Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals

RATIONALE: Although interferon (IFN)-gamma release assays are approved for the diagnosis of latent tuberculosis infection (LTBI), limited data exist regarding their performance in HIV infection. OBJECTIVES: To compare tuberculin skin test (TST) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In-Tube (QFT) for the diagnosis of LTBI in HIV-infected adults. METHODS: A total of 294 HIV-infected subjects sampled from two San Francisco cohorts underwent TST, using 5 TU of purified protein derivative, and QFT, measuring IFN-gamma response to Mycobacterium tuberculosis-specific RD-1 antigens. MAIN RESULTS: Of 294 participants, 205 (70%) returned for an evaluable TST. Concordance between QFT and TST was 89.3% (kappa=0.37, p=0.007). However, in subjects with positive test results by either TST or QFT, only 28% (8/29) had positive test results by both modalities. TST-positive/QFT-negative discordant results were found in 5.1% of subjects and TST-negative/QFT-positive discordance in 5.6%. Indeterminate QFT results occurred in 5.1%, all due to a failure to respond to the phytohemagglutinin-positive control. Subjects with a CD4(+) count of less than 100 cells/mm(3) had a relative risk of an indeterminate result of 4.24 (95% confidence interval, 1.55-11.61; p=0.003) compared with those with a CD4(+) count of 100 or more. CONCLUSIONS: Overall concordance between QFT and TST in HIV infection was high, but agreement among subjects with positive tests by either modality was low.     

Choosing an appropriate cutting point for conversion in annual tuberculin skin testing

A previous report from our institution showed that the use of a two-step tuberculin testing program in new employees reduced the apparent rate of conversion in annual skin testing by eliminating the effect of the booster phenomenon. However, the converter rate subsequently remained too high. We propose that the use of 10 mm of induration as the cutting point gave a high rate of false conversion in our area of high prevalence of sensitivity to nontuberculous mycobacteria. A change to 15 mm of duration as the cutting point reduced our conversion rate from 2.6 to 1.2%, identified a group who demonstrated continued large tuberculin reactions at repeat testing, and eliminated age dependency from our converter population. We propose the choice of 15 mm of induration as the appropriate cutting point in annual employee tuberculin skin testing programs in areas in which sensitivity to nontuberculous mycobacteria is common.     

Boosted tuberculin skin testing in hemodialysis patients

BACKGROUND: Tuberculosis remains a significant health problem for patients receiving long-term hemodialysis (HD). The tuberculin skin test (TST) is an important method of detecting Mycobacterium tuberculosis infection. Cutaneous anergy decreases the accuracy of the test in these patients. Higher and repeating doses have been mentioned in the immunosuppressed patients. This study examined the significance and frequency of the booster phenomenon in 2-step tuberculin testing of these patients. METHODS: A total of 106 outpatients in a hospital-based HD center in Turkey were screened with 5 and 10 tuberculin units (TU) and Candida antigen. To determine the frequency of booster phenomenon, patients with <10 mm indurations to the initial TST with 5 TU were given a second test with 10 TU, 7 days later. RESULTS: Forty (37.7%) of 106 patients had a significant tuberculin reaction (>or=10 mm) on the initial TST with 5 TU. The booster effect was detected in 16 (24.3%) of 66 patients who had a negative reaction (相似文献   

A new method for testing tuberculin skin reactivity--chamber test

The Mantoux test and a chamber tuberculin test applied to the surface of the skin in 4 concentrations were performed on 229 children and 516 adults. The results were recorded at 72 hours. There was a significant correlation between the two tests. The chamber tuberculin test is technically easy, painless and atraumatic. It gives an opportunity of using a full range of concentrations of tuberculin resulting in a quantitative measurement of sensitivity in one and the same test procedure.     

The significance of the tuberculin skin test in elderly persons

Study of 49,467 persons over age 50 in Arkansas nursing homes afforded insight into the significance of the tuberculin skin test in the elderly. Whereas only 15% to 20% of persons showed a significant (10 mm or more) reaction to tuberculin on admission, 2% to 3% of these developed tuberculosis. Persons having no reactions comprised two subsets: a small group who died at an increased rate and were probably anergic, and a larger group who survived as well as persons who had reactions. Minor increases in reaction size with repeated testing appeared to be due to immunologic recall. However, conversions of 12 mm or more from a documented negative result indicated spread of infection. When not treated preventively, 7.6% (women) to 12.7% (men) of definite converters developed tuberculosis. The increase in number of persons showing positive reactions after entry may have been due to rapid demise of the anergic subset, improvement in nutrition of survivors, or unsuspected spread of tuberculous infection.     

Two-step tuberculin skin testing in our hospital employees

To evaluate the baseline values of tuberculin reaction, two-step tuberculin skin testing was carried out in 365 employees of our hospital. We defined strongly response group when the size of erythema showed more than 30 mm or who showed strongly positive reaction. Two-step tuberculin skin testing was carried out in 165 hospital employees excluding those who were defined as the strongly response group in the first testing. 80 hospital employees (48.5%) became strongly response group by the second tuberculin skin testing. Altogether, 76.7% of all employees were strongly response group either by the first time or the second tuberculin skin testing. The size of erythema and that of induration showed 13.2 +/- 12.6 mm (mean +/- SD), 6.9 +/- 9.2 mm increase, respectively, in the two-step tuberculin skin testing, so-called Booster phenomenon. We could not know the true tuberculin reaction status by the single tuberculin skin testing. Therefore, two-step tuberculin skin testing is important as one of an infection prevention countermeasures in the hospital workers.     

Cost-effectiveness analysis of recruitment strategies in a community-based intervention study of HIV-infected persons

This paper describes and evaluates recruitment methods used to reach adults with HIV infection and to enroll eligible candidates in a randomized trial of aerobic exercise. Potential participants residing in the metropolitan Washington DC area were recruited from January 1994 to December 1996. The yield and associated cost of clinic centre site-visit (CSV) recruitment are compared to similar outcomes for community-based (CB) recruitment strategies, which consisted of presentations to local groups, mail/phone canvasses of caregivers, neighbourhood network promotion, public site postings and print media notices. Of 833 HIV infected adults ascertained during the recruitment phase as prospective study candidates, 66.7% were initially contacted during CSV recruitment. The remainder, 33.3% were CB recruits. The percentage of screened candidates who were subsequently enrolled in the study was 13.5% for CSV recruitment and 21% for CB recruitment. Ascertainment and screening costs combined were $158 per CB recruit compared to $232 per CSV recruit. Using multiple recruitment approaches we successfully achieved our enrollment goal of at least 100 volunteers from diverse populations by the end of the planned recruitment period.     

Utilization of a basic care and prevention package by HIV-infected persons in Uganda

Opportunistic infections are the leading cause of mortality among HIV-infected people. Several simple interventions prevent illness, prolong life, or prevent HIV transmission from HIV-infected people in Africa. These include: cotrimoxazole prophylaxis; insecticide-treated bed nets; supplies for household water treatment and safe storage; materials promoting family voluntary counselling and testing (VCT); and condoms. We provided these interventions to adults and children with HIV who were members of the AIDS Support Organization in Uganda. To evaluate use of this basic care and prevention package, we surveyed a representative sample of 112 clients of TASO in their homes. Among respondents, 95% reported taking cotrimoxazole everyday, 89% said they had slept under a bednet the night before, 65% reported current treatment of household drinking water, 89% of sexually active respondents reported using condoms, and 96% reported family use of VCT. Household observations verified that use of cotrimoxazole, bednets, and water treatment products were consistent with reported use. This evaluation suggests successful distribution and use of basic care and prevention services at an AIDS organization in Uganda.     

Factors associated with tuberculin skin test reactivity among HIV-infected people in Bangkok

INH preventive therapy (IPT) has been shown in several randomized controlled trials to reduce the risk of developing active TB in tuberculin skin test (TST) or purified protein derivative (PPD) positive HIV infected individuals. Detection of latent tuberculosis by TST and determination of factors associated with the PPD positivity in HIV-infected persons are important for the targeting of chemoprophylaxis. Six hundred asymptomatic and early symptomatic HIV-infected subjects attending the AIDS Clinic of the Chulalongkorn University Hospital, Bangkok, Thailand were enrolled in two randomized clinical trials of chemoprophylaxis against TB from December 1994 to December 1996. The availability of baseline characteristics, including TST reactivity, among these participants enabled a cross-sectional analysis of factors associated with PPD positivity. The results showed that 117 (19.5%) were PPD positive and 483 (80.5%) were PPD negative with ages 18-65 years (median 29 years). HIV exposure category was 46.2%, 34.5%, and 6.7% for heterosexual contact, commercial sex work, and homosexual and bisexual male contact respectively. The median CD4 cell count was 315/mm3 (range, 5-1,074/mm3). HIV exposure category and CD4 cell count were significantly associated with PPD status. Homosexual/bisexual contact had 3 times higher risk of PPD positivity than heterosexual contact (adjusted OR=2.9; 95% CI, 1.4-6.1) and risk of PPD positivity was higher among patients with CD4 cell counts of 200-500/ mm3 (adjusted OR=1.8; 95% CI, 1.0-3.1) and above 500/mm3 (adjusted OR=3.4; 95% CI, 1.7-6.7) when compared to patients with CD4 cell counts of less than 200/mm3. The HIV-infected persons in Bangkok with homosexual/bisexual contact are at higher risk for latent TB. Population-based tuberculin screening without accompanying HIV testing cannot be used to estimate the prevalence of actual latent TB in a population where HIV infection is widespread, such as in Thailand.     

Tuberculosis screening among HIV-infected patients: tuberculin skin test vs. interferon-gamma release assay

National guidelines recommend screening for latent tuberculosis infection (LTBI) in all HIV-infected patients. Thus, the objective of this study was to measure protocol adherence to national guidelines regarding LTBI screening for HIV-infected patients entering care at an urban primary care clinic specializing in HIV care, identify clinical and other characteristics associated with adherence, and determine whether transitioning from the tuberculin skin test (TST) to the interferon-gamma release assay (IGRA) improved adherence. We conducted a retrospective study using protocol adherence to LTBI screening guidelines within twelve months of entering care at an HIV clinic as the primary outcome. Successful protocol adherence was defined as the placement and reading of a TST, performance of an IGRA, or a note in study clinic records documenting prior testing or treatment for tuberculosis in an outside setting. Multivariable modified Poisson regression models were used in analyses. Overall, 32% (n?=?118/372) of patients received LTBI screening within twelve months of entering care. Protocol adherence to LTBI screening guidelines increased from 28% to 37% following the transition from TST to IGRA screening. IGRA screening [adjusted prevalence ratio: 1.45, 95% confidence limits: (1.07, 1.96)], male sex [1.47 (1.05, 2.07)], transfer patient status [1.51 (1.05, 2.18)], and greater than one year of clinic attendance [1.62 (1.06, 2.48)] were independently associated with protocol adherence. Among patients without prior LTBI screening or treatment, patients entering the clinic in 2013 under the IGRA screening protocol were more likely to be screened for LTBI compared to patients entering under the TST screening protocol (34.3% vs. 9.7%, p?相似文献   

Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific interferon-gamma assay.

Recently, interferon-gamma release assays (IGRA) for specific diagnosis of Mycobacterium tuberculosis infection have become available. In recent UK tuberculosis (TB) guidelines, it has been advised to screen for latent M. tuberculosis infection using the tuberculin skin test (TST), followed by IGRA if the TST is positive. Since TST can boost immune responses to tuberculin, the present authors evaluated whether TST administration affects the result of QuantiFERON-TB Gold in-tube (QFT-GIT), a whole blood-based IGRA. QFT-GIT was performed on the day of TST administration and the day of reading in 15 TST-negative subjects, 46 TST-positive subjects with recent or remote exposure to M. tuberculosis and five cured TB patients. No systematic boosting of QFT-GIT responses from negative to positive was observed. Only in a few TST-positive persons did TST enhance pre-existing QFT-GIT responses. Screening for latent Mycobacterium tuberculosis infection using tuberculin skin testing followed by interferon-gamma release assays on the day of reading is a reliable approach, as the specificity of QuantiFERON-TB Gold in-tube is not affected by prior tuberculin skin test administration.     

Transmission of Mycobacterium tuberculosis undetected by tuberculin skin testing

RATIONALE: The development of tuberculin skin test (TST) positivity following infection by Mycobacterium tuberculosis is not invariable and may depend on bacillary as well as host factors. OBJECTIVES: First, to compare the diagnostic performance of the TST and a form of in vitro IFN-gamma release assay (IFNGRA) in the circumstances of a contact investigation prompted by an unusually severe index case of infectious pulmonary tuberculosis. Second, to investigate the ability of the strain of M. tuberculosis responsible to induce cytokine secretion from monocytes in vitro. METHODS: A routine TST-based tuberculosis-contact screening procedure supplemented by the use of an "in house" IFNGRA that assays the T-cell response to the M. tuberculosis-specific antigens ESAT-6, CFP-10 (presented as a fusion protein within the inactivated adenylate cyclase of Bordetella pertussis), and purified protein derivative of M. tuberculosis. Isolation and genetic typing of the strain of M. tuberculosis responsible, and investigation of its ability to induce cytokine secretion from monocytes in vitro. MEASUREMENTS AND MAIN RESULTS: TST screening suggested a low rate of transmission with just 2/75 unequivocally positive responses. By contrast, the IFNGRA suggested an infection rate of 16/75 (22%). When compared with two reference strains of M. tuberculosis (H37Rv and CDC1551), the outbreak strain induced lower levels of tumor necrosis factor-alpha and interleukin-12p40 (p < 0.04), cytokines associated with the development of delayed-type hypersensitivity. CONCLUSIONS: These data suggest that infection by M. tuberculosis can be undetected by TST, and that this may partially relate to strain differences in immunogenicity.     

Density of tuberculin skin reaction and its association with tuberculosis infection as defined by dual tuberculin testing.

OBJECTIVE: To determine whether the density of tuberculin skin reactions is associated with tuberculosis infection. METHODS: In a national tuberculin survey in Tanzania, 1983-1987, all eligible children in a random sub-sample of schools underwent dual tuberculin skin testing with PPD-RT23 and PPD-scrofulaceum. The density of reactions to RT23 was classified as proposed by Palmer. A larger reaction to PPD-scrofulaceum than to PPD-RT23 is suggestive of infection with environmental mycobacteria. Tuberculosis infection was defined based on dual skin test results applying a range of possible definitions. RESULTS: A total of 10,782 children aged 5-14 years and without BCG scar were included in the analysis. Large skin reactions to RT23 were generally firmer than small ones. After taking the size of the skin reaction to RT23 into account, its density was not associated with the size of the skin reaction against PPD-scrofulaceum. In particular, the density of reactions in the range 6-11 mm was not associated with tuberculosis infection according to any of the definitions used. CONCLUSION: This study suggests that the density of reaction was not associated with tuberculosis infection in Tanzanian school children after taking the size of the induration into account.