| Objectives:To learn about the epidemic situation of drug-resistant tuberculosis in Shangdong province,the drug-resistant condition of first level antibacterial agents;to discuss risk factors related to the occurrence of Shandong tuberculosis drug-resistance,the interaction,acting way and strengthen among different factors;to discuss the interaction of mycoba-cterium tuberculosis genovariation and environmental factors and its relation with the occ-urrence of drug-resistant tuberculosis,so as to grasp the baseline materials about the epide-mic of drug-resistant tuberculosis in Shandong province and provide reference for the pre-vention and control measures of drug-resistant tuberculosis.MethodsPopulation-based epidemiological studies on tuberculosis were carried out.An epide-miological investigation was conducted on hospitalized patients with smear-positive tuber-culosis in Shandong Chest Hospital from 2013 to 2014.Proportion method of drug sensi-tive test that was recommended by WHO/IUATLD was adopted to detect the sensitivity of mycobacterium tuberculosis isolated strains to four common-used first line antitubercular agents and then drug-resistant spectrum analysis was conducted.GenoTypeMTBDRplus rapid testing method was adopted to detect rpoB and katG gene of mycobacterium tubercu-losis isolated strains.SAS9.0 and SPSS20.0 software were adopted to conduct data analy-sis and t test,?~2 test and single-factor non-conditional logistic analysis were used to cond-uct single factor analysis.Multi-factor nonconditional logistic regression model was used to analyze the risk factors related to the occurrence of drug-resistant tuberculosis.Cross-over analysis was adopted to conduct effect analysis on geneenvironment interaction.Results1.The epidemic condition of drug-resistant tuberculosis in Shandong provinceThe total drug resistance rate of mycobacterium tuberculosis to four kinds of first line anti-tb drugs,which are INH,RFP,SM,EMZ,was 23.77%,the single drug resistance was10.7%,the multiple drug resistance rate was 4.97%and the multi-drug resistance rate was8.58%;the total drug resistance rate at the first treatment was 18.02%,the multiple drug resistance rate was 4.36%and the multi-drug resistance rate was 3.32%,separately lower than the total drug resistance rate(51.11%),the multiple drug resistance rate(7.90%),the multi-drug resistance rate(8.58%)of retreatment and the difference had statistical signifi-cance(P<0.05).The single-drug resistance rates of first treatment and retreatment were se-parately 10.29%and 9.65%and the difference had no statistical significance.The drug-resistance syn-positions of mycobacterium tuberculosis on four first-line dr-ugs were separately S(17.94%),H(13.38%),R(12.61%),E(3.09%),the drug resistance rate of patients receiving retreatment was higher than patients receiving first treatment and the difference had statistical significance(P<0.05).The drug-resistance syn-positions of si-ngle drug-resistance were:S(6.13%),H(2.15%),R(1.42%),E(0.17%);the drug-resistance rate of INH,RFP of patients receiving retreatment was higher than that of patients recei-ving first treatment,SM drug-resistance rate of patients receiving first treatment was high-er than that of patients receiving retreatment and the difference had statistical signific-ance.The proportion of drug resistance rate of H+S and R+S among multi-drug-resistance was the highest,both 2.27%.The drug resistance rate of the retreatment group was higher than the first treatment group and the difference had statistical significance(P<0.05).Among multi-drug resistance,the proportion of H+R+S resistance and H+R+S+E resistance are the highest,separately 1.66%,1.14%.The drug resistance rate of the retreatment group was hi-gher than that of the first treatment group and the difference had statistical significance(P<0.05).There was no statistical difference in the distribution of drug-resistant TB in sex(?~2=0.943,P=0.331),age(?~2=5.696,P=0.127).The drug resistance rate of the underdevelo-ped region was higher than that of the developed region(?~2=8.978,P=0.003).There was no statistical difference in the distribution of multiple drug-resistant TB in sex(?~2=0.574,P=0.541),region(?~2=2.258,P=0.113).The multi-drug resistance rate of the age group over 60 was lower than the age group younger than 20(?~2=11.780,P=0.001),the age group of 20~40(?~2=10,470,P=0.001)and the age group of 40-60(?~2=6.816,P=0.009).2.Analysis on TB drug resistance risk factorsSingle factor logistic regression analysis showed that sex,regional,and pleural thicke-ning and initial treatment of tuberculosis was statistically associated with single drug resis-tance(P<0.05).Region,regular drug use,haemoptysis,past medical history,cavity,tub-erculosis antibody,smear level,course of the disease and liver damage were statistically a-ssociated with the generation of single-drug resistance of tuberculosis retreatment(P<0.05).Age was statistically associated with the generation of multi-drug resistance of tuberculosis first treatment(P<0.05).Age,region,regular drug use,cough,past medical history,diabe-tes,cavity,smear level,course of the disease and liver damage were statistically associated with the generation of multi-drug resistance of tuberculosis retreatment(P<0.05).Multiva-riable logistic regression analysis showed that sex,regionwere statistically associated with the generation of single-drug resistance of tuberculosis first treatment(P<0.05).Reg-ion,cavity,course of the disease and liver damage were statistically associated with the generation of single-drug resistance of tuberculosis retreatment(P<0.05).Age,region,cavity,smear level,course of the disease and liver damage were statistically associated with the generation of multi-drug resistance of tuberculosis retreatment(P<0.05).3.Interaction of multiple drug-resistance tuberculosis gene and environmentThere were interactions of additive model between katG gene mutation and retreat-ment,cavity.These two factors had synergistic effect of additive model.The S values of in-teraction index were separately 3.561,2.797,the attributing interaction percentage AP(AB)were separately 71.8%,64.2%;katG gene had interactions of negative additive with old age group,these two factors had antagonism of additive model.The S value of interaction index was 0.335 and the attributing interaction percentage AP(AB)was 18.99%.Conclusions1.The drug-resistant condition of tuberculosis is very seriousand direction observed therapy short course should be implemented during the treatment management process of patients with tuberculosis to improve the compliance with medication,improve the succe-ssful rate of treatment and reduce the occurrence of drug-resistant tuberculosis.The drug-resistance sequence of mycobacterium tuberculosis's total drug-resistant rate are streptom-ycin,isoniazid,rifampin,and ethambutol and the drug-resistant rate of streptomycin is rel-atively high,so the usage of streptomycinas antibiotic should be reduced,so as to reduce the drug-resistance rate of streptomycin.The medical health facilities in underdeveloped regions should be improved and knowledge about tuberculosisshould be publicized among residents,so as to strengthen their conscious about tuberculosis.2.Male and underdeveloped region are risk factors of single drug-resistance of tuber-culosisinitial-treatment.The undeveloped region,hemoptysis,past medical history,delayed disease course and liver damage are risk factors of single drug-resistance of tuberculo-sisretreatment.Low-age crowds,underdevelopment region,cavity,smear level increasing,delayed disease course and liver damage are risk factors of multi-drug-resistance of tuber-culosis retreatment.3.There are interactions between katG gene mutation in patients with multiple drug resistance and retreatment,low age group and cavity. |
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