Use Of Interferon-gamma Release Assays Research Articles

P124 Use of interferon-gamma release assay (IGRA) and tuberculin skin test (TST) for tuberculosis screening in patients candidates for anti-TNF terapy in inflammatory bowel disease (IBD)

indexes of treatment response. Aim of this study was to evaluate the use of soluble transferrin receptor/log10 ferritin index (sTfR-F) as a predictor of the effectiveness of intravenous iron in IBD-associated anemia. Methods: 54 patients with IBD were included in this study (30 men, 22 ulcerative colitis, 32 Crohn’s disease). Intravenous ferric carboxymaltose was administered at a maximum dose of 15mg/kg or 1000mg within 15 min. Anemia was defined as hemoglobin Hb 2 g/dl) was observed in 66.7% of the patients. Mean CRP and ESR values were not statistically significant different between the two phases of the study and no significant correlation between CRP and sTfR-F index was found. Intravenous ferric carboxymaltose infusion had as a result a significant reduction of sTfR-F index at week 4 compared to week 0 (p 1.4 had a sensitivity of 91.8% and specificity of 94.4% in the prediction of the hemopoietic response. Conclusions: sTfR-F index is a highly reliable predictive index of the effectiveness of intravenous ferric carboxymaltose infusion in IBD-associated anemia.

Effectiveness of interferon-gamma release assays for differentiating intestinal tuberculosis from Crohn’s disease: A meta-analysis

To investigate the clinical usefulness of interferon-gamma release assays (IGRAs) in the differential diagnosis of intestinal tuberculosis (ITB) from Crohn's disease (CD) by meta-analysis. A systematic search of English language studies was performed. We searched the following databases: Medline, Embase, Web of Science and the Cochrane Library. The Standards for Reporting Diagnostic Accuracy initiative and Quality Assessment for Studies of Diagnostic Accuracy tool were used to assess the methodological quality of the studies. Sensitivity, specificity, and other measures of the accuracy of IGRAs in the differential diagnosis of ITB from CD were pooled and analyzed using random-effects models. Receiver operating characteristic curves were applied to summarize overall test performance. Two reviewers independently judged study eligibility while screening the citations. Five studies met the inclusion criteria. The average inter-rater agreement between the two reviewers for items in the quality checklist was 0.95. Analysis of IGRAs for the differential diagnosis of ITB from CD produced summary estimates as follows: sensitivity, 0.74 (95%CI: 0.68-0.80); specificity, 0.87 (95%CI: 0.82-0.90); positive likelihood ratio, 5.98 (95%CI: 3.79-9.43); negative likelihood ratio, 0.28 (95%CI: 0.18-0.43); and diagnostic odds ratio, 26.21 (95%CI: 14.15-48.57). The area under the curve was 0.92. The evaluation of publication bias was not significant (P = 0.235). Although IGRAs are not sensitive enough, they provide good specificity for the accurate diagnosis of ITB, which may be helpful in the differential diagnosis of ITB from CD.

Does an interferon-gamma release assay change practice in possible latent tuberculosis?

Suspected latent tuberculosis infection (LTBI) is a common reason for referral to TB clinics. Interferon-gamma release assays (IGRAs) are more specific than tuberculin skin tests (TSTs) for diagnosing LTBI. The aim of this study is to determine if IGRA changes practice in the management of cases referred to a TB clinic for possible LTBI. A prospective study was performed over 29 months. All adult patients who had TST, CXR & IGRA were included. The original decision regarding TB chemoprophylaxis was made by TB team consensus, based on clinical history and TST. Cases were then analysed with the addition of IGRA to determine if this had altered management. An independent physician subsequently reviewed the cases. Of 204 patients studied, 68 were immunocompromised. 120 patients had positive TSTs. Of these, 36 (30%) had a positive QFT and 84 (70%) had a negative QFT. Practice changed in 78 (65%) cases with positive TST, all avoiding TB chemoprophylaxis due to QFT. Of the immunocompromised patients, 17 (25%) underwent change of practice. No cases of active TB have developed. This study demonstrates a significant change of clinical practice due to IGRA use. Our findings support the NICE 2011 recommendations.

Interferon-gamma release assay: use and misuse

Interferon-gamma release assays are being increasingly used worldwide for the diagnosis of latent tuberculosis (TB) in patients of all ages, including children [1]. A PubMed search with ‘interferon-gamma release assays’ as keyword revealed a total of 1077 references, up to 100 of which had been released in 2012, including several reviews. In national and international guidelines such as CDC [2], ECDC [3], Canadian [4], French [5] and UK [6] guidelines, interferon-gamma release assays are used either in place of or in addition to the tuberculin skin test for latent TB diagnosis, indicating the lack of clear evidence regarding the use of interferon-gamma release assays. There are two major interferon-gamma release assays available: the quantiFERON-TB Gold in-Tube assay, which is an ELISA from Cellestis (Chadstone, Australia), and the T-SPOT.TB assay, which is an enzyme-linked immunospot assay from Oxford Immunotec (Abingdon, UK). The development of these tests opens to a fruitful market. ‘We now have market penetration about 2 million tests per year—about 1 QFT test every 15 seconds’ said Ron Pitcher in the Cellestis 2010 Annual Report (available at: http://www.cellestis.com/ IRM/Company/ShowPage.aspx?CPID= 1807E 850 tested positive with both tests, none were preventively treated, eight were finally diagnosed with active TB, and four others progressed to TB within 4–24 months [10]. In this study, the preventive treatment would have be given to 842 persons to prevent four active TB cases. This demonstrates the poor cost-effectiveness of systematic screening. However, in TB-exposed individuals, 2.3–14.6% of those with positive tuberculin skin test results or interferon-gamma release assay results, respectively, will develop active TB [11]. The main purpose of interferon-gamma release assays is to allow the treatment of patients with latent TB at risk of developing active TB, such as TB-exposed individuals or immunocompromised patients. Only patients who would benefit from preventive treatment should be tested. The decision to test presupposes a decision to treat if the test result is positive. Misuse: There is no indication for the use of these tests in systematic screening. Because the available evidence is currently inconsistent, interferon-gamma release assays should not be used to monitor response to TB therapy. Neither tuberculin skin tests nor interferon-gamma release assays can distinguish between active and latent infection, and for this reason the test is not accurate for the diagnosis of active TB [12], which relies on the identification of M. tuberculosis. Use: Typically, interferon-gamma release assays can be used in persons with an increased risk of new TB, such as asymptomatic person after close contact with an active case of pulmonary/respiratory TB, and in patients with an increased risk of TB reactivation, such as patients infected with human immunodeficiency virus, those with transplants, lymphoma, leukaemia, head and neck cancer, chemotherapy, or other therapeutic immunosuppression, and those who will be treated with tumour necrosis factor-a inhibitors.

Tuberculin skin test in bacille Calmette–Guérin-vaccinated children: how should we interpret the results?

The tuberculin skin test (TST) is the most useful method for the diagnosis of tuberculosis (TB). There is no evidence about the effect of bacillus Calmette-Guerin (BCG) vaccine on the interpretation of TST results. The aim of this study was to evaluate TST results in a population of immigrants and adopted children, analyzing the effect of the vaccine on TST. Cross-sectional observational study including immigrants or adopted children evaluated in our unit between January 2003 and December 2008 was made. Children diagnosed with TB, live attenuated virus vaccinated 2 months earlier, HIV-infected, chronically ill, or under treatment with immunosuppressive agents were excluded. TST was considered the dependent variable. Independent variables were gender, age, geographical origin, BCG scar, nutritional status, immune status, and intestinal parasites infestation. One thousand seventy-four children were included, 69.6 % are female; their origin includes China (34.7 %), Latin America (20.8 %), India/Nepal (19.4 %), Eastern Europe (15.7 %), and Africa (9.3 %). BCG scar was present in 79 % of children. Mantoux = 0 mm in 84.4 %, <10 mm in 4.1 %, and ≥10 mm in 11.4 %. Only two variables, age and BCG scar, influenced TST result. Risk of a TST false-positive due to BCG disappears 3 years after vaccine administration. A history of BCG vaccination at birth does not interfere with TST results in children >3 years old. Under 3 years of age, BCG does interfere with and may cause a false-positive TST result. In these cases, the use of interferon-gamma release assays (IGRAs) is recommended. If IGRAs are not available or when results are indeterminate, ignoring the antecedent of the vaccine is recommended.

Interferon-Γ Release Assays for the Diagnosis and Mycobacterium Tuberculosis Infection in Children: A Systematic Review and Meta-Analysis

Data regarding the use of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis are accumulating. We systematically searched PubMed, EMBASE and Cochrane and performed pooled estimates of sensitivity and specificity of QuantiFERON-TB Gold In Tube (QFT-G-IT) and T-SPOT.TB compared to tuberculin skin test (TST). For studies assessing sensitivity, children had to have active tuberculosis. Specificity data were derived from children classified as non-infected. Eleven studies were included in the sensitivity analysis for TST, 10 for QFT-G-IT, and 9 for T-SPOT.TB. Eight studies were included in specificity analysis for TST, 8 for QFT-G-IT, and 7 for T-SPOT.TB. Pooled QFT-G-IT sensitivity was 0.79 (95% CI:0.70-0.89) pooled T-SPOT.TB sensitivity was 0.74 (95% CI:0.59-0.90) and pooled TST sensitivity was 0.82 (95% CI:0.72-0.93). Pooled QFT-G-IT and T-SPOT.TB specificities were 0.95 (95% CI:0.93- 0.97) and 0.96 (95% CI:0.93-1.00), respectively. Pooled TST specificity was significantly lower 0.83 (95% CI:0.74-0.92). IGRA performance in children showed no better sensitivity than TST, but higher specificity.

Rapid diagnosis of Mycobacterium tuberculosis infection in children using interferon-gamma release assays (IGRAs)

Diagnosis of tuberculosis (TB) in children by the tuberculin skin test (TST) poses a diagnostic challenge for physicians due to its low specificity and cross-reactivity with nontuberculous mycobacteria and bacille Calmette-Guerin (BCG). Although interferon-gamma release assays (IGRAs) have been shown as novel TST alternatives for diagnosis of latent TB infection (LTBI) in adults, their effectiveness is less clear in children. The present study examined QuantiFERON-TB Gold (QFT-G) responses and IFN-gamma production capacity of TST-positive children, younger children ≤5 years. A total of 517 children of whom 434 were TST positive ranging in age from 1 month to 18 years were evaluated by the QFT-G. Of the 517 children, 434 (84%) were TST positive, 25 (5.8%) of whom were found to be QFT-G positive and 25 (5.4%) with an indeterminate response. Of the 517 children, 355 (68.7%) were previously BCG immunized and 310/355 (87.3%) were TST positive including 18/27 (66.7%) QFT-positive children. Adequate IFN-gamma production by purified TB peptides or mitogen was observed in 92.8% of children, 29.6% of whom were <5 years. This study shows that the QFT-G assay is useful for diagnosis of LTBI. The finding of 5.8% positive QFT-G in 434 TST-positive children underscores the superior specificity of the QFT-G than the TST and its greater cost effectiveness in preventing unnecessary and potentially toxic treatment in children. The study suggests that the majority of positive TST in children represent false-positive reactions and supports the use of IGRAs for diagnosis of LTBI in children, including those <5 years of age.

Interferon-gamma release assay as a diagnostic test for tuberculosis-associated uveitis

BackgroundTo study the use of interferon-gamma release assay (IFN-γ) (IGRAs) as a diagnostic test for tuberculosis (TB)-associated uveitis (TAU).DesignProspective cohort study.ParticipantsConsecutive new patients (n=162) with clinical ocular signs suggestive of TAU, seen >1 year period at a single tertiary center.MethodsAll subjects underwent investigations to rule out underlying disease, including T-SPOT.TB and tuberculin skin test (TST). Twenty-one subjects with underlying disease and three with interdeterminate T-SPOT.TB results were excluded. Those with T-SPOT.TB- or TST-positive results were referred to infectious diseases physician for evaluation. Anti-TB therapy (ATT) was prescribed if required. Patients' treatment response and recurrence were monitored for six months after completion of ATT, if given; or 1 year if no ATT was given.Main outcome measureDiagnosis of TAU.ResultsMean age of study cohort (n=138) was 46.8±15.3 years. Majority were Chinese (n=80, 58.0%) and female (n=75, 54.3%). TST was more sensitive than T-SPOT.TB (72.0% vs36.0%); but T-SPOT.TB was more specific (75.0% vs51.1%) for diagnosing TAU. Patients with either a T-SPOT.TB (1.44; 95% confidence intervals (CI), 0.86–2.42) or TST (1.47; 95% CI, 1.12–1.94)-positive result are more likely to have TAU. The accuracy of diagnosing TAU increases when both tests are used in combination (area under the receiver operator curve=0.665; 95% CI, 0.533–0.795). Patients with both tests positive are 2.16 (95% CI, 1.23–3.80) times more likely to have TAU. Negative T-SPOT.TB or TST results do not exclude TAU (negative likelihood ratios <1.0).ConclusionsWe recommend using a combination of clinical signs, IGRA, and TST to diagnose TAU.

Factors Associated with Indeterminate and False Negative Results of QuantiFERON-TB Gold In-Tube Test in Active Tuberculosis

BackgroundThe sensitivities and specificities of interferon-gamma release assays (IGRAs) vary among different population studies, and the data on the routine use of IGRAs are limited. The aim of this study was to evaluate the role of QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of active tuberculosis.MethodsWe conducted a prospective study, enrolling 77 patients with suspected pulmonary tuberculosis (TB), at a secondary care teaching hospital in Seoul.ResultsIn total, 12 (15.6%) patients showed indeterminate results due to positive control failure on the QFT-GIT test. Indeterminate results were significantly associated with the elderly, history of the intensive care unit stay, lymphocytopenia, especially low CD4 count, increased C-reactive protein and decreased protein levels. Of the 77 patients, 44 (57.1%) were diagnosed with active pulmonary tuberculosis, and the percentage of false negative results of the QFT-GIT was 36.4% (vs. 31.8% with TST). In the TB group with >65 years old (n=12), the proportions of the indeterminate (33.3% vs. 3.1%) and the false negative results (58.3% vs. 25.0%) of the QFT-GIT were significantly higher than in the younger TB group (n=32).ConclusionIndeterminate and false negative results of QFT-GIT test were not infrequent in tuberculosis, especially in the elderly. Care should be considered for the interpretation with the elderly, immunocompromised, chronic and severely diseased patients.

Cost-effectiveness analysis of targeted and sequential screening strategies for latent tuberculosis

No cost-effectiveness studies of testing for latent tuberculosis infection have incorporated both targeted testing and the use of interferon-gamma release assays (IGRAs) in heterogeneous populations. To examine the cost-effectiveness of universal vs. targeted and sequential testing strategies and the use of tuberculin skin testing (TST) vs. IGRAs. Using a decision-analytic model, incremental cost-effectiveness ratios were calculated in 2009 among nine potential strategies for screening recruits. A societal perspective was taken over a 20-year analytic horizon, discounting future costs at 3% annually. Sensitivity analyses were conducted to determine how changes in assumptions affected the estimates. Targeted strategies cost over US$250 000 per case prevented, whereas universal testing strategies cost over US$700 000 per incremental case prevented in base case and most sensitivity analyses. Targeted testing offered the best value in this population, although it was still relatively expensive compared to no testing. Sequential testing with both TST and IGRAs provided a poor incremental value compared to targeted and universal testing strategies. Targeted testing using TST was slightly more cost-effective than targeted testing using either QuantiFERON®-TB Gold In-Tube or T-SPOT®.TB, but these estimates were very sensitive to changes in model assumptions.

Cost Effectiveness of Interferon Gamma Release Assays vs. Tuberculin Skin Tests in Healthcare Workers

A cost benefit analysis project using interferon gamma release assays (IGRAs) as an alternative to tuberculin skin tests (TSTs) for screening healthcare workers for latent tuberculosis infection (LTBI) and active tuberculosis (TB) disease showed an improved accuracy of results. In 2001, the FDA approved the use of IGRAs as an aid for screening latent and active TB. IGRAs detect the release of IFN-y from lymphocytes of sensitized persons when their blood is incubated with peptide mixtures stimulating two TB proteins called ESAT-6 and CFP-10. These proteins are secreted by all M. tuberculosis and pathogenic M. bovis strains, but are absent from all BCG vaccine strains and commonly encountered non-tuberculosis mycobacterium. In our facility, there are approximately 200 employees who are required to have an annual TB screening. Difficulties have been encountered in using the TST with maintaining compliance, accuracy of administration and interpretation of results.

Use of Interferon-Gamma Release Assay for Latent Tuberculosis Infection Screening in Older Adults Exposed to Tuberculosis in a Nursing Home

To assess the additive value of a newly marketed interferon-gamma release assay, QuantiFERON-TB Gold In-Tube (QFT-GIT), to a single tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) in older adults who have been exposed to TB in a nursing home. Contact tracing included clinical examination, chest radiography, TST, and QFT-GIT in TST-negative people (TST< 5 mm). A private nursing home. Seventy-seven individuals (63 elderly residents, 14 young employees) who had been exposed to an active TB case in a private nursing home. Comparison of TST and QFT-GIT in older adults who have been exposed to TB. For the TST, the positive response rate was 31.7% (n=20) of elderly residents and 43% (n=6) of staff. Positive QFT-GIT results were obtained in seven (16.3%) elderly residents with negative TST, six of whom were aged 80 and older. QFT-GIT increased the percentage of possible LTBI in this group from 31.7% to 42.9%. QFT-GIT has a significant additive value to single TST for detecting LTBI in institutionalized older adults, identifying infected subjects anergic to the TST.

Usefulness of Interferon-Gamma Release Assay for Diagnosis of Tuberculous Fistulae in Ano

Purpose: Interferon gamma release assays (QuantiFERON-TB Gold in Tube test [QFT-GIT]); Cellestis Limited, Victoria, Australia) have been studied for diagnosing pulmonary tuberculosis (TB) or latent TB but there have been no reports on the usefulness of this assay in diagnosing tuberculous anal fistula in actual clinical practices. In this study, we evaluated its diagnostic usefulness in patients with suspected tuberculous anal fistula. Methods: We conducted a retrospective analysis of 119 patients with suspected tuberculous anorectal fistula from May 2007 to May 2009. Diagnosis of tuberculous fistula was concluded by identification of acid-fast bacilli, typical caseating granuloma and successful clinical response to anti-TB chemotherapy. All patients underwent the QFT-GIT and all patients diagnosed with tuberculous anal fistula were analyzed. Results: Of the 119 patients with suspected TB fistula, 51 (43%) patients were classified as having TB fistula, including 31 with confirmed tuberculosis and 20 with probable tuberculosis, and other 68 (57%) were classified as not having tuberculosis. Among the 51 patients with TB fistula, Chronic caseating granuloma, acid-fast bacilli stain, and successful clinical response to anti-TB treatment were positive in 27 (52.9%), 4 (7.8%), and 20 (39.2%), respectively. Of the 51 with TB fistula, 44 had positive QFT-GIT results and 7 had negative results. The sensitivity and specificity of the assay were 86% and 85%, and positive predictive value (PPV) and negative predictive value (NPV) were 81% and 89%, respectively. Conclusion: QFT-GIT is a simple, sensitive, and specific method for the diagnosis of clinically highly suspected TB fistula.

Interferon-gamma release assays for the diagnosis of TB pleural effusions: hype or real hope?

T-cell interferon-gamma release assay (IGRA) use in tuberculosis (TB) contact screening and latent TB diagnosis is established and supported by American and European guidelines. However, questions remain regarding their clinical utility beyond conventional tests in the investigation of suspected active TB. We review the evidence base for IGRAs in the diagnosis or exclusion of pleural TB. The specificity of IGRAs for diagnosis of active TB disease is limited by an inability to distinguish latent disease. The test's sensitivity when applied to the blood of patients with active TB is diminished by compartmentalizing of sensitized T cells at the disease site. To circumnavigate these problems, recent studies explore the value of applying IGRAs to pleural fluid. Results have varied between patient populations, but the strategy does not appear to completely eliminate false-positive results. Accurate biomarkers of pleural TB are useful, particularly for their negative predictive value. IGRAs are technically more complicated and expensive than established biomarkers, and their diagnostic performance for active pleural TB is highly variable between studies and settings. Currently, there is inadequate evidence to support the use of IGRAs in the diagnosis or exclusion of active pleural TB, particularly in centres where adenosine deaminase and interferon-gamma assays are available.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-γ release assay vs. tuberculin skin test

Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

Usefulness of interferon-gamma release assays for diagnosing TB infection and problems with these assays

The specificity of the tuberculin skin test (TST) in the diagnosis of tuberculosis infection is seriously compromised because of extensive use of the bacille Calmette-Guérin (BCG) vaccination. The interferon-gamma release assay (IGRA), a new diagnostic using Mycobacterium tuberculosis-specific antigens has been introduced in response to these needs. In this review, published findings on the performance of the QuantiFERON-TB (QFT), one of the IGRA formats, are summarized and discussed. In addition to its high specificity, the QFT has considerably high sensitivity, comparable with or superior to that of the TST, if applied to patients with active tuberculosis as a surrogate of latent tuberculosis infection. When applied to patients with immunosuppression, such as aging patients, or those with HIV infection, those with immunosuppressive drug therapies, or those with renal hemodialysis, QFT is shown to be more robust than the TST. As regards the dynamics of QFT responses to chemotherapy, there are many reports showing a decrease in responses during the treatment, which indicates the possibility that QFT could be used as a tool for monitoring the progress of treatment. However, there are discordant reports that warrant further study.

The Value of Interferon Gamma Release Assays for Diagnosis Infection With Mycobacterium Tuberculosis During an Annual Screening of Health Care Workers

The Value of Interferon Gamma Release Assays for Diagnosis Infection With Mycobacterium Tuberculosis During an Annual Screening of Health Care Workers

Tuberculosis screening of travelers to higher-incidence countries: A cost-effectiveness analysis

BackgroundTravelers to countries with high tuberculosis incidence can acquire infection during travel. We sought to compare four screening interventions for travelers from low-incidence countries, who visit countries with varying tuberculosis incidence.MethodsDecision analysis model: We considered hypothetical cohorts of 1,000 travelers, 21 years old, visiting Mexico, the Dominican Republic, or Haiti for three months. Travelers departed from and returned to the United States or Canada; they were born in the United States, Canada, or the destination countries. The time horizon was 20 years, with 3% annual discounting of future costs and outcomes. The analysis was conducted from the health care system perspective. Screening involved tuberculin skin testing (post-travel in three strategies, with baseline pre-travel tests in two), or chest radiography post-travel (one strategy). Returning travelers with tuberculin conversion (one strategy) or other evidence of latent tuberculosis (three strategies) were offered treatment. The main outcome was cost (in 2005 US dollars) per tuberculosis case prevented.ResultsFor all travelers, a single post-trip tuberculin test was most cost-effective. The associated cost estimate per case prevented ranged from $21,406 for Haitian-born travelers to Haiti, to $161,196 for US-born travelers to Mexico. In all sensitivity analyses, the single post-trip tuberculin test remained most cost-effective. For US-born travelers to Haiti, this strategy was associated with cost savings for trips over 22 months. Screening was more cost-effective with increasing trip duration and infection risk, and less so with poorer treatment adherence.ConclusionA single post-trip tuberculin skin test was the most cost-effective strategy considered, for travelers from the United States or Canada. The analysis did not evaluate the use of interferon-gamma release assays, which would be most relevant for travelers who received BCG vaccination after infancy, as in many European countries. Screening decisions should reflect duration of travel, tuberculosis incidence, and commitment to treat latent infection.

T-cell assays for the diagnosis of latent tuberculosis infection: moving the research agenda forward

For nearly a century, the tuberculin skin test was the only tool available for the detection of latent tuberculosis infection. A recent breakthrough has been the development of T-cell-based interferon-gamma release assays. Current evidence suggests interferon-gamma release assays have higher specificity than the tuberculin skin test, better correlation with surrogate markers of exposure to Mycobacterium tuberculosis in low-incidence settings, and less cross-reactivity as a result of BCG vaccination compared with the tuberculin skin test. The body of literature supporting the use of interferon-gamma release assays has rapidly expanded. However, several unresolved and unexplained issues remain. To address these issues, a group of experts met in Geneva, Switzerland, in March, 2006, to discuss the research evidence on T-cell-based assays, their clinical usefulness, limitations, and directions for future research, with a specific focus on resource-limited and high HIV prevalence settings. On the basis of 2 days of discussions, a comprehensive research agenda was generated, which will propel the field forward by stimulating focused high-impact research and encourage the investment of resources needed to tackle priority research questions, especially in resource-limited settings. Ultimately, if adequately financed, the research findings will inform appropriate use of novel latent tuberculosis infection diagnostics in global tuberculosis control.

Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay

BackgroundThe whole-blood interferon-gamma release assay (IGRA) is recommended in some settings as an alternative to the tuberculin skin test (TST). Outcomes from field implementation of the IGRA for routine tuberculosis (TB) testing have not been reported. We evaluated feasibility, acceptability, and costs after 1.5 years of IGRA use in San Francisco under routine program conditions.MethodsPatients seen at six community clinics serving homeless, immigrant, or injection-drug user (IDU) populations were routinely offered IGRA (Quantiferon-TB). Per guidelines, we excluded patients who were <17 years old, HIV-infected, immunocompromised, or pregnant. We reviewed medical records for IGRA results and completion of medical evaluation for TB, and at two clinics reviewed TB screening logs for instances of IGRA refusal or phlebotomy failure.ResultsBetween November 1, 2003 and February 28, 2005, 4143 persons were evaluated by IGRA. 225(5%) specimens were not tested, and 89 (2%) were IGRA-indeterminate. Positive or negative IGRA results were available for 3829 (92%). Of 819 patients with positive IGRA results, 524 (64%) completed diagnostic evaluation within 30 days of their IGRA test date. Among 503 patients eligible for IGRA testing at two clinics, phlebotomy was refused by 33 (7%) and failed in 40 (8%). Including phlebotomy, laboratory, and personnel costs, IGRA use cost $33.67 per patient tested.ConclusionIGRA implementation in a routine TB control program setting was feasible and acceptable among homeless, IDU, and immigrant patients in San Francisco, with results more frequently available than the historically described performance of TST. Laboratory-based diagnosis and surveillance for M. tuberculosis infection is now possible.