tested for HIV before (aOR 3.72; 95%CI 1.42–9.75) was associated with long health service delay. Health service delay contributed 50% of the total delay. Ninety-one percent (231) of patients had visited one or more health care providers before they were diagnosed, for an average (median) of 4 visits (range 1–30). All but four patients had systemic symptoms by the time the diagnosis of TB was made.Conclusions/SignificanceDiagnostic delay among tuberculosis patients in Kampala is common and long. This reflects patients waiting too long before seeking care and health services waiting until systemic symptoms are present before examining sputum smears; this results in missed opportunities for diagnosis.

Feasibility, reliability and validity of health-related quality of life questionnaire among adult pulmonary tuberculosis patients in urban Uganda: cross-sectional study

BackgroundDespite the availability of standard instruments for evaluating health-related quality life (HRQoL), the feasibility, reliability, and validity of such instruments among tuberculosis (TB) patients in different populations of sub-Saharan Africa where TB burden is of concern, is still lacking.ObjectiveWe established the feasibility, reliability, and validity of the Medical Outcomes Survey (MOS) in assessing HRQoL among patients with pulmonary tuberculosis in Kampala, Uganda.MethodsIn a cross-sectional study, 133 patients with known HIV status and confirmed pulmonary TB disease were recruited from one public and one private hospital. Participants were enrolled based on duration of TB treatment according to the following categories: starting therapy, two months of therapy, and eight completed months of therapy. A translated and culturally adapted standardized 35-item MOS instrument was administered by trained interviewers. The visual analogue scale (VAS) was used to cross-validate the MOS.ResultsThe MOS instrument was highly acceptable and easily administered. All subscales of the MOS demonstrated acceptable internal consistency with Cronbach's alpha above 0.70 except for role function that had 0.65. Each dimension of the MOS was highly correlated with the dimension measured concurrently using the VAS providing evidence of validity. Construct validity demonstrated remarkable differences in the functioning status and well-being among TB patients at different stages of treatment, between patients attending public and private hospitals, and between men and women of older age. Patients who were enrolled from public hospital had significantly lower HRQoL scores (0.78 (95% confidence interval (CI); 0.64-0.95)) for perceived health but significantly higher HRQoL scores (1.15 (95% CI; 1.06-1.26)) for health distress relative to patients from private hospital. Patients who completed an 8 months course of TB therapy had significantly higher HRQoL scores for perceived health (1.93 (95% CI; 1.19-3.13)), health distress subscales (1.29 (95% CI; 1.04-1.59)) and mental health summary scores (1.27 (95% CI; 1.09-1.48)) relative to patients that were starting therapy in multivariable analysis. Completion of 8 months TB therapy among patients who were recruited from the public hospital was associated with a significant increase in HRQoL scores for quality of life subscale (1.26 (95% CI; 1.08-1.49)), physical health summary score (1.22 995% CI; 1.04-1.43)), and VAS (1.08 (95% CI; 1.01-1.15)) relative to patients who were recruited from the private hospital. Older men were significantly associated with lower HRQoL scores for physical health summary score (0.68 (95% CI; 0.49-0.95)) and VAS (0.87 (95% CI; 0.75-0.99)) relative to women of the same age group. No differences were seen between HIV positive and HIV negative patients.ConclusionThe study provides evidence that the MOS instrument is valid, and reliably measures HRQoL among TB patients, and can be used in a wide variety of study populations. The HRQoL differed by hospital settings, by duration of TB therapy, and by gender in older age groups.

Severity of Human Immunodeficiency Virus Infection Is Associated with Decreased Phase Angle, Fat Mass and Body Cell Mass in Adults with Pulmonary Tuberculosis Infection in Uganda

Although coinfection with tuberculosis and human immunodeficiency virus (HIV) is emerging as a major problem in many developing countries, nutritional status has not been well characterized in adults with tuberculosis and HIV infection. We compared nutritional status between 261 HIV-positive and 278 HIV-negative adults with pulmonary tuberculosis in Kampala, Uganda, using anthropometry and bioelectrical impedance analysis. Among 163 HIV-positive and 199 HIV-negative men, intracellular water-to-extracellular water (ICW:ECW) ratio was 1.48 +/- 0.26 and 1.59 +/- 0.48 (P = 0.006) and phase angle was 5.42 +/- 1.05 and 5.76 +/- 1.30 (P = 0.009), respectively. Among 98 HIV-positive and 79 HIV-negative women, ICW:ECW was 1.19 +/- 0.16 and 1.23 +/- 0.15 (P = 0.11) and phase angle was 5.35 +/- 1.27 and 5.43 +/- 0.93 (P = 0.61), respectively. There were no significant differences in BMI, body cell mass, fat mass or fat-free mass between HIV-positive and HIV-negative adults. Among HIV-positive subjects, BMI, ICW:ECW, body cell mass, fat mass and phase angle were significantly lower among those with CD4(+) lymphocytes < or = 200 cells/microL compared with those who had > 200 cells/microL. In sub-Saharan Africa, coinfection with pulmonary tuberculosis and HIV is associated with smaller body cell mass and intracellular water, but not fat-free mass, and by large differences in ICW:ECW and phase angle alpha.

The Influence of Human Immunodeficiency Virus Infection on Tuberculosis in Kampala. Uganda

The clinical, radiographic, and microbiologic features of 59 patients with pulmonary tuberculosis in Kampala, Uganda were studied and correlated with the serologic reactivity to the human immunodeficiency virus (HIV) of these patients. Two-thirds of the patients with tuberculosis were HIV-seropositive. Histories of fever and weight loss were more prominent in HIV-seropositive patients, and perihilar and basilar infiltrative diseases were more frequently seen in HIV-seropositive patients. Although all patients responded similarly to drug therapy, cutaneous drug reactions were seen in nearly one-third of HIV-seropositive patients receiving thiacetazone.