Valiantsin Rusovich

Alarming levels of drug-resistant tuberculosis in Belarus: results of a survey in Minsk

Resistance to anti-tuberculosis (TB) medicines is a major public health threat in most countries of the former Soviet Union. As no representative and quality-assured information on the magnitude of this problem existed in Belarus, a survey was conducted in the capital city of Minsk. Between November 2009 and December 2010, 156 consecutively diagnosed new and 68 previously treated culture-positive TB patients residing in Minsk were enrolled in the survey. Mycobacterium tuberculosis isolates were obtained from each patient and tested for susceptibility to first- and second-line anti-TB drugs. Multidrug-resistant (MDR)-TB was found in 35.3% (95% CI 27.7–42.8) of new patients and 76.5% (95% CI 66.1–86.8) of those previously treated. Overall, nearly one in two patients enrolled had MDR-TB. Extensively drug-resistant TB was reported in 15 of the 107 MDR-TB patients (14.0%, 95% CI 7.3–20.7). Patients <35 yrs of age have shown a two times higher odds ratio of multidrug-resistant TB than those aged >35 yrs. The findings of this survey in Minsk city are alarming and represent the highest proportions of MDR-TB ever recorded in the world. This study greatly contributes to the understanding of the burden of drug-resistant TB in urban areas of Belarus.

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.

Monitoring Therapy Adherence 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.

Bacille Calmette-Guérin vaccination: The current situation in Europe

Tuberculosis is a major public health priority. This is not only because of its daunting morbidity and mortality rates, both globally and in Europe (summarised in figs 1 and 2) [1, 3–5], but also because of the natural history of the disease. Active (contagious) tuberculosis disease occurs after a period of latency (or subclinical infection), and different risk factors [6–13], in combination with latent infection, introduce challenges to prevention, diagnosis and treatment of the disease. Vaccination against tuberculosis, if effective, would be therefore critical to control and elimination strategies [14–16]. The bacille Calmette–Guerin (BCG) vaccine is, from a historical perspective, a milestone of tuberculosis control (figs 3–7). During the first half of the 20th century, it was administered ubiquitously throughout Europe, but is now recommended by the World Health Organization (WHO) to be given once at birth, specifically in tuberculosis-endemic areas. Figure 1– Global estimated tuberculosis (TB) incidence rates, 2011. Reproduced from [1] with permission from the publisher. Figure 2– World Health Organization European Region estimated tuberculosis incidence rates per 100 000 population, 2011. Data from the United Nations Administrated Province of Kosovo (in accordance with Security Council Resolution 1244 (1999)) is not included in the figures reported for Serbia. Reproduced from [2] with permission from the publisher. Figure 3– Wooden mask worn by health workers to announce a forthcoming vaccination campaign (Republic of Benin). Image courtesy of J.P. Zellweger. Figure 4– “To defeat tuberculosis is easy with the BCG”. Advertisement in a peripheral tuberculosis dispensary, dating from the time of French colonisation ( circa 1950) (Republic of Benin). Image courtesy of J.P. Zellweger. Figure 5– French Ministry of Health educational poster supporting bacille Calmette–Guerin vaccination. Image courtesy of J.P. Zellweger. Figure 6– Tuberculosis/HIV-infected children in Myanmar. ©2012 Matthieu Zellweger (with AIDSpartners.org)/matthieuzellweger.com. Figure 7– Romania, 1974. …

Digital health for the End TB Strategy: developing priority products and making them work

In 2014, the World Health Organization (WHO) developed the End TB Strategy in response to a World Health Assembly Resolution requesting Member States to end the worldwide epidemic of tuberculosis (TB) by 2035. For the strategys objectives to be realised, the next 20 years will need novel solutions to address the challenges posed by TB to health professionals, and to affected people and communities. Information and communication technology presents opportunities for innovative approaches to support TB efforts in patient care, surveillance, programme management and electronic learning. The effective application of digital health products at a large scale and their continued development need the engagement of TB patients and their caregivers, innovators, funders, policy-makers, advocacy groups, and affected communities. In April 2015, WHO established its Global Task Force on Digital Health for TB to advocate and support the development of digital health innovations in global efforts to improve TB care and prevention. We outline the groups approach to stewarding this process in alignment with the three pillars of the End TB Strategy. The supplementary material of this article includes target product profiles, as developed by early 2016, defining nine priority digital health concepts and products that are strategically positioned to enhance TB action at the country level. Priority digital health products will be profiled and developed to support the scale-up of WHOs End TB Strategy http://ow.ly/4mRRjR

Poor treatment outcomes among multidrug-resistant tuberculosis patients in Gomel Region, Republic of Belarus

SETTINGS Tuberculosis (TB) health facilities in the Gomel Region, Republic of Belarus-settings with a high burden of multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE To determine treatment outcomes among MDR-TB patients diagnosed in 2009-2010 and factors associated with unsuccessful outcomes (death, failure and loss to follow-up). DESIGN Retrospective cohort study involving a review of an electronic patient database maintained under the National Tuberculosis Control Programme. RESULTS Of 517 patients diagnosed, 78 (15%) did not start treatment. Among 439 patients who started treatment (84% males, median age 45 years, 15% HIV-infected), 291 (66%) had unsuccessful outcomes (35% deaths, 18% treatment failure and 13% lost to follow-up). Multivariate regression analysis showed that patients aged ⩾45 years (aRR 1.2, 95%CI 1.1-1.3), HIV-infected patients and those not receiving antiretroviral therapy (ART) (aRR 1.5, 95%CI 1.4-1.6) and those with a previous history of anti-tuberculosis treatment (aRR 1.2, 95%CI 1.1-1.4) had significantly higher risk of unsuccessful outcomes. CONCLUSION Treatment outcomes among MDR-TB patients were poor, with high rates of death, failure and loss to follow-up (including pre-treatment loss to follow-up). Urgent measures to increase ART uptake among HIV-infected MDR-TB patients, improved access to second-line anti-tuberculosis drug susceptibility testing and comprehensive patient support measures are required to address this grim situation.

Video-observed treatment for tuberculosis patients in Belarus: findings from the first programmatic experience

The treatment of tuberculosis requires daily intake of multiple medications for between 6 months and 2 years, or more [1, 2]. This long duration predisposes to the interruption of medications with the risk of the emergence of drug resistance, death, disease persistence and continued transmission of tuberculosis in the community. Directly observed treatment, together with patient support, has been recommended to improve adherence [3]. However, daily treatment observation presents challenges for both patients and observers, which have limited its implementation [4]. Digital technologies, like video (or virtually)-observed treatment (VOT) can help bridge the gap between patients and health services and promote adherence [5]. VOT usually requires patients to film themselves taking medications on a computer or mobile device and then transmit these images to a remote observer via the internet [6–9]. Video technology has been available for more than a decade, but the increasing availability of smartphones and broadband internet is making VOT practical to implement even in resource-constrained settings. Belarus has started implementing video-observed treatment for patients with tuberculosis using smartphones http://ow.ly/q1dM307W7hC

Bedaquiline in the multidrug-resistant tuberculosis treatment: Belarus experience

Background/objective: Outcomes of treatment for multidrug-resistant tuberculosis (MDR-TB) remain poor worldwide. Among patients with MDR-TB in Belarus who started treatment in 2012, only 54% completed it successfully, with treatment failure reported in 22% of the patients; additionally, 11% died and 13% were lost to follow-up or remained unevaluated. In Belarus, to improve outcomes, bedaquiline was introduced in MDR-TB treatment in June 2015. The national TB program developed measures to monitor safety and effectiveness of bedaquiline-containing regimens in line with the World Health Organization recommendations. Methods: After enrollment of patients, clinical, radiological, laboratory, and microbiological data were carefully collected at start, during treatment, and at follow-up. A total of 197 patients were enrolled: male, 140 (71%); female, 57 (29%); new TB cases, 83 (42%); previously treated, 114 (58%); extensively drug-resistant-TB (XDR-TB), 128 (65%), pre-XDR-TB (fluoroquinolone resistant), 34 (17%), pre-XDR-TB (injectables resistant), 25 (13%), and other MDR-TB cases, 10 (5%). Results: According to the intermediate analysis, 186 patients currently are continuing with the treatment, two patients died, and nine patients were lost to follow-up. Sputum culture conversion were observed in 186 patients (94%) at 6 months and one (0.5%) of these 197 patients started treatment; six patients (3%) remain sputum culture positive. The safety data were as follows: 135 patients (68%) experienced metabolism and nutrition disorders (hyperuricemia being the most common), 127 patients (64%) experienced hepatobiliary disorders (hepatic functions abnormality being the most common), 93 patients (47%) experienced electrolyte disorders (hypomagnesemia being the most common), 80 patients (41%) experienced cardiac disorders (abnormal electrocardiogram and arrhythmia being the most common), 68 patients (35%) experienced gastrointestinal system disorders (nausea, vomiting, and abdominal pain being the most common disorders), 54 patients (27%) experienced blood and the lymphatic system disorders (low platelet count being the most common), 42 patients (21%) experienced renal and urinary disorders (creatinine clearance decrease being the most common), 40 patients (20%) experienced nervous system disorders (headache, dizziness, and paresthesia being the most common ones), 36 patients (18%) experienced skin and subcutaneous tissue disorders (rush and pruritus being the most common), 35 patients (17%) experienced ear and labyrinth disorders (tinnitus and decreased hearing being the most common ones), 32 patients (15%) experienced psychiatric disorders (insomnia being the most common disorder), and 30 patients (14%) experienced infections and infestations (candidiasis being the most common). The most adverse events were mild or moderate in severity and reversible. One death was possibly related to MDR-TB therapy. Conclusion: Our interim results on safety and effectiveness of bedaquiline-containing regimens in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) patients are encouraging. They will add value to understanding role and place of this new anti-TB drug in M/XDR-TB treatment.

Indicators of rifampicin-resistant TB response in Belarus, 2009-2014

Tuberculosis (TB) strains with rifampicin-resistance (RR-TB) and multidrug-resistance (RR-TB plus resistance to isoniazid; MDR-TB) are less amenable to treatment than drug-susceptible TB. TB patients in Belarus have the highest risk worldwide for MDR-TB (34% in new; 69% in retreatment cases). We use surveillance data collected by the national TB programme to generate and discuss key indicators for RR-/MDR-TB response in the country in recent years. Total TB notifications have declined substantially in Belarus between 2006 and 2014 (6,065 to 4,274). Between 2006 and 2010, detection of RR-/MDR-TB cases increased, then plateaued and declined after 2012. Coverage of testing for RR-/MDR-TB in bacteriologically-confirmed TB cases reached 97% in new and 84% in retreatment. Enrolment on treatment increased between 2010 and 2012, and then declined but still at levels exceeding cases detected. Treatment success improved in successive years but remains low (54% in 2012 cohort) as a result of failure of treatment (22%), death (11%) and interruption (10%). In recent years Belarus has mounted a substantial response to RR-/MDR-TB. High levels of enrolment may indicate efforts to treat patients diagnosed in previous years but also re-registration of cases within the same year. Treatment success could be improved with enhanced treatment regimens and increased efforts to treat patients earlier and to support adherence.