Digital health solutions and integrated COVID-19 and TB services to help recover TB care and prevention services in the COVID-19 pandemic: A descriptive study in four high TB burden countries.

BACKGROUND: The measures undertaken to control COVID-19 have disrupted many platforms including tuberculosis (TB) healthcare services. Consequently, declines in TB notifications have been observed in various countries. We visualized changes over time in TB and SARS-CoV-2 infection notifications and reported on country-specific strategies to retain TB care and prevention services in Kyrgyzstan, Nigeria, Tanzania, and Vietnam. METHODS: We collected and visualized quarterly, retrospective, and country-specific data (Quarter (Q) 1 2018- Q1 2021) on SARS-CoV-2 infection and TB notifications. Additionally, we conducted a country-specific landscape assessment on COVID-19 measures, including lockdowns, operational level strategy of TB care and prevention services, and strategies employed to recover and retain those services. We used negative binomial regression models to assess the association between the installation of COVID-19 measures and changes in TB notifications. RESULTS: TB notifications declined in Kyrgyzstan and Vietnam, and (slightly) increased in Nigeria and Tanzania. The changes in TB notifications were associated with the installation of various COVID-19 prevention measures for Kyrgyzstan and Vietnam (declines) and Nigeria (increases). All countries reported reduced TB screening and testing activities. Countries reported the following strategies to retain TB prevention and care services: digital solutions for treatment adherence support, capacity building, and monitor & evaluation activities; adjustment in medication supply/delivery & quantity, including home delivery, pick up points, and month supply; integrated TB/COVID-19 screening & diagnostic platform; and the use of community health care workers. CONCLUSION: Following the COVID-19 pandemic, we did not observe consistent changes in TB notifications across countries. However, all countries reported lower operating levels of TB prevention and care services. Digital health solutions, community-based interventions, and the integration of COVID-19 and TB testing services were employed to recover and retain those services.

The yield of chest X-ray based versus symptom-based screening among patients with diabetes mellitus in public health facilities in Addis Ababa, Ethiopia.

Background: Patients with diabetes mellitus (DM) are at increased risk of developing TB, but the best screening algorithm for early detection and treatment of TB remains unknown. Our objective was to determine if combining routine chest X-ray screening could have a better yield compared with symptom-based screening alone. Methods: We conducted this cross-sectional study between September 2020 and September 2021 in 26 public health facilities in Addis Ababa, Ethiopia. All DM patients attending the clinics during the study period were offered chest X-ray and symptom screening simultaneously followed by confirmatory Xpert testing. We analyzed the number and proportion of patients with TB by the diagnostic algorithm category and performed binary logistic regression analysis to identify predictors of TB diagnosis. Results: Of 7394 patients screened, 54.6 % were female, and their median age was 53 years. Type-2 diabetes accounted for 89.6 % of all participants of the patients. Of 172 symptomatic patients, chest X-ray suggested TB in 19, and 11 of these were confirmed to have TB (8 bacterilogicially confirmed and 3 clinically diagnosed). Only 2 of the 152 asymptomatic patients without X-ray findings had TB (both bacteriologically confirmed). X-ray was not done for one patient. On the other hand, 28 of 7222 symptom-negative patients had X-ray findings suggestive of TB, and 7 of these were subsequently confirmed with TB (6 clinically diagnosed). When combined with 8 patients who were on treatment for TB at the time of the screening, the overall point prevalence of TB was 380 per 100,000. The direct cost associated with the X-ray-based screening was 42-times higher. Conclusion: Chest X-ray led to detection of about a third of TB patients which otherwise would have been missed but the algorithm is more expensive. Its full cost implication needs further economic evaluation.

High rates of undiagnosed diabetes mellitus among patients with active tuberculosis in Addis Ababa, Ethiopia.

Background: Tuberculosis (TB) and diabetes mellitus (DM) have negative synergistic impact on each other. Global guidelines recommend collaborative efforts to address this synergy, but implementation has been slow. Part of the reason is lack of adequate evidence on the operational feasibility of existing tools and mechanisms of collaboration. The objective of this study was to assess the yield of DM screening among TB patients using risk scoring tools combined with blood tests as a feasible strategy for early detection to improve TB/DM treatment outcomes. Methods: Between September 2020 and December 2021, we conducted a cross-sectional study among patients receiving TB treatment in public health facilities in Addis Ababa, Ethiopia. Trained health workers collected data on symptoms and risk scoring checklists before testing for random and fasting blood glucose levels. We used logistic regression analyses techniques to determine factors associated with increased DM detection. A receiver-operating characteristic curve was constructed to determine the performance of the risk scoring checklist. Results: Of 2381 TB patients screened, 197 (8.3%) had DM of which 48.7% were newly diagnosed. Having a family history of DM predicted DM with Odds Ratio (OR) of 5.36 (95% Confidence Interval, [3.67, 7.83]) followed by age ≥ 45 years (OR = 4.64, [3.18, 6.76]). Having one or more "symptoms" of DM was a significant predictor (OR 2.88, 95% CI, 2.06-4.01). Combining risk scores with symptoms predicted DM diagnosis with sensitivity of 94.7%, but specificity was low at 29.4%. In patients with known treatment outcome status, death rate was high. Conclusions: Almost a half of TB patients with DM did not know their status. A simple tool that combined risk factors with symptoms accurately predicted a subsequent diagnosis of DM. Such tools can help avoid high rates of death among TB patients suffering from DM through early detection.

Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis.

INTRODUCTION: Bedaquiline, pretomanid and linezolid (BPaL) is a new all oral, 6-month regimen comprised of bedaquiline, the new drug pretomanid and linezolid, endorsed by the WHO for use under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB). We quantified per-patient treatment costs and the 5-year budgetary impact of introducing BPaL in Indonesia, Kyrgyzstan and Nigeria. METHODS: Per-patient treatment cost of BPaL regimen was compared head-to-head with the conventional XDR-TB treatment regimen for respective countries based on cost estimates primarily assessed using microcosting method and expected frequency of each TB service. The 5-year budget impact of gradual introduction of BPaL against the status quo was assessed using a Markov model that represented patient's treatment management and outcome pathways. RESULTS: The cost per patient completing treatment with BPaL was US$7142 in Indonesia, US$4782 in Kyrgyzstan and US$7152 in Nigeria - 57%, 78% and 68% lower than the conventional regimens in the respective countries. A gradual adoption of the BPaL regimen over 5 years would result in an 5-year average national TB service budget reduction of 17% (US$128 780) in XDR-TB treatment-related expenditure in Indonesia, 15% (US$700 247) in Kyrgyzstan and 32% (US$1 543 047) in Nigeria. CONCLUSION: Our study demonstrates that the BPaL regimen can be highly cost-saving compared with the conventional regimens to treat patients with XDR-TB in high drug-resistant TB burden settings. This supports the rapid adoption of the BPaL regimen to address the significant programmatic and clinical challenges in managing patients with XDR-TB in high DR-TB burden countries.

High Levels of Treatment Success and Zero Relapse in Multidrug-Resistant Tuberculosis Patients Receiving a Levofloxacin-Based Shorter Treatment Regimen in Vietnam.

Vietnam has been using a levofloxacin-based shorter treatment regimen (STR) for rifampicin resistant/multidrug-resistant tuberculosis (RR/MDR-TB) patients since 2016 on a pilot basis. This regimen lasts for 9-11 months and is provided to RR/MDR-TB patients without second-line drug resistance. We report the treatment outcomes and factors associated with unsuccessful outcomes. We conducted a cohort study involving secondary analysis of data extracted from electronic patient records maintained by the national TB program (NTP). Of the 302 patients enrolled from April 2016 to June 2018, 259 (85.8%) patients were successfully treated (246 cured and 13 'treatment completed'). Unsuccessful outcomes included: treatment failure (16, 5.3%), loss to follow-up (14, 4.6%) and death (13, 4.3%). HIV-positive TB patients, those aged ≥65 years and patients culture-positive at baseline had a higher risk of unsuccessful outcomes. In a sub-group of patients enrolled in 2016 (n = 99) and assessed at 12 months after treatment completion, no cases of relapse were identified. These findings vindicate the decision of the Vietnam NTP to use a levofloxacin-based STR in RR/MDR-TB patients without second-line drug resistance. This regimen may be considered for nationwide scale-up after a detailed assessment of adverse drug events.

Quality Tuberculosis Care in Indonesia: Using Patient Pathway Analysis to Optimize Public-Private Collaboration.

Background: Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world's "missing" TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. Methods: A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. Results: The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. Conclusions: The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers.

Health system factors influencing management of multidrug-resistant tuberculosis in four European Union countries - learning from country experiences.

BACKGROUND: In the European Union and European Economic Area only 38% of multidrug-resistant tuberculosis patients notified in 2011 completed treatment successfully at 24 months' evaluation. Socio-economic factors and patient factors such as demographic characteristics, behaviour and attitudes are associated with treatment outcomes. Characteristics of healthcare systems also affect health outcomes. This study was conducted to identify and better understand the contribution of health system components to successful treatment of multidrug-resistant tuberculosis. METHODS: We selected four European Union countries to provide for a broad range of geographical locations and levels of treatment success rates of the multidrug-resistant tuberculosis cohort in 2009. We conducted semi-structured interviews following a conceptual framework with representatives from policy and planning authorities, healthcare providers and civil society organisations. Responses were organised according to the six building blocks of the World Health Organization health systems framework. RESULTS: In the four included countries, Austria, Bulgaria, Spain, and the United Kingdom, the following healthcare system factors were perceived as key to achieving good treatment results for patients with multidrug-resistant tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems that ensure access to a full course of treatment and support for multidrug-resistant tuberculosis patients; patient-centred approaches with strong intersectoral collaboration that address patients' emotional and social needs; motivated and dedicated healthcare workers with sufficient mandate and means to support patients; and cross-border management of multidrug-resistant tuberculosis to secure continuum of care between countries. CONCLUSION: We suggest that the following actions may improve the success of treatment for multidrug-resistant tuberculosis patients: deployment of rapid molecular diagnostic tests; development of context-specific treatment guidance and criteria for hospital admission and discharge in the European context; strengthening patient-centred approaches; development of collaborative mechanisms to ensure cross-border care, and development of long-term sustainable financing strategies.

Infection control and tuberculosis among health care workers in Viet Nam, 2009-2013: a cross-sectional survey.

BACKGROUND: Data on tuberculosis (TB) among health care workers (HCW) and TB infection control (TBIC) indicators are rarely available at national level. We assessed multi-year trends in notification data of TB among HCW and explored possible associations with TBIC indicators. METHODS: Notified TB incidence among HCW and 3 other TBIC indicators were collected annually from all 64 provincial and 3 national TB facilities in Vietnam. Time trends in TB notification between 2009 and 2013 were assessed using linear regression analysis. Multivariate regression models were applied to assess associations between the facility-specific 5-year notification rate and TBIC indicators. RESULTS: Forty-seven (70 %) of 67 facilities contributed data annually over five years; 15 reported at least one HCW with TB in 2009 compared to six in 2013. The TB notification rate dropped from 593 to 197 per 100,000 HCW (ptrend = 0.02). Among 104 TB cases reported, 30 were employed at TB wards, 24 at other clinical wards, ten in the microbiology laboratory, six at the MDR-TB ward, and 34 in other positions. The proportion of facilities with a TBIC plan and focal person remained relatively stable between 70 % and 84 %. The proportion of facilities providing personal protective equipment (PPE) to their staff increased over time. Facilities with a TBIC focal person were 7.6 times more likely to report any TB cases than facilities without a focal person. CONCLUSIONS: The TB notification rates among HCW seemed to decrease over time. Availability of PPE increased over the same period. Appointing a TBIC focal person was associated with reporting of TB cases among HCW. It remains unclear whether TBIC measures helped in reduction of the TB notification rates in HCW.

Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda.

INTRODUCTION: There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey. METHODS: Publications citing the 2008 research agenda and normative documents were reviewed for evidence gaps. Gaps were formulated into questions and grouped as in the 2008 research agenda: Laboratory Support, Treatment Strategy, Programmatically Relevant Research, Epidemiology, and Management of Contacts. A survey was distributed through snowball sampling to identify research priorities. Respondent priority rankings were scored and summarized by mean. Sensitivity analyses explored weighting and handling of missing rankings. RESULTS: Thirty normative documents and publications were reviewed for stated research needs; these were collapsed into 56 research questions across 5 categories. Of more than 500 survey recipients, 133 ranked priorities within at least one category. Priorities within categories included new diagnostics and their effect on improving treatment outcomes, improved diagnosis of paucibacillary and extra pulmonary TB, and development of shorter, effective regimens. Interruption of nosocomial transmission and treatment for latent TB infection in contacts of known MDR-TB patients were also top priorities in their respective categories. Results were internally consistent and robust. DISCUSSION: Priorities retained from the 2008 research agenda include shorter MDR-TB regimens and averting transmission. Limitations of recent advances were implied in the continued quest for: shorter regimens containing new drugs, rapid diagnostics that improve treatment outcomes, and improved methods of estimating burden without representative data. CONCLUSION: There is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

The Effects of Psycho-Emotional and Socio-Economic Support for Tuberculosis Patients on Treatment Adherence and Treatment Outcomes - A Systematic Review and Meta-Analysis.

BACKGROUND: There is uncertainty about the contribution that social support interventions (SSI) can have in mitigating the personal, social and economic costs of tuberculosis (TB) treatment on patients, and improving treatment outcomes. OBJECTIVE: To identify psycho-emotional (PE) and socio-economic (SE) interventions provided to TB patients and to assess the effects of these interventions on treatment adherence and treatment outcomes. SEARCH STRATEGY: We searched PubMed and Embase from 1 January 1990-15 March 2015 and abstracts of the Union World Conference on Lung Health from 2010-2014 for studies reporting TB treatment adherence and treatment outcomes following SSI. SELECTION CRITERIA: Studies measuring the effects of PE or SE interventions on TB treatment adherence, treatment outcomes, and/or financial burden. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed titles and abstracts for inclusion of articles. One reviewer reviewed full text articles and the reference list of selected studies. A second reviewer double checked all extracted information against the articles. MAIN RESULTS: Twenty-five studies were included in the qualitative analysis; of which eighteen were included in the meta-analysis. Effects were pooled from 11 Randomized Controlled Trials (RCTs), including 9,655 participants with active TB. Meta-analysis showed that PE support (RR 1.37; CI 1.08-1.73), SE support (RR 1.08; CI 1.03-1.13) and combined PE and SE support (RR 1.17; CI 1.12-1.22) were associated with a significant improvement of successful treatment outcomes. Also PE support, SE support and a combination of these types of support were associated with reductions in unsuccessful treatment outcomes (PE: RR 0.46; CI 0.22-0.96, SE: RR 0.78; CI 0.69-0.88 and Combined PE and SE: RR 0.42; CI 0.23-0.75). Evidence on the effect of PE and SE interventions on treatment adherence were not meta-analysed because the interventions were too heterogeneous to pool. No evidence was found to show whether SE reduced the financial burden for TB patients. DISCUSSION AND CONCLUSIONS: Our review and meta-analysis concluded that PE and SE interventions are associated with beneficial effects on TB treatment outcomes. However, the quality of evidence is very low and future well-designed evaluation studies are needed.