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    Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of Antibody-Mediated Immunity against Mycobacterium tuberculosis
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    Abstract:
    SUMMARY Fifty years after the introduction of the first effective antimicrobial agents against Mycobacterium tuberculosis, this pathogen continues to be a tremendous public health problem. The rise in the number of resistant strains and the difficulties involved in the therapy of tuberculosis in immunocompromised AIDS patients have renewed the interest in the development of effective vaccines. To evaluate whether a potential vaccine against tuberculosis could prevent infection by eliciting a protective antibody response, we reviewed the history of antibody-mediated immunity against tuberculosis. Review of the literature of the past 100 years demonstrates that there is sufficient evidence to conclude that antibody-mediated immunity can modify the course of infection in certain situations. Based on our findings and on what is known in other systems, we propose that the role of antibody-mediated immunity to M. tuberculosis be reexamined, using advanced technology.
    ABSTRACT Background Studies on human intraocular tuberculosis (IOTB) are extremely challenging. For understanding the pathogenesis of IOTB, it is important to investigate the mycobacterial transcriptional changes in ocular environment. Methods Mice were challenged intravenously with Mycobacterium tuberculosis H37Rv and at 45 days post-infection, experimental IOTB was confirmed based on bacteriological and molecular assays. M. tuberculosis transcriptome was analyzed in the infected eyes using microarray technology. The identified M. tuberculosis signature genes were further validated and investigated in human IOTB samples using real-time polymerase chain reaction. Results Following intravenous challenge with M. tuberculosis, 45% (5/12) mice showed bacilli in the eyes with positivity for M. tuberculosis ribonucleic acid in 100% (12/12), thus confirming the paucibacillary nature of IOTB similar to human IOTB. M. tuberculosis transcriptome in these infected eyes showed significant upregulation of 12 M. tuberculosis genes and five of these transcripts (Rv0962c, Rv0984, Rv2612c, Rv0974c and Rv0971c) were also identified in human clinically confirmed cases of IOTB. Conclusions Differentially expressed mycobacterial genes identified in an intravenously challenged paucibacillary mouse IOTB model and presence of these transcripts in human IOTB samples highlight the possible role of these genes for survival of M. tuberculosis in the ocular environment, thus contributing to pathogenesis of IOTB.
    Pathogenesis
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    Current theory in the molecular epidemiology of tuberculosis holds that tuberculosis cases harboring Mycobacterium tuberculosis strains with a common deoxyribonucleic acid (DNA) fingerprint are the result of recent M. tuberculosis transmission. Here we propose a mathematical approach independent of DNA fingerprinting to estimating the percentage of recent transmissions responsible for current tuberculosis incidence. The “short-term reproductive number” of tuberculosis is defined as the average number of tuberculosis cases developing within 1 year of infection. Multiplying the short-term reproductive number by the number of tuberculosis cases in each year and dividing by the subsequent year’s tuberculosis case burden equals the proportion of tuberculosis cases in the subsequent year that are due to recent transmission. We carried out separate calculations for human immunodeficiency virus (HIV)-negative and HIV-positive tuberculosis cases. We applied the model to pulmonary (infectious) tuberculosis cases diagnosed in New York City during 1989–1993, using tuberculosis and AIDS surveillance data. Model-based estimates of the proportion of tuberculosis due to recent transmission were lower than estimates based on DNA fingerprints. Reconciliation of these divergent estimates may require the re-estimation of model parameters from data collected de novo, additional model development, and further advances in DNA fingerprinting methods.
    Tuberculosis caused by Mycobacterium tuberculosis, is still one of the major global health problems. The conventional diagnostic tests for tuberculosis are not sensitive enough and time consuming. Seroimmunologic diagnostic test is one of the early diagnostic technologies in the tuberculosis control and prevention, so much attention has been focused on the development of novel immunological assays of tuberculosis recently. Potential value of Mycobacterium tuberculosis RD region-encoded proteins have been evaluated for rapid diagnosis of tuberculosis these years. In this review, advances in the diagnosis of tuberculosis based on the RD region antigens were discussed.
    Tuberculosis diagnosis
    Mycobacterium tuberculosis complex
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    Certain populations of Mycobacterium tuberculosis go undetected by standard diagnostics but can be enumerated using limiting dilution assays. These differentially detectable M. tuberculosis (DD M. tuberculosis) populations may have relevance for persistence due to their drug tolerance. It is unclear how well DD M. tuberculosis from patients is modeled by a recently developed
    Tuberculosis diagnosis
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    Introduction. Relapses of tuberculosis are fairly rare nowdays and they represent the onset of tuberculosis two, or more than two years after completion of previous treatment. Material and Methods. In the previous period, relapses of tuberculosis occurred in 141 patients (87 male and 54 female). Their mean age was 46.2 years. Results. Relapses of tuberculosis occurred after 11.3 years, on average. All patients presented with pulmonary tuberculosis, and two patients also had pulmonary and extrapulmonary tuberculosis(bones). Resistance was one of the statistically significant factors for relapse of tuberculosis. Resistance to one antituberculotic agent was most common - 8 patients, resistance to two drugs - 4 patients, resistance to three drugs - 4 patients, resistance to four drugs in 5 patients. Due to these findings on resistant strains of mycobacterium tuberculosis, a huge number of patients with relapses of tuberculosis had full recovery and completed the treatment. Conclusion. The importance of resistant strains of mycobacterium tuberculosis is really huge in our conditions. The findings of these resistant strains of mycobacterium tuberculosis and adequate medical treatment are obligatory nowadays. .
    Mycobacterium tuberculosis complex
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    Objective To study the contribution of exogenous reinfeciton to tuberculosis recurrence. Methods Mycobacterium tuberculosis isolates from patients who had experienced 2 successive tuberculosis episodes during the years from January 1999 to March 2004 were genotyped by mycobacterial interspersed repetitive units (MIRU) method. The cause of tuberculosis recurrence was determined by comparing the MIRU pattern of Mycobacterium tuberculosis isolates responsible for different tuberculosis episodes from patients. Results Of 37 qualified patients with recurrent tuberculosis, the isolates from 25 patients in their two tuberculosis episodes showed different MIRU patterns, indicating that 68% recurrent patients were due to exogenous reinfection. The exogenous reinfection rate decreased with the age from 3/3 (under 30 years) to 73% (11/15, 30 to 60 years) and 58% (11/19, over 60 years). The frequency of exogenous reinfection increased with the tuberculosis recurrent interval. Within 6 months, the exogenous reinfection accounted for 58% (7/12) of all the recurrentce, while for the time more than one year, the percentage increased to 79% (11/14). Conclusions Exogenous reinfection was a major cause of tuberculosis recurrence in Shanghai. MIRU genotyping method is useful to study the cause of tuberculosis recurrence.
    Mycobacterium tuberculosis complex
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    There is considerable variability in the outcome of Mycobacterium tuberculosis infection. We hypothesized that Mycobacterium africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease.In a cohort study of patients with tuberculosis and their household contacts in The Gambia, we categorized 1808 HIV-negative tuberculosis contacts according to exposure to M. tuberculosis or M. africanum. Positive skin test results indicated transmission, and development of tuberculosis during 2 years of follow-up indicated progression to disease.Transmission rates were similar, but rates of progression to disease were significantly lower in contacts exposed to M. africanum than in those exposed to M. tuberculosis (1.0% vs. 2.9%; hazard ratio [HR], 3.1 [95% confidence interval {CI}, 1.1-8.7]). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR relative to M. africanum, 6.7 [95% CI, 2.0-22]).M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that tuberculosis variability matters in clinical settings and should be accounted for in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection.
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