Mycobacterium tuberculosis infection in two East African oryxes

Tuberculous lesions were observed at necropsy of 2 East African oryxes (Oryx gazella beisa) at a municipal zoological park in Jackson, Ms. Microscopic examination revealed granulomas containing acid-fast bacilli in the lungs and liver of both animals, as well as in the uterus and mediastinal lymph nodes of 1 animal. Mycobacterium tuberculosis was isolated from the tissues of both oryxes and from fluid aspirated from the mammary gland of 1 oryx; the organism was pathogenic for guinea pigs but not for rabbits.     

Infection with Mycobacterium tuberculosis complicating a pulmonary sequestration

Pulmonary sequestration is a relatively rare malformation. Infection with common pyogenes is a frequent feature in the evolution of this disease. We report a case of intralobar sequestration infected with Mycobacterium tuberculosis in the absence of any other site of tuberculous infection. The patient underwent surgical removal of the affected lobe and subsequent antituberculous chemotherapy. At 1-year follow-up his clinical status is excellent.     

Detection of HIV infection in pulmonary tuberculosis patients

Well documented 112 pulmonary tuberculosis patients were studied for the prevalence of human immunodeficiency virus (HIV) seropositivity by using two antibody screening tests along with western blot test. Nineteen of the pulmonary tuberculosis patients were HIV seropositive, 12 were acid-fast bacillus smear positive; 12 patients were tuberculin skin test positive and 15 patients were culture positive. As the incidence of HIV infection is increasing in India, it is observed that patients co-infected with HIV and TB are also on the rise. Recognition of the dual infection and taking adequate steps to deal with this epidemic are needed.     

PCR-based rapid detection of Mycobacterium tuberculosis in blood from immunocompetent patients with pulmonary tuberculosis

A PCR test based on insertion sequence IS1081 was developed to detect Mycobacterium tuberculosis complex organisms in the peripheral blood. The method was applied to blood samples from immunocompetent individuals with localized pulmonary tuberculosis. Seven of 16 (43.75%) blood samples were found to be positive for the circulating DNA copies of M. tuberculosis complex.     

Diagnosis of pulmonary tuberculosis by the amplicor test for Mycobacterium tuberculosis in induced sputum

The polymerase chain reaction (PCR) technique was compared with the conventional smear and culture method for the detection and identification of Mycobacterium tuberculosis in 25 induced sputa samples. Sputum induction was performed with an ultrasonic nebulizer using 3% hypertonic saline in 27 previously untreated patients suspected of active pulmonary tuberculosis clue to chest X-ray findings, but who were unable to spontaneously expectorate sputum. All patients received anti-tuberculosis drugs for at least 6 months after sputum induction. Two patients could not expectorate sputum after hypertonic saline inhalation. Microscopy failed to detect positive acid-fast bacilli in 25 induced sputa samples. Induced sputa were both PCR- and culture-positive for 10 patients, PCR-positive and culture-negative for 4 patients, and PCR-negative and culture-positive for 2 patients. These results suggest that the PCR method is useful in diagnosing tuberculosis in induced sputum, and that the results of PCR and culture Procedures can complement each other.     

Predictive value of contact investigation for identifying recent transmission of Mycobacterium tuberculosis

BACKGROUND: Abciximab (ReoPro; Eli Lilly and Co, Indianapolis, IN) is a monoclonal antibody that binds to the platelet glycoprotein IIb/IIIa receptor and produces powerful inhibition of platelet function. Clinical trials of abciximab in patients undergoing coronary angioplasty have demonstrated a reduction in thrombotic complications and have encouraged the widespread use of this agent. We have observed a substantial incidence of excessive bleeding among patients who receive abciximab and subsequently require emergency cardiac operations. METHODS: The records of 11 consecutive patients who required emergency cardiac operations after administration of abciximab and failed angioplasty or stent placement were reviewed. RESULTS: The interval from the cessation of abciximab administration to operation was critical in determining the degree of coagulopathy after cardiopulmonary bypass. The median values for postoperative chest drainage (1,300 versus 400 mL; p < 0.01), packed red blood cells transfused (6 versus 0 U; p = 0.02), platelets transfused (20 versus 0 packs; p = 0.02), and maximum activated clotting time (800 versus 528 seconds; p = 0.01) all were significantly greater in the early group (cardiac operation < 12 hours after abciximab administration; n = 6) compared with the late (cardiac operation >12 hours after abciximab administration; n = 5) group. CONCLUSIONS: This report suggests that the antiplatelet agent abciximab is associated with substantial bleeding when it is administered within 12 hours of operation.     

Nontuberculous Mycobacterium pulmonary infection with pleural effusion caused by Mycobacterium kansasii

A 28 year-old man was admitted to our hospital because of fever, cough and chest pain. A chest X-ray film taken on admission showed infiltrate in the left upper lung field with ipsilateral pleural effusion. Microscopical examinations of stained specimens of sputa and pleural effusions disclosed no acid-fast bacilli. The level of adenosine deaminase (ADA) in pleural effusion was 46.4 IU/l. A tuberculin skin test was moderately positive. The most probable diagnosis was pulmonary tuberculosis with pleural effusion. Isoniazid (INH) and rifampicin (RFP) were administered on the 5th hospital day and continued to lower the fever and reduce the pleural effusion. The cultured specimens of sputa and pleural effusions yielded Mycobacterium kansasii. After six months of treatment, chest X-ray film showed improvement and the administration of INH, RFP was discontinued without recurrence.     

Activation of human dendritic cells following infection with Mycobacterium tuberculosis

Dendritic cells (DC) play an essential role in the initiation of primary T cell responses to foreign Ag. It is likely that these potent APC are critical in the initiation of immune responses to pathogens, such as bacteria or parasites. However, little is known about the interaction of these important APC with pathogens. To address this issue, the interaction of the bacterium Mycobacterium tuberculosis with human DC was studied. DC generated from human peripheral blood by short term culture in medium containing recombinant human cytokines granulocyte-macrophage-CSF and IL-4 were capable of phagocytosing M. tuberculosis. Infection of DC with live M. tuberculosis bacilli resulted in increased APC surface expression of the costimulatory molecules CD54, CD40, and B7.1, as well as MHC class I molecules. In addition, infected DC secreted elevated levels of inflammatory cytokines, including TNF-alpha, IL-1, and IL-12. M. tuberculosis-infected human monocytes also secreted inflammatory cytokines, but exhibited no enhancement of costimulatory or MHC class I molecule expression. These data indicate that infection with M. tuberculosis results in the direct activation and maturation of these DC. In vivo, such activation may facilitate migration to the lymph nodes, and enhance presentation of Ag to T cells, thereby facilitating the induction of the immune response against this pathogen.     

Clinical efficacy of the amplified Mycobacterium tuberculosis direct test for the diagnosis of pulmonary tuberculosis

The amplified Mycobacterium tuberculosis direct test (MTD) is a rapid diagnostic test based on a nucleic acid amplification technique, which can be used directly on processed clinical specimens. We evaluated the clinical utility of the MTD for diagnosing pulmonary tuberculosis by comparing the sensitivity and specificity of the test with acid-fast smear, mycobacterial culture, and clinical evaluation. The study included 844 respiratory tract specimens from 421 patients, which were submitted to the microbiology laboratory of our urban teaching hospital over a 6-mo period. Compared with culture, MTD had a sensitivity of 93.6% and specificity of 97.8%. MTD was more sensitive in detecting pulmonary tuberculosis in patients with previously undiagnosed disease (74.7%) than in those with established disease receiving chemotherapy (29.2%), and in smear-positive (95.5%) than in smear-negative (70.0%) disease. There were two false positive MTD results in patients with nontuberculous mycobacteria, for a specificity in this population of 97.3%. We conclude that MTD, when used in conjunction with routine smear and culture, is a useful rapid diagnostic test for suspected pulmonary tuberculosis.     

Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management

Tuberculosis is a serious opportunistic infection in transplant recipients. On the basis of the compilation of published reports in the literature, the incidence of Mycobacterium tuberculosis infection in organ transplant recipients worldwide ranged from 0.35% to 15%. Nonrenal transplantation (P = .004), rejection within 6 months before the onset of tuberculosis (P = .02) and type of primary immunosuppressive regimen (P = .007) were predictors of M. tuberculosis infection occurring within 12 months after transplantation. Thirty-three percent (155) of 476 transplant patients with tuberculosis had disseminated infection; receipt of OKT3 or anti-T cell antibodies (P = .005) was a significant predictor of disseminated tuberculosis. Overall, the mortality rate among 499 patients was 29%; disseminated infection (P = .0003), prior rejection (P = .006), and receipt of OKT3 or anti-T cell antibodies (P = .0013) were significant predictors of mortality in patients with tuberculosis. Clinically significant hepatotoxicity due to isoniazid occurred in 2.5%, 4.5%, and 41% of renal, heart and lung, and liver transplant recipients, respectively. The diagnosis and effective management of tuberculosis after transplantation warrant recognition of the unique epidemiological and clinical characteristics of tuberculosis in transplant recipients.     

Fatal pulmonary infection with Mycobacterium celatum in an apparently immunocompetent patient

Mycobacterium celatum is a recently described mycobacterium isolated from patients who have suppressed cell-mediated immunity, such as AIDS. We present here, to our knowledge, the first report of a fatal pulmonary infection caused by M. celatum in a 73-year-old immunocompetent female patient. The mycobacterium was identified by a 16S rRNA sequence analysis.     

Risk factors for pulmonary tuberculosis in bone marrow transplant recipients

Little is known about the profile of infection with Mycobacterium tuberculosis in bone marrow transplant (BMT) recipients. Of five BMT series with a total of more than 5,000 patients, only 10 cases of M. tuberculosis infection were described, with an overall incidence of 0.19%. We have conducted a prospective evaluation of 183 consecutive BMT recipients, and 10 patients were found to develop pulmonary tuberculosis post-BMT, yielding an incidence of 5.5%. We described the clinical features of these 10 patients, and analyzed the risk factors for development of tuberculosis using age- and sex-matched case control subjects who did not develop the disease. The median age of the 10 patients who developed tuberculosis was 29 yr (range, 17 to 40 yr). The median time for onset of symptoms was 150 d (range, 23 to 550 d), mainly presenting with fever and cough, with infiltrates on chest radiograph. Respiratory tract specimens, mostly sputum, yielded positive smears for acid-fast bacilli in three and positive M. tuberculosis culture in eight, whereas lung tissue histology was the first diagnostic test in two patients. Treatment with standard antituberculosis drugs for a longer duration was highly effective, with no excessive side effects. Risk factors identified for development of tuberculosis included allogeneic BMT (p < 0.05, relative risk [RR] = 23.7), total body irradiation (p < 0. 05, RR = 4.9), and chronic graft-versus-host disease (GVHD) (p < 0. 05, RR = 3.6). It is postulated that chronic GVHD predisposed to development of tuberculosis mainly via disruption of host reconstitution of immune defenses against M. tuberculosis.     

Down-regulation of CD1 on antigen-presenting cells by infection with Mycobacterium tuberculosis

Intracellular pathogens have developed efficient evasion strategies to survive the defenses of the host immune system. In this study, we describe a new escape mechanism utilized by Mycobacterium tuberculosis that involves the down-regulation of the Ag-presenting molecule CD1 from the cell surface of CD1+ APCs. The loss of CD1 from the cell surface is associated with a complete inhibition of the ability of the infected cells to present Ag to CD1-restricted T cells. The down-regulation of Ag-presenting molecules on CD1+ APC by infection with M. tuberculosis is unique for CD1, since the expression of the classical Ag-presenting molecules MHC class I and MHC class II is not influenced. Our data show that efficient down-regulation of CD1 requires infection of the cells with live mycobacteria, since heat killing of the bacteria completely abrogates the effect. The observed down-regulation is not due to the secretion of cytokines or other host- or pathogen-derived factors. Investigation of upstream events responsible for the down-regulation of CD1 revealed that infection with live M. tuberculosis decreased the steady state CD1-mRNA levels. This study introduces a novel evasion mechanism of M. tuberculosis that could contribute to persistence of intracellular infection by avoiding immune recognition.     

Release of superoxide anion from activated mouse peritoneal macrophages during Mycobacterium tuberculosis infection

Mouse peritoneal macrophage monolayers infected with M. tuberculosis were cultured in RPMI up to 7 days. Release of superoxide was assayed on different days in presence or absence of Phorbol myristate acetate (PMA), a known stimulator of NADPH oxidase which is involved superoxide production. Basal level of superoxide release was significantly higher in M. tuberculosis infected peritoneal mouse macrophages (P < 0.01) as compared to normal mouse macrophages. When normal and tuberculoid macrophage cultures were stimulated with PMA, increased superoxide anion release was observed in both the cultures but the increase of superoxide was significantly higher in normal macrophages as compared to tuberculoid stimulated macrophages. Superoxide release was maximum in 4 day old cultured macrophages and gradually it declined in older cultures by day 7, both in vitro and in vivo. A defective macrophage function in killing of M. tuberculosis bacilli was observed after 4 days of in vitro and in vivo cultures.     

Inhibition of pulmonary granuloma formation in mice by treatment with Mycobacterial protoplasm and immuno-suppressants and its relation to protection against aerosol infection with virulent Mycobacterium tuberculosis

Because the pulmonary granuloma formation by mycobacterial cell walls (CW) is likely mediated by cellular immunity, the effect of specific antigens and various immunosuppressants on pulmonary granuloma formation and protection against virulent m. tuberculosis, strain H37Rv was investigated in mice immunized with oil-treated CW from BCG or M. Tuberculosis, strain Aoyama B. Results of desensitization experiments with specific antigens showed that multiple intravenous injections of BCG protoplasm inhibited the footpad delayed hypersensitivity, macrophage migration inhibitory activity of lung cells and pulmonary granuloma formation as well as the enhancement of resistance against aerosol challenge with M, tuberculosis, strain H37Rv. However, treatment with nonspecific immunosuppressants like con A, silica or carrageenan induced only abrogation of footpad delayed hypersensitivity but not prevention of pulmonary granuloma formation or resistance against aerosol challenge. These results suggest a close relationship between pulmonary granuloma formation and protection against H37Rv in mice immunized with oil-treated mycobacterial CW.