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PubMed2005

[Hepatosplenic tuberculosis in children].

Isolated tuberculous involvement of the liver and spleen is infrequent. We report such a case in a child. The differential diagnosis of isolated multi-nodular diseases of the liver and spleen is reviewed.

Child↗
PubMed1998

[Disseminated tuberculosis in non-immunocompromised host: three case reports].

INTRODUCTION: Disseminated tuberculosis, i.e., tuberculosis involving lung, liver, spleen, bone marrow and lymph nodes is rare (2.8%), particularly when immunocompromised diathesis is lacking. EXEGESIS: We report three cases of disseminated tuberculosis confirmed by bacteriology or histology, which occurred in non-immunocompromised patients. Disease evolution under antituberculous treatment was favorable in two cases and fatal in the third one. CONCLUSION: Disseminated tuberculosis must be suspected when miliary pulmonary lesions are associated with hematologic abnormalities, even in non-immunocompromised host. Early treatment is mandatory to avoid fatal outcome.

Adult↗
PubMedDate not supplied

CT appearances in abdominal tuberculosis. A pictorial essay.

Abdominal tuberculosis continues to be endemic in the developing world and has shown a resurgence in the West. Computed tomography (CT) evaluation is singularly informative as it demonstrates involvement of the bowel, peritoneum, lymph nodes, and solid organs in a single examination. A spectrum of CT findings in an immunocompetent population is presented, ranging from subtle to advanced and common to rare. Genitourinary tuberculosis and tuberculosis in AIDS are excluded as they merit separate discussions.

Humans↗
PubMed2003

The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice.

Long-term survival of nonreplicating Mycobacterium tuberculosis (Mtb) is ensured by the coordinated shutdown of active metabolism through a broad transcriptional program called the stringent response. In Mtb, this response is initiated by the enzymatic action of RelMtb and deletion of relMtb produces a strain (H37RvDeltarelMtb) severely compromised in the maintenance of long-term viability. Although aerosol inoculation of mice with H37RvDeltarelMtb results in normal initial bacterial growth and containment, the ability of this strain to sustain chronic infection is severely impaired. Significant histopathologic differences were noted in lungs and spleens of mice infected with H37RvDeltarelMtb compared with controls throughout the course of the infection. Microarray analysis revealed that H37RvDeltarelMtb suffers from a generalized alteration of the transcriptional apparatus, as well as specific changes in the expression of virulence factors, cell-wall biosynthetic enzymes, heat shock proteins, and secreted antigens that may alter immune recognition of the recombinant organism. Thus, RelMtb is critical for the successful establishment of persistent infection in mice by altering the expression of antigenic and enzymatic factors that may contribute to successful latent infection.

Adaptation, Physiological↗
PubMed1966

Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues.

A previously reported form of microbial persistence whereby large populations of tubercle bacilli can be made to "vanish" uniformly from the tissues of mice has been shown to occur generally throughout each group of animals subjected to the experimental procedure; it does not reflect the eradication of the bacilli in the majority of animals with their persistence and ultimate revival in only a minority. The one demonstrable alteration of the tubercle bacilli while "vanished" is that they are sterile. Thus, they are undetectable by cell-free culture, tissue culture, and blind animal passage, i.e. by any method based on microbial multiplication. Whether they have also undergone alteration in morphology and persist in some unconventional form cannot be stated. Acid-fast forms similar to tubercle bacilli can be detected in small numbers by intensified microscopic search of tissue homogenates but the relationship of these forms to the sterile bacilli that ultimately revive is unclear. Thus, the persisting tubercle bacilli are more correctly designated as being in a "sterile state" than one of true latency. The uniform induction of the sterile state is a specific phenomenon requiring the participation of both the nicotinamide derivative, pyrazinamide, and isoniazid. Once assumed, this sterile state is relatively stable and the time required for revival of the tubercle bacilli in the spleens in one-half the animals is seven months. This process can be speeded up by the administration of large doses of cortisone in the third or fourth month after sterilization but revival is not significantly affected by the administration of cortisone earlier.

Animals↗
PubMed1966

Microbial persistence. II. Characteristics of the sterile state of tubercle bacilli.

The capability of tubercle bacilli to assume a long continued sterile state in the tissues when exposed to pyrazinamide and isoniazid is a highly specific drug-microbe phenomenon in which host participation is not critical. Although it is the pyrazinamide that possesses the sterilizing type of action, the role of the isoniazid is specific and essential. The isoniazid serves to convert a phenomenon that occurs irregularly with pyrazinamide alone into one that occurs with a high degree of uniformity. The observations suggest a competition between isoniazid and the pyrazinamide (or its parent nicotinamide) for a site or entrance in or on the tubercle bacilli and for sterilization, the isoniazid apparently must reach the site first. The rare failures to attain complete sterilization, appear to depend on the emergence of pyrazinamide-resistance which prevents the necessary dependent action of the two drugs. Populations already in the sterile state are nevertheless subject to a continued drug influence. Whether this represents a direct action on the sterile bacilli or an indirect effect produced by making the environment hostile to microbial revival, cannot be determined from the present observations.

Animals↗
PubMed1997

Sites of tuberculous involvement in patients with AIDS. Autopsy findings and evaluation of gallium imaging.

The purpose of this study was to review autopsy and gallium scan findings in two different acquired immune deficiency syndrome (AIDS) patient populations who had a confirmed diagnosis of tuberculosis (TB) to identify organs involved and accuracy of clinical diagnosis. The first group was comprised of 29 autopsies between January 1982 and December 1994, including only 18 patients who were diagnosed before death. Organs most commonly involved were the lymph nodes (59%), lungs (56%), spleen (53%), liver (45%), and kidneys (37%). Other opportunistic infections were present in 18 (59%) of autopsies, with more than one opportunistic infection present in 11 (37%) of the autopsies. Lungs were involved in 79% of all autopsies. The second population group included 94 patients with AIDS with a proven diagnosis of TB, only 24 of whom had gallium scans in the period between January 1992 and December 1994. Chest x-ray results were negative in 4 patients (17%); gallium scan results were positive in 16 patients (66%). The reasons for false-negative gallium scan results were due to anti-tuberculous treatment for periods varying from 2-21 months in 7 patients or the presence of extra pulmonary tuberculosis. The sites of TB involvement in the chest were: lung parenchyma in 5 patients (19%, 4 in mid and lower lung, and 1 in upper fields). There was lymph node involvement in all 16 patients (24 locations with mediastinal involvement in 23%, supraclavicular 23%, axillary 11%, retroperitoneal 11%, and inguinal region in 4%. We conclude that (1) tuberculosis in patients with AIDS behaves similar to primary tuberculosis; (2) the combination of chest x-ray and gallium imaging is sensitive for the diagnosis of pulmonary tuberculosis in patients with AIDS; (3) the involvement of mediastinal lymph nodes in gallium scans in the presence or absence of chest x-ray abnormalities should raise the possibility of TB involvement in patients with human immunodeficiency virus; (4) anti-TB treatment decreases the sensitivity of gallium scan.

AIDS-Related Opportunistic Infections↗
PubMed1994

In vivo activity of paromomycin against susceptible and multidrug-resistant Mycobacterium tuberculosis and M. avium complex strains.

Encouraged by in vitro results, we have assessed the in vivo activity of paromomycin (PRM) against Mycobacterium tuberculosis, multidrug-resistant (MDR) M. tuberculosis (resistant to isoniazid, rifampin, and streptomycin), and Mycobacterium avium complex in C57BL/6 mice and their beige counterparts. In all these experiments, PRM was effective in preventing mortality from a mycobacterial infection and was significantly more active than the drug-free control (P < 0.0005) in reducing the CFU relative to the mean log CFU in the lungs, livers, and spleens of infected animals. In the drug-susceptible M. tuberculosis experiment, PRM given at 100 and 200 mg/kg of body weight was significantly less active than isoniazid at 25 mg/kg (P < 0.0005) in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. In the MDR M. tuberculosis experiment, PRM given at 200 mg/kg was effective, relative to the drug-free control, in reducing the mean log CFU of an isolate of M. tuberculosis resistant to isoniazid, rifampin, and streptomycin. In the M. avium complex experiment, PRM given at 200 mg/kg was as effective as amikacin at 50 mg/kg in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. On the basis of our experiments, we believe that PRM has promising activity in vivo in the treatment of infections caused by M. tuberculosis, MDR M. tuberculosis, and M. avium complex.

Animals↗
PubMed1984

Efficacy of Mycobacterium bovis BCG vaccination in mice undergoing prior pulmonary infection with atypical mycobacteria.

The efficacy of Mycobacterium bovis BCG immunization in mice with established pulmonary infections caused by atypical mycobacteria was studied. In all four strains of Mycobacterium tested (M. kansasii, M. simiae, M. avium, and M. scrofulaceum), intravenous inoculation with 10(6) BCG had no discernible effect upon the course of atypical mycobacterial infection within the lungs; despite this, however, all BCG-vaccinated groups of mice were fully resistant to a subsequent acute aerogenic challenge with M. tuberculosis H37Rv, regardless of the presence of the pulmonary atypical mycobacterial infections. Furthermore, animals infected with M. kansasii, M. simiae, or M. avium but not vaccinated with BCG expressed considerable antituberculous resistance within the lungs, resulting in significant prolonged survival of these animals. The relevance of these findings to the expression of antituberculous resistance in human populations in areas in which atypical mycobacteria are endemic and the failure of these findings to support the hypothesis that prior contact with atypical mycobacteria might in some way jeopardize or interfere with the efficacy of subsequent BCG vaccination are discussed.

Animals↗
PubMed1997

Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae.

A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-gamma) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-gamma. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.

Administration, Oral↗