A Study Of Risk Factors For Drug Resistance And Adverse Reactions Among Pulmonary Tuberculosis Patients

BackgroundTuberculosis is a kind of infectious diseases caused by Mycobacterium tuberculosis, the source of infection for the diseases is smear-positive pulmonary tuberculosis patients, and the route of transmission is by droplets spread. People are generally susceptible to tuberculosis. In 2014, about 9.6 million patients were incident TB cases worldwide,13 million were prevalent cases, and about 1.1 million people died from TB. Global TB control is still severe. Drug resistance and adverse reactions during treatment are important factors that affect the effect of tuberculosis control. In 2014 the prevalence of multidrug resistant tuberculosis (MDR-TB) among global new cases was 3.3%, and the prevalence among re-treatment cases was 20%, and the prevalences were 5.7% and 26% respectively in China. The drug-resistant TB has been proposed as one of the four challenges in World Health Organization’s the end TB Strategy. The common candidate risk factors for drug resistant TB in individual-level include age. gender, level of education, occupation, previous anti-TB treatment, but the findings from different studies were not always consistent due to small study areas, underrepresented samples and small sample sizes. As an important risk factor for patients’ adherence, adverse reactions are not studied adequately. Moreover. adverse reactions can recur during follow-up, so the common models for follow-up data such as Cox proportional hazard model are not applicable for this data.ObjectiveThis study used a follow-up data collected from tuberculosis patients during anti-TB treatment in 8 provinces, explored the risk factors for drug resistant TB and adverse reactions respectively, and aimed to discover characteristics of patients with high risk of drug resistance and/or adverse reactions and provide scientific guidance for TB prevention and control.MethodsThe data used in this study was from National Science and Technology major project study of clinical occurrence pattern and early-warning model for drug resistance tuberculosis. The project followed up new tuberculosis cases and re-treatment cases enrolled from 8 areas:Shanghai, Tianjin, Henan, Hebei, Guangxi, Guangzhou, Chongqing, and Yunnan, and collected and recorded each participant’s characteristics, clinical check results and information about adverse reactions. This study applied methods of descriptive statistics to describe the characteristics of patients with drug resistance tuberculosis and/or adverse reactions, then used logistic models to explore the relationship between drug resistance tuberculosis and univariate factors and multivariate factors; for adverse reactions, univariate factors were assessed by Cox proportional hazard models, and multivariate factors were assessed by shared frailty model.Main results1. Tuberculosis drug resistanceIn new tuberculosis patients, the prevalence of MDR-TB was 3.7%, and that of XDR-TB was 0.8%; in re-treatment cases, the prevalences were 20.1% and 2.5% respectively. New and re-treatment cases had different risk factors. In new cases, the risk factor for drug resistance was region (Eastern vs. Central, OR=0.4,95% CI:0.3-0.6, P<0.001; West vs. Central, OR=0.4,95% CI:0.3-0.6, P<0.001); risk factors for MDR included:region (Eastern vs. Central, OR=0.5,95%CI:0.2-1.0, P=0.04; West vs. Central, OR=0.4,95% CI:0.2-1.0, P=0.04) and the females (OR=2.0,95% CI: 1.1-3.7, P=0.02). In re-treatment cases, the risk factor for drug resistance was peasants (OR=5.5,95% CI:1.9-15.7, P=0.002). While for MDR, the risk factors included:region (West vs. Central, OR=0.3,95% CI:0.1-0.7, P=0.01), peasants (OR=3.0,95% CI:1.2-8.0, P=0.02) and the total previous drug intake (OR=1.1,95% CI:1.0-1.1, P=0.001).2. Adverse reactions during anti-TB treatmentThe adverse reactions rate in Chinese tuberculosis patients was 22.1%(95% CI, 20.3-23.9). The liver damage rate ranked first and was up to 9.8%(95% CI,8.5-11.1). The rate of gastrointestinal reactions was 6.3%(95% CI,5.3-7.4), ranking second. The risk factors for adverse reactions during anti-TB treatment included:region (West vs. Central, HR=1.6,95% CI:1.3-2.1, P<0.001), smoking status (HR=1.6,95% CI: 1.3-1.9, P<0.001), symptom scores (HR=1.04,95% CI:1.02-1.07, P=0.002) and TB knowledge scores (HR=0.7,95% CI:0.7-0.8,P<0.001). Further studies found that the risk factors for liver injury included:region (Eastern vs. Central, HR=1.6,95% CI: 1.1-2.2, P=0.01) and the males (HR= 1.6,95% CI:1.0-2.5, P=0.03). For the gastrointestinal reactions, the risk factors were:region (Eastern vs. Central, HR= 0.3, 95% CI:0.2-0.6, P=0.01), the males (HR=0.6,95% CI:0.3-0.9, P=0.02), middle school and the higher education levels (HR= 0.5,95% CI:0.4-0.8, P<0.001), smoking status (HR=2.1,95% CI:1.2-3.7, P=0.01), symptom scores (HR=1.1,95% CI:1.0-1.1, P=0.01) and TB knowledge scores (HR=0.7,95% CI:0.6-1.0, P=0.02).Conclusions1. In new tuberculosis cases, the prevalences of drug-resistant TB varied by regions, and females had higher risk for MDR;2. In re-treatment cases, peasants were more likely to acquire drug-resistant TB and MDR-TB;3. The epidemic of adverse reactions during anti-TB treatment was serious in China. In all the adverse reactions, liver injury and gastrointestinal reactions occurred most frequently;4. There was regional difference in Chinese adverse reactions during anti-TB treatment. The risk factors for adverse reactions included:current smokers, high symptoms score, low tuberculosis knowledge scores and long distance from medical institutions.