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Tuberculosis (TB) remains a major public health challenge and the most frequent cause of illness and death among persons living with HIV (PLHIV) (1). Globally, TB occurs in congregate settings [...]

Tuberculosis (TB) is the leading cause of illness and death globally among persons living with HIV (PLHIV) (1,2). In 2021, among [approximately equal to] 38.4 million PLHIV worldwide, 703,000 TB [...]

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges.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]

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. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis of tuberculosis, especially by using rapid molecular assays, can reduce transmission of drug resistant tuberculosis in communities. However, the frequency of resistance conferring mutations varies with geographic location of Mycobacterium tuberculosis, and this affects the efficiency of rapid molecular assays in detecting resistance. This has created need for characterizing drug resistant isolates from different settings to investigate frequencies of resistance conferring mutations. Here, we describe the prevalence and patterns of rifampicin- and isoniazid- resistance conferring mutations in isolates from Uganda, which could be useful in the management of MDR-TB patients in Uganda and other countries in sub-Saharan Africa. Results: Ninety seven M. tuberculosis isolates were characterized, of which 38 were MDR, seven rifampicin-resistant, 12 isoniazid-mono-resistant, and 40 susceptible to rifampicin and isoniazid. Sequence analysis of the rpoB rifampicin-resistance determining region (rpoB/RRDR) revealed mutations in six codons: 588, 531, 526, 516, 513, and 511, of which Ser531Leu was the most frequent (40%, 18/45). Overall, the three mutations (Ser531Leu, His526Tyr, Asp516Tyr) frequently associated with rifampicin-resistance occurred in 76% of the rifampicin resistant isolates while 18% (8/45) of the rifampicin-resistant isolates lacked mutations in rpoB/RRDR. Furthermore, sequence analysis of katG and inhA gene promoter revealed mainly the Ser315Thr (76%, 38/50) and C(-15)T (8%, 4/50) mutations, respectively. These two mutations combined, which are frequently associated with isoniazid-resistance, occurred in 88% of the isoniazid resistant isolates. However, 20% (10/50) of the isoniazid-resistant isolates lacked mutations both in katG and inhA gene promoter. The sensitivity of sequence analysis of rpoB/RRDR for rifampicin-resistance via detection of high confidence mutations (Ser531Leu, His526Tyr, Asp516Tyr) was 81%, while it was 77% for analysis of katG and inhA gene promoter to detect isoniazid-resistance via detection of high confidence mutations (Ser315Thr, C(-15)T, T(-8)C). Furthermore, considering the circulating TB genotypes in Uganda, the isoniazid-resistance conferring mutations were more frequent in M. tuberculosis lineage 4/sub-lineage Uganda, perhaps explaining why this genotype is weakly associated with MDR-TB. Conclusion: Sequence analysis of rpoB/RRDR, katG and inhA gene promoter is useful in detecting rifampicin/isoniazid resistant M. tuberculosis isolates in Uganda however, about ≤20% of the resistant isolates lack known resistance-conferring mutations hence rapid molecular assays may not detect them as resistant. [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: Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in sub-Saharan Africa (SSA) is reportedly low compared to other regions. These estimates are based on data reported to the World Health Organization (WHO) on drug resistance surveys, which may suffer from a reporting bias. We set out to evaluate the variation in prevalence of drug resistant tuberculosis (DR-TB) and its determinants across SSA countries among new and previously treated TB patients. Methods: The aim was to perform a systematic review and meta-analysis of DR-TB prevalence and associated risk factors in SSA. PubMed, EMBASE, Cochrane and bibliographies of DR-TB studies were searched. Surveys at national or sub-national level, with reported DR-TB prevalence (or sufficient data to calculate a prevalence) to isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) conducted in SSA excluding the Republic of South Africa, published between 2003 and 2013 with no language restriction were considered. Two authors searched and reviewed the studies for eligibility and extracted the data in pre-defined forms. Forest plots of all prevalence estimates by resistance outcome were performed. Summary estimates were calculated using random effects models, when appropriate. Associations between any DR-TB and MDR-TB with potential risk factors were examined through subgroup analyses stratified by new and previously treated patients. Results: A total of 726 studies were identified, of which 27 articles fulfilled the inclusion criteria. Studies reported drug susceptibility testing (DST) results for a total of 13,465 new and 1,776 previously treated TB patients. Pooled estimate of any DR-TB prevalence among the new cases was 12.6% (95% CI 10.6-15.0) while for MDR-TB this was 1.5% (95% CI 1.0-2.3). Among previously treated patients, these were 27.2% (95% CI 21.4-33.8) and 10.3% (95% CI 5.8-17.4%), respectively. DR-TB (any and MDR-TB) did not vary significantly with respect to study characteristics. Conclusions: The reported prevalence of DR-TB in SSA is low compared to WHO estimates. MDR-TB in this region does not seem to be driven by the high HIV prevalence rates [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]

Understanding the circulating Mycobacterium tuberculosis resistance mutations is vital for better TB control strategies, especially to inform a new MDR-TB treatment programme. We complemented the phenotypic drug susceptibility testing (DST) based drug resistance surveys (DRSs) conducted in Uganda between 2008 and 2011 with Whole Genome Sequencing (WGS) of 90 Mycobacterium tuberculosis isolates phenotypically resistant to rifampicin and/or isoniazid to better understand the extent of drug resistance. A total of 31 (34.4 %) patients had MDR-TB, 5 (5.6 %) mono-rifampicin resistance and 54 (60.0 %) mono-isoniazid resistance by phenotypic DST. Pyrazinamide resistance mutations were identified in 32.3% of the MDR-TB patients. Resistance to injectable agents was detected in 4/90 (4.4%), and none to fluoroquinolones or novel drugs. Compensatory mutations in rpoC were identified in two patients. The sensitivity and specificity of drug resistance mutations compared to phenotypic DST were for rpoB 88.6% and 98.1%, katG 60.0% and 100%, fabG1 16.5% and 100%, katG and/or fabG1 71.8% and 100%, embCAB 63.0% and 82.5%, rrs 11.4% and 100%, rpsL 20.5% and 95.7% and rrs and/or rpsL 31.8% and 95.7%. Phylogenetic analysis showed dispersed MDR-TB isolate, with only one cluster of three Beijing family from South West Uganda. Among tuberculosis patients in Uganda, resistance beyond first-line drugs as well as compensatory mutations remain low, and MDR-TB isolates did not arise from a dominant clone. Our findings show the potential use of sequencing for complementing DRSs or surveillance in this setting, with good specificity compared to phenotypic DST. The reported high confidence mutations can be included in molecular assays, and population-based studies can track transmission of MDR-TB including the Beijing family strains in the South West of the country. [ABSTRACT FROM AUTHOR]

Communicable diseases, alone or in combination with malnutrition, account for most deaths in complex emergencies including refugee settings. Tuberculosis and HIV/AIDS are increasingly becoming an important cause of morbidity and mortality in refugee settings. We described the treatment outcomes of TB patients and explored factors associated with treatment outcomes among TB patients attending two facilities in Kyangwali Refugee Settlement in Kikuube District, 2016-2017. We abstracted data on laboratory-confirmed patient data from TB registers from 2016 to 2017, in Kikuube Health Centre IV and Rwenyawawa Health Centre II, both located in Kyangwali Refugee Settlement. We abstracted data on socio-demographic variables including age and sex. Other variables were height, weight, final treatment outcomes, demographics, HIV status, TB treatment category, and history of TB. Treatment outcomes were categorized into favorable (including patients who were cured or those who completed treatment) and unfavorable (those in whom treatment failed, those who died, those lost to follow-up, or those not evaluated). We used logistic regression to identify factors associated with unfavorable treatment outcomes. We identified a total of 254 TB patients with a median age of 36 (IQR 26-48) years; 69% (175) were male and 54% (137) were refugees. The median weight was 50.4 kg (range 4-198). Overall, 139 (55%) had favorable outcomes while 115 (45%) had unfavorable outcomes. Refugees formed 53% (71) of those with favorable outcomes and 47% (63) of those with unfavorable outcomes 63(47%). We found that increasing age was statistically associated with unfavorable outcomes, while diagnosis with MDR-TB was associated with decreased odds for unfavorable treatment outcomes. The treatment success rate was lower compared to 85% recommended by WHO. However, the rates are similar to that reported by other studies in Uganda. Innovative approaches to improve treatment success rates with particular focus on persons aged 41-80 years should be devised., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Nguna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.)