Analysis On Clinical Features And Pathogenic Characteristics Of Tuberculosis Patients With Multiple Treatment History

Modern TB control program based on Directly Observed Treatment (DOTS) has been implemented since1990s in China. This anti-TB strategy has made a significant contribution to improve the cure rate of TB patients and reduce the incidence of drug-resistant tuberculosis. But considering the disease burden, China remains to be one of countries with the highest TB burden. In2010, there were about49.9million active cases and3.4million multidrug resistant (MDR) TB patients15years old and above in China.DOTS could provide free chemotherapy for patients who failed the first treatment, but not for cases with multiple treatment history. Patients with multiple treatment histories are often unable to obtain further diagnosis and treatment due to poverty, which might result in sickness for a long time. From the point of view of public health, these people could be the source of MDR-TB. Setting in ten counties respectively from Guangdong, Sichuan, Shandong, Henan and Neimenggu provinces, this study attempted to describe the clinic features and pathogenic characteristics of tuberculosis patients with multiple treatment histories from multi-disciplinary perspective in terms of field epidemiology and molecular epidemiology.Objectives:to describe demographic characteristics and clinical features of the patients and analysis their impact on drug-resistant TB; to identify the drug resistance genotypes and its association with phenotype; to study the genetic diversity of Mycobacterium tuberculosis and analyze the impact of recent transmission on the epidemic of tuberculosis.The methods used in this study and main results are described as follows:1. A cross-sectional study using questionnaire interviews was conducted in ten counties in Guangdong, Sichuan, Shandong, Henan and Neimenggu provinces.328tuberculosis patients with at least2previous treatment episodes were recruited during April1to August31in2011.Among328patients,228(69.51%) patients had received2previous treatments,78(23.78%) patients had been treated for more than3times and289patients were culture-positive pulmonary TB patients.233(71.25%) and175(53.51%) patients received standard regimens in the first and second treatment respectively and the cure rate of these patients was significantly higher than those who didn’t take standard regimens (first treatment:χ2=27.65, p<0.001; second treatment:χ2=32.29, p<0.001). Multivariate analysis showed that annual household income (OR=5.549,95%CI:1.712～17.986) and number of treatments (OR=4.618,95%CI:1.675～12.736) were independent factors influencing the occurrence of drug resistant tuberculosis. TB prevention and control institutions are the preferred selection of TB patients to seek medical and health services.207(63.11%) and220(67.07%) patients were treated in TB prevention and control institutions withinthe first and second treatment episodes. In TB prevention and control institutions, most patients (first treatment:83.09%; second treatment:58.18%) received standard regimens recommended by the Ministry of Health and showed better compliance. Patients needed to spend several thousand to tens of thousands of health expenditure during previous treatments and they still faced a heavy financial burden while seeking healthcare.2. The cross-sectional study on the epidemic of drug-resistant TB. The proportion method was used for drug susceptibility test for the41st-line anti-TB drugs to acquire drug-resistant phenotypes of M.TB strains. Among328subjects,240patients were resistance to at least one of the first-line drugs and the total drug resistant TB rate was73.17%.47(16.40%) patients were sensitive to all1st-line drugs.49patients were resistant to only one1st-line drugs.167patients were resistant to both Rifampicin and Isoniazid and the rate of MDR-TB were50.91%. the primary drug resistance rates for the41st-line drugs were:67.94%for Rifampicin,65.16%for Isoniazi,52.96%for Streptomycin and32.75%for Ethambutol.Furthermore, previous treatment history (≥3times/2times:OR=4.618,95%C1:1.675-12.736) and family annual income (<6000/>20000:OR=5.549,95%CI:1.712-17.986) were associated with drug-resistant TB. Previous treatment history (>3times/2times:OR=4.369,95%CI:1.540～12.394) and family annual income (<6000/>20000:OR=4.589,95%CI:1.352～15.574) were associated with MDR-TB.DNA sequencing of resistance related genes was applied to investigate the drug-resistance genotype and its association with the corresponding drug resistance phenotype.70(42.17) of120RIF resistant isolates had genetic mutation in rpoB gene and single-nucleotide substitution in codon531,526and516took account for47.14%,21.43%and32.86%.55(45.83%) of120INH resistant isolates had single-nucleotide substitution in codon315of katG.3. Study on the genetic diversity of Mycobacterium tuberculosis. Two genotyping methods, including dtm-PCR and VNTR-MIRU, were used in this study. Dtm-PCR identified128(77.11%) isolates that presented the Beijing family Spoligotype. MIRU typing determined163genotypes from166isolates in this study, including3cluters (including6isolates) and160unique patterns. The clutering proportion was3.61%and it was relatively small according to other studies, indicating that the incidence of TB in these patients is mainly the result of reactivation of previously infected M.TB and recent transmission accounts for a low percentage of the incidence.Multivariate analysis showed that patients with multiple previous treatments (≥3times/2tirnes:OR:29.316,95%CI:1.105-77.745) were more likely to be clustered. We didn’t find age, gender and drug-resistant TB had statistical significant impact on clustering.