Incomplete tissue product tracing during an investigation of a tissue-derived tuberculosis outbreak.

In the United States, there is currently no system to track donated human tissue products to individual recipients. This posed a challenge during an investigation of a nationwide tuberculosis outbreak that occurred when bone allograft contaminated with Mycobacterium tuberculosis (Lot A) was implanted into 113 patients in 18 US states, including 2 patients at 1 health care facility in Colorado. A third patient at the same facility developed spinal tuberculosis with an isolate genetically identical to the Lot A outbreak strain. However, health care records indicated this patient had received bone allograft from a different donor (Lot B). We investigated the source of this newly identified infection, including the possibilities of Lot B donor infection, product switch or contamination during manufacturing, product switch at the health care facility, person-to-person transmission, and laboratory error. The findings included gaps in tissue traceability at the health care facility, creating the possibility for a product switch at the point of care despite detailed tissue-tracking policies. Nationally, 6 (3.9%) of 155 Lot B units could not be traced to final disposition. This investigation highlights the critical need to improve tissue-tracking systems to ensure unbroken traceability, facilitating investigations of recipient adverse events and enabling timely public health responses to prevent morbidity and mortality.

Monkeypox Virus Infections After 2 Preexposure Doses of JYNNEOS Vaccine - United States, May 2022-May 2024.

Two doses of JYNNEOS vaccine are effective in preventing many mpox cases and can reduce the severity of symptoms in infected persons. However, infections among fully vaccinated persons can occur. During May 2022-May 2024, a total of 271 mpox cases among fully vaccinated persons were reported to CDC from 27 U.S. jurisdictions. These reported infections are estimated to have occurred in <1% of fully vaccinated persons. Compared with cases among unvaccinated persons, infections among fully vaccinated persons were more likely to occur among non-Hispanic White men aged 30-39 years, were associated with increased numbers of sexual partners, and resulted in less severe disease (p<0.001). Among infections in fully vaccinated persons with complete data, infections after vaccination were reported more commonly after receipt of heterologous (subcutaneous and intradermal) (46%) or homologous subcutaneous (32%) JYNNEOS vaccination than after homologous intradermal (22%) vaccination. Disparate time intervals from vaccination to infection among fully vaccinated persons suggest that immunity is not waning. The median interval between the second vaccine dose and illness onset was longer for cases among persons who had received 2 intradermal doses (median = 363 days; IQR = 221-444 days) compared with cases in persons who had received 2 subcutaneous doses (median = 263 days; IQR = 47-334 days) (p<0.001). The implications of this finding are not known; however, these data should increase confidence in the effectiveness of vaccine doses that were administered intradermally, the preferred method of administration during the peak of the outbreak when vaccine supply was limited. Persons recommended to receive the JYNNEOS vaccine should receive 2 doses, irrespective of the route of administration, and at this time, additional doses are not recommended for the affected population.

Clinical Testing Guidance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis in Patients with Community-Acquired Pneumonia for Primary and Urgent Care Providers.

Coccidioidomycosis, histoplasmosis, and blastomycosis are underrecognized and frequently misdiagnosed fungal infections that can clinically resemble bacterial and viral community-acquired pneumonia (CAP). This guidance is intended to help clinicians in outpatient settings test for these fungal diseases in patients with CAP to reduce misdiagnoses, unnecessary antibacterial use, and poor outcomes.

Fatal Invasive Mold Infections after Transplantation of Organs Recovered from Drowned Donors, United States, 2011-2021.

Drowned organ donors can be exposed to environmental molds through the aspiration of water; transplantation of exposed organs can cause invasive mold infections in recipients. We describe 4 rapidly fatal cases of potentially donor-derived invasive mold infections in the United States, highlighting the importance of maintaining clinical suspicion for these infections in transplant recipients.

Suspected Legionella Transmission from a Single Donor to Two Lung Transplant Recipients - Pennsylvania, May 2022.

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor's cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care-associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May-June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

Impact of the COVID-19 pandemic on blood donation and transfusions in the United States in 2020.

INTRODUCTION: Reports have suggested the COVID-19 pandemic resulted in blood donation shortages and adverse impacts on the blood supply. Using data from the National Blood Collection and Utilization Survey (NBCUS), we quantified the pandemic's impact on red blood cell (RBC) and apheresis platelet collections and transfusions in the United States during year 2020. METHODS: The 2021 NBCUS survey instrument was modified to include certain blood collection and utilization variables for 2020. The survey was distributed to all US blood collection centers, all US hospitals performing ≥1000 surgeries annually, and a 40% random sample of hospitals performing 100-999 surgeries annually. Weighting and imputation were used to generate national estimates for whole blood and apheresis platelet donation; RBC and platelet transfusion; and convalescent plasma distribution. RESULTS: Whole blood collections were stable from 2019 (9,790,000 units; 95% CI: 9,320,000-10,261,000) to 2020 (9,738,000 units; 95% CI: 9,365,000-10,110,000). RBC transfusions decreased by 6.0%, from 10,852,000 units (95% CI: 10,444,000-11,259,000) in 2019 to 10,202,000 units (95% CI: 9,811,000-10,593,000) in 2020. Declines were steepest during March-April 2020, with transfusions subsequently rebounding. Apheresis platelet collections increased from 2,359,000 units (95% CI: 2,240,000-2,477,000) in 2019 to 2,408,000 units (95% CI: 2,288,000-2,528,000) in 2020. Apheresis platelet transfusions increased from 1,996,000 units (95% CI: 1,846,000-2,147,000) in 2019 to 2,057,000 units (95% CI: 1,902,000-2,211,000) in 2020. CONCLUSION: The COVID-19 pandemic resulted in reduced blood donations and transfusions in some months during 2020 but only a minimal annualized decline compared with 2019.

Continued stabilization of blood collections and transfusions in the United States: Findings from the 2021 National Blood Collection and Utilization Survey.

BACKGROUND: National Blood Collection and Utilization Surveys (NBCUS) have reported decreases in U.S. blood collections and transfusions since 2008. The declines began to stabilize in 2015-2017, with a subsequent increase in transfusions in 2019. Data from the 2021 NBCUS were analyzed to understand the current dynamics of blood collection and use in the United States. METHODS: In March 2022, all community-based (53) and hospital-based (83) blood collection centers, a randomly selected 40% of transfusing hospitals performing 100-999 annual inpatient surgeries, and all transfusing hospitals performing ≥1000 annual inpatient surgeries were sent a 2021 NBCUS survey to ascertain blood collection and transfusion data. Responses were compiled, and national estimates were calculated for the number of units of blood and blood components collected, distributed, transfused, and outdated in 2021. Weighting and imputation were applied to account for non-responses and missing data, respectively. RESULTS: Survey response rates were 92.5% (49/53) for community-based blood centers, 74.7% (62/83) for hospital-based blood centers, and 76.3% (2102/2754) for transfusing hospitals. Overall, 11,784,000 (95% confidence interval [CI], 11,392,000-12,177,000) whole blood and apheresis red blood cell (RBC) units were collected in 2021, a 1.7% increase from 2019; 10,764,000 (95% CI, 10,357,000-11,171,000) whole blood-derived and apheresis RBC units were transfused, a 0.8% decrease. Total platelet units distributed increased by 0.8%; platelet units transfused decreased by 3.0%; plasma units distributed increased by 16.2%; and plasma units transfused increased by 1.4%. DISCUSSION: The 2021 NBCUS findings demonstrate a stabilization in U.S. blood collections and transfusions, suggesting a plateau has been reached for both.

Supplemental findings of the 2021 National Blood Collection and Utilization Survey.

BACKGROUND: The Department of Health and Human Services' National Blood Collection and Utilization Survey (NBCUS) has been conducted biennially since 1997. Data are used to estimate national blood collection and use. Supplemental data from the 2021 NBCUS not presented elsewhere are presented here. METHODS: Data on survey participation, donor characteristics, blood component cost, transfusion-associated adverse reactions, and implementation of blood safety measures, including pathogen-reduction of platelets, during 2021, were analyzed. Comparisons are made to 2019 survey data where available (2013-2019 for survey participation). RESULTS: During 2021, there were 11,507,000 successful blood donations in the United States, a 4.8% increase from 2019. Persons aged 45-64 years accounted for 42% of all successful blood donations. Donations by persons aged 65 years and older increased by 40.7%, while donations among minorities and donors aged <25 years decreased. From 2019 to 2021, the median price hospitals paid per unit of leukoreduced red blood cells, leukoreduced and pathogen-reduced apheresis platelets, and fresh frozen plasma increased. The largest increase in price per unit of blood component in 2021 was for leukoreduced apheresis platelets, which increased by ~$51. Between 2019 and 2021, the proportion of transfusing facilities reporting use of pathogen-reduced platelets increased, from 13% to 60%. Transfusion-related adverse reactions declined slightly between 2019 and 2021, although the rate of transfusion-transmitted bacterial infections remained unchanged. CONCLUSION: During 2021, blood donations increased nationally, although donations from those aged <25 years and minorities declined. The prices hospitals paid for most blood products increased, as did the use of pathogen-reduced platelets.

Suspected Legionella Transmission from a Single Donor to Two Lung Transplant Recipients - Pennsylvania, May 2022.

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor's cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care-associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May-June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

Updated U.S. Public Health Service Guideline for Testing of Transplant Candidates Aged <12 Years for Infection with HIV, Hepatitis B Virus, and Hepatitis C Virus - United States, 2022.

The U.S. Public Health Service (PHS) has periodically published recommendations about reducing the risk for transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) through solid organ transplantation (1-4). Updated guidance published in 2020 included the recommendation that all transplant candidates receive HIV, HBV, and HCV testing during hospital admission for transplant surgery to more accurately assess their pretransplant infection status and to better identify donor transmitted infection (4). In 2021, CDC was notified that this recommendation might be unnecessary for pediatric organ transplant candidates because of the low likelihood of infection after the perinatal period and out of concern that the volume of blood drawn for testing could negatively affect critically ill children.* CDC and other partners reviewed surveillance data from CDC on estimates of HIV, HBV, and HCV infection rates in the United States and data from the Organ Procurement & Transplantation Network (OPTN)† on age and weight distributions among U.S. transplant recipients. Feedback from the transplant community was also solicited to understand the impact of changes to the existing policy on organ transplantation. The 2020 PHS guideline was accordingly updated to specify that solid organ transplant candidates aged <12 years at the time of transplantation who have received postnatal infectious disease testing are exempt from the recommendation for HIV, HBV, and HCV testing during hospital admission for transplantation.

Successive Norovirus Outbreaks at an Event Center - Nebraska, October-November, 2017.

In October 2017, the Nebraska Department of Health and Human Services (NDHHS) was notified by a local health department of a gastrointestinal illness outbreak among attendees of a wedding reception at facility A, an event center. Shortly thereafter, state and local public health officials began receiving reports of similar gastrointestinal illness among attendees of subsequent facility A events. An investigation was initiated to identify cases, establish the cause, assess possible transmission routes, and provide control recommendations. Overall, 159 cases consistent with norovirus infection (three confirmed and 156 probable) were identified among employees of facility A and attendees of nine facility A events during October 27-November 18, 2017. The investigation revealed a public vomiting episode at the facility on October 27 and at least one employee involved with preparing and serving food who returned to work <24 hours after symptom resolution, suggesting that a combination of contaminated environmental surfaces and infected food handlers likely sustained the outbreak. Recommendations regarding sanitation and excluding ill employees were communicated to facility A management. However, facility A performed minimal environmental cleaning and did not exclude ill employees. Consequently, transmission continued. To prevent persistent norovirus outbreaks in similar settings, public health officials should ensure that involved facilities implement a comprehensive prevention strategy as early as possible that includes extensive sanitation and strict exclusion of ill food handlers for at least 48 hours after symptom resolution (1).

Evaluation of Placental and Fetal Tissue Specimens for Zika Virus Infection - 50 States and District of Columbia, January-December, 2016.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection.

Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Through Solid Organ Transplantation and Outcomes of Coronavirus Disease 2019 Among Recent Transplant Recipients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmissible through lung transplantation, and outcomes among infected organ recipients may be severe. Transmission risk to extrapulmonary organ recipients and recent (within 30 days of transplantation) SARS-CoV-2-infected recipient outcomes are unclear. Methods: During March 2020-March 2021, potential SARS-CoV-2 transmissions through solid organ transplantation were investigated. Assessments included SARS-CoV-2 testing, medical record review, determination of likely transmission route, and recent recipient outcomes. Results: During March 2020-March 2021, approximately 42 740 organs were transplanted in the United States. Forty donors, who donated 140 organs to 125 recipients, were investigated. Nine (23%) donors and 25 (20%) recipients were SARS-CoV-2 positive by nucleic acid amplification test (NAAT). Most (22/25 [88%]) SARS-CoV-2-infected recipients had healthcare or community exposures. Nine SARS-CoV-2-infected donors donated 21 organs to 19 recipients. Of these, 3 lung recipients acquired SARS-CoV-2 infections from donors with negative SARS-CoV-2 testing of pretransplant upper respiratory tract specimens but from whom posttransplant lower respiratory tract (LRT) specimens were SARS-CoV-2 positive. Sixteen recipients of extrapulmonary organs from SARS-CoV-2-infected donors had no evidence of posttransplant COVID-19. All-cause mortality within 45 days after transplantation was 6-fold higher among SARS-CoV-2-infected recipients (9/25 [36%]) than those without (6/100 [6%]). Conclusions: Transplant-transmission of SARS-CoV-2 is uncommon. Pretransplant NAAT of lung donor LRT specimens may prevent transmission of SARS-CoV-2 through transplantation. Extrapulmonary organs from SARS-CoV-2-infected donors may be safely usable, although further study is needed. Reducing recent recipient exposures to SARS-CoV-2 should remain a focus of prevention.

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.