Characteristics of and Deaths among 333 Persons with Tuberculosis and COVID-19 in Cross-Sectional Sample from 25 Jurisdictions, United States.

Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB-COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 [95% CI 0.8‒1.4]). Among TB-COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB-COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.

Evidence, Experience, Expertise, and the US Coronavirus Disease 2019 Public Health Response.

The U.S. Centers for Disease Control and Prevention (CDC), state, tribal, and local health departments assess available and promising interventions and individual and population health outcomes when crafting public health recommendations. This supplement provides a snapshot of some of the science, experience, and expertise supporting the COVID-19 response.

Novel 6-Month Treatment for Drug-Resistant Tuberculosis, United States.

The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.

The Advisory Committee on Immunization Practices' Interim Recommendations for Additional Primary and Booster Doses of COVID-19 Vaccines - United States, 2021.

Three COVID-19 vaccines are currently approved under a Biologics License Application (BLA) or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP) in the United States: the 2-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine (1,2) (Box 1). In August 2021, FDA amended the EUAs for the two mRNA COVID-19 vaccines to allow for an additional primary dose in certain immunocompromised recipients of an initial mRNA COVID-19 vaccination series (1). During September-October 2021, FDA amended the EUAs to allow for a COVID-19 vaccine booster dose following a primary mRNA COVID-19 vaccination series in certain recipients aged ≥18 years who are at increased risk for serious complications of COVID-19 or exposure to SARS-CoV-2 (the virus that causes COVID-19), as well as in recipients aged ≥18 years of Janssen COVID-19 vaccine (1) (Table). For the purposes of these recommendations, an additional primary (hereafter additional) dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. A booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death.

Response to Isoniazid-Resistant Tuberculosis in Homeless Shelters, Georgia, USA, 2015-2017.

In 2008, an outbreak of isoniazid-resistant tuberculosis was identified among residents of homeless shelters in Atlanta, Georgia, USA. When initial control efforts involving standard targeted testing failed, a comprehensive approach that involved all providers of services for the homeless successfully interrupted the outbreak.

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

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.

Associations Between Neighborhood Characteristics, Social Cohesion, and Perceived Sex Partner Risk and Non-Monogamy Among HIV-Seropositive and HIV-Seronegative Women in the Southern U.S.

Neighborhood social and physical factors shape sexual network characteristics in HIV-seronegative adults in the U.S. This multilevel analysis evaluated whether these relationships also exist in a predominantly HIV-seropositive cohort of women. This cross-sectional multilevel analysis included data from 734 women enrolled in the Women's Interagency HIV Study's sites in the U.S. South. Census tract-level contextual data captured socioeconomic disadvantage (e.g., tract poverty), number of alcohol outlets, and number of non-profits in the census tracts where women lived; participant-level data, including perceived neighborhood cohesion, were gathered via survey. We used hierarchical generalized linear models to evaluate relationships between tract characteristics and two outcomes: perceived main sex partner risk level (e.g., partner substance use) and perceived main sex partner non-monogamy. We tested whether these relationships varied by women's HIV status. Greater tract-level socioeconomic disadvantage was associated with greater sex partner risk (OR 1.29, 95% CI 1.06-1.58) among HIV-seropositive women and less partner non-monogamy among HIV-seronegative women (OR 0.69, 95% CI 0.51-0.92). Perceived neighborhood trust and cohesion was associated with lower partner risk (OR 0.83, 95% CI 0.69-1.00) for HIV-seropositive and HIV-seronegative women. The tract-level number of alcohol outlets and non-profits were not associated with partner risk characteristics. Neighborhood characteristics are associated with perceived sex partner risk and non-monogamy among women in the South; these relationships vary by HIV status. Future studies should examine causal relationships and explore the pathways through which neighborhoods influence partner selection and risk characteristics.

Patient Report and Review of Rapidly Growing Mycobacterial Infection after Cardiac Device Implantation.

Mycobacterial infections resulting from cardiac implantable electronic devices are rare, but as more devices are implanted, these organisms are increasingly emerging as causes of early-onset infections. We report a patient with an implantable cardioverter-defibrillator pocket and associated bloodstream infection caused by an organism of the Mycobacterium fortuitum group, and we review the literature regarding mycobacterial infections resulting from cardiac device implantations. Thirty-two such infections have been previously described; most (70%) were caused by rapidly growing species, of which M. fortuitum group species were predominant.When managing such infections, clinicians should consider the potential need for extended incubation of routine cultures or dedicated mycobacterial cultures for accurate diagnosis; combination antimicrobial drug therapy, even for isolates that appear to be macrolide susceptible, because of the potential for inducible resistance to this drug class; and the arrhythmogenicity of the antimicrobial drugs traditionally recommended for infections caused by these organisms.

Community-based HCV screening: knowledge and attitudes in a high risk urban population.

BACKGROUND: In an attempt to curtail the rising morbidity and mortality from undiagnosed HCV (hepatitis C virus) in the United States, screening guidelines have been expanded to high-risk individuals and persons born 1945-1965. Community-based screening may be one strategy in which to reach such persons; however, the acceptance of HCV testing, when many high-risk individuals may not have access to HCV specific medications, remains unknown. METHODS: We set out to assess attitudes about HCV screening and knowledge about HCV disease at several community-based testing sites that serve high-risk populations. This assessment was paired with a brief HCV educational intervention, followed by post-education evaluation. RESULTS: Participants (n = 140) were surveyed at five sites; two homeless shelters, two drug rehabilitation centers, and a women's "drop-in" center. Personal acceptance of HCV testing was almost unanimous, and 90% of participants reported that they would still want to be tested even if they were unable to receive HCV treatment. Baseline hepatitis C knowledge was poor; however, the brief educational intervention significantly improved knowledge and increased acceptability of testing when medical access issues were explicitly stated. CONCLUSIONS: Despite inconsistencies in access to care and treatment, high-risk communities want to know their HCV status. Though baseline HCV knowledge was poor in this population, a brief on-site educational intervention improved both knowledge and acceptability of HCV testing and care. These data support the establishment of programs that utilize community-based screening, and also provide initial evidence for acceptance of the implementation of the recently expanded screening guidelines among marginalized communities.

The footprint of old syphilis: using a reverse screening algorithm for syphilis testing in a U.S. Geographic Information Systems-Based Community Outreach Program.

The impact of syphilis reverse sequence screening has not been evaluated in community outreach. Using reverse sequence screening in neighborhoods identified with geographic information systems, we found that among 239 participants, 45 (19%) were seropositive. Of these, 3 (7%) had untreated syphilis, 33 (73%) had previously treated syphilis infection, and 9 (20%) had negative nontreponemal test results.

Fluoroquinolone-resistant latent tuberculosis infection: A literature review and case series of 5 patients treated with linezolid monotherapy.

Latent tuberculosis infection (LTBI) constitutes an important public health problem because of risk of progression to TB disease. Effective treatment of multi-drug resistant (MDR) LTBI would prevent progression to MDR TB disease, which would improve patient and public health outcomes. The majority of MDR LTBI treatment studies have focused on the use of fluoroquinolone-based antibiotic regimens. Options for and experience in the treatment of fluoroquinolone-resistant MDR LTBI are limited in the published literature and not comprehensively addressed in current guidelines. In this review, we share our experience with the treatment of fluoroquinolone-resistant MDR LTBI with linezolid. We discuss treatment options for MDR TB that provide context for predicting effective MDR LTBI treatment, with a focus on the microbiologic and pharmacokinetic properties of linezolid that support its use. We then summarize the evidence for treatment of MDR LTBI. Finally, we present our experiences treating fluoroquinolone-resistant MDR LTBI with linezolid with an emphasis on dosing considerations to optimize efficacy and minimize potential toxicities.

Evolution of drug-resistant viral populations during interruption of antiretroviral therapy.

Analysis of a large number of HIV-1 genomes at multiple time points after antiretroviral treatment (ART) interruption allows determination of the evolution of drug-resistant viruses and viral fitness in vivo in the absence of drug selection pressure. Using a parallel allele-specific sequencing (PASS) assay, potential primary drug-resistant mutations in five individual patients were studied by analyzing over 18,000 viral genomes. A three-phase evolution of drug-resistant viruses was observed after termination of ART. In the first phase, viruses carrying various combinations of multiple-drug-resistant (MDR) mutations predominated with each mutation persisting in relatively stable proportions while the overall number of resistant viruses gradually increased. In the second phase, viruses with linked MDR mutations rapidly became undetectable and single-drug-resistant (SDR) viruses emerged as minority populations while wild-type viruses quickly predominated. In the third phase, low-frequency SDR viruses remained detectable as long as 59 weeks after treatment interruption. Mathematical modeling showed that the loss in relative fitness increased with the number of mutations in each viral genome and that viruses with MDR mutations had lower fitness than viruses with SDR mutations. No single viral genome had seven or more drug resistance mutations, suggesting that such severely mutated viruses were too unfit to be detected or that the resistance gain offered by the seventh mutation did not outweigh its contribution to the overall fitness loss of the virus. These data provide a more comprehensive understanding of evolution and fitness of drug-resistant viruses in vivo and may lead to improved treatment strategies for ART-experienced patients.

Predictors of latent tuberculosis treatment initiation and completion at a U.S. public health clinic: a prospective cohort study.

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) is a key component in U.S. tuberculosis control, assisted by recent improvements in LTBI diagnostics and therapeutic regimens. Effectiveness of LTBI therapy, however, is limited by patients' willingness to both initiate and complete treatment. We aimed to evaluate the demographic, medical, behavioral, attitude-based, and geographic factors associated with LTBI treatment initiation and completion of persons presenting with LTBI to a public health tuberculosis clinic. METHODS: Data for this prospective cohort study were collected from structured patient interviews, self-administered questionnaires, clinic intake forms, and U.S. census data. All adults (>17 years) who met CDC guidelines for LTBI treatment between January 11, 2008 and May 6, 2009 at Wake County Health and Human Services Tuberculosis Clinic in Raleigh, North Carolina were included in the study. In addition to traditional social and behavioral factors, a three-level medical risk variable (low, moderate, high), based on risk factors for both progression to and transmission of active tuberculosis, was included for analysis. Clinic distance and neighborhood poverty level, based on percent residents living below poverty level in a person's zip code, were also analyzed. Variables with a significance level <0.10 by univariate analysis were included in log binomial models with backward elimination. Models were used to estimate risk ratios for two primary outcomes: (1) LTBI therapy initiation (picking up one month's medication) and (2) therapy completion (picking up nine months INH therapy or four months rifampin monthly). RESULTS: 496 persons completed medical interviews and questionnaires addressing social factors and attitudes toward LTBI treatment. 26% persons initiated LTBI therapy and 53% of those initiating completed therapy. Treatment initiation predictors included: a non-employment reason for screening (RR 1.6, 95% CI 1.0-2.5), close contact to an infectious TB case (RR 2.5, 95% CI 1.8-3.6), regular primary care(RR 1.4, 95% CI 1.0-2.0), and history of incarceration (RR 1.7, 95% CI 1.0-2.8). Persons in the "high" risk category for progression/transmission of TB disease had higher likelihood of treatment initiation (p < 0.01), but not completion, than those with lower risk. CONCLUSIONS: Investment in social support and access to regular primary care may lead to increased LTBI therapy adherence in high-risk populations.

Factors Associated With Receiving Longer Than Recommended Therapy Among Culture-Negative Pulmonary Tuberculosis Patients.

Background: US tuberculosis (TB) guidelines recommend treatment ≥6 months with a regimen composed of multiple effective anti-TB drugs. Since 2003, a 4-month regimen for a specific subset of TB patients has also been recommended. Methods: We used 2011-2018 US National Tuberculosis Surveillance System data to characterize factors associated with 4-month (111-140 days) therapy among adult patients who had completed treatment and were potentially eligible at that time for 4-month therapy (culture-negative pulmonary-only TB, absence of certain risk factors, and initial treatment that included pyrazinamide). We used modified Poisson regression with backward elimination of main effect variables to calculate adjusted relative risks (aRRs). Results: During 2011-2018, 63 393 adults completed TB treatment: 5560 (8.8%) were potentially eligible for 4-month therapy; of these, 5560 patients (79%) received >4-month therapy (median, 193 days or ∼6 months). Patients with cavitary disease were more likely to receive >4-month therapy (aRR, 1.10; 95% CI, 1.07-1.14) vs patients without cavitary disease. Patients more likely to receive 4-month therapy included patients treated by health departments vs private providers only (aRR, 0.94; 95% CI, 0.91-0.98), those in the South and West vs the Midwest, non-US-born persons (aRR, 0.95; 95% CI, 0.91-0.99) vs US-born persons, and aged 25-64 years vs 15-24 years. Conclusions: Most patients potentially eligible for 4-month therapy were treated with standard 6-month courses. Beyond clinical eligibility criteria, other patient- and program-related factors might be more critical determinants of treatment duration.

Association of Tumor Necrosis Factor α Inhibitor Use with Diagnostic Features and Mortality of Tuberculosis in the United States, 2010-2017.

BACKGROUND: An elevated risk of tuberculosis (TB) disease in persons who have received tumor necrosis factor alpha inhibitor medications (TNF-α 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-α inhibitors. RESULTS: Of 70 129 TB cases analyzed, 504 (0.7%) of the patients had TNF-α inhibitor use reported at TB diagnosis. Patients with TNF-α inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF-α inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P < .001). Patients receiving TNF-α 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-α inhibitors (adjusted odds ratio, 1.46 [95% confidence interval, .95-2.26]). CONCLUSIONS: Clinicians evaluating TNF-α 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-α inhibitor therapy before TB diagnosis was noted.