Missed Tuberculosis Diagnoses: Analysis of Pediatric Autopsy Data From General Hospitals in Lviv, Ukraine.

We reviewed autopsy data from general hospitals in Lviv, Ukraine to understand pediatric mortality due to tuberculosis (TB). We identified 14 (0.6%) of 2345 autopsied children with unrecognized or untreated TB. More sensitive TB diagnostics for children and improved strategies for identifying which children require TB evaluation are urgently needed.

Incidence and Mortality of Extrapulmonary Tuberculosis in Ukraine: Analysis of National Surveillance Data.

BACKGROUND: Improved understanding of the epidemiology and mortality risk factors of extrapulmonary tuberculosis (EPTB) may facilitate successful diagnosis and management. METHODS: We analyzed national surveillance data from Ukraine to characterize EPTB subtypes (ie, localized in different anatomic sites). We calculated annual reported incidence, stratified by age, sex, and human immunodeficiency virus (HIV) status. Using Cox regression, we estimated mortality risk factors. RESULTS: Between January 2015 and November 2018, 14 062 adults/adolescents (≥15 years) and 417 children (<15 years) had EPTB with or without concomitant pulmonary TB. The most commonly reported EPTB subtypes were pleural, peripheral lymph node, and osteoarticular. Most EPTB subtype notifications peaked at age 30-39 years and were higher in males. In adults/adolescents, most peripheral TB lymphadenitis, central nervous system (CNS) TB, and abdominal TB occurred in those with untreated HIV. CNS TB notifications in people without HIV peaked before age 5 years. Adults/adolescents with CNS TB (adjusted hazard ratio [aHR]: 3.22; 95% CI: 2.89-3.60) and abdominal TB (aHR: 1.83; 95% CI: 1.59-2.11) were more likely to die than those with pulmonary TB. Children with CNS TB were more likely to die (aHR: 88.25; 95% CI: 43.49-179.10) than those with non-CNS TB. Among adults/adolescents, older age and HIV were associated with death. Rifampicin resistance was associated with mortality in pleural, peripheral lymph node, and CNS TB. CONCLUSIONS: We identified the most common EPTB subtypes by age and sex, patterns of EPTB disease by HIV status, and mortality risk factors. These findings can inform diagnosis and care for people with EPTB.

MOLECULAR EPIDEMIOLOGY APPROACH TO TACKLE TREATMENT FAILURE IN DRUG RESISTANT TUBERCULOSIS (DR-TB).

OBJECTIVE: The aim: To analyze molecular epidemiology features of M. tuberculosis in Kyiv oblast; and to identify the safest mode of TB treatment, which will allow clinicians to minimize the risk of drug-resistant strains nosocomial transmission. PATIENTS AND METHODS: Materials and methods: 55 isolates of M. tuberculosis were collected in January-April, 2018 from 31 patients with new cases and 24 patients with re-treatment cases of sputum culture-positive pulmonary TB, in Kyiv oblast, Ukraine. DNA samples extracted from all the isolates were used for 15-loci MIRU-VNTR molecular typing with further M. tuberculosis strains comparison by means of MIRU-VNTRplus web tool (http://www.miru-vntrplus.org). RESULTS: Results: Phylogenetic tree that reflects strains interrelationship reveals four main clusters, the largest of which spans 34 isolates. The presence of two big subclusters with 10 and 7 identical genotypes inside the largest cluster strongly suggests their tight epidemiologic relationship. Smaller clusters consist of five (Harlem), three (URAL), and two unidentified isolates. 10 singletons were detected, among which LAM, URAL and Cameroon lineages were identified; in these cases, epidemiological connection was presumably ruled out. CONCLUSION: Conclusions: High clustering level of isolates of M. tuberculosis suggests possible contact between patients from whom these isolates were obtained. Predominance of Beijing family in the clusters is associated with high DR-TB level, at least in eastern European countries. Similarity of the clusters isolated from different patients in a household or a hospital suggests high probability of recent disease transmission. Clustering genotypes from households and hospital wards can be a surrogate criterion of infection control effectiveness.

Influence of crystallizing agent on sugar quality.

BACKGROUND: One of the important processes in sugar production is massecuite boiling. The intensification of this process is possible by reducing the boiling time and thus improving the quality of the finished product. This study examines the methods of massecuite boiling by using different types of crystal formers: powdered sugar, a standard factory suspension, and the crystal former "Ester K 01", as well as a comparison of their direct effects on the quality of the finished product. METHODS: All laboratory tests of crystal-forming agents were carried out using syrup taken from sugar factories. Laser diffractometry was used to determine the particle size (dispersion) of the crystalforming agents. Prepared syrup samples were used to obtain the massecuite, which was boiled in a laboratory vacuum evaporator in conditions maximally adapted to production. Sugar was obtained by separating the massecuite in a laboratory vacuum filtration. All the studies of qualitative and quantitative indicators of products and intermediates were performed using standard methods. RESULTS: The particle size distribution was determined and the curves of the differential size distribution of sugar fineness were given. The most uniform particle distribution was noted using "Ester K 01" crystal former. The duration of massecuite boiling was studied and a comparative characteristic of the quality indicators was provided for the obtained massecuite and massecuite syrup in accordance with the type of crystal former used. The highest sucrose content was observed in the sugar sample obtained using the "Ester K 01" crystallizing agent. This sample also had the lowest ash content. Microphotographs of the sugar crystals were provided with fixation of their size after 5, 10, and 20 minutes of adding various types of crystallizing agent, and the morphology of the sugar crystals in the finished massecuite was studied. The most equal crystals were produced using an "Ester K 01" crystallizing agent and a standard factory suspension in comparison to massecuite made with icing sugar. The granulometric composition of sugar crystals obtained with different crystal formers was also compared in this research. The crystal former "Ester K 01" was studied in production and laboratory conditions, and the crystallizing agents' comparative characteristics were also given. CONCLUSIONS: In conclusion, the usage of the crystallizing agent "Ester K 01" in the fully automated proces conditions for producing massecuite would be recommended by us. It will allow more uniform granulometric composition of sugar to be obtained.

Clinical manifestations and epidemiology of adolescent tuberculosis in Ukraine.

BACKGROUND: During adolescence, childhood and adult forms of tuberculosis (TB) overlap, resulting in diverse disease manifestations. Knowing which patient characteristics are associated with which manifestations may facilitate diagnosis and enhance understanding of TB pathophysiology. METHODS: In this cross-sectional study, we included 10-19-year-olds in Ukraine's national TB registry who started TB treatment between 2015 and 2018. Using multivariable regression, we estimated associations between patient characteristics and four presentations of TB: pleural, extrathoracic, cavitary and rifampicin-resistant (RR). We also described the epidemiology of adolescent TB in Ukraine. RESULTS: Among 2491 adolescent TB cases, 88.4% were microbiologically confirmed. RR-TB was confirmed in 16.9% of new and 29.7% of recurrent cases. Of 88 HIV-infected adolescents, 59.1% were not on antiretroviral therapy at TB diagnosis. Among 10-14-year-olds, boys had more pleural disease (adjusted OR (aOR) 2.12, 95% CI: 1.08-4.37). Extrathoracic TB was associated with age 15-19 years (aOR 0.26, 95% CI: 0.18-0.37) and HIV (aOR 3.25, 95% CI: 1.55-6.61 in 10-14-year-olds; aOR 8.18, 95% CI: 3.58-17.31 in 15-19-year-olds). Cavitary TB was more common in migrants (aOR 3.53, 95% CI: 1.66-7.61) and 15-19-year-olds (aOR 4.10, 95% CI: 3.00-5.73); among 15-19-year-olds, it was inversely associated with HIV (aOR 0.32, 95% CI: 0.13-0.70). RR-TB was associated with recurrent disease (aOR 1.87, 95% CI: 1.08-3.13), urban residence (aOR 1.27, 95% CI: 1.01-1.62) and cavitation (aOR 2.98, 95% CI: 2.35-3.78). CONCLUSIONS: Age, sex, HIV and social factors impact the presentation of adolescent TB. Preventive, diagnostic and treatment activities should take these factors into consideration.

Patients' perspectives of tuberculosis treatment challenges and barriers to treatment adherence in Ukraine: a qualitative study.

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine. DESIGN: Qualitative study. SETTING: TB treatment facilities in Kyiv Oblast, Ukraine. PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015. METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO's framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified risk correlates of non-adherence. RESULTS: Among 60 participants, 19 (32.8%) were HIV positive, 12 (20.3%) had substance use disorder and 9 (15.0%) had not completed TB treatment. Respondents discussed the psychological distress associated with hospital-based TB care, as well as perceived unsupportive, antagonistic interactions with TB providers as major challenges to treatment adherence. An additional barrier to successful treatment completion included the financial toll of lost income during TB treatment, which was exacerbated by the additional costs of ancillary medications and transportation to ambulatory TB clinics. The high pill burden of TB treatment also undermined adherence. These challenges were endorsed among participants with and without major risk factors for non-adherence. CONCLUSIONS: Our findings highlight important barriers to TB treatment adherence in this study population and suggest specific interventions that may be beneficial in mitigating high rates of poor treatment outcomes for TB in Ukraine.

Pediatric Multidrug-resistant Tuberculosis in Kyiv City, Ukraine.

Few reports have described pediatric Multidrug-resistant Tuberculosis (MDR-TB) in the former Soviet republics, despite the fact that these countries have the highest proportion of TB cases that are MDR. We aimed to examine pediatric MDR-TB in Ukraine. This retrospective cohort study included all children <18 years of age who started undergoing MDR-TB treatment between January 1, 2011 and July 31, 2016 at Kyiv City Pediatric TB Hospital. From each child's clinical chart, we abstracted demographic and clinical data. Using Fisher's exact test, we compared characteristics between children with microbiologically confirmed vs. probable (i.e., clinically diagnosed) MDR-TB. The study population included 20 children with a median age of 5 years. At diagnosis, 12 (60%) had intrathoracic lymphadenopathy as their only radiographic abnormality, and two (10%) were asymptomatic. Children with confirmed MDR-TB were more likely to be adolescents or have radiologic abnormalities in addition to intrathoracic lymphadenopathy. Median treatment duration was 20 months. Eighteen (90%) children were treated successfully. The remaining two were transferred to another facility, and their final outcomes were unknown. The excellent outcomes in this cohort are consistent with high treatment success rates for pediatric MDR-TB reported in other parts of the world.

Risk factors for poor multidrug-resistant tuberculosis treatment outcomes in Kyiv Oblast, Ukraine.

BACKGROUND: Ukraine is among ten countries with the highest burden of multidrug- resistant TB (MDR-TB) worldwide. Treatment success rates for MDR-TB in Ukraine remain below global success rates as reported by the World Health Organization. Few studies have evaluated predictors of poor MDR-TB outcomes in Ukraine. METHODS: We conducted a retrospective analysis of patients initiated on MDR-TB treatment in the Kyiv Oblast of Ukraine between January 01, 2012 and March 31st, 2015. We defined good treatment outcomes as cure or completion and categorized poor outcomes among those who died, failed treatment or defaulted. We used logistic regression analyses to identify baseline patient characteristics associated with poor MDR-TB treatment outcomes. RESULTS: Among 360 patients, 65 (18.1%) achieved treatment cure or completion while 131 (36.4%) died, 115 (31.9%) defaulted, and 37 (10.3%) failed treatment. In the multivariate analysis, the strongest baseline predictors of poor outcomes were HIV infection without anti-retroviral therapy (ART) initiation (aOR 10.07; 95% CI 1.20-84.45; p 0.03) and presence of extensively-drug resistant TB (aOR 9.19; 95% CI 1.17-72.06; p 0.03). HIV-positive patients initiated on ART were not at increased risk of poor outcomes (aOR 1.43; 95% CI 0.58-3.54; p 0.44). There was no statistically significant difference in risk of poor outcomes among patients who received baseline molecular testing with Gene Xpert compared to those who were not tested (aOR 1.31; 95% CI 0.63-2.73). CONCLUSIONS: Rigorous compliance with national guidelines recommending prompt initiation of ART among HIV/TB co-infected patients and use of drug susceptibility testing results to construct treatment regimens can have a major impact on improving MDR-TB treatment outcomes in Ukraine.

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine.

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high.     We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes. Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes. Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) defaulted. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 - 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 - 12.43; p 0.01) were at increased risk of poor outcomes. Alcohol abuse (OR 1.81; 95% CI 0.93 - 3.55; p 0.08) and smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) were also associated with poor treatment outcomes. Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

Tuberculosis-HIV co-infection in Kiev City, Ukraine.

In 2004, we tested all patients with newly diagnosed tuberculosis (TB) for HIV in Kiev City. The results were compared to information from medical records of 2002, when co-infection prevalence was 6.3%. Of 968 TB patients, 98 (10.1%) were HIV infected. TB-HIV co-infection is increasing, especially in injecting drug users.