Characteristics, Comorbidities, and Data Gaps for Coronavirus Disease Deaths, Tennessee, USA.

As of March 2021, coronavirus disease (COVID-19) had led to >500,000 deaths in the United States, and the state of Tennessee had the fifth highest number of cases per capita. We reviewed the Tennessee Department of Health COVID-19 surveillance and chart-abstraction data during March 15‒August 15, 2020. Patients who died from COVID-19 were more likely to be older, male, and Black and to have underlying conditions (hereafter comorbidities) than case-patients who survived. We found 30.4% of surviving case-patients and 20.3% of deceased patients had no comorbidity information recorded. Chart-abstraction captured a higher proportion of deceased case-patients with >1 comorbidity (96.3%) compared with standard surveillance deaths (79.0%). Chart-abstraction detected higher rates of each comorbidity except for diabetes, which had similar rates among standard surveillance and chart-abstraction. Investing in public health data collection infrastructure will be beneficial for the COVID-19 pandemic and future disease outbreaks.

Bedaquiline for the Treatment of Multidrug-resistant Tuberculosis in the United States.

BACKGROUND: In 2012, the Food and Drug Administration approved use of bedaquiline fumarate as part of combination therapy for multidrug-resistant tuberculosis (MDR TB). We describe treatment outcomes, safety, and tolerability of bedaquiline in our case series. METHODS: Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through 4 TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events. RESULTS: Of 14 patients, 7 (50%) had MDR, 4 (29%) had pre-extensively drug-resistant (XDR), and 3 (21%) had XDR TB. All had pulmonary TB, 5 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear positive. One patient (7%) had HIV coinfection, 5 (36%) had diabetes mellitus, and 5/14 (36%) had previous treatment TB. All patients were non-US-born and 5/14 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26-116); 5 after starting bedaquiline. Twelve (86%) completed treatment and 1 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. Common adverse events were peripheral neuropathy 7/14 (50%), not customarily associated with bedaquiline use, and QTc prolongation 6/14 (43%). CONCLUSIONS: Of 14 patients, 1 (7%) had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series (7%) support use of bedaquiline for the treatment of MDR/XDR TB.

Gaps in the care cascade for screening and treatment of refugees with tuberculosis infection in Middle Tennessee: a retrospective cohort study.

BACKGROUND: Treatment of tuberculosis infection (TBI) in individuals at high risk for tuberculosis (TB) disease is a priority for TB elimination in the US. Newly arrived refugees in Middle Tennessee are screened for TBI, but factors associated with gaps in the TBI care cascade are not well characterized. METHODS: We assessed the TBI care cascade from US entry to completion of treatment for refugees who resettled in Middle Tennessee from 2012 through 2016. We assessed factors associated with treatment initiation and completion using logistic regression models. RESULTS: Of 6776 refugees who completed initial health screening, 1681 (25%) screened positive for TBI, 1208 were eligible for treatment, 690 started treatment, and 432 completed treatment. Male sex (Odds Ratio [OR]: 1.42; 95% Confidence Interval [CI]: 1.06, 1.89) and screening with interferon gamma release assay compared to tuberculin skin test (OR: 2.89; 95% CI: 1.59, 5.27) were associated with increased treatment initiation; living farther away from TB clinic was associated with decreased treatment initiation (OR: 0.91; 95% CI: 0.83, 0.99). Existing diabetes (OR: 7.27; 95% CI: 1.93, 27.30), receipt of influenza vaccination (OR: 1.65; 95% CI: 1.14, 2.40) and region of origin from South-Eastern or Southern Asia (ORSEAsia: 2.30; 95% CI: 1.43, 3.70; ORSAsia: 1.64; 95% CI: 1.02, 2.64) were associated with increased treatment completion. Six refugees developed TB disease after declining (n = 4) or partially completing (n = 2) TBI treatment; none who completed treatment developed TB disease. CONCLUSIONS: We determined gaps in the TBI care cascade among refugees in Middle Tennessee. Further assessment of barriers to treatment initiation and completion and interventions to assist refugees are warranted to improve these gaps and prevent TB disease.

TB-free Ebeye: Results from integrated TB and noncommunicable disease case finding in Ebeye, Marshall Islands.

Background: Tuberculosis (TB) incidence rates in the Republic of the Marshall Islands are among the highest in the world, 480/100,000 in 2017. In response, the Health Ministry completed islandwide screening in Ebeye Island in 2017. Methods: Participants were interviewed to obtain TB history, exposures, and symptoms. TB assessment included chest radiography with sputum collection for GeneXpert® MTB-RIF if indicated. TB diagnosis was made by consensus of visiting TB experts. Participants were also screened for Hansen's disease (HD) and diabetes mellitus (DM). For persons aged ≥21 years, blood pressure, cholesterol, and blood glucose were assessed. Results: A total of 5,166 persons (90.0 % of target population) completed screening leading to the identification of 39 new cases of TB (755/100,000) and 14 persons with HD (270/100,000). DM was detected in 1,096 persons (27 %), including in 351 persons not previously diagnosed. The rate of hypertension was 61 % and of hypercholesterolemia was 15 %. New or prevalent TB diagnosis was associated with newly diagnosed or history of DM (aOR 4.68, 2.15-10.20). Conclusions: In Ebeye, an integrated TB screening campaign found TB, HD, DM, and hypertension. TB and DM were strongly associated.

High proportion of fluoroquinolone-resistant Mycobacterium tuberculosis isolates with novel gyrase polymorphisms and a gyrA region associated with fluoroquinolone susceptibility.

Fluoroquinolone resistance in Mycobacterium tuberculosis can be conferred by mutations in gyrA or gyrB. The prevalence of resistance mutations outside the quinolone resistance-determining region (QRDR) of gyrA or gyrB is unclear, since such regions are rarely sequenced. M. tuberculosis isolates from 1,111 patients with newly diagnosed culture-confirmed tuberculosis diagnosed in Tennessee from 2002 to 2009 were screened for phenotypic ofloxacin resistance (>2 µg/ml). For each resistant isolate, two ofloxacin-susceptible isolates were selected: one with antecedent fluoroquinolone exposure and one without. The complete gyrA and gyrB genes were sequenced and compared with M. tuberculosis H37Rv. Of 25 ofloxacin-resistant isolates, 11 (44%) did not have previously reported resistance mutations. Of these, 10 had novel polymorphisms: 3 in the QRDR of gyrA, 1 in the QRDR of gyrB, and 6 outside the QRDR of gyrA or gyrB; 1 did not have any gyrase polymorphisms. Polymorphisms in gyrA codons 1 to 73 were more common in fluoroquinolone-susceptible than in fluoroquinolone-resistant strains (20% versus 0%; P = 0.016). In summary, almost half of fluoroquinolone-resistant M. tuberculosis isolates did not have previously described resistance mutations, which has implications for genotypic diagnostic tests.

Elephant-to-human transmission of tuberculosis, 2009.

In 2009, the Tennessee Department of Health received reports of 5 tuberculin skin test (TST) conversions among employees of an elephant refuge and isolation of Mycobacterium tuberculosis from a resident elephant. To determine the extent of the outbreak and identify risk factors for TST conversion, we conducted a cohort study and onsite assessment. Risk for conversion was increased for elephant caregivers and administrative employees working in the barn housing the M. tuberculosis-infected elephant or in offices connected to the barn (risk ratio 20.3, 95% confidence interval 2.8-146.7). Indirect exposure to aerosolized M. tuberculosis and delayed or inadequate infection control practices likely contributed to transmission. The following factors are needed to reduce risk for M. tuberculosis transmission in the captive elephant industry: increased knowledge about M. tuberculosis infection in elephants, improved infection control practices, and specific occupational health programs.

Black race, sex, and extrapulmonary tuberculosis risk: an observational study.

BACKGROUND: Extrapulmonary tuberculosis is likely a marker of underlying immune compromise. Our objective was to determine race and sex differences in extrapulmonary tuberculosis risk in order to identify the optimal population in which to assess for host factors associated with extrapulmonary tuberculosis. METHODS: We performed an observational study of all tuberculosis cases reported to the Tennessee Department of Health, January 1, 2000 to December 31, 2006. We compared the incidence of extrapulmonary tuberculosis by race and sex. We also examined risk factors associated with extrapulmonary disease among all persons with tuberculosis. RESULTS: Extrapulmonary tuberculosis incidence per 100,000 population was 5.93 in black men, 3.21 in black women, 1.01 in non-black men, and 0.58 in non-black women. Among those with tuberculosis, black women were most likely to have extrapulmonary disease (38.6%), followed by black men (28.1%), non-black women (24.6%) and non-black men (21.1%). In multivariate logistic regression among persons with tuberculosis, black women (OR 1.82 (95% CI 1.24-2.65), p = 0.002), black men (OR 1.54 (95% CI 1.13-2.09, p = 0.006), foreign birth (OR 1.55 (95% CI 1.12-2.14), p = 0.009), and HIV infection (OR 1.45 (95% CI 0.99-2.11), p = 0.06) were associated with extrapulmonary tuberculosis. CONCLUSIONS: Black men and black women had the highest incidence of extrapulmonary tuberculosis, and high odds of extrapulmonary disease among persons with tuberculosis. These data suggest that factors in addition to tuberculosis exposure contribute to extrapulmonary tuberculosis risk in blacks.

Fluoroquinolone resistance in Mycobacterium tuberculosis: the effect of duration and timing of fluoroquinolone exposure.

RATIONALE: Fluoroquinolones are the most commonly prescribed antibiotic class in the United States. They have the potential to become first-line antituberculosis therapy, but the effect of fluoroquinolone use on fluoroquinolone resistance in Mycobacterium tuberculosis is not well characterized. OBJECTIVES: To determine the prevalence of and risk factors for fluoroquinolone-resistant tuberculosis in a large United States population. METHODS: We identified all people with culture-confirmed tuberculosis enrolled in TennCare (Medicaid) and reported to the Tennessee Department of Health from January 2002 to December 2006. People with fluoroquinolone-resistant M. tuberculosis isolates (cases) were compared with those with susceptible isolates (control subjects). Fluoroquinolone resistance was determined by agar proportion using ofloxacin 2 microg/ml. Outpatient fluoroquinolone exposure in the 12 months before tuberculosis diagnosis was ascertained from TennCare pharmacy data. MEASUREMENTS AND MAIN RESULTS: Of 640 study patients, 116 (18%) had fluoroquinolone exposure in the 12 months before diagnosis, and 16 (2.5%; 95% confidence interval [CI], 1.4-4.0%) M. tuberculosis isolates were fluoroquinolone resistant. Among the 54 patients with more than 10 days of fluoroquinolone exposure, 7 (13%) had fluoroquinolone resistance. In multivariable logistic regression analyses using propensity score to control for age, sex, race, HIV serostatus, and site of disease, more than 10 days of fluoroquinolone exposure before tuberculosis diagnosis was associated with fluoroquinolone resistance (odds ratio 7.0; 95% CI, 2.3-20.6; P = 0.001). Fluoroquinolone exposure for more than 10 days that occurred more than 60 days before tuberculosis diagnosis was associated with the highest risk of resistance (20.8%; odds ratio 17.0; 95% CI, 5.1-56.8; P < 0.001 compared with no exposure). CONCLUSIONS: Overall, fluoroquinolone resistance was relatively low. However, receipt of fluoroquinolones for more than 10 days, particularly more than 60 days before tuberculosis diagnosis, was associated with a high risk of fluoroquinolone-resistant tuberculosis.

Public health response to a multidrug-resistant tuberculosis outbreak among Guatemalans in Tennessee, 2007.

BACKGROUND: In June 2007, the Tennessee Department of Health notified the Centers for Disease Control and Prevention of four multidrug-resistant tuberculosis (MDR TB) cases in individuals of Guatemalan descent, and requested onsite epidemiologic assistance to investigate this outbreak. METHODS: A case was defined as either culture-confirmed MDR TB with a drug-susceptibility pattern closely resembling that of the index case, or a clinical diagnosis of active TB disease and corroborated contact with a person with culture-confirmed MDR TB. Medical records were reviewed, and patients and their contacts were interviewed. RESULTS: Five secondary TB cases were associated with the index case. Of 369 contacts of the index case, 189 (51%) were evaluated. Of those, 97 (51%) had positive tuberculin skin test (TST) results, 79 (81%) began therapy for latent TB infection (LTBI), and 38 (48%) completed LTBI therapy. CONCLUSION: Despite consistent follow up by public health officials, a low proportion of patients diagnosed with LTBI completed therapy. Clinicians and public health practitioners who serve immigrant communities should be vigilant for MDR TB.

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

: 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.

Increasing outpatient fluoroquinolone exposure before tuberculosis diagnosis and impact on culture-negative disease.

BACKGROUND: Fluoroquinolones are widely used to treat routine bacterial infections, but they are also potential first-line antituberculosis agents. Empirical fluoroquinolone therapy can delay the diagnosis of tuberculosis and cause resistance in Mycobacterium tuberculosis. Rates of fluoroquinolone exposure before tuberculosis diagnosis and the impact of fluoroquinolones on culture-negative tuberculosis have not been previously reported. METHODS: All newly diagnosed tuberculosis cases reported to the Tennessee Department of Health between January 1, 2000, and December 31, 2004, were cross-matched with the TennCare (Medicaid) pharmacy database to assess for outpatient fluoroquinolone use in the 12 months before tuberculosis diagnosis. RESULTS: Of 1,562 tuberculosis cases reported, 1,055 occurred in TennCare participants; of these 1,055 TennCare patients, 507 were enrolled in TennCare more than 300 days during the year before tuberculosis diagnosis. Of the 507 patients, 119 (23%) received a fluoroquinolone before tuberculosis diagnosis. The proportion of fluoroquinolone-exposed patients increased from 9% in 2000 to 41% in 2004 (chi(2) test for trend P <.001). In multivariate logistic regression analysis, factors associated with fluoroquinolone exposure were older age (odds ratio [OR], 1.03 per year; 95% confidence interval [CI], 1.02-1.04) and year of diagnosis (OR, 1.64 per 1-year increase; 95% CI, 1.39-1.93); human immunodeficiency virus infection tended to be associated with increased exposure (OR, 1.94; 95% CI, 0.97-3.90). After controlling for age, sex, race, site of disease, human immunodeficiency virus, and year of diagnosis, prior fluoroquinolone exposure was not associated with culture-negative tuberculosis (OR, 0.81; 95% CI, 0.41-1.60). CONCLUSIONS: Fluoroquinolone use before tuberculosis diagnosis increased significantly during the study period. However, fluoroquinolone exposure was not associated with an increased risk of culture-negative tuberculosis.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities.

Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Exposure to pulmonary tuberculosis in a neonatal intensive care unit: unique aspects of contact investigation and management of hospitalized neonates.

OBJECTIVE: We describe the investigation of a tuberculosis (TB) exposure in which a neonatal intensive care unit (NICU) respiratory therapist was the index patient, as well as the rationale by which exposed infants were managed and possible explanations for the lack of transmission to these patients. DESIGN: Description of an exposure investigation. SETTING: Academic, level IV NICU of a tertiary care children's hospital. PARTICIPANTS: Contacts of a respiratory therapist with pulmonary TB disease, including household members, healthcare coworkers, and infant patients. RESULTS: In addition to 5 household contacts, 248 healthcare coworkers and 180 infant patients were identified as possibly exposed during the 24 days that the index patient worked between December 3, 2004, and January 30, 2005. Tuberculin skin tests (TSTs) were performed for 233 of the 235 contacts with the greatest degree of exposure (household and coworker contacts) who had a previously documented negative TST result or whose TST status was unknown prior to the investigation. No cases of latent tuberculosis infection or TB disease were identified. Because of characteristics of the index case, the exposure duration and setting, the infants' small lung volumes, and lack of evidence of transmission to higher-risk contacts, infants were not clinically evaluated or empirically treated for TB disease. Surveillance for subsequent illness was carried out by primary healthcare providers and parents. No TB disease or unexplained illness in these infants was reported in the 20 months following the exposure. CONCLUSION: After limited hospital exposure to a healthcare worker with pulmonary TB disease who is not highly contagious, neonates can be safely managed without specific evaluation for TB disease or empirical treatment.

Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones.

Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case-control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002-December 2009). Each fluoroquinolone-resistant case (n=25) was matched to two fluoroquinolone-susceptible controls (n=50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal-Wallis, P=0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR=1.79, 95% CI 1.22-2.64), but duration of exposure to older fluoroquinolones was not (OR=0.94, 95% CI 0.50-1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors.