Background.Almost one-fifth of United States tuberculosis cases are extrapulmonary; unexplained slower annual case count decreases have occurred in extrapulmonary tuberculosis (EPTB), compared with ...annual case count decreases in pulmonary tuberculosis (PTB) cases. We describe the epidemiology of EPTB by means of US national tuberculosis surveillance data. Methods.US tuberculosis cases reported from 1993 to 2006 were classified as either EPTB or PTB. EPTB encompassed lymphatic, pleural, bone and/or joint, genitourinary, meningeal, peritoneal, and unclassified EPTB cases. We excluded cases with concurrent extrapulmonary-pulmonary tuberculosis and cases of disseminated (miliary) tuberculosis. Demographic characteristics, drug susceptibility test results, and risk factors, including human immunodeficiency virus (HIV) status, were compared for EPTB and PTB cases. Results.Among 253,299 cases, 73.6% were PTB and 18.7% were EPTB, including lymphatic (40.4%), pleural (19.8%), bone and/or joint (11.3%), genitourinary (6.5%), meningeal (5.4%), peritoneal (4.9%), and unclassified EPTB (11.8%) cases. Compared with PTB, EPTB was associated with female sex (odds ratio OR, 1.7; 95% confidence interval CI, 1.7–1.8) and foreign birth (OR, 1.5; CI, 1.5–1.6), almost equally associated with HIV status (OR, 1.1; CI, 1.1–1.1), and negatively associated with multidrug resistance (OR, 0.6; CI, 0.5–0.6) and several tuberculosis risk factors, especially homelessness (OR, 0.3; CI, 0.3–0.3) and excess alcohol use (OR, 0.3; CI, 0.3–0.3). Slower annual decreases in EPTB case counts, compared with annual decreases in PTB case counts, from 1993 through 2006 have caused EPTB to increase from 15.7% of tuberculosis cases in 1993 to 21.0% in 2006. Conclusions.EPTB epidemiology and risk factors differ from those of PTB, and the proportion of EPTB has increased from 1993 through 2006. Further study is needed to identify causes of the proportional increase in EPTB.
Summary Since 1989, the USA has been pursuing the goal of tuberculosis elimination. After substantial progress during the past two decades, the rate of tuberculosis cases in the USA each year has now ...levelled off and remains well above the elimination threshold. Both epidemiological data and modelling underline the necessity of addressing latent tuberculosis infection if further progress is to be made in eliminating the disease. In this Personal View we explore next steps towards elimination. Given the estimated prevalence of latent tuberculosis infection, compared with the limited testing and treatment that currently occur, a major new effort is required. This effort should consist of a surveillance system or registry to monitor progress, scale-up of targeted testing for latent tuberculosis infection in at-risk populations, scale-up of short-course treatment regimens, engagement of affected communities and medical providers who serve those communities, and increased public health staffing for implementation and oversight. Such an effort would benefit greatly from the development of new tools, such as tests that better indicate reactivation risk, and even shorter latent tuberculosis infection treatment regimens than currently exist.
Reexamining the prevalence of persons infected with tuberculosis (TB) is important to determine trends over time. In 2011-2012 a TB component was included in the National Health and Nutrition ...Examination Survey (NHANES) to estimate the reservoir of persons infected with TB.
Civilian, noninstitutionalized U.S. population survey participants aged 6 years and older were interviewed regarding their TB history and eligibility for the tuberculin skin test (TST) and interferon gamma release assay (IGRA) blood test. Once eligibility was confirmed, both tests were conducted. Prevalence and numbers of TST positive (10 mm or greater), IGRA positive, and both TST and IGRA positive were calculated by adjusting for the complex survey design after applying corrections for item nonresponse and digit preference in TST induration measurements. To examine TST positivity over time, data from NHANES 1999-2000 were reanalyzed using the same statistical methods. The TST was performed using Tubersol, a commercially available purified protein derivative (PPD), rather than PPD-S, which was the antigen used in NHANES 1999-2000. Prior patient history of TB vaccination was not collected in this study nor were patients examined for the presence of a Bacillus of Calmette and Guerin (BCG) vaccine scar.
For NHANES 2011-2012, TST and IGRA results were available for 6,128 (78.4%) and 7,107 (90.9%) eligible participants, respectively. There was no significant difference between the percentage of the U.S. population that was TST positive in 2011-2012 (4.7% 95% CI 3.4-6.3; 13,276,000 persons) compared with 1999-2000 (4.3%; 3.5-5.3). In 2011-2012 the percentage that was IGRA positive was 5.0% (4.2-5.8) and double TST and IGRA positivity was 2.1% (1.5-2.8). The point estimate of IGRA positivity prevalence in foreign-born persons (15.9%; 13.5-18.7) was lower than for TST (20.5%; 16.1-25.8) in 2011-2012. The point estimate of IGRA positivity prevalence in U.S.-born persons (2.8%; 2.0-3.8) was higher than for TST (1.5%; 0.9-2.6).
No statistically significant decline in the overall estimated prevalence of TST positivity was detected from 1999-2000 to 2011-2012. The prevalence of TB infection, whether measured by TST or IGRA, remains lower among persons born in the United States compared with foreign-born persons.
Background. Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent ...tuberculosis infection LTBI). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. Methods. A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results. Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. Conclusions. These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection ...LTBI). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.
A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach.
Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional.
These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
Patients receiving anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy are at increased risk for tuberculosis and other granulomatous diseases, but little is known about illness caused by ...nontuberculous mycobacteria (NTM) in this setting. We reviewed the US Food and Drug Administration MedWatch database for reports of NTM disease in patients receiving anti-TNF-alpha therapy. Of 239 reports collected, 105 (44%) met NTM disease criteria. Median age was 62 years; the majority of patients (66, 65%) were female, and most (73, 70%) had rheumatoid arthritis. NTM infections were associated with infliximab (n = 73), etanercept (n = 25), and adalimumab (n = 7); most patients were taking prednisone (n = 68, 65%) or methotrexate (n = 58, 55%) concurrently. Mycobacteria avium (n = 52, 50%) was most commonly implicated, and 9 patients (9%) had died at the time their infections were reported. A high rate of extrapulmonary manifestations (n = 46, 44%) was also reported.
Isoniazid is an efficacious treatment for latent tuberculosis. Concerns remain, however, regarding hepatotoxicity associated with this medication. In addition, adherence may be suboptimal because at ...least 6 months of treatment is required. We extracted information from our latent tuberculosis treatment database to determine adverse effects and treatment completion rates associated with the use of isoniazid at a county tuberculosis clinic. Outcomes were available for 3,788 patients started on isoniazid between 1999 and 2002. Six hundred seventy-two patients (18%) experienced one or more adverse effects, including 10 (0.3%) determined to have isoniazid-associated liver injury. No hospitalizations or deaths occurred in patients experiencing an adverse effect. A higher incidence of adverse effects was associated with increasing age. Sixty-four percent of patients completed at least 6 months of isoniazid. Higher completion rates were associated with younger age, Hispanic ethnicity, and non-U.S. country of birth. Lower completion rates were associated with being homelessness, using excess alcohol, and having experienced an adverse effect. In summary, we conclude that in our clinic population isoniazid is a safe therapy for latent tuberculosis, but its effectiveness is limited by modest completion rates.
Mycobacterium tuberculosis (Mtb) infection may cause overt disease or remain latent. Interferon gamma release assays (IGRAs) detect Mtb infection, both latent infection and infection manifesting as ...overt disease, by measuring whole-blood interferon gamma (IFN-γ) responses to Mtb antigens such as early secreted antigenic target-6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7. Due to a lack of adequate diagnostic standards for confirming latent Mtb infection, IGRA sensitivity for detecting Mtb infection has been estimated using patients with culture-confirmed tuberculosis (CCTB) for whom recovery of Mtb confirms the infection. In this study, cytokines in addition to IFN-γ were assessed for potential to provide robust measures of Mtb infection.
Cytokine responses to ESAT-6, CFP-10, TB7.7, or combinations of these Mtb antigens, for patients with CCTB were compared with responses for subjects at low risk for Mtb infection (controls). Three different multiplexed immunoassays were used to measure concentrations of 9 to 20 different cytokines. Responses were calculated by subtracting background cytokine concentrations from cytokine concentrations in plasma from blood stimulated with Mtb antigens.
Two assays demonstrated that ESAT-6, CFP-10, ESAT-6+CFP-10, and ESAT-6+CFP-10+TB7.7 stimulated the release of significantly greater amounts of IFN-γ, IL-2, IL-8, MCP-1 and MIP-1β for CCTB patients than for controls. Responses to combination antigens were, or tended to be, greater than responses to individual antigens. A third assay, using whole blood stimulation with ESAT-6+CFP-10+TB7.7, revealed significantly greater IFN-γ, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1β, and TNF-α responses among patients compared with controls. One CCTB patient with a falsely negative IFN-γ response had elevated responses with other cytokines.
Multiple cytokines are released when whole blood from patients with CCTB is stimulated with Mtb antigens. Measurement of multiple cytokine responses may improve diagnostic sensitivity for Mtb infection compared with assessment of IFN-γ alone.
Background. Understanding the epidemiology of human Mycobacterium bovis tuberculosis (TB) in the United States is imperative; this disease can be foodborne or airborne, and current US control ...strategies are focused on TB due to Mycobacterium tuberculosis and airborne transmission. The National TB Genotyping Service's work has allowed systematic identification of M. tuberculosis-complex isolates and enabled the first US-wide study of M. bovis TB. Methods. Results of spacer oligonucleotide and mycobacterial interspersed repetitive units typing were linked to corresponding national surveillance data for TB cases reported for the period 2004–2005 and select cases for the period 1995–2003.We also used National TB Genotyping Service data to evaluate the traditional antituberculous drug resistance-based case definition of M. bovis TB. Results. Isolates from 165 (1.4%) of 11,860 linked cases were identified as M. bovis. Patients who were not born in the United States, Hispanic patients, patients <15 years of age, patients reported to be HIV infected, and patients with extrapulmonary disease each had increased adjusted odds of having M. bovis versus M. tuberculosis TB. Most US-born, Hispanic patients with TB due to M. bovis (29 90.6% of 32) had extrapulmonary disease, and their overall median age was 9.5 years. The National TB Genotyping Service's data indicated that the pyrazinamide- based case definition's sensitivity was 82.5% (95% confidence interval; 75.3%–87.9%) and that data identified 14 errors in pyrazinamide-susceptibility testing or reporting. Conclusions. The prevalence of extrapulmonary disease in the young, US-born Hispanic population suggests recent transmission of M. bovis, possibly related to foodborne exposure. Because of its significantly different epidemiologic profile, compared with that of M. tuberculosis TB, we recommend routine surveillance of M. bovis TB. Routine surveillance and an improved understanding of M. bovis TB transmission dynamics would help direct the development of additional control measures.
Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment ...response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden.
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