The Application Study On The Value Of IGRA In The Diagnosis And Treatment Of TB

Background and objectiveAround the world, tuberculosis is still one of the diseases with the highestincidence and death rate among all infectious diseases till now. By estimating there arearound9,000,000new cases, and about2,000,000died of tuberculosis every year.Tuberculosis can be infected both human beings and animals by Mycobacteriumtuberculosis (MTB). It is an infectious disease with the highest death rate resulted fromsingle pathogens. China is one of the countries with high tuberculosis burden. Thenational tuberculosis epidemic survey in2000showed that the infectious rate of all ageswere44.5%, among which active tuberculosis patients were4,510,000and the annualcasualties were up to1,300,000. The death rate accounted65.1%among the deathcaused by all forms of infectious and parasitic diseases, and it was nearly double that ofall other forms of infectious and parasitic diseases. Because of the wide spread ofhuman immunodeficiency virus(HIV) and the gradually increasing of drug-resistant, TBMycobacterium tuberculosis, this old disease brings about wide concern among peopleagain and has become one of the main infectious diseases damaging human being’shealth.The reason that the epidemic situation wasn’t controlled well around the world liedpartly in the slow development of the testing method in the field of diagnosing thedisease. In the past100years, TST has been used as the major method to diagnoselatent tuberculosis infection (LTBI), but its application in the clinical treatment has beenlimited because of the following reasons. First, it can’t distinguish a recent infectionfrom the old ones. Then a false positive reaction may result from the cross immunityamong TST, BCG and natural mycobacterium infections. The second reason is that afalse negative reaction exists in immunosuppressive group and an error may happen injudgment of the result. However, with the continuing efforts of many scholars, whole blood Interferon gamma release assays (IGRA) has finally been developed to diagnosethe potential tuberculosis infection. Due to being free from the influence of the elementslike BCG and natural mycobacterium infections, it has been applied widely in thedeveloped countries like Japan, the U.S. and some countries in Europe. On the contrary,in the countries with extensive epidemic situation like China, there is not elaboraterelevant study about its application value, which needs further evaluation. Althoughwith more experience of the application of IGRA in the area of LTBI and it has beenrecommended as one part of the national guiding lines for LTBI, it still remainsunknown whether the technology is applicable in BCG vaccination setting like in China.In clinical, under the different environments such as the treating process of potentialinfection or the active adult tuberculosis incidence, a series of IGRA study showed avariety of different results in the reactions to the treatment. Among them, somedecreased, while others increased or kept no change. Furthermore, no reasonablemechanism can explain these contradict results till now. Although IGRA has beenconfirmed in its diagnostic value for LTBI, it is still remains a question in the diagnosisof active tuberculosis including the diagnosis of tuberculosis pleurisy. All of thesequestions need to be studied and evaluated further.Methods:1. Evaluation on the value of IGRA in diagnosing LTBI and the comparison toTST in a tuberculosis outbreak.The520volunteers were divided into six groups based upon the risk of exposure,the Condition logistic regression was conducted by using different TST cutoff andIGRA with exposure level to compare the value of diagnosing LTBI. And binaryLogistic regression was conducted using the cases as independent variable and the othervariable as covariate variable to find the high risk factors which might cause thedevelopment of tuberculosis disease. Also we’d like to explore the prevention andcontrol strategy of shcool tuberculosis outbreak through the screening results.2. Evaluation on the value of IGRA and the comparison to the increase value ofTST in diagnosing LTBI.In the tuberculosis outbreak, comparing the correlation and the diagnosis value ofIGRA and TSTC with the three different exposing groups divided according to theprevious TST cutoff group（TST＜5mm,5≤TST＜10mm, TST≥10mm）. Throughcomparing the consistency between IGRA and TSTC also the different combinationresults of them, evaluating their relationship with different exposing levels. 3. Evaluation on the value of IGRA in the efficacy of anti-tuberculosischemotherapy.In the tuberculosis outbreak, the IGRA were retested again after six months amongthe three different groups (the patients, the close contacts with preventive treatment, andthe close contacts without preventive treatment). To explore the application value ofIGRA in the aspect of clinical curative effect and immunity mechanism, the results ofIGRA and the level of IFN-γ were compared inside the group and among the threedifferent groups.4. Evaluation on the value of IGRA in diagnosing the tuberculous pleurisy.Among all the patients, IGRA were done by using the patients’ blood, pleuraleffusion, and the cells separated from the effusion respectively and the results of themwere compared with the result of testing IFN–γ level alone in the pleural effusion. Todetect the IFN–γ, ademosine deaminase (ADA) and TB-Tb level among the groups oftuberculous pleurisy, malignant pleural effussion and the pleural effission caused byother reasons, and conduct the receiver operating curve (ROC) analysis to compare thediagnostic value of them at the same time.Results1. Evaluation on the value of IGRA and the comparison to TST in a tuberculosisoutbreak.The agreement between IGRA and TST was poor. IGRA is closely corelated to theexposing level, which was a high risk factor to cause tuberculosis. Neither IGRA norTST could identify all the cases. However,95%tuberculosis cases could be identified ifwe selected all of the subjects in the highest exposure level and IGRA (+) used in otherlevels.2. Evaluation on the value of IGRA and the comparison to the increase value ofTST in diagnosing LTBI.According the mean diameter (DI) of TST before the outbreak (TST＜5mm,5≤TST＜10mm, TST≥10mm) the volunteers were divided into three groups, and the DIturned into8.22±5.94mm、6.78±4.57mm、3.68±3.42mm after the outbreakrespectively. The kappa value of the three groups of TSTC+and IGRA+are0.541、0.219and0.045respectively. Before the outbreak, for the group that TST less than5mm, TSTC+rate was closely related to the exposing level(P<0.05), and no suchcorrelation appeared in other groups(P>0.05). While IGRA+was closely related to allthe three different exposing groups(P<0.05). The detection rate for IGRA+/TSTC+、 IGRA+/TSTC-decreased with the decrease of the level of exposure, while thedetection rate for IGRA-/TSTC-increased with the decrease of exposing level.3. Evaluation on the value of IGRA in the efficacy of anti-tuberculosischemotherapy.The TST and IGRA were retested after six months again, and the mean value of thegeneral level of IGRA in the follow-up test obviously decreased with statisticallydramatic change among the3groups (patients group, the group who receivedpreventive anti-tuberculosis treatment and the group of contacts without preventive anti-tuberculosis treatment), but there is no significant difference in the value of IGRA(before and after the follow-up test) and the reversion rate.While most cases in the three groups had a conversion to positive, some subjectshad a reversion to negative.45out of98contacts’ IGRA+had a reversion to negative (45.92%), who didn’treceive the anti-tuberculosis treatment, and14contacts’ TST turned into negative(14.29%). On the other hand, among59cases who were IGRA+/TSTC-withoutchemotherapy,31IGRA+cases turned into negative(52.54%) and31TST conversionnegative cases turned into positive(52.54%).4. Evaluation on the value of IGRA in diagnosing the tuberculous pleurisy.The best cutoff of IFN-γ was5IU/ml in tuberculous pleurisy, which was figured byadopting ROC analysis based on the clinical diagnosis result as the golden standard.The result was determined as positive when the value≥5IU/ml, otherwise as negative.Among the cases with tuberculous pleurisy, there was no significant difference for theIGRA positive rate between blood and pleural effusion, the same to the results of cellsseparated from the pleural effusion and fixed with the same concentration. and detectingthe IFN-γ singly. But in all tests, the sensitivity and conformance of detecting IFN-γalone in pleural effusion was highest.The comparison of ROC analysis between IFN-γ and ADA、TB-AB showed thatthe area under the curve in all parameters, including sensitivity, specificity and thepredictive value of positive and negative were all highest if only IFN-γ in pleuraleffusion was tested.The area below the curve increased to0.977from0.924in ROC analysis withtesting IFN-γ, ADA, and TB-Ab jointly.Conclusions1. IGRA was superior to TST in diagnosing LTBI. In TB outbreak, IGRA and exposing level were the high risk factors for the development to active tuberculosis.When conducting the strategy of chemotherapy for group infection, a recommendedpreventive treatment regimen during a TB outbreak should be based on the level ofexposure in conjunction with the IGRA results.2. TSTC was affected by the previous DI of TST when used to diagonose therecent LTBI contact. The diagnositic value was highly effective when previous TSTwas below5mm. Compared with TST conversion IGRA was superior in diagnosingLIBI, meanwhile it could identify the recent infection at the early stage.3. Chemotherapy was not the major reason which led to the IGRA level change.4. The simple test of IFN-γ level in pleural effusion was a relatively accuratediagnosing tool for tuberculous pleurisy. It would increase the diagnosing value totuberculous pleurisy with the combination test of IFN-γ, ADA and TB-Ab.