The Role of Endotoxin in Sterile Inflammation After Implanted Acellular Dermal Matrix: Red Breast Syndrome Explained?

BACKGROUND: Red breast syndrome (RBS) is a noninfectious erythema associated with acellular dermal matrix (ADM). The underlying cause remains unknown despite multiple suggested etiologies. No similar presentations to RBS have been reported in other anatomic regions. OBJECTIVES: The authors sought to describe and identify a common etiology for ADM-associated sterile inflammation in the breast and upper extremity. METHODS: A retrospective review of medical complaints reported to MTF Biologics (Edison, NJ) from July 1, 2017 to January 3, 2018 was performed. Inventory samples were tested for endotoxin content in endotoxin units (eu) via the Limulus Amebocyte Lysate method to determine a common etiology for sterile inflammation. RESULTS: Cases of RBS and upper extremity sterile inflammation, "red hand syndrome," are presented. Two patients developed RBS following implantation of ADM from the same donor; associated grafts in inventory had endotoxin levels of 167 eu and 320 eu per graft, respectively. Two patients developed red hand syndrome after joint arthroplasty with ADM from another donor; associated graft in inventory showed an endotoxin level of 1282 eu. Cultures were obtained and negative in 3 of the 4 cases. Since endotoxin screening of ADM donor lots began in January 2018 at MTF Biologics, no cases of sterile inflammation have been reported from screened units through December 31, 2018 (RBS rate, 39/15,529 [0.25%] vs 0/18,275 [0%], P < 0.0001). CONCLUSIONS: The sterile inflammatory response in RBS and newly reported red hand syndrome may be attributable to the presence of endotoxin in implanted ADM. Endotoxin screening has been adopted by MTF Biologics with a significant decrease in reported reactions.

Mycoplasma hominis Infections Transmitted Through Amniotic Tissue Product.

Background: Mycoplasma hominis is a commensal genitourinary tract organism that can cause infections outside the genitourinary tract. We investigated a cluster of M. hominis surgical site infections in patients who underwent spine surgery, all associated with amniotic tissue linked to a common donor. Methods: Laboratory tests of tissue product from the donor, including culture, quantitative real-time polymerase chain reaction (qPCR), and whole-genome sequencing were performed. Use of this amniotic tissue product was reviewed. A multistate investigation to identify additional cases and locate any unused products was conducted. Results: Twenty-seven tissue product vials from a donor were distributed to facilities in 7 states; at least 20 vials from this donor were used in 14 patients. Of these, 4 of 14 (29%) developed surgical site infections, including 2 M. hominis infections. Mycoplasma hominis was detected by culture and qPCR in 2 unused vials from the donor. Sequencing indicated >99% similarity between patient and unopened vial isolates. For 5 of 27 (19%) vials, the final disposition could not be confirmed. Conclusions: Mycoplasma hominis was transmitted through amniotic tissue from a single donor to 2 recipients. Current routine donor screening and product testing does not detect all potential pathogens. Clinicians should be aware that M. hominis can cause surgical site infections, and may not be detected by routine clinical cultures. The lack of a standardized system to track tissue products in healthcare facilities limits the ability of public health agencies to respond to outbreaks and investigate other adverse events associated with these products.

Transmission of Hepatitis A Virus through Combined Liver-Small Intestine-Pancreas Transplantation.

Although transmission of hepatitis A virus (HAV) through blood transfusion has been documented, transmission through organ transplantation has not been reported. In August 2015, state health officials in Texas, USA, were notified of 2 home health nurses with HAV infection whose only common exposure was a child who had undergone multi-visceral organ transplantation 9 months earlier. Specimens from the nurses, organ donor, and all organ recipients were tested and medical records reviewed to determine a possible infection source. Identical HAV RNA sequences were detected from the serum of both nurses and the organ donor, as well as from the multi-visceral organ recipient's serum and feces; this recipient's posttransplant liver and intestine biopsy specimens also had detectable virus. The other organ recipients tested negative for HAV RNA. Vaccination of the donor might have prevented infection in the recipient and subsequent transmission to the healthcare workers.

A model to estimate the probability of human immunodeficiency virus and hepatitis C infection despite negative nucleic acid testing among increased-risk organ donors.

BACKGROUND: In 2013, guidelines were released for reducing the risk of viral bloodborne pathogen transmission through organ transplantation. Eleven criteria were described that result in a donor being designated at increased infectious risk. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission risk from an increased-risk donor (IRD), despite negative nucleic acid testing (NAT), likely varies based on behavior type and timing. METHODS: We developed a Monte Carlo risk model to quantify probability of HIV among IRDs. The model included NAT performance, viral load dynamics, and per-act risk of acquiring HIV by each behavior. The model also quantifies the probability of HCV among IRDs by non-medical intravenous drug use (IVDU). RESULTS: Highest risk is among donors with history of unprotected, receptive anal male-to-male intercourse with partner of unknown HIV status (MSM), followed by sex with an HIV-infected partner, IVDU, and sex with a commercial sex worker. CONCLUSION: With NAT screening, the estimated risk of undetected HIV remains small even at 1 day following a risk behavior. The estimated risk for HCV transmission through IVDU is likewise small and decreases quicker with time owing to the faster viral growth dynamics of HCV compared with HIV. These findings may allow for improved organ allocation, utilization, and recipient informed consent.

Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure - United States, September 2016.

CDC has updated its interim guidance for persons with possible Zika virus exposure who are planning to conceive (1) and interim guidance to prevent transmission of Zika virus through sexual contact (2), now combined into a single document. Guidance for care for pregnant women with possible Zika virus exposure was previously published (3). Possible Zika virus exposure is defined as travel to or residence in an area of active Zika virus transmission (http://www.cdc.gov/zika/geo/index.html), or sex* without a condom† with a partner who traveled to or lived in an area of active transmission. Based on new though limited data, CDC now recommends that all men with possible Zika virus exposure who are considering attempting conception with their partner, regardless of symptom status,§ wait to conceive until at least 6 months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Recommendations for women planning to conceive remain unchanged: women with possible Zika virus exposure are recommended to wait to conceive until at least 8 weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Couples with possible Zika virus exposure, who are not pregnant and do not plan to become pregnant, who want to minimize their risk for sexual transmission of Zika virus should use a condom or abstain from sex for the same periods for men and women described above. Women of reproductive age who have had or anticipate future Zika virus exposure who do not want to become pregnant should use the most effective contraceptive method that can be used correctly and consistently. These recommendations will be further updated when additional data become available.

Screening of Blood Donations for Zika Virus Infection - Puerto Rico, April 3-June 11, 2016.

Transfusion-transmitted infections have been documented for several arboviruses, including West Nile and dengue viruses (1). Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes that has been identified as a cause of congenital microcephaly and other serious brain defects (2), became recognized as a potential threat to blood safety after reports from a 2013-2014 outbreak in French Polynesia. Blood safety concerns were based on very high infection incidence in the population at large during epidemics, the high percentage of persons with asymptomatic infection, the high proportion of blood donations with evidence of Zika virus nucleic acid upon retrospective testing, and an estimated 7-10-day period of viremia (3). At least one instance of transfusion transmission of Zika virus has been documented in Brazil after the virus emerged there, likely in 2014 (4). Rapid epidemic spread has followed to other areas of the Americas, including Puerto Rico.

Microsporidiosis acquired through solid organ transplantation: a public health investigation.

BACKGROUND: Encephalitozoon cuniculi, a microsporidial species most commonly recognized as a cause of renal, respiratory, and central nervous system infections in immunosuppressed patients, was identified as the cause of a temporally associated cluster of febrile illness among 3 solid organ transplant recipients from a common donor. OBJECTIVE: To confirm the source of the illness, assess donor and recipient risk factors, and provide therapy recommendations for ill recipients. DESIGN: Public health investigation. SETTING: Two transplant hospitals and community interview with the deceased donor's family. PATIENTS: Three transplant recipients and the organ donor. MEASUREMENTS: Specimens were tested for microsporidia by using culture, immunofluorescent antibody, polymerase chain reaction,immunohistochemistry, and electron microscopy. Donor medical records were reviewed and a questionnaire was developed to assess for microsporidial infection. RESULTS: Kidneys and lungs were procured from the deceased donor and transplanted to 3 recipients who became ill with fever 7 to 10 weeks after the transplant. Results of urine culture, serologic,and polymerase chain reaction testing were positive for E. cuniculi of genotype III in each recipient; the organism was also identified in biopsy or autopsy specimens in all recipients. The donor had positive serologic test results for E. cuniculi. Surviving recipients received albendazole. Donor assessment did not identify factors for suspected E. cuniculi infection. LIMITATION: Inability to detect organism by culture or polymerase chain reaction in donor due to lack of autopsy specimens. CONCLUSION: Microsporidiosis is now recognized as an emerging transplant-associated disease and should be considered in febrile transplant recipients when tests for routinely encountered agents are unrevealing. Donor-derived disease is critical to assess when multiple recipients from a common donor are ill.

Measurements of human herpesvirus 8 viral load in blood before and after leukoreduction filtration.

BACKGROUND: Human herpesvirus 8 (HHV-8) is likely transmitted through blood transfusion in high-prevalence areas. The efficacy of leukoreduction filtration for reducing HHV-8 in blood has not been reported. STUDY DESIGN AND METHODS: Blood was drawn from 45 human immunodeficiency virus-positive men either with Kaposi's sarcoma (KS; n=21) or without KS (n=24) and subject to leukoreduction filtration. HHV-8 viral load was measured in plasma and in blood before and after filtration. RESULTS: Twelve subjects, all with KS, had detectable HHV-8 viremia before filtration with viral loads of 10(2) to 10(5) copies/mL (mean, 3 × 10(4) copies/mL). After filtration, seven of 12 subjects no longer had detectable HHV-8 in their blood, and five of 12 subjects had detectable HHV-8 that was 90% reduced on average from prefiltration levels. The presence of HHV-8 in the blood after filtration was strongly associated with prefiltration viral loads greater than 1000 copies/mL and the presence of cell-free virus in plasma. None of the subjects without KS had detectable levels of HHV-8 virus in blood before or after filtration. CONCLUSION: Cell-associated HHV-8 appeared to be effectively removed by leukoreduction filtration. Cell-free HHV-8 was present in 42% of subjects as 1% to 20% of the total virus which was not removed by filtration.

HIV screening practices for living organ donors, New York State, 2010: need for standard policies.

Our survey of kidney and liver transplant centers in New York State found a wide variation among transplant centers in evaluation and screening for HIV risk and infection among prospective living donors. Survey results underscore the need to standardize practices. A recent transmission of human immunodeficiency virus (HIV) from a living donor to a kidney recipient revealed a possible limitation in existing screening protocols for HIV infection in living donors. We surveyed kidney and liver transplant centers (N = 18) in New York State to assess HIV screening protocols for living donors. Although most transplant centers evaluated HIV risk behaviors in living donors, evaluation practices varied widely, as did the extent of HIV testing and prevention counseling. All centers screened living donors for serologic evidence of HIV infection, either during initial evaluation or ≥1 month before surgery; however, only 50% of transplant centers repeated HIV testing within 14 days before surgery for all donors or donors with specific risk behaviors. Forty-four percent of transplant centers used HIV nucleic acid testing (NAT) to screen either all donors or donors with recognized risk behaviors, and 55% never performed HIV NAT. Results suggest the need to standardize evaluation of HIV risk behaviors and prevention counseling in New York State to prevent acquisition of HIV by prospective living organ donors, and to conduct HIV antibody testing and NAT as close to the time of donation as possible to prevent HIV transmission to recipients.

Fatal group C streptococcal infection due to transfusion of a bacterially contaminated pooled platelet unit despite routine bacterial culture screening.

BACKGROUND: An elderly man with chronic myelomonocytic leukemia developed respiratory distress and died less than 48 hours after transfusion of a pool of eight whole blood-derived platelets (PLTs). Blood cultures from the recipient and cultures of remnants from the pooled PLT bag grew group C streptococci (GCS). An investigation was conducted to identify both the infection's source and the reasons for the false-negative screening result. STUDY DESIGN AND METHODS: Red blood cell (RBC) units (cocomponent from the eight donations) were traced, quarantined, and cultured. Specimens from the implicated donor were obtained. Isolates were identified and typed by 16S rRNA and pulsed-field gel electrophoresis (PFGE). The blood center screening method was reviewed. RESULTS: beta-Hemolytic GCS, cultured from 1 of 8 RBC units, linked the fatal case to a single donor. The donor's throat swab collected 20 days after donation was positive for the presence of GCS, identified as Streptococcus dysgalactiae subsp. equisimilis. Isolates from the recipient, RBC unit, residual PLTs, and donor's throat swab were indistinguishable by PFGE. The donor denied any symptoms of infection before or after donation. PLT bacterial screening at the blood center was performed using a commercially available bacterial detection system (BacT/ALERT, bioMérieux) with a threshold of 15 colony-forming units per bag. CONCLUSION: An asymptomatic donor was implicated as the source of GCS-contaminated PLTs. Current screening methods for PLTs are not sufficient to detect all bacterial contamination. Pooled PLTs are a particular challenge because the small volume of individual units places limits on culturing strategies. Improved detection of bacterial contamination of PLTs is needed.

Human tissue oversight in hospitals: an AABB survey.

BACKGROUND: Reports of human tissue allograft-transmitted infections have underscored the need for better accounting of allografts in health-care facilities. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) implemented new storage and issuance tissue standards for hospital oversight as of July 1, 2005. This study sought to survey hospital tissue responsibilities. STUDY DESIGN AND METHODS: The AABB Tissue Task Force conducted a Web-based survey distributed to all 904 hospital institutional members in January 2005. The survey asked about tissue type used, breadth of responsibility, hospital department involvement, and views on AABB involvement. Data from 402 of 904 (45%) respondents were tabulated and analyzed. RESULTS: Among the 402 respondents, 325 (81%) used allogeneic and/or autologous human tissue. The most frequently used tissues were musculoskeletal (n = 240, 74%) and skin (n = 169, 52%) allografts. The department of surgery (e.g., operating room; n = 245, 76%) most often had responsibility for tissue use, followed by the blood bank (i.e., transfusion service; n = 164, 51%); surgery most frequently had responsibility for all tissue types except peripheral blood progenitor cells. Only 32 of 402 (8%) respondents had plans for increased oversight in the next 12 months; 129 of 178 (72%) thought there was a role for AABB in developing guidance on hospital tissue responsibilities. CONCLUSIONS: In this survey, most AABB member hospital respondents indicated facility use of allogeneic and/or autologous tissues. Although tissue allograft responsibility by surgery was extensive, hospital blood banks also had significant involvement. Few blood banks, however, plan increased oversight in the near future. Given JCAHO standards, blood banks have an opportunity to assist their hospital in planning for assigned tissue responsibilities and oversight to ensure patient safety.

Possible transmission of human herpesvirus-8 by blood transfusion in a historical United States cohort.

BACKGROUND: Transmission of human herpesvirus-8 (HHV-8) by blood transfusion in the United States appears plausible but has not been demonstrated. The objective of this study was to evaluate evidence of HHV-8 transmission via blood transfusion. STUDY DESIGN AND METHODS: Serum specimens were collected before and 6 months after surgery from 406 patients who enrolled in the Frequency of Agents Communicable by Transfusion study (FACTS) in Baltimore, Maryland, from 1986 to 1990. The change in HHV-8 serostatus was measured by a lytic-antigen immunofluorescence assay. RESULTS: Of the 284 patients who were initially HHV-8-seronegative and who received transfusions, 2 seroconverted, 1 with a postsurgery antibody titer of 1:160 and the other with a titer of 1:1280. These patients received 12 and 13 units of blood, respectively. None of the HHV-8-seronegative patients who did not receive transfusions seroconverted. If seroconversion was caused by transfused blood, the transmission risk per transfused component was 0.082 percent. CONCLUSIONS: This is the first report suggesting transmission of HHV-8 via blood components in the United States. Because linked donor specimens were not available, other routes of transmission cannot be excluded; however, the evidence is consistent with infection being caused by transfusion. Future studies should include contemporary US populations with linked donor specimens and populations at higher risk for HHV-8 infection.