J. Steve Kammerer

Human Tuberculosis due to Mycobacterium bovis in the United States, 1995-2005

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 Services 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 Services data indicated that the pyrazinamide-based case definitions 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.

Estimating the Burden of Tuberculosis among Foreign- Born Persons Acquired Prior to Entering the U.S., 2005- 2009

Background The true burden of reactivation of remote latent tuberculosis infection (reactivation TB) among foreign-born persons with tuberculosis (TB) within the United States is not known. Our study objectives were to estimate the proportion of foreign-born persons with TB due reactivation TB and to describe characteristics of foreign-born persons with reactivation TB. Methods We conducted a cross-sectional study of patients with an M. tuberculosis isolate genotyped by the U.S. National TB Genotyping Service, 2005–2009. TB cases were attributed to reactivation TB if they were not a member of a localized cluster of cases. Localized clusters were determined by a spatial scan statistic of cases with isolates with matching TB genotype results. Crude odds ratios and 95% confidence intervals were used to assess relations between reactivation TB and select factors among foreign-born persons. Main Results Among the 36,860 cases with genotyping and surveillance data reported, 22,151 (60%) were foreign-born. Among foreign-born persons with TB, 18,540 (83.7%) were attributed to reactivation TB. Reactivation TB among foreign-born persons was associated with increasing age at arrival, incidence of TB in the country of origin, and decreased time in the U.S. at the time of TB diagnosis. Conclusions Four out of five TB cases among foreign-born persons can be attributed to reactivation TB and present the largest challenge to TB elimination in the U.S. TB control strategies among foreign-born persons should focus on finding and treating latent tuberculosis infection prior to or shortly after arrival to the United States and on reducing the burden of LTBI through improvements in global TB control.

Estimated Rate of Reactivation of Latent Tuberculosis Infection in the United States, Overall and by Population Subgroup

We estimated the rate of reactivation tuberculosis (TB) in the United States, overall and by population subgroup, using data on TB cases and Mycobacterium tuberculosis isolate genotyping reported to the Centers for Disease Control and Prevention during 2006-2008. The rate of reactivation TB was defined as the number of non-genotypically clustered TB cases divided by the number of person-years at risk for reactivation due to prevalent latent TB infection (LTBI). LTBI was ascertained from tuberculin skin tests given during the 1999-2000 National Health and Nutrition Examination Survey. Clustering of TB cases was determined using TB genotyping data collected by the Centers for Disease Control and Prevention and analyzed via spatial scan statistic. Of the 39,920 TB cases reported during 2006-2008, 79.7% were attributed to reactivation. The overall rate of reactivation TB among persons with LTBI was estimated as 0.084 (95% confidence interval (CI): 0.083, 0.085) cases per 100 person-years. Rates among persons with and without human immunodeficiency virus coinfection were 1.82 (95% CI: 1.74, 1.89) and 0.073 (95% CI: 0.070, 0.075) cases per 100 person-years, respectively. The rate of reactivation TB among persons with LTBI was higher among foreign-born persons (0.098 cases/100 person-years; 95% CI: 0.096, 0.10) than among persons born in the United States (0.082 cases/100 person-years; 95% CI: 0.080, 0.083). Differences in rates of TB reactivation across subgroups support current recommendations for targeted testing and treatment of LTBI.

DNA Fingerprinting of Mycobacterium tuberculosis Isolates from Epidemiologically Linked Case Pairs

DNA fingerprinting was used to evaluate epidemiologically linked case pairs found during routine tuberculosis (TB) contact investigations in seven sentinel sites from 1996 to 2000. Transmission was confirmed when the DNA fingerprints of source and secondary cases matched. Of 538 case pairs identified, 156 (29%) did not have matching fingerprints. Case pairs from the same household were no more likely to have confirmed transmission than those linked elsewhere. Case pairs with unconfirmed transmission were more likely to include a smear-negative source case (odds ratio [OR] 2.0) or a foreign-born secondary case (OR 3.4) and less likely to include a secondary case <15 years old (OR 0.3). Our study suggests that contact investigations should focus not only on the household but also on all settings frequented by an index case. Foreign-born persons with TB may have been infected previously in high-prevalence countries; screening and preventive measures recommended by the Institute of Medicine could prevent TB reactivation in these cases.

Tuberculosis in Older Adults in the United States, 1993–2008

OBJECTIVES: To describe older adults with tuberculosis (TB) and compare demographic, diagnostic, and disease characteristics and treatment outcomes between older and younger adults with TB.

Isoniazid-Monoresistant Tuberculosis in the United States, 1993 to 2003

BACKGROUND Seven percent of tuberculosis (TB) cases reported to the US National Tuberculosis Surveillance System in 2005 had Mycobacterium tuberculosis isolates with resistance to at least isoniazid. METHODS We undertook this study to describe demographic characteristics, risk factor information, and treatment outcomes for persons with isoniazid-monoresistant (resistant to isoniazid and susceptible to rifampin, pyrazinamide, and ethambutol hydrochloride) TB compared with persons with TB susceptible to all first-line anti-TB drugs. RESULTS The numbers of isoniazid-monoresistant TB cases increased from 303 (4.1%) in 1993 to 351 (4.2%) in 2005. In our multivariate analysis of all TB cases reported from 1993 to 2003, the races/ethnicities of patients with isoniazid-monoresistant TB were significantly more likely to be US-born Asian/Pacific Islander (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.4-2.6), foreign-born Asian/Pacific Islander (1.8; 1.4-2.1), foreign-born black non-Hispanic (1.4; 1.1-1.7), or US-born Hispanic (1.3; 1.1-1.5). Isoniazid monoresistance was also associated with failure to complete therapy within 1 year (aOR, 1.7; 95% CI, 1.5-1.8), a history of TB (1.5; 1.3-1.7), and correctional facility residence (1.5; 1.2-1.7). CONCLUSIONS Isoniazid-monoresistant TB did not decline from January 1, 1993, through December 31, 2005, despite national downward trends observed in overall TB cases and in multidrug-resistant TB cases. Physicians must ensure completion of treatment for patients taking isoniazid as part of their TB or latent TB infection therapy. In addition, physicians should maintain heightened vigilance for isoniazid resistance when evaluating certain at-risk populations for TB and latent TB infection.

Tuberculosis in South Asians Living in the United States, 1993-2004

BACKGROUND Patients with tuberculosis (TB) in the United States are often described in 2 broad categories, US-born and foreign-born, which may mask differences among different immigrant groups. We determined characteristics of patients born in South Asia and diagnosed as having TB in the United States. METHODS All 224,101 TB cases reported to the US National Tuberculosis Surveillance System from the 50 states and the District of Columbia from 1993 to 2004 were included. We used descriptive analysis and logistic regression to explore differences among patients born in South Asia, other foreign-born, and US-born TB patients. RESULTS Half of the South Asian TB patients (50.5%) in our study were in the 25- to 44-year-old age group, compared with 40.1% of other foreign-born TB patients and 31.8% of US-born TB patients. Compared with other foreign-born TB patients, South Asians were more likely to have extrapulmonary disease (odds ratio [OR], 1.7), more likely to be uninfected with human immunodeficiency virus (HIV) (OR, 5.8) but also more likely not to be offered HIV testing (OR, 9.4) or not to accept an HIV test if offered (OR, 11.8), and more likely not to be homeless (OR, 2.9) or not to use drugs or excess alcohol (OR, 2.7). CONCLUSIONS South Asian TB patients in the United States are younger and more commonly develop extrapulmonary TB than other foreign-born patients. New TB control strategies that target younger patients and that encourage HIV testing and inform physicians about high extrapulmonary TB in the absence of common risk factors in South Asians are needed.

Recent Transmission of Tuberculosis - United States, 2011-2014.

Tuberculosis is an infectious disease that may result from recent transmission or from an infection acquired many years in the past; there is no diagnostic test to distinguish the two causes. Cases resulting from recent transmission are particularly concerning from a public health standpoint. To describe recent tuberculosis transmission in the United States, we used a field-validated plausible source-case method to estimate cases likely resulting from recent transmission during January 2011–September 2014. We classified cases as resulting from either limited or extensive recent transmission based on transmission cluster size. We used logistic regression to analyze patient characteristics associated with recent transmission. Of 26,586 genotyped cases, 14% were attributable to recent transmission, 39% of which were attributable to extensive recent transmission. The burden of cases attributed to recent transmission was geographically heterogeneous and poorly predicted by tuberculosis incidence. Extensive recent transmission was positively associated with American Indian/Alaska Native (adjusted prevalence ratio [aPR] = 3.6 (95% confidence interval [CI] 2.9–4.4), Native Hawaiian/Pacific Islander (aPR = 3.2, 95% CI 2.3–4.5), and black (aPR = 3.0, 95% CI 2.6–3.5) race, and homelessness (aPR = 2.3, 95% CI 2.0–2.5). Extensive recent transmission was negatively associated with foreign birth (aPR = 0.2, 95% CI 0.2–0.2). Tuberculosis control efforts should prioritize reducing transmission among higher-risk populations.

Unexpected decline in tuberculosis cases coincident with economic recession - United States, 2009

BackgroundSince 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB.MethodsWe analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred.ResultsThe overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P < .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission.ConclusionsOur assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States.

A Field-Validated Approach Using Surveillance and Genotyping Data to Estimate Tuberculosis Attributable to Recent Transmission in the United States

Tuberculosis genotyping data are frequently used to estimate the proportion of tuberculosis cases in a population that are attributable to recent transmission (RT). Multiple factors influence genotype-based estimates of RT and limit the comparison of estimates over time and across geographic units. Additionally, methods used for these estimates have not been validated against field-based epidemiologic assessments of RT. Here we describe a novel genotype-based approach to estimation of RT based on the identification of plausible-source cases, which facilitates systematic comparisons over time and across geographic areas. We compared this and other genotype-based RT estimation approaches with the gold standard of field-based assessment of RT based on epidemiologic investigation in Arkansas, Maryland, and Massachusetts during 1996-2000. We calculated the sensitivity and specificity of each approach for epidemiologic evidence of RT and calculated the accuracy of each approach across a range of hypothetical RT prevalence rates plausible for the United States. The sensitivity, specificity, and accuracy of genotype-based RT estimates varied by approach. At an RT prevalence of 10%, accuracy ranged from 88.5% for state-based clustering to 94.4% with our novel approach. Our novel, field-validated approach allows for systematic assessments over time and across public health jurisdictions of varying geographic size, with an established level of accuracy.