Diagnosis Of Tuberculosis In Patients Research Articles

An Alternative for Improving the Diagnosis of Smear-Negative Tuberculosis and Other Bronchopulmonary Disorders in Cuba

The diagnosis of tuberculosis in patients with negative acid-fast bacillus smears poses a challenge to both clinicians and public health authorities. In an attempt to aid diagnosis in such cases, an expert committee was established in Ciudad de La Habana, Cuba in 1995. The aim of this study was to describe the progress of the committee's work and the corresponding results for the period 1996 through 2003. For each patient studied by the commission, we analyzed the following data: patient's residence and referring center, tentative diagnosis proposed by the attending physician, history of antibiotic treatment, and final diagnosis made by the commission. Of the 1703 patients studied, 84.8% were from La Habana, 48.4% were 55 years or older, and 63.8% were men. Between 2001 and 2003, 11.3% of patients were already on antituberculosis treatment when their case was studied by the commission. The corresponding percentage for 1996 through 2000 was 16.9% (P=.001). Active tuberculosis was confirmed in 43.1% of a total of 918 patients with full test results during the period 1996 through 2000 and in 52.2% of a total of 619 patients (52.2%) during the period 2001 through 2003 (P< .001). Of 344 patients with suspected pulmonary tuberculosis and negative acid-fast bacillus smears between 2001 and 2003, 128 (37.2%) were diagnosed with active tuberculosis. These findings indicate that the work of the commission is viable, sustainable, and useful for preventing overdiagnosis and inappropriate treatment, and that it also serves an educational purpose.

Prospective Study of Sputum Induction, Gastric Washing, and Bronchoalveolar Lavage for the Diagnosis of Pulmonary Tuberculosis in Patients Who Are Unable to Expectorate

Many adults with pulmonary tuberculosis are unable to expectorate. Gastric washing, sputum induction using nebulized hypertonic saline, and bronchoscopy with bronchoalveolar lavage have all been used to obtain specimens for diagnosis, but to our knowledge, the timing and volume of induced sputum have not been well studied, and these 3 methods have not been compared. The study recruited consecutive adult inpatients with chest radiography findings suggestive of tuberculosis who were unable to expectorate. Subjects provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3. In addition, gastric washing specimens were collected on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage. The study recruited 140 subjects. Among 107 subjects who provided 3 gastric washing specimens and at least 3 induced sputum specimens, 43% had cultures positive for Mycobacterium tuberculosis. Use of 3 induced sputum samples detected more cases than did use of 3 gastric washings (39% vs. 30%; P=.03). Among 79 subjects with culture results for all 5 induced sputum specimens, there was no difference in yield between samples obtained by induced sputum induction performed in a single day or that performed over 3 days (34% vs. 37%; P=.63). There was no association between sputum volume and positive culture results. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy. Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously. Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay.

R2190 Comparison of real-time PCR and BDProbeTec ET system for rapid diagnosis of tuberculosis patients

R2190 Comparison of real-time PCR and BDProbeTec ET system for rapid diagnosis of tuberculosis patients

Tuberculosis in patients undergoing maintenance haemodialysis and renal transplantation.

The difficulty in diagnosis of tuberculosis in patients with chronic renal failure or on immunosuppressive therapy is discussed. Anti-tuberculous therapy was required in 19 out of 315 patients who received a renal transplant in the Urology Unit, Hammersmith Hospital, between February 1961 and December 1979. Twelve patients were from overseas. Their management and the effect of anti-tuberculous therapy on the immunosuppressed patient were also studied. The disease was treated successfully in 18 patients, even though there were problems with diagnosis. The patient who died had active tuberculosis on post-morten examination. Prophylaxis should be considered in patients who have had tuberculosis in the past and may have received inadequate treatment.

Prognostic variables for high titres in a fluorescent antibody test to diagnose tuberculosis

The four hospitals and a tuberculosis clinic in the province of Zeeland, The Netherlands. To assess the usefulness of PPD antibody measurement in the diagnosis of tuberculosis in patients admitted to hospital. Sixty-one patients presenting with active tuberculosis, and 215 control patients were included in the study. Initial serum PPD antibody titres were determined with a macrophage uptake Fluorescent antibody test (MuFat) to construct a discrimination model between Tuberculosis (TB) and non-TB. We also retrospectively collected clinical parameters of the TB patients at presentation. Univariate and multivariate logistic regression are used to identify variables predicting high antibody titres. In TB patients, the presence of clinical symptoms (OR=10.63) and the presence of at least two concurrent non-lymph node disease localizations outside thorax and abdomen (OR=13.94) are necessary and sufficient to predict high titres. The logistic model shows a significant contribution of the 2log (titre) to the discrimination between TB and non-TB patients. At a cut-off value of 128, a specificity, sensitivity, and positive predictive and negative predictive values of 97%, 39%, 80% and 85%, respectively, are calculated in the study cohort. Our data suggest an application of the test at high cut-off values for timely diagnosis of difficult-to-diagnose TB patients. The results of this retrospective study will have to be confirmed in further prospective studies.

Detection of Mycobacterium Tuberculosis in Bronchial Specimens Using a Polymerase Chain Reaction in Patients with Bronchial Anthracofibrosis

Background : To Investigate the association between bronchial anthracofibrosis (AF) and tuberculosis (TB), and the clinical utility of a polymerase chain reaction (PCR) on bronchial specimens for rapid diagno-sis of active pulmonary TB in patients with bronchial AF. Method : Thirty patients (25 women and 5 men ranging in age from 53 to 88), who were diagnosed with bronchial AF by a bronchoscopic exami-nation, were enrolled in this study. PCR targeting the IS6110 segment of Mycobacterium tuberculosis was performed on the bronchial wash fluid and anthracofibrotic bronchial tissue. The PCR results were compared with the bacteriological, histological, and clinical findings. Results : Eighteen of the 30 patients (60%) were associated with TB, nine of whom were confirmed as having active TB. The remaining 9 had a past history of TB. The sputum or bronchial aspirate AFB smear, culture, and histological findings were positive in 4 (13%), 9 (30%), and 5 (17%) patients, respectively. PCR of the AF tissue and bronchial wash fluid was positive in 5 (17%) and 11 (37%) of the 30 patients, respectively. PCR was more sensitive than the AFB smears for diagnosing pulmonary TB (22 % us 89 %, respectively, p

Profile of a 24 kDa Mycobacterium tuberculosis antigen in the urine samples of tuberculosis patients under therapy regime

Secretion of a low molecular weight (24 kDa) Mycobacterium tuberculosis-specific antigen was analysed in the urine samples of tuberculosis patients under antimycobacterial therapy regime. The urine samples of sputum-positive and culture-positive tuberculosis patients under therapy regime were collected after 2, 3, 4, 5 and 6 months of antimycobacterial therapy. After concentration of the samples by ultrafiltration the proteins were resolved by SDS–PAGE. The antibodies raised in rabbits against M. tuberculosis strain H37Ra were used to check specificity of the bands by Western blotting. It was found that the tuberculosis patients secreted a 24 kDa M. tuberculosis-specific antigen in their urine. This band was present in the samples taken upto 5 months of drug therapy but was absent in the samples taken after 6 months of antimycobacterial therapy. This study gives evidence in support of the continuation of chemotherapy of tuberculosis patients for at least 6 months. Also, the 24 kDa excreted/secreted antigen can be used as a marker for monitoring the drug therapy as well as for the diagnosis of tuberculosis patients. Moreover, the urine sample taken in the study is a non-invasive and safer sampling method as compared to sampling blood or sputum which is the usual procedure in these patients.

Clinical evaluation of the Roche AMPLICOR PCR Mycobacterium tuberculosis test for detection of M. tuberculosis in respiratory specimens

The reliability of the Roche AMPLICOR Mycobacterium tuberculosis test (AMPLICOR MTB) for the diagnosis of pulmonary tuberculosis was evaluated by testing 956 respiratory specimens from 502 patients and comparing results with results by culture and medical history. Of those 135 specimens that were culture positive for mycobacteria, 61 specimens from 31 patients grew M. tuberculosis. Fifty-two specimens were smear positive for acid-fast bacteria (AFB); M. tuberculosis was isolated from 41 of these specimens. On initial testing, the sensitivity and specificity of the AMPLICOR MTB assay, compared with culture, were 78.7 and 99.3%, respectively. After resolution of discrepancies (by review of medical history), the sensitivity, specificity, and positive and negative predictive values of the AMPLICOR MTB assay were 79.4, 99.6, 92.6, and 98.6%, respectively. Two specimens from two patients with no clinical evidence of tuberculosis were AMPLICOR MTB positive and culture positive for Mycobacterium avium complex. For AFB smear-positive specimens, the sensitivity, specificity, and positive and negative predictive values of AMPLICOR MTB were 97.6, 100, 100, and 90.9%, respectively. For AFB smear-negative specimens, the sensitivity, specificity, and positive and negative predictive values of AMPLICOR MTB were 40.0, 99.5, 69.2, and 98.7%, respectively. Our results support the use of AMPLICOR MTB for rapid diagnosis of tuberculosis in patients whose respiratory specimens are AFB smear positive. Further studies are needed to determine the most clinically relevant and cost-effective use of this assay with AFB smear-negative specimens.

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 β-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.

Utility of the Gallium-67 Citrate Scan for the Early Diagnosis of Tuberculosis in Patients Infected with the Human Immunodeficiency Virus

Diagnosis of tuberculosis in patients infected with the human immunodeficiency virus (HIV) is sometimes difficult because of atypical clinical and radiographic findings. The aim of this retrospective study was to determine the utility of a gallium-67 citrate scan (67Ga scan) of the chest for the early diagnosis of tuberculosis in patients infected with HIV. We selected 174 67Ga scans performed as a part of the clinical evaluation of 145 HIV-infected patients with normal pulmonary parenchyma (seen on chest radiographs) and fever of unknown origin. Scans were evaluated as to whether there was uptake in lymphoid regions (a positive 67Ga scan) or not (a negative scan). Tuberculosis was the most common condition associated with a positive 67Ga scan (48[72.7%] of 66 positive 67Ga scans). Nodal uptake had a 72.7% positive predictive value and a 92.6% negative predictive value for tuberculosis. In our experience, 67Ga scanning is a useful tool for the clinical evaluation of HIV-infected patients with unexplained fever. In areas with a high prevalence of tuberculous infection, a 67Ga scan of an HIV-infected patients that shows nodal uptake allows the clinician to initiate prompt empirical antituberculous therapy while waiting for culture results. Conversely, a 67Ga scan that does not show nodal uptake makes the diagnosis of tuberculosis unlikely.

The role of fiberoptic bronchoscopy for diagnosis of pulmonary tuberculosis in patients at risk for AIDS

The role of fiberoptic bronchoscopy for diagnosis of pulmonary tuberculosis in patients at risk for AIDS

Yield of Bronchoscopy for the Diagnosis of Tuberculosis in Patients with Human Immunodeficiency Virus Infection

The efficacy of bronchoscopy for the diagnosis of tuberculosis in patients infected with human immunodeficiency virus (HIV) has not been systematically evaluated. We therefore compared the diagnostic yield of bronchoscopy in 67 HIV-infected and 45 non-HIV-infected patients with culture-proven pulmonary tuberculosis. In all cases, acid-fast smears of sputum were negative or not obtained prior to bronchoscopy. Prebronchoscopic sputum culture yielded Mycobacterium tuberculosis in 34 (89 percent) of 38 HIV-infected patients and 26 (93 percent) of 28 non-HIV-infected patients from whom specimens were obtained. Bronchoscopy provided an early diagnosis of tuberculosis (positive acid-fast smear or granulomata on biopsy) in 23 (34 percent) of the HIV-infected patients and 20 (44 percent) of the patients without HIV infection. The sensitivities of the acid-fast smear and of mycobacterial culture of bronchoscopic specimens and postbronchoscopic sputum were similar in patients with or without HIV infection. In HIV-infected patients, granulomatous inflammation was noted on transbronchial biopsy in 11 (19 percent) of 59 patients with HIV infection, compared to 16 (43 percent) of 37 patients without HIV infection (p = 0.01). Nevertheless, transbronchial biopsy provided the exclusive means for an early diagnosis of tuberculosis in six (10 percent) of 59 HIV-infected patients. We conclude that the yield of bronchoscopy for the diagnosis of pulmonary tuberculosis in HIV-infected patients is similar to that in patients without HIV infection, and that transbronchial biopsy provides incremental diagnostic information not available from evaluation of sputum or bronchoalveolar lavage fluid.

Bacteremia Due to Mycobacterium tuberculosis in Patients with Human Immunodeficiency Virus Infection

Mycobacterium tuberculosis bacteremia is being reported more frequently in patients with human immunodeficiency virus, type 1 (HIV-1) infection. We report 9 patients with bacteremia due to M. tuberculosis and HIV infection who were identified over a 36-month period. Of the 9 patients studied, 8 were male, 8 were black, 6 were born in Haiti, 3 were homeless, 2 were intravenous drug users, and 1 was homosexual. At the time of diagnosis, 3 patients had the acquired immunodeficiency syndrome (AIDS) and 5 patients had CD4 lymphocyte counts less than or equal to 170 cells/mm3, indicating marked immunodeficiency. All 9 patients presented with temperature greater than 38.3 degrees C, 5 (50%) had abnormal chest roentgenogram on admission, and each of the patients tested had elevations of at least 2 liver function tests. Eight patients (80%) had M. tuberculosis isolated from sputum or other body fluids and tissues. All blood isolates of M. tuberculosis were identified from Dupont Isolator tubes. Antibiotic-resistant isolates of M. tuberculosis were cultured from 3 of the 6 patients born in Haiti. One patient died before diagnosis and received no antimycobacterial therapy; 7 of the remaining 8 patients appeared to respond to treatment. Our data, and a review of the literature, suggest that bacteremia due to M. tuberculosis is becoming more frequent, and that blood cultures may be helpful in establishing or confirming a diagnosis of tuberculosis in patients with HIV-1 infection.

Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection

purpose: To determine the frequency with which the diagnosis of tuberculosis is delayed in patients with concomitant human immunodeficiency virus (HIV) infection, and to identify reasons for such delays. patients and methods: We reviewed medical records of 52 consecutive HIV-infected patients with culture-proven tuberculosis seen at a 1,900-bed general hospital serving a predominantly indigent population in Los Angeles, where the prevalences of HIV infection and tuberculosis are high. The late-treatment (LT) group consisted of 25 patients in whom tuberculosis was untreated prior to death (n = 6) or treated more than 22 days after presentation (n = 19). The early-treatment (ET) group comprised 27 patients in whom antituberculous therapy was begun less than 16 days after presentation. results: Symptoms, physical and laboratory findings, chest roentgenographic abnormalities suggestive of tuberculosis (hilar adenopathy, pleural effusion, miliary pattern, cavitation, predominant upper lobe infiltrate), and frequencies of concomitant nontuberculous disease were similar in LT and ET groups. Delayed diagnosis of tuberculosis was attributable to errors in management in 21 (84%) of 25 LT group patients. The most common error was failure to obtain at least three sputum samples for acid-fast smear and mycobacterial culture in patients with clinical and chest roentgenographic findings compatible with tuberculosis (15 cases). Acid-fast sputum smears were positive in 25 (61%) of 41 cases of pulmonary tuberculosis. Acid-fast smears of stool were positive in eight (42%) of 19 cases. Blood cultures yielded Mycobacterium tuberculosis in 18 (38%) of 48 cases. conclusions: Delayed therapy of tuberculosis in HIV-infected patients at our medical center was common and was not due to atypical manifestations of tuberculosis. In most cases, delays could have been avoided if adequate numbers of sputum samples for acid-fast smear and mycobacterial culture had been obtained, and if empiric antituberculous therapy had been given to symptomatic patients in whom chest roentgenographic findings were suggestive of mycobacterial disease.

Value of ELISA Using A60 Antigen in the Diagnosis of Active Pulmonary Tuberculosis

This investigation was undertaken to assess the effectiveness of an enzyme-linked immunosorbent assay (ELISA) using A60 antigen in ascertaining diagnosis in hospitalized patients suspected to have pulmonary tuberculosis (TB) but with negative sputum stains. Cultures were performed to confirm active or inactive disease. IgG and IgM antibody activity was determined by adding a 1:100 dilution of serum to plates coated with A60 antigen. After addition of peroxidase-conjugated antihuman IgG or IgM and color development, optical density (OD) was determined. A total of 83 patients was studied, taking into account their current disease status and prior history. Using as a cutoff value the mean value +/- 2 SD measured in the negative culture, no TB history group, that is, OD = 0.50 for IgG measurements and 0.43 for IgM measurements, the sensitivity, specificity, and positive predictive value of IgG measurements were equal to 48, 71, and 50%, respectively. Using IgM measurements, these parameters were equal to 76, 98, and 95%, respectively. Combining the results of IgG and IgM measurements, sensitivity, specificity, and positive predictive value were equal to 68, 100, and 100%, respectively. Thus, the ELISA described here can greatly facilitate the diagnosis of TB in patients with negative smears.

Anterior Segment Upper Lobe Tuberculosis in the Adult: Occurrence in Primary and Reactivation Disease

Nine patients with pulmonary tuberculosis involving predominantly or exclusively the anterior segment of one or both upper lobes were seen over a five-year period. The incidence of anterior segment upper lobe tuberculosis was 6.3 percent of 142 patients presenting with pulmonary tuberculosis during the same time period. Five of the nine patients with anterior segment upper lobe involvement had reactivation disease. An increased incidence of advanced age, diabetes, associated malignant neoplasms, alcoholism, and steroid use were noted in those patients with anterior segment involvement, although only the occurrence of diabetes was statistically significant. We suggest vigilance with regard to the diagnosis of tuberculosis in patients who are elderly, diabetic, or alcohol abusers, particularly where the roentgenographic appearance of anterior segment upper lobe involvement would tend to favor an alternative diagnosis.

Transbronchial Biopsy Culture in Pulmonary Tuberculosis

Fiberoptic bronchoscopy is well established as a useful tool in the diagnosis of suspected cases of pulmonary tuberculosis that are sputum smear-negative. However, little attention has been focused on the role of transbronchial biopsy culture in the bacteriologic diagnosis of the disease. In this series of 12 patients with culture-proven pulmonary tuberculosis, we reviewed the results of transbronchial biopsy culture in comparison to the culture of prebronchoscopy sputa, postbronchoscopy sputa and bronchial washings. We found that transbronchial biopsy culture yielded positive cultures in only 16 percent (2/12) of these cases of proven tuberculosis and that transbronchial biopsy culture was not an exclusive source of culture-positive material in any of the patients studied. Although fiberoptic bronchoscopy may be quite helpful in establishing the diagnosis of tuberculosis in patients that are sputum smear-negative, our findings indicate that culture of transbronchial biopsy specimens contribute little to the bacteriologic diagnosis.

Lymphocyte transformation. An aid in the diagnosis of tuberculosis in patients with nonreactive skin tests.

Lymphocyte transformation in vitro after exposure to purified protein derivative (PPD) was demonstrated in 7 patients with proved or probable active tuberculosis who failed to react to intradermal PPD. Six of the 7 ultimately became reactive to PPD 19 days to 3 months after in vitro transformation was first observed. It is suggested that the lymphopenia observed in these patients might have been responsible for the lack of intradermal reactivity. The lymphocyte transformation test appears to offer a valuable addition to the clinical armamentarium available for the diagnosis of tuberculosis.