| ObjectiveTo investigate the prevalence of latent TB infection (LTBI) and its related factors among the intimate contactors of active pulmonary tuberculosis patients through the field epidemiology survey, aim to provide the basis for decreasing the incidence of LTBI and TB. To explore the possible environmental risk factors of LTBI and pulmonary tuberculosis; relationship between the+874T/A single nucleotide polymorphisms (SNP) in interferon-r (IFN-γ) gene, the-1082G/A SNP in interleukin-10(IL-10), the-308G/A SNP in tumor necrosis factor-α gene of population and susceptibility to LTBI and pulmonary tuberculosis, and further to explore the interaction with environmental factors to LTBI and pulmonary tuberculosis.Methods1. Cross sectional study:From the February of2010to the December of2010,982persons closely contacted with pulmonary tuberculosis patients were enrolled from seven districts of Shanghai. Questionnaire interview was applied to investigate the socio-demographic and clinical information related to LTBI. The T-SPOT.TB method was used to detect LTBI in the studied subjects. Prevalence of LTBI were acquired, χ2test and unconditional logistic regression were occupied to identify the risk factors associated with LTBI among the contacts.2. Case control study:Between1st May2011and15th December2011,109pulmonary tuberculosis cases meeting to standard coming from MinHang Center for Disease Control and Prevention were collected, LTBI and non tuberculsos infection were enrolled from the survey of the prevalence of LTBI in the intimate contactors with active pulmonary tuberculosis patients in Shanghai,183LTBI and314non tuberculsos infection were enrolled in this study. Face to face interviews were carried out to collect their socio-demographic and clinical information, and blood samples were collected after informed consent. The+874IFN-γT/A,-1082IL-10G/A,-308 TNF-α G/A SNP were detected in subjects by polymerase chain reaction (PCR) and DN A sequencing. EpiData3.0software and SPSS16.0statistical software were use to input and analyze data,χ2test and unconditional logistic regression were occupied to measure the relationship between environmental factors, genetic polymorphisms, and the possible gene-environment and gene-gene interaction in the risk of LTBI and pulmonary tuberculosis by calculating odds ratio(OR) and95%confidence interval(95%CI).Results1. Cross sectional study:Totally,982intimate contactors of active pulmonary tuberculosis patients were collect questionnaires and blood samples, among them13persons were excluded for basic information missing or T-SPOT.TB test failure, finally969contacts were enrolled in this study. T-SPOT.TB test identified288(29.7%) contacts with the positive result, among them one person were further diagnosed with TB; meanwhile without clinical sign and symptom relevant to TB under the further medical examination, the rest287contacts were defined with LTBI. The prevalence of LTBI was different between districts, lowest in ChangNing district (19.9%) and highest in PuDong district (45.0%). No difference in prevalence was seen in male and female. The risk of LTBI was increased along with the increase of age, the tendency was especially apparent in the age greater than30years old population. In multivariate logistic analysis, compared with contact with sputum negative TB patients, contact with sputum positivity TB patients significantly increased the risk of LTBI (33.9%vs19.4%;OR,2.24;95%CI:1.59-3.16); compared with other contact place, contact within the family is also a risk factors of LTBI (32.3%vs21.3%;OR,1.52;95%CI:1.06-2.18); compared with contact place area<60m2, contact place area was between60and120m2(OR,0.69;95%CI:0.51-0.94)å'Œ>120m2(OR,0.49;95%CI:0.30-0.80) were protective factors for TB infection; the time of contact is also associated with LTBI (OR,1.003;95%CI:1.001-1.005).2. Case control study:Totally,109pulmonary tb patients(men67.9%) were enrolled in this study with the average age of44.5±17.2,183LTBI(men38.6%, age in mean of50.5±18.1years old) and314non tb infection(men38.6%, age in mean of49.4±18.4years old)were encruited.The result from unconditional logistic regression suggested that contact with sputum positivity TB patients could increase the risk of LTBI with aOR of2.33(95%CI:1.27-4.27); contact with TB patients who has a cough sympton could increase the risk of LTBI with aOR of1.84(95%CI:1.11-3.06). We didn’t found the relationship between the time of contact, the area and the ventilation of the contact place, gender, age, nutrition, floating population, education,+874IFN-y T/A,-1082IL-10G/A,-308TNF-a G/A SNP with the risk of LTBI.The result from unconditional logistic regression suggested that male is a risk factors of LTBI with a aOR of3.34(95%CI:2.02-5.50); malnutrition (BMK18.5) could increase the risk of pulmonary TB with aOR of2.29(95%CI:1.25-4.20); floating population could increase the risk of pulmonary TB with aOR of53.61(95%CI:87.06-999.99); compared with+874IFN-y TT genotype, subjects with AA and TA/AA genotype has aORs of4.88(95%CI:1.61-14.86),2.58(95%CI:1.11-6.00), respectively; compared with-1082IL-10GG genotype, subjects with GA, AA genotype has aORs of0.19(95%CI:0.06-0.62),0.20(95%CI:0.06-0.66), respectively; compared with-308TNF-a GG genotype, subjects with GA and GA/AA has aORs of5.47(95%CI:2.33-12.86),4.36(95%CI:1.99-9.57), respectively. We didn’t found the relationship of age, education with the risk of pulmonary TB.Compared with wild genotypes of+874IFN-γ and-308TNF-α, subjects with+874IFN-γ variant genotype (TA or AA) and-308TNF-a GG genotype had a significant lower risk of LTBI (OR,0.55;95%CI:0.35-0.86), we didn’t found any relationship between+874IFN-y and-1082IL-10,-1082IL-10and-308TNF-a to LTBI. Compared with subjects with-1082IL-10variant genotype (GA or AA) and contact with sputum negative TB patients, subjects with-1082IL-10variant genotype (GA or AA) and contact with sputum positivity TB patients had a significant higher risk LTBI. we didn’t found any relationship between+874IFN-y and the sputum result of TB patients,-308TNF-a and the sputum result of TB patients to LTBI.The ORs for interaction of+874IFN-y and-1082IL-10,+874IFN-y and-308TNF-a,-1082IL-10and-308TNF-a were1.95(95%CI:0.45-8.44, p=0.374),2.05(95%CI:0.73-5.78,p=0.173),3.08(95%CI:0.52-18.23,p=0.216), respectively. The ORs for interaction of+874IFN-y,-1082IL-10,-308TNF-a SNP, and BMI were3.08(95%CI:0.82-11.61, p=0.097),2.71(95%CI:0.28-26.76,p=0.393),1.21(95%CI:0.33-4.38, p=0.775), respectively. We did not found a positive multiple interaction between IFN-y+874, IL-10-1082, TNF-α-308SNP and the BMI to pulmonary TB; and the interaction between IFN-y+874and IL-10-1082, IFN-y+874and TNF-α-308, IL-10-1082and TNF-α-308SNP to pulmonary TB.ConclusionThe prevalence of LTBI among the intimate contactors with active pulmonary tuberculosis patients was high in ShangHai. Household was the main place of contact, the contact duration, area and ventilation condition of the contact place are associated with the LTBI. Male, malnutrition, floating population+874IFN-y AA,308TNF-a AA SNP are risk factors of pulmonary TB but not of LTBI,-1082IL-10AA is protective factor of pulmonary TB but not of LTBI. Contact with patients who has a cough symptom or positive sputum are risk factors of LTBI. Suggest that timely treatment for TB patients, especially sputum positive TB patients or patients who has a cough symptom, should be of top priorities for TB control in contact in Shanghai, and house-hold contact follow up is important for TB intervention, especially those with a poor ventilation condition or small area of the contact place. In order to decreasing the pulmonary TB incidence, closely attention should be payed to carry malnutrition or floating population among LTBI, preventive treatment should be given if is possible. |
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