Determinants of multidrug-resistant tuberculosis (MDR-TB) in Belarus
Alena SkrahinaHenadz HurevichAksana ZalutskayaEvgeni SahalchykAndrei AstraukoSven HoffnerValiantsin RusovichAndrei DaduPierpaolo de ColombaniMasoud DaraWayne Van GemertMatteo Zignol
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Abstract:
Introduction. A nationwide survey to investigate risk factors for multidrug-resistant tuberculosis (MDR-TB) was conducted in Belarus in 2010-2011. A total of 1,344 TB patients were enrolled.
Results. MDR-TB was found in 32.3% (95% CI: 29.7-35.0) and 75.6% (95% CI: 72.1-78.9) of new and previously treated patients, respectively. History of previous treatment for TB was the strongest independent risk factor for MDR-TB (Odds Ratios [OR] 6.1, 95%CI: 4.8-7.71) followed by HIV infection (OR 2.2, 95%CI: 1.4-3.5). Other independent risk factors were young 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 in such a way as to be unable to 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).
Discussion. MDR-TB is a widespread problem in Belarus, with very high levels documented countrywide. The convergence of the MDR-TB and HIV epidemics and association between MDR-TB and numerous risk factors calls for stronger collaboration between TB and HIV control programmes and a more targeted approach to high-risk groups. Adherence to TB treatment could be improved by integrating treatment for alcohol use disorders into TB services and enhancing patient incentives and enablers.Keywords:
Alcohol abuse
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The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing in high human immunodeficiency virus (HIV) prevalence settings, with high associated mortality. Treatment outcomes in HIV-co-infected adults and children are poorly documented.To systematically assess treatment outcomes among HIV-MDR-TB co-infected patients.We searched two databases and the proceedings of an annual international conference up to November 2014 for studies reporting on major clinical outcomes among HIV-MDR-TB-co-infected adults and children, and pooled the results using random-effects meta-analysis.Of 4812 abstracts and articles screened, 30 studies providing data on 2578 adults and 147 children were included. Overall pooled treatment success was 56.9% (95% confidence interval [CI] 46.2-67.6), 49.9% (95%CI 38.5-61.2) among adults and 83.4% (95%CI 74.7-92) among children. Mortality was 38% in adults (95%CI 28-48.1) and 11.4% (95%CI 5.8-17.1) in children. Loss to follow-up was higher among adults (16.1%, 95%CI 9-23.2) than among children (3.9%, 95%CI 0.9-6.9). Adverse events were experienced by the majority of patients; however, this was inconsistently documented. The use of fluoroquinolones, aminoglycosides and Group IV drugs appeared to be associated with treatment success.The proportion of HIV-MDR-TB-co-infected patients achieving treatment success was similar to success rates reported among MDR-TB patients in general, regardless of HIV status; however, mortality was higher, particularly among adults, highlighting the need for early diagnosis and more effective treatment regimens.
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Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control. Given expanding global access to antiretroviral therapy (ART) and second-line TB drugs, more data are needed on experiences treating MDR-TB and HIV co-infection in resource-poor settings.To describe the clinical characteristics, management, outcomes, and factors associated with survival among HIV-positive individuals receiving treatment for MDR-TB.This was a retrospective case series of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima, Peru. We used Cox proportional hazards regression models to identify risk factors for mortality.A total of 31 (57%) of the cohort died on treatment, with the majority of deaths due to MDR-TB. Low baseline weight predicted a three-fold increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving highly active ART experienced a significantly lower rate of death compared to those who were not (aHR 0.4, 95%CI 0.2-0.9).Early ART is likely a key component of effective MDR-TB management in co-infected individuals.
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Background: Multidrug-resistant tuberculosis (MDR-TB) causes significant problem and cost for national TB control program.MDR-TB constitutes an increasing public health concern globally.The prevalence of MDR-TB is as high as 50%.One third of all newly detected TB patients are infected with MDR strains.This study aimed to analyze the bio-psychosocial determinants of MDR-TB in Surakarta, Central Java.Subjects and Method: This was a case control study conducted in Dr. Moewardi Hospital and BBKPM, Surakarta, from September to November 2017.A sample consisting of 76 MDR-TB patients and 228 non MDR-TB patients were selected for this study by fixed disease sampling.The dependent variable was MDR-TB.The independent variables were age, drug-taking adherence, depression, comorbidity, drug side-effect, drug-taking supervisor, and family income.The data were collected using a set of questionnaire and analyzed by path analysis.Results: MDR-TB directly increased with the lack of drug-taking adherence (b= -1.7; 95% CI= -2.23 to -1.07; p= 0.001) and comorbidity (b= 1.5; 95% CI= 0.76 to 2.30; p= 0.001).MDR-TB indirectly increased with depression, drug side effect, weak drug-taking supervision, and older age.Conclusion: MDR-TB directly increases with the lack of drug-taking adherence and comorbidity.MDR-TB indirectly increases with depression, drug side effect, weak drug-taking supervision, and older age.
Depression
Multi-drug-resistant tuberculosis
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Background: In Sub-Saharan Africa, the fight against tuberculosis (TB) has encountered a great challenge because of the emergence of drug resistant TB strains and the high prevalence of HIV infection. The aim of this meta-analysis was to determine the association of drug-resistant TB with anti-TB drug treatment history and HIV co-infection.Methods: After electronic based literature search in the databases of Medline, HINARI, EMBASE and the Cochrane library, article selection and data extraction were carried out. HIV co-infection and previous history of TB treatment were used as predictors for the occurrence of any anti-TB drug resistant or multiple drug resistant TB (MDR-TB). The risk ratios for each included study and for the pooledsample were computed using the random-effects model. Heterogeneity test, sensitivity analyses and funnel plots were also done.Results: The pooled analysis showed that the risk of developing drug-resistant TB to at least one anti-TB drug was about 3 times higher in individuals who had a previous history of anti-TB treatment than new TB cases. The risk of having MDR-TB in previously anti-TB treated TB cases was more than 5-fold higher than that of new TB cases. Resistance to Ethambutol and Rifampicin was more than fivefold higher among the previously treated with anti-TB drugs. However, HIV infection was not associated with drug-resistant TB.Conclusion: There was a strong association of previous anti-TB treatment with MDR-TB. Primary treatment warrants special emphasis, and screening for anti-TB drugs sensitivity has to be strengthened.Keywords: drug resistance, HIV, meta-analysis, previous treatment, tuberculosis, Sub-Saharan Africa
Drug resistant tuberculosis
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BACKGROUND: Brazil ranks 14 th worldwide in the number of TB cases and 19 th in terms of TB-HIV co-infected cases. This study aims at identifying clinical and demographic factors associated with unsuccessful treatment outcomes (loss to follow-up, treatment failure and death) of HIV-positive patients with multidrug-resistant TB (MDR-TB) in Rio de Janeiro State, Brazil. METHODS: This was a retrospective cohort study of MDR-TB cases notified from 2000 to 2016 in RJ. Cox proportional hazard regression models were used to assess risk factors associated with unsuccessful treatment in HIV-positive patients with MDR-TB. RESULTS: Among 2,269 patients, 156 (6.9%) were HIV-positive and had a higher proportion of unsuccessful treatment outcomes (52.6%) than HIV-negative cases (43.7%). All HIV-positive cases with extensively drug-resistant TB (XDR-TB) had unsuccessful treatment outcomes. Multivariate analysis shows that previous MDR-TB treatment (HR 1.97, 95% CI 1.22–3.18) and illicit drugs use (HR 1.68, 95% CI 1.01–2.78) were associated with a greater hazard of unsuccessful treatment outcomes, while 6-month culture conversion (HR 0.48, 95% CI 0.27–0.84) and use of antiretroviral therapy (ART) (HR 0.51, 95% CI 0.32–0.80) were predictors of reduced risk. CONCLUSIONS: Unsuccessful treatment was higher among HIV patients with MDR-TB than among HIV-negative patients. Prompt initiation of ART and effective interventions are necessary to improve treatment adherence and prevent retreatment cases.
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The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear.To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana.Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs).A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4).We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.
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Rifampin monoresistant tuberculosis (RMR-TB) is increasingly identified because of scale-up of rapid molecular tests. The longitudinal association of RMR-TB, multidrug-resistant TB (MDR-TB), and HIV/AIDS is incompletely described.We examined clinical characteristics and treatment outcomes of patients with RMR-TB, isoniazid monoresistant TB (IMR-TB), MDR-TB, and drug-susceptible TB during a 16-year period (1993-2008) in California. TB cases were cross-matched with the state HIV/AIDS registry, and HIV prevalence denominators modeled using nonparametric backcalculation.Of 42,582 TB cases, 178 (0.4%), 3469 (8.1%), and 635 (1.5%) were RMR-TB, IMR-TB, and MDR-TB, respectively. From the pre-HAART (1993-1996) to HAART (2005-2008) era, RMR-TB rates declined rapidly (12.0 vs. 0.5 per 100,000) among patients with HIV infection. The proportion of patients for whom rifampin resistance indicated RMR-TB (rather than MDR-TB) decreased from 31% [95% confidence interval (CI) 26-38%] to 11% (95% CI 5-19%). In multivariate analysis controlling for HIV coinfection and other covariates, patients with RMR-TB were twice as likely to die as patients with drug-sensitive TB (relative risk 1.94, 95% CI 1.40-2.69).RMR-TB/HIV rates declined substantially over time in association with improved TB control and HIV control in California. Mortality among patients with RMR-TB was high, even after adjusting for HIV status.
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Background: The increasing burden of multidrug-resistant tuberculosis (MDR-TB) in HIV infected individuals is a serious threat to global tuberculosis control programs. The study aimed to summarize the available evidences on the association of HIV infection and the development of MDR-TB and, finally, to provide an up-to-datepooled estimate of risks.Methods: We searched on PubMed, Google Scholar, and ScienceDirect databases to select eligible studies for our systematic review and meta-analysis, published between January 1, 2010, and July 30,2019. Two sets of reviewers independently extracted data and assessed the methodological quality of the studies using the Newcastle-Ottawa Scale. Subgroup analysis was pre-specified to perform according to the continent, country, income level, study design, mean/median age, and type of MDR-TB. The random-effects model was used to obtain the pooled odds ratio of the crude association between HIV infection and MDR-TB with a 95% confidence interval. We investigated the potential publication bias by checking funnel plot asymmetry and using the Egger’s test. Moreover, we assessed the heterogeneity using Cochran’s Q test and the I2 statistic. Findings: We identified 1496 studies through a database search, and after subsequent elimination based on our eligibility criteria, we selected 47 articles, including 60,754 participants. The pooled odds ratio was 1.47 (95% CI= 1.19-1.81) with substantial heterogeneity (I2=80.49%), and there was no evidence of publication bias (p=0.13). Subgroup analysis revealed that the estimated pooled odds ratio for European countries (OR=2.31, 95% CI= 1.80-2.96, I2=32.26%) was higher than the other three continents (South American, Asia, and Africa). Further analysis showed that the effect estimate was higher for primary MDR-TB (OR=3.13, 95% CI= 1.59-6.13, I2=13.13%) with no heterogeneity among the studies. There was also a trend towards increased risk of MDR-TB for HIV patients of 40 years and older (OR=1.96, 95% CI= 1.41-2.73, I2=69.11%) and women HIV patients (OR=1.97, 95% CI 1.03-3.78, I2=80.35%). The MDR-TB is found to be significant in high burden of TB/HIV countries (OR=1.51, 95% CI= 1.18-1.92, I2=78.1%) and in high-income countries (OR=2.64, 95% CI= 2.01-3.48, I2=15.01%).Interpretation:The risk of MDR-TB increases significantly among HIV infected individuals from the last decade. The most considerable burden of MDR-TB in HIV individuals was found in Europe and the women HIV patients with age 40 years and older are most in the risk of MDR-TB.Funding Statement: The authors stated: "There was a student seed fund for this study. The corresponding author had full access to all study data and the authorized person for the final submission of the paper for publication."Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The protocol was registered with PROSPERO-CRD42019132752.
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Zimbabwe.To investigate the determinants of multidrug-resistant tuberculosis (MDR-TB) among previously treated TB patients.A 1:3 case-control study with bivariate analysis and logistic regression.Risk factors for MDR-TB were history of nursing an MDR-TB patient (adjusted OR [aOR] 4.46, 95%CI 2.02-9.88), history of hospitalisation for 3 days (aOR 2.91, 95%CI 1.62-5.23) and history of foreign travel and stay outside Zimbabwe (aOR 2.68, 95%CI 1.46-4.91). Protective factors were previous successful treatment (aOR 0.05, 95%CI 0.02-0.11), history of supervision by a health worker/village health worker (aOR 0.34, 95%CI 0.19-0.60) and having been treated not more than once previously for TB (aOR 0.18, 95%CI 0.08-0.38). No association between human immunodeficiency virus (HIV) infection and MDR-TB (aOR 1.00, 95%CI 0.53-1.88) was observed. However, among HIV-infected patients, those with CD4 <200 cells/mm3 were more likely to develop MDR-TB (aOR 4.62, 95%CI 2.49-8.53).Individual, service-related, social and demographic factors interact to determine multidrug resistance among previously treated TB patients. Infection control, treatment adherence, reduction of side effects and drug susceptibility testing must be strengthened to reduce the MDR-TB burden in Zimbabwe.
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The effect of HIV on tuberculosis (TB) treatment outcomes has not been well established. We aimed to assess the impact of HIV infection on TB treatment outcomes by using data from notifiable disease surveillance in Europe.We analyzed the treatment outcomes of TB cases reported from nine European countries during 2010-2012. We investigate the effect of HIV on TB treatment outcomes using a multilevel and a multinomial logistic model, and considering the interaction between HIV and multidrug-resistant (MDR) TB.A total of 61,138 TB cases including 5.5% HIV-positive were eligible for our analysis. In the multilevel model adjusted for age and an interaction with MDR TB, HIV was significantly associated with lower treatment success in all MDR strata [non-MDR TB: odds ratio (OR) 0.24 CI (confidence interval) 0.20-0.29; unknown MDR TB status: OR 0.26 CI 0.23-0.30; MDR TB: OR 0.57 CI 0.35-0.91]. In the multinomial regression model, HIV-positive cases had significantly higher relative risk ratio (RRR) for death (non-MDR TB: RRR 4.30 CI 2.31-7.99; unknown MDR TB status: 5.55 CI 3.10-9.92; MDR TB: 3.59 CI 1.56-8.28) and being 'still on treatment' (non-MDR TB: RRR 7.27 CI 3.00-17.6; unknown MDR TB status: 5.36 CI 2.44-11.8; MDR TB: 3.76 CI 2.48-5.71). We did not find any significant association between HIV and TB treatment failure (non-MDR TB: RRR 0.50 CI 0.15-1.67; unknown MDR TB status: 1.51 CI 0.86-2.64; MDR TB: 0.51 CI 0.13-1.87).This large study confirms that HIV is a strong risk factor for an adverse TB treatment outcome, which is mainly manifested by an increased risk of death and still being on TB treatment.
Multi-drug-resistant tuberculosis
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