Operational research as an instrument to address the critical gaps for effective treatment of tuberculosis in eastern Europe and central Asia.

Editorial.

Do catastrophic costs impact treatment outcomes in people with rifampicin-resistant tuberculosis in the Republic of Moldova?

The Republic of Moldova is among the 30 Rifampicin-Resistant and/or Multidrug-Resistant (RR/MDR) Tuberculosis (TB) high burden countries in the world. Despite free TB diagnostics and treatment, TB patients face substantial economic losses and this may impact overall treatment outcomes. We assessed if there is an association between TB-related catastrophic costs and TB treatment outcomes. We conducted a cohort study using data from patient records and a survey that quantified catastrophic costs among RR/MDR-TB affected households in the Republic of Moldova in 2016. We included adult patients (age ≥18 years) with RR/MDR-TB who had been in inpatient (intensive phase) or outpatient (continuous phase) treatment for at least 2 months. Unfavourable treatment outcome, such as failure, death or lost to follow-up, was the primary outcome variable. The definition of catastrophic TB-related costs followed the World Health Organisation (WHO) guidelines: costs due to TB ≥20% of annual household income. Log-binomial regression was used to assess association between the outcome and catastrophic TB-related costs adjusting for other socio-demographic, behavioural and clinical covariates.  In total 287 RR/MDR-TB patients (78% males, mean age 42 years) were included. Of them, 30% experienced catastrophic TB-related costs. Overall, one in five patients (21%) had unfavourable treatment outcome, such as treatment failure (5%), death (8%) or lost to follow-up (8%). The experience of catastrophic TB-related costs was not associated with unfavourable treatment outcome [adjusted relative risk (aRR)=0.88, 95% CI: 0.50-1.50]. Major factors independently associated with unfavourable TB treatment outcomes were poverty (aRR=2.07; 95% CI: 1.06-4.07), urban residence (aRR=1.99; 95% CI: 1.12-3.52) and positive HIV (Human Immunodeficiency Virus) status (aRR=2.61; 95% CI: 1.31-4.89). As a result, we failed to find an association between catastrophic costs and treatment outcomes of RR/MDR-TB patients in the Republic of Moldova. However, we found that patients from poor households and urban areas were twice more likely to achieve unfavourable TB treatment outcomes disregarding whether they experienced catastrophic costs or not. Also, TB/HIV patients and urban residents were identified as the most vulnerable groups with higher risk of unfavourable treatment outcome and TB-related costs.

Factors associated with unfavourable treatment outcomes among people with rifampicin-resistant tuberculosis in Armenia, 2014-2017.

Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) is recognized as a major public health concern globally. In Armenia, the proportion of RR/MDR-TB is increasing among all people affected with TB. We conducted a nationwide cohort study involving analysis of programmatic data to investigate the rates of and factors associated with unfavourable treatment outcomes among patients with RR/MDR-TB registered by the national TB programme from 2014 to 2017 in Armenia. We used Cox regression to identify factors associated with the outcome. Among 451 RR/MDR-TB patients, 80% were men and median age was 46 years. Of them, 53 (11.8%) had Extensively Drug-Resistant Tuberculosis (XDR-TB) and 132 (29.3%) had pre-XDR-TB. Almost half (224, 49.7%) of the patients had unfavourable treatment outcome, which included 26.8% Loss To Follow-Up (LTFU), 13.3% failures and 9.5% deaths. In multivariable analysis, people with pre-XDR-TB [adjusted Hazard Ratio [aHR] 3.13, 95% confidence intervals [CI] 2.16-4.55] and XDR-TB (aHR 4.08, 95% CI 2.45-6.79) had a higher risk of unfavourable outcomes. Patients receiving home-based treatment (71/451, 15.7%) and treatment with new drugs (172/451, 38.1%) had significantly lower risk (aHR 0.45, 95% CI 0.28-0.72 and aHR 0.26, 95% CI 0.18-0.39) of unfavourable treatment outcome.  The proportion of MDR-TB patients reaching favourable treatment outcome in Armenia was substantially lower than the recommended level (75%). The most common treatment outcome was LTFU indicating the need for further assessment of underlying determinants. Home-based treatment looks promising and future studies are required to see if expanding it to all RR/MDR-TB patients is feasible and cost-effective.

Depression and anxiety symptoms among people with rifampicin-resistant tuberculosis receiving in-patient care in the National Pulmonology Reference Institute in Romania.

Mental health comorbidities are common among tuberculosis patients, with higher prevalence among people with rifampicin-resistant/multidrug-resistant (RR/MDR) tuberculosis.  TB and depression share common risk factors adding to the overall disease burden. There is limited evidence about prevalence of depression and anxiety symptoms among tuberculosis patients in Romania. We assessed the prevalence of depression and anxiety symptoms and their evolution over the course of the treatment in RR/MDR-TB patients receiving in-patient care at the National Institute of Pneumonology (NIP) "Marius Nasta" in Romania during May-September 2020. We conducted a cohort study and used the Hospital Anxiety and Depression Scale (HADS) to assess the prevalence of depression and anxiety (defined as score≥ 8) symptoms at admission (baseline) and the second month of in-patient treatment (follow-up). Difference between baseline and follow-up depression and anxiety symptoms were assessed using McNemar test. Binary logistic regression was used to evaluate the association between sociodemographic and clinical characteristics with the presence of depression and anxiety symptoms at baseline. The cohort included 46 patients, 63% were male, mean age was 46 (±13.3) years. The prevalence of depression and anxiety in our cohort was 46% and 43% at baseline respectively, and 50% and 39%, at the follow-up respectively. About one third (7/25) of patients who had normal HADS depression score at baseline, had an increase above the threshold at the second month of treatment. No statistical difference in prevalence of depression or anxiety was found between the baseline and second month of treatment. Unadjusted analysis showed that odds of depression at baseline was lower in patients with education above 8th grade compared to patients with education below 8th grade (odds ratio=0.2, 95% confidence interval: 0.1,0.8, p=0.026). The study revealed high prevalence of depression and anxiety among RR/MDR-TB patients admitted to the NIP, underlining the necessity of evaluating the mental health of TB patients and linking them to appropriate care.

Monitoring Therapy Compliance of Tuberculosis Patients by using Video-Enabled Electronic Devices.

A recent innovation to help patients adhere to daily tuberculosis (TB) treatment over many months is video (or virtually) observed therapy (VOT). VOT is becoming increasingly feasible as mobile telephone applications and tablet computers become more widely available. Studies of the effectiveness of VOT in improving TB patient outcomes are being conducted.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Drug-resistant tuberculosis in the WHO European Region: an analysis of surveillance data.

To review the latest information about levels of anti-tuberculosis (TB) drug resistance in the European Region of the World Health Organization (WHO) and time-trends in multidrug-resistant TB (resistance to isoniazid and rifampicin; MDR-TB) over the past fifteen years. We analysed data on drug resistance among new and previously treated TB cases reported from 1997 to 2012. Data are collected in surveys of representative samples of TB patients or from surveillance systems based on diagnostic drug susceptibility testing. A total of 15.7% (95% confidence limits (CI): 9.5-21.9) of new and 45.3% (95%CI: 39.2-51.5) of previously treated TB cases are estimated to have MDR-TB in the Region. Extensively drug-resistant TB (MDR-TB and resistance to fluoroquinolones and second-line injectables; XDR-TB) had been reported by 38 of the 53 countries of the region (72%). The proportion of MDR-TB cases with XDR-TB is 11.4% (95%CI: 8.6-14.2). Between 1997 and 2012, population rates of MDR-TB declined in Estonia, Latvia and Germany and increased in the United Kingdom, Sweden and Tomsk Oblasts of the Russian Federation. Surveillance of drug resistance has been strengthened in the WHO European Region, which has the highest proportions of MDR-TB and XDR-TB ever reported globally. More complete data are needed particularly from the Russian Federation.

PASS to End TB in Europe: Accelerated efforts on prevention and systematic screening to end tuberculosis in the WHO European Region by 2030.

OBJECTIVES: Outline the objectives, methods, and initial stages of the Prevention and Systematic Screening (PASS) initiative, a complimentary element of the innovative new approach of technical assistance mechanisms of WHO and its partners to countries aligned to the Regional TB Action Plan to End TB in the European Region by 2030. DESIGN: To provide an objective and critical overview of the existing landscape on TB epidemic in the WHO European Region (the European Region) and ii) identify the strategic significance of proactive measures aimed at approaching TB pre-elimination in the Region. RESULTS: Interventions primarily include systematic screening for TB disease and treatment for TB infection (TBI). CONCLUSIONS: PASS to End TB is an exemplary initiative of how technical and funding partners are joining hands to support national health programmes to work towards global commitments to curb major public health challenges like TB.

Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country.

Multidrug-resistant tuberculosis (MDR-TB) is a major concern in countries of the former Soviet Union. The reported risk of resistance among tuberculosis (TB) cases in the Republic of Moldova is among the highest in the world. We aimed to produce high-resolution spatial maps of MDR-TB risk and burden in this setting. We analysed national TB surveillance data collected between 2007 and 2010 in Moldova. High drug susceptibility testing coverage and detailed location data permitted identification of subregional areas of higher MDR-TB risk. We investigated whether the distribution of cases with MDR-TB risk factors could explain this observed spatial variation in MDR-TB. 3447 MDR-TB cases were notified during this period; 24% of new and 62% of previously treated patients had MDR-TB. Nationally, the estimated annual MDR-TB incidence was 54 cases per 100 000 persons and >1000 cases per 100 000 persons within penitentiaries. We identified substantial geographical variation in MDR-TB burden and hotspots of MDR-TB. Locations with a higher percentage of previously incarcerated TB cases were at greater risk of being MDR-TB hotspots. Spatial analyses revealed striking geographical heterogeneity of MDR-TB. Methods to identify locations of high MDR-TB risk and burden should allow for better resource allocation and more appropriate targeting of studies to understand local mechanisms driving resistance.

Multidrug-resistant tuberculosis in Belarus: the size of the problem and associated risk factors.

OBJECTIVE: To assess the problem of multidrug-resistant tuberculosis (MDR-TB) throughout Belarus and investigate the associated risk factors. METHODS: In a nationwide survey in 2010-2011, 1420 tuberculosis (TB) patients were screened and 934 new and 410 previously treated cases of TB were found to meet the inclusion criteria. Isolates of Mycobacterium tuberculosis from each eligible patient were tested for susceptibility to anti-TB drugs. Sociobehavioural information was gathered in interviews based on a structured questionnaire. FINDINGS: MDR-TB was found in 32.3% and 75.6% of the new and previously treated patients, respectively, and, 11.9% of the 612 patients found to have MDR-TB had extensively drug-resistant TB (XDR-TB). A history of previous treatment for TB was the strongest independent risk factor for MDR-TB (odds ratio, OR: 6.1; 95% confidence interval, CI: 4.8-7.7). The other independent risk factors were human immunodeficiency virus (HIV) infection (OR: 2.2; 95% CI: 1.4-3.5), age < 35 years (OR: 1.4; 95% CI: 1.0-1.8), history of imprisonment (OR: 1.5; 95% CI: 1.1-2.0), disability sufficient to prevent work (OR: 1.9; 95% CI: 1.2-3.0), alcohol abuse (OR: 1.3; 95% CI: 1.0-1.8) and smoking (OR: 1.5; 95% CI: 1.1-2.0). CONCLUSION: MDR-TB is very common among TB patients throughout Belarus. The numerous risk factors identified for MDR-TB and the convergence of the epidemics of MDR-TB and HIV infection call not only for stronger collaboration between TB and HIV control programmes, but also for the implementation of innovative measures to accelerate the detection of TB resistance and improve treatment adherence.

Résumé OBJECTIF: Évaluer le problème de la tuberculose multirésistante (TB-MR) sur le territoire biélorusse et explorer les facteurs de risque associés. MÉTHODES: Au cours d'une enquête nationale menée en 2010-2011, 1420 cas de tuberculose (TB) ont été dépistés et 934 cas nouveaux ainsi que 410 cas précédemment traités ont été jugés conformes aux critères d'inclusion. Des isolats de Mycobacterium tuberculosis provenant de chaque patient admissible ont été testés pour leur sensibilité envers les médicaments antituberculeux. Des informations sociocomportementales ont été recueillies lors d'entretiens basés sur un questionnaire structuré. RÉSULTATS: La TB-MR a été détectée dans respectivement 32,3% et 75,6% des cas nouveaux et des cas traités antérieurement, et 11,9% des 612 patients porteurs de la TB-MR présentaient une forme de tuberculose ultrarésistante (TB-UR). Un historique de traitement antérieur pour la TB représentait le principal facteur de risque indépendant pour la TB-MR (rapport des cotes, RC: 6,1; intervalle de confiance à 95%, IC: 4,8 à 7,7). Les autres facteurs de risque indépendants comprenaient l'infection par le virus d'immunodéficience humaine (VIH) (RC: 2,2; IC à 95%: 1,4 à 3,5), l'âge <35 ans (RC: 1,4 ; IC à 95%: 1,0 à 1,8), un historique d'emprisonnement (RC: 1,5; IC à 95%: 1,1 à 2,0), une invalidité suffisante pour empêcher le travail (RC: 1,9 ; IC à 95%: 1,2 à 3,0), l'alcoolisme (RC: 1,3; IC à 95%: 1,0 à 1,8) et le tabagisme (RC: 1,5; IC à 95%: 1,1 à 2,0). CONCLUSION: La TB-MR est très fréquente chez les patients atteints de tuberculose en Bélarus. Les nombreux facteurs de risque identifiés pour la TB-MR et la convergence entre l'épidémie de TB-MR et l'infection par le VIH exigent non seulement de renforcer la collaboration entre les programmes antituberculeux et de lutte contre le VIH, mais aussi la mise en œuvre de mesures innovantes pour accélérer la détection de la résistance à la tuberculose et améliorer l'observance du traitement.

Resumen OBJETIVO: Evaluar el problema de la tuberculosis multirresistente (TB-MR) en Bielorrusia e investigar los factores de riesgo asociados. MÉTODOS: En una encuesta a nivel nacional llevada a cabo entre 2010 y 2011, se evaluó a 1420 pacientes con tuberculosis (TB) y se consideró que 934 nuevos casos de TB y 410 casos de TB previamente tratados reunían los criterios de inclusión. Se analizaron cepas de Mycobacterium tuberculosis de cada paciente elegible con el fin de determinar la susceptibilidad a los fármacos antituberculosos. Se recopiló información socioconductual mediante entrevistas basadas en un cuestionario estructurado. RESULTADOS: Se detectó TB-MR en el 32,3% y el 75,6% de los pacientes de nuevo diagnóstico y tratados previamente, respectivamente, y se observó que el 11,9% de los 612 pacientes con TB-MR presentaba tuberculosis ultrarresistente (TB-XR). Los antecedentes de tratamiento previo de la TB resultaron ser el factor de riesgo independiente que más predispone a sufrir TB-MR (razón de posibilidades, OR: 6,1; intervalo de confianza del 95%, IC: 4,8­7,7). Los demás factores de riesgo independientes fueron el virus de la inmunodeficiencia humana (VIH) (OR: 2,2; IC del 95%: 1,4­3,5), edad < 35 años (OR: 1,4; IC del 95%: 1,0­1,8), antecedentes de encarcelamiento (OR: 1,5; IC del 95%: 1,1­2,0), incapacidad suficiente para impedir el trabajo (OR: 1,9; IC del 95%: 1,2­3,0), alcoholismo (OR: 1,3; IC del 95%: 1,0­1,8) y tabaquismo (OR: 1,5; IC del 95%: 1,1­2,0). CONCLUSIÓN: La TB.MR es muy frecuente entre los pacientes con tuberculosis en Bielorrusia. Los numerosos factores de riesgo identificados para la TB-MR, unidos a la convergencia de las epidemias de TB-MR y la infección por el VIH, exigen no solo una mayor colaboración entre los programas de control de la TB y del VIH, sino también la aplicación de medidas innovadoras destinadas a acelerar la detección de la resistencia a la TB y mejorar el cumplimiento terapéutico.

Epidemiology of tuberculosis in WHO European Region and public health response.

PURPOSE: To provide an overview of the tuberculosis (TB) and multi-drug resistant tuberculosis (MDR-TB) in the WHO European Region and evolution of public health response with focus on extra-pulmonary tuberculosis and Pott's disease. METHODS: Authors reviewed regional strategic documents related to TB. The epidemiologic data were reviewed and analyzed. RESULTS: In the absence of associated pulmonary TB, Pott's disease is reported as extra-pulmonary TB (up to 47 % of all TB cases in some settings). Due to limitations of the surveillance system, the epidemiology of Pott's disease and its treatment success are unknown. The Stop TB Strategy and Consolidated Action Plan to Prevent and Combat M/XDR-TB provide comprehensive roadmaps to address all types of TB. CONCLUSIONS: There is a need to further analyze country data to document the extent of Pott's disease and develop specific guidelines for timely diagnosis and treatment of Pott's disease.

National policies for delivering tuberculosis, HIV and hepatitis B and C virus infection services for refugees and migrants among Member States of the WHO European Region.

BACKGROUND/OBJECTIVE: Refugees and migrants to the World Health Organization (WHO) European Region are disproportionately affected by infections, including tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis B and C (HBV/HCV) compared with the host population. There are inequities in the accessibility and quality of health services available to refugees and migrants in the Region. This has consequences for health outcomes and will ultimately impact the ability to meet Regional infection elimination targets. METHODS: We reviewed academic and grey literature to identify national policies and guidelines for TB/HIV/HBV/HCV specific to refugees and migrants in the Member States of the WHO European Region and to identify: (i) evidence informing policy and (ii) barriers and facilitators to policy implementation. RESULTS: Relatively few primary national policy/guideline documents were identified which related to refugees and migrants and TB [14 of 53 Member States (26%), HIV (n = 15, 28%) and HBV/HCV (n = 3, 6%)], which often did not align with the WHO recommendations, and for some countries, violated refugees' and migrants' human rights. We found extreme heterogeneity in the implementation of the WHO- and European Centre for Disease Prevention and Control (ECDC)-advocated policies and recommendations on the prevention, diagnosis, treatment and care of TB/HIV/HBV/HCV infection among migrants across the Member States of the WHO European Region.There is great heterogeneity in implementation of WHO- and ECDC-advocated policies on the prevention, diagnosis, treatment and care of TB/HIV/HBV/HCV infection in refugees and migrants across the Member States in the Region. CONCLUSION: More transparent and accessible reporting of national policies and guidelines are required, together with the evidence base upon which these policy decisions are based. Political engagement is essential to drive the changes in national legislation to ensure equitable and universal access to the diagnosis and care for infectious diseases.

Diagnostic Procedures, Diagnoses, and Treatment Outcomes of Patients with Presumptive Tuberculosis Pleural Effusion in Uzbekistan.

Tuberculosis (TB) pleural effusion (TPE) is the second most common manifestation of extrapulmonary TB (EPTB), which remains a great diagnostic challenge worldwide. In Uzbekistan, there has been no formal evaluation of the actual practices of diagnosing and treating TPE. Our cohort study therefore aimed to describe the frequency and types of different diagnostic procedures of TPE during 2017-2018 and assess the association of baseline characteristics and establish diagnostic methods with TB treatment outcomes. In total, 187 patients with presumptive TPE were assessed, and 149 had a confirmed diagnosis of TPE (other diagnoses included cancer n = 8, pneumonia n = 17, and 13 cases were unspecified). TB was bacteriologically confirmed in 22 (14.8%), cytologically confirmed in 64 (43.0%), and histologically confirmed in 16 (10.7%) patients. Hepatitis was the only co-morbidity significantly associated with unsuccessful treatment outcomes (RR 4.8; 95%CI: 1.44-15.98, p value 0.011). Multivariable regression analysis showed that drug-resistant TB was independently associated with unsuccessful TB treatment outcome. (RR 3.83; 95%CI: 1.05-14.02, p value 0.04). Multidisciplinary approaches are required to maximize the diagnostic accuracy of TPE and minimize the chances of misdiagnosis. TPE patients with co-infections and those with drug resistance should be more closely monitored to try and ensure successful TB treatment outcomes.

Tuberculosis Notification Trends and Treatment Outcomes in Penitentiary and Civilian Health Care Sectors in the WHO European Region.

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.

Short and long-term outcomes of video observed treatment in tuberculosis patients, the Republic of Moldova.

INTRODUCTION: The Republic of Moldova is among the 18 high priority countries for tuberculosis (TB) in Europe. This study compared adherence and short and long-term TB treatment outcomes for TB patients who experienced asynchronous Video Observed Treatment (aVOT) during three months of outpatient treatment versus Directly Observed Treatment (DOT) in operational conditions in 2016-2017 in Chisinau. METHODOLOGY: We used secondary data from the 2016-2017 Randomized Clinical Trial (RCT) that piloted the aVOT Strategy in Chisinau and data from the national TB register. Relative risk was selected as a measure of association in analysis of treatment strategies (aVOT and DOT under operational conditions) and short and long-term treatment outcomes. RESULTS: From 647 TB patients included in the study, 169 followed the treatment strategy in the RCT (83 in aVOT and 86 in DOT) and 478 were on DOT in operational conditions. Those in aVOT were more likely to have favourable short-term outcome than patients with DOT in operational conditions (RR 0.07; p < 0.001). TB recurrence as an indicator for the long-term outcome, was observed in group with DOT in operational conditions (40 cases, p = 0.006). CONCLUSIONS: This study demonstrated that the aVOT treatment strategy was associated with better adherence and both short and long-term TB treatment favourable outcomes. aVOT as a new patient-centred approach supporting TB patients on improving treatment adherence and outcomes might be recommended as an alternative to DOT strategy in the Republic of Moldova.

Incidence Rate and Risk Factors for Tuberculosis among People Living with HIV: A 2015-2017 Cohort from Tashkent, Uzbekistan.

People living with the human immunodeficiency virus (PLHIV) have a higher risk of developing active tuberculosis (TB) disease, and TB remains a major cause of death in PLHIV. Uzbekistan is facing a substantial TB epidemic, which increases the risk of PLHIV developing active TB. Our retrospective cohort study aimed to evaluate the incidence rate and assess the risk factors for developing active TB among PLHIV. We collected secondary data extracted from medical charts of all patients, newly diagnosed at the AIDS Center in Tashkent, during the period of 2015-2017. The incidence rate of TB among PLHIV was 5.1 (95% CI: 4.5-6.0) per 1000 person/month. Adjusted regression analysis showed three major risk factors for TB, namely, being less than 15 years old (hazard ratio (HR) 5.83; 95% CI: 3.24-10.50, p value = 0.001),low CD4 count (adjusted hazard ratio(aHR) 21.0; 95% CI: 9.25-47.7, p value < 0.001), and antiretroviral therapy (ART) interruption/not receiving ART (aHR 5.57; 95% CI: 3.46-8.97 and aHR 6.2; 95% CI: 3.75-10.24, p value < 0.001, respectively) were significantly associated with developing active TB among PLHIV. Our findings indicate that taking prescribed ART without interruptions and maintaining CD4cell counts higher than 320 cells/µL are essential to prevent the development of active TB among PLHIV.

Operational Research to Inform Programmatic Approaches to the Management of Tuberculosis in Uzbekistan.

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

Drug-resistant tuberculosis in eastern Europe and central Asia: a time-series analysis of routine surveillance data.

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 decline 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. FUNDING: United States Agency for International Development.

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study.

BACKGROUND: In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. METHODS: Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. FINDINGS: Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. INTERPRETATION: Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.