Globally, tuberculosis (TB) is the leading cause of infectious disease mortality; however, clinicians in the United States are increasingly unfamiliar with TB and the recommended tests and treatment for latent TB infection. Compared with adults, children who develop TB more often develop severe disease, and children < 2 years are particularly susceptible to developing TB disease after initial infection. Nurse practitioners who work in primary care are on the front lines of identifying children at high risk and obtaining testing and treatment. This article reviews the clinical course for identifying children at risk for TB and provides updated guidelines for testing and treatment.

BACKGROUND: Mycobacterium tuberculosis transmission through solid organ transplantation has been well described, but transmission through transplanted tissues is rare. We investigated a tuberculosis outbreak in the USA linked to a bone graft product containing live cells derived from a single deceased donor. METHODS: In this outbreak report, we describe the management and severity of the outbreak and identify opportunities to improve tissue transplant safety in the USA. During early June, 2021, the US Centers for Disease Control and Prevention (CDC) worked with state and local health departments and health-care facilities to locate and sequester unused units from the recalled lot and notify, evaluate, and treat all identified product recipients. Investigators from CDC and the US Food and Drug Administration (FDA) reviewed donor screening and tissue processing. Unused product units from the recalled and other donor lots were tested for the presence of M tuberculosis using real-time PCR (rt PCR) assays and culture. M tuberculosis isolates from unused product and recipients were compared using phylogenetic analysis. FINDINGS: The tissue donor (a man aged 80 years) had unrecognised risk factors, symptoms, and signs consistent with tuberculosis. Bone was procured from the deceased donor and processed into 154 units of bone allograft product containing live cells, which were distributed to 37 hospitals and ambulatory surgical centres in 20 US states between March 1 and April 2, 2021. From March 3 to June 1, 2021, 136 (88%) units were implanted into 113 recipients aged 24-87 years in 18 states (some individuals received multiple units). The remaining 18 units (12%) were located and sequestered. 87 (77%) of 113 identified product recipients had microbiological or imaging evidence of tuberculosis disease. Eight product recipients died 8-99 days after product implantation (three deaths were attributed to tuberculosis after recognition of the outbreak). All 105 living recipients started treatment for tuberculosis disease at a median of 69 days (IQR 56-81) after product implantation. M tuberculosis was detected in all eight sequestered unused units tested from the recalled donor lot, but not in lots from other donors. M tuberculosis isolates from unused product and recipients were more than 99·99% genetically identical. INTERPRETATION: Donor-derived transmission of M tuberculosis via bone allograft resulted in substantial morbidity and mortality. All prospective tissue and organ donors should be routinely assessed for tuberculosis risk factors and clinical findings. When these are present, laboratory testing for M tuberculosis should be strongly considered. FUNDING: None.

BACKGROUND: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. METHODS: We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. RESULTS: Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]). CONCLUSIONS: MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52-74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults.

BACKGROUND: Clinical severity of coronavirus disease 2019 (COVID-19) may vary over time; trends in clinical severity at admission during the pandemic among hospitalized patients in the United States have been incompletely described, so a historical record of severity over time is lacking. METHODS: We classified 466677 hospital admissions for COVID-19 from April 2020 to April 2021 into 4 mutually exclusive severity grades based on indicators present on admission (from most to least severe): Grade 4 included intensive care unit (ICU) admission and invasive mechanical ventilation (IMV); grade 3 included non-IMV ICU and/or noninvasive positive pressure ventilation; grade 2 included diagnosis of acute respiratory failure; and grade 1 included none of the above indicators. Trends were stratified by sex, age, race/ethnicity, and comorbid conditions. We also examined severity in states with high vs low Alpha (B.1.1.7) variant burden. RESULTS: Severity tended to be lower among women, younger adults, and those with fewer comorbidities compared to their counterparts. The proportion of admissions classified as grade 1 or 2 fluctuated over time, but these less-severe grades comprised a majority (75%-85%) of admissions every month. Grades 3 and 4 consistently made up a minority of admissions (15%-25%), and grade 4 showed consistent decreases in all subgroups, including states with high Alpha variant burden. CONCLUSIONS: Clinical severity among hospitalized patients with COVID-19 has varied over time but has not consistently or markedly worsened over time. The proportion of admissions classified as grade 4 decreased in all subgroups. There was no consistent evidence of worsening severity in states with higher vs lower Alpha prevalence.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the COVID-19 pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From December 14, 2020 to April 30, 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of SARS-CoV-2 infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring.

CONTEXT: Local agencies across the United States have identified public health isolation sites for individuals with coronavirus disease 2019 (COVID-19) who are not able to isolate in residence. PROGRAM: We describe logistics of establishing and operating isolation and noncongregate hotels for COVID-19 mitigation and use the isolation hotel as an opportunity to understand COVID-19 symptom evolution among people experiencing homelessness (PEH). IMPLEMENTATION: Multiple agencies in Atlanta, Georgia, established an isolation hotel for PEH with COVID-19 and noncongregate hotel for PEH without COVID-19 but at risk of severe illness. PEH were referred to the isolation hotel through proactive, community-based testing and hospital-based testing. Daily symptoms were recorded prospectively. Disposition location was recorded for all clients. EVALUATION: During April 10 to September 1, 2020, 181 isolation hotel clients (77 community referrals; 104 hospital referrals) were admitted a median 3 days after testing. Overall, 32% of community referrals and 7% of hospital referrals became symptomatic after testing positive; 83% of isolation hotel clients reported symptoms at some point; 93% completed isolation. Among 302 noncongregate hotel clients, median stay was 18 weeks; 61% were discharged to permanent housing or had a permanent housing discharge plan. DISCUSSION: Overall, a high proportion of PEH completed isolation at the hotel, suggesting a high level of acceptability. Many PEH with COVID-19 diagnosed in the community developed symptoms after testing, indicating that proactive, community-based testing can facilitate early isolation. Noncongregate hotels can be a useful COVID-19 community mitigation strategy by bridging PEH at risk of severe illness to permanent housing.

OBJECTIVES: Persons experiencing homelessness (PEH) are disproportionately affected by tuberculosis (TB). We estimate area-specific rates of TB among PEH and characterize the extent to which available data support recent transmission as an explanation of high TB incidence. METHODS: We estimated TB incidence among PEH using National Tuberculosis Surveillance System data and population estimates for the US Department of Housing and Urban Development's Continuums of Care areas. For areas with TB incidence higher than the national average among PEH, we estimated recent transmission using genotyping and a plausible source-case method. For cases with ≥1 plausible source case, we assessed with TB program partners whether available whole-genome sequencing and local epidemiologic data were consistent with recent transmission. RESULTS: During 2011-2016, 3164 TB patients reported experiencing homelessness. National incidence was 36 cases/100,000 PEH. Incidence estimates varied among 21 areas with ≥10,000 PEH (9-150 cases/100,000 PEH); 9 areas had higher than average incidence. Of the 2349 cases with Mycobacterium tuberculosis genotyping results, 874 (37%) had ≥1 plausible source identified. In the 9 areas, 23%-82% of cases had ≥1 plausible source. Of cases with ≥1 plausible source, 63% were consistent and 7% were inconsistent with recent transmission; 29% were inconclusive. CONCLUSIONS: Disparities in TB incidence for PEH persist; estimates of TB incidence and recent transmission vary by area. With a better understanding of the TB risk among PEH in their jurisdictions and the role of recent transmission as a driver, programs can make more informed decisions about prioritizing TB prevention strategies.

BACKGROUND: Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. METHODS: We conducted a retrospective observational cohort investigation of 297 adults admitted to eight academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI) for predictors of invasive mechanical ventilation (IMV) and death. RESULTS: Compared with age <45 years, ages 65-74 years and ≥75 years were predictors of IMV (aOR 3.12, CI 1.47-6.60; aOR 2.79, CI 1.23-6.33) and the strongest predictors for death (aOR 12.92, CI 3.26-51.25; aOR 18.06, CI 4.43-73.63). Comorbidities associated with death (aORs from 2.4 to 3.8, p <0.05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Pre-hospital use vs. non-use of angiotensin receptor blockers (aOR 2.02, CI 1.03-3.96) and dihydropyridine calcium channel blockers (aOR 1.91, CI 1.03-3.55) were associated with death. CONCLUSIONS: After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.

The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged >/=18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age >/=65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.

Tuberculosis (TB) in pregnancy poses a substantial risk of morbidity to both the pregnant woman and the fetus if not diagnosed and treated in a timely manner. Assessing the risk of having Mycobacterium tuberculosis infection is essential to determining when further evaluation should occur. Obstetrician-gynecologists are in a unique position to identify individuals with infection and facilitate further evaluation and follow up as needed. A TB evaluation consists of a TB risk assessment, medical history, physical examination, and a symptom screen; a TB test should be performed if indicated by the TB evaluation. If a pregnant woman has signs or symptoms of TB or if the test result for TB infection is positive, active TB disease must be ruled out before delivery, with a chest radiograph and other diagnostics as indicated. If active TB disease is diagnosed, it should be treated; providers must decide when treatment of latent TB infection is most beneficial. Most women will not require latent TB infection treatment while pregnant, but all require close follow up and monitoring. Treatment should be coordinated with the TB control program within the respective jurisdiction and initiated based on the woman's risk factors including social history, comorbidities (particularly human immunodeficiency virus [HIV] infection), and concomitant medications.

BACKGROUND: Persons living with HIV are more likely to have tuberculosis (TB) disease attributed to recent transmission (RT) and to die during TB treatment than persons without HIV. We examined factors associated with RT or mortality among TB/HIV patients. METHODS: Using National TB Surveillance System data from 2011 to 2016, we calculated multivariable adjusted odds ratios (aOR) with 99% confidence intervals (CI) to estimate associations between patient characteristics and RT or mortality. Mortality analyses were restricted to 2011-2014 to allow sufficient time for reporting outcomes. RESULTS: TB disease was attributed to RT in 491 (20%) of 2415 TB/HIV patients. RT was more likely among those reporting homelessness (aOR, 2.6; CI, 2.0, 3.5) or substance use (aOR,1.6; CI, 1.2, 2.1) and among blacks (aOR,1.8; CI, 1.2, 2.8) and Hispanics (aOR, 1.8; CI, 1.1, 2.9); RT was less likely among non-US-born persons (aOR, 0.2; CI, 0.2, 0.3). The proportion who died during TB treatment was higher among persons with HIV than without (8.6% versus 5.2%; p < 0.0001). Among 2273 TB/HIV patients, 195 died during TB treatment. Age >/= 65 years (aOR, 5.3; CI, 2.4, 11.6), 45-64 years (aOR, 2.2; CI, 1.4, 3.4), and having another medical risk factor for TB (aOR, 3.3; CI, 1.8, 6.2) were associated with death; directly observed treatment (DOT) for TB was protective (aOR, 0.5; CI, 0.2, 1.0). CONCLUSIONS: Among TB/HIV patients, blacks, Hispanics, and those reporting homelessness or substance use should be prioritized for interventions that decrease TB transmission. Improved adherence to treatment through DOT was associated with decreased mortality, but additional interventions are needed to reduce mortality among older patients and those TB/HIV patients with another medical risk factor for TB.

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.

In March 2018, the Kanawha-Charleston Health Department (KCHD) in West Virginia began investigating a cluster of reported hepatitis A virus (HAV) infections. Twelve specimens tested by CDC’s Division of Viral Hepatitis laboratory confirmed that patients were infected with an HAV strain (genotype 1B) reported in ongoing hepatitis A outbreaks in multiple states, primarily among persons who use drugs and persons experiencing homelessness (1). In August 2018, because of ongoing reporting of cases, the West Virginia Bureau of Public Health requested epidemiologic assistance from CDC in responding to the outbreak.

On April 10, 2017, a middle-aged man from Eastern Europe was evaluated at a hospital with cough, chest pain, weakness, and weight loss. A sputum sample was smear-positive for acid-fast bacilli (AFB), and chest radiograph and chest computerized tomography scan showed bilateral pulmonary, cavitary disease with vertebral involvement. He was given standard first-line therapy (HRZE): isoniazid, rifampin, pyrazinamide, and ethambutol. Among three of the patient’s family members evaluated as part of the contact investigation, his wife tested positive for tuberculosis (TB) infection via QuantiFERON-TB Gold In-Tube test and was treated for latent TB infection with 4 months of rifampin.*

Treatment of latent tuberculosis infection (LTBI) is critical to the control and elimination of tuberculosis disease (TB) in the United States. In 2011, CDC recommended a short-course combination regimen of once-weekly isoniazid and rifapentine for 12 weeks (3HP) by directly observed therapy (DOT) for treatment of LTBI, with limitations for use in children aged <12 years and persons with human immunodeficiency virus (HIV) infection (1). CDC identified the use of 3HP in those populations, as well as self-administration of the 3HP regimen, as areas to address in updated recommendations. In 2017, a CDC Work Group conducted a systematic review and meta-analyses of the 3HP regimen using methods adapted from the Guide to Community Preventive Services. In total, 19 articles representing 15 unique studies were included in the meta-analysis, which determined that 3HP is as safe and effective as other recommended LTBI regimens and achieves substantially higher treatment completion rates. In July 2017, the Work Group presented the meta-analysis findings to a group of TB experts, and in December 2017, CDC solicited input from the Advisory Council for the Elimination of Tuberculosis (ACET) and members of the public for incorporation into the final recommendations. CDC continues to recommend 3HP for treatment of LTBI in adults and now recommends use of 3HP 1) in persons with LTBI aged 2-17 years; 2) in persons with LTBI who have HIV infection, including acquired immunodeficiency syndrome (AIDS), and are taking antiretroviral medications with acceptable drug-drug interactions with rifapentine; and 3) by DOT or self-administered therapy (SAT) in persons aged >/=2 years.

Background: RCTs demonstrated the newest LTBI regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), as efficacious as 9 months of isoniazid (9H) with a greater completion rate (82% versus 69%); however, 3HP has not been assessed in routine health care settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions (ADRs), and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children 2-17 years had the highest completion rate, 94.5% (155/164). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% CI, 0.23-0.85]; P = .014), and highest in persons ≥65 years (RR, 1.72 [95% CI, 1.25-2.35] P = .001). In multivariable analyses, discontinuation was lowest among contacts of patients with TB disease (adjusted relative risk [ARR], 0.68 [95% CI, 0.52-0.89]; P = .005), and students (ARR, 0.45 [95% CI, 0.21-0.98]; P = .044); highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P=.013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). ADRs were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine health care settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Background: Evidence-based recommendations for treating persons having presumed latent tuberculosis infection (LTBI) after contact to infectious multidrug-resistant tuberculosis (MDR TB) are lacking because published data consist of small observational studies. TB incidence in persons treated for latent multidrug-resistant-TB infection (MDR LTBI) is unknown. Methods: We conducted a systematic review of studies published (1/1/1994-12/31/2014) to analyze TB incidence, treatment completion and discontinuation, and cost effectiveness. We considered contacts with LTBI effectively treated if they were on ≥ one medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment versus non-treatment outcomes and performed meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. Results: We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR LTBI; 10 presented outcomes only for treated contacts, and five presented outcomes only for untreated contacts. The estimated MDR TB incidence reduction was 90% (9%-99%) using data from five comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Conclusions: Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR LTBI, suggesting effectiveness in prevention of progression to MDR TB, and confirmed cost effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.