Heterogeneity of antibody response to myobacterial antigens in different clinical manifestations of pulmonary tuberculosis.

Different clinical outcomes of tuberculosis can be related to the balance between cell-mediated and humoral immunity. In this prospective study we examined the humoral immune responses to recombinant and native mycobacterial antigens in relation to clinical presentations of pulmonary TB. Two hundred and fifteen serum samples were examined including: non-cavitary (n=120), cavitary (n=65), caseous pneumonia (n=12), and disseminated TB (n=18). ELISA tests detecting IgG, IgA, and IgM against antigens: 38 kDa and 16 kDa, 38 kDa and lipoarabinomannan (LAM) were used. Univariate and multivariate logistic regression analyses were carried out to find the association between the antibody level and demographic or clinical characteristics. The relationships among specific antibody profiles and the phase of the disease in relation to demographic (age and sex) and clinico-radiological factors were investigated by measuring serum antibody levels (IgG, IgA, and IgM) to 38 kDa and 16 kDa recombinant M. tuberculosis antigens and to LAM - native mycobacterial antigen. The results show that the radiological extent of the disease is the strongest factor associated with IgG antibody production. Patients with more extensive pulmonary TB showed higher titers of IgG antibody to M. tuberculosis antigens (P<0.0001). The highest IgG and IgA level were observed in fibro-cavernous TB. The presence of cavity was associated only with IgG anti 38+16 kDa (P<0.001). IgA level was the highest in caseous pneumonia. IgM antibody production was not associated with any clinical and radiological factor, but only with the male gender. Age was independently and inversely associated with IgG anti 38 kDa+LAM level and IgM anti 38 kDa+LAM. We conclude that the humoral immune response to mycobacterial antigens is highly heterogeneous and varies with the stage of TB. IgG antibody level is higher in most advanced and extensive forms of the disease.

Diagnostic value of different serological tests for tuberculosis in Poland.

The aim of the study was to test the diagnostic accuracy of several serological assays for the diagnosis of tuberculosis (TB) in the Polish population. ELISA based assays detecting: 38 kDa+LAM - MycoM, MycoA and MycoG, 38 kDa - Pathozyme TB complex, 38 kDa+16 kDa - Pathozyme TB complex plus were used. The humoral immune response was analyzed in a group of 319 TB patients (289 adults and 30 children) and in a control group consisting of 66 sarcoidosis cases, 16 cases of mycobacterial infections other than tuberculosis, 35 lung cancer patients, and 70 healthy volunteers. Among the TB patients, there were 267 cases of pulmonary TB and 52 cases of extrapulmonary TB. Sensitivity varied between 32% (IgM) and 63% (IgA) and increased in culture positive tuberculosis and in chronic cases. Specificity was the highest for the tests based on recombinant antibodies (98%). Sensitivity of the IgG test in extrapulmonary TB was comparable with that in pulmonary TB. Overall, sensitivity of the examined tests was lower in children than in adults, but it varied depending on the age and phase of the disease. We conclude that the ELISA-based tests may be a useful tool for improving the diagnosis of TB, especially in adults and in those countries where the prevalence of culture positive and chronic cases is high.

[Value of the immunochromatographic assay for detecting IgG antibodies against 38 kDa mycobacterial antigen in diagnosis of tuberculosis]. / Przydatnosc testu immunochromatograficznego wykrywajacego przeciwciala IgG przeciwko antygenowi pratka 38 kDa w rozpoznawaniu gruzlicy.

Despite of a fast development in the techniques of rapid identification of mycobacteria by molecular genetic techniques, serodiagnosis may be of special values as non-expensive, easy to perform method. Several serodiagnostic tests, principally those using immunoenzymatic (ELISA) methodology are available. The goal of our study was to evaluate one step coloured immunochromatographic assay detecting IgG antibodies against antigen 38 kDa (Rapid Test TB). Our material consisted of 278 serum samples--tuberculosis (n = 155), healthy (n = 36), sarcoidosis (n = 50), lung cancer (n = 25) mycobacterial infections other than tuberculosis (n = 12). Tuberculosis group consisted of new culture positive cases (n = 66), new culture negative cases (n = 23), chronic cases (n = 43) and extrapulmonary TB (n = 23). Specificity of 96% and sensitivity of 54% was obtained. In pulmonary TB sensitivity of 50% and in extrapulmonary TB of 74% was obtained. In chronic cases sensitivity of 70% and in new cases of 40% was received. Sensitivity of 44% in new culture positive cases and 30% in new culture negative cases was obtained. We conclude that immunochromatographic test may be a very useful tool improving tuberculosis diagnosis, especially in extrapulmonary tuberculosis. Strip test may be an interesting alternative as it is an extremely simple, rapid, and cheap technique.

[Usefulness of measuring serum IGG antibodies against A60 mycobacterial antigen for diagnosis of tuberculosis]. / Przydatnosc oznaczania w surowicy przeciwcial IgG przeciwko antygenowi A60 w diagnostyce gruzlicy pluc.

Measurement of antimycobacterial antibody may be used as potential diagnostic tool in tuberculosis. The aim of the study was to evaluate the diagnostic value of serum IgG level against A60 mycobacterial antigen measured by ELISA method. Material consisted of 144 persons divided into 5 groups (76 tuberculosis patients, 20 sarcoidosis patients, 17 lung cancer patients, 8 patients with mycobacterial infections other than tuberculosis and 23 healthy controls). In the tuberculosis group there were 50 culture positive cases and 26 culture negative ones, 43 new cases and 32 chronic cases. Positive results were obtained in 51% of tuberculosis patients. Sensitivity increased to 62% in culture positive group and 63% in chronic cases. Specificity of the test was 96%. The results indicate that Immunozyme Mycobacterium test is a valuable tool in tuberculosis diagnosis.

[Diagnostic value of IgG antibody levels against 38 kDa mycobacterial antigen]. / Wartosc diagnostyczna poziomu przeciwcial IgG przeciwko antygenowi 38 kDa pratka gruzlicy.

Tuberculosis diagnosis bases on clinical and radiological symptoms and identification of mycobacteria. Accuracy of both methods is limited. Therefore reliable serological test would have considerable advantage. The present study was aimed at evaluating IgG-mediated immune response against specific mycobacterial antigens 38 kDa in group of 200 patients and control subjects. Our material consisted of 104 tuberculosis patients, 25 with sarcoidosis, 24 with lung cancer, 13 with bacterial or fungal pulmonary infection, 8 with mycobacterial infections other than tuberculosis and 26 healthy persons. We used commercially available ELISA based kits (Pathozyme TB-complex). Specificity of 100% and sensitivity of 49% was achieved. Sensitivity increased to 59% in chronic cases and to 52% in culture positive cases. Sensitivity decreased to only 14% in group of new culture negative cases. Measurement of IgG serum level against 38 kDa can be helpful in tuberculosis diagnosis. As the test lacks falsely positive results it indicates its high positive predictive value.

[Reasons for chronic sputum culture positive tuberculosis--evaluation based on personal experience]. / Przyczyny prezewleklego pratkowania chroników--ocena na podstawie doswiadczen wlasnych.

It is commonly believed that chronic sputum positivity in treated pulmonary tuberculosis is caused by the patients' noncompliance. We have undertaken retrospective analysis of the records of 59 patients to verify reasons of treatment failure. The group consisted of 12 women and 47 men aged between 22 to 87 (median: 47) who were sputum culture positive from 1 to 12 years (x = 3.4). According to the retrospective analysis 44 patients showed more than one reason for treatment failure. In 36 cases improper therapy was responsible for treatment failure involving insufficient number of drugs in 28 cases, untimely termination of treatment in 14 cases, inadequate drugs in 11 cases, poor control of treatment in 5 cases and insufficient doses of drugs in 1 case. The patients' noncompliance was the main reason in 33 cases, allergy and adverse reaction to drugs were the reasons of failure of the therapy in 21 cases. 18 patients (30.5%) showed primary drug resistance. The patients' records analysis revealed that the drug resistance rate was related to the duration of treatment. At the beginning every patient was resistant to 2 drugs on average while at the end of the treatment the number increased to 4. In spite of this only 31 patients (52.5%) received other than first line drugs.

[Treatment of patients for chronic pulmonary tuberculosis with expectoration--selection and tolerance to drugs]. / Leczenie chorych na gruzlice pluc przewlekle pratkujacych--dobór i tolerancja leków.

In retrospective analysis of 48 patients with chronic pulmonary tuberculosis we concluded that in spite of increasing drug resistance to first line drugs only 52% chronics received other than first line antituberculous drugs. Our treatment was based on the selection of drugs according to susceptibility tests. 4-6 drugs were used at the beginning of treatment. 13 patient were excluded of the group. Of remaining 35 chronics sputum conversion was achieved in 30 cases (85.7%). Our successful treatment of patients with chronic tuberculosis was based on the following principles: treatment with other than first line antituberculous drugs and treatment with the combination of 5 or 6 drugs selected on susceptibility tests in the initial phase continuing with 2-3 drugs for 12-18 months after sputum conversion. Ofloxacin improves the efficacy of regimens used for treatment of chronic tuberculosis.

[Treatment of patients with chronic pulmonary tuberculosis with expectoration--evaluation of effectiveness]. / Leczenie chorych na gruzlice pluc przewlekle pratkujacych--ocena skutecznosci.

48 patients with chronic pulmonary tuberculosis (10 women and 38 men) aged between 22 and 87 years were treated. They were sputum culture positive from 1 to 12 years (x = 3.6). In chronics all patients but one were resistant to one or more drugs (average to 4 drugs). Control group consisted of 29 patients with recently diagnosed pulmonary tuberculosis sensitive to all drugs. Treatment of chronics based on: selection of drugs according to susceptibility test, using of 4-6 antituberculous drugs, treatment for not less than one year after sputum culture conversion. Control group was treated with standard therapy consisted of 3 or 4 drugs. Out of 48 chronics 13 patients dropped out due to: drug toxicity in 5 cases, noncompliance in 5 cases and death in 3 cases (in 2nd and 5th months of treatment). Of remaining 35 chronics sputum conversion was achieved in 30 cases (85.7%) average after 9 weeks. In control group 3 patients died during 2 weeks of treatment and remaining patients became sputum culture negative after average 6 weeks. Difference is significant (p = 0.006).

[Reasons for chronic expectoration in patients with pulmonary tuberculosis registered in the Central Tuberculosis Registry]. / Przyczyny przewleklego pratkowania u chorych na gruzlice pluc zarejestrowanych w Centralnym Rejestrze Gruzlicy.

The aim of the retrospective population-based study was to identify reasons for failure of sputum culture negativity from the 12th month on since the start of chemotherapy of pulmonary tuberculosis (PTB). Medical records of 97 patients with PTB (85 men and 12 women) remaining sputum culture positive for over 12 months, reported to the Central TB Registry (1988-1990), were reviewed. The mean age was 46.7 years. There were 39.2% blue collar workers, 18.6% peasants, 21.6% unemployed, 14.4% pensioners. Only 4.1% constituted persons with education above elementary level. 44 patients abused alcohol, 13 of them had severe alcohol related health problems. Initial susceptibility tests were done in 79 subjects, showing resistance to at least one drug in 15. In 21 subjects the new resistance occurred during observation. The mean period until conversion of sputum culture was 23.5 months. Sputum culture conversion was finally achieved in 63 (64.9%) subjects. The reasons for delayed sputum culture conversion were identified in 86 persons. The main reason for long duration of positive sputum culture in 75 (87.2%) subjects was poor compliance. In 7 (8.1%) cases evident treatment error was relevant. Serious adverse reactions to drugs were responsible in 4 (4.6%).

[Surgical treatment of patients with multi-resistant pulmonary tuberculosis--case reports]. / Leczenie chirurgiczne chorych na gruzlice pluc oporna na leki przeciwpratkowe--opis przypadków.

Two patients with multidrug-resistant pulmonary tuberculosis were surgically treated after 3 and 7 years of unsuccessful chemotherapy. There was pneumonectomy in one case and lobectomy with segmentectomy in the second. Pneumonectomy was complicated by bronchopleural fistula. Both patients become sputum culture negative after surgical treatment but first patient died 5 months after surgery because of acute hepatitis.

[Reasons for chronic expectoration--case reports]. / Przyczyny przewleklego pratkowania--opis przypadków.

To illustrate reasons for chronic culture positive pulmonary tuberculosis 4 patients are presented. In two cases the reasons for treatment failure were on the doctors' side. In one case a doctor used an insufficient number of drugs, in the second case the treatment was too short. In the third case there were more than one reason for treatment failure: the patients' poor compliance, and the doctors' fault: an inadequate choice of drugs. In the last case adverse reactions to drugs caused the treatment failure.

[Tuberculosis of the bones and joints]. / Gruzlica kosci i stawów.

The incidence of tuberculosis has increased over the last several years. Bones and joints tuberculosis makes 20% of all extrapulmonary locations of tuberculosis. In Poland this form of tuberculosis is underdiagnosed. We present three cases with tuberculosis of bones, joints and lung to remind the basic principles of diagnosis and treatment.

[Incidence of tuberculosis in patients with hematologic malignancies]. / Czestosc wystepowania gruzlicy u chorych na nowotwory ukladu krwiotwórczego.

The analysis of the incidence of tuberculosis in patients with hematological malignancies was performed in 2,025 patients hospitalized in internal clinic. Only in 42 cases tuberculosis was noticed.

[Studies on the effectiveness of a new model for treating tuberculosis with prolonged administration of isoniazid]. / Badania nad skutecznoscia nowego modelu leczenia gruzlicy z przedluzonym stosowaniem hydrazydu kwasu izonikotynowego.

The aim of the study was to determine the therapeutical effectiveness of a new regimen in freshly diagnosed cases of pulmonary tuberculosis. In this model PZA and SM were excluded, but INH administration was prolonged. Instead of INH and RMP a combined drug was given--RIFAMAZIDE (Polfa). Therapy was carried out in three stages: I stage lasting 3 months during which Rifamazide (600 mg RMP, 300 mg INH) and EMB (25 mg per kg b.w.) was given; II stage-during which Rifamazide was given (2 tablets.) for 3 months; III stage--INH monotherapy (300 mg daily) was continued for 6 months. During the first stage all patients were hospitalized at the Institute of Tuberculosis. The second stage was carried out under supervision of an out-patient clinic. During the third stage patients received their INH at their homes. The study group consisted initially of 58 patients, of which 11 were dropped out due to primary resistance, change of therapy, non-compliance, and non-tolerance of drugs. The final evaluation was carried out basing on results from 47 patients. In all patients a negative sputum culture was achieved. In most during the first two months of therapy. All demonstrated improvement in radiological evaluation. In 38 patients the follow-up lasted 2-6 years, in the remaining nine 2 years. Recurrencies were not observed. Good acceptation by the patients of Rifamazide was found.