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We report that unsuccessful treatment outcomes were 11.8% for tuberculosis (TB) disease and 21.8% for TB infection among persons deprived of liberty in Uganda Prisons Service facilities. Remedial efforts should include enhancing referral networks to ensure treatment continuity, strengthening data systems for complete outcome documentation, and prioritizing short-course treatment regimens. [ABSTRACT FROM AUTHOR]

During October 2016–March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming. [ABSTRACT FROM AUTHOR]

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013–2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges. [ABSTRACT FROM AUTHOR]

Background: The management and control of pulmonary bacteriologically confirmed (PBC) tuberculosis (TB) also known as infectious TB is important not only to monitor for resistance but also to check for severity, treatment response and limit its spread.Method: A retrospective analysis of diagnosis smear results of PBC TB patients in Kampala district registered between January 2012 and December 2015 at 65 TB diagnosis and treatment units (DTUs) was done.Results: Of the 10,404 records; 6551 (63.0%) belonged to PBC TB patients, 3734 (57.0%) of whom were male. Sputum smear microscopy was the diagnostic test most commonly used 4905 (74.9%) followed by GeneXpert testing, 1023 (15.6%). Majority, 1951 (39.8%), of the PBC TB patients had a smear positivity grading of 3+ (> 10 acid-fast bacillus (AFB)/Fields). Public facilities diagnosed more PBC TB patients compared to private facilities, 3983 (60.8%) vs 2566 (39.2%). From 2012 through 2015, there was a statistically significant increase in PBC TB patients enrolled on anti-TB treatment from 1389 to 2194 (p = 0.000). The percentage of HIV positive co-infected PBC TB patients diagnosed decreased from 597(43%) to 890(40.6%) (p = 0.000) within same period. Linkage to HIV care improved from 229 (34.4%) in 2012 to 464 (52.1%) in 2015 (p = 0.000). The treatment success rate (TSR) for PBC TB patients improved from 69% in 2012 to 75.5% by end of 2015 (p = 0.001) with an improvement in cure rate from 52.3% to 62% (p = 0.000). There was an observed significant decrease in TB related mortality from 8.9 to 6.4% (p = 0.013).Conclusion: The proportion of diagnosed PBC TB patients increased from 2012 to 2015. PBC TB patients diagnosed with 3+ smear positivity grading results consistently contributed to the highest proportion of diagnosed PBC TB patients from 2012 to 2015. This could be due to the delay in diagnosis of TB patients because of late presentation of patients to clinics. A prospective study of PBC TB patients diagnosed with 3+ smear positivity grading may elucidate the reasons for the delay to diagnosis. Further, we propose a study of wider scope to estimate how many people a single PBC TB patient is likely to infect with TB before being diagnosed and treated. [ABSTRACT FROM AUTHOR]

Background: The road map for childhood tuberculosis launched in 2013 provided strong renewed efforts focused towards zero deaths due to tuberculosis in children. From 2010, there were efforts to improve childhood tuberculosis diagnosis in Kampala and this study aimed to document the trend and outcome of tuberculosis in children over the period.Methods: This was a retrospective study of tuberculosis data for Kampala city for the period 2011-2015. We extracted data from the unit TB registers in the 52 Diagnostic and treatment units (DTUs) in the Kampala. We report on data for children 0 to 14 years.Results: We accessed 33,221 TB patient records of which 2333 (7.0% 95% CI 6.7 to 7.3) were children. The proportion of children with pulmonary TB was 80% (1870/2333) (95% CI 76.7 to 83.7 and extra-pulmonary TB accounted for 20% (463/2333) (CI 18.3 to 21.5). Among pulmonary TB cases, the clinically diagnosed were 82% (1530/1870) (95% CI 80.0 to 83.5) while the bacteriologically confirmed were 18% (340/1870) (95% CI 16.5 to 20.0). Among the bacteriologically confirmed, 45% (154/340) (95% CI 40.1 to 50.6) were smear positive. During the study period 2011 through 2015, the childhood TB notification rate declined as follows; 105, 76, 72, 88, and 74 per 100,000 respectively. The treatment success rate increased from 78% in 2011 to 83% in 2015.Conclusions: The TB notification rate among children in Kampala city showed a large decline during the period 2011 to 2015. There was a slight improvement in the treatment success rate among the children. [ABSTRACT FROM AUTHOR]

Background: The global tuberculosis (TB) estimate in 2011 was 500,000 cases among children under 15 years representing 5.7 % of all cases and 64, 000 deaths among HIV negative children representing 6.5 % of the total deaths. In Uganda, the child TB cases reported in 2012 made up less than 3 % of the total cases while recent modelling estimates it at 15-20 % of adult cases. Mapping of these cases in Kampala district most especially for the children under five years would reflect recent transmission in the various communities in the district. We therefore conducted a retrospective study of reported child TB cases in Kampala district Uganda for 2009-2010 to provide an estimate of child TB incidence and map the cases.Methods: This was a retrospective cross-sectional study on data collected from the health unit TB registers in the five divisions of Kampala district, Uganda. The data was a starting point in preparation for a TB Vaccine study in children. The extracted data spanned a period from 1st January 2009 to 31st December 2010. The projected population of children below 15 years was 637,922 in 2009 and 744,750 in 2010 for Kampala district. We based our projections on the National Bureau of Statistics most recent census report of 2002 before the study duration while assuming a population growth rate of 3.7 % each year. We captured the data into EPI DATA 3.1 and analysed it using STATA version 12.Results: We accessed 15,499 records and analysed 1167 records that were of children below 15 years old. The child TB cases represented 7.5 % (7.3 in 2009 & 7.6 % in 2010) of all the registered cases in Kampala district. The females were 47 % and the median age was 4 years (IQR 1, 10). The percent of children less than 5 years old was 54 %. The percent of pulmonary TB cases was 89 % (1041/1167) with 15 % smear positive. The proportion of extra-pulmonary TB cases was 11 % (126/1167). Among those that tested for HIV, 60 % (359/620) had test results available with an HIV co-infection rate of 47 % (168/359). Antiretroviral treatment uptake was 24 % among the co-infected. The incidence of child TB in Kampala was 56 (95 % CI 50-62) per 100,000 in 2009 and 44 (95 % CI 40-49) per 100,000 in 2010. Most of the TB cases (60 % (410/685)) in Kampala live in slum areas.Conclusion: There was a higher child TB incidence of 56 per 100,000 in 2009 compared with 44 per 100,000 in 2010. The percentage of child TB cases was much higher at 7.5 % of all the reported TB cases than the WHO reported national average. For the review period, the TB cases clustered in particular slums in Kampala district. [ABSTRACT FROM AUTHOR]

Background The global increase in the burden of multidrug-resistant tuberculosis (MDR-TB) underscores an urgent need for data on factors involved in generation and spread of TB drug resistance. We performed molecular analyses on a representative sample of Mycobacterium tuberculosis (MTB) isolates. Basing on findings of the molecular epidemiological study in Kampala, we hypothesized that the predominant MTB strain lineage in Uganda is negatively associated with anti-TB drug resistance and we set out to test this hypothesis. Methods We extracted DNA from mycobacterial isolates collected from smear-positive TB patients in the national TB drug resistance survey and carried out IS6110-PCR. To identify MTB lineages/sub lineages RT-PCR SNP was performed using specific primers and hybridization probes and the 'melting curve' analysis was done to distinguish the Uganda II family from other MTB families. The primary outcome was the distribution of the Uganda II family and its associations with anti-TB drug resistance and HIV infection. Results Out of the 1537 patients enrolled, MTB isolates for 1001 patients were available for SNP analysis for identification of Uganda II family, of which 973 (97%) had conclusive RT-PCR results. Of these 422 (43.4%) were of the Uganda II family, mostly distributed in the south west zone (55.0%; OR = 4.6 for comparison with other zones; 95% CI 2.83-7.57; p < 0.001) but occurred in each of the other seven geographic zones at varying levels. Compared to the Uganda II family, other genotypes as a group were more likely to be resistant to any anti-TB drug (ORadj =2.9; 95% CI 1.63-5.06; p = 0.001) or MDR (ORadj 4.9; 95% CI, 1.15-20.60; p = 0.032), even after adjusting for geographic zone, patient category, sex, residence and HIV status. It was commonest in the 25-34 year age group 159/330 (48.2%). No association was observed between Uganda II family and HIV infection. Conclusion The Uganda II family is a major cause of morbidity due to TB in all NTLP zones in Uganda. It is less likely to be resistant to anti-TB drugs than other MTB strain lineages. [ABSTRACT FROM AUTHOR]

Background: Multidrug resistant and extensively drug resistant tuberculosis (TB) have become major threats to control of tuberculosis globally. The rates of anti-TB drug resistance in Uganda are not known. We conducted a national drug resistance survey to investigate the levels and patterns of resistance to first and second line anti-TB drugs among new and previously treated sputum smear-positive TB cases. Methods: Sputum samples were collected from a nationally representative sample of new and previously treated sputum smear-positive TB patients registered at TB diagnostic centers during December 2009 to February 2011 using a weighted cluster sampling method. Culture and drug susceptibility testing was performed at the national TB reference laboratory. Results: A total of 1537 patients (1397 new and 140 previously treated) were enrolled in the survey from 44 health facilities. HIV test result and complete drug susceptibility testing (DST) results were available for 1524 (96.8%) and 1325 (85.9%) patients, respectively. Of the 1209 isolates from new cases, resistance to any anti-TB drug was 10.3%, 5% were resistant to isoniazid, 1.9% to rifampicin, and 1.4% were multi drug resistant. Among the 116 isolates from previously treated cases, the prevalence of resistance was 25.9%, 23.3%, 12.1% and 12.1% respectively. Of the 1524 patients who had HIV testing 469 (30.7%) tested positive. There was no association between anti-TB drug resistance (including MDR) and HIV infection. Conclusion: The prevalence of anti-TB drug resistance among new patients in Uganda is low relative to WHO estimates. The higher levels of MDR-TB (12.1%) and resistance to any drug (25.3%) among previously treated patients raises concerns about the quality of directly observed therapy (DOT) and adherence to treatment. This calls for strengthening existing TB control measures, especially DOT, routine DST among the previously treated TB patients or periodic drug resistance surveys, to prevent and monitor development and transmission of drug resistant TB. [ABSTRACT FROM AUTHOR]

Background: Drug resistance among tuberculosis patients in sub-Saharan Africa is increasing, possibly due to association with HIV infection. We studied drug resistance and HIV infection in a representative sample of 533 smear-positive tuberculosis patients diagnosed in Kampala, Uganda. Methods/Principal Findings: Among 473 new patients, multidrug resistance was found in 5 (1.1%, 95% CI 0.3-2.5) and resistance to any drug in 57 (12.1%, 9.3-15.3). Among 60 previously treated patients this was 7 (11.7%, 4.8-22.6) and 17 (28.3%; 17.5-41.4), respectively. Of 517 patients with HIV results, 165 (31.9%, 27.9-36.1) tested positive. Neither multidrug (adjusted odds ratio (ORadj) 0.7; 95% CI 0.19-2.6) nor any resistance (ORadj 0.7; 0.43-1.3) was associated with HIV status. Primary resistance to any drug was more common among patients who had worked in health care (ORadj 3.5; 1.0-12.0). Conclusion/Significance: Anti-tuberculosis drug resistance rates in Kampala are low and not associated with HIV infection, but may be associated with exposure during health care. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis is a leading cause of morbidity and mortality in developing countries. Drug resistance, a huge problem in this contagious disease, is driven by point mutations in the Mycobacterium tuberculosis genome however, their frequencies vary geographically and this affects applicability of molecular diagnostics for rapid detection of resistance. Here, we report the frequency and patterns of mutations associated with resistance to second-line anti-TB drugs in multidrug-resistant (MDR) M. tuberculosis isolates from eSwatini, Somalia and Uganda that were resistant to a second-line anti-TB drug.Methods: The quinolone resistance determining region (QRDR) of gyrA/gyrB genes and the drug resistance associated fragment of rrs gene from 80 isolates were sequenced and investigated for presence of drug resistance mutations. Of the 80 isolates, 40 were MDR, of which 28 (70%) were resistant to a second-line anti-TB injectable drug, 18 (45%) were levofloxacin resistant while 12 (30%) were extensively drug resistant (XDR). The remaining 40 isolates were susceptible to anti-TB drugs. MIRU-VNTR analysis was performed for M/XDR isolates.Results: We successfully sub-cultured 38 of the 40 M/XDR isolates. The gyrA resistance mutations (Gly88Ala/Cys/Ala, Ala90Val, Ser91Pro, Asp94Gly/Asn) and gyrB resistance mutations (Asp500His, Asn538Asp) were detected in 72.2% (13/18) and 22.2% (4/18) of the MDR and levofloxacin resistant isolates, respectively. Overall, drug resistance mutations in gyrA/gyrB QRDRs occurred in 77.8% (14/18) of the MDR and levofloxacin resistant isolates. Furthermore, drug resistance mutations a1401g and g1484 t in rrs occurred in 64.3% (18/28) of the MDR isolates resistant to a second-line anti-TB injectable drug. Drug resistance mutations were not detected in drug susceptible isolates.Conclusions: The frequency of resistance mutations to second-line anti-TB drugs in MDR-TB isolates resistant to second line anti-TB drugs from eSwatini, Somalia and Uganda is high, implying that rapid molecular tests are useful in detecting second-line anti-TB drug resistance in those countries. Relatedly, the frequency of fluoroquinolone resistance mutations in gyrB/QRDR is high relative to global estimates, and they occurred independently of gyrA/QRDR mutations implying that their absence in panels of molecular tests for detecting fluoroquinolone resistance may yield false negative results in our setting. [ABSTRACT FROM AUTHOR]

Despite remarkable progress in controlling HIV and TB, Uganda is one of the 30 high-burden TB/HIV countries. Approximately 53,000 Ugandans had a new HIV diagnosis in 2019, and approximately 88,000 Ugandans had a TB diagnosis in 2020. Fellows in the Uganda Public Health Fellowship Program (UPHFP) work directly with the Ministry of Health AIDS and TB Control Programs, the U.S. Centers for Disease Control and Prevention, UPHFP supervisors, and implementing partners to investigate and evaluate HIV-related and TB-related issues. These activities have contributed to the Uganda HIV and TB programs. UPHFP fellows complete projects in 7 competency domains, including outbreak investigations, surveillance evaluations, and data quality improvement. Priority HIV/AIDS/TB information gaps/topics are identified in consultation with key stakeholders, and fellows complete projects to guide program improvements and policy decisions. During 2015-2020, UPHFP fellows implemented 127 HIV and TB projects covering key program areas in AIDS and TB control programs, including care and treatment (16 projects), TB/HIV (18), prevention of mother-to-child HIV transmission (24), key and priority populations (9), pre-exposure and post-exposure prophylaxis (7), adolescent girls and young women (6), service delivery (13), and diagnosis of TB including drug-resistant TB and TB in high-risk groups (32). These projects have helped improve retention, quality of care, and treatment outcomes for people living with HIV, HIV and TB coinfected patients, and TB patients. They have also contributed to the decrease in pediatric TB and infant HIV positivity rates and improved service delivery for key populations. UPHFP results were disseminated to relevant stakeholders such as government departments, implementing partners, districts, and the general community and guided decision making. UPHFP has significantly improved HIV and TB control in Uganda. Other countries with similar programs could benefit from this approach and utilize program fellows to support HIV and TB control., (© Ario et al.)

Background: The End TB Strategy aims to reduce new tuberculosis (TB) cases by 90% and TB-related deaths by 95% between 2015 - 2035. We determined the trend of case notification rates (CNRs) and treatment outcomes of TB cases with and without HIV co-infection in rural Uganda to provide an interim evaluation of progress towards this global target in rural settings., Methods: We extracted retrospective programmatic data on notified TB cases and treatment outcomes from 2015 - 2019 for eight districts in rural Uganda from the District Health Information System 2. We estimated CNRs as the number of TB cases per 100,000 population. Treatment success rate (TSR) was calculated as the sum of TB cure and treatment completion for each year. Trends were estimated using the Mann-Kendall test., Results: A total of 11,804 TB cases, of which 5,811 (49.2%) were HIV co-infected, were notified. The overall TB CNR increased by 3.7-fold from 37.7 to 141.3 cases per 100,000 population in 2015 and 2019 respectively. The increment was observed among people with HIV (from 204.7 to 730.2 per 100,000, p = 0.028) and HIV-uninfected individuals (from 19.9 to 78.7 per 100,000, p = 0.028). There was a decline in the TSR among HIV-negative TB cases from 82.1% in 2015 to 63.9% in 2019 (p = 0.086). Conversely, there was an increase in the TSR among HIV co-infected TB cases (from 69.9% to 81.9%, p = 0.807)., Conclusion: The CNR increased among people with and without HIV while the TSR reduced among HIV-negative TB cases. There is need to refocus programs to address barriers to treatment success among HIV-negative TB cases., (© 2022. The Author(s).)

Background: Following initiation of MDR-TB treatment, patients have a choice to receive follow up DOT supervision at either the central initiating facility or at a peripheral facility., Objectives: We describe the adherence patterns of MDR-TB patients undergoing DOT supervision at the two health facility categories during intensive phase of treatment., Methods: We used a retrospective cohort of patients initiated on MDR TB treatment at Mulago National Referral Hospital between 2014 and 2016. We extracted data from the National Tuberculosis and Leprosy Program records and analysed these using STATA V14., Result: Majority (84.01%) of the patients received their DOT supervision from the peripheral facilities. Males made up 62.1% of patients, and 91.2% had had their household contacts screened for MDR-TB. 26.5% of the patients on peripheral DOT supervision had good adherence to treatment protocol compared to 0% among patients on central initiating health facility DOT supervision. Among the patients with good adherence, 24.1% had contacts screened for MDR-TB as compared to 3.6% with poor adherence., Conclusion: More patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settingsMore patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settings., (© 2020 Mukasa J et al.)

While old age is a known risk factor for developing active tuberculosis (TB), studies on TB in the population aged 60 years and older (considered elderly in this study) are few, especially in the developing world. Results of the TB prevalence survey in Uganda found high TB prevalence (570/100,000) in people over 65. We focused on treatment outcomes in the elderly to understand this epidemic better. We conducted a retrospective analysis of data from TB facility registers in Kampala City for the period 2014-2015. We analyzed the 2014-15 cohort with respect to age, sex, disease class, patients' human immunodeficiency virus (HIV) and directly observed therapy (DOT) status, type of facility, and treatment outcomes and compared findings in the elderly (≥60) and younger (<60) age groups. Of 15,429 records, 3.3% (514/15,429) were for elderly patients. The treatment success rate (TSR) among elderly TB patients (68.3%) was lower than that of the non-elderly (80.9%) and the overall TSR 80.5%, (12,417/15,429) in Kampala. Although the elderly were less likely to test positive for HIV than the young (AOR 0.39; 95% CI 0.33-0.48, p<0.001), they had a two-fold higher risk of unfavorable treatment outcomes (AOR 2.14; CI 1.84-2.72, p<0.001) and were more likely to die while on treatment (AOR 1.86; CI 1.27-2.73; p = 0.001). However, there was no statistically significantly difference between treatment outcomes among HIV-positive and HIV-negative elderly TB patients. Compared to the younger TB patients, elderly TB patients have markedly poorer treatment outcomes, although TB/HIV co-infection rates in this age group are lower., Competing Interests: The authors have declared that no competing interests exist.

Surveillance of the circulating Mycobacterium tuberculosis complex (MTC) strains in a given locality is important for understanding tuberculosis (TB) epidemiology. We performed molecular epidemiological studies on sputum smear-positive isolates that were collected for anti-TB drug resistance surveillance to establish the variability of MTC lineages with anti-TB drug resistance and HIV infection. Spoligotyping was performed to determine MTC phylogenetic lineages. We compared patients' MTC lineages with drug susceptibility testing (DST) patterns and HIV serostatus. Out of the 533 isolates, 497 (93.2%) had complete DST, PCR, and spoligotyping results while 484 (90.1%) participants had results for HIV testing. Overall, the frequency of any resistance was 75/497 (15.1%), highest among the LAM (34.4%; 95% confidence interval [CI], 18.5 to 53.2) and lowest among the T2 (11.5%; 95% CI, 7.6 to 16.3) family members. By multivariate analysis, LAM (adjusted odds ratio [OR(adj)], 5.0; 95% CI, 2.0 to 11.9; P < 0.001) and CAS (OR(adj), 2.9; 95% CI, 1.4.0 to 6.3; P = 0.006) families were more likely to show any resistance than was T2. All other MTC lineages combined were more likely to be resistant to any of the anti-TB drugs than were the T2 strains (OR(adj), 1.7; 95% CI, 1.0 to 2.9; P = 0.040). There were no significant associations between multidrug resistance and MTC lineages, but numbers of multidrug-resistant TB strains were small. No association was established between MTC lineages and HIV status. In conclusion, the T2 MTC lineage negatively correlates with anti-TB drug resistance, which might partly explain the reported low levels of anti-TB drug resistance in Kampala, Uganda. Patients' HIV status plays no role with respect to the MTC lineage distribution., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)