Outbreak of pulmonary tuberculosis in which tuberculosis developed from QuantiFERON-TB second generation (QFT-2G) test negative persons

PURPOSE: To clarify the points to be considered when QFT-2G tests are used in the contacts examination by public health center. OBJECT & METHOD: We analyzed the results of contacts examination on 43 workplace colleagues (39 y/o and younger) of a pulmonary tuberculosis patient (bII2, Gaffky 9, cough for 1.5 months). RESULTS: After two months of the last contact with the index case, tuberculin skin tests, QFT-2G tests and chest X-rays were undertaken. After 6 months, chest X-rays were taken, and after 9 months, QFT-2G tests and chest CT scans were also undertaken. The tuberculin skin tests after two months showed a bimodal distribution, and 10 were QFT-2G positive and 2 showed doubtful reaction. The latter 12 persons underwent chemoprophylaxis. After 6 months, however, out of 31 QFT-2G negative persons, 2 developed pulmonary tuberculosis. Moreover, after 9 months, chest CT scans revealed 5 pulmonary tuberculosis patients. Three out of 7 new patients showed positive or doubtful reactions in QFT-2G tests undertaken after 9 months. DISCUSSION AND CONCLUSION: The sensitivity of QFT-2G tests is reported to be 80 to 90%, and the possibility of false negative is not negligible. We propose measures for public health center to conduct the contacts examination as follows; In case of high QFT-2G positive (including doubtful reaction) rate and/or a bimodal distribution of tuberculin skin test result, many infected persons are likely to be included in the group; and the following measures are recommended; 1) Necessity of chemoprophylaxis should be judged considering both tuberculin skin test results and the situation of contact with the index case, and not only by QFT-2G test results. 2) QFT-2G negative persons also need to be followed with chest X-rays.     

Whole lung tuberculosis. A disease with high mortality which is frequently misdiagnosed.

The mortality rate of WLTB was significantly higher than non-WLTB in 45 of 516 cases of PTB in a 24-month period. There is no known underlying disease predisposing to WLTB. Clinically, the patients were significantly more toxic and had lower serum albumin and hemoglobin levels than non-WLTB patients. They had a lower rate of positive PPD tuberculin skin tests. The chest roentgenograms revealed three patterns: (1) DBS type in 15--all with multiple or diffuse opacities with or without cavitations; (2) DHS type in 20--eight with typical miliary lesions and 12 with atypical miliary patterns; (3) combined focal PTB and DHS type in ten. We found that atypical chest roentgenographic patterns were common in WLTB and frequently led to misdiagnosis. The delayed diagnosis and treatment of this advanced disease resulted in the high mortality. Early, empirical antituberculosis chemotherapy is indicated and life-saving.     

Pleuritis as a manifestation of reactivation tuberculosis

PURPOSE: The purpose of this study was to determine the frequency with which tuberculous pleuritis is a manifestation of reactivation tuberculosis and to compare the clinical manifestations of reactivation tuberculous pleuritis with "classic" tuberculous pleuritis, in which chest roentgenograms reveal no parenchymal infiltrates. PATIENTS AND METHODS: We evaluated the medical records of 59 patients in whom tuberculous pleuritis was confirmed by histologic findings or mycobacterial culture. Twenty-seven patients (46%) had typical chest roentgenographic findings of reactivation tuberculosis, whereas 32 (54%) had classic tuberculous pleuritis. The clinical and laboratory features of these two groups were compared. RESULTS: Symptoms were more prolonged and pleural fluid glucose and lactate dehydrogenase concentrations were more markedly abnormal in patients with reactivation pleuritis than in those with classic pleuritis, suggesting a more chronic inflammatory process in the former group. Compared with patients with classic tuberculous pleuritis, those with reactivation pleuritis had a lower frequency of reactive tuberculin skin tests (61% versus 88%) and granulomatous pleural inflammation (25% versus 72%), but a higher bacillary burden, manifest by a higher frequency of positive sputum smears for acid-fast bacilli (50% versus 0%) and positive mycobacterial cultures from sputum (60% versus 23%) and pleural fluid (91% versus 66%). CONCLUSIONS: In contrast to previous reports, tuberculous pleuritis was a manifestation of reactivation tuberculosis in 46% (27 of 59) of patients. Tuberculous pleuritis is a more chronic process in patients with reactivation disease than in those with classic pleuritis. The lower frequency of reactive tuberculin skin tests and granuloma formation, combined with the higher bacillary burden in patients with reactivation pleuritis, suggest that these patients mount a less effective immune response to Mycobacterium tuberculosis infection than do patients with the classic form of tuberculous pleuritis.     

Unrecognised tuberculosis in HIV-infected patients: sputum culture is a useful tool.

Diagnosis of tuberculosis is challenging, especially in human immunodeficiency virus (HIV) positive persons who may have atypical clinical and radiographic features. We report the isolation of Mycobacterium tuberculosis from sputum samples of 10 (4%) HIV-positive persons who were asymptomatic with normal chest radiographs and negative sputum smears for acid-fast bacilli. Six of them had strongly positive tuberculin reactions while four were severely immunosuppressed. Our observation highlights the utility of routine sputum culture in the diagnosis of tuberculosis in high-risk individuals.     

The low yield of routine radiographic screening of tuberculin-positive hospital employees

On the basis of limited benefit in relation to cost, mass radiographic screening for tuberculosis was challenged and abandoned in the 1970s. In the 1980s the value of such periodic screening of hospital employees with known positive tuberculin reactions was queried on the same grounds but without comparable data. We report here the results of 11 years of radiographic screening of tuberculin-positive employees of a university hospital. Although 3900 chest films were obtained at considerable cost, only one proved and six suspect cases of tuberculosis were detected, all of which were symptomatic. Even in the absence of symptoms all could have been identified by other screening criteria, five on the basis of recent tuberculin conversion and two as tuberculin-positive new employees. These data support the recent statement that periodic chest roentgenograms of hospital employees with known positive reactions to tuberculin skin testing are not justified.     

Decision analysis, public health policy, and isoniazid chemoprophylaxis for young adult tuberculin skin reactors

As part of a plan to eliminate tuberculosis in America, tuberculin skin testing was advised for all US citizens, with isoniazid chemopreventive therapy administered to appropriate positive reactors. Implementation of this plan, however, may be limited by concerns over which skin test reactors should receive isoniazid therapy. Recent decision analyses suggest that, contrary to American Thoracic Society guidelines, asymptomatic skin test reactors under age 35 years with normal chest roentgenograms and no predisposing conditions to tuberculosis reactivation will not benefit from isoniazid chemopreventive therapy. Repeated analysis of these studies reveals that calculated life expectancy depends on estimates of the probability of certain chance outcomes. If the isoniazid-related hepatitis case-fatality rate is below 1%, isoniazid chemopreventive therapy appears to be beneficial. A literature review suggests that this rate is indeed this low. If the tuberculosis case-fatality rate is above 6.7%, also supported by the literature, the advantages of isoniazid therapy are further increased. This repeated analysis should reassure physicians that isoniazid chemoprophylaxis for tuberculin skin test reactors is beneficial to the individual and consonant with public health policies.     

Tuberculosis in physicians. Compliance with preventive measures

Compliance with public health recommendations for tuberculosis control was evaluated by a survey of 4,417 physicians who had not contracted tuberculosis during medical school nor during the 4 decades after graduation through 1981. Thirty-one percent of the cohort had been vaccinated with bacille Calmette-Guérin (BCG) and 47% considered themselves tuberculin-positive. Thirty-two percent of 1,088 physicians who graduated after 1974 had been exposed to 3 or more patients with infectious tuberculosis in the previous year. Fifty-eight percent of 738 unimmunized, tuberculin-negative physicians who had been exposed to one or more patients with infectious tuberculosis in the previous year had tuberculin tests every 1 to 2 yr. Forty-nine percent of 597 unimmunized tuberculin reactors with similar occupational exposure had chest roentgenograms every 1 to 2 yr. The BCG-vaccinated physicians were less likely to have frequent tuberculin tests but no different frequency of chest roentgenograms. Eight percent of 1,460 unimmunized tuberculin reactors received isoniazid chemoprophylaxis, including 39% of 128 tuberculin reactors who graduated after 1974 (the majority of the latter were younger than 35 yr of age). Of 66 physicians who had active tuberculosis during medical school or after graduation, 20 (30%) had not received any antituberculosis chemotherapy, whereas 2 of 46 who did, received chemotherapy only after a second episode of tuberculosis. In summary, our study documents poor compliance by physicians with recommended policies for the prevention of tuberculosis in health care workers.     

The usefulness of two-step tuberculin skin testing in nosocomial infection cases]

The usefulness of the two-step tuberculin skin test in the preceding year for the contact investigation was reported, when a pulmonary tuberculosis patient was discovered in our hospital. Four persons showed stronger reaction than the results in two-step tuberculin skin test in the preceding year after nosocomial infection. One of them was diagnosed as pulmonary tuberculosis by chest radiograph, and antituberculosis chemotherapy was started. Other three started chemoprophylaxis. The chemoprophylaxis subjects might increase 4, if basic value of tuberculin reaction had not been available by two-step tuberculin skin test in the previous year. We could identify persons in whom tuberculin reaction became stronger by comparing the test results after exposure with the result of two-step tuberculin skin test in the preceding year. It is considered that two-step tuberculin skin test is very useful to efficiently execute the protective measure.     

Utility of the lateral chest radiograph in the evaluation of patients with a positive tuberculin skin test result

STUDY OBJECTIVES: In the United States, chest radiographs are performed on patients with positive tuberculin skin test (TST) results. It is not known whether, in addition to a single posteroanterior radiograph, a lateral chest radiograph is clinically indicated or cost-effective. We sought to determine the utility of the lateral chest radiograph in evaluating TST-positive adults. DESIGN: Cross-sectional study. SETTING: Tertiary-care hospital. PATIENTS: Adults with positive TST results. MEASUREMENTS: Findings on posteroanterior radiographs alone were compared to posteroanterior and lateral chest radiographs. RESULTS: In 2 of 535 cases (0.4%), lateral chest radiographs revealed a calcified granuloma not visible on posteroanterior radiographs. This finding did not alter patient management. In all other cases, lateral radiographs only confirmed findings seen on posteroanterior chest radiographs. CONCLUSION: Treatment altering findings were always visible on posteroanterior radiographs alone. These results suggest that lateral chest radiographs are not useful in evaluating adults with positive TST results.     

Evaluation of a rapid-format antibody test and the tuberculin skin test for diagnosis of tuberculosis in two contrasting endemic settings.

OBJECTIVE AND SETTING: We evaluated a rapid-format antibody card test and the tuberculin skin test for diagnosis of active tuberculosis (TB) in high (Cairo, Egypt) and low (St. Louis, USA) prevalence areas. DESIGN: Prospective study of hospitalized TB patients and controls with other chest diseases. RESULTS: Test performance varied significantly in the two study sites. The antibody test detected 87% of 71 smear-positive pulmonary TB cases (86% of smear-negative pulmonary cases and 48% of TB meningitis cases) in Egypt; specificity was 82%. The tuberculin test was highly sensitive in Egypt in subjects with pulmonary TB (100%) but not in those with meningitis (23%); specificity was 70%. The sensitivity and specificity of the antibody test in St. Louis were 29% and 79%, respectively; 50% of St. Louis TB cases and 15% of controls had positive tuberculin tests. CONCLUSIONS: This convenient antibody card test may have value for diagnosis of patients suspected of having TB in high prevalence areas like Egypt. However, the specificity of the test is too low for it to be useful as a screening test. Our results suggest that neither the antibody test nor the tuberculin test have much diagnostic utility in low prevalence settings like St. Louis.     

The role of the chest roentgenogram in febrile neutropenic patients

In a retrospective review of patients with neutropenia and fever, we sought to determine how often roentgenograms detected pulmonary disease, especially pneumonia, not suggested by signs and symptoms. Further, we sought to determine how often therapy was changed as a result of roentgenographic findings. Overall, 41 (22%) of 187 chest roentgenograms obtained during initial febrile episodes, recurrent fevers, or persistent fevers were abnormal. While most patients had signs and symptoms suggesting the presence of pulmonary disease, 17% had roentgenographic abnormalities detected in the absence of such findings. During initial febrile episodes, therapy was not changed in response to findings on the chest roentgenogram. However, during episodes of persistent or recurrent fever, findings on chest roentgenograms led to changes in therapy in eight (61%) of 13 episodes of which six (40%) resulted in clinical improvement. Chest roentgenograms were therefore found to be an important diagnostic tool in evaluating recurrent or persistent fever in the neutropenic patient but of little use during initial febrile episodes.     

The correlation of subcarinal density visualized on plain chest roentgenograms with computed tomographic scans

A prospective evaluation of 212 paired chest roentgenograms and computed tomographic (CT) scans was performed to determine the predictive value of detecting subcarinal adenopathy by finding increased subcarinal density on routine roentgenograms. Based on CT criteria for subcarinal lymphadenopathy, 37 true-positive and 124 true-negative cases of subcarinal adenopathy were found in 161 patients. Evaluation of density in the subcarinal area on the routine posteroanterior (PA) chest roentgenograms in these patients demonstrated a sensitivity of 72 percent and specificity of 96 percent for the detection of adenopathy when compared with established CT criteria. False-positive and false-negative appraisals of central mediastinal density on routine roentgenograms appear to be due to the super-imposition of other masses, bullae, or lack of appropriate roentgenographic contrast. The accuracy of predicting the presence or absence of subcarinal adenopathy from routine chest roentgenograms suggests that this observation is clinically useful and should be routinely evaluated.     

The value of portable chest roentgenography in adult respiratory distress syndrome. Comparison with computed tomography

In 17 patients with adult respiratory distress syndrome, we used data derived from computed tomographic (CT) scan densitometric analysis to validate the value of portable chest roentgenograms in objectively estimating the amount of pulmonary edema. Chest roentgenograms and CT scans were taken in the same ventilatory conditions (apnea at 10 cm H2O of positive end-expiratory pressure [PEEP]); blood gas samples and hemodynamic parameters were collected at the same time. Roentgenographic analysis was undertaken by independent observers using two standardized scoring systems proposed in the literature. CT scan analysis was performed using the CT number frequency distribution and the gas lung volume (measured by helium dilution technique) to estimate quantitatively the lung density, the lung weight, and the percentage of normally aerated and nonaerated tissue. Knowing the mean CT number of the pulmonary parenchyma in a group of normal subjects, we also inferred the ideal lung weight expected in the study population and computed the excess tissue mass as the difference between actual and ideal lung weight. Both the roentgenographic scoring systems showed direct correlation with the pulmonary impairment as detected by CT scan densitometric analysis (CT number, percentage of nonaerated tissue, lung weight, and excess tissue mass; p less than 0.01) and inverse relation with the percentage of normally aerated tissue (p less than 0.01). We also found a relationship between roentgenographic scores and the impairment in gas exchange as detected by shunt fraction (p less than 0.05). We conclude that standardized reading of portable chest roentgenograms by means of scoring tables is a valuable tool in estimating the amount of pulmonary edema in a patient with adult respiratory distress syndrome.     

Enzyme-linked immunospot and tuberculin skin testing to detect latent tuberculosis infection

RATIONALE: Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a new blood test to diagnose LTBI. OBJECTIVE: To compare the ELISPOT and the tuberculin skin test for detecting LTBI in contacts of patients with tuberculosis. METHODS: Prospective study of 413 contacts of patients with tuberculosis. MEASUREMENTS AND MAIN RESULTS: Because there is no gold standard for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test cannot be directly measured. For each contact, we therefore estimated the likelihood of having LTBI by calculating a contact score that quantified exposure to and infectiousness of the index case. We analyzed the relationship of contact score to ELISPOT and tuberculin skin test results. The likelihood of a positive ELISPOT (p = 0.0005) and a tuberculin skin test (p = 0.01) increased significantly with rising contact scores. The contact score was more strongly related to the ELISPOT than to the tuberculin skin test results, although this difference was not statistically significant. Among U.S.-born persons and those who were not vaccinated with bacille Calmette-Guérin, approximately 30% had positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette-Guérin-vaccinated persons were significantly more likely to have a positive tuberculin skin test than a positive ELISPOT result (p < 0.0001). CONCLUSIONS: Compared with the tuberculin skin test, the ELISPOT appears to be at least as sensitive for diagnosis of LTBI in contacts of patients with tuberculosis.     

The use of sputum cultures in the evaluation of immigrants classified as tuberculosis suspects

Because of possible deficiencies in the evaluation, based on symptoms and chest roentgenogram review, of new immigrants classified during the visa application process as tuberculosis suspects, a prospective (cohort) and a retrospective (case control) study were done to test the usefulness of routinely obtaining sputum specimens for culture in that setting. In the prospective study, 249 consecutive classified immigrants who were considered on the basis of clinical and roentgenographic findings to have nonprogressive tuberculosis submitted at least two sputums for culture: 13 (5.2%) had at least one culture positive for M. tuberculosis. Immigrants younger than 50 yr of age and refugees from Kampuchea and Laos had a fivefold to tenfold elevated risk of having a positive sputum culture. The cost per case detected of obtaining and processing sputum cultures was estimated to be +1,996 to +2,994. In the case-control study, 37 classified immigrants evaluated from 1981 through 1986 who had sputum cultures positive for M. tuberculosis even though they fulfilled clinical and roentgenographic criteria for nonprogressive tuberculosis served as control subjects. Several demographic, clinical, and roentgenographic factors were associated with an increased risk of being culture-positive: age younger than 50 yr, a positive tuberculin test, report of a cough, and a cavitary lesion on chest roentgenogram. The history of prior receipt of antituberculosis drugs was associated with having a negative culture, including a marked dose-response effect.     

Calcinosis of the arterial ligament and tuberculous adenitis of the aortic window in children: computerized tomography

The paper provides a retrospective analysis of scans of chest computed tomography (CT) in children who had different forms of intrathoracic or were tuberculin positive. The children had no cardiovascular diseases or clinical signs of Botallo's duct patency. CT was performed without contrast reinforcement. Arterial ligament calcification (ALC) was detected in 16 children, of them 9 had concurrently tuberculous adenopathy of several groups, as well as aortic window nodes being in 2. ALC was the only respiratory alteration in 7 children. The calcified aortic ligament was misinterpreted as the calcified lymph node of the aortic window.     

Evaluation of a third sequential tuberculin skin test in a chronic care population

To evaluate factors that might influence the accuracy of tuberculin tests in identifying elderly persons recently infected with Mycobacterium tuberculosis, we performed as many as 3 sequential administrations of 5 tuberculin units of purified protein derivative in 1,726 persons residing in chronic care facilities. Significant reactions (greater than or equal to 10 mm of induration) to 1 of 3 tests were found in 702 (40.7%) persons. Of these, 68% were found with Test 1, 22.5% with Test 2, and 9.5% with Test 3. Of 1,146 persons with nonsignificant reactions to Test 1, 13.8% had significant reactions on Test 2, and of 769 persons with nonsignificant reactions to Tests 1 and 2, 8.7% had significant reactions on Test 3. Males, nonwhites, and persons between 50 and 79 yr of age had a greater proportion of significant reactions for each of the first 2 tests but not for the third test. These data indicate that continued boosting of the tuberculin reaction occurs in a substantial number of persons who receive a third sequential test. Marked increases in the size of reactions caused by boosting may explain high apparent conversion rates found in facilities where the third test is delayed for one year.     

Evaluation of serological diagnosis tests for tuberculosis in hemodialysis patients

Patients receiving hemodialysis are generally considered to be at increased risk of developing tuberculosis. In the current study, in order to evaluate the usefulness of serological tests in dialysis patients, serum antibodies for tuberculous glycolipids antigen (TBGL) and for lipoarabinomannan (LAM) were measured in hemodialysis patients. The present study included 243 hemodialysis patients. Serum antibodies for TBGL and LAM were measured. Tuberculin skin tests were carried out and chest X-rays evaluated at the same time. There were no patients with active tuberculosis at the time of blood sampling. Thirty-six patients (14.8%) and 25 patients (10.3%) were positive for anti-TBGL antibody and anti-LAM antibody, respectively. One hundred and fifty-five patients (63.8%) were positive for tuberculin skin testing and 123 patients (50.6%) had old pulmonary tuberculosis on their chest X-ray. There was no significant correlation between the results of anti-TBGL antibody and anti-LAM antibody. There were no relationships among the results of tuberculin skin test and the two serological tests. However, positivity of anti-TBGL antibody and anti-LAM antibody was significantly higher in patients with findings of old tuberculosis on the chest X-ray than those without findings. The current results show that these serological tests are positive more frequently in hemodialysis patients without any proof of active tuberculosis than in healthy subjects (2%) and careful interpretation is necessary for relevant results.     

Esophageal tuberculosis: mimicry of gastrointestinal malignancy

A case of tuberculous involvement of the esophagus was studied in an adult with mediastinal lymphadenopathy unrecognized by roentgenography of the chest. The roentgenographic and endoscopic features in this case were more consistent with malignancy than with tuberculosis. Nineteen additional cases from the English-language literature were reviewed. Although esophageal tuberculosis is a rare disease, it should be strongly suspected in a patient with dysphagia who has a positive tuberculin skin test, active pulmonary disease, or mediastinal adenopathy.