Clinical Predictors of 3-Months Isoniazid Rifapentine (3HP) - Related Adverse Drug Reactions (ADR) During Tuberculosis Preventive Therapy. (PAnDoRA-3HP study): An Observational Study Protocol.

Introduction: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for Tuberculosis Preventive Therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs. Our study aims to describe the pharmacokinetic and pharmacogenomics of 3HP used for TPT, the ADRs and their association with completion rates, and TPT outcomes, providing vital insights for TB control strategies in resource-limited settings. Methods: This is an observational cohort study with a nested case-control study. We enrolled consecutive patients initiated on TPT using the 3HP regimen. These are followed up bi-weekly and then monthly during the active phase of treatment and 3 monthly for 2 years following completion of TPT. ADR evaluation includes clinical assessment and liver function tests. Cases are selected from those who experience ADRs, and controls from those who do not. Serum isoniazid and rifapentine concentrations are measured and pharmacogenomic analysis for NAT2 and CYP2E1 polymorphisms are done. Participants are followed up for 2 years to determine TPT outcomes. Analysis: The safety profile of 3HP will be assessed using descriptive statistics, including proportions of patients experiencing ADRs and grade 3 or above events related to treatment. Chi-square tests and regression models will determine predictors of ADRs and their impact on treatment completion. Pharmacokinetic-pharmacodynamic modeling will establish population parameters and factors influencing rifapentine and isoniazid concentrations.

The effect of biomass smoke exposure on quality-of-life among Ugandan patients treated for tuberculosis: A cross-sectional analysis.

More than half the global population burns biomass fuels for cooking and home heating, especially in low-middle income countries. This practice is a prominent source of indoor air pollution and has been linked to the development of a variety of cardiopulmonary diseases, including Tuberculosis (TB). The purpose of this cross-sectional study was to investigate the association between current biomass smoke exposure and self-reported quality of life scores in a cohort of previous TB patients in Uganda. We reviewed medical records from six TB clinics from 9/2019-9/2020 and conducted phone interviews to obtain information about biomass smoke exposure. A random sample of these patients were asked to complete three validated quality-of-life surveys including the St. Georges Respiratory Questionnaire (SGRQ), the EuroQol 5 Dimension 3 Level system (EQ-5D-3L) which includes the EuroQol Visual Analog Scale (EQ-VAS), and the Patient Health Questionnaire 9 (PHQ-9). The cohort was divided up into 3 levels based on years of smoke exposure-no-reported smoke exposure (0 years), light exposure (1-19 years), and heavy exposure (20+ years), and independent-samples-Kruskal-Wallis testing was performed with post-hoc pairwise comparison and the Bonferroni correction. The results of this testing indicated significant increases in survey scores for patients with current biomass exposure and a heavy smoke exposure history (20+ years) compared to no reported smoke exposure in the SGRQ activity scores (adj. p = 0.018) and EQ-5D-3L usual activity scores (adj. p = 0.002), indicating worse activity related symptoms. There was a decrease in EQ-VAS scores for heavy (adj. p = 0.007) and light (adj. p = 0.017) exposure groups compared to no reported exposure, indicating lower perceptions of overall health. These results may suggest worse outcomes or baseline health for TB patients exposed to biomass smoke at the time of treatment and recovery, however further research is needed to characterize the effect of indoor air pollution on TB treatment outcomes.

Tuberculosis and diabetes mellitus comorbidity in an adult Ugandan population.

BACKGROUND: Diabetes mellitus (DM) has a direct impact on the clinical manifestation and prognosis of active tuberculosis disease (TB) and is known to increase the chance of developing the condition. We sought to determine the prevalence of DM in adult Ugandan patients with recently diagnosed TB and the associated sociodemographic, anthropometric, and metabolic characteristics of TB-DM comorbidity. METHODS: In this cross-sectional study conducted at the adult TB treatment centres of three tertiary healthcare facilities in Uganda, we screened adult participants with recently diagnosed TB (diagnosed in < 2 months) for DM. All participants were screened with five tests; initially with a random blood glucose (RBG) test, and then later with fasting blood glucose (FBG), laboratory-based glycated hemoglobin (HbA1c), point-of-care (POC) HbA1c, and oral glucose tolerance test (OGTT) if the RBG was ≥ 6.1 mmol/l. The WHO guidelines for diagnosing and managing DM were used to support the DM diagnosis. To identify the factors associated with DM-TB comorbidity, logistic regression was used. RESULTS: A total of 232 participants with recently diagnosed TB were screened for DM. Of these, 160 (69%) were female. The median (IQR) age, body mass index, and RBG of all study participants was 35 (27-42) years, 19.2 (17.6-21.3) kg/m2, and 6.1 (5.5-7.2) mmol/l, respectively. About half of the participants (n = 117, 50.4%) had RBG level ≥ 6.1 mmol/l. Of these, 75 (64.1%) participants returned for re-testing. Diabetes mellitus was diagnosed in 32 participants, corresponding to a prevalence of 13.8% (95% CI 9.9-18.9). A new diagnosis of DM was noted in 29 (90.6%) participants. On logistic regression, age ≥ 40 years was associated with increased odds of TB and DM comorbidity (AOR 3.12, 95% CI 1.35-7.23, p = 0.008) while HIV coinfection was protective (AOR 0.27, 95% CI 0.10-0.74, p = 0.01). CONCLUSION: TB and DM comorbidity was relatively common in this study population. Routine screening for DM in adult Ugandan patients with recently diagnosed TB especially among those aged ≥ 40 years and HIV-negative patients should be encouraged in clinical practice.

Diagnostic accuracy of two confirmatory tests for diabetes mellitus in adult Ugandans with recently diagnosed tuberculosis.

Objective: The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB. Methods: A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG. Results: Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9-18.9].The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47-0.90] and 0.65 [95% CI 0.43-0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4-90.1] and 74.6% [95% CI 62.5-84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40-57.9] and 95.3% (86.9-99.0%), respectively. Conclusion: FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.

Appropriate diabetes test in patients with tuberculosis Diabetes mellitus (DM) is a common condition in patients with tuberculosis and proactively screening for the condition is encouraged in all adult patients with tuberculosis. In this study, a total of 232 adult Ugandans with recently diagnosed tuberculosis were screened for DM using random glucose test, fasting blood glucose test, glycated haemoglobin test and an oral glucose tolerance test (OGTT), as the gold-standard and reference test. Compared with the OGTT, a fasting blood glucose test was noted to be a better screening test for diabetes mellitus than glycated haemoglobin in these patients and may be used as a follow-up test to random blood glucose in the screening and diagnosis of DM in adult Ugandans with tuberculosis.

Community-based directly observed therapy is effective and results in better treatment outcomes for patients with multi-drug resistant tuberculosis in Uganda.

BACKGROUND: Health facility-based directly observed therapy (HF DOT) is the main strategy for the management of patients with drug-resistant tuberculosis (DR TB) in Uganda, however, this still yields sub-optimal treatment outcomes. We set out to assess the effectiveness of community-based directly observed therapy (CB DOT) for the treatment of DR TB in Uganda. METHODS: Using a previously developed patient-centered model for CB DOT, we assigned community health workers (CHWs) as primary caregivers to patients diagnosed with DR TB. CHWs administered daily DOT to patients in their homes. Once a month, patients received travel vouchers to attend clinic visits for treatment monitoring. We assessed the effectiveness of this model using a quasi-experimental pre and post-study. From December 2020 to March 2022, we enrolled adult DR-TB patients on the CB DOT model. We collected retrospective data from patients who had received care using the HF DOT model during the year before the study started. The adjusted effect of CB DOT versus HF DOT on DR TB treatment success was estimated using modified Poisson regression model with robust cluster variance estimator. RESULTS: We analyzed data from 264 DR TB patients (152 HF DOT, 112 CB DOT). The majority were males (67.8%) with a median age of 36 years (IQR 29 to 44 years). Baseline characteristics were similar across the comparison groups, except for educational level, regimen type, and organizational unit with age being borderline. The treatment success rate in the CB DOT group was 12% higher than that in the HF DOT (adjusted prevalence ratio (aPR)= 1.12 [95%CI 1.01, 1.24], P-value=0.03). Males were less likely to achieve treatment success compared to their female counterparts (aPR=0.87 [95% CI 0.78, 0.98], P-value=0.02). A total of 126 (47.7%) of 264 patients reported at least one adverse event. The HF DOT group had a higher proportion of patients with at least one adverse event compared to the CB DOT group (90/152 [59.2%] versus 36/112 [32.1], P-value<0.01). The model was acceptable among patients (93.6%) and health workers (94.1%). CONCLUSIONS: CB DOT for DR-TB care is effective and results in better treatment outcomes than HF DOT. The cost-effectiveness of this model of care should be further evaluated.

Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda.

Tuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda. HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda were retrospectively reviewed. Estimated trends of TPT (given as Isoniazid monotherapy) uptake and completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models. On average, a total of 39,774 PLHIV aged 15 years and above were eligible for TPT each calendar year at the six health facilities. Across all 4 years, more than 70% were females (range: 73.5% -74.6%) and the median age ranged from 33 to 34 years. From 2016 quarter one to 2019 quarter two, TPT uptake was consistently below 25%, but, as expected, the uptake significantly increased by about 3-folds from 22.1% to 61.2%, in 2019 quarter two (i.e. before the roll-out of the 100-day accelerated TPT intervention) and quarter three (i.e. after the roll-out of the 100-day accelerated TPT intervention) respectively. This increase remained highly significant even after adjusting for patients' baseline characteristics (adjusted prevalence ratio [aPR] = 2.58 [95%CI 2.45, 2.72], P-value<0.001). TPT completion was consistently high at above 70% at most of the time, but, it increased significantly among those initiated during 2018 quarter four and in the subsequent two quarters after the roll-out of the 100-day accelerated TPT intervention (i.e. TPT completion was: 83.2%, 95.3%, and 97.1% among individuals initiated during 2018 quarter4, and 2019 quarters 1 and 2, respectively). The increase in TPT completion during this period remained significant even after adjusting for patients' baseline characteristics (aPR [95%CI] = 1.09 [1.04, 1.14], P value<0.001, and 1.10 [1.05,1.15], P value<0.001, for individuals initiated during 2019 quarter 1, and 2, respectively compared to those initiated during 2018 quarter 4). Not on ART or newly started on ART compared to ART experienced, and pregnant at TPT initiation compared to not pregnant were associated with poor TPT completion, whereas older age (≥25 years versus 15-24 years) was associated with higher TPT completion. The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines. Future analysis with additional years of data post 100-days TPT intervention is required to evaluate the sustainability of the observed gains.

Ending tuberculosis in a post-COVID-19 world: a person-centred, equity-oriented approach.

The COVID-19 pandemic has disrupted systems of care for infectious diseases-including tuberculosis-and has exposed pervasive inequities that have long marred efforts to combat these diseases. The resulting health disparities often intersect at the individual and community levels in ways that heighten vulnerability to tuberculosis. Effective responses to tuberculosis (and other infectious diseases) must respond to these realities. Unfortunately, current tuberculosis programmes are generally not designed from the perspectives of affected individuals and fail to address structural determinants of health disparities. We describe a person-centred, equity-oriented response that would identify and focus on communities affected by disparities, tailor interventions to the mechanisms by which disparities worsen tuberculosis, and address upstream determinants of those disparities. We detail four key elements of the approach (data collection, programme design, implementation, and sustainability). We then illustrate how organisations at multiple levels might partner and adapt current practices to incorporate these elements. Such an approach could generate more substantial, sustainable, and equitable reductions in tuberculosis burden at the community level, highlighting the urgency of restructuring post-COVID-19 health systems in a more person-centred, equity-oriented way.

A comparative analysis of two national tuberculosis reporting systems and their impact on tuberculosis case notification in Uganda.

Background: Before 2018, the use of parallel tuberculosis (TB) reporting systems was resource intensive with duplication of efforts and hence the need to select one that contributed to better TB case notification at the National TB and Leprosy Program (NLTP) in Uganda. We sought to analyse the difference in reporting rates between the two systems in order to improve NTLP TB case notification rates, logistics management, and planning for better health service delivery initiatives. Methods: We conducted a comparative study to assess TB case notification between the web-based DHIS2 and the district TB supervisor-led health management information system between January 2016 to December 2017. We used Poisson regression analysis to assess the statistical differences in reporting rates between the two reporting systems. Results: The association between TB case notification and the type of reporting system was statistically significant (Prob > chi2 = 0.0000). The Incident Rate Ratio (IRR) for the web-enabled DHIS2 system versus the district TB supervisor-led health management information system was 1.106625. Conclusion: The web-based integrated DHIS2 system was more effective in reporting missing TB cases. It presents an opportunity for better planning and allocation of resources for improved service delivery in a low-income setting.

Feasibility of a multifaceted intervention to improve treatment initiation among patients diagnosed with TB using Xpert MTB/RIF testing in Uganda.

BACKGROUND: One in five patients diagnosed with TB in Uganda are not initiated on TB treatment within two weeks of diagnosis. We evaluated a multifaceted intervention for improving TB treatment initiation among patients diagnosed with TB using Xpert® MTB/RIF testing in Uganda. METHODS: This was a pre-post interventional study at one tertiary referral hospital. The intervention was informed by the COM-B model and included; i) medical education sessions to improve healthcare worker knowledge about the magnitude and consequences of pretreatment loss to follow-up; ii) modified laboratory request forms to improve recording of patient contact information; and iii) re-designed workflow processes to improve timeliness of sputum testing and results dissemination. TB diagnostic process and outcome data were collected and compared from the period before (June to August 2019) and after (October to December 2019) intervention initiation. RESULTS: In September 2019, four CME sessions were held at the hospital and were attended by 58 healthcare workers. During the study period, 1242 patients were evaluated by Xpert® MTB/RIF testing at the hospital (679 pre and 557 post intervention). Median turnaround time for sputum test results improved from 12 hours (IQR 4-46) in the pre-intervention period to 4 hours (IQR 3-6) in the post-intervention period. The proportion of patients started on treatment within two weeks of diagnosis improved from 59% (40/68) to 89% (49/55) (difference 30%, 95% CI 14%-43%, p<0.01) while the proportion of patients receiving a same-day diagnosis increased from 7.4% (5/68) to 25% (14/55) (difference 17.6%, 95% CI 3.9%-32.7%, p<0.01). CONCLUSION: The multifaceted intervention was feasible and resulted in a higher proportion of patients initiating TB treatment within two weeks of diagnosis.

Patient and health system level barriers to and facilitators for tuberculosis treatment initiation in Uganda: a qualitative study.

BACKGROUND: The WHO END TB strategy targets to place at least 90% of all patients diagnosed with Tuberculosis (TB) on appropriate treatment. In Uganda, approximately 20% of patients diagnosed with TB are not initiated on TB treatment. We sought to identify the patient and health system level barriers to and facilitators for TB treatment initiation in Uganda. METHODS: We conducted the study at ten public health facilities (three primary care, four district and three tertiary referral hospitals). We carried out in-depth interviews with patients diagnosed with TB and key informant interviews with health managers. In addition, we held focus group discussions with healthcare workers involved in TB care. Data collection and thematic analysis of transcripts was informed by the Capability, Opportunity, Motivation and Behavior (COM-B) model. We identified relevant intervention functions using the Behavior Change Wheel. RESULTS: We interviewed 79 respondents (31 patients, 10 health managers and 38 healthcare workers). Common barriers at the health facility level included; lack of knowledge about the proportion of patients not initiated on TB treatment (psychological capability); difficulty accessing sputum results from the laboratory as well as difficulty tracing patients due to inadequate recording of patient addresses (physical opportunity). At the patient level, notable barriers included long turnaround time for sputum results and lack of transport funds to return to health facilities (physical opportunity); limited TB knowledge (psychological capability) and stigma (social opportunity). The most important facilitators identified were quick access to sputum test results either on the date of first visit (same-day diagnosis) or on the date of first return and availability of TB treatment (physical opportunity). We identified education, restructuring of the service environment to improve sputum results turnaround time and enablement to improve communication of test results as relevant intervention functions to alleviate these barriers to and enhance facilitators for TB treatment initiation. CONCLUSION: We found that barriers to treatment initiation existed at both the patient and health facility-level across all levels of the (Capability, Opportunity and Motivation) model. The intervention functions identified here should be tested for feasibility.

Developing a patient-centered community-based model for management of multi-drug resistant tuberculosis in Uganda: a discrete choice experiment.

BACKGROUND: The advent of all-oral regimens for the management of multi-drug resistant tuberculosis (MDR-TB) makes the implementation of community-based directly observed therapy (CB-DOT) a possibility for this group of patients. We set out to determine patient preferences for different attributes of a community-based model for the management of MDR-TB in Uganda. METHODS: The study was conducted at five tertiary referral hospitals. We used a parallel convergent mixed methods study design. To collect quantitative data, we conducted a discrete choice experiment (DCE) with three different attributes of community-based care (DOT provider, location of care, and type of support) combined into eight choice sets, each with two options and an opt-out. We elicited patient reasons for selection of each choice set using qualitative methods. We fitted a mixed logit choice model to determine patient preferences for different attributes of community-based care and estimated the relative importance of each attribute using the range method. and used deductive thematic analysis to understand the reasons for the choices made. RESULTS: From December 2019 to January 2020, we interviewed 103 patients with MDR-TB. We found that all the three attributes considered were important predicators of choice. The relative importance of each attribute was as follows; the type of additional support (relative importance 36.2%), the location of treatment delivery (33.5%), and the type of DOT provider (30.3%). Participants significantly valued treatment delivered by community health workers (CHWs) or expert clients over that delivered by a family member, treatment delivered at home over that delivered at the workplace, and monthly travel vouchers as the form of additional support over phone call or SMS reminders. Subgroup analyses showed significant differences in preference across HIV status, age groups and duration on MDR-TB treatment, but not across gender. The preferred model consisted of a CHW giving DOT at home and travel vouchers to enable attendance of monthly clinic follow-up visits to tertiary referral hospitals for treatment monitoring. Qualitative interviews revealed that patients perceived CHWs as knowledgeable and able to offer psychosocial support. Patients also preferred to take medication at home to save both time and money and lower the risk of facing TB stigma. CONCLUSION: People with MDR-TB prefer to be supported to take their medicine at home by a member of their community. The effectiveness of this model of care is being further evaluated.

Integrating interferon-gamma release assay testing into provision of tuberculosis preventive therapy is feasible in a tuberculosis high burden resource-limited setting: A mixed methods study.

The World Health Organization recommends the scale-up of tuberculosis preventive therapy (TPT) for persons at risk of developing active tuberculosis (TB) as a key component to end the global TB epidemic. We sought to determine the feasibility of integrating testing for latent TB infection (LTBI) using interferon-gamma release assays (IGRAs) into the provision of TPT in a resource-limited high TB burden setting. We conducted a parallel convergent mixed methods study at four tertiary referral hospitals. We abstracted details of patients with bacteriologically confirmed pulmonary tuberculosis (PBC TB). We line-listed household contacts (HHCs) of these patients and carried out home visits where we collected demographic data from HHCs, and tested them for both HIV and LTBI. We performed multi-level Poisson regression with robust standard errors to determine the associations between the presence of LTBI and characteristics of HHCs. Qualitative data was collected from health workers and analyzed using inductive thematic analysis. From February to December 2020 we identified 355 HHCs of 86 index TB patients. Among these HHCs, uptake for the IGRA test was 352/355 (99%) while acceptability was 337/352 (95.7%). Of the 352 HHCs that were tested with IGRA, the median age was 18 years (IQR 10-32), 191 (54%) were female and 11 (3%) were HIV positive. A total of 115/352 (32.7%) had a positive IGRA result. Among HHCs who tested negative on IGRA at the initial visit, 146 were retested after 9 months and 5 (3.4%) of these tested positive for LTBI. At multivariable analysis, being aged ≥ 45 years [PR 2.28 (95% CI 1.02, 5.08)], being employed as a casual labourer [PR 1.38 (95% CI 1.19, 1.61)], spending time with the index TB patient every day [PR 2.14 (95% CI 1.51, 3.04)], being a parent/sibling to the index TB patients [PR 1.39 (95% CI 1.21, 1.60)] and sharing the same room with the index TB patients [PR 1.98 (95% CI 1.52, 2.58)] were associated with LTBI. Implementation challenges included high levels of TB stigma and difficulties in following strict protocols for blood sample storage and transportation. Integrating home-based IGRA testing for LTBI into provision of TB preventive therapy in routine care settings was feasible and resulted in high uptake and acceptability of IGRA tests.

Provision of Decentralized TB Care Services: A Detect-Treat-Prevent Strategy for Children and Adolescents Affected by TB.

In this review, we discuss considerations and successful models for providing decentralized diagnosis, treatment, and prevention services for children and adolescents. Key approaches to building decentralized capacity for childhood TB diagnosis in primary care facilities include provider training and increased access to child-focused diagnostic tools and techniques. Treatment of TB disease should be managed close to where patients live; pediatric formulations of both first- and second-line drugs should be widely available; and any hospitalization should be for as brief a period as medically indicated. TB preventive treatment for child and adolescent contacts must be greatly expanded, which will require home visits to identify contacts, building capacity to rule out TB, and adoption of shorter preventive regimens. Decentralization of TB services should involve the private sector, with collaborations outside the TB program in order to reach children and adolescents where they first enter the health care system. The impact of decentralization will be maximized if programs are family-centered and designed around responding to the needs of children and adolescents affected by TB, as well as their families.

Implementation of an Effective Decentralised Programme for Detection, Treatment and Prevention of Tuberculosis in Children.

Childhood tuberculosis (TB) is consistently under-detected in most high-burden countries, including Uganda, especially in young children at high risk for severe disease and mortality. TB preventive treatment (TPT) for high-risk child contacts is also poorly implemented. The centralised concentration of services for child TB at the referral level is a major challenge in the prevention, detection and treatment of TB in children. In 2015, the DETECT Child TB Project was implemented in two districts of Uganda and involved decentralisation of healthcare services for child TB from tertiary to primary healthcare facilities, along with establishing linkages to support community-based household contact screening and management. The intervention resulted in improved case finding of child and adult TB cases, improved treatment outcomes for child TB and high uptake and completion of TPT for eligible child contacts. A detailed description of the development and implementation of this project is provided, along with findings from an external evaluation. The ongoing mentorship and practical support for health workers to deliver optimal services in this context were critical to complement the use of training and training tools. A summary of the project's outcomes is provided along with the key challenges identified and the lessons learnt.

Risk factors for mortality among patients diagnosed with multi-drug resistant tuberculosis in Uganda- a case-control study.

BACKGROUND: The World Health Organization (WHO) End TB strategy aims to reduce mortality due to tuberculosis (TB) to less than 5% by 2035. However, mortality due to multidrug-resistant tuberculosis (MDR-TB) remains particularly high. Globally, almost 20% of patients started on MDR-TB treatment die during the course of treatment every year. We set out to examine the risk factors for mortality among a cohort of patients diagnosed with MDR-TB in Uganda. METHODS: We conducted a case-control study nested within the national MDR-TB cohort. We defined cases as patients who died from any cause during the course of MDR-TB treatment. We selected two controls for each case from patients alive and on MDR-TB treatment at the time that the death occurred (incidence-density sampling). We matched the cases and controls on health facility at which they were receiving care. We performed conditional logistic regression to identify the risk factors for mortality. RESULTS: Data from 198 patients (66 cases and 132 controls) started on MDR-TB treatment from January 1 to December 31, 2016, was analyzed for this study. Cases were similar to controls in age/sex distribution, occupation and history of TB treatment. However, cases were more likely to be HIV infected while controls were more likely to have attained secondary level education. On multivariate regression analysis, co-infection with HIV (aOR 1.9, 95% CI [1.1-4.92] p = 0.05); non-adherence to MDR-TB treatment (aOR 1.92, 95% CI [1.02-4.83] p = 0.04); age over 50 years (aOR 3.04, 95% CI [1.13-8.20] p = 0.03); and having no education (aOR 3.61, 95% CI [1.1-10.4] p = 0.03) were associated with MDR-TB mortality. CONCLUSION: To mitigate MDR-TB mortality, attention must be paid to provision of social support particularly for older persons on MDR-TB treatment. In addition, interventions that support treatment adherence and promote early detection and management of TB among HIV infected persons should also be emphasized.

Comparative yield of different active TB case finding interventions in a large urban TB project in central Uganda: a descriptive study.

INTRODUCTION: Systematic screening for TB among patients presenting to care and among high risk populations is recommended to improve TB case finding. We aimed to describe the comparative yield of three TB screening approaches implemented by a large urban TB project in central Uganda. METHODS: We abstracted data on the screening cascade from 65 health facilities and their surrounding communities (numbers screened, with presumptive TB, receiving a diagnostic test and diagnosed with TB) from the different clinic and community TB registers. RESULTS: From January 2018 to December 2019, 93,378 (24%) of all patients screened at health facilities had presumptive TB; 77,381 (82.9%) received a diagnostic test and 14,305 (18.5%) were diagnosed with TB. The screening yield (the number of patients diagnosed with TB out of all patients screened) was 0.3% and was three times higher among men than women (0.6% vs 0.2% p<0.01). During targeted community screening interventions, 9874 (21.1%) of all patients screened had presumptive TB; 7034 (71.2%) of these received a diagnostic test and 1699 (24.2%) were diagnosed with TB. The screening yield was higher among men, (3.7% vs 3.3% p<0.01) and highest among children 0-14 (4.8% vs 3.2% p<0.01). CONCLUSION: Targeted community TB screening interventions improve access to TB diagnosis for men and children 0-14 years.

Comparative yield of different active TB case finding interventions in a large urban TB project in central Uganda: a descriptive study

Introduction: Systematic screening for TB among patients presenting to care and among high risk populations is recom- mended to improve TB case finding. We aimed to describe the comparative yield of three TB screening approaches imple- mented by a large urban TB project in central Uganda. Methods: We abstracted data on the screening cascade from 65 health facilities and their surrounding communities (num- bers screened, with presumptive TB, receiving a diagnostic test and diagnosed with TB) from the different clinic and com- munity TB registers. Results: From January 2018 to December 2019, 93,378 (24%) of all patients screened at health facilities had presumptive TB; 77,381 (82.9%) received a diagnostic test and 14,305 (18.5%) were diagnosed with TB. The screening yield (the number of patients diagnosed with TB out of all patients screened) was 0.3% and was three times higher among men than women (0.6% vs 0.2% p<0.01). During targeted community screening interventions, 9874 (21.1%) of all patients screened had presumptive TB; 7034 (71.2%) of these received a diagnostic test and 1699 (24.2%) were diagnosed with TB. The screening yield was higher among men, (3.7% vs 3.3% p<0.01) and highest among children 0-14 (4.8% vs 3.2% p<0.01). Conclusion: Targeted community TB screening interventions improve access to TB diagnosis for men and children 0-14 years

Patient and health system factors associated with pretreatment loss to follow up among patients diagnosed with tuberculosis using Xpert® MTB/RIF testing in Uganda.

BACKGROUND: In 2018, Uganda started only 65% of persons with incident tuberculosis on treatment. Pretreatment loss to follow up is an important contributor to suboptimal treatment coverage. We aimed to describe the patient and health facility-level characteristics associated with pretreatment loss to follow up among patients diagnosed with pulmonary tuberculosis at public health facilities in Uganda. METHODS: At ten public health facilities, laboratory register data was used to identify patients aged ≥ 15 years who had a positive Xpert®MTB/RIF test. Initiation on TB treatment was ascertained using the clinical register. Factors associated with not being initiated on TB treatment within two weeks of diagnosis were examined using a multilevel logistic regression model accounting for clustering by health facility. RESULTS: From January to June 2018, 510 patients (61.2% male and 31.5% HIV co-infected) were diagnosed with tuberculosis. One hundred (19.6%) were not initiated on TB treatment within 2 weeks of diagnosis. Not having a phone number recorded in the clinic registers (aOR 7.93, 95%CI 3.93-13.05); being HIV-infected (aOR 1.83; 95% CI: 1.09-3.26) and receiving care from a high volume health facility performing more than 12 Xpert tests per day (aOR 4.37, 95%CI 1.69-11.29) and were significantly associated with pretreatment loss to follow up. CONCLUSION: In public health facilities in Uganda, we found a high rate of pretreatment loss to follow up especially among TBHIV co-infected patients diagnosed at high volume health facilities. Interventions to improve the efficiency of Xpert® MTB/RIF testing, including monitoring of the TB care cascade should be developed and implemented.

Estimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda.

INTRODUCTION: Tuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda. METHODS: At ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU. RESULTS: Of 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61-6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%-11.6%) to 10.2% (95% CI 7.7%-13.4%). CONCLUSION: Patients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.