Publications by authors named "Randall Reves"

54 Publications

Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study.

Lancet Infect Dis 2021 Sep 6. Epub 2021 Sep 6.

Division of Tuberculosis Elimination, US Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups.

Methods: In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10-99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at ClinicalTrials.gov, NCT01622140.

Findings: Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6-1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9-2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8-1·0) and 1·3 (1·2-1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (p<0·0001). Test agreement was higher between the two IFN-γ release assays than between TST and either IFN-γ release assay, regardless of birthplace. κ agreement was particularly low between TST and IFN-γ release assays in non-US-born children younger than 5 years.

Interpretation: Our findings support the preferential use of IFN-γ release assays for the diagnosis of latent tuberculosis in high-risk populations, especially in very young and older people born outside the USA.

Funding: US Centers for Disease Control and Prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(21)00145-6DOI Listing
September 2021

Impact of T-Cell Xtend on T-SPOT. Assay in High-Risk Individuals after Delayed Blood Sample Processing.

J Clin Microbiol 2021 04 20;59(5). Epub 2021 Apr 20.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA

T-SPOT. (T-SPOT) is an interferon gamma release assay (IGRA) used to detect infection with based on the number of spot-forming T cells; however, delays in sample processing have been shown to reduce the number of these spots that are detected following laboratory processing. Adding T-Cell Xtend (XT) into blood samples before processing reportedly extends the amount of time allowed between blood collection and processing up to 32 h. In this study, paired blood samples from 306 adolescents and adults at high risk for latent tuberculosis (TB) infection (LTBI) or progression to TB disease were divided into three groups: (i) early processing (∼4.5 h after collection) with and without XT, (ii) delayed processing (∼24 h after collection) with and without XT, and (iii) early processing without XT and delayed processing with XT. The participants' paired samples were processed at a local laboratory and agreement of qualitative and quantitative results was assessed. The addition of XT did not consistently increase or decrease the number of spots. In groups 1, 2, and 3, samples processed with XT had 13% (10/77), 28.0% (30/107), and 24.6% (30/122), respectively, more spots, while 33.8% (26/77), 26.2% (28/107), and 38.5% (47/122) had fewer spots than samples processed without XT. The findings suggest that XT does not reliably mitigate the loss of spot-forming T cells in samples with processing delay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.00120-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091829PMC
April 2021

Our love-hate relationship with pyrazinamide.

Authors:
Randall Reves

Clin Infect Dis 2020 Oct 3. Epub 2020 Oct 3.

Division of Infectious Diseases, Department of Medicine and School of Public Health, University of Colorado Denver, Aurora, Colorado.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1505DOI Listing
October 2020

Tuberculosis Screening, Testing, and Treatment of US Health Care Personnel: ACOEM and NTCA Joint Task Force on Implementation of the 2019 MMWR Recommendations.

J Occup Environ Med 2020 07;62(7):e355-e369

American College of Occupational and Environmental Medicine, Elk Grove, Illinois.

: On May 17, 2019, the US Centers for Disease Control and Prevention and National Tuberculosis Controllers Association issued new Recommendations for Tuberculosis Screening, Testing, and Treatment of Health Care Personnel, United States, 2019, updating the health care personnel-related sections of the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005. This companion document offers the collective effort and experience of occupational health, infectious disease, and public health experts from major academic and public health institutions across the United States and expands on each section of the 2019 recommendations to provide clarifications, explanations, and considerations that go beyond the 2019 recommendations to answer questions that may arise and to offer strategies for implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JOM.0000000000001904DOI Listing
July 2020

Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020.

MMWR Recomm Rep 2020 02 14;69(1):1-11. Epub 2020 Feb 14.

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15585/mmwr.rr6901a1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041302PMC
February 2020

Interferon-γ Release Assays in Children <15 Years of Age.

Pediatrics 2020 01;145(1)

Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.

Objectives: The tuberculin skin test (TST) has been preferred for screening young children for latent tuberculosis infection (LTBI) because of concerns that interferon-γ release assays (IGRAs) may be less sensitive in this high-risk population. In this study, we compared the predictive value of IGRAs to the TST for progression to tuberculosis disease in children, including those <5 years old.

Methods: Children <15 years old at risk for LTBI or progression to disease were tested with TST, QuantiFERON-TB Gold In-Tube test (QFT-GIT), and T-SPOT. test (T-SPOT) and followed actively for 2 years, then with registry matches, to identify incident disease.

Results: Of 3593 children enrolled September 2012 to April 2016, 92% were born outside the United States; 25% were <5 years old. Four children developed tuberculosis over a median 4.3 years of follow-up. Sensitivities for progression to disease for TST and IGRAs were low (50%-75%), with wide confidence intervals (CIs). Specificities for TST, QFT-GIT, and T-SPOT were 73.4% (95% CI: 71.9-74.8), 90.1% (95% CI: 89.1-91.1), and 92.9% (95% CI: 92.0-93.7), respectively. Positive and negative predictive values for TST, QFT-GIT, and T-SPOT were 0.2 (95% CI: 0.1-0.8), 0.9 (95% CI: 0.3-2.5), and 0.8 (95% CI: 0.2-2.9) and 99.9 (95% CI: 99.7-100), 100 (95% CI: 99.8-100), and 99.9 (95% CI: 99.8-100), respectively. Of 533 children with TST-positive, IGRA-negative results not treated for LTBI, including 54 children <2 years old, none developed disease.

Conclusions: Although both types of tests poorly predict disease progression, IGRAs are no less predictive than the TST and offer high specificity and negative predictive values. Results from this study support the use of IGRAs for children, especially those who are not born in the United States.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2019-1930DOI Listing
January 2020

Clinical Characteristics of Active Tuberculosis Diagnosed After Starting Treatment for Latent Tuberculosis Infection.

Clin Infect Dis 2020 08;71(5):1320-1323

University of Colorado School of Medicine, Aurora, Colorado, USA.

Although rare, subclinical tuberculosis disease can be missed during evaluations for latent tuberculosis infection, and can manifest with symptoms during latent tuberculosis treatment. Among over 8000 patients treated for latent tuberculosis we found no evidence of acquired drug resistance, underscoring the safety of rifampin monotherapy for latent tuberculosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz1157DOI Listing
August 2020

Strong Community-Public Health Partnerships May Help Us Move Closer to Tuberculosis Elimination.

Am J Public Health 2019 07;109(7):958-959

The authors are with the Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, and the Denver Metro Tuberculosis Program, Denver, CO.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2105/AJPH.2019.305133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603450PMC
July 2019

Tuberculosis Screening, Testing, and Treatment of U.S. Health Care Personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019.

MMWR Morb Mortal Wkly Rep 2019 May 17;68(19):439-443. Epub 2019 May 17.

The 2005 CDC guidelines for preventing Mycobacterium tuberculosis transmission in health care settings include recommendations for baseline tuberculosis (TB) screening of all U.S. health care personnel and annual testing for health care personnel working in medium-risk settings or settings with potential for ongoing transmission (1). Using evidence from a systematic review conducted by a National Tuberculosis Controllers Association (NTCA)-CDC work group, and following methods adapted from the Guide to Community Preventive Services (2,3), the 2005 CDC recommendations for testing U.S. health care personnel have been updated and now include 1) TB screening with an individual risk assessment and symptom evaluation at baseline (preplacement); 2) TB testing with an interferon-gamma release assay (IGRA) or a tuberculin skin test (TST) for persons without documented prior TB disease or latent TB infection (LTBI); 3) no routine serial TB testing at any interval after baseline in the absence of a known exposure or ongoing transmission; 4) encouragement of treatment for all health care personnel with untreated LTBI, unless treatment is contraindicated; 5) annual symptom screening for health care personnel with untreated LTBI; and 6) annual TB education of all health care personnel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15585/mmwr.mm6819a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522077PMC
May 2019

Latent tuberculosis infection: Opportunities and challenges.

Respirology 2018 10 14;23(10):893-900. Epub 2018 Jun 14.

Denver Health and Hospital Authority, Denver Public Health Department, CO, USA.

Diagnosing and treating latent tuberculosis (TB) infection (LTBI) is recognized by the World Health Organization as an important strategy to accelerate the decline in global TB and achieve TB elimination. Even among low-TB burden countries that have achieved high rates of detection and successful treatment for active TB, a number of barriers have prevented implementing or expanding LTBI treatment programmes. Of those infected with TB, relatively few will develop active disease and the current diagnostic tests have a low predictive value. LTBI treatment using isoniazid (INH) has low completion rates due to the long duration of therapy and poor tolerability. Both patients and physicians often perceive the risk of toxicity to be greater than the risk of reactivation TB. As a result, LTBI treatment has had a limited or negligible role outside of countries with high resources and low burden of disease. New tools have emerged including the interferon-gamma release assays that more accurately diagnose LTBI, particularly in people vaccinated with Bacillus Calmette-Guerin (BCG). Shorter, better tolerated treatment using rifamycins are proving safe and effective alternatives to INH. While still imperfect, TB prevention using these new diagnostic and treatment tools appear cost effective in modelling studies in the United States and have the potential to improve TB prevention efforts globally. Continued research to understand the host-organism interactions within the spectrum of LTBI is needed to develop better tools. Until then, overcoming the barriers and optimizing our current tools is essential for progressing toward TB elimination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/resp.13346DOI Listing
October 2018

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

Lancet Respir Med 2018 04;6(4):265-275

Academic Tuberculosis Program, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ.

Methods: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology.

Findings: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1-7·3), but no significant effect on mortality (aOR 0·7, 0·4-1·1) or acquired rifampicin resistance (aOR 0·1, 0·0-1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2-0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates.

Interpretation: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis.

Funding: World Health Organization and Canadian Institutes of Health Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(18)30078-XDOI Listing
April 2018

In reply: We and our patients must demand better TB diagnostics.

Int J Tuberc Lung Dis 2017 12;21(12):1316

University of Colorado Denver, Denver, CO, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5588/ijtld.17.0458-2DOI Listing
December 2017

Better Completion of Pediatric Latent Tuberculosis Treatment Using 4 Months of Rifampin in a US-based Tuberculosis Clinic.

Pediatr Infect Dis J 2018 03;37(3):224-228

Background: Children less than 5 years of age have the highest age-specific rate of progression from latent tuberculosis infection (LTBI) to active disease. Therefore, regimens for treatment of pediatric LTBI must be not only efficacious but practical enough to overcome the unique childhood barriers to regimen adherence. Since 2012, a 4-month regimen of daily rifampin (4R) has been the standard recommendation for pediatric LTBI at the Denver Metro Tuberculosis Clinic.

Methods: Using univariate and multivariate analyses, we compared treatment completion rates between 4R and 9-month isoniazid (9H) regimens for all pediatric patients treated for LTBI at the Denver Metro Tuberculosis Clinic between January 1, 2006, and December 31, 2015, and assessed the influence of clinical and demographic characteristics on successful completion of the 2 regimens.

Results: There were 395 children in the 4R cohort and 779 in the 9H cohort. Completion rates overall were significantly higher for 4R than 9H (83.5% vs. 68.8%, P < 0.001). Drug toxicity leading to treatment noncompletion was low in both groups (1.5% in 4R and 0.7% in 9H, P = 0.23), and no patient progressed to active tuberculosis in either cohort. The 9H cohort was more likely to fail treatment completion because of barriers potentially related to the longer duration of treatment such as relocation or loss to follow-up.

Conclusions: Pediatric patients were significantly more likely to complete LTBI treatment using a 4R than with a 9-month isoniazid regimen. Better completion rates of 4R may increase efficacy of tuberculosis prevention and decrease demand on public health resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000001721DOI Listing
March 2018

Is it time to rethink the role of AFB smears?

Int J Tuberc Lung Dis 2017 07;21(7):720

University of Colorado Denver, Denver, COUSA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5588/ijtld.17.0323DOI Listing
July 2017

The cost of the failure to eliminate tuberculosis in the United States.

Int J Tuberc Lung Dis 2017 01;21(1):120

Independent public health consultant, Orinda, CO, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5588/ijtld.16.0708DOI Listing
January 2017

Highly Multiplexed Proteomic Analysis of Quantiferon Supernatants To Identify Biomarkers of Latent Tuberculosis Infection.

J Clin Microbiol 2017 02 16;55(2):391-402. Epub 2016 Nov 16.

Denver Health and Hospital Authority and Denver Public Health, Denver, Colorado, USA

The tests for diagnosing latent tuberculosis infection (LTBI) are limited by a poor predictive value for identifying people at the highest risk for progressing to active tuberculosis (TB) and have various sensitivities and specificities in different populations. Identifying a more robust signature for LTBI is important for TB prevention and elimination. A pilot study was conducted with samples from immigrants to the United States that were screened for LTBI by the three commercially approved tests, namely, the tuberculin skin test (TST), the Quantiferon-TB Gold in-tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). QFT-GIT supernatants from 13 people with concordant positive results and 26 people with concordant negative results were analyzed via the highly multiplexed SOMAscan proteomic assay. The proteins in the stimulated supernatants that distinguished LTBI from controls included interleukin-2 (IL-2), monocyte chemotactic protein 2 (MCP-2), interferon gamma inducible protein-10 (IP-10), interferon gamma (IFN-γ), tumor necrosis factor superfamily member 14 (TNFSF14, also known as LIGHT), monokine induced by gamma interferon (MIG), and granzyme B (P <0.00001). In addition, antigen stimulation increased the expression of heparin-binding EGF-like growth factor (HB-EGF) and activin AB in LTBI samples. In nil tubes, LIGHT was the most significant marker (P <0.0001) and was elevated in LTBI subjects. Other prominent markers in nonstimulated QFT-GIT supernatants were the complement-3 components C3b, iC3b, and C3d, which were upregulated in LTBI and markedly decreased upon stimulation. We found known and novel proteins that warrant further studies for developing improved tests for LTBI, for predicting progression to active disease, and for discriminating LTBI from active TB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.01646-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5277508PMC
February 2017

Screening for Latent Tuberculosis Infection: A Key Step Toward Achieving Tuberculosis Elimination in the United States.

JAMA Intern Med 2016 10;176(10):1439-1440

Department of Medicine, National Jewish Health, University of Colorado, Denver.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamainternmed.2016.5464DOI Listing
October 2016

Blood transcriptional signatures for tuberculosis diagnosis: a glass half-empty perspective.

Lancet Respir Med 2016 06;4(6):e28

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA; Pulmonary, Critical Care, and Sleep Medicine Section, Yale School of Medicine, New Haven, CT, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(16)30038-8DOI Listing
June 2016

High Rates of Tuberculosis and Opportunities for Prevention among International Students in the United States.

Ann Am Thorac Soc 2016 Apr;13(4):522-8

2 Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado; and.

Rationale: Foreign-born persons traveling on a student visa are not currently screened for tuberculosis on entry into the United States, despite residing in the United States for up to several years.

Objectives: To characterize the risk of tuberculosis in international students entering the United States and to identify strategies for early diagnosis and prevention in this population.

Methods: Data were collected in 18 tuberculosis control jurisdictions in the United States. A cohort of 1,268 foreign-born patients of known visa status, diagnosed with active tuberculosis between 2004 and 2007, was used for analysis. Incidence rates were estimated on the basis of immigration data from study jurisdictions.

Measurements And Main Results: Tuberculosis was diagnosed in 46 student residents, providing an annual estimate of 308 cases nationally. The estimated tuberculosis case rate in student residents was 48.1 cases per 100,000 person-years (95% confidence interval, 35.6-64.8), more than twice that of the general foreign-born population. Students identified by tuberculosis screening programs were more likely to be diagnosed within 6 months of U.S. arrival (75 vs. 6%; P < 0.001), and those with pulmonary disease were less likely to have a positive sputum smear for acid-fast bacilli compared with those not screened (18 vs. 63%; P = 0.05). In unscreened students, 71% were diagnosed more than 1 year after U.S. arrival and only 6% were previously treated for latent tuberculosis infection.

Conclusions: The tuberculosis case rate in foreign-born students is significantly higher than in other foreign-born individuals. Screening this group after arrival to the United States is an effective strategy for earlier diagnosis of active tuberculosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.201508-547OCDOI Listing
April 2016

Tuberculosis Contact Investigations--United States, 2003-2012.

MMWR Morb Mortal Wkly Rep 2016 Jan 1;64(50-51):1369-74. Epub 2016 Jan 1.

Mycobacterium tuberculosis is transmitted through the air from an infectious patient (index patient) to other persons (contacts) who share space. Exposure to M. tuberculosis can result in tuberculosis (TB) disease or latent TB infection (LTBI), which has no clinical symptoms or radiologic evidence of disease. The cycle of transmission can be ended by isolating and treating patients with TB disease, examining contacts, and treating LTBI to prevent progression to TB disease. CDC systematically collects aggregate data on contact investigations from the 50 states, the District of Columbia (DC), and Puerto Rico. Data from 2003-2012 were analyzed for trends in yields from contact investigations, in terms of numbers of contacts elicited and examined and the estimated number of TB cases averted through treatment of LTBI among contacts in 2012. During 2003-2012, the number of TB cases decreased, while the number of contacts listed per index patient with contacts elicited increased. In 2012, U.S. public health authorities reported 9,945 cases of TB disease (1) and 105,100 contacts. Among these contacts, 84,998 (80.9%) were examined; TB was diagnosed in 532 (0.6%) and LTBI in 15,411 (18.1%). Among contacts with LTBI, 10,137 (65.8%) started treatment, and 6,689 (43.4% of all contacts with LTBI) completed treatment. By investigating contacts in 2012, an estimated 128 TB cases (34% of all potential cases) over the initial 5 years were averted, but an additional 248 cases (66%) might have been averted if all potentially contagious TB patients had contacts elicited, all contacts were examined, and all infected contacts completed treatment. Enhancing contact investigation activities, particularly by ensuring completion of treatment by contacts recently infected with M. tuberculosis, is essential to achieve the goal of TB elimination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15585/mmwr.mm6450a1DOI Listing
January 2016

Blood Transcriptional Biomarkers for Active Tuberculosis among Patients in the United States: a Case-Control Study with Systematic Cross-Classifier Evaluation.

J Clin Microbiol 2016 Feb 18;54(2):274-82. Epub 2015 Nov 18.

Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, Colorado, USA.

Unlabelled: Blood transcriptional signatures are promising for tuberculosis (TB) diagnosis but have not been evaluated among U.S.

Patients: To be used clinically, transcriptional classifiers need reproducible accuracy in diverse populations that vary in genetic composition, disease spectrum and severity, and comorbidities. In a prospective case-control study, we identified novel transcriptional classifiers for active TB among U.S. patients and systematically compared their accuracy to classifiers from published studies. Blood samples from HIV-uninfected U.S. adults with active TB, pneumonia, or latent TB infection underwent whole-transcriptome microarray. We used support vector machines to classify disease state based on transcriptional patterns. We externally validated our classifiers using data from sub-Saharan African cohorts and evaluated previously published transcriptional classifiers in our population. Our classifier distinguishing active TB from pneumonia had an area under the concentration-time curve (AUC) of 96.5% (95.4% to 97.6%) among U.S. patients, but the AUC was lower (90.6% [89.6% to 91.7%]) in HIV-uninfected Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 90.0% (87.7% to 92.3%) and 82.9% (80.8% to 85.1%) when tested in U.S.

Patients: Our classifier distinguishing active TB from latent TB had AUC values of 95.9% (95.2% to 96.6%) among U.S. patients and 95.3% (94.7% to 96.0%) among Sub-Saharan Africans. Previously published comparable classifiers had AUC values of 98.0% (97.4% to 98.7%) and 94.8% (92.9% to 96.8%) when tested in U.S.

Patients: Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable across populations and can be explored as screening assays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.01990-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733166PMC
February 2016

Transnational Record Linkage for Tuberculosis Surveillance and Program Evaluation.

Public Health Rep 2015 Sep-Oct;130(5):475-84

Denver Public Health Department, Denver Metro Tuberculosis Control Program, Denver, CO ; University of Colorado Denver, Division of Pulmonary Sciences and Critical Care Medicine, Aurora, CO.

Objective: Pre-immigration tuberculosis (TB) screening, followed by post-arrival rescreening during the first year, is critical to reducing TB among foreign-born people in the United States. However, existing U.S. public health surveillance is inadequate to monitor TB among immigrants during subsequent years. We developed and tested a novel method for ascertaining post-U.S.-arrival TB outcomes among high-TB-risk immigrant cohorts to improve surveillance.

Methods: We used a probabilistic record linkage program to link pre-immigration screening records from U.S.-bound immigrants from the Philippines (n=422,593) and Vietnam (n=214,401) with the California TB registry during 2000-2010. We estimated sensitivity using Monte Carlo simulations to account for uncertainty in key inputs. Specificity was evaluated by using a time-stratified approach, which defined false-positives as TB records linked to pre-immigration screening records dated after the person had arrived in the United States.

Results: TB was reported in 4,382 and 2,830 people born in the Philippines and Vietnam, respectively, in California during the study period. Of these TB cases, records for 973 and 452 cases of people born in the Philippines and Vietnam, respectively, were linked to pre-immigration screening records. Sensitivity and specificity of linkage were 89% (90% credible interval [CrI] 83, 97) and 100%, respectively, for the Philippines, and 90% (90% CrI 83, 98) and 99.9%, respectively, for Vietnam.

Conclusion: Electronic linkage of pre-immigration screening records to a domestic TB registry was feasible, sensitive, and highly specific in two high-priority immigrant cohorts. Transnational record linkage can be used for program evaluation and routine monitoring of post-U.S.-arrival TB risk among immigrants, but requires interagency data sharing and collaboration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529832PMC
http://dx.doi.org/10.1177/003335491513000511DOI Listing
December 2015

Preventing Infectious Pulmonary Tuberculosis Among Foreign-Born Residents of the United States.

Am J Public Health 2015 Sep 16;105(9):e81-8. Epub 2015 Jul 16.

Amy L. Davidow is with Rutgers Biological and Health Sciences, New Jersey Medical School, Department of Preventive Medicine and Community Health, Newark. Dolly Katz and Smita Ghosh are with Centers for Disease Control and Prevention, Division of TB Elimination, Atlanta, GA. Henry Blumberg is with Emory University School of Medicine, Department of Medicine, Atlanta. Ashutosh Tamhane is with University of Alabama at Birmingham, Department of Medicine. Anna Sevilla is with Global TB Institute, Rutgers Biological and Health Sciences. Randall Reves is with Denver Health and Hospitals Authority, Denver, CO.

Objectives: We described risk factors associated with infectious tuberculosis (TB) and missed TB-prevention opportunities in foreign-born US residents, who account for almost two thirds of the nation's TB patients.

Methods: In a cross-sectional study at 20 US sites of foreign-born persons diagnosed with TB in 2005 through 2006, we collected results of sputum smear microscopy for acid-fast bacilli (a marker for infectiousness) and data on visa status, sociodemographics, TB-related care seeking, and latent TB infection (LTBI) diagnosis opportunities.

Results: Among 980 persons with pulmonary TB who reported their visa status, 601 (61%) were legal permanent residents, 131 (13.4%) had temporary visas, and 248 (25.3%) were undocumented. Undocumented persons were more likely than permanent residents to have acid-fast bacilli-positive smears at diagnosis (risk ratio = 1.3; 95% confidence interval = 1.2, 1.4). Of those diagnosed 1 year or more after arrival, 57.3% reported LTBI screening opportunities; fewer than 25% actually were. Undocumented persons reported fewer LTBI screening opportunities and were less likely to be tested.

Conclusions: Progress toward TB elimination in the United States depends upon expanding opportunities for regular medical care and promotion of LTBI screening and treatment among foreign-born persons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2105/AJPH.2015.302662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539796PMC
September 2015

In reply.

Authors:
Randall R Reves

Int J Tuberc Lung Dis 2015 Apr;19(4):495

Denver Public Health Department, Denver, CO USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5588/ijtld.14.0861-2DOI Listing
April 2015

Evaluation of QuantiFERON-TB gold in-tube and tuberculin skin tests among immigrant children being screened for latent tuberculosis infection.

Pediatr Infect Dis J 2015 Jan;34(1):35-9

From the *Centers for Disease Control and Prevention, Atlanta, GA; †Methodist Hospital Research Institute, Houston, TX; and ‡Denver Health and Hospital Authority, Denver, CO.

Background: Centers for Disease Control and Prevention requirements for pre-immigration tuberculosis (TB) screening of children 2- to 14-years old permit a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Few data are available on the performance of IGRAs versus TSTs in foreign-born children.

Methods: We compared the performance of TST and QuantiFERON-TB (QFT) Gold In-Tube in children 2- to 14-years old applying to immigrate to the United States from Mexico, the Philippines and Vietnam, using diagnosis of TB in immigrating family members as a measure of potential exposure.

Results: We enrolled 2520 children: 664 (26%) were TST+ and 142 (5.6%) were QFT+. One hundred and eleven (4.4%) were TST+/QFT+, 553 (21.9%) were TST+/QFT- and 31 (1.2%) were TST-/QFT+. Agreement between tests was poor (κ = 0.20). Although positive results of both tests were significantly associated with older age (relative risks [RR] TST+, 1.64; 95% confidence interval [CI]: 1.36-1.97; RR QFT+, 3.05; 95% CI: 1.72-5.38) and with the presence of TB in at least 1 immigrating family member (RR TST+, 1.40; 95% CI: 1.12-1.75; RR QFT+ 2.24; 95% CI: 1.18-4.28), QFT+ results were more strongly associated with both predictive variables.

Conclusions: The findings support the preferential use of QFT over TST for pre-immigration screening of foreign-born children 2 years of age and older and lend support to the preferential use of IGRAs in testing foreign-born children for latent TB infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000000494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136477PMC
January 2015

Update in tuberculosis and nontuberculous mycobacterial infections 2013.

Am J Respir Crit Care Med 2014 Apr;189(8):894-8

1 Department of Medicine, University of Colorado, Denver, Colorado.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201402-0210UPDOI Listing
April 2014

Epidemiology of tuberculosis in young children in the United States.

Pediatrics 2014 Mar 10;133(3):e494-504. Epub 2014 Feb 10.

Department of Epidemiology, University of Washington, Seattle, Washington;

Objectives: To estimate tuberculosis (TB) rates among young children in the United States by children's and parents' birth origins and describe the epidemiology of TB among young children who are foreign-born or have at least 1 foreign-born parent.

Methods: Study subjects were children <5 years old diagnosed with TB in 20 US jurisdictions during 2005-2006. TB rates were calculated from jurisdictions' TB case counts and American Community Survey population estimates. An observational study collected demographics, immigration and travel histories, and clinical and source case details from parental interviews and health department and TB surveillance records.

Results: Compared with TB rates among US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. Most TB cases (53%) were among the 29% of children who were US born with foreign-born parents. In the observational study, US-born children with foreign-born parents were more likely than foreign-born children to be infants (30% vs. 7%), Hispanic (73% vs. 37%), diagnosed through contact tracing (40% vs. 7%), and have an identified source case (61% vs. 19%); two-thirds of children were exposed in the United States.

Conclusions: Young children who are US born of foreign-born parents have relatively high rates of TB and account for most cases in this age group. Prompt diagnosis and treatment of adult source cases, effective contact investigations prioritizing young contacts, and targeted testing and treatment of latent TB infection are necessary to reduce TB morbidity in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2013-2570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135007PMC
March 2014

Tuberculosis screening by tuberculosis skin test or QuantiFERON-TB Gold In-Tube Assay among an immigrant population with a high prevalence of tuberculosis and BCG vaccination.

PLoS One 2013 19;8(12):e82727. Epub 2013 Dec 19.

Denver Health and Hospital Authority, Denver, Colorado, United States of America.

Rationale: Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth.

Objectives: 1. Compare the sensitivity of QuantiFERON-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR.

Methods: We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR.

Results: The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15-19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants.

Conclusions: During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082727PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868593PMC
October 2014
-->