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.

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.

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.

Households experiencing catastrophic costs due to tuberculosis in Uganda: magnitude and cost drivers.

BACKGROUND: Tuberculosis (TB) patients in Uganda incur large costs related to the illness, and while seeking and receiving health care. Such costs create access and adherence barriers which affect health outcomes and increase transmission of disease. The study ascertained the proportion of Ugandan TB affected households incurring catastrophic costs and the main cost drivers. METHODS: A cross-sectional survey with retrospective data collection and projections was conducted in 2017. A total of 1178 drug resistant (DR) TB (44) and drug sensitive (DS) TB patients (1134), 2 weeks into intensive or continuation phase of treatment were consecutively enrolled across 67 randomly selected TB treatment facilities. RESULTS: Of the 1178 respondents, 62.7% were male, 44.7% were aged 15-34 years and 55.5% were HIV positive. For each TB episode, patients on average incurred costs of USD 396 for a DS-TB episode and USD 3722 for a Multi drug resistant tuberculosis (MDR TB) episode. Up to 48.5% of households borrowed, used savings or sold assets to defray these costs. More than half (53.1%) of TB affected households experienced TB-related costs above 20% of their annual household expenditure, with the main cost drivers being non-medical expenditure such as travel, nutritional supplements and food. CONCLUSION: Despite free health care in public health facilities, over half of Ugandan TB affected households experience catastrophic costs. Roll out of social protection interventions like TB assistance programs, insurance schemes, and enforcement of legislation related to social protection through multi-sectoral action plans with central NTP involvement would palliate these costs.

Applying a Three-Tier Approach to Address Gaps in Oral Pre-Exposure Prophylaxis Uptake and Continuity in Uganda: A Mixed Methods Approach.

BACKGROUND: We describe a 3-tier approach involving a gap analysis, root cause analysis, and pre-exposure prophylaxis (PrEP) collaborative to understand the gap and identify and address the main barriers to oral PrEP uptake and continuity in Uganda. METHODS: We used a mixed methods design with retrospective, cross-sectional, and prospective components. The gap analysis involved descriptive analysis of PrEP uptake and continuity. The RCA identified the main barriers to initiation and continuity on PrEP among 1,334 clients who declined to start PrEP and 1,266 who missed their appointment but were at risk. The PrEP collaborative tested changes mapped onto specific barriers to optimize the PrEP clinical service delivery. A trend analysis of routinely collected data of the PrEP cascade determined significant shifts and trends in PrEP uptake and continuity. RESULTS: Only 60% of the high-risk population eligible for PrEP were enrolled, while fewer than 30% of the cumulative number of PrEP users were refilled each quarter. Uncertainty and fear of side effects, perceptions about the harmfulness of the medication, perceived inability to adhere to PrEP, and stigma were the main reasons why clients rejected PrEP. Lack of access to the facility, side effects, pill burden, stigma, perceived low-risk exposure to HIV, and preference of staying at work as opposed to picking up refills affected continuity on PrEP. The collaborative registered statistically significant shifts in PrEP enrollment from 64% to 89% and continuity from 51% to 78% between July 21 and November 22 following the collaborative intervention. CONCLUSIONS: We recommend using a 3-tier approach for other similar implementation contexts to strengthen PrEP programming, given the marked statistical shift in PrEP uptake and continuity. This begins with understanding the gap and barriers to use among clients, followed by mapping interventions to specific barriers through a quality improvement collaborative.

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.

Tuberculosis yield among contacts of non-pulmonary bacteriologically confirmed index TB patients in the urban setting of central Uganda.

BACKGROUND: The World Health Organization (WHO) recommends systematic and active investigation of TB contacts. However, lower priority is given to contact investigation among other non-pulmonary bacteriologically confirmed (PBC) cases; it thus contributes to the scarce information on the yield of TB among contacts of index TB patients without microbiological confirmation (non-PBC patients). This study therefore aimed at establishing the yield of TB among contacts of PBC and non-PBC index TB patients in the urban setting of central Uganda. METHODS: We abstracted data from the Uganda national TB contact investigation registers present at 48 health facilities for the period January 2018 to August 2020. The screening yield for both PBC and non-PBC, timing of TB diagnosis among contacts were determined. Logistic regression was used to examine predictors for diagnosing contacts as non PBC TB patients. RESULTS: From January 2018 to August 2020, 234 persons were diagnosed with TB from a total of 14,275 contacts traced for both PBC and non-PBC TB index patients at 48 facilities. Of these, 100(42.7%) were contacts of non-PBC index patients. TB screening yield was higher among contacts of non PBC 100(2.0%) compared to 134(1.4%) among contacts of PBC index patients. For both groups, over 80% of their contacts were diagnosed with TB within 3 months from the day of TB treatment start of the index case. On multivariate logistic regression the only predictor for diagnosing contacts as non PBC TB patients was age under15 years (adjusted odds ratio [aOR] 7.53, 95% CI [3.27-17.3] p = <0.05). CONCLUSION: The yield of TB among contacts of non-PBC index case is nearly the same for contacts of PBC index cases and most contacts were diagnosed with TB disease during the intensive TB treatment phase of the index case. There was no association between the type of TB (PBC, non-PBC) disease diagnosed in the contacts, and that of index TB patients. To improve TB case-finding, emphasis should be placed on contact investigation for household and close contacts of all other index cases with pulmonary tuberculosis regardless of whether PBC or non-PBC during the intensive phase of treatment.

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.

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.

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.

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