SEARCH · PubMed Health

Results for “Tuberculosis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed1980

Tuberculosis register and surveillance system of tuberculosis in the Czech Socialist Republic.

The policy of tuberculosis control in the Czechoslovak Socialist Republic has proved effective during the past 20 years under unfavourable epidemiological conditions. At present, however, it ceased to meet the requirements of the changing tuberculosis epidemiological situation. On the basis of data obtained from long-term follow-up of epidemiological indices and longitudinal epidemiological studies there was prepared a new system of compulsory reports on tuberculosis cases, supplemented with continuous supervision of persons registered for tuberculosis, and a proposal of centralized processing of the collected data. Starting January 1, 1981 a register of tuberculosis is planned in the Czech Socialist Republic which will utilize modern computer methods for ensuring the following objectives: 1. to establish data for operative and complex evaluation of epidemiological situation on tuberculosis in districts, regions and the total of Czech Socialist Republic, 2. to provide conditions for assessment of effectivity of tuberculosis control methods, to collect and evaluate data on basic economic aspects of tuberculosis control, 4. in a national project to elaborate and propose essential measures for the surveillance of tuberculosis applicable to existing conditions within the Czechoslovak Socialist Republic. The organization of the proposed tuberculosis register is described.

Czechoslovakia↗

PubMed1998

Influence of the human immunodeficiency virus in the incidence of tuberculosis in a cohort of intravenous drug users: effectiveness of anti-tuberculosis chemoprophylaxis.

SETTING: A residential program in Barcelona for drug addicts (therapeutic community) admitted between November 1988 and March 1992, and followed until September 1994. OBJECTIVE: To study the incidence of tuberculosis as related to the presence of tuberculosis infection and/or human immunodeficiency virus (HIV) infection, and to evaluate the protective effect of chemoprophylaxis with isoniazid. DESIGN: Prospective cohort study. Incidence rates were compared using the Chi-square test for cohort studies. The effectiveness of chemoprophylaxis was evaluated by the Kaplan-Meier method at the univariate level, and by logistic regression models and proportional risks analysis at the multivariate level. RESULTS: During the study of 361 individuals without previous known tuberculosis or history of anti-tuberculosis chemoprophylaxis, 25 developed tuberculosis, an overall incidence rate of 1.79/100 person-years. For HIV-positive persons, the incidence rate was 3.25/100 person-years, compared with 0.30/100 in those who were HIV-negative (P < 0.05). The highest incidence rates occurred among HIV-positive persons who did not receive chemoprophylaxis and who were either anergic (HIV-positive, purified protein derivative [PPD]-negative, Multitest-negative) or who were infected with Mycobacterium tuberculosis (PPD+), 10.0/100 person-years and 4.64/100 person-years, respectively. Of the 53 persons who received chemoprophylaxis, three developed tuberculosis, an incidence rate of 1.4/100 person-years. In comparison, in the group of 51 patients who were designated to receive chemoprophylaxis but where none was actually taken, 17 developed tuberculosis, an incidence rate of 5.7/100 person-years (P = 0.03). CONCLUSION: HIV-infected intravenous drug users, particularly those who are anergic or who are PPD positive, are at increased risk of developing tuberculosis. Anti-tuberculosis chemoprophylaxis proved effective in this population.

AIDS-Related Opportunistic Infections↗

PubMed2000

[Incidence of tuberculosis in Spain: results of the Multicenter Project of Tuberculosis Research (MPTR). Work Group of the MPTR].

BACKGROUND: The objective of this project was to gain a better understanding of the incidence of all forms of tuberculosis and to describe the clinical-epidemiological characteristics of tuberculosis cases in Spain. METHODS: After active search through 14 registers, we identified cases of tuberculosis within 13 Spanish Autonomous Communities with populations that represented almost 67% of the total population of Spain. The study period was between May 1996-April 1997. RESULTS: The global incidence of all forms of tuberculosis was 38.51 cases per 100,000 inhabitants with some variations between the communities (range: 16.20/100,000-70.75/100,000). A positive smear in the sputum was discovered for 36% of all cases and 49.3% of the cases of pulmonary or miliary tuberculosis. This represented a incidence rate of 13.83 per 100,000 inhabitants (range 4.55/100,000-28.10/100,000). Men presented higher rates of incidence than women (52.70/100,000 versus 24.87/100,000). Concerning age groups, 25-34 years and 75 or more years were the most affected (61.35/100,000 and 59.35/100,000, respectively)). The most frequent sites of the disease were pulmonary, pleural and lymphatic (69.7%, 11.2% and 8.8% respectively) followed by disseminated forms (6.6%). Tuberculosis patients infected with HIV represented 17.7% of the study (range: 7%-27.2%) resulting in a incidence rate of AIDS/tuberculosis of 6.80 per 100,000 inhabitants (range: 2.33/100,000-8.23/100,000). CONCLUSIONS: The results of the Multicentric Project for Tuberculosis Research (MPTR) confirm the importance of tuberculosis in Spain and shows an important interaction between tuberculosis and HIV.

AIDS-Related Opportunistic Infections↗

PubMed2001

Pattern of mycobacterial resistance to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the state of Qatar after the implementation of DOTS and a limited expatriate screening programme.

OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis to four anti-tuberculosis drugs in pulmonary tuberculosis patients in the State of Qatar after the implementation of DOTS and an expatriate screening programme on arrival. METHOD: A state-wide, population-based, retrospective analysis of all cases of pulmonary tuberculosis with positive M. tuberculosis culture reported to the Division of Public Health TB Unit from January 1996 to December 1998. M. tuberculosis sensitivity testing was done by the Bactec method for isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). The results were interpreted as a daily change of the growth index of test vials (with drug) compared with controls. RESULTS: There were 406 isolates with positive M. tuberculosis culture. Sixty-one (15%) were resistant to one or more of the four anti-tuberculosis drugs, of which 58 (95%) were from newly diagnosed cases (primary) and three (5%) were from previously treated cases (acquired). Primary resistance was as follows: any resistance 15%, INH 12.4%, RMP 2%, SM 5.2%, EMB 0.8% and multidrug resistance (MDR, resistance to INH and RMP at least) was found in 0.8%. Acquired resistance was as follows: any resistance 15%, INH 15%, RMP 5%, SM 5% and MDR 5%. CONCLUSION: The prevalence of resistance to four anti-tuberculosis drugs is strikingly low due to the limited expatriate screening programme (chest radiography) and implementation of DOTS. The four-drug regimen is recommended for the initial phase of therapy until the results of sensitivity testing are known.

Adolescent↗

PubMed2004

[Clinical forms of new cases of tuberculosis at Kaunas Romainiai Tuberculosis Hospital in 1998-2001].

Totally 1427 patients with tuberculosis were investigated in Kaunas Romainiai Tuberculosis Hospital. All patients belonged to the first category (new cases positive for mycobacterium tuberculosis, or severe tuberculosis). Infiltrated and disseminated tuberculosis were the most frequent clinical forms. The frequency of infiltrated tuberculosis ranged from 57.36 to 68.8%, and disseminated tuberculosis ranged from 18.52 to 30.36%. The most frequent complications were bleeding from the lungs and chronic cor pulmonale. The resistance to isoniazid, rifampicin and streptomycin was investigated. Multi-drug resistant tuberculosis did not exceed 1%. We suggest that so few cases of multi-drug resistant tuberculosis are due to implementation of WHO treatment standards.

Adolescent↗

PubMed1998

Differential T cell responses to Mycobacterium tuberculosis ESAT6 in tuberculosis patients and healthy donors.

Vaccination against and diagnosis of tuberculosis are still insufficient. Proteins secreted by Mycobacterium tuberculosis induce strong immune responses in tuberculosis and constitute prime candidates for development of novel vaccines against tuberculosis as well as for immunodiagnostic assays. We investigated the role of the secreted proteins MPT63, MPT64 and ESAT6 from M. tuberculosis in healthy individuals and tuberculosis patients. None of the secreted proteins stimulated peripheral blood mononuclear cells from healthy donors. In contrast, CD4+ T cells from many tuberculosis patients were stimulated in an MHC class II-restricted fashion by ESAT6, but not by MPT63 or MPT64. T cell reactivities of tuberculosis patients were focused on the N-terminal region of ESAT6. The ESAT6 T cell epitopes were presented by different HLA-DR phenotypes. Cell cultures responding to either ESAT6 or synthetic peptides thereof showed mRNA transcripts for macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein (MCP)-1 or IL-8 and production of IFN-gamma and MIP-1alpha. Our results suggest that the secreted M. tuberculosis proteins MPT63, MPT64 or ESAT6 do not stimulate unprimed T cells, and that ESAT6 may be a potential candidate antigen for detection of clinical disease.

Adult↗

PubMed2004

The endocrinology of adrenal tuberculosis: the effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function.

Tuberculosis may affect many of the endocrine glands including the hypothalamus, pituitary, thyroid and adrenals. The most commonly involved endocrine organ in tuberculosis is the adrenal gland. Adrenal glands may be directly or indirectly affected by tuberculosis. Tuberculous Addison's disease is still an important cause of primary adrenocortical insufficiency particularly in the developing countries. Recent improvements in imaging techniques and modern endocrinological tests for the investigation of adrenal function have given us greater insight into the endocrinology of adrenal tuberculosis. Hypothalamo-pituitary-adrenal (HPA) axis is also involved in tuberculosis and recent findings revealed that HPA axis is activated rather than underactivated in active pulmonary tuberculosis. Activated HPA axis in tuberculosis causes increased cortisol secretion which results in a shift in the Th1/Th2 balance towards Th2. T cell dysfunction due to high cortisol and low DHEAS levels may be responsible for immunologically-mediated tissue damage in tuberculosis. In this review, recent findings concerning the adrenocortical function, radiological changes in adrenal glands and HPA axis involvement in tuberculosis are discussed.

Addison Disease↗

PubMed1990

Correlation between culture of Mycobacterium tuberculosis and IgG antibody to Mycobacterium tuberculosis antigen-5 in the cerebrospinal fluid of patients with tuberculous meningitis.

A retrospective study was made of the correlation between culture of Mycobacterium tuberculosis and detection of IgG antibody to M. tuberculosis antigen-5 in cerebrospinal fluid (CSF) by means of an enzyme linked immunosorbent assay (ELISA). Mycobacterium tuberculosis was cultured from the CSF in 14 of 70 patients with a clinical diagnosis of tuberculous meningitis (TBM). IgG antibody to M. tuberculosis antigen-5 was demonstrated in significant titres (80-640) in all 14 culture-positive patients. Thus, positive correlation was observed between culture of M. tuberculosis and detection of IgG antibody in the CSF. As a result of this observation, the CSF from 56 culture-negative patients with a clinical diagnosis TBM was specifically investigated for the detection of IgG antibody to M. tuberculosis antigen-5 and the findings were correlated with those of culture-positive patients. The assay was positive in 34 of 56 patients, the antibody titre ranging between 80 and 640. In the CSF of 70 patients with non-tuberculous neurological diseases, the assay was negative at a dilution of 1 in 80. Thus, detection of IgG antibody to M. tuberculosis antigen-5 by indirect ELISA carried 100% specificity and 60.7% sensitivity for a tuberculous aetiology in culture-negative patients with TBM. The results of this study suggest that indirect ELISA for IgG antibody to M. tuberculosis antigen-5 in CSF holds definite promise in diagnosis of TBM, particularly when repeated cultures of CSF are negative for M. tuberculosis.

Antibodies, Bacterial↗

PubMed1995

Humoral response to Mycobacterium tuberculosis-specific antigens in African tuberculosis patients with high prevalence of human immunodeficiency virus infection.

SETTING: The applicability of serodiagnosis of tuberculosis using Mycobacterium tuberculosis-complex-specific antigens in a Tanzanian population with high prevalence of HIV. OBJECTIVE: This study was performed to evaluate the usefulness, sensitivity and specificity of serology using M. tuberculosis-specific antigens in the diagnosis of tuberculosis in patients with and without HIV co-infection. DESIGN: Patients with proven pulmonary and extrapulmonary tuberculosis at a major referral centre in Tanzania were enrolled in the study. The control group consisted of patients without a history of previous tuberculosis admitted to the trauma ward and of healthy volunteers. Sera were analysed by an enzyme linked immunoassay (ELISA) using two M. tuberculosis specific proteins as antigen: the 38 kDa protein [3T] and a 17 kDa protein. In addition was recorded presence or absence of BCG scar and tuberculin sensitivity and the sera were tested for HIV and analysed for beta-2-microglobulin content. RESULT: Sensitivity and specificity were markedly reduced in tuberculosis patients with HIV co-infection compared to patients without this disease (73% and 70% versus 52% and 50% respectively). CONCLUSION: Serology for diagnosis of tuberculosis is not feasible in an HIV endemic region.

Antibodies, Bacterial↗

PubMed2005

A new vaccine against tuberculosis shows greater protection in a mouse model with progressive pulmonary tuberculosis.

SETTING: The effectiveness of Bacillus Calmette-Guerin (BCG) vaccination in reducing tuberculosis (TB) prevalence rates is poor, resulting in urgent need for improved immunization programs, with new and more effective vaccines against TB. OBJECTIVE: To develop a recombinant Tice BCG vaccine against TB that overexpresses the 38-kDa antigen of Mycobacterium tuberculosis in order to protect against infection by M. tuberculosis H37Rv and hyper-virulent M. tuberculosis Beijing genotype. DESIGN: M. tuberculosis 38-kDa protein was cloned into a mycobacterial shuttle plasmid, which was used to overexpress the 38 kDa protein in BCG Tice to produce the recombinant vaccine, rBCG38 Tice (rBCG38). RESULTS: Compared with BCG Tice, which conferred little protection against the Beijing strain of M. tuberculosis, vaccination with the rBCG38 increased survival of mice infected with either M. tuberculosis H37Rv or a Beijing strain of M. tuberculosis, isolate 9501000. Vaccination with either BCG Tice or rBCG38 resulted in enhanced protection against mycobacterial growth in lung tissue by reducing the number of colony-forming units (CFU). The vaccine induced a strong and highly significant Th1 response, shown by the high level of IL-2 and IFN-gamma cytokine producer cells found in the lungs of challenged mice, and an increase in the IgG2a:IgG1 ratio found in the pooled sera of the vaccinated mice. CONCLUSIONS: This study showed that rBCG38 vaccine induced a strong Th1 response, demonstrated by the high levels of IL-2 and IFN-gamma producer cells and IgG2a. Protection was mediated for as long as 6 and 4 months after challenge with M. tuberculosis H37Rv and Beijing genotypes, respectively.

Animals↗

PubMed2000

Infectiousness of Mycobacterium tuberculosis in HIV-1-infected patients with tuberculosis: a prospective study.

BACKGROUND: Previous studies concerning the relative infectiousness of HIV-1-positive individuals with pulmonary tuberculosis have produced conflicting results. Thus, we assessed the effect of HIV-1 on the infectiousness of Mycobacterium tuberculosis in a prospective study. METHODS: We organised in Santo Domingo, Dominican Republic, a cohort study of household contacts of HIV-1-positive and HIV-1-negative individuals with newly diagnosed pulmonary tuberculosis. Household contacts were assessed at their houses at baseline and followed up for 14 months for evidence of M tuberculosis infection and tuberculosis with a multi-step tuberculin skin test, anergy skin test, physical examinations, chest radiographs, and sputum smears. FINDINGS: Tuberculin induration of 5 mm or greater was seen in 153 (61%) of 252 household contacts of HIV-1-positive index cases and in 418 (76%) of 551 household contacts of HIV-1-negative index cases (odds ratio 0.49 [95% CI 0.35-0.67], p=0.00001). In multivariate logistic-regression analysis after allowance for between-household variation in tuberculin response, HIV-1 infection of the index case remained inversely associated with the tuberculin response of the household contacts (0.52 [0.29-0.93], p=0.02). When the analysis was restricted to household contacts aged between 2 years and 15 years the adjusted association remained significant (0.37 [0.14-0.98], p=0.04). Among household contacts who had a negative tuberculin skin test at baseline, conversion to tuberculin skin test positivity was less frequent among household contacts of HIV-1-positive index cases (cut-off > or =5 mm: 32/131 [24%] vs 71/204 [35%], p=0.05; cut-off > or =10 mm: 23/153 [15%] vs 55/245 [22%], p=0.07). INTERPRETATION: These data suggest that HIV-1-positive individuals with tuberculosis are less likely than HIV-1-negative individuals with tuberculosis to transmit M tuberculosis to their close contacts. No changes in the current policy regarding tuberculosis contact tracing are needed in the presence of HIV-1.

AIDS-Related Opportunistic Infections↗

PubMed2003

Detection of Mycobacterium tuberculosis DNA from peripheral blood in patients with HIV-seronegative and new cases of smear-positive pulmonary tuberculosis by polymerase chain reaction.

Tuberculosis is still one of the most important cause of mortality and morbidity in many countries and there is a need for new methods for accurate and rapid diagnosis of tuberculosis. To determine the sensitivity and specificity of polymerase chain reaction (PCR) method, we have evaluated Mycobacterium tuberculosis DNA in peripheral blood samples with PCR technique in adult patients with human immunodeficiency virus (HIV)-negative and new cases of smear-positive pulmonary tuberculosis. We investigated the relationship between characteristic of the patients, radiological extension of the disease, sputum smear grade, presence of cavity, body-mass index (BMI) serum albumin level, total delay time and PCR positivity. Forty patients (33 male and 7 female; mean age 37.8 +/- 14.1) and 20 healthy control subjects (13 male and 7 female; mean age 35.6 +/- 7.3) were enrolled in this study. PCR was positive in 16 of 40 (40%) patients with pulmonary tuberculosis and negative in 24 of 40 (60%). None of the healthy controls had positive PCR results. The overall sensitivity specificity and accuracy of the PCR assay was 40, 100 and 60%, respectively. We found the positive correlation between PCR positivity and sputum smear grade (r=0.46, P=0.003) radiological extension of the disease (r=0.69, P=0.001), presence of cavity (r=0.90, P=0.001). We conclude that the detection of M. tuberculosis DNA from peripheral blood by PCR technique is useful for the rapid diagnosis of tuberculosis patients with HIV-negative. Hematogenous dissemination was important in tuberculosis patients and peripheral blood samples were suitable and easy materials. However, standardization of the PCR method must be ensured for the diagnosis of tuberculosis.

Adult↗

PubMed2002

Serum cytokine concentrations do not parallel Mycobacterium tuberculosis-induced cytokine production in patients with tuberculosis.

We measured serum cytokine concentrations and Mycobacterium tuberculosis-stimulated cytokine production by peripheral blood mononuclear cells (PBMCs) obtained from persons infected with M. tuberculosis. Serum interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) concentrations were elevated in patients with tuberculosis compared with healthy persons who had reactions to tuberculin skin tests, but IL-18 concentrations were not. In contrast, M. tuberculosis-stimulated PBMCs from patients with tuberculosis produced less IFN-gamma and IL-18 but similar amounts of IL-10, compared with PBMCs from healthy subjects who had reactions to tuberculin skin tests. Pretreatment of PBMCs from healthy subjects with reaction to tuberculin with serum from patients with tuberculosis inhibited IFN-gamma production in response to M. tuberculosis, and inhibition was blocked by anti-IL-10. Thus, serum concentrations of IFN-gamma, IL-18, and IL-10 do not parallel M. tuberculosis-induced cytokine levels, and increased IL-10 serum levels in patients with tuberculosis inhibit IFN-gamma production in response to mycobacterial antigens.

Cell Culture Techniques↗

PubMed2004

Immune response to postprimary tuberculosis in mice: Mycobacterium tuberculosis and Miycobacterium bovis bacille Calmette-Guérin induce equal protection.

We addressed the question of whether protective immunity induced by natural infection with Mycobacterium tuberculosis and that induced by vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) differ in the murine model. We infected mice with M. tuberculosis Erdman, cured them by chemotherapy, and subsequently reinfected them with a low dose of M. tuberculosis H37Rv. The course of tuberculosis was compared with that in mice previously vaccinated with BCG Danish 1331. Protection against postprimary M. tuberculosis infection did not differ significantly between the 2 groups. After challenge infection, numbers of interferon- gamma -positive splenocytes did not differ between mice with primary infection and vaccinated mice. Splenocytes from primary M. tuberculosis-infected mice conferred marginally higher protection than did those from BCG-vaccinated mice. Serum transfer did not protect against reinfection in either group. Our data emphasize that natural infection with M. tuberculosis and vaccination with BCG do not differ in their capacity to induce protective immunity against tuberculosis and support the notions that reinfection contributes to the development of active disease and that any novel vaccine against tuberculosis has to perform better than both vaccination with BCG and immunity evoked by natural infection.

Animals↗

PubMed1999

Dynamics of plasma cytokine levels in patients with advanced HIV infection and active tuberculosis: implications for early recognition of patients with poor response to anti-tuberculosis treatment.

OBJECTIVE: To examine whether the serial measurement of plasma cytokine levels can assist in the early recognition of AIDS/tuberculosis patients with poor response to anti-tuberculosis treatment. DESIGN: Longitudinal, prospective cohort study. SETTING: A university hospital, the largest centre for HIV/AIDS patients in Taiwan. METHODS: Between January 1997 and September 1998, 25 consecutive patients with advanced HIV infection and suspected tuberculosis were enrolled in the study. Plasma samples were obtained on day 1 (baseline), 3, 7 and 14 of anti-tuberculosis treatment and the levels of tumour necrosis factor-alpha (TNF-alpha) were measured. Patients were classified as either responders or non-responders according to the results of assessment of symptoms and follow-up cultures during the sixth and eighth week of anti-tuberculosis treatment. Thirty consecutive HIV-negative tuberculosis patients were also enrolled in the study. RESULTS: The data of a total of 16 AIDS patients (median CD4 cell count 16 x 10(6)/l; 12 responders and four non-responders) and 21 HIV-negative patients (16 responders and five non-responders), whose tuberculosis was culture-proven, were included for analysis. In responders, TNF-alpha levels declined remarkably within the first week of anti-tuberculosis treatment; however, the decline of TNF-alpha levels in non-responders was significantly less [the median ratio of TNF-alpha level on day 7 to that at baseline was 0.32 versus 0.85 (P < 0.001) in AIDS patients; 0.34 versus 0.80 (P = 0.001) in HIV-negative patients). The lack of a > or = 50% reduction in pre-treatment TNF-alpha levels during the first week of treatment was strongly associated with a poor response to anti-tuberculosis treatment (P = 0.001 in AIDS patients; P < 0.001 in HIV-negative patients). CONCLUSION: Serial measurement of plasma TNF-alpha levels may help to assess the response to anti-tuberculosis treatment in AIDS patients, in spite of very low CD4 cell counts. Failure of TNF-alpha levels to decline by > or = 50 % of pre-treatment levels in the first week of treatment may be an early surrogate marker of a poor response.

AIDS-Related Opportunistic Infections↗

PubMed2003

Changes in avidity and level of immunoglobulin G antibodies to Mycobacterium tuberculosis in sera of patients undergoing treatment for pulmonary tuberculosis.

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens.

Antibodies, Bacterial↗

PubMed1992

Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis.

We have studied the capacity of a selected fraction of Mycobacterium tuberculosis extracellular proteins (EP) released into broth culture by mid-logarithmic-growth-phase organisms to induce cell-mediated immune responses and protective immunity in a guinea pig model of pulmonary tuberculosis. Guinea pigs infected with M. tuberculosis by aerosol but not uninfected control guinea pigs exhibit strong cell-mediated immune responses to EP, manifest by dose-dependent cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. Guinea pigs immunized subcutaneously with EP but not sham-immunized control guinea pigs also develop strong cell-mediated immune responses to EP, manifest by dose-dependent cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. EP is nonlethal and nontoxic to guinea pigs upon subcutaneous immunization. Guinea pigs immunized with EP and then challenged with aerosolized M. tuberculosis exhibit protective immunity. In five independent experiments, EP-immunized guinea pigs were consistently protected against clinical illness, including weight loss. Compared with EP-immunized guinea pigs, sham-immunized control guinea pigs lost 12.9 +/- 2.0% (mean +/- SE) of their total weight. EP-immunized guinea pigs also had a 10-fold reduction in viable M. tuberculosis bacilli in their lungs and spleens (P = 0.004 and 0.001, respectively) compared with sham-immunized control animals. In the two experiments in which some guinea pigs died after aerosol challenge, EP-immunized animals were protected from death. Whereas all 12 (100%) EP-immunized guinea pigs survived challenge with aerosolized M. tuberculosis, only 6 of 12 (50%) sham-immunized control guinea pigs survived challenge (P = 0.007, Fisher exact test). This study demonstrates that actively growing M. tuberculosis cells release immunoprotective molecules extracellularly, that a subunit vaccine against tuberculosis is feasible, and that extracellular molecules of M. tuberculosis are potential candidates for a subunit vaccine.

Aerosols↗

PubMed1991

Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis.

In this study we established the usefulness of DNA fingerprinting for the epidemiology of tuberculosis on the basis of the DNA polymorphism generated by the insertion sequence (IS) IS986. Although clinical isolates of Mycobacterium tuberculosis displayed a remarkably high degree of restriction fragment length polymorphism, we showed that transposition of this IS element is an extremely rare event in M. tuberculosis complex strains grown either in vitro or in vivo for long periods of time. The M. tuberculosis and Mycobacterium africanum strains tested in this study contained 6 to 17 IS copies. In the Mycobacterium bovis strains, the copy numbers ranged between 1 and 5, and all 27 M. bovis BCG strains investigated invariably contained a single IS copy. This copy was located at a unique chromosomal position, reinforcing the idea that the frequency of IS transposition is very low in M. tuberculosis complex strains. Various microepidemics are described in which each microepidemic corresponds to a particular fingerprint type. The extent of similarity between Dutch and African strains was quantitatively assessed by computer-assisted analysis of DNA fingerprints. The results indicate that M. tuberculosis strains from regions in central Africa, where tuberculosis is highly prevalent, are generally more related to each other than isolates from the Netherlands, where the transmission rate is low and where the majority of the tuberculosis cases are presumed to be the result of reactivation of previously contracted M. tuberculosis infections.

Africa↗