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Epidemic Characteristics Of Drug-Resistant Tuberculosis And Genotyping Of Mycobacterium Tuberculosis

Posted on:2014-02-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:D LuoFull Text:PDF
GTID:1224330398473724Subject:Epidemiology and Health Statistics
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Objectives To understand the epidemic characteristics, spectrum and related factors of drug-resistant TB in guangxi; To know genotype and its distribution of MTB, to discuss the characteristics of MTB’clusters’and its related factors, the relation between Beijing strain and drug-resistant. To provide the reference for TB control and lay the foundation for further molecular biology research.Methods A population-based molecular epidemiological studies of tuberculosis was carried out by a method of combination of field epidemiology and the modern molecular biology technology. Sample size was calculated according to the cross-sectional survey statistical requirements, sputum smear-positive TB patients in30counties were selected by random cluster sampling method. Basic information and related epidemiological data of patients was collected from questionnaire and medical records. First-line and second-line anti-tb drugs sensitivity test was performed. The VNTR genotyping technology was used to identify the genotype of mycobacterium tuberculosis. RD105deletion test and RD207deletion test were used to identify the "Beijing family " strains of MTB in order to determine the distribution of "Beijing family" strains and finding the best way to identify "Beijing family " strains of MTB in Guangxi province. Quality control throughout the whole research process. Data were double entered into Epidate3.1and analyaed using SPSS19.0.Results1. Drug-resistant tuberculosis epidemic in guangxi:The overall rate of resistance to anti-tb drugs(including INH,RFP,EMB,SM,KM,OFX)was16.45%, the single-resistance rate was7.88%, the poly-resistance rate was2.67%, MDR rate was5.90%, XDR rate was0.19%. The overall rate (32.98%), single-resistance rate (10.47%), poly-resistance rate (4.19%)、MDR rate (18.32%) were higher in re-treated patients than those in initial patients (11.31%,7.08%,2.20%,2.03%)(P=0.00, P=0.00, P=0.03, P=0.00). The sequence of resistance rate of6anti-tuberculosis drugs was in turn to INH (11.55%), RFP (7.88%), SM (7.26%), EMB (4.35%), OFX (2.67%)and KM (0.43%). The resistance rates of6anti-tuberculosis drugs in re-treated patients were higher than in initial patient, respectively(P=0.00). The INH resistant rate was the highest both in re-treat patients and initial patient,it was7.32%and25.13%, respectively. The single-resistant rate to INH (46.45%) took the highest proportion among all the drugs, followed by resistance to SM(30.71%). There were10kinds of different forms of poly-resistance, the form’INH+SM’ accounted for the largest proportion in both initial and re-treated patients.51%of the INH resistance strains were MDR strains,when75%of the RFP resistance strains were MDR strains, the MDR proportion in RFP strains was higher than in INH strains.The OFX resistant rate was related to first-line anti-tb drug resistance and MDR. The OFX resistant rate in first-line drug resistant strains was13.62%, which was higher than in first-line drugs sensitive strains (P=0.00, OR=0.00,95%CI=12.15-57.93). The OFX resistant rate in MDR strains was30.53%, which was higher than in nor MDR strains (P=0.00, OR=47.14,95%CI=23.79-93.41).85.71%of the KM resistant strains was isolated from re-treated patients,7KM resistant strains were resistance to at least one first-line drug at the same time.The distribution of Drug-resistant TB showed no statistical significance difference in different gender (X2=2.40, P=0.12) and age groups (X2=5.74, P=5.74). MDR rate in41-60years group was higher than in≤20years groups (X2=5.52, P=0.02) and>60years groups (X2=5.25, P=5.25). The Drug-resistant rate was higher in the west area and middle aera than in the east area.(X2=8.46, P=0.00; X2=4.29, P=0.04); MDR rate was higher in south and west aeras than in middle and east aeras (P<0.05).2. Factors related to drug resistance:female, treatment times and treatment interruption times were related to the drug resistance of the re-treated patients (P<0.05), family economic income, treatment times and treatment interruption times were associated with re-treated patients with MDR (P<0.05), according to multi-factor unconditioned logistic regression analysis.3. Distribution of mycobacterium tuberculosis genotype in guangxi: guangxi had a high level of MTB gene polymorphism.There was a total of964genotypes, of which779(59.47%) were single genotypes, other531(40.53%) were classified as185genotypes. Of1310MTB strains,746(57.0%)were Beijing strains,564(43.0%) were nor-Beijing strains. Of all Beijing strains,313(42.0%) were old type strains,433(58.0%) were modern strains. The original Beijing strains and3subgroup were found in the nor-Beijing strains,accounted for7.4%,45.6%,30.7%and7.4%respectively. 4. Clusters characteristics and its related factors of MTB:The clusters rate of drug-sensitive strains was higher than drug-resistance strains (24.40%vs.9.55%, P=0.000) and MDR strains (24.40%vs.8.97%, P=0.004).The clusters rate of Beijing strain was higher than nor-Beijing strains (40.88%vs.37.77%, P=0.032). The clusters ratio of drug-ensitive strains was higher than that of drug-resistant strains and MDR strains, the clusters ratio of Beijing strain was higher than that of nor-Beijing family strains. Patients aged between40and60had a greater probability to be clusters vs.aged less than20(P=0.04).5. Relationship between Beijing genotype and drug resistance:Beijing strains did not show statistical significance relation with drug-resistant.6. RD207deletion test for Beijing strains identifying in Guangxi:A total of1611MTB strains was included in RD207deletion test for Beijing strains identified,of which866(53.76%) were Beijing strains,553(34.32%) were nor-Beijing strains,160(9.93%) were mixed infection with Beijing strains and nor-Beijing strains.(160/1611),32(1.99%) could not amplify target fragment. For the detection power on mixed infection, RD207deletion test was better than RD105deletion test.Conclusions1. The overall drug-resistance rate in guangxi was low,but MDR situation was serious.75%RFP resistant strains were MDR, so RFP resistance should be wary of MDR in clinical. SM has a great value on anti-tuberculosis. OFX resistance was linked to the first line anti-tuberculosis drug resistance and MDR,it shoud be paid more attention on clinical treatment regimen. The distribution of Drug-resistant TB showed no statistical significance difference in different gender and age groups,but he Drug-resistant rate was higher in the west area and middle aera than in the east area. MDR rate was higher in41-60years group than in age groups,and was higher in south and west aeras than in middle and east aeras. Women, treated many times and treatment interrupted many times were the risk factors of drug-resistant;low income, treated many times and treatment interrupted many times were the risk factors of MDR. Acquired drug resistance was one of the most important reasons for drug-resistant TB.2. MTB gene polymorphism showed a high level in guangxi. Beijing genotype and nor-Beijing genotype took a same proportion. The clusters rate and ratio of drug-sensitive strains were higher than that of drug-resistant and MDR strains. The clusters rate and ratio of Beijing strains were higher than that of nor-Beijing strain. Clusters were associated with age. Beijing genotype had no link to drug-resistanceand and MDR.3. Combination of RD105and RD207deletion test should be used for Beijing strain identifying in Guangxi.
Keywords/Search Tags:drug-resistant TB, related factors, genotyping, VNTR, RD105, RD207
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