Analysis On The Effect Of Mycobacterium Vaccae Combined Chemotherapy On The Initial Treatment Of The Elder Patients With Pulmonary Tuberculosis

BackgroundEpidemic tendency of pulmonary tuberculosis shows that the peak of the morbidity of pulmonary tuberculosis is moving to that in the elderly. The global TB epidemic is characterized by a common phenomenon which forms the elderly pulmonary tuberculosis peak. Most of the elderly pulmonary tuberculosis is insecondary infection in which many causes of the disease are focuses of primary infections or focuses of latent infections recrudescence. As there is the thymus involution in old age the composition and activity of T lymphocyte subsets decrease which lead to cellular immune function degraded and"resurgence"of latent bacterium that is known as the incidence of endogenous. For these reasons hypoimmunity can immediately cause the development of the elderly tuberculosis. Many studies have shown that the pathology of the elderly pulmonary tuberculosis is characterize by cheesy necrosis tissue, in which there were a lot of mycobacterium tuberculosis, without the surrounding epithelial cells, Langerhas giant cells and inflammatory cells such as lymphocytes. The abnormal pathological changes are caused by the cellular immunocompromise or lack of cellular immune function. Therefore, its clinical manifestation was usually made the lesions broad, more cavities,higher sputum smear positive rates and lower cure rates.The outcome in the elderly pulmonary tuberculosis after treated was closely related to immune function, especially cellular immunologic function. As a result of immune organs declined with age, these made immunologic function disorder in the elderly, which made them bary-response,low tolerance and bary-tissue repair for antituberculosis chemotherapy. Thus only antituberculosis chemotherapy could not receive satisfactory effect.Now a large number of studies both at home and abroad have confirmed that regular antituberculosis chemotherapy combined with immunotherapy had better effects on the elderly pulmonary tuberculosis patients. M. vaccae vaccine is an immunomodulator made by inactivation and purification of Mycobacterium vaccae. M. vaccae vaccine was a only immune preparation recommended by the tuberculosis research and development's program which was the combination of antituberculosis chemotherapy and immunotherapy, proposed by World Health Organization(WHO) in 1990s . Now many studies have shown that although M. vaccae vaccine was helpful for the elderly patients, whether or not its efficacy was related to improving immunologic function or antituberculosis chemotherapy need to be further explored.In this study, the analysis of prospective cohort study to be: According to the cellular immune function of the elderly initial treatment patients with smear positive to group before treated, the curative effects of the chemotherapy combined with M. vaccae vaccine and alone chemotherapy were compared and analyzed between the two groups, which provided a new method for treating elderly pulmonary tuberculosis patients.ObjectivesTo investigate the changes of the immunization, the nutritional status and the clinical effects of the elderly initial treatment patients with smear positive (including the cellular immune function in normal and low) treated by Mycobacterium vaccae vaccine combined with chemotherapy in order to determine the necessity of adjunctive immunotherapy and to provide new methods and evidences for the future in treating elderly pulmonary tuberculosis patients.Methods80 cases of the elderly patients (their age≥60 )with newly registered were selected as observations in our hospital from 1 January, 2006 to30 December ,2008. The patients were divided into abnormal group(groupⅠ) and the normal group(GroupⅡ)of the 40 cases in each group according to the percentage of serous CD4+T lymphocyte before treating. Each group patients were randomly selected to treatment group with M. vaccae vaccine adjuvant therapy and control group. All the patients received antituberculosis chemotherapy. A few examinations were performed before and after treatment (at the end of 2,4,5,6months),such as checking body weight , blood analysis , liver function , renal function , seralbumin , T lymphocyte subsets , sputum samples checking , chest X-rays (CXR), serum tuberculosis antibody , purified protein derivative (PPD)test .Some adverse reactions were observed in the course of treatment, such as erythra,fever,induration of skin,liver and kidney dysfunction and so on. Management practices: supervision of the entire process.Results(1)CD3+ , CD4+ lymphocyte percentages , CD4+ / CD8+ ratio were significantly higher at the end of 2 , 6 months after treatment than those before treatment (P<0.05), and CD8+T cell lower in treatment group (P<0.05). There were more significantly improvement in T lymphocyte subsets in treatment group than those in control group at the end of 2 months (P<0.05). The average diameters of induration in PPD test after treating at the end of 2,6 months more significantly increased than that before treatment in treatment group. The average diameter in treatment group more significantly increased than that in control group when 2 months (P<0.05). And at the end of 6 months PPD-IgG positive rate was lower in treatment group than those before and control group (P<0.05). Nutritional status: Seralbumin(ALB),total lymphocyte count(TLC),body mass index(BMI),hemoglobin(HB) were significantly higher after treatment than those before treatment in treatment group(P<0.05), in which ALB,BMI is higher than control group (P<0.05).(2)CD3+ , CD4+ lymphocyte percentages , CD4+/CD8+ ratio were significantly higher at the end of 2 , 6 months after treatment than those before treatment (P<0.05) and CD8+T cell lower in treatmentⅠgroup (P<0.05). There were more significantly improvement in T lymphocyte subsets in treatmentⅠgroup than those in controlⅠgroup (P<0.05). The extent of reaction in tuberculin test in the corresponding time period in treatmentⅠgroup was more intensive than that before treatment and than that in controlⅠgroup (P<0.05). PPD-IgG positive rate in the end of 2 months after treatment was higher, and in the end of 6 months lower than that before treatment. ALB,TLC,BMI and HB were significantly higher than that before at the end of 6 months in treatmentⅠgroup , and higher than that in controlⅠgroup (P<0.05).(3)CD3+ , CD4+ lymphocyte percentages , CD4+/CD8+ ratio in the end of 2 months after treatment were significantly higher compared with that before treatment and CD8+T cell lower in treatmentⅡgroup(P<0.05).There were no significant differences between before treatment and controlⅡgroup about cellular immunity function(P>0.05). The average diameter in treatmentⅡgroup more significantly increased than that before treatment (P<0.05). And PPD-IgG positive rate in the end of 6 months was lower than that before treatment. There was no significantly difference between treatmentⅡgroup and controlⅡgroup (P>0.05).(4)In control group there were significantly different in CD3+ , CD4+ lymphocyte percentages , CD4+/CD8+ ratio at the end of 2 months after treatment than that before treatment (P<0.05),and CD8+T lymphocyte percentages lower than that before treatment (P<0.05).There was no significant difference in PPD test reactive average diameter and PPD-IgG positive rate among before treatment and at the end of 2,6 months (P>0.05).(5)CD3+ , CD4+ lymphocyte percentages,CD4+/CD8+ ratio in the end of 2 ,6months after treatment were significantly higher in controlⅠgroup compared with that before treatment and CD8+T lymphocyte percentage in controlⅠgroup was lower than that before treatment (P<0.05).The extent of reaction in tuberculin test in the corresponding time period in controlⅠgroup was more intensive than that before treatment (P<0.05). There was no difference about PPD-IgG positive rate between before treatment at the end of 2,6 months (P>0.05). ALB at the end of 6 months in controlⅠgroup was significantly higher than that before treatment (P<0.05).(6)There was no significantly difference in cellular immunologic function, nutritional state compared with those before treatment at the end of 2,6 months (P>0.05) in controlⅡgroup.(7)Sputum negative conversion rate in treatment group was significantly higher than that in control group at the end of 2 months (P<0.05).At the end of 6 months the lesions improvement was higher in treatment group than that in control group. The cavity closure rate in treatment group was signicantly higher than that in control group.(8)Sputum negative conversion rate in strengthening chemotherapy phase in treatmentⅠgroup was significantly higher than that in controlⅠgroup (P<0.05). At the end of 2,4,6 months the lesions improvement and the cavity closures in treatmentⅠgroup were higher than that in the controⅠgroup.(9)There were no significantly differences in the sputum negative conversion rate,the lesions improvement rate and the cavity closures between treatmentⅡgroup and controlⅡgroup.Conclusions(1)It is significant that the effect of Mycobacterium vaccae vaccin on the elderly patients who had abnormal CD4+T cell before treatment. It could significantly improve cellular immunologic function and nutritional state, and speed up the sputum negative conversion rates and the lesions absorption.(2)The cellular immunologic function and ALB after only chemotherapy is improved compared with those before treatment for the elderly patients who had abnormal CD4+T cell. However, these curative effects in the control group were lower than those in the treatment group.(3)Mycobacterium vaccae vaccin could improve their cellular immunologic function for the elderly patients who had normal CD4+T cell. However, there was no significant difference between the control and the treatment groups. No differences were found in the nutritional state and clinical curative effect at the end of 6 months compared with before treatment and control group.(4)There was no difference in the cellular immunologic function and nutritional state after only chemotherapy in the elderly patients who had normal CD4+T cell compared with those in prior treatment and those in the treatment group .