BACKGROUND: An elevated risk of tuberculosis (TB) disease in persons who have received tumor necrosis factor alpha inhibitor medications (TNF- inhibitors) has been reported for nearly two decades, but clinical diagnostic features and outcomes of TB in this population remain poorly described. METHODS: We analyzed national surveillance data for TB cases among persons aged 15 years and older reported in the United States during 2010-2017 and associated mortality data reported through 2019 to describe the clinical characteristics of those receiving TNF- inhibitors. RESULTS: Of 70129 TB cases analyzed, 504 (0.7%) of the patients had TNF- inhibitor use reported at TB diagnosis. Patients with TNF- inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF- inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P<.001). Patients receiving TNF- inhibitors were less likely to have acid-fast bacilli noted on sputum smear microscopy (25.6% vs 39.1%, P=.04), and more likely to have drug-resistant disease (13.5% vs 10.0%, P<.001). TB-attributed deaths did not significantly differ between patients receiving and not receiving TNF- inhibitors (adjusted odds ratio, 1.46 [95% confidence interval, .95-2.26]). CONCLUSIONS: Clinicians evaluating TNF- inhibitor-treated patients should have a high index of suspicion for TB and be aware that extrapulmonary or sputum smear-negative TB disease is more common in these patients. No significantly diminished survival of TB patients treated with TNF- inhibitor therapy before TB diagnosis was noted.

SETTING: Lebanon is a relatively low TB-burden country, but has a high proportion of extrapulmonary tuberculosis (EPTB). Concern has been expressed that Syrian-born refugees could add to the TB burden and rates of EPTB: since 2011, >1 000 000 Syrian refugees have entered Lebanon.OBJECTIVE: The Lebanese National Tuberculosis Programme (NTP) sought to identify factors for the high proportion of EPTB and to assess the potential impact of Syrian refugees.DESIGN: NTP line-listed data from 2014-2015 were analyzed with logistic regression identified risk factors for EPTB. A trend analysis for 2011-2015 assessed TB burden by nationality and site of TB.RESULTS: Of 1347 reported TB cases from 2014 to 2015, 507 (38%) were EPTB and 46% were Lebanese. In analysis limited to Lebanese-born, the proportion of EPTB cases was relatively stable, 47% in 2011 and 52% in 2015. Modeling identified risk factors for EPTB as being female (aOR 1.79, 95%CI 1.39-2.32) and 5-15 years old (aOR 3.31, 95%CI 1.47-7.45) compared with children aged <5 years. Between 2011 and 2015, the proportion of TB cases among Syrian-born increased from 3% in 2011 to 21% in 2015 (P < 0.001); however, the proportion of EPTB versus PTB cases among Syrians remained stable (P = 0.264).CONCLUSION: Syrian TB cases increased almost 10-fold in five years (2011-2015) but their contribution to EPTB did not change. The high proportion of EPTB in Lebanon and those aged 5-15 years merits further investigation.

INTRODUCTION: Diabetes might confer a modestly increased risk of latent tuberculosis infection, which without treatment can progress to active tuberculosis disease. Three recent analyses of the National Health and Nutrition Examination Survey found a positive association between diabetes and a positive test for Mycobacterium tuberculosis infection. This study examines whether prevalence of a positive test still varies by diabetes status after stratifying by race/ethnicity. METHODS: This cross-sectional analysis used the public-use National Health and Nutrition Examination Survey 2011-2012 data sets and was conducted in 2018-2019. Interview and examination results for 5,560 adult participants yielded estimates for 219 million U.S. adults in the 4 largest race/ethnicity groups. The weighted prevalence of positive tuberculin skin test or interferon-gamma release assay by diabetes status was ascertained in each group. RESULTS: Among white and black adults, diabetes was associated with no difference in positive skin test prevalence and little difference in positive interferon-gamma release assay prevalence. The positive assay prevalence difference was +14.5% (95% CI=2.3%, 26.7%) among Hispanic and +9.9% (95% CI=1.2%, 18.6%) among Asian adults, when comparing those with diabetes with those with neither diabetes nor prediabetes. Based on assay results, 23.6% (95% CI=14.0%, 36.9%) of Hispanic and 27.2% (95% CI=19.6%, 36.5%) of Asian adults with diabetes also had latent tuberculosis infection. CONCLUSIONS: Hispanic and Asian subpopulation results drove much of the previously reported positive association between diabetes and a positive test for M. tuberculosis infection. Hispanic and Asian adults with diabetes might particularly benefit from screening and treatment for latent tuberculosis infection.

BACKGROUND: A single 2-year National Health and Nutrition Examination Survey (NHANES) cycle is designed to provide accurate and stable estimates of conditions with prevalence of at least 10%. Recent NHANES-based estimates of a tuberculin skin test >/=10 mm in the noninstitutionalized U.S. civilian population are at most 6.3%. METHODS: NHANES included a tuberculin skin test in 1971-1972, 1999-2000, and 2011-2012. We examined the robustness of NHANES-based estimates of the U.S. population prevalence of a skin test >/=10 mm with a bias analysis that considered the influence of non-U.S. birth distributions and within-household skin test results, reclassified borderline-positive results, and adjusted for tuberculin skin test item nonresponse. RESULTS: The weighted non-U.S. birth distribution among NHANES participants was similar to that in the overall U.S. population; further adjustment was unnecessary. We found no evidence of bias due to sampling multiple participants per household. Prevalence estimates changed 0.3% with reclassification of borderline-positive tuberculin skin test results and 0.2%-0.3% with adjustment for item nonresponse. CONCLUSIONS: For estimating the national prevalence of a tuberculin skin test >/=10 mm during these three survey cycles, a conventional NHANES analysis using the standard participant weights and masked design parameters that are provided in the public-use datasets appears robust.

SETTING: Sixteen South African correctional facilities.OBJECTIVE: To determine the prevalence of and risk factors for tuberculosis (TB) in South African correctional facilities using data collected during a TB screening program in South African correctional facilities in 2015.DESIGN: Inmates in 16 South African correctional facilities were screened for TB from January to December 2015. Inmates reporting >/=1 TB symptom or having an abnormal computer-assisted digital chest X-ray (CXR) provided sputum. Abnormal CXRs were interpreted by a radiologist. Sputum was tested for Mycobacterium tuberculosis using Xpert((R)) MTB/RIF. Data from 16 South African correctional facilities were used in regression analysis, and prevalence estimates calculated for 12 South African correctional facilities with >30% screening coverage.RESULTS: In 12 South African correctional facilities included in the prevalence estimates, 837 inmates had TB disease (2653/100 000) as indicated by current TB treatment or screening-identified TB by radiologist or Xpert. Previous TB was associated with increased odds of screening-identified TB in HIV-positive inmates (OR 4.3, 95%CI 2.5-7.3). For HIV-negative inmates, previous TB (adjusted OR [aOR] 4.9, 95%CI 1.7-14.1) and self-reported symptoms vs. none (1 symptom, aOR 8.8, 95%CI 1.2-67.7; >2 symptoms, aOR 21.7, 95%CI 3.0-158.8) were independently associated with increased odds of screening-identified TB.CONCLUSIONS: Routine TB screening, including CXR, is needed in South African correctional facilities to identify and refer inmates with active TB.

Background: Tuberculosis (TB) Regional Training and Medical Consultation Centers (RTMCCs) were established in 2005 for TB medical consultation, training and education in the United States. A medical consultation database (MCD) captured all consultations provided by RTMCCs; we report on those provided from June 1, 2010 to May 31, 2014. Method(s): All MCD consultations during 2010-2014 were categorized into: provider type, setting, consultation topic, and patient age. We analyzed data frequencies and performed subgroup analyses by RTMCC, by TB incidence for the geographical area, and by year of consultation. End-user satisfaction was assessed by a 2016 telephone evaluation of RTMCC services. Result(s): A total of 11,074 consultations were delivered, with 10,754 (97.1%) in the U.S. and its current or former territories. Of these, 6018 (56%) were for high, 2443 (22.7%) for medium, and 2293 (21.3%) for low TB incidence settings. Most were for adults (81.3%) and answered within 24 h (96.2%). Nearly 2/3 consultations originated from health departments; providers included mostly physicians (44.3%) or nurses (37.6%). Common consult categories included TB disease (47.7%), case management (29.8%), latent TB infection (19.3%), diagnosis (16.1%), pharmacology (14.7%) and adverse side effects (14.3%). Among adverse side effects, hepatotoxicity was most common (39.6%). Volume and nature of consult requests remained relatively stable over the four-year period. Feedback from a 2016 CDC evaluation indicated overall satisfaction with RTMCC medical consultation services. Conclusion(s): RTMCCS were an important source of TB medical consultation over the time-frame of this assessment and provided quality expert consultation within 24 h. RMTCCs represent a reservoir of TB subject-matter expertise in the United States.

The National Health and Nutrition Examination Survey (NHANES) has tested for Mycobacterium tuberculosis infection three times: in 1971–1972, 1999–2000, and 2011–2012. Based on tuberculin skin test results, the estimated national prevalence of latent tuberculosis infection (LTBI) among adults was 11–18% in 1971–1972 but has remained less than or equal to 6% in subsequent NHANES cycles (1–4). A single 2-year NHANES cycle is designed to produce accurate and stable estimates for conditions with at least 10% prevalence in the noninstitutionalized civilian U.S. population (5–7), suggesting that NHANES might no longer be as nationally representative for LTBI as it is for more common health conditions. Approximately 30 counties were selected for each 2-year cycle (5). We wished to examine whether persons in selected counties might have been systematically more or less likely to have a positive tuberculin skin test result than their counterparts in the approximately 3,100 counties that were not selected for NHANES participation.

We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system.

We agree with the excellent summary provided by Reves and Benjamin of the important, but insufficient, progress toward tuberculosis (TB) elimination (<1 case per million population) in the United States over the past two decades. Furthermore, we concur with the need to advance the argument in favor of additional investments required to eliminate TB by providing an estimate of future expected benefits. | | While we did not model future projected savings in our report,1 we have undertaken relatively simple retrospective modeling to estimate the reduction in TB cases and societal benefits had TB elimination been achieved in 1995 and sustained through 2014. From this we estimate that during 1995–2014 from 430 397 to 604 494 TB cases would have been averted (Figure 1), at estimated benefits of US $19.9 billion to $27.7 billion, including the value of deaths prevented and the costs to treat drug-resistant TB disease (Figure 2). Projected cases averted and cost savings for two decades into the future would also be anticipated to be substantial, although somewhat less, because even with a flat case rate the projected case counts for the next two decades would be less than those that actually occurred between 1995 and 2014.

BACKGROUND: Following a concerted public health response to the resurgence of tuberculosis (TB) in the United States in the late 1980s, annual TB incidence decreased substantially. However, no estimates exist of the number and cost savings of TB cases averted. METHODS: TB cases averted in the United States during 1995-2014 were estimated: Scenario 1 used a static 1992 case rate; Scenario 2 applied the 1992 rate to foreign-born cases, and a pre-resurgence 5.1% annual decline to US-born cases; and a statistical model assessed human immunodeficiency virus and TB program indices. We applied the cost of illness to estimate the societal benefits (costs averted) in 2014 dollars. RESULTS: During 1992-2014, 368 184 incident TB cases were reported, and cases decreased by two thirds during that period. In the scenarios and statistical model, TB cases averted during 1995-2014 ranged from approximately 145 000 to 319 000. The societal benefits of averted TB cases ranged from US$3.1 to US$6.7 billion, excluding deaths, and from US$6.7 to US$14.5 billion, including deaths. CONCLUSIONS: Coordinated efforts in TB control and prevention in the United States yielded a remarkable number of TB cases averted and societal economic benefits. We illustrate the value of concerted action and targeted public health funding.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The lack of capacity to provide laboratory confirmation of a diagnosis of tuberculosis disease (TB) is contributing to enormous gaps in the ability to find, treat and follow TB patients. WHO estimates that globally only about 57% of the notified new cases of pulmonary TB in 2012 and about 19% of rifampicin-resistant TB cases were laboratory confirmed. The Cepheid Xpert((R)) MTB/RIF assay has been credited with revolutionizing laboratory testing to aid in the diagnosis of TB and rifampicin-resistant TB. This semi-automated test can detect both the causative agent of TB and mutations that confer rifampicin resistance from clinical specimens within 2 h after starting the test. In this article, we review the performance of the test, its pathway to regulatory approval and endorsement, guidelines for its use and lessons learned from the implementation of the test in low-burden, high-resource countries and in high-burden, low-resource countries.

Effective Diagnosis and Treatment of Latent Tuberculosis infection (LTBI) to prevent progression to tuberculosis (TB) disease is one of the priority strategies for control, prevention, and eventual elimination of TB in the United States. Recent mathematical TB transmission modeling has shown that substantial improvements in addressing LTBI will be needed to eliminate TB before the 22nd century.1 Effective management of LTBI has been hampered by limitations of both treatment regimens and diagnostic tools. The advent of medication regimens with much shorter durations (eg, 12 weekly doses of isoniazid and rifapentine) than the current standard of 9 months of isoniazid is likely to lead to higher rates of treatment completion. Efforts have also been directed at finding a replacement for the tuberculin skin test (TST), which despite its many limitations has been the mainstay of LTBI diagnosis. | Beginning in the 1990s, interferon-γ–release assays (IG-RAs) were developed to diagnose LTBI. Currently, 2 US Food and Drug Administration-approved IGRAs are commercially available, QuantiFERON TB Gold In-Tube (Cellestis/Qiagen) and T-SPOT.TB (Oxford Immunotec). These blood tests detect ex vivo interferon-γ production by peripheral blood mononuclear cells exposed to peptides designed to simulate Mycobacterium tuberculosis antigens. Interferon-γ–release assays offer several practical and theoretical advantages over TST. Interferon-γ–release assays require only 1 patient visit as opposed to 2 for TST (1 visit for placement and 1 visit for reading 48-72 hours later). Interferon-γ–release assays use an objective measurement of interferon-7 production as opposed to human measurement of induration for TST. Also, IGRAs use peptides simulating specific M tuberculosis antigens (early secretory antigenic target 6 [ESAT-6], culture filtrate protein 10 [CFP-10], TB7.7), whereas TST uses purified protein derivative. Purified protein derivative contains numerous M tuberculosis antigens that cross-react with bacille Calmette-Guérin (BCG) and many nontuberculous mycobacteria. ESAT-6, CFP-10, and TB7.7 are found in very few nontuberculous mycobacteria and not found in BCG.

Operational research in low-income countries has a key role in filling the gap between what we know from research and what we do with that knowledge-the so-called know-do gap, or implementation gap. Planned research that does not tangibly affect policies and practices is ineffective and wasteful, especially in settings where resources are scarce and disease burden is high. Clear parameters are urgently needed to measure and judge the success of operational research. We define operational research and its relation with policy and practice, identify why operational research might fail to affect policy and practice, and offer possible solutions to address these shortcomings. We also propose measures of success for operational research. Adoption and use of these measures could help to ensure that operational research better changes policy and practice and improves health-care delivery and disease programmes.

Infectious respiratory pathogens were the suspected cause of 480 outbreaks investigated by the Centers for Disease Control and Prevention's Epidemic Intelligence Service officers during 1946-2005. All epidemic-assistance investigation reports and associated articles from scientific journals were reviewed. Investigations identified 25 different infectious respiratory pathogens including, most frequently, tuberculosis, influenza, and legionellosis. Other bacterial-, viral-, and fungal-related pathogens also were identified. Epidemic-assistance investigations were notable for first identifying Legionnaires disease and Pontiac fever, hantavirus pulmonary syndrome, and new strains of human and avian influenza, as well as emerging challenges (e.g., multidrug-resistant tuberculosis and pneumococcus). The investigations provided clinical insights into such diseases as pulmonary anthrax and identified high risks of serious respiratory illnesses for persons infected with human immunodeficiency virus, other immunocompromised persons, and persons with diabetes. They identified settings placing persons at high risk of acquiring disease, including nursing homes, prisons, homeless shelters, and hospitals. Travel also placed persons at risk. Key environmental factors related to spread of diseases and occupational risks for brucellosis and psittacosis were identified. The outbreak investigations constitute a wealth of prevention experience and provide the basis for recommendations to mitigate outbreaks and reduce future risks.

SUMMARY: We present a mathematical transmission model of tuberculosis in the USA. The model is calibrated to recent trends of declining incidence in the US-born and foreign-born populations and is used in assessing relative impacts of treatment of latently infected individuals on elimination time, where elimination is defined as annual incidence <1 case/million. Provided current control efforts are maintained, elimination in the US-born population can be achieved before the end of this century. However, elimination in the foreign-born population is unlikely in this timeframe even with higher rates of targeted testing and treatment of residents of and immigrants to the USA with latent tuberculosis infection. Cutting transmission of disease as an interim step would shorten the time to elimination in the US-born population but foreign-born rates would remain above the elimination target.

BACKGROUND: Since 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Our 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.

BACKGROUND: In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. METHODS: In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per muL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. FINDINGS: Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3.4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2.0%) in 1006 allocated to the continued isoniazid group (incidence 1.26% per year vs 0.72%; hazard ratio 0.57, 95% CI 0.33-0.99, p=0.047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0.26, 0.09-0.80, p=0.02), whereas participants who were tuberculin skin test-negative received no significant benefit (0.75, 0.38-1.46, p=0.40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0.50, 95% CI 0.26-0.97). Severe adverse events and death were much the same in the control and continued isoniazid groups. INTERPRETATION: In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. FUNDING: US Centers for Disease Control and Prevention and US Agency for International Development.

We reflect on remarkable accomplishments in global tuberculosis (TB) control and identify persistent obstacles to the successful elimination of TB from the United States and globally. One hundred and twenty nine years after Koch's discovery of the etiologic agent of TB, this health scourge continues to account for 9.4 million cases and 1.7 million deaths annually worldwide. Implementation of the Directly Observed Treatment Short-course strategy from 1995 through 2009 has saved 6 million lives. TB control is increasingly being achieved in countries with high-income economies, yet TB continues to plague persons living in countries with low-income and lower-middle-income economies. To accelerate progress against the global effects of disease caused by TB and achieve its elimination, we must bridge 3 key gaps in implementation, knowledge, and ambition.

ON APRIL 17, 2009 the fi rst cases of infl uenza due to | a novel strain of swine-origin infl uenza A (H1N1) were | reported in the United States.1 As of 29 April 2009, | 91 cases had been confi rmed in the United States, and | 57 in several other countries (Mexico, Canada, United | Kingdom, Spain, Germany, New Zealand, Israel, and | Australia).2 With evidence of sustained human-tohuman transmission of this novel virus in more than | two countries, the World Health Organization (WHO) | raised the global pandemic alert to phase 5.3 Early reports of the 2009 pandemic infl uenza A outbreak suggested considerable morbidity, with, as a distinctive | feature, its occurrence in students and other relatively | young adults.4 To detect the spread of the virus and | characterize its clinical spectrum, newly developed | diagnostic tests were quickly made available by the | Cen ters for Disease Control and Prevention (CDC) | to state health departments and WHO collaborating | centers for infl uenza and other laboratories around | the world.5,6

An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year. Although tuberculosis (TB) occurs predominantly in resource-limited countries, it also occurs in the United States. During 1985-1992, the United States was confronted with an unprecedented TB resurgence. This resurgence was accompanied by a rise in multidrug-resistant TB (MDR TB), which is defined as TB that is resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin. In addition, virtually untreatable strains of M. tuberculosis are emerging globally. Extensively drug-resistant (XDR) TB is defined as MDR TB that also is resistant to the most effective second-line therapeutic drugs used commonly to treat MDR TB: fluoroquinolones and at least one of three injectable second-line drugs used to treat TB (amikacin, kanamycin, or capreomycin). XDR TB has been identified in all regions of the world, including the United States. In the United States, the cost of hospitalization for one XDR TB patient is estimated to average $483,000, approximately twice the cost for MDR TB patients. Because of the limited responsiveness of XDR TB to available antibiotics, mortality rates among patients with XDR TB are similar to those of TB patients in the preantibiotic era. In January 1992, CDC convened a Federal TB Task Force to draft an action plan to improve prevention and control of drug-resistant TB in the United States (CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992;41([No. RR-11]). In November 2006, CDC reconvened the Task Force to draft an updated action plan to address the issue of MDR TB and XDR TB. Task Force members were divided into nine response areas and charged with articulating the most pressing problems, identifying barriers to improvement, and recommending specific action steps to improve prevention and control of XDR TB within their respective areas. Although the first priority of the Federal TB Task Force convened in 2006 was to delineate objectives and action steps to address MDR TB and XDR TB domestically, members recognized the necessity for TB experts in the United States to work with the international community to help strengthen TB control efforts globally. TB represents a substantial public health problem in low- and middle-income countries, many of which might benefit from assistance by the United States. In addition, the global TB epidemic directly affects the United States because the majority of all cases of TB and 80% of cases of MDR TB reported in the United States occur among foreign-born persons. For these reasons, the Action Plan also outlines potential steps that U.S. government agencies can take to help solve global XDR TB problems. Unless the fundamental causes of MDR TB and XDR TB are addressed in the United States and internationally, the United States is likely to experience a growing number of cases of MDR TB and XDR TB that will be difficult, if not impossible, to treat or prevent. The recommendations provided in this report include specific action steps and new activities that will require additional funding and a renewed commitment by government and nongovernment organizations involved in domestic and international TB control efforts to be implemented effectively. The Federal TB Task Force will coordinate activities of various federal agencies and partner with state and local health departments, nonprofit and TB advocacy organizations in implementing this plan to control and prevent XDR TB in the United States and to contribute to global efforts in the fight against this emerging public health crisis.