Risk Factors For Drug-resistant Tuberculosis Research Articles

Audit of risk factors of drug-sensitive, drug-resistant tuberculosis disease, a case-control study of patients registered under NTEP, Gujarat.

Characterizing risk factors for drug-resistant tuberculosis (TB) is critical to guide targeted interventions in high-burden settings like India. We aimed to identify socioeconomic, lifestyle, and clinical factors associated with drug-sensitive and drug-resistant TB acquisition. A comparative cross-sectional study recruited 350 bacteriologically confirmed TB patients registered under the National Tuberculosis Elimination Program (NTEP) in Gujarat, India, and 300 matched participants without active/past TB. Multinomial logistic regression analyzed risk factors for 200 drug-sensitive and 150 drug-resistant TB cases compared to participants without active or past TB. Key factors independently associated with higher adjusted odds ratios (aOR) of both TB types included low socioeconomic status (SES) (drug-sensitive TB: aOR 1.7, 95% CI 1.2-2.5; drug-resistant TB: aOR 2.2, 95% CI 1.3-3.7), crowding (>5 persons/room) (drug-sensitive TB: aOR 1.6, 95% CI 1.1-2.3; drug-resistant TB: aOR 1.9, 95% CI 1.2-2.9), undernutrition (drug-sensitive TB: aOR 1.6, 95% CI 1.1-2.3; drug-resistant TB: aOR 2.0, 95% CI 1.2-3.2), smoking (drug-sensitive TB: aOR 1.5, 95% CI 1.0-2.3; drug-resistant TB: aOR 1.7, 95% CI 1.1-2.7), and indoor air pollution (drug-sensitive TB: aOR 1.5, 95% CI 1.0-2.2; drug-resistant TB: aOR 1.8, 95% CI 1.2-2.8). Marked social determinants and clinical risks drive heightened susceptibility for both TB types in India, while prior inadequate treatment and nosocomial exposures selectively enable additional drug resistance. Holistic prevention policies jointly targeting transmission, vulnerability, and curative factors are imperative.

Trends and risk factors for drug-resistant tuberculosis among children in Sichuan, China: A 10-year retrospective analysis, 2013-2022.

To investigate the status of the drug-resistant tuberculosis (DR-TB) among children in Sichuan, and to find out the risk factors and high-risk population related to drug resistance among children. The clinical data of tuberculosis patients ≤14 years old with culture-confirmed tuberculosis hospitalized in Chengdu Public Health Clinical Center from January 2013 through December 2022 were collected. Clinical data such as gender, age, ethnicity, history of anti-TB treatment, history of exposure to tuberculosis, nutritional status, and specific drug resistance of the children were collected and recorded. The drug resistance of children in different age groups (0-4 years old, 5-9 years old, 10-14 years old) and different periods (2013-2017 and 2018-2022) were grouped and compared. Logistic regression analysis was to analyze analysis of risk factors of drug resistance in children. A total of 438 children with culture-confirmed tuberculosis were screened. Among them, 26.19% (11/42) were 0 to 4 years old, 33.33% (22/66) were 5 to 9 years old, and 36.67% (121/330) were 10 to 14 years old among the resistant children. There was no statistically significant difference in the resistance rate among the 3 groups (P = .385). The proportions of DR-TB, monoresistant tuberculosis, polydrug-resistant tuberculosis were decreased during 2019 to 2022 compared with 2013 to 2017 (P < .0001). The resistance rates of drug resistant, monoresistant, polydrug-resistant, isoniazid-resistant, and rifampicin resistant during 2018 to 2022 were decreased compared with those from 2013 to 2017 (P < .05), but the multi-drug resistance rate was not decreased (P = .131, without statistical difference). The results of logistic regression analysis showed that male gender OR = 1.566 (95% CI 1.035-2.369), a history of antituberculosis therapy OR = 4.049 (95% CI 1.442-11.367), and pulmonary and extrapulmonary tuberculosis OR = 7.335 (95% CI 1.401-38.392) were risk factors for the development of drug resistance; but fever OR = 0.581 (95% CI 0.355-0.950) was Protective factor. The total drug resistance rate of children in Sichuan showed a downward trend, but the rate of multi-drug-resistant tuberculosis was still at a high level, and the form of drug resistance was still severe. Absence of fever, male, retreatment, and pulmonary concurrent with extrapulmonary tuberculosis are risk factors for DR-TB in children.

Risk factors for drug-resistant tuberculosis, the association between comorbidity status and drug-resistant patterns: a retrospective study of previously treated pulmonary tuberculosis in Shandong, China, during 2004–2019

ObjectiveThis study was designed to identify the risk factors for drug-resistant tuberculosis (DR-TB) and the association between comorbidity and drug resistance among retreated pulmonary tuberculosis (PTB).DesignA retrospective study was conducted...

Risk factors for drug-resistant tuberculosis at a referral centre in Toronto, Ontario, Canada: 2010–2016

Risk factors for drug-resistant tuberculosis at a referral centre in Toronto, Ontario, Canada: 2010–2016

Risk factors for drug-resistant tuberculosis at a referral centre in Toronto, Ontario, Canada: 2010-2016.

Drug-resistant tuberculosis (TB) poses a major public health concern worldwide. However, no studies have addressed risk factors for drug resistance in Ontario, which has its own unique profile of immigrants. We evaluated demographic and clinical risk factors for drug-resistant TB among patients treated at West Park Healthcare Centre, located in Toronto, Ontario (Canada). All patients who were diagnosed with TB and treated at West Park Healthcare Centre between January 2010 and December 2016 were included in this retrospective cohort study. Characteristics of patients with isoniazid mono-resistant (INH-R) TB and multidrug resistant (MDR) TB were compared to patients with drug-susceptible TB with bivariate and multivariable logistic regression. Risk factors for INH-R TB included younger age (younger than 35 years), prior TB treatment, non-diabetic and birth in a non-South-East Asian country, but only the latter two factors were significant in multivariable analysis. On the other hand, we found younger generation (younger than 65 years), birth in European region, recent arrival to Canada (fewer than 120 months), prior treatment and human immunodeficiency virus (HIV) infection were associated with MDR-TB, among which younger age (younger than 35 years), more recent immigration (fewer than 24 months), prior treatment and HIV infection were significant in multivariable analysis. These findings may be of use to TB clinicians in the province by informing the initial empiric antibiotic regimen prescribed while awaiting phenotypic drug susceptibility testing and assisting in decisions regarding whether to request rapid molecular drug susceptibility testing.

Determinants of Drug Resistance in Previously-Treated Pulmonary Tuberculosis Patients Registered at a Chest Clinic in South Delhi, India.

Introduction Drug-resistant tuberculosis (DR-TB) is a major concern to effective control of tuberculosis (TB) in India and the likelihood of drug resistance increases with repeated exposure to anti-TB drugs. India has emerged as one of the leading contributors of DR-TB in the world posing a major threat to TB control. In the current study, we aim to find the burden and factors associated with drug resistance in previously treated pulmonary TB patients.Methods A cross-sectional study was conducted among 230 previously treated pulmonary TB patients registered with Directly Observed Treatment, Short-course (DOTS) centers under Nehru Nagar Chest clinic in Delhi, India. The participants were selected consecutively as they registered with the chest clinic. A predesigned, pretested, semi-structured questionnaire in the Hindi language used to collect socio-demographic data and factors associated with the development of drug resistance. Physical examination of all the participants was done (height, weight, pallor). Data were analyzed using SPSS version 21. Binary logistic regression analysis was used to identify independent risk factors of drug resistance.Results Of 230 previously treated pulmonary TB patients, 80 (34.8% (95% CI:28.7-40.9%)) were drug-resistant. Age (p=0.021), ever consumption of alcohol (p= 0.001), pallor (p=0.06), BMI (p=0.028), fasting blood sugar (p=0.001), treatment failure (p=0.005) and the number of prior courses of anti-tuberculosis treatment (ATT) taken (p=0.004) were significantly associated with drug resistance. On applying binary logistic regression analysis, independently associated factors with drug resistance were ever consumption of alcohol, pallor, high fasting blood sugar level, previous treatment failure patients and the number of prior courses of ATT (p<0.05).Conclusion The findings of this study revealed that patients who had pallor, high fasting blood sugar, treatment failure and who had two or more prior courses of ATT were more likely to have DR-TB. Identifying the risk factors for drug-resistant TB is essential in facilitating the government to draw public health interventions. Further research is warranted to explore the causal associations.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

ObjectiveTo investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB). MethodsA total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. ResultsAmong 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation. ConclusionThis study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community

BackgroundMultidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.MethodsWe performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1∶1∶1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.ResultsWe enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4–414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1–13.3] and 6.1 [CI 1.8–21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3–52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0–27.6).DiscussionIn this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.

Contribution of rural-to-urban migration in the prevalence of drug resistant tuberculosis in China

Increased drug resistance rates to the first-line anti-tuberculosis drugs and multidrug resistance (MDR) were observed in China. The objectives of this study were to determine the prevalence and risk factors for drug-resistant tuberculosis (TB) in urban China and, more specifically, to determine the contribution of migration to case burden and drug resistance rates of urban cities. A facility-based epidemiological study of all active TB patients reported in the four districts of Shanghai and Ningbo between April 1, 2008 and March 31, 2009 was conducted. Residents had significantly higher drug-resistance rates than migrants (any drug resistance: 29.8% vs. 23.5%, respectively, P = 0.038; MDR: 10.9% vs. 6.1%, P = 0.048). Previously treated migrant patients were more likely to harbor drug-resistant TB and MDR-TB than new migrant cases, with adjusted odds ratios of 3.85 and 6.52, respectively. In total, 46.2% of the previously treated cases were resistant to INH, 38.5% to SM, 33.3% to RMP and 30.8% to EMB, while 13.1%, 17.5%, 7.0% and 6.8% of new cases were resistant to the four agents, respectively. To prevent the transmission of drug-resistant TB among migrants and residents, improved case management and appropriate treatment regimens should be sustained to prevent acquired drug resistance.

An Integrated Approach to Rapid Diagnosis of Tuberculosis and Multidrug Resistance Using Liquid Culture and Molecular Methods in Russia

ObjectiveTo analyse the feasibility, cost and performance of rapid tuberculosis (TB) molecular and culture systems, in a high multidrug-resistant TB (MDR TB) middle-income region (Samara, Russia) and provide evidence for WHO policy change.MethodsPerformance and cost evaluation was conducted to compare the BACTEC™ MGIT™ 960 system for culture and drug susceptibility testing (DST) and molecular systems for TB diagnosis, resistance to isoniazid and rifampin, and MDR TB identification compared to conventional Lowenstein-Jensen culture assays.Findings698 consecutive patients (2487 sputum samples) with risk factors for drug-resistant tuberculosis were recruited. Overall M. tuberculosis complex culture positivity rates were 31.6% (787/2487) in MGIT and 27.1% (675/2487) in LJ (90.5% and 83.2% for smear-positive specimens). In total, 809 cultures of M. tuberculosis complex were isolated by any method. Median time to detection was 14 days for MGIT and 36 days for LJ (10 and 33 days for smear positive specimens) and indirect DST in MGIT took 9 days compared to 21 days on LJ. There was good concordance between DST on LJ and MGIT (96.8% for rifampin and 95.6% for isoniazid). Both molecular hybridization assay results correlated well with MGIT DST results, although molecular assays generally yielded higher rates of resistance (by approximately 3% for both isoniazid and rifampin).ConclusionWith effective planning and logistics, the MGIT 960 and molecular based methodologies can be successfully introduced into a reference laboratory setting in a middle incidence country. High rates of MDR TB in the Russian Federation make the introduction of such assays particularly useful.

High prevalence of multidrug-resistant tuberculosis in Georgia

Tuberculosis (TB) has emerged as a serious public health problem in the country of Georgia. However, little or no data exist on rates and risk factors for drug-resistant TB, including multidrug-resistant (MDR)-TB, in Georgia. To assess the prevalence and risk factors for drug-resistant TB. A cross-sectional prospective survey of patients with suspected pulmonary TB was carried out at four sentinel sites (Tbilisi, Zugdidi, Kutaisi, and Batumi) in Georgia between January 1, 2001 and December 31, 2004. Among 1422 patients with suspected pulmonary TB, 996 (70.0%) were culture positive; 931/996 (93.5%) had drug susceptibility testing performed. Overall, 64.0% of patients (48.3% of new and 85.3% of retreatment cases) had positive cultures for Mycobacterium tuberculosis resistant to >or=1 first-line antituberculosis drugs. The overall prevalence of MDR-TB was 28.1% (10.5% of newly diagnosed patients and 53.1% of retreatment cases). In multivariate analysis, risk factors for MDR-TB included: being a retreatment case (prevalence ratio (PR)=5.28, 95% CI 3.95-7.07), history of injection drug use (PR=1.59, 95% CI 1.21-2.09), and female gender (PR=1.36, 95% CI 1.12-1.65). MDR-TB has emerged as a serious public health problem in Georgia and will greatly impact TB control strategies.

Explaining risk factors for drug-resistant tuberculosis in England and Wales: contribution of primary and secondary drug resistance

Drug-resistant tuberculosis can be transmitted (primary) or develop during the course of treatment (secondary). We investigated risk factors for each type of resistance. We compared all patients in England and Wales with isoniazid- and multidrug-resistant tuberculosis in two time-periods (1993-1994 and 1998-2000) with patients with fully sensitive tuberculosis, examining separately patients without and with previous tuberculosis (a proxy for primary and secondary drug-resistant tuberculosis). Patients with previous tuberculosis smear positivity and arrival in the United Kingdom <5 years were strongly associated with multidrug resistance and isoniazid resistance. In patients with no previous tuberculosis HIV infection, residence in London and foreign birth were risk factors for multidrug resistance, and non-white ethnicity, residence in London and HIV infection for isoniazid resistance. Risk factors for each type of resistance differ. Elevated risks associated with London residence, HIV positivity, and ethnicity were mainly seen in those without previous tuberculosis (presumed transmission).