Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Time to blood pressure control and predictors among patients receiving integrated treatment for hypertension and HIV based on an adapted WHO HEARTS implementation strategy at a large urban HIV clinic in Uganda.

In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged ≥ 18 years and initiated Amlodipine 5 mg mono-therapy for BP (140-159)/(90-99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP < 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637-0.917) were associated with longer time to BP control, while being on ART for >10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126-1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings.

Spatial distribution and temporal trends of tuberculosis case notifications, Uganda: a ten-year retrospective analysis (2013-2022).

BACKGROUND: Uganda has a high incidence and prevalence of tuberculosis (TB). Analysis of spatial and temporal distribution of TB is an important tool for supporting spatial decision-making, planning, and policy formulations; however, this information is not readily available in Uganda. We determined the spatial distribution and temporal trends of tuberculosis notifications in Uganda, 2013-2022. METHODS: We conducted a retrospective analysis of routinely-generated program data reported through the National TB and Leprosy Programme (NTLP) surveillance system. We abstracted data on all TB cases diagnosed from 2013 to 2022 by district and region. We drew choropleth maps for Uganda showing the TB case notification rates (CNR) per 100,000 and calculated the CNR using the cases per district as the numerator and individual district populations as the denominators. Population estimates were obtained from the 2014 National Population and Housing Census, and a national growth rate of 3% was used to estimate the annual population increase. RESULTS: Over the entire study period, 568,957 cases of TB were reported in Uganda. There was a 6% annual increase in TB CNR reported from 2013 (134/100,000) to 2022 (213/100,000) (p-value for trend p < 0.00001). Cases were reported from all 12 Ministry of Health regions during the entire period. The distribution of CNR was heterogeneous throughout the country and over time. Moroto, Napak and Kampala districts had consistently high CNR throughout the ten years. Kalangala district had lower CNR from 2013 to 2018 but high CNR from 2019 to 2022. Moroto region, in the northeast, had consistently high CNR while Mbale and Soroti regions in Eastern Uganda had the lowest CNR throughout the ten years. CONCLUSION: There was an overall increasing trend in TB CNR from 2013 to 2022. We recommend that the National TB program institutes intensified measures aided by more funding to mitigate and reverse the negative impacts of the COVID-19 pandemic on TB.

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys.

Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%-56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27-2.40) and symptomatic TB (OR 1.49, 95% CI 1.34-1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17-2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55-1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70-3.62) for subclinical TB and OR 1.43, 95% CI 0.59-3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0-85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Using the RE-AIM framework to evaluate the implementation and effectiveness of a WHO HEARTS-based intervention to integrate the management of hypertension into HIV care in Uganda: a process evaluation.

BACKGROUND: World Health Organization (WHO) HEARTS packages are increasingly used to control hypertension. However, their feasibility in persons living with HIV (PLHIV) is unknown. We studied the effectiveness and implementation of a WHO HEARTS intervention to integrate the management of hypertension into HIV care. METHODS: This was a mixed methods study at Uganda's largest HIV clinic. Components of the adapted WHO HEARTS intervention were lifestyle counseling, free hypertension medications, hypertension treatment protocol, task shifting, and monitoring tools. We determined the effectiveness of the intervention among PLHIV by comparing hypertension and HIV outcomes at baseline and 21 months. The RE-AIM framework was used to evaluate the implementation outcomes of the intervention at 21 months. We conducted four focus group discussions with PLHIV (n = 42), in-depth interviews with PLHIV (n = 9), healthcare providers (n = 15), and Ministry of Health (MoH) policymakers (n = 2). RESULTS: Reach: Among the 15,953 adult PLHIV in the clinic, of whom 3892 (24%) had been diagnosed with hypertension, 1133(29%) initiated integrated hypertension-HIV treatment compared to 39 (1%) at baseline. Among the enrolled patients, the mean age was 51.5 ± 9.7 years and 679 (62.6%) were female. EFFECTIVENESS: Among the treated patients, hypertension control improved from 9 to 72% (p < 0.001), mean systolic blood pressure (BP) from 153.2 ± 21.4 to 129.2 ± 15.2 mmHg (p < 0.001), and mean diastolic BP from 98.5 ± 13.5 to 85.1 ± 9.7 mmHg (p < 0.001). Overall, 1087 (95.9%) of patients were retained by month 21. HIV viral suppression remained high, 99.3 to 99.5% (p = 0.694). Patients who received integrated hypertension-HIV care felt healthy and saved more money. Adoption: All 48 (100%) healthcare providers in the clinic were trained and adopted the intervention. Training healthcare providers on WHO HEARTS, task shifting, and synchronizing clinic appointments for hypertension and HIV promoted adoption. IMPLEMENTATION: WHO HEARTS intervention was feasible and implemented with fidelity. Maintenance: Leveraging HIV program resources and adopting WHO HEARTS protocols into national guidelines will promote sustainability. CONCLUSIONS: The WHO HEARTS intervention promoted the integration of hypertension management into HIV care in the real-world setting. It was acceptable, feasible, and effective in controlling hypertension and maintaining optimal viral suppression among PLHIV. Integrating this intervention into national guidelines will promote sustainability.

Integrated multi-month dispensing of antihypertensive and antiretroviral therapy to sustain hypertension and HIV control.

Multi-month dispensing (MMD) is a patient-centered approach in which stable patients receive medicine refills of three months or more. In this pre-post longitudinal study, we determined hypertension and HIV treatment outcomes in a cohort of hypertensive PLHIV at baseline and 12 months of receiving integrated MMD. At each clinical encounter, one healthcare provider attended to both hypertension and HIV needs of each patient in an HIV clinic. Among the 1,082 patients who received MMD, the mean age was 51 (SD = 9) years and 677 (63%) were female. At the start of MMD, 1,071(98.9%) patients had achieved HIV viral suppression, and 767 (73.5%) had achieved hypertension control. Mean blood pressure reduced from 135/87 (SD = 15.6/15.2) mmHg at the start of MMD to 132/86 (SD = 15.2/10.5) mmHg at 12 months (p < 0.0001). Hypertension control improved from 73.5% to 78.5% (p = 0.01) without a significant difference in the proportion of patients with HIV viral suppression at baseline and at 12 months, 98.9% vs 99.0% (p = 0.65). Patients who received MMD with elevated systolic blood pressure at baseline were less likely to have controlled blood pressure at 12 months (OR-0.9, 95% CI, 0.90,0.92). Overall, 1,043 (96.4%) patients were retained at 12 months. Integrated MMD for stable hypertensive PLHIV improved hypertension control and sustained optimal HIV viral suppression and retention of patients in care. Therefore, it is feasible to provide integrated MMD for both hypertension and HIV treatment and achieve dual control in the setting of sub-Saharan Africa.

Improved hypertension control at six months using an adapted WHO HEARTS-based implementation strategy at a large urban HIV clinic in Uganda.

OBJECTIVES: To adapt a World Health Organization HEARTS-based implementation strategy for hypertension (HTN) control at a large urban HIV clinic in Uganda and determine six-month HTN and HIV outcomes among a cohort of adult persons living with HIV (PLHIV). METHODS: Our implementation strategy included six elements: health education, medication adherence, and lifestyle counseling; routine HTN screening; task shifting of HTN treatment; evidence-based HTN treatment protocol; consistent supply of HTN medicines free to patients; and inclusion of HTN-specific monitoring and evaluation tools. We conducted a pre-post study from October 2019 to March 2020 to determine the effect of this strategy on HTN and HIV outcomes at baseline and six months. Our cohort comprised adult PLHIV diagnosed with HTN who made at least one clinic visit within two months prior to study onset. FINDINGS: We enrolled 1,015 hypertensive PLHIV. The mean age was 50.1 ± 9.5 years and 62.6% were female. HTN outcomes improved between baseline and six months: mean systolic BP (154.3 ± 20.0 to 132.3 ± 13.8 mmHg, p < 0.001); mean diastolic BP (97.7 ± 13.1 to 85.3 ± 9.5 mmHg, p < 0.001) and proportion of patients with controlled HTN (9.3% to 74.1%, p < 0.001). The HTN care cascade also improved: treatment initiation (13.4% to 100%), retention in care (16.2% to 98.5%), monitoring (16.2% to 98.5%), and BP control among those initiated on HTN treatment (2.2% to 75.2%). HIV cascade steps remained high (> 95% at baseline and six months) and viral suppression was unchanged (98.7% to 99.2%, p = 0.712). Taking ART for more than two years and HIV viral suppression were independent predictors of HTN control at six months. CONCLUSIONS: A HEARTS-based implementation strategy at a large, urban HIV center facilitates integration of HTN and HIV care and improves HTN outcomes while sustaining HIV control. Further implementation research is needed to study HTN/HIV integration in varied clinical settings among diverse populations.

Theory-Informed Design of a Tailored Strategy for Implementing Household TB Contact Investigation in Uganda.

Since 2012, the World Health Organization has recommended household contact investigation as an evidence-based intervention to find and treat individuals with active tuberculosis (TB), the most common infectious cause of death worldwide after COVID-19. Unfortunately, uptake of this recommendation has been suboptimal in low- and middle-income countries, where the majority of affected individuals reside, and little is known about how to effectively deliver this service. Therefore, we undertook a systematic process to design a novel, theory-informed implementation strategy to promote uptake of contact investigation in Uganda, using the COM-B (Capability-Opportunity-Motivation-Behavior) model and the Behavior Change Wheel (BCW) framework. We systematically engaged national, clinic-, and community-based stakeholders and collectively re-examined the results of our own formative, parallel mixed-methods studies. We identified three core behaviors within contact investigation that we wished to change, and multiple antecedents (i.e., barriers and facilitators) of those behaviors. The BCW framework helped identify multiple intervention functions targeted to these antecedents, as well as several policies that could potentially enhance the effectiveness of those interventions. Finally, we identified multiple behavior change techniques and policies that we incorporated into a multi-component implementation strategy, which we compared to usual care in a household cluster-randomized trial. We introduced some components in both arms, including those designed to facilitate initial uptake of contact investigation, with improvement relative to historical controls. Other components that we introduced to facilitate completion of TB evaluation-home-based TB-HIV evaluation and follow-up text messaging-returned negative results due to implementation failures. In summary, the Behavior Change Wheel framework provided a feasible and transparent approach to designing a theory-informed implementation strategy. Future studies should explore the use of experimental methods such as micro-randomized trials to identify the most active components of implementation strategies, as well as more creative and entrepreneurial methods such as human-centered design to better adapt the forms and fit of implementation strategies to end users.

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.

Accuracy and Incremental Yield of the Chest X-Ray in Screening for Tuberculosis in Uganda: A Cross-Sectional Study.

The WHO END TB strategy requires ≥90% case detection to combat tuberculosis (TB). Increased TB case detection requires a more sensitive and specific screening tool. Currently, the symptoms recommended for screening TB have been found to be suboptimal since up to 44% of individuals with TB are asymptomatic. The chest X-ray (CXR) as a screening tool for pulmonary TB was evaluated in this study, as well as its incremental yield in TB diagnosis using a cross-sectional study involving secondary analysis of data of 4512 consented/assented participants ≥15 years who participated in the Uganda National TB prevalence survey between 2014 and 2015. Participants with a cough ≥2 weeks, fever, weight loss, and night sweats screened positive for TB using the symptoms screening method, while participants with a TB defining abnormality on CXR screened positive for TB by the CXR screening method. The Löwenstein-Jensen (LJ) culture was used as a gold standard for TB diagnosis. The CXR had 93% sensitivity and 65% specificity compared to LJ culture results, while symptoms had 76% sensitivity and 31% specificity. The screening algorithm involving the CXR in addition to symptoms led to a 38% increment in the yield of diagnosed tuberculosis. The number needed to screen using the CXR and symptoms screening algorithm was 32 compared to 45 when the symptoms are used alone. Therefore, the CXR in combination with symptoms is a good TB screening tool and increases the yield of diagnosed TB.

Adherence to the MDR-TB intensive phase treatment protocol amongst individuals followed up at central and peripheral health care facilities in Uganda - a descriptive study.

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.

Pre-diagnostic drop out of presumptive TB patients and its associated factors at Bugembe Health Centre IV in Jinja, Uganda.

BACKGROUND: Drop out of presumptive TB individuals before making a final diagnosis poses a danger to the individual and their community. We aimed to determine the proportion of these presumptive TB drop outs and their associated factors in Bugembe Health Centre, Jinja, Uganda. METHODS: We used data from the DHIS2, presumptive and laboratory registers of Bugembe Health Centre IV for 2017. Descriptive statistics were used to summarize the population characteristics. A modified Poisson regression model via the generalized linear model (GLM) with log link and robust standard errors was used for bivariate and multivariate analysis.We used data from the DHIS2, presumptive and laboratory registers of Bugembe Health Centre IV for 2017. Descriptive statistics were used to summarize the population characteristics. A modified Poisson regression model via the generalized linear model (GLM) with log link and robust standard errors was used for bivariate and multivariate analysis. RESULT: Among the 216 registered presumptive TB patients who were less than 1% of patients visiting the outpatients' department, 40.7% dropped out before final diagnosis was made. Age and HIV status were significantly associated with pre-diagnostic drop out while gender and distance from the health center were not. CONCLUSION: A high risk to individuals and the community is posed by the significant proportion of presumptive TB patients dropping out before final diagnosis. Health systems managers need to consider interventions targeting young persons, male patients, HIV positive persons.

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.

Challenges with scale-up of GeneXpert MTB/RIF® in Uganda: a health systems perspective.

BACKGROUND: Many high burden countries are scaling-up GeneXpert® MTB/RIF (Xpert) testing for tuberculosis (TB) using a hub-and-spoke model. However, the effect of scale up on reducing TB has been limited. We sought to characterize variation in implementation of referral-based Xpert TB testing across Uganda, and to identify health system factors that may enhance or prevent high-quality implementation of Xpert testing services. METHODS: We conducted a cross-sectional study triangulating quantitative and qualitative data sources at 23 community health centers linked to one of 15 Xpert testing sites between November 2016 and May 2017 to assess health systems infrastructure for hub-and-spoke Xpert testing. Data sources included a standardized site assessment survey, routine TB notification data, and field notes from site visits. RESULTS: Challenges with Xpert implementation occurred at every step of the diagnostic evaluation process, leading to low overall uptake of testing. Of 2192 patients eligible for TB testing, only 574 (26%) who initiated testing were referred for Xpert testing. Of those, 54 (9.4%) were Xpert confirmed positive just under half initiated treatment within 14 days (n = 25, 46%). Gaps in required infrastructure at 23 community health centers to support the hub-and-spoke system included lack of refrigeration (n = 14, 61%) for sputum testing and lack of telephone/mobile communication (n = 21, 91%). Motorcycle riders responsible for transporting sputum to Xpert sites operated variable with trips once, twice, or three times a week at 10 (43%), nine (39%) and four (17%) health centers, respectively. Staff recorded Xpert results in the TB laboratory register at only one health center and called patients with positive results at only two health centers. Of the 15 Xpert testing sites, five (33%) had at least one non-functioning module. The median number of tests per day was 3.57 (IQR 2.06-4.54), and 10 (67%) sites had error/invalid rates > 5%. CONCLUSIONS: Although Xpert devices are now widely distributed throughout Uganda, health system factors across the continuum from test referral to results reporting and treatment initiation preclude effective implementation of Xpert testing for patients presenting to peripheral health centers. Support for scale up of innovative technologies should include support for communication, coordination and health systems integration.

Quality of care for patients evaluated for tuberculosis in the context of Xpert MTB/RIF scale-up.

RATIONALE: Many high-burden countries are scaling-up Xpert MTB/RIF using a hub-and-spoke model. We evaluated the quality of care for patients undergoing TB evaluation at microscopy centers (spokes) linked to Xpert testing sites (hubs) in Uganda. OBJECTIVES: To characterize the extent to which patients were receiving care in accordance with international and national guidelines. METHODS: We conducted a prospective cohort study of all adults with presumptive pulmonary TB at 24 health centers linked to Xpert testing sites. Health center staff photographed TB registers, and uploaded photos to a secure server bi-weekly. We assessed the proportion of patients (1) initiating testing; (2) completing testing; and (3) treated for confirmed TB within 14 days. MEASUREMENTS AND MAIN RESULTS: Between January to December 2017, 6744 patients underwent evaluation for pulmonary TB. Only 1316 patients had sputum referred for Xpert testing, including 1075/3229 (33.3%) people living with HIV and 241/3515 (6.9%) without HIV. Of 119 patients confirmed to have TB by Xpert testing, 44 (36%) did not initiate treatment. There were significant losses along the entire diagnostic cascade of care, with only 5330/6744 (79.0%) patients having samples referred for sputum-based testing, 2978/5330 (55.9%) patients completing recommended testing if referred, and 313/418 (74.9%) patients initiating treatment within 14 days if confirmed to have TB. CONCLUSIONS: Although coverage of Xpert testing services across Uganda is high, the quality of care delivered to patients undergoing TB evaluation remains poor. Further research is needed to identify health system interventions to facilitate uptake of Xpert testing and high-quality care.

Screening tuberculosis patients for diabetes mellitus in a routine program setting in Kampala, Uganda: a cross-sectional study.

Background: Uganda is located in East Africa and is among the countries with the lowest income globally. The ten health centres in this project serve populations in the under-privileged communities of Kampala. The objective of the study was to implement diabetes mellitus (DM) screening among tuberculosis (TB) patients in a routine program setting with limited resources and high human immunodeficiency virus (HIV) prevalence. Methods: A descriptive cross-sectional observational study was conducted in ten health centres in Kampala, Uganda. As part of a project to implement DM screening in a routine setting, TB patients were screened for DM by trained health workers. A fasting blood glucose (FBG) value ≥7.0mmol/l was considered to indicate DM. For this study, aggregate data was collected and analysed using SPSS for Windows, version 13.0. Results:  Among 4,590 TB patients registered, 4,016 (88.0%) were screened with random blood glucose (RBG). Of those with RBG ≥6.1mmol/l, 1,093 (83.3%) were screened with FBG. In total, 92 (2.3%) patients were diagnosed with DM and 66 (71.8%) of them were newly diagnosed. The proportion of TB patients screened with FBG in the health centres varied from 58.2% to 100%. The proportion of patients screened with FBG and the prevalence of DM were significantly higher in private health centres compared with public health centres. The health centres in peri-urban areas screened more patients with RBG than those in urban areas. Health centres without DM services screened a larger number of patients with RBG and FBG than those with DM services. Conclusions: It appears feasible to implement screening TB patients for DM in routine program settings with limited resources and high HIV prevalence. Its introduction requires close collaboration between TB and DM services. The challenges identified need government attention and certain institutional and service-related factors need to be better managed at times.

Anti-retroviral therapy scale-up and its impact on sex-stratified tuberculosis notification trends in Uganda.

INTRODUCTION: In order to end the tuberculosis (TB) epidemic by 2035, countries must achieve a 10% annual decline in tuberculosis incidence rates by 2025. Provision of antiretroviral therapy (ART) has been associated with population level decreases in TB notification rates. We aimed to assess whether the progressive scale-up of ART provision over the past nine years has had an effect on population level trends of TB notification in Uganda stratified by sex and HIV status. METHODS: The study area consisted of Kampala and eight surrounding districts. Annual TB notifications and mid-year populations were used to calculate notification rates per 100,000 population from the study area. Numbers alive and retained on ART were used to calculate ART coverage, overall and by sex. TB notification rates (TBNRs) overall and stratified by sex and HIV status were calculated for the period 2009 to 2017. Trends in TBNRs before and after rollout of universal ART for pregnant women in 2013 were examined using Poisson regression models. To gain insight into the trends in CD4+ T-cell counts at ART initiation over the study period, we performed a sub analysis of patient level data from the Infectious Diseases Institute clinic. RESULTS: From 2009 to 2017, ART coverage increased by 27.6% among men and by 35.4% among women. TBNRs declined during the same period. Overall, the average annual percentage decline in TBNRs was -3.5% (95%CI -3.7% to -3.3%), (-2.3% (95%CI -2.6% to -1.9%) in men and -5.4% (95%CI -5.7% to -5.0%) in women). ART coverage increased after 2013 but this was not associated with an accelerated decline in overall TBNRs among HIV-positive persons -3.6% before 2013 and -5.2% after 2013; p = 0.33. The proportion of patients initiating ART with CD4+ T-cell count ≤ 200 cells/mL did not decrease significantly after 2013 (42.2% to 32.2%, p = 0.05). CONCLUSIONS: Although ART scale-up was temporally associated with a decline in TB notification rates, the achieved rates of decline are below those required to achieve the End TB Targets. Additional investments in tuberculosis control should include efforts to promote earlier care seeking and ART initiation among HIV-positive persons.

Home-based tuberculosis contact investigation in Uganda: a household randomised trial.

INTRODUCTION: The World Health Organization (WHO) recommends household tuberculosis (TB) contact investigation in low-income countries, but most contacts do not complete a full clinical and laboratory evaluation. METHODS: We performed a randomised trial of home-based, SMS-facilitated, household TB contact investigation in Kampala, Uganda. Community health workers (CHWs) visited homes of index patients with pulmonary TB to screen household contacts for TB. Entire households were randomly allocated to clinic (standard-of-care) or home (intervention) evaluation. In the intervention arm, CHWs offered HIV testing to adults; collected sputum from symptomatic contacts and persons living with HIV (PLWHs) if ≥5 years; and transported sputum for microbiologic testing. CHWs referred PLWHs, children <5 years, and anyone unable to complete sputum testing to clinic. Sputum testing results and/or follow-up instructions were returned by automated SMS texts. The primary outcome was completion of a full TB evaluation within 14 days; secondary outcomes were TB and HIV diagnoses and treatments among screened contacts. RESULTS: There were 471 contacts of 190 index patients allocated to the intervention and 448 contacts of 182 index patients allocated to the standard-of-care. CHWs identified 190/471 (40%) intervention and 213/448 (48%) standard-of-care contacts requiring TB evaluation. In the intervention arm, CHWs obtained sputum from 35/91 (39%) of sputum-eligible contacts and SMSs were sent to 95/190 (50%). Completion of TB evaluation in the intervention and standard-of-care arms at 14 days (14% versus 15%; difference -1%, 95% CI -9% to 7%, p=0.81) and yields of confirmed TB (1.5% versus 1.1%, p=0.62) and new HIV (2.0% versus 1.8%, p=0.90) diagnoses were similar. CONCLUSIONS: Home-based, SMS-facilitated evaluation did not improve completion or yield of household TB contact investigation, likely due to challenges delivering the intervention components.

Chronic Respiratory Symptoms and Lung Abnormalities Among People With a History of Tuberculosis in Uganda: A National Survey.

BACKGROUND: People with pulmonary tuberculosis are at risk of developing chronic respiratory disorders due to residual lung damage. To date, the scope of the problem in high-burden tuberculosis countries is relatively unknown. METHODS: Chronic respiratory symptoms (cough and phlegm lasting >2 weeks) and radiological lung abnormalities were compared between adults with and without a history of tuberculosis among the general population of Uganda. Multivariable regression models were used to estimate odds ratios (ORs) with adjustment for age, gender, smoking, education, setting, and region. Random effects models accounted for village clustering effect. RESULTS: Of 45293 invited people from 70 villages, 41154 (90.9%) participated in the survey. A total of 798 had a history of tuberculosis and, among them, 16% had respiratory symptoms and 41% X-ray abnormalities. Adjusted ORs showed strong evidence for individuals with a history of tuberculosis having increased risk of respiratory symptoms (OR, 4.02; 95% confidence interval [CI], 3.25-4.96) and X-ray abnormalities (OR, 17.52; 95% CI, 14.76-20.79), attributing 6% and 24% of the respective population risks. CONCLUSIONS: In Uganda, a history of tuberculosis was a strong predictor of respiratory symptoms and lung abnormalities, before older age and smoking. Eliminating tuberculosis disease could reduce the prevalence of chronic respiratory symptoms as much as eliminating smoking.

Improving TB case notification in northern Uganda: evidence of a quality improvement-guided active case finding intervention.

BACKGROUND: Strategies to identify and treat undiagnosed prevalent cases that have not sought diagnostic services on their own, are necessary to treat TB in patients earlier and interrupt transmission. Late presentation for medical services of symptomatic patients require special efforts to detect early and notify TB in high risk populations. An intervention that combined quality improvement with facility-led active case finding (QI-ACF) was implemented in 10 districts of Northern Uganda with the highest TB burden to improve case notification among populations at highest risk of TB. METHODS: Using QI-ACF intervention approach in 48 facilities, we; 1) targeted key vulnerable populations, 2) engaged district and facility teams in TB systems strengthening, 3) conducted systematic screening and diagnosis in vulnerable groups (people living with HIV, fishing communities, and prisoners), and 4) trained health workers on national x-ray diagnosis guidelines for smear-negative patients. Facility-led QI-ACF meant that health care providers identified the target population, mobilized and massively screened suspects, and addressed gaps in documentation. Chest X-ray diagnosis was promoted for smear-negative TB among those suspects whose sputum examination was negative. The effect of the intervention on case notification was then assessed separately over the post intervention period. RESULTS: Over all TB case notification in the intervention districts increased from 171 to 223 per 100,000 population between the baseline months of October-December 2016 and end line month of April-June 2017. TB patient contacts had the majority of TB positive cases identified during active case finding (40, 6.1%). Fishing communities had the highest TB positivity rate at 6.8%. Prisoners accounted for the lowest number of TB positive cases at 34 (2.3%). CONCLUSION: Targeting should be applied at all levels of TB intervention to improve yield: targeting districts and facilities with the lowest rates of case notification and targeting index patient contacts, HIV clients, and fishing communities. Screening tools are useful to guide health workers to identify presumptive cases. Efforts to improve availability of x-ray for TB diagnosis contributed to almost half of the new cases identified. Having all HIV patients who were eligible for viral load provide sputum for TB screening proved easy to implement.