Background Tuberculosis (TB) is the leading cause of mortality by an infectious disease worldwide. Despite national and international efforts, the world is not on track to end TB by 2030. Antibiotic treatment of TB is longer than for most infectious diseases and is complicated by frequent adverse events. To counter emerging Mycobacterium tuberculosis drug resistance and provide effective, safe drug treatments of shorter duration, novel anti-TB medicines, and treatment regimens are needed. Through a joint global effort, more candidate medicines are in the clinical phases of drug development than ever before. Objectives To review anti-TB medicines and treatment regimens under clinical evaluation for the future treatment of drug-susceptible and drug-resistant TB. Sources Pre-clinical and clinical studies on novel anti-TB drugs. Content Description of novel protein synthesis inhibitors (oxazolidinones and oxaboroles), respiratory chain inhibitors (diarylquinolines and cytochrome bc1 complex inhibitor), cell wall inhibitors (decaprenylphosphoryl-β-d-ribose 2′-epimerase, inhibitors, thioamides, and carbapenems), and cholesterol metabolism inhibitor currently evaluated in clinical trials and novel clinical trial platforms for the evaluation of treatment regimens, rather than single entities. Implications A large number of potential anti-TB candidate medicines and innovations in clinical trial design for the evaluation of regimens, rather than single medicines, provide hope for improvements in the treatment of TB.

Technical advances in diagnostic techniques have permitted the possibility of multi-disease-based approaches for diagnosis and treatment monitoring of several infectious diseases, including tuberculosis (TB), human immunodeficiency virus (HIV), viral hepatitis and sexually transmitted infections (STI). However, in many countries, diagnosis and monitoring, as well as disease response programs, still operate as vertical systems, potentially causing delay in diagnosis and burden to patients and preventing the optimal use of available resources. With countries facing both human and financial resource constraints, during the COVID-19 pandemic even more than before, it is important that available resources are used as efficiently as possible, potential synergies are leveraged to maximise benefit for patients, continued provision of essential health services is ensured. For the infectious diseases, TB, HIV, hepatitis C (HCV) and STI, sharing devices and integrated services starting with rapid, quality-assured, and complete diagnostic services is beneficial for the continued development of adequate, efficient and effective treatment strategies. Here we explore the current and future potential (as well as some concerns), importance, implications and necessary implementation steps for the use of platforms for multi-disease testing for TB, HIV, HCV, STI and potentially other infectious diseases, including emerging pathogens, using the example of the COVID-19 pandemic.

In Belarus and several EECA countries, periodic population-based chest X-ray “fluorography programme” use as a mass screening tool for the diagnosis of tuberculosis (TB) has been used for decades. This mass screening has also often been justified for the early detection of lung cancer (LC), although no mortality benefits were demonstrated by screening with chest X-ray in international randomized trials. In Belarus, fluorography testing is mandatory every one to three years for all adults depending on age and the so-called “risk groups”. The World Bank and WHO estimate that Belarus spends USD11 million annually on mass fluorography screening and advocate for more targeted screening approaches to increase diagnostic yield for TB and not to use it for screening for LC. The study is a retrospective review of medical records to assess the yield of fluorography to detect true cases of LC and/or TB in asymptomatic patients in two rural and two urban districts in Belarus for 2015–2017 with positive screening results for presumed of TB or LC. The study provided the rationale to implement the improved policy and practices regarding the role of fluorography in the early detection of LC and TB in Belarus and elsewhere.

Tuberculosis (TB) remains a public health burden in the Republic of Karakalpakstan, Uzbekistan. This region-wide retrospective cohort study reports the treatment outcomes of patients registered in the TB electronic register and treated with first-line drugs in the TB Programme of the Republic of Karakalpakstan from 2005–2020 and factors associated with unfavourable outcomes. Among 35,122 registered patients, 24,394 (69%) patients were adults, 2339 (7%) were children, 18,032 (51%) were male and 19,774 (68%) lived in rural areas. Of these patients, 29,130 (83%) had pulmonary TB and 7497 (>22%) had been previously treated. There were 7440 (21%) patients who had unfavourable treatment outcomes. Factors associated with unfavourable treatment outcomes included: increasing age, living in certain parts of the republic, disability, pensioner status, unemployment, being HIV-positive, having pulmonary TB, and receiving category II treatment. Factors associated with death included: being adult and elderly, living in certain parts of the republic, having a disability, pensioner status, being HIV-positive, and receiving category II treatment. Factors associated with failure included: being adolescent, female, having pulmonary TB. Factors associated with loss to follow-up included: being male, disability, pensioner status, unemployment, receiving category II treatment. In summary, there are sub-groups of patients who need special attention in order to decrease unfavourable treatment outcomes.

BACKGROUND: Distinguishing TB relapse from re-infection is important from a clinical perspective to document transmission patterns. We investigated isolates from patients classified as relapse to understand if these were true relapses or re-infections. We also investigated shifts in drug susceptibility patterns to distinguish acquired drug resistance from re-infection with resistant strains.METHODS: Isolates from pulmonary TB patients from 2009 to 2017 were analysed using whole-genome sequencing (WGS).RESULTS: Of 11 patients reported as relapses, WGS results indicated that 4 were true relapses (single nucleotide polymorphism difference ≤5), 3 were re-infections with new strains, 3 were both relapse and re-infection and 1 was a suspected relapse who was later categorised as treatment failure based on sequencing. Of the 9 patients who went from a fully susceptible to a resistant profile, WGS showed that none had acquired drug resistance; 6 were re-infected with new resistant strains, 1 was probably infected by at least two different genotype strains and 2 were phenotypically misclassified.CONCLUSIONS: WGS was shown to distinguish between relapse and re-infection in an unbiased way. The use of WGS minimises the risk of false classification of treatment failure instead of re-infection. Furthermore, our study showed that strains without major genetic differences can cause re-infection.

Background Essential health services, including for tuberculosis (TB), are being affected by public health and social measures (PHSM) introduced to control COVID-19. In many settings, TB resources, facilities and equipment are being redirected towards COVID-19 response. Aim We sought to assess the COVID-19 pandemic’s impact on TB services in the World Health Organization (WHO) European Region. Methods The fifty-three European Region Member States were asked to report qualitative and quantitative data in quarter one and two (Q1 and Q2) 2020. TB notifications were triangulated with the severity score on domestic movement restrictions to assess how they may have influenced TB detection. Results Twenty-nine countries reported monthly TB notifications for the first half of 2019 and 2020. TB notifications decreased by 35.5% during Q2 2020 compared with Q2 2019, which is six-fold more than the average annual decrease of 5.1% documented during 2015–2019. The number of patients enrolled in rifampicin-resistant/multidrug-resistant TB treatment also decreased dramatically in Q2 2020, by 33.5%. The highest movement restriction severity score was observed between April and May 2020, which coincided with the highest observed decrease in TB notifications. Conclusion A decrease in TB detection and enrolment to treatment may cause increases in TB burden and threatens the Region’s ability to reach the TB targets of the 2030 Sustainable Development Goals, still this might be mitigated with rapid restoration of TB services and the implementation of targeted interventions during periods with severe PHSM in place, such as those introduced in response to the COVID-19 pandemic.

Background: Treatment success for patients with rifampicin resistant (RR) TB was only 70% in Belarus in 2017. Modified shorter all-oral treatment regimen was developed by Republican Scientific and Practical Centre on Pulmonology and Phthisiatry of Belarus following WHO recommendations on priority grouping of anti-TB medicines for RR-TB treatment. Objective: To summarize the initial outcomes and its determinants of modified shorter treatment regimen for laboratory-confirmed RR and fluoroquinolone sensitive TB patients in programmatic conditions. Methods: This was a prospective study of standardized regimen containing bedaquiline, levofloxacin, linezolid, clofazimine and cycloserine. Bedaquiline was used for 24 weeks, while remaining medicines were used for 9 months. Results: Of 222 patients who met the study inclusion criteria and were successively enrolled from 2018 to 2019, 90,1% had bacteriologically favourable outcome, 4,1% died, 1,3% failed and 4,5% were lost to follow-up. The treatment success was: - significantly higher among patients who converted to smear negative during the first month of treatment (OR=5, 95% CI 1.92-13.7); - not significantly affected by BMI, co-infections with HIV or hepatitis C; - significantly lower among patients with bilateral pulmonary cavitary lesions at treatment start (OR=0.29, 95% CI 0.1-0.7) and those, who was not converted to smear negative by the end of second month of treatment (0.59, 95% CI 0.3-0.9). Conclusions: Modified shorter all-oral RR-TB regimen shows excellent treatment outcomes. Patients with radiologically extensive disease at treatment start and those, with later conversion to smear negative have lower chances for cure.

Treatment outcomes for Multidrug/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) remain poor across the globe and in the Russian Federation. Treatment of XDR-TB is challenging for programmes and patients often resulting in low success rates and onward transmission of drug-resistant strains. Analysis of factors affecting culture conversion rate among XDR-TB patients may serve as a basis for optimization of treatment regimens. We conducted a retrospective cohort study using health records from 54 patients with pulmonary XDR-TB treated at a tertiary level facility in the Russian Federation. The study population included adult patients with culture-positive pulmonary XDR-TB who started treatment between 1 January 2018-30 June 2019. Culture conversion was defined as two consecutive negative cultures, collected at least 30 days apart. The date of sputum culture conversion was taken from the first of two consecutive negative sputum cultures fulfilling these criteria. We measured time to culture conversion using cumulative incidence functions accounting for competing risks and applied binary cause-specific Cox regressions to assess associated factors. Sputum culture conversion was recorded for 43 (79.6%) patients. Median time to culture conversion adjusted for competing risk of loss to follow up was 4 months [95% confidence interval (CI): 2–5]. The number of patients who had culture converted by treatment months 2, 4, and 6 were 12 (22%), 29 (54%) and 38 (70%) respectively. In unadjusted analysis, positive baseline sputum smear microscopy [hazard ratio (HR): 0.34, 95% CI: 0.18-0.66; p=0.001), hepatitis C (HR: 0.35, 95% CI: 0.14-0.89; p=0.023], and human immunodeficiency virus (HR: 0.30 95%, CI: 0.09-0.97; p=0.045), and receipt of fewer than 4 effective drugs in the treatment regimen (HR: 0.13, 95% CI: 0.03-0.60; p=0.009) were associated with delayed culture conversion. When compared to their combined use, patients receiving regimens with bedaquiline only (HR: 0.12, 95% CI: 0.03-0.49; p=0.003) or linezolid only (HR: 0.21, 95% CI: 0.06-0.69; p=0.010) were less likely to achieve timely culture conversion. Factors delaying sputum culture conversion should be considered in the management of patients with XDR-TB and considered by clinicians for regimen design and treatment strategies. Our study outlines the importance of simultaneous inclusion of bedaquiline and linezolid in treatment regimens for patients with XDR-TB to reduce time to sputum conversion and increase treatment success.

Setting: Tuberculosis (TB) morbidity in penitentiary sectors is one of the major barriers to ending TB in the World Health Organization (WHO) European Region. Objectives and design: a comparative analysis of TB notification rates during 2014–2018 and of treatment outcomes in the civilian and penitentiary sectors in the WHO European Region, with an assessment of risks of developing TB among people experience incarceration. Results: in the WHO European Region, incident TB rates in inmates were 4–24 times higher than in the civilian population. In 12 eastern Europe and central Asia (EECA) countries, inmates compared to civilians had higher relative risks of developing TB (RR = 25) than in the rest of the region (RR = 11), with the highest rates reported in inmates in Azerbaijan, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, and Ukraine. The average annual change in TB notification rates between 2014 and 2018 was −7.0% in the civilian sector and −10.9% in the penitentiary sector. A total of 15 countries achieved treatment success rates of over 85% for new penitentiary sector TB patients, the target for the WHO European Region. In 10 countries, there were no significant differences in treatment outcomes between civilian and penitentiary sectors. Conclusion: 42 out of 53 (79%) WHO European Region countries reported TB data for the selected time periods. Most countries in the region achieved a substantial decline in TB burden in prisons, which indicates the effectiveness of recent interventions in correctional institutions. Nevertheless, people who experience incarceration remain an at-risk population for acquiring infection, developing active disease and unfavourable treatment outcomes. Therefore, TB prevention and care practices in inmates need to be improved.

Globally, an estimated 10 million people fell ill with tuberculosis (TB) in 2019, a number that has been declining very slowly in recent years [...].

Background: New and repurposed TB drugs and shorter regimens can radically change the landscape for treating MDR-TB. In December 2019, the WHO issued “Rapid Communication” related to MDR-TB management; WHO reiterated their earlier recommendation that a majority of MDR-TB patients are to receive all-oral treatment regimens, and now allows for shorter duration regimens to be considered under special conditions. Methods: In October 2018 Belarus started to use mSTR for MDR-TB under operational research conditions which include: study protocol; ethics committee review; treatment delivery under WHO-recommended standards. Thirty-nine-week regimen with Lvx, Bdq, Lnz, Cfz and Cs was selected. To be included patients should have laboratory confirmed TB with initial resistance to at least R. Exclusion criteria are: resistance to or previous treatment with any drug of the regimen; QTcF interval longer than 500 msec; ALT/AST more than 5 times higher than upper limits. Results: By 1st February 2020, the programme has included 300 patients. Of them 73 had final treatment outcomes: the median age was 45 years; 79% males; with co-morbidity: HIV - 5%, HCV - 7, DM - 4, Harmful use of alcohol - 15%. The following final treatment outcomes were recorded: treatment success: 67 (91%); lost to follow up: 2 (3%); death: 4 (6%). All deaths were not due to TB or medication. The adverse events were mild and did not prompt the treatment to be stopped. Conclusions: The use of mSTR for MDR-TB under operational research conditions in Belarus shows promising results. The experience gained can promote further expansion of mSTR use to programmatic level.

There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether sub-groups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM.

Background Among all WHO regions, the WHO European Region has the highest proportion of drug-resistant tuberculosis among new and retreated cases. The 18 high-priority countries in eastern Europe and central Asia account for 85% of the tuberculosis incidence and more than 90% of drug-resistant tuberculosis cases emerging in the region. We aimed to analyse time-series trends in notification rates of drug-resistant tuberculosis among new tuberculosis cases in the 18 high-priority countries in the WHO European Region. Methods We used country data stored in WHO's global tuberculosis database. For each country, we calculated annual notification rates per 100 000 population of new tuberculosis cases and of drug-resistant tuberculosis among new cases reported from Jan 1, 2000, to Dec 31, 2017. We computed annual percentage changes of notification rates and identified time-points of significant change in trends using the joinpoint regression method. Findings All 17 countries with data (no data available from Turkmenistan) showed a significant dedine in new tuberculosis notification rates in the most recent years since the last joinpoint if one was identified. Notification rates of drug-resistant tuberculosis showed diverse trends, with substantial year-to-year variation. In the most recent years, notification rates of drug-resistant tuberculosis among new tuberculosis cases were decreasing in two countries (Estonia and Latvia), increasing in eight countries (Azerbaijan, Kyrgyzstan, Moldova [Republic of Moldova], Romania, Russia [Russian Federation], Tajikistan, Ukraine, and Uzbekistan), and stable in seven countries (Armenia, Belarus, Bulgaria, Georgia, Kazakhstan, Lithuania, and Turkey). Interpretation Our findings suggest that countries in the WHO European Region are more successful in controlling drug-susceptible tuberculosis than drug-resistant forms, and as a result, the proportion of drug-resistant strains among newly notified patients with tuberculosis is increasing in many settings. Two countries showed that it is possible to decrease incidence of both drug-susceptible and drug-resistant tuberculosis. If no additional efforts are made in prevention and care of patients with drug-resistant tuberculosis, further decline of the tuberculosis burden will be halted. Further studies are needed to investigate the success stories and document the most effective interventions to reach the target to end tuberculosis by 2030. Copyright (C) 2019. World Health Organization. Published by Elsevier Ltd. All rights reserved.

Background: Recommended by WHO people-centered integrated care and the use of e-health approach are important components of proper management of TB patients. Video observed treatment (VOT) is in line with both components. With the Global Fund’s support a pilot VOT project was expanded across the country in Belarus as of October 2016. Methods: Patients were provided with smartphones and internet access, and briefed on how to record and transmit video files to trained clinic staff. Measures to monitor outcomes of VOT treatment prospectively in the countrywide cohort were developed. Results: By February 1, 2020, 1111 drug susceptible and drug resistant TB patients across the country were recruited: median age 36 years; 64% male; 54% employed, 4% students, 38% unemployed, 4% on maternity leave; 41% with DS-TB, 59% with RR/MDR-TB, including 14% with XDR-TB. Final treatment outcomes were recorded in 816: DS-TB (n=656) treatment success - 97%; RR/MDR-TB (n=160) treatment success - 87%. In both cohorts lost to follow up (LTFU) was 2% only (LTFU was 12% - in countrywide RR/MDR-TB cohort). Conclusions: In addition to high levels of patient acceptability and treatment adherence our data demonstrate excellent treatment outcomes using VOT in DS-TB and RR/MDR-TB patients.