Mycobacterium tuberculosis RD-Rio Strain in Kazakhstan.

Mycobacterium tuberculosis RD-Rio strains are still rare in the former Soviet Union countries and Asia. We describe a strain in Kazakhstan that belongs to the RD-Rio secondary branch, which is endemic to northwest Russia and eastern Europe. Although RD-Rio strains are frequently multidrug resistant, this heterogeneous branch included only drug-susceptible isolates.

Effectiveness of four vaccines in preventing SARS-CoV-2 infection in Almaty, Kazakhstan in 2021: retrospective population-based cohort study.

Background: In February 2021 Kazakhstan began offering COVID-19 vaccines to adults. Breakthrough SARS-CoV-2 infections raised concerns about real-world vaccine effectiveness. We aimed to evaluate effectiveness of four vaccines against SARS-CoV-2 infection. Methods: We conducted a retrospective cohort analysis among adults in Almaty using aggregated vaccination data and individual-level breakthrough COVID-19 cases (≥14 days from 2nd dose) using national surveillance data. We ran time-adjusted Cox-proportional-hazards model with sensitivity analysis accounting for varying entry into vaccinated cohort to assess vaccine effectiveness for each vaccine (measured as 1-adjusted hazard ratios) using the unvaccinated population as reference (N = 565,390). We separately calculated daily cumulative hazards for COVID-19 breakthrough among vaccinated persons by age and vaccination month. Results: From February 22 to September 1, 2021, in Almaty, 747,558 (57%) adults were fully vaccinated (received 2 doses), and 108,324 COVID-19 cases (11,472 breakthrough) were registered. Vaccine effectiveness against infection was 79% [sensitivity estimates (SE): 74%-82%] for QazVac, 77% (SE: 71%-81%) for Sputnik V, 71% (SE: 69%-72%) for Hayat-Vax, and 70% (SE: 65%-72%) for CoronaVac. Among vaccinated persons, the 90-day follow-up cumulative hazard for breakthrough infection was 2.2%. Cumulative hazard was 2.9% among people aged ≥60 years versus 1.9% among persons aged 18-39 years (p < 0.001), and 1.2% for people vaccinated in February-May versus 3.3% in June-August (p < 0.001). Conclusion: Our analysis demonstrates high effectiveness of COVID-19 vaccines against infection in Almaty similar to other observational studies. Higher cumulative hazard of breakthrough among people ≥60 years of age and during variant surges warrants targeted booster vaccination campaigns.

Therapies for people hospitalized with COVID-19 and alignment with national clinical guidelines in a large hospital, Almaty, Kazakhstan, 2020-2021.

Background: Clinical practice guidelines were continually changing during the COVID-19 pandemic to reflect the best available evidence for a novel virus. In Kazakhstan, the national clinical guidelines for COVID-19 patient care were regularly modified and it was not known if and to what extent these guidelines were being followed in practice. Methods: We conducted a sub-analysis of data collected from an observational study among people hospitalized with COVID-19 in a large infectious disease hospital in Almaty in four cross-sections of increased COVID-19 incidence: T1 (1 June-30 August 2020); T2 (1 October-31 December 2020); T3 (1 April-31 May 2021); and T4 (1 July-26 October 2021). Modifications to the national COVID-19 treatment guidelines were identified and clinical data were abstracted from electronic medical records. We assessed frequency of antibiotic, glucocorticoid, anticoagulant, and antiviral administered in each period and determined if these aligned with national clinical guidelines. We used multivariable logistic regression to compare practices across periods. Results: Six modifications were made to national COVID-19 treatment guidelines during this study. Of 1,146 people hospitalized with COVID-19, 14% were in T1, 14% in T2, 22% in T3, and 50% in T4. Anticoagulant treatment was administered to 87% (range: 56%-95%), antibiotic treatment to 60% (range: 58%-64%), glucocorticoid to 55% (range: 43%-64%) and antiviral therapy 15% (range: 7%-22%). Majority of treatments were not aligned with national guidelines, including 98% of anticoagulant use, 95% of antibiotic use, 56% of glucocorticoid use, and 56% of antiviral use. There were no significant changes in practice following changes in guidelines for antibiotic use (64% in T1 to 58% in T2, p = 0.30). There was significant increase in use of anticoagulant (84% in T2 vs. 95% in T3, p < 0.01), glucocorticoid (43% in T2 vs. 64% in T3, p < 0.01), and antiviral treatment (7% in T3 vs. 15% in T4, p < 0.01) after guidelines updates. Conclusion: The majority of treatments administered to people hospitalized with COVID-19 in four periods of high incidence in Almaty were not aligned with updated clinical guidelines. Antibiotic misuse was markedly high throughout. Increased awareness and training on clinical practice guidelines as updates are released may help improve adoption of evidence-based practices.

COVID-19 pandemic and other factors associated with unfavorable tuberculosis treatment outcomes-Almaty, Kazakhstan, 2018-2021.

Introduction: The COVID-19 pandemic negatively influenced the availability of tuberculosis (TB) services, such as detection, diagnosis and treatment, around the world, including Kazakhstan. We set out to estimate the COVID-19 pandemic influence on TB treatment outcomes by comparing outcomes among people starting treatment before the pandemic (2018-2019) and during the pandemic (2020-2021) and to determine risk factors associated with unfavorable outcomes. Methods: We conducted a retrospective cohort study among all people newly diagnosed with drug-sensitive pulmonary or extrapulmonary TB at least 18 years old who initiated treatment from 2018 to 2021 in Almaty. We abstracted data from the national electronic TB register. Unfavorable treatment outcomes were ineffective treatment, death, loss to follow-up, results not evaluated, and transferred. We used multivariable Poisson regression to calculate adjusted relative risk (aRR) and 95% confidence intervals (95%CI). Results: Among 1548 people newly diagnosed with TB during the study period, average age was 43 years (range 18-93) and 52% were male. The number of people initiating treatment was higher before than the pandemic (935 vs. 613, respectively). There was significantly different proportions before compared to during the pandemic for people diagnosed through routine screening (39% vs. 31%, p < 0.001), 60 years and older (16% vs. 22%, p = 0.005), and with diabetes (5% vs. 8%, p = 0.017). There was no difference in the proportion of HIV (8% in both periods). Unfavorable outcomes increased from 11 to 20% during the pandemic (aRR = 1.83; 95% CI: 1.44-2.31). Case fatality rose from 6 to 9% (p = 0.038). Risk factors for unfavorable TB treatment outcomes among all participants were being male (aRR = 1.44, 95%CI = 1.12-1.85), having HIV (aRR = 2.72, 95%CI = 1.99-3.72), having alcohol use disorder (aRR = 2.58, 95%CI = 1.83-3.62) and experiencing homelessness (aRR = 2.94, 95%CI = 1.80-4.80). Protective factors were being 18-39 years old (aRR = 0.33, 95%CI = 0.24-0.44) and 40-59 years old (aRR = 0.56, 95%CI = 0.41-0.75) compared to 60 years old and up. Conclusion: COVID-19 pandemic was associated with unfavorable treatment outcomes for people newly diagnosed with drug-sensitive TB in Almaty, Kazakhstan. People with fewer comorbidities were at increased risk. Results point to the need to maintain continuity of care for persons on TB treatment, especially those at higher risk for poor outcomes during periods of healthcare service disruption.

Factors associated with COVID-19 vaccine confidence among primary care providers in Kazakhstan, March-April 2021.

Introduction: Vaccination is a critical public health intervention, and vaccine hesitancy is a major threat. Globally, confidence in COVID-19 vaccines has been low, and rates of routine immunizations decreased during the COVID-19 pandemic. Because healthcare providers are a trusted source of information on vaccination in Kazakhstan, it was vital to understand their knowledge, attitudes and practices (KAP) related to both routine and COVID-19 vaccines. Methods: From March to April 2021, we conducted a cross-sectional study among the healthcare providers responsible for vaccination in 54 primary care facilities in three cities in Kazakhstan. All consenting providers anonymously completed structured online questionnaires at their place of work. A provider was classified as having COVID-19 vaccine confidence if they planned to get a COVID-19 vaccine, believed that COVID-19 vaccines are important to protect their community and either believed the vaccine was important to protect themselves or believed that getting a vaccine was safer than getting COVID-19. Statistical analysis included chi-square, Spearman's rank correlation coefficient, and Poisson regression. Results: Of 1,461 providers, 30% had COVID-19 vaccine confidence, 40% did not, and 30% would refuse vaccination. Participants were mostly female (92%) and ≤ 35 years old (57%). Additionally, 65% were nurses, 25% were family physicians, and 10% were pediatricians. Adequate KAP for routine vaccines was low (22, 17, and 32%, respectively). Adequate knowledge was highest among pediatricians (42%) and family physicians (28%) and lowest among nurses (17%). Misconceptions about vaccines were high; 54% believed that influenza vaccines cause flu, and 57% believed that there is a scientifically proven association between vaccination and autism and multiple sclerosis. About half (45%) of the practitioners felt confident answering patient vaccine-related concerns. In adjusted models, COVID-19 vaccine confidence was positively associated with adequate knowledge of vaccines (prevalence ratio: 1.2, 95% confidence interval: 1.0-1.4) and adequate attitudes related to routine vaccines (3.1, 2.7-3.6). Conclusion: Our study uncovers critical areas for interventions to improve KAP related to routine immunizations and COVID-19 vaccine confidence among providers in Kazakhstan. The complex relationship between KAP of routine vaccines and COVID-19 vaccine confidence underscores the importance of addressing vaccine hesitancy more broadly and not focusing solely on COVID-19.

Corrigendum: Factors associated with COVID-19 vaccine confidence among primary care providers in Kazakhstan, March-April 2021.

[This corrects the article DOI: 10.3389/fpubh.2023.1245750.].

Outbreak of acute gastroenteritis associated with drinking water in rural Kazakhstan: A matched case-control study.

We conducted an outbreak investigation from June 3 to 15th in a rural village in northern Kazakhstan, after surveillance showed an increase in gastroenteritis. Cases were residents who presented for medical treatment for diarrhea, fever (>37.5 °C), vomiting, or weakness from May 14 to June 15, 2021. Controls were residents matched by age ±2 years at a ratio of two controls for every case. Cases and controls were interviewed using structured questionnaires. We abstracted clinical data from medical records. We mapped cases and assessed risk for disease using conditional multivariable logistic regression. We identified 154 cases of acute gastroenteritis (attack rate of ~26 per 1,000 inhabitants). Symptoms were diarrhea, fever, vomiting, weakness, and decreased appetite. Among cases that participated (n = 107), 74% reported having drank unboiled tap water vs 18% of controls (n = 219). This was the only risk factor associated with disease (adjusted odds ratio: 18; 95% CI 9-35). Drinking water from a dispenser or carbonated drinks was protective. The city has two water supply networks; cases were clustered (107 cases in 79 households) in one. The investigation found that monitoring of quality and safety of water according to national regulations had not been conducted since 2018. No fatalities occurred, and no associated cases were reported after our investigation. Results suggest that untreated tap water was the probable source of the outbreak. The water supply had been cleaned and disinfected twice by the facility 2 days before our investigation began. Recommendations were made for regular monitoring of water supply facilities with rapid public notification when issues are detected to reduce likelihood of future drinking water associated outbreaks.

Factors Associated with an Outbreak of COVID-19 in Oilfield Workers, Kazakhstan, 2020.

From March to May 2020, 1306 oilfield workers in Kazakhstan tested positive for SARS-CoV-2. We conducted a case-control study to assess factors associated with SARS-CoV-2 transmission. The cases were PCR-positive for SARS-CoV-2 during June-September 2020. Controls lived at the same camp and were randomly selected from the workers who were PCR-negative for SARS-CoV-2. Data was collected telephonically by interviewing the oil workers. The study had 296 cases and 536 controls with 627 (75%) men, and 527 (63%) were below 40 years of age. Individual factors were the main drivers of transmission, with little contribution by environmental factors. Of the twenty individual factors, rare hand sanitizer use, travel before shift work, and social interactions outside of work increased SARS-CoV-2 transmission. Of the twenty-two environmental factors, only working in air-conditioned spaces was associated with SARS-CoV-2 transmission. Communication messages may enhance workers' individual responsibility and responsibility for the safety of others to reduce SARS-CoV-2 transmission.

Universal Access to Xpert MTB/RIF Testing for Diagnosis of Tuberculosis in Uzbekistan: How Well Are We Doing?

As per national guidelines in Uzbekistan, all presumptive tuberculosis patients should be tested using the Xpert MTB/RIF assay for diagnosing tuberculosis. There is no published evidence how well this is being implemented. In this paper, we report on the Xpert coverage among presumptive tuberculosis patients in 2018 and 2019, factors associated with non-testing and delays involved. Analysis of national aggregate data indicated that Xpert testing increased from 24% in 2018 to 46% in 2019, with variation among the regions: 21% in Tashkent region to 100% in Karakalpakstan. In a cohort (January-March 2019) constituted of 40 randomly selected health facilities in Tashkent city and Bukhara region, there were 1940 patients of whom 832 (43%, 95% confidence interval (CI): 41-45%) were not Xpert-tested. Non-testing was significantly higher in Bukhara region (73%) compared to Tashkent city (28%). In multivariable analysis, patient's age, distance between primary health centre (PHC) and Xpert laboratory, diagnostic capacity and site of PHC were associated with non-testing. The median (interquartile range) duration from date of initial visit to PHC to receiving results was 1 (1-2) day in Tashkent city compared to 3 (1-6) days in Bukhara region (p-value < 0.001). While there is commendable progress, universal access to Xpert testing is not a reality yet.

Treatment Outcomes of Isoniazid-Resistant (Rifampicin Susceptible) Tuberculosis Patients in Uzbekistan, 2017-2018.

Tuberculosis patients "resistant to isoniazid and susceptible to rifampicin (Hr-TB)" remain neglected, despite a high burden and poor outcomes. The World Health Organization (WHO) recommends a 6 month regimen consisting of levofloxacin, rifampicin, ethambutol, and pyrazinamide (LRZE) to treat Hr-TB. In contrast, Uzbekistan uses a 9 month regimen (LRZE plus a second-line injectable in the first 3 months). We aimed to assess the treatment outcomes of this novel regimen among Hr-TB patients treated in two regions of Uzbekistan (Fergana and Bukhara) in 2017-2018. We conducted a cohort study involving secondary analysis of routine surveillance data. Of 132 Hr-TB patients, 105 (80%) were successfully treated. Death was the predominant unsuccessful outcome (13, 10%) followed by "treatment failure" (10, 8%) and "lost to follow-up" (4, 2%). High treatment success is an indicator of the potential effectiveness of the novel regimen and adds to the limited global evidence on this issue. However, the sample size was small and there was no comparison group. Since the study was conducted in two regions of Uzbekistan only, the findings have limited generalizability. We recommend future research using an adequate sample size and an appropriate study design (randomized controlled trial or prospective cohort with a control group receiving the WHO-recommended regimen).

Primary healthcare centers engagement in tuberculosis treatment in Ukraine.

INTRODUCTION: We assessed the influence of a result-based financing (RBF) model, which included incentives for Primary Healthcare facilities on TB treatment outcomes. METHODOLOGY: We compared TB patients > 17 years and their treatment outcomes among those who did and did not benefit from RBF-model in 14 districts of Odeska oblast, Ukraine in 2017. Log-binomial regression was used to examine factors associated with being included in RBF-model. RESULTS: Of 2,269 reported TB patients, 308 (14%) were included in RBF-model. Most patients in the RBF-model were from rural areas 229 (74%), unemployed 218 (71%), and HIV-infected 131 (43%). Individuals from urban areas (Adjusted risk ratio, ARR =0.9, 95% Confidence Interval, CI:0.89-0.94), having drug-resistant TB (ARR = 0.3, 95% CI: 0.18-0.45), and relapse TB (ARR = 0.6, 95% CI:0.40-0.83) were less likely to be included in RBF-model. Favorable outcomes in new/relapse cases with RBF-model was 89% compared with 41% (p < 0.001) without RBF. Similarly, for other retreatment this was 83% versus 40% (p < 0.001). Failures in the no-RBF group was 29% for new and relapse cases while for other retreatment cases, it was 26% (significantly higher than in the RBF-model). CONCLUSION: RBF-model is effective in achieving high levels of favorable TB treatment outcomes. Almost three-in-ten TB patients in non-RBF category failed TB treatment despite having drug-susceptible TB. Efforts are now needed to include it within ongoing public health reforms and assess the feasibility of scaling-up this intervention through implementation research and dedicated funding.

Strategies for active detection of tuberculosis in Ukraine: Comparative effectiveness amongst key populations (2014-2018).

INTRODUCTION: Ukraine has gaps in Tuberculosis (TB) service coverage, especially in key populations (KPs). We compared effectiveness of three different strategies for active TB detection among KPs and their linkage to TB treatment during three time periods. METHODOLOGY: The KPs included people who inject drugs (PWID), sex workers (SW), men who have sex with men (MSM) and groups at-risk of TB (ex-prisoners, Roma and homeless). The active case finding included decentralized symptom screening and specimen collection (2014, strategy-1), decentralized screening with patient referred for specimen collection (2015-2017, strategy-2) and strategy-2 plus GeneXpert (2018, strategy-3). RESULTS: In total 680,760 KPs were screened, of whom 68% were PWID. TB case detection per 100,000 populations was 1,191 in strategy-1, 302 in strategy-2, and 235 in strategy-3. The number needed to screen (NNS) to identify one case was respectively 84, 332, and 425. TB detection was highest among homeless (range: 1,839-2,297 per 100,000 population). The lowest detection was among the MSM and SW. Between 2014 and 2018, 82-94% of all diagnosed TB patients in KPs started TB treatment. CONCLUSIONS: The active case finding in KPs increased detection of TB cases in Ukraine, and the majority of diagnosed KPs initiated TB treatment. Centralization of diagnosis reduced the effectiveness of TB screening. Each region in Ukraine should assess the composition and the needs of KPs which will allow for adoption of specific strategies to detect TB among KPs with high TB prevalence.