Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells - United States, 2023.

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.

Transmission of Mycobacterium tuberculosis to Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021-August 2022.

A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste.

Tuberculosis Outbreaks in State Prisons, United States, 2011-2019.

Objectives. To understand the frequency, magnitude, geography, and characteristics of tuberculosis outbreaks in US state prisons. Methods. Using data from the National Tuberculosis Surveillance System, we identified all cases of tuberculosis during 2011 to 2019 that were reported as occurring among individuals incarcerated in a state prison at the time of diagnosis. We used whole-genome sequencing to define 3 or more cases within 2 single nucleotide polymorphisms within 3 years as clustered; we classified clusters with 6 or more cases during a 3-year period as tuberculosis outbreaks. Results. During 2011 to 2019, 566 tuberculosis cases occurred in 41 state prison systems (a median of 3 cases per state). A total of 19 tuberculosis genotype clusters comprising 134 cases were identified in 6 state prison systems; these clusters included a subset of 5 outbreaks in 2 states. Two Alabama outbreaks during 2011 to 2017 totaled 20 cases; 3 Texas outbreaks during 2014 to 2019 totaled 51 cases. Conclusions. Only Alabama and Texas reported outbreaks during the 9-year period; only Texas state prisons had ongoing transmission in 2019. Effective interventions are needed to stop tuberculosis outbreaks in Texas state prisons. (Am J Public Health. 2022;112(8):1170-1179. https://doi.org/10.2105/AJPH.2022.306864).

Analysis of Severe Adverse Events Reported Among Patients Receiving Isoniazid-Rifapentine Treatment for Latent Mycobacterium tuberculosis Infection-United States, 2012-2016.

We analyzed data from 2012 to 2016 for patients who were hospitalized or who died after ≥1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberculosis infection. No patients died; 15 were hospitalized. Nine patients experienced hypotension, and 5 had elevated serum aminotransferases, reinforcing the need for vigilant monitoring during treatment.

Update: Characteristics of Health Care Personnel with COVID-19 - United States, February 12-July 16, 2020.

As of September 21, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 6,786,352 cases and 199,024 deaths in the United States.* Health care personnel (HCP) are essential workers at risk for exposure to patients or infectious materials (1). The impact of COVID-19 on U.S. HCP was first described using national case surveillance data in April 2020 (2). Since then, the number of reported HCP with COVID-19 has increased tenfold. This update describes demographic characteristics, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions, stratified by vital status, among 100,570 HCP with COVID-19 reported to CDC during February 12-July 16, 2020. HCP occupation type and job setting are newly reported. HCP status was available for 571,708 (22%) of 2,633,585 cases reported to CDC. Most HCP with COVID-19 were female (79%), aged 16-44 years (57%), not hospitalized (92%), and lacked all 10 underlying medical conditions specified on the case report form† (56%). Of HCP with COVID-19, 641 died. Compared with nonfatal COVID-19 HCP cases, a higher percentage of fatal cases occurred in males (38% versus 22%), persons aged ≥65 years (44% versus 4%), non-Hispanic Asians (Asians) (20% versus 9%), non-Hispanic Blacks (Blacks) (32% versus 25%), and persons with any of the 10 underlying medical conditions specified on the case report form (92% versus 41%). From a subset of jurisdictions reporting occupation type or job setting for HCP with COVID-19, nurses were the most frequently identified single occupation type (30%), and nursing and residential care facilities were the most common job setting (67%). Ensuring access to personal protective equipment (PPE) and training, and practices such as universal use of face masks at work, wearing masks in the community, and observing social distancing remain critical strategies to protect HCP and those they serve.

Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 - COVID-NET, 13 States, March 1-August 22, 2020.

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that causes COVID-19; to date, such data have been limited. During March 1-August 22, 2020, approximately one in four hospitalized women aged 15-49 years with COVID-19 was pregnant. Among 598 hospitalized pregnant women with COVID-19, 54.5% were asymptomatic at admission. Among 272 pregnant women with COVID-19 who were symptomatic at hospital admission, 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. During COVID-19-associated hospitalizations, 448 of 458 (97.8%) completed pregnancies resulted in a live birth and 10 (2.2%) resulted in a pregnancy loss. Testing policies based on the presence of symptoms might miss COVID-19 infections during pregnancy. Surveillance of pregnant women with COVID-19, including those with asymptomatic infections, is important to understand the short- and long-term consequences of COVID-19 for mothers and newborns. Identifying COVID-19 in women during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel. Pregnant women and health care providers should be made aware of the potential risks for severe COVID-19 illness, adverse pregnancy outcomes, and ways to prevent infection.

COVID-19-Associated Hospitalizations Among Health Care Personnel - COVID-NET, 13 States, March 1-May 31, 2020.

Health care personnel (HCP) can be exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), both within and outside the workplace, increasing their risk for infection. Among 6,760 adults hospitalized during March 1-May 31, 2020, for whom HCP status was determined by the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), 5.9% were HCP. Nursing-related occupations (36.3%) represented the largest proportion of HCP hospitalized with COVID-19. Median age of hospitalized HCP was 49 years, and 89.8% had at least one underlying medical condition, of which obesity was most commonly reported (72.5%). A substantial proportion of HCP with COVID-19 had indicators of severe disease: 27.5% were admitted to an intensive care unit (ICU), 15.8% required invasive mechanical ventilation, and 4.2% died during hospitalization. HCP can have severe COVID-19-associated illness, highlighting the need for continued infection prevention and control in health care settings as well as community mitigation efforts to reduce transmission.

Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Bacillus Calmette-Guérin Cases Reported to the National Tuberculosis Surveillance System, United States, 2004-2015.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is used as a vaccine to protect against disseminated tuberculosis (TB) and as a treatment for bladder cancer. We describe characteristics of US TB patients reported to the National Tuberculosis Surveillance System (NTSS) whose disease was attributed to BCG. We identified 118 BCG cases and 91,065 TB cases reported to NTSS during 2004-2015. Most patients with BCG were US-born (86%), older (median age 75 years), and non-Hispanic white (81%). Only 17% of BCG cases had pulmonary involvement, in contrast with 84% of TB cases. Epidemiologic features of BCG cases differed from TB cases. Clinicians can use clinical history to discern probable BCG cases from TB cases, enabling optimal clinical management. Public health agencies can use this information to quickly identify probable BCG cases to avoid inappropriately reporting BCG cases to NTSS or expending resources on unnecessary public health interventions.

The importance of clinical surveillance in detecting legionnaires' disease outbreaks: a large outbreak in a hospital with a Legionella disinfection system-Pennsylvania, 2011-2012.

BACKGROUND: Healthcare-associated Legionnaires' disease (LD) is a preventable pneumonia with a 30% case fatality rate. The Centers for Disease Control and Prevention guidelines recommend a high index of suspicion for the diagnosis of healthcare-associated LD. We characterized an outbreak and evaluated contributing factors in a hospital using copper-silver ionization for prevention of Legionella growth in water. METHODS: Through medical records review at a large, urban tertiary care hospital in November 2012, we identified patients diagnosed with LD during 2011-2012. Laboratory-confirmed cases were categorized as definite, probable, and not healthcare associated based on time spent in the hospital during the incubation period. We performed an environmental assessment of the hospital, including collection of samples for Legionella culture. Clinical and environmental isolates were compared by genotyping. Copper and silver ion concentrations were measured in 11 water samples. RESULTS: We identified 5 definite and 17 probable healthcare-associated LD cases; 6 case patients died. Of 25 locations (mostly potable water) where environmental samples were obtained for Legionella-specific culture, all but 2 showed Legionella growth; 11 isolates were identical to 3 clinical isolates by sequence-based typing. Mean copper and silver concentrations were at or above the manufacturer's recommended target for Legionella control. Despite this, all samples where copper and silver concentrations were tested showed Legionella growth. CONCLUSIONS: This outbreak was linked to the hospital's potable water system and highlights the importance of maintaining a high index of suspicion for healthcare-associated LD, even in the setting of a long-term disinfection program.

Racial disparities in invasive Streptococcus pneumoniae infections, 1998-2009.

BACKGROUND: Before the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), invasive pneumococcal disease (IPD) rates among blacks were twice the rates in whites. We measured the effects of trends in PCV7-type and non-PCV7-type IPD rates on racial disparities in overall IPD and estimated the proportion of IPD caused by serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: We analyzed data from the Active Bacterial Core surveillance system, which performs active, laboratory- and population-based surveillance for IPD for 29.2 million people in the United States, for the period 1998-2009. For patients with unknown race, we multiplied imputed race to calculate age-, race-, and serotype-specific IPD incidence rates. RESULTS: During 1998-2009, 47 449 IPD cases were identified; race was unknown for 5419 (11%). After multiple imputation, 31 981 (67%) patients were considered white and 13 750 (29%) black. PCV7-type IPD rates in all ages in both races decreased to <1 case per 100 000, whereas there were no decreases in overall IPD rates after 2002. By 2009, PCV13 serotypes caused 71% of cases among whites aged <5 years compared with 58% among blacks (P < .01). PCV13 serotypes caused 50% of IPD cases in whites aged ≥5 years compared with 43% among blacks (P < .01). CONCLUSIONS: Despite near elimination of PCV7-type IPD in both races, overall disparities in IPD rates persisted because non-PCV7-type IPD rates are higher among blacks. Whereas PCV13 introduction may reduce racial disparities in IPD, higher valency conjugate vaccines and strategies to directly address underlying causes are needed to eliminate IPD disparities.

Trends in tuberculosis clinicians' adoption of short-course regimens for latent tuberculosis infection.

Objective: Little is known about regimen choice for latent tuberculosis infection in the United States. Since 2011, the Centers for Disease Control and Prevention has recommended shorter regimens-12 weeks of isoniazid and rifapentine or 4 months of rifampin-because they have similar efficacy, better tolerability, and higher treatment completion than 6-9 months of isoniazid. The objective of this analysis is to describe frequencies of latent tuberculosis infection regimens prescribed in the United States and assess changes over time. Methods: Persons at high risk for latent tuberculosis infection or progression to tuberculosis disease were enrolled into an observational cohort study from September 2012-May 2017, tested for tuberculosis infection, and followed for 24 months. This analysis included those with at least one positive test who started treatment. Results: Frequencies of latent tuberculosis infection regimens and 95% confidence intervals were calculated overall and by important risk groups. Changes in the frequencies of regimens by quarter were assessed using the Mann-Kendall statistic. Of 20,220 participants, 4,068 had at least one positive test and started treatment: 95% non-U.S.-born, 46% female, 12% <15 years old. Most received 4 months of rifampin (49%), 6-9 months of isoniazid (32%), or 12 weeks of isoniazid and rifapentine (13%). Selection of short-course regimens increased from 55% in 2013 to 81% in late 2016 (p < 0.001). Conclusions: Our study identified a trend towards adoption of shorter regimens. Future studies should assess the impact of updated treatment guidelines, which have added 3 months of daily isoniazid and rifampin to recommended regimens.

Acute Cardiac Events During COVID-19-Associated Hospitalizations.

BACKGROUND: COVID-19 is associated with cardiac complications. OBJECTIVES: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults. METHODS: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes. RESULTS: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not. CONCLUSIONS: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Developing National Genotype-Independent Indicators for Recent Mycobacterium Tuberculosis Transmission Using Pediatric Cases-United States, 2011-2017.

INTRODUCTION: Pediatric tuberculosis (TB) cases are sentinel events for Mycobacterium tuberculosis transmission in communities because children, by definition, must have been infected relatively recently. However, these events are not consistently identified by genotype-dependent surveillance alerting methods because many pediatric TB cases are not culture-positive, a prerequisite for genotyping. METHODS: We developed 3 potential indicators of ongoing TB transmission based on identifying counties in the United States with relatively high pediatric (aged <15 years) TB incidence: (1) a case proportion indicator: an above-average proportion of pediatric TB cases among all TB cases; (2) a case rate indicator: an above-average pediatric TB case rate; and (3) a statistical model indicator: a statistical model based on a significant increase in pediatric TB cases from the previous 8-quarter moving average. RESULTS: Of the 249 US counties reporting ≥2 pediatric TB cases during 2009-2017, 240 and 249 counties were identified by the case proportion and case rate indicators, respectively. The statistical model indicator identified 40 counties with a significant increase in the number of pediatric TB cases. We compared results from the 3 indicators with an independently generated list of 91 likely transmission events involving ≥2 pediatric cases (ie, known TB outbreaks or case clusters with reported epidemiologic links). All counties with likely transmission events involving multiple pediatric cases were identified by ≥1 indicator; 23 were identified by all 3 indicators. PRACTICE IMPLICATIONS: This retrospective analysis demonstrates the feasibility of using routine TB surveillance data to identify counties where ongoing TB transmission might be occurring, even in the absence of available genotyping data.

Tuberculosis Outbreak Associated With Delayed Diagnosis and Long Infectious Periods in Rural Arkansas, 2010-2018.

OBJECTIVES: During 2010-2018, the Arkansas Department of Health reported 21 genotype-matched cases of tuberculosis (TB) among residents of a rural county in Arkansas with a low incidence of TB and in nearby counties. The Arkansas Department of Health and the Centers for Disease Control and Prevention investigated to determine the extent of TB transmission and provide recommendations for TB control. METHODS: We reviewed medical and public health records, interviewed patients, and reviewed patients' social media posts to describe patient characteristics, identify epidemiologic links, and establish likely chains of transmission. RESULTS: We identified 21 cases; 11 reported during 2010-2013 and 10 during 2016-2018. All case patients were US-born non-Hispanic Black people. Eighteen case patients had the outbreak genotype, and 3 clinically diagnosed (non-culture-confirmed) case patients had epidemiologic links to patients with the outbreak genotype. Social media reviews revealed epidemiologic links among 10 case patients not previously disclosed during interviews. Eight case patients (38%) had ≥1 health care visit during their infectious period, and 7 patients had estimated infectious periods of >12 months. CONCLUSIONS: Delayed diagnoses and prolonged infectiousness led to TB transmission in this rural community. TB education and awareness is critical to reducing transmission, morbidity, and mortality, especially in areas where health care providers have limited TB experience. Use of social media can help elucidate people at risk, especially when traditional TB investigation techniques are insufficient.

Molecular surveillance for large outbreaks of tuberculosis in the United States, 2014-2018.

OBJECTIVE: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018. METHODS: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases. RESULTS: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission. CONCLUSION: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity.

Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report.

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.