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PubMed2000

High frequencies of circulating IFN-gamma-secreting CD8 cytotoxic T cells specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in M. tuberculosis-infected subjects without disease.

MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for protective immunity to Mycobacterium tuberculosis in animal models but their role in humans remains unclear. We therefore studied subjects who had successfully contained M. tuberculosis infection in vivo, i.e. exposed healthy household contacts and individuals with inactive self-healed pulmonary tuberculosis. Using the ELISPOT assay for IFN-gamma, we screened peptides from ESAT-6, a secreted antigen that is highly specific for M. tuberculosis. We identified a novel nonamer epitope: unstimulated peripheral blood-derived CD8 T cells displayed peptide-specific IFN-gamma release ex vivo while CD8 T cell lines and clones exhibited HLA-A68.02-restricted cytolytic activity and recognized endogenously processed antigen. The frequency of CD8 CTL specific for this single M. tuberculosis epitope, 1/2500 peripheral blood lymphocytes, was equivalent to the combined frequency of all IFN-gamma-secreting purified protein derivative-reactive T cells ex vivo. This highly focused CTL response was maintained in an asymptomatic contact over 2 years and is the most potent antigen-specific antimycobacterial CD8 CTL response hitherto described. Thus, human M. tuberculosis-specific CD8 CTL are not necessarily associated with active disease per se. Rather, our results are consistent with a protective role for these ESAT-6-specific CD8 T cells in the long-term control of M. tuberculosis in vivo in humans.

Amino Acid Sequence↗

PubMed2000

Juvenile fulminant adnexal tuberculosis caused by gastrointestinal tuberculosis immediately after ovarian cystectomy.

Genital fulminant tuberculosis is rarely a primary site of infection. We report a case of juvenile adnexal tuberculosis possibly related to tuberculosis immediately after cystectomy in the ileocecal region in a virginal girl. A 13-year-old virginal girl visited our clinic because of a huge ovarian tumor, which was resected by cystectomy. On postoperative day 39, fever episodes were noted, and she received antibiotics, which were not effective. An abscess developed in the region of the cecum and the right adnexa. Laparotomy revealed chronic abscess formation, especially in the right adnexa. Resection of the abscess was done. The pathological diagnosis was tuberculosis with caseation, although bacterial culture and molecular biological diagnosis for Mycobacterium tuberculosis were negative in sputum, vaginal discharge, urine, and stool of the patient and her family. She was placed on anti-tuberculosis drugs, including isoniazid, rifampicin, and ethambutol, and this regimen was effective. This patient represents a rare case of fulminant adnexal tuberculosis without pulmonary disease.

Adnexa Uteri↗

PubMed2005

Spoligotyping of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Mumbai, India.

Tuberculosis remains a major health problem in India, with 2 million new cases and 421,000 deaths each year. In this paper, we describe the spoligotyping results of 216 Mycobacterium tuberculosis culture isolates from patients with pulmonary tuberculosis in Mumbai, India. As spoligotyping data from India have rarely been described until now, and as there is limited information on the major circulating clades of M. tuberculosis, the data obtained were also compared to an international spoligotype database (SpolDB4) that contained patterns from 22,546 isolates from more than 100 countries. Eighty-four (39%) of the isolates were definitively marked as orphan strains, indicating the paucity of such data from India. The remaining 132 isolates clustered among 59 shared types; among these, 42 shared types were already present in the database, 17 were newly created, and 5 of them were specifically reported from Mumbai. A total of 9 major types in this study clustered 32% of the isolates. At the phylogenetic level, 30% of the isolates belonged to the Central Asian families CAS1 and CAS2, of the major genetic group (MGG) 1, 29% to MGG 2 and 3 families (spacers 33-36 missing) and 17% to the ancestral East African Indian (EAI) family. Finally, nearly 10% of the isolates belonged to the W-Beijing family in a broad sense, also in the MGG 1 group. In conclusion, historic clones of the MGG 1 group of M. tuberculosis are responsible for roughly 60% of all tuberculosis cases in Mumbai. Together with the fact that organisms presumably of European descent (such as the Haarlem family) were only rarely found, our observations suggest that tuberculosis in Mumbai, India is essentially caused by historical clones of tubercle bacilli undergoing active circulation due to uncontrolled demography, high prevalence of the disease, and a paucity of resources.

Adult↗

PubMed1995

A multiplex polymerase chain reaction for distinguishing Mycobacterium tuberculosis from Mycobacterium tuberculosis complex.

A multiplex polymerase chain reaction has been developed which is able to distinguish Mycobacterium tuberculosis from other members of the M. tuberculosis complex. The assay is based on the simultaneous amplification of two different targets: a 396bp region from the mtp40 species-specific gene sequence of M. tuberculosis and a 245bp fragment from the M. tuberculosis complex insertion sequence IS986. Results have been obtained for 54 mycobacterial strains including five non-M. tuberculosis complex isolates. All 49 strains of the M. tuberculosis complex were positive for IS986 but only the 27 M. tuberculosis isolates were positive for both IS986 and mtp40.

Base Sequence↗

PubMed1996

Clinical evaluation of a rapid immunochromatographic assay based on the 38 kDa antigen of Mycobacterium tuberculosis on patients with pulmonary tuberculosis in China.

SETTING: A rapid membrane-based antibody assay capable of diagnosing pulmonary tuberculosis within 15 min has been developed using the 38 kDa antigen from Mycobacterium tuberculosis. OBJECTIVE: To determine the specificity and sensitivity of this assay and evaluate its usefulness in a clinical setting. DESIGN: Sera from patients with active pulmonary tuberculosis were obtained from three hospitals in China. The control groups consisted of patients who were diagnosed with lung diseases other than tuberculosis and healthy subjects. RESULTS: Antibody was detected in 54 of 61 (89%) sputum positive patients and 67 of 91 (74%) sputum negative patients who had been clinically diagnosed as having active pulmonary tuberculosis. Five out of 56 (9%) patients with respiratory diseases other than tuberculosis and 1 out of 30 (3%) healthy controls had a positive antibody response. The overall specificity of the assay was 93% and the positive predictive value was 95%. We conclude that this assay is rapid, sensitive and specific and will be a valuable aid in the clinical diagnosis of pulmonary tuberculosis.

Adult↗

PubMed2006

[Consensus document on treatment of tuberculosis exposure and latent tuberculosis infection in children].

INTRODUCTION: The most important causes of the current tuberculosis pandemic are poverty, HIV infection, drug resistance, and the spread of infection by patients with latent tuberculosis infection. In industrialized countries, the main reasons for the increase of this disease are immigration from developing countries and the lack of effective surveillance programs. The situation of children is even more serious as they are more vulnerable to the disease than adults. The children most at risk are those who live with adults at risk for tuberculosis, immigrant children, and adoptees from developing countries. Although children are bacilliferous only exceptionally, the appropriate management of bacilliferous tuberculosis exposure and latent tuberculosis infection in children contributes to the creation of close surveillance of nuclear families and rigorous study of contacts. Moreover, it could prevent serious forms of the disease, which are more frequent in children. OBJECTIVE: The principal objective of this second consensus document of the Spanish Society of Pediatric Infectious Diseases (Sociedad Española de Infectología Pediátrica [SEIP]) is to unify the criteria for the treatment of tuberculosis exposure and latent tuberculosis infection in children. A further aim is to increase awareness of the need for strict detection measures in high-risk populations among health authorities.

Algorithms↗

PubMed1998

Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis.

We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (rGroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN-gamma secretion showed that the most frequently recognized antigen was ESAT-6, followed by MPT59, GroES, MPB70, MPT64, DnaK, GroEL and PstS. The frequency of ESAT-6 responders, as measured both by proliferation (18/19) and secretion of IFN-gamma (16/19) was comparable to the results obtained with whole-cell M. tuberculosis, MT-CF and M. bovis BCG. We also observed that most of the high responders to complex antigens recognized all of the antigens tested (covariation), demonstrating that the repertoire of human T-cell specificities induced by natural infection is directed towards several unrelated culture filtrate as well as somatic-derived protein antigens. In conclusion, the results obtained suggest that the cellular immune response in humans is directed against several important target antigens of M. tuberculosis and that some antigens, such as ESAT-6, are recognized by a high number of individuals. Such antigens represent candidates to be used for development of specific diagnostic reagents or in subunit vaccines.

Antigens, Bacterial↗

PubMed2006

Nosocomial transmission of Mycobacterium tuberculosis in kangaroo mother care units: a risk in tuberculosis-endemic areas.

BACKGROUND AND AIM: Kangaroo mother care (KMC) has become the standard of care for low-risk preterm babies born in developing countries. However, the potential risk of nosocomial transmission of Mycobacterium tuberculosis within KMC units, particularly in tuberculosis-endemic areas, has not been explored. We report an infant (sentinel case) who was admitted to our paediatric intensive care unit (PICU) with extensive pulmonary tuberculosis. METHODS AND RESULTS: When interviewed, the mother reported no household contact with a tuberculosis source case, but mentioned that she shared a KMC room with someone who had symptoms suspicious of tuberculosis. We found molecular evidence that nosocomial transmission of M. tuberculosis occurred within the KMC unit and conducted a contact investigation of all infants exposed to this infectious source case during her stay in the KMC unit. CONCLUSION: We present the findings of the contact investigation and discuss the implications of these findings for KMC units, particularly in tuberculosis-endemic areas.

Contact Tracing↗

PubMed1993

Mycobacterium tuberculosis in household contacts of human immunodeficiency virus type 1-seropositive patients with active pulmonary tuberculosis in Kinshasa, Zaire.

Rates of infection with Mycobacterium tuberculosis were compared in Kinshasa, Zaire, in 521 household contacts of 74 human immunodeficiency virus type 1 (HIV-1)-seropositive index patients and in 692 household contacts of 95 HIV-1-seronegative [corrected] index patients with sputum smear-positive pulmonary tuberculosis: No difference was noted between contacts of HIV-1-seropositive and -seronegative patients. The increasing prevalence of M. tuberculosis infection with increasing age was similar in household contacts of seropositive and seronegative patients; by age 16 years, 75% were purified protein derivative-positive. The similarly low rates of M. tuberculosis infection in household contacts of HIV-1-seropositive and -seronegative index patients with sputum smear-positive pulmonary tuberculosis indicates that HIV-1-seropositive patients with pulmonary tuberculosis are not more infectious than HIV-1-seronegative patients with pulmonary tuberculosis.

Adolescent↗

PubMed2000

A clinical, microbiological and economic analysis of a national service for the rapid molecular diagnosis of tuberculosis and rifampicin resistance in Mycobacterium tuberculosis.

A clinical, microbiological and economic study of a national rapid molecular service for the identification of Mycobacterium tuberculosis and the determination of rifampicin resistance in smear-positive sputum samples (and other primary specimens) was performed. Ninety-one primary specimens, of which 55 were smear-positive sputum, were examined by molecular and conventional assays. Concordance of molecular results from smear-positive sputum specimens with tuberculosis diagnosis and rifampicin resistance by conventional analysis was 52 (94.5%) of 55 and 44 (91.7%) of 48, respectively. Concordance of molecular analysis on all primary specimens was 81 (89.0%) of 91 (diagnosis) and 55 (90.2%) of 61 (rifampicin resistance). Approximately 28 days were saved in the time to diagnosis by using the molecular assay. Hospitals can reduce the cost of inappropriate isolation of patients with risk factors for multiple drug-resistant tuberculosis (MDRTB) who subsequently are shown to have drug-sensitive tuberculosis. At one hospital potential annual savings were between pound sterling 50000 and pound sterling 150000. Of the nine MDRTB cases identified, all had a previous diagnosis of tuberculosis, 78% were born overseas, 44% were known to be non-compliant with therapy, but only one case (12.5%) was HIV positive. HIV status was not significantly different between MDRTB and drug-sensitive tuberculosis cases. Over 75% of specimens were taken while the patient was on therapy. Isolates from >50% of the MDRTB cases were resistant to three or more drugs and one was resistant to seven drugs. All patients were placed on additional therapy once the molecular result was known; this was subsequently modified based on the results of in-vitro drug susceptibility testing. All survived at least 6 months of follow-up. There was no difference in the proportion of successful cultures from smear-positive samples from patients with drug-sensitive tuberculosis or MDRTB who were on therapy. Molecular rifampicin resistance assays are reliable for diagnosis in cases with smear-positive disease.

Adult↗

PubMed1996

Comparison of two 2,3-diacyl trehalose antigens from Mycobacterium tuberculosis and Mycobacterium fortuitum for serology in tuberculosis patients.

Immunoglobulin G antibodies against two 2,3-diacyl trehalose (DAT) antigens from Mycobacterium tuberculosis (DATT) and Mycobacterium fortuitum (DATF) were studied by enzyme-linked immunosorbent assay of 356 serum samples. The sera were obtained from non-tuberculosis-infected individuals (282 serum samples) and tuberculosis patients (74 serum samples). Non-tuberculosis-infected individuals were healthy people (120 serum samples; positive purified-protein-derivative skin test, 60 patients; negative purified-protein-derivative skin test, 60 patients) patients with nontuberculosis lung disease (59 serum samples), contacts of sputum-smear-positive tuberculosis patients (57 serum samples), and human immunodeficiency virus-infected patients with nontuberculosis lung disease (46 serum samples). Of the 74 patients with tuberculosis, 14 were human immunodeficiency virus infected. The sensitivity of the method using DATT was 44.5%, and that with DATF was 48.6%. The specificities with both antigens were 99.1%. There were no significant differences between the mean values for both antigens (P = 0.2815). We therefore concluded that both antigens were interchangeable. As M. fortuitum, a fast-growing mycobacterium, could be a good source of antigen DAT, these results deserve consideration in the serology of tuberculosis.

Antibodies, Bacterial↗

PubMed2006

Influenza virus NS vectors expressing the mycobacterium tuberculosis ESAT-6 protein induce CD4+ Th1 immune response and protect animals against tuberculosis challenge.

Infection with Mycobacterium tuberculosis remains a major cause of morbidity and mortality all over the world. Since the effectiveness of the only available tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is suboptimal, there is a strong demand to develop new tuberculosis vaccines. As tuberculosis is an airborne disease, the intranasal route of vaccination might be preferable. Live influenza virus vaccines might be considered as potential vectors for mucosal immunization against various viral or bacterial pathogens, including M. tuberculosis. We generated several subtypes of attenuated recombinant influenza A viruses expressing the 6-kDa early secretory antigenic target protein (ESAT-6) of M. tuberculosis from the NS1 reading frame. We were able to demonstrate the potency of influenza virus NS vectors to induce an M. tuberculosis-specific Th1 immune response in mice. Moreover, intranasal immunization of mice and guinea pigs with such vectors induced protection against mycobacterial challenge, similar to that induced by BCG vaccination.

Animals↗

PubMed1998

Use of Mycobacterium tuberculosis complex-specific antigen cocktails for a skin test specific for tuberculosis.

The tuberculin skin test currently used to diagnose infection with Mycobacterium tuberculosis has poor diagnostic value, especially in geographic areas where the prevalence of tuberculosis is low or where the environmental burden of saprophytic, nontuberculous mycobacteria is high. Inaccuracy of the tuberculin skin test often reflects a low diagnostic specificity due to the presence in tuberculin of antigens shared by many mycobacterial species. Thus, a skin test specific for tuberculosis requires the development of new tuberculins consisting of antigens specific to M. tuberculosis. We have formulated cocktails of two to eight antigens of M. tuberculosis purified from recombinant Escherichia coli. Multiantigen cocktails were evaluated by skin testing guinea pigs sensitized with M. bovis BCG. Reactivity of multiantigen cocktails was greater than that of any single antigen. Cocktail activity increased with the number of antigens in the cocktail even when the same amount of total protein was used for cocktails and for each single antigen. A cocktail of four purified antigens specific for the M. tuberculosis complex elicited skin test responses only in BCG-immunized guinea pigs, not in control animals immunized with M. avium. These findings open the way to designing a multiantigen formulation for a skin test specific for tuberculosis.

Animals↗

PubMed2004

Evaluation of T-cell responses to novel RD1- and RD2-encoded Mycobacterium tuberculosis gene products for specific detection of human tuberculosis infection.

The tuberculin skin test for diagnosing Mycobacterium tuberculosis infection suffers from antigenic cross-reactivity of purified protein derivative with BCG, resulting in poor specificity in BCG-vaccinated populations. Comparative genomics has identified several genetic regions in M. tuberculosis and M. bovis that are deleted in M. bovis BCG. Proteins encoded in these regions will form the basis of new specific T-cell-based blood tests that do not cross-react with BCG, but only two, early secretory antigen target 6 and culture filtrate protein 10, have been studied in detail in humans. We investigated four novel gene products, encoded by RD2 (Rv1989c) and RD1 (Rv3873, Rv3878, and Rv3879c), that are absent from most or all of the vaccine strains of BCG, respectively. Sixty-seven overlapping peptides were tested in ex vivo gamma interferon enzyme-linked immunospot assays in 49 patients with culture-confirmed tuberculosis and 38 healthy BCG-vaccinated donors. Forty-five percent (95% confidence interval [CI], 31 to 57%) and 53% (95% CI, 39 to 67%) of the tuberculosis patients responded to Rv3879c and Rv3873, respectively, identifying these proteins as major M. tuberculosis T-cell antigens in humans, while 35 and 25% of the patients responded to Rv3878 and Rv1989c, respectively. Of the 38 BCG-vaccinated donors, 1 (2.6%) responded to peptides from Rv3878 and Rv3879c, 3 (7.9%) responded to Rv3873, and none responded to Rv1989c. Exclusion of cross-reactive peptides encoded in conserved motifs of Rv3873, a PPE family member, increased its specificity to 97.4%. The high specificity of Rv3879c peptides and nonconserved Rv3873 sequences, together with their moderate sensitivity in tuberculosis patients, identifies these peptides as candidates for inclusion in new T-cell-based tests for M. tuberculosis infection.

Adolescent↗

PubMed2006

Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis.

Approximately one-third of the human population is latently infected with Mycobacterium tuberculosis, comprising a critical reservoir for disease reactivation. Despite the importance of latency in maintaining M. tuberculosis in the human population, little is known about the mycobacterial factors that regulate persistence and reactivation. Previous in vitro studies have implicated a family of five related M. tuberculosis proteins, called resuscitation promoting factors (Rpfs), in regulating mycobacterial growth. We studied the in vivo role of M. tuberculosis rpf genes in an established mouse model of M. tuberculosis persistence and reactivation. After an aerosol infection with the M. tuberculosis Erdman wild type (Erdman) or single-deletion rpf mutants to establish chronic infections in mice, reactivation was induced by administration of the nitric oxide (NO) synthase inhibitor aminoguanidine. Of the five rpf deletion mutants tested, one (deltaRv1009) exhibited a delayed reactivation phenotype, manifested by delayed postreactivation growth kinetics and prolonged median survival times among infected animals. Immunophenotypic analysis suggested differences in pulmonary B-cell responses between Erdman- and deltaRv1009-infected mice at advanced stages of reactivation. Analysis of rpf gene expression in the lungs of Erdman-infected mice revealed that relative expression of four of the five rpf-like genes was diminished at late times following reactivation, when bacterial numbers had increased substantially, suggesting that rpf gene expression may be regulated in a growth phase-dependent manner. To our knowledge, deltaRv1009 is the first M. tuberculosis mutant to have a specific defect in reactivation without accompanying growth defects in vitro or during acute infection in vivo.

Animals↗

PubMed1994

Evaluation of Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test and PCR for direct detection of Mycobacterium tuberculosis in clinical specimens.

The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTD) is a direct specimen assay for the identification of Mycobacterium tuberculosis from respiratory samples. rRNA is amplified, and the product is detected with a specific chemiluminescent probe. We performed a retrospective evaluation of three separate respiratory specimens from each of 250 patients by using the AMTD and compared the results with those of microscopy, culturing, and a patient chart review. From the latter results, 198 patients (594 specimens) were found negative for M. tuberculosis by culturing and clinical criteria. The overall specificity of the AMTD after discrepancy resolution was 98.5% (585 of 594). There were 52 patients with culture-proven and/or clinically diagnosed tuberculosis. Of these 156 specimens, the organism was cultured from 142 (91%), and acid-fast microscopy was positive for 105 (67.3%). The AMTD was positive for 142 (91%) specimens from these patients. Tuberculosis patient samples were tested by a PCR assay which uses primers for amplification of the IS6110 insertion sequence of the M. tuberculosis complex. The PCR assay detected 144 of the 156 (92.3%) specimens. Overall, when three specimens per patient were examined, the AMTD found all 52 patients positive for tuberculosis, while the PCR assay found 51 patients positive by agarose gel analysis and all 52 patients positive by Southern blot hybridization.

Bacteriological Techniques↗

PubMed1997

Detection of lipoarabinomannan antibodies in patients with newly acquired tuberculosis and patients with relapse tuberculosis.

A commercially available dot immunoassay that employs the lipoarabinomannan antigen was evaluated for the serologic diagnosis of tuberculosis. The test showed a high specificity (100%); however, its sensitivity was low (18.5%). Antibodies to lipoarabinomannan were detected in the sera of 7 of 71 patients with newly acquired tuberculosis and in sera of 10 of 21 patients with relapse tuberculosis. It has been shown by others that sera from patients with relapse tuberculosis had a higher concentration of antibodies and reacted with a greater variety of antigens (native culture filtrates of Mycobacterium tuberculosis H37Rv) than did sera from patients with newly acquired tuberculosis. Our data confirm the results of these previous studies as far as lipoarabinomannan is concerned. We conclude that the differences in the production of antibodies shown by the two groups of tuberculous patients (new and relapse) must be taken into account when assessing the usefulness of serologic tests for the diagnosis of tuberculosis.

Antibodies, Bacterial↗

PubMed1998

Molecular fingerprinting of Mycobacterium tuberculosis and risk factors for tuberculosis transmission in Paris, France, and surrounding area.

Forty-three percent of the tuberculosis cases reported in France are from the Ile de France region. The incidence of tuberculosis in this region is 33 cases per 100,000 inhabitants, twice the national average. A restriction fragment length polymorphism (RFLP) analysis was performed with clinical isolates of Mycobacterium tuberculosis isolated during 1995 in 10 hospitals in Paris and surrounding areas to detect tuberculosis transmission and define the factors associated with clustering in this population. The molecular markers used were the insertion sequence IS6110 and the direct repeat (DR) sequence. Social, demographic, and clinical data were collected from the patients' medical files. Ten patients with isolates with a single copy of IS6110 were excluded from further analysis. Twenty-four patients with false-positive cultures due to laboratory contamination (based on RFLP analysis with IS6110 and examination of patient data) were also excluded. The study was then conducted with 272 strains isolated from 272 patients. Further fingerprinting was performed by using the DR element with strains with patterns by RFLP analysis with IS6110 that differed by one band only and strains with identical patterns by RFLP analysis with IS6110 and with low numbers of copies of IS6110. The combined use of both markers identified unique patterns for 177 strains and clustered 95 (35.7%) strains in 26 groups, each containing isolates from 2 to 12 patients. The clustering was strongly associated with homelessness and the male sex. It was not associated with age, birth in a foreign country, human immunodeficiency virus positivity, or residence in hostels or prison. Isolates from homeless people were often included in large clusters, and homeless people could be the source of tuberculosis transmission for more than 50% of the clustered patients. These results suggest that homeless people play a key role in the spread of M. tuberculosis in the community and that poor socioeconomic conditions are the main risk factors associated with active tuberculosis transmission.

AIDS-Related Opportunistic Infections↗