A Modeling Study Recurrent Tuberculosis Towards End TB Strategy - China, 2025-2035.

What is already known about this topic?: The recurrence of tuberculosis (TB) following successful treatment presents a significant challenge. What is added by this report?: Achieving the global End TB Strategy milestones and targets with the current strategies in China is challenging. However, interventions following recovery to prevent recurrence, in conjunction with preventive treatment for latent TB infection (LTBI), will aid in meeting these objectives. What are the implications for public health practice?: Implementing interventions to mitigate recurrence is essential for improving TB control strategies both in China and worldwide. Concurrently, the development of new drugs and vaccines should focus on preventing TB recurrence.

Evaluation of drug-resistant tuberculosis treatment outcome in Limpopo province, South Africa.

BACKGROUND: South Africa has the second-highest tuberculosis (TB) incidence globally. Drug-resistant TB (DR-TB) treatment has less successful treatment outcomes as compared with susceptible TB, and it hinders TB control and management programmes. AIM: This study aimed to evaluate drug-resistant TB treatment outcomes and factors associated with successful treatment outcomes. SETTING: The study was conducted in five districts in Limpopo province. METHODS: The study design was retrospective and descriptive. Patients' demographic data, data on clinical characteristics and treatment outcomes data were extracted from the electronic drug-resistant tuberculosis register (EDRWeb) database system for the period, 2010-2018, in Limpopo province. Frequency, percentages and bivariate and multivariate logistic regression were used to analyse data using Statistical Package for Social Sciences version 27.0. The significance difference was determined at a 95% confidence interval and p 0.05. RESULTS: A total of 385 drug-resistant records were included in this study. The treatment success rate was 223 (57.9%). A total of 197 (51.2%) patients were cured, 26 (6.8%) completed treatment, 19 (4.9%) treatment failure, 62 (16.1%) died, 78 (20.6%) were recorded as the loss to follow-up, 1 (0.3%) moved to another country and 2 (0.5%) were transferred out. CONCLUSION: The treatment success rate was 57.9%, which is still below targets set by National Strategic Plan in South Africa and World Health Organization End TB targets.Contribution: The findings of the study reveal that to achieve successful DR-TB control programme and attain End TB targets, monitoring of treatment outcomes is crucial.

Yes, we have the power to end TB!

Robust efforts are essential to sustain and increase the advancements made in battling TB, as well as to tackle persistent issues that have caused the fight against the disease to be uneven. The End TB Strategy proposes that new technologies are to be developed by 2025 to encourage a quick growth in TB occurrence diminishment. This calls for a cross-sectoral focus on creating and distributing suitable medical and programmatic modernizations in a fair manner. However, many difficulties and differences still exist in the realms of research and development regarding vaccines, drugs, technical advances, and services related to TB. Therefore, priority needs to be given to overcoming these difficulties and discrepancies for a better future. On World TB Day 2023, SEAR Union, TB Alliance, the National Institute of Advanced Studies (NIAS) and Open Source Pharma Foundation (OSPF) gathered to discuss an important topic under the heading: "YES, WE HAVE THE POWER TO END TB!" With a commitment to putting the patient first and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to end TB globally. They advocate for strengthening access to TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. Furthermore, they recognize the importance of reducing stigma and integrating patient voices in this endeavour. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable.

Catastrophic "costs": A hindrance to eliminate tuberculosis.

Globally, one quarter of the population is infected with TB; and only a small proportion of those infected will become sick. Tuberculosis along with poverty disproportionately affects the households causing a financial burden and catastrophic costs (if the total costs incurred by a household's exceeds 20% of its annual income), which could be direct or indirect and procuring detrimental effects on the effective strategic plans. Out of all diseases, India accounts for 18% of the catastrophic health expenditure including tuberculosis. Therefore, an utmost need for a national cost survey either separately or combined with other health surveys should be held for the comprehension of the baseline burden of Tuberculosis in the affected households, to identify the predictors of catastrophic costs, and simultaneously, intensive research and appropriate innovations are needed to assess the effectiveness of the measures undertaken for the reduction of the proportionate patients who overlook catastrophic costs.

Programmatic management of tuberculosis preventive therapy: Past, present, future.

BACKGROUND: Tuberculosis (TB) infection (TBI) is an emerging public health priority, involving about one-fourth of the world population. Because patients with TBI are the reservoir for TB, stopping the progression to active disease by preventive treatment is one of the main interventions needed to achieve TB elimination. As of today, the proportion of people with TBI receiving treatment is minimal at the global level, mostly because current international policies recommend systematic testing and treatment for less than 2% of infected people. PRESENT: FACTS AND GAPS: The programmatic management of TB preventive treatment involves a set of cascading interventions, of which the effectiveness is limited by the poor predictivity of diagnostic tests, the length and the potential toxicity of treatment, and the suboptimal prioritization within global policies. Partly because of this, competing priorities and the lack of adequate funding are significant barriers for scale-up, particularly in low- and middle-income countries. MONITORING AND EVALUATION: To date, there is no universal system of monitoring and evaluation for the programmatic management of TB preventive treatment elements, and just a few countries use the standard recording and reporting tools, contributing to leaving TBI a neglected condition. CONCLUSION: Better financed research and resources reallocation are essential steps to progress toward TB elimination worldwide.

Availability and costs of medicines for the treatment of tuberculosis in Europe.

OBJECTIVES: To evaluate the access to comprehensive diagnostics and novel antituberculosis medicines in European countries. METHODS: We investigated the access to genotypic and phenotypic Mycobacterium tuberculosis drug susceptibility testing and the availability of antituberculosis drugs and calculated the cost of drugs and treatment regimens at major tuberculosis treatment centres in countries of the WHO European region where rates of drug-resistant tuberculosis are the highest among all WHO regions. Results were stratified by middle-income and high-income countries. RESULTS: Overall, 43 treatment centres from 43 countries participated in the study. For WHO group A drugs, the frequency of countries with the availability of phenotypic drug susceptibility testing was as follows: (a) 75% (30/40) for levofloxacin, (b) 82% (33/40) for moxifloxacin, (c) 48% (19/40) for bedaquiline, and (d) 72% (29/40) for linezolid. Overall, of the 43 countries, 36 (84%) and 24 (56%) countries had access to bedaquiline and delamanid, respectively, whereas only 6 (14%) countries had access to rifapentine. The treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was available only in 17 (40%) of the 43 countries. The median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for 6 months), and extensively drug-resistant tuberculosis (including bedaquiline, delamanid, and a carbapenem) were €44 (minimum-maximum, €15-152), €764 (minimum-maximum, €542-15152), and €8709 (minimum-maximum, €7965-11759) in middle-income countries (n = 12) and €280 (minimum-maximum, €78-1084), €29765 (minimum-maximum, €11116-40584), and €217591 (minimum-maximum, €82827-320146) in high-income countries (n = 29), respectively. DISCUSSION: In countries of the WHO European region, there is a widespread lack of drug susceptibility testing capacity to new and repurposed antituberculosis drugs, lack of access to essential medications in several countries, and a high cost for the treatment of drug-resistant tuberculosis.

Corrigendum: Impact of the COVID-19 pandemic on the diagnosis of tuberculosis in Brazil: Is the WHO end TB strategy at risk?

[This corrects the article DOI: 10.3389/fphar.2022.891711.].

Impact of the COVID-19 Pandemic on the Diagnosis of Tuberculosis in Brazil: Is the WHO End TB Strategy at Risk?

Background: In 2014, the World Health Organization (WHO) launched the "post-2015 End TB strategy", that aims to end the global tuberculosis (TB) epidemic by 2030. However, the COVID-19 pandemic has severely impacted global public health and the strict measures to control the coronavirus spread can affect the management of other diseases, such as TB. Herein, we aimed to assess the impact of the COVID-19 pandemic on the diagnosis of TB in Brazil, during 2020. Methods: We carried out an ecological and population-based study, using spatial analysis techniques. The variables used were the new cases of TB, pulmonary tuberculosis (PTB), and also baciloscopy-positive (BP) cases in Brazil between 2015 and 2020. The percentage of changes (% change) was calculated to verify if there was an increase or decrease of TB cases in 2020, along with time trend analyses given by Joinpoint regression model. Also, interrupted time series analyses were used to assess the trend of TB diagnosis before and after the onset of the COVID-19 in Brazil. Spatial distribution maps were elaborated, considering the % change of each Brazilian state. Findings: Data analyses showed a reduction in the diagnosis of TB (-8.3%) and PTB (-8.1%) in Brazil after the irruption of the COVID-19 pandemic. Likewise, 22 states depicted a reduction in TB diagnosis. An expressive reduction of BP cases (-17.1%) was also observed. Interestingly, interrupted time series analysis showed decline in TB and PTB diagnoses from March 2020. Spatial analyses revealed that all states had a progressive reduction of TB, PTB and PB cases, from March on, with the highest percentages of reduction in December (-100% to -75%). Interpretation: Taken together, our analyses demonstrated a reduction in TB diagnosis after the irruption of the COVID-19 pandemic in Brazil and its regions, signaling a serious impact on the WHO "End TB Strategy" global plan.

Prediction of different interventions on the burden of drug-resistant tuberculosis in China: a dynamic modelling study.

BACKGROUND: Tuberculosis (TB) is one of the top 10 causes of death worldwide. The World Health Organization adopted the 'End TB Strategy' to end the global TB epidemic by 2035. However, achieving this goal will be difficult using current measures. METHODS: A Susceptible-Exposed-Infectious-Recovered (SEIR) model that distinguishes drug-sensitive (DS) and drug-resistant (DR) TB in the entire Chinese population was established. Goodness-of-fit tests and sensitivity analyses were used to assess model performance. Predictive analysis was performed to assess the effect of different prevention and control strategies on DR-TB. RESULTS: We used parameter fitting to determine the basic reproduction number of the model as R0 = 0.6993. The predictive analysis led to two major projections that can achieve the goal by 2035. First, if the progression rate of latently infected people reaches 10%, then there will be 92.2% fewer cases than in 2015. Second, if the cure rate of DR-TB increases to 40%, then there will be 91.5% fewer cases than in 2015. A combination of five interventions could lead to earlier achievement of the 2035 target. CONCLUSION: We found that reducing the probability of transmission and the rate of disease progression in patients with DR-TB and improving treatment compliance and the cure rate of patients with DR-TB can contribute to attaining the goal of the End TB Strategy.

The WHO Global Tuberculosis 2021 Report - not so good news and turning the tide back to End TB.

OBJECTIVE: To review the data presented in the 2021 WHO global TB report and discuss the current constraints in the global response. INTRODUCTION AND METHODS: The WHO global TB reports, consolidate TB data from countries and provide up to date assessment of the global TB epidemic. We reviewed the data presented in the 2021 report. RESULTS: We noted that the 2021 WHO global TB report presents a rather grim picture on the trajectory of the global epidemic of TB including a stagnation in the annual decline in TB incidence, a decline in TB notifications and an increase in estimated TB deaths. All the targets set at the 2018 United Nations High Level Meeting on TB were off track. INTERPRETATION AND CONCLUSION: The sub-optimal global performance on achieving TB control targets in 2020 is attributed to the on-going COVID-19 pandemic, however, TB programs were already off track well before the onset of the pandemic, suggesting that the pandemic amplified an already fragile global TB response. We emphasize that ending the global TB epidemic will require bold leadership, optimization of existing interventions, widespread coverage, addressing social determinants of TB and importantly mobilization of adequate funding required for TB care and prevention.

Protocol for the Addressing the Social Determinants and Consequences of Tuberculosis in Nepal (ASCOT) pilot trial.

BACKGROUND: The World Health Organization's End TB (tuberculosis) Strategy advocates social and economic support for TB-affected households but evidence from low-income settings is scarce. We will evaluate the feasibility and acceptability of a locally-appropriate socioeconomic support intervention for TB-affected households in Nepal. METHODS: We will conduct a pilot randomised-controlled trial with mixed-methods process evaluation in four TB-endemic, impoverished districts of Nepal: Pyuthan, Chitwan, Mahottari, and Morang. We will recruit 128 people with TB notified to the Nepal National TB Program (NTP) and 40 multisectoral stakeholders including NTP staff, civil-society members, policy-makers, and ASCOT (Addressing the Social Determinants and Consequences of Tuberculosis) team members. People with TB will be randomised 1:1:1:1 to four study arms (n=32 each): control; social support; economic support; and combined social and economic (socioeconomic) support. Social support will be TB education and peer-led mutual-support TB Clubs providing TB education and stigma-reduction counselling. Economic support will be monthly unconditional cash transfers during TB treatment with expectations (not conditions) of meeting NTP goals. At 0, 2, and 6 months following TB treatment initiation, participants will be asked to complete a survey detailing the social determinants and consequences of TB and their feedback on ASCOT. Complementary process evaluation will use focus group discussions (FGD), key informant interviews (KII), and a workshop with multi-sectoral stakeholders to consider the challenges to ASCOT's implementation and scale-up. A sample of ~100 people with TB is recommended to estimate TB-related costs. Information power is estimated to be reached with approximately 25 FGD and 15 KII participants. CONCLUSIONS: The ASCOT pilot trial will both generate robust evidence on a locally-appropriate, socioeconomic support intervention for TB-affected households in Nepal and inform a large-scale future ASCOT trial, which will evaluate the intervention's impact on catastrophic costs mitigation and TB outcomes. The trial is registered with the ISRCTN ( ISRCTN17025974).

Determinants of drug resistant & drug sensitive tuberculosis patients from North India-a case control study.

BACKGROUND AND OBJECTIVE: The burden of drug resistant tuberculosis (DRTB) has posed a huge challenge to for the governments, throughout the world. India has 27% of the global DRTB burden with incidence of 130,000 cases. India has kept an ambitious target of elimination of tuberculosis by 2025 which requires understanding and mitigating various determinants of DRTB. METHODS: The retrospective case control study was undertaken from May to September 2019 among drugresistant (cases) and drug sensitive (controls) tuberculosis patients from two districts of Himachal Pradesh, India. A total of 211 participants were recruited in the study, which includes all 102 cases and randomly selected, age and sex matched 109 controls. A semi structured questionnaire, adapted from a study by Lobo et al, was used for assessing the determinants of DRTB and DSTB. The data collection was undertaken from district and block level health care facilities followed by home visits to patients. Multivariate logistic regression was used to determine risk factors associated with DRTB. RESULTS: Diagnostic delay (aOR-7.72, p value 0.000), history of treatment default (aOR-2.97, self history of tuberculosis (aOR 1.42, p value 0.01), migration (aOR-4.84, p value 0.000), smoking (aOR-2.70, p value 0.014), and belonging to rural area (aOR-2.62, p value- 0.013) were found as independent risk factors for the occurrence of DRTB. CONCLUSION: The risk factors identified in the study should be prioritized by the policy makers, implementators and educators for framing appropriate policies in TB control programme in India. The diagnostic delay as a risk factor merits active case finding of TB patients and educating health care staff and community.

Rate of treatment success and associated factors in the program for drug-susceptible tuberculosis in the Forest Region, Republic of Guinea, 2010-2017: A real-world retrospective observational cohort study.

OBJECTIVES: To analyze the treatment success rate (TSR = sum of cured or treatment completed) in the tuberculosis (TB) program for drug-susceptible TB (DS-TB) at the "Centre Hospitalier Régional Spécialisé" in Macenta, Forest Region, Republic of Guinea. METHODS: This cohort study included patients who started treatment for DS-TB between 2010 and 2017. Data collection was part of the documentation for the national TB program. Descriptive analysis was applied to determine the TSR in various patient groups. Further, logistic regression was performed to determine factors influencing the TSR in new and relapsed cases versus all other previously treated cases. A subgroup analysis for only microbiologically confirmed pulmonary TB was added. RESULTS: The study included 3969 patients. The TSR increased from 68.3% in 2010 to 80.8% in 2017 (p < 0.001). Mortality (11.2%) mainly occurred in early treatment months, while loss to follow-up (5.9%) increased towards later treatment months. Risk factors for low TSR were advanced age, positive HIV status, long travel distances (>100 km) to the clinic, and late treatment refill. CONCLUSION: The TSR in the Forest Region of Guinea remained below the WHO goal of 90%. Reaching this target remains a challenge in rural areas with high early mortality and increased risk of loss to follow-up.

New Developments and Insights in the Improvement of Mycobacterium tuberculosis Vaccines and Diagnostics Within the End TB Strategy.

PURPOSE OF REVIEW: The alignment of sustainable development goals (SDGs) with the End Tuberculosis (TB) strategy provides an integrated roadmap to implement key approaches towards TB elimination. This review summarizes current social challenges for TB control, and yet, recent developments in TB diagnosis and vaccines in the context of the End TB strategy and SDGs to transform global health. RECENT FINDINGS: Advances in non-sputum based TB biomarkers and whole genome sequencing technologies could revolutionize TB diagnostics. Moreover, synergistic novel technologies such as mRNA vaccination, nanovaccines and promising TB vaccine models are key promising developments for TB prevention and control. SUMMARY: The End TB strategy depends on novel developments in point-of-care TB diagnostics and effective vaccines. However, despite outstanding technological developments in these fields, TB elimination will be unlikely achieved if TB social determinants are not fully addressed. Indeed, the End TB strategy and SDGs emphasize the importance of implementing sustainable universal health coverage and social protection.

Prevalence of Diabetes in Tuberculosis Patients in Kathmandu Valley, Nepal.

In this descriptive cross-sectional study, the data on the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients at the Urban Directly Observed Treatment Centers in the Kathmandu, Bhaktapur, and Lalitpur districts of Nepal were collected. The prevalence of DM was assessed in 67 previously treated TB (PTTB) and 214 new TB patients. DM was diagnosed in 8 PTTB and 20 new TB patients. Clinical interviews identified 14 patients with DM, rapid blood glucose test was used to diagnose DM in 4 patients, and oral glucose tolerance test was used to diagnose DM in another 4 patients. Impaired glucose tolerance and impaired fasting glycemia were observed in 8 and 5 patients, respectively. The 18-24-year age group had the largest number of new TB patients (82, 38.3%). However, the incidence of DM among TB patients was higher in the >35-year age group. Moreover, DM was diagnosed in 24.2% of PTTB patients and in 23.1% of new TB patients. To determine the impact of DM screening in TB patients, a larger number of samples should be analyzed. DM screening for patients with TB is expected to start in developing countries. This should be initiated by conducting clinical interviews about DM and glucose tests using rapid kits.

What is operational research and how can national tuberculosis programmes in low- and middle-income countries use it to end TB?

Despite considerable progress over the years, tuberculosis (TB) still remains the top cause of death among the infectious diseases and has devastating socio-economic consequences for people in low- and middle-income countries. To add to this, the emergence of the COVID-19 pandemic has worsened delivery of TB care across the globe. As a global community, we have committed to end the TB epidemic by 2030. The World Health Organization has framed a strategy to achieve this goal which consists of three pillars namely i) integrated patient-centred care and prevention, ii) bold policies and systems and iii) intensified research and innovation. An analysis of the performance of national tuberculosis programmes (NTPs) across the globe against the ten priority indicators recommended for monitoring the end TB strategy show that there are huge gaps at every step in the cascade of care of TB patients. In our view, these gaps reflect suboptimal implementation of existing strategies known to be efficacious and operational research (OR) is one of the best available tools to plug the gaps. In this paper, we define what operational research is and how it differs from other kinds of research. We also share our views and experiences about how operational research can be used by NTPs to identify implementation gaps and their reasons, and develop and test possible solutions - which are then integrated to make changes to policy and practice and eventually improve programme outcomes. OR can be defined as research into interventions, strategies and tools which produces practical useable knowledge that can be used to enhance the quality, coverage, effectiveness and efficiency of disease control programmes, health services or health systems in which the research is conducted. The key steps in integrating operational research in the NTPs include: i) securing political commitment reflected by inclusion of OR in the national strategic plans of NTPs and earmarked funding, ii) having a critical mass of dedicated and trained human resources in OR within the NTP, iii) setting research priorities and steering the direction of research in the country, iv) using output-oriented models of capacity building such as the Structured Operational Research Training Initiative (SORT IT) model and building communities of practice, v) harnessing existing capacity in the country by forging partnerships with academia, vi) NTP-led nationwide, multicentre OR studies, vii) providing access to anonymized patient and programme surveillance data, vii) creating a forum for evidence dissemination and fostering policy change and ix) monitoring and accountability. In conclusion, ending the TB epidemic will not be possible without new tools (diagnostics, drugs, vaccines) and a multi-sectoral response involving stakeholders beyond the health ministry, including private providers, patients and communities. However, timely conduct of operational research to fine-tune programme implementation and ensuring proper deployment of new tools will be equally crucial to maximize the effectiveness and efficiency of interventions and ultimately contribute towards ending TB.

Solutions to improve the latent tuberculosis Cascade of Care in Ghana: a longitudinal impact assessment.

BACKGROUND: Loss of patients in the latent tuberculosis infection (LTBI) cascade of care is a major barrier to LTBI management. We evaluated the impact and acceptability of local solutions implemented to strengthen LTBI management of household contacts (HHCs) at an outpatient clinic in Ghana. METHODS: Local solutions to improve LTBI management were informed by a baseline evaluation of the LTBI cascade and questionnaires administered to index patients, HHCs, and health care workers at the study site in Offinso, Ghana. Solutions aimed to reduce patient costs and improve knowledge. We evaluated the impact and acceptability of the solutions. Specific objectives were to: 1) Compare the proportion of eligible HHCs completing each step in the LTBI cascade of care before and after solution implementation; 2) Compare knowledge, attitude, and practices (KAP) before and after solution implementation, based on responses of patients and health care workers (HCW) to structured questionnaires; 3) Evaluate patient and HCW acceptability of solutions using information obtained from these questionnaires. RESULTS: Pre and Post-Solution LTBI Cascades included 58 and 125 HHCs, respectively. Before implementation, 39% of expected < 5-year-old HHCs and 66% of ≥5-year-old HHCs were identified. None completed any further cascade steps. Post implementation, the proportion of eligible HHCs who completed identification, assessment, evaluation, and treatment initiation increased for HHCs < 5 to 94, 100, 82, 100%, respectively, and for HHCs ≥5 to 96, 69, 67, 100%, respectively. Pre and Post-Solutions questionnaires were completed by 80 and 95 respondents, respectively. Study participants most frequently mentioned financial support and education as the solutions that supported LTBI management. CONCLUSION: Implementation of locally selected solutions was associated with an increase in the proportion of HHCs completing all steps in the LTBI cascade. Tuberculosis programs should consider prioritizing financial support, such as payment for chest x-rays, to support LTBI cascade completion.