Donor-derived Disease Transmission Research Articles

Vigilance Data in Organ Donation and Solid Organ Transplantation in Germany: Six Years of Experience 2016-2022.

The reporting of serious adverse events (SAE) and serious adverse reactions (SAR) is an essential part of an effective vigilance and surveillance system (V&S) in organ donation and transplantation. All SAE and SAR reported to the German organ procurement organization (DSO) between 2016 and 2022 were analyzed. In case of a possible transmission of a disease to one or more recipients, an assessment of imputability was done according to the grading system of the US Disease Transmission Advisory Committee (DTAC). 543 SAE and SAR cases were reported to the DSO and analyzed in detail. 53 of the 543 reports (9.8%) were proven or probable (P/P) transmissions of infectious diseases, malignancies or other diseases to 75 recipients. Infections were the most frequently reported P/P disease transmission occurrences (30/53, 57%). In case of disease transmission, the mortality of the recipients was high (17/75, 23%), especially when a malignant disease was transmitted (11/22, 50 %). Donor-Derived disease transmission is a rare event (53/8,519; 0.6 %), but when it occurs can lead to significant morbidity and mortality.

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID‐19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (−90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (−45%), and other organs saw similar decreases: lung (−70%), heart (−43%), and liver (−37%). Deceased donors recovered dropped from 260 to 163 (−45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (−67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID‐19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

Rapid screening for safety of donation from donors with central nervous system malignancies.

With the increasing demand on organ transplants, it has become a common practice to include patients with primary central nervous system (CNS) malignancies as donors given the suggested low probability metastatic spread outside of the CNS. However, an extra-CNS spread of the disease cannot be excluded raising potential risks of cancer transmission from those donors. In order to balance between the risk of donor-derived disease transmission and the curative benefit for the recipient, a careful donor and organ selection is important. We performed a literature research and summarized all reported studies of organ transplants from donors suffered from primary CNS malignancies and determined the risk of tumor transmission to recipients. There were 22 cases of transplant-transmitted CNS tumors onto recipients since 1976. The association risks of cancer transmission were attributed to donor tumor histology, disruption of the blood-brain barrier, cerebrospinal fluid extra-CNS, and false diagnosis of primary intracranial tumor as well as the molecular properties of the primary tumor such as the existence of EGFR-amplification. The association risks and features of CNS tumors transmission recipients indicated that we need to reassess our thresholds for the potential fatal consequences of these donors.

S2592 Donor Derived HSV Hepatitis in a Kidney Transplant Patient

INTRODUCTION: It is estimated that worldwide 66% of the population is infected with herpes simplex virus type 1 (HSV-1). Despite its commonality, liver manifestations are particularly infrequent, and in most cases can lead to fulminant liver disease. In especially rare cases the infection has been reported as being donor-derived after a solid organ transplant leading to HSV hepatitis as shown in this case. CASE DESCRIPTION/METHODS: Forty-three-year-old male with end-stage renal disease presented 10 days after undergoing a deceased donor kidney transplant with a fever of 102.4ºF and diarrhea over 3 days. Initial labs show a WBC of 13 × 10^3 uL, INR of 1.9, total bilirubin 1.2 mg/dL, alkaline phosphatase 127 IU/L, alanine aminotransferase (ALT) > 5000 IU/L, aspartate aminotransferase (AST) 6,788 IU/L. He previously had no known liver disease. Empiric antibiotics were started with cefepime and vancomycin and with suspicion for HSV hepatitis, acyclovir 750mg every 8 hours. In the pre-transplant workup 6 months prior, the HSV 1 and 2 PCR, Hepatitis A, B and C panel were all negative. His medication list included levofloxacin, allopurinol and atorvastatin. Immunosuppression was tacrolimus 4mg twice daily, mycophenolic acid 1 gm twice daily and prednisone 20mg twice daily. The liver enzymes peaked at ALT > 5000 IU/L and AST > 10,000 IU/L and INR of 3.2 after 24 hours. He had no signs of encephalopathy and/or metabolic acidosis and repeat serology Hepatitis A, B, C were negative. Viral loads for HBV DNA, HCV RNA, EBV and CMV were all undetectable. HSV 1 PCR serum was not detected however HSV 2 PCR serum was > 1.0 × 10^8 copies/ mL. Later, a trans-jugular liver biopsy confirmed the diagnosis showing sub-massive hepatic necrosis with HSV. Necrosis involved 60-70% of hepatocytes and immunostain for HSV was strongly positive in necrotic areas. After 11 days of treatment with acyclovir 750mg every 8 hours his labs improved with an INR of 1.2, ALT 325 IU/L, AST 46 IU/L. HSV 2 PCR viral load trended down to 70,070 copies/mL. He remained asymptomatic and was eventually discharged home. DISCUSSION: Although rare, HSV hepatitis is a life threatening disease that we see in 75% of cases lead to liver transplantation or death. Early identification and treatment is particularly important since serology is unreliable and cutaneous lesions only occur in about 30% of cases. Without therapy one report shows in donor derived disease transmission mortality is 100%. In this clinical scenario with high suspicion, treatment can never be delayed.Figure 1.: This graph shows 8 days prior to presentation normal LFTs. Upon admission LFTs are elevated and is the day treatment began. Over time we see the gradual improvement while on treatment.

Donor-Derived Disease Transmission in Lung Transplantation

Understanding the risk of donor-derived infection, particularly in the lung transplant population, should reduce discarding organs without risk. Ongoing regulatory efforts and improved clinician awareness can help improve organ supply and post-transplantation outcomes. Infections can be divided into expected and unexpected. Syndromes that manifest in the early-post-transplant period should raise concern of a donor-derived transmission. Emerging data suggests that donors with certain bacterial infections can be safely used while donors with HCV infection can be a useful source of previously discarded organs. Donor-derived disease transmission events are rare. Thoughtful donor and recipient screening can mitigate the risk of disease transmission through organ transplantation and may identify donor organs that can be safely used.

Pediatrics and donor-derived disease transmission: The US OPTN experience.

PDDTE are tracked by the OPTN Ad Hoc DTAC. Specific evaluation of potential transmissions from pediatric deceased donors or the impact of donor-derived disease transmissions to pediatric organ recipients has not been previously undertaken. PDDTE reported to the DTAC between 2008 and 2013 were reviewed, characterized as proven, probable, possible, IWDT, unlikely, or excluded for both the whole event and each individual recipient. Pediatric donors and recipients were defined as being 0-17years of age. Analysis was undertaken to characterize potential disease transmission from pediatric donors to adult or pediatric recipients and also to evaluate potential transmission from all donors to pediatric recipients. P/P cases were further analyzed. A total of 5238 pediatric deceased US donors accounted for 17456 organ transplants during the study period; 103 PDDTE reports arose from these donors (2.0%). PDDTE were characterized as P/P (15%), possible (13%), IWDT (9%), unlikely, and excluded (63%). Disease was transmitted to 22 of 54 potentially exposed (adult and pediatric) recipients with six attributable deaths. An infectious pathogen accounted for 13/15 of the P/P PDDTE associated with pediatric donors, affecting 19 of 50 potentially exposed recipients and resulting in five deaths. Four separate viral pathogens from six donors accounted for P/P transmissions to 11 recipients with the unanticipated transmission of CMV most common. No pediatric donor transmitted HIV, HBV, or HCV. Bacteria, fungi, and parasites accounted for three (all staphylococci), three (Zygomycetes and Histoplasma), and two (both Toxoplasma) P/P transmissions from seven donors, respectively. From the recipient side, 11/11,188 pediatric recipient deceased and living donor transplants during the study period were associated with a P/P PDDTE (<0.1%) with infectious pathogens accounting for 9/11 P/P events. Infections were split among pathogen categories (bacteria 2, viruses 3, parasites 3, and fungi 1). Reporting rates of PDDTE involving pediatric donors were very low and similar to rates from all donors, with resulting P/P transmissions occurring in only 0.1% of exposed recipients, but transmissions were associated with six deaths. Rates of P/P transmission to pediatric recipients from any donor (<0.1%) were also very low and similar to that of all recipients. Additional studies are needed to compare the pattern and outcome of donor-derived disease transmission from and to pediatric and adult donor and recipients.

(846) - Donor Derived Disease Transmission Events in Thoracic Organ Transplantation: Data Reviewed by the OPTN Ad Hoc Disease Transmission Advisory Committee

(846) - Donor Derived Disease Transmission Events in Thoracic Organ Transplantation: Data Reviewed by the OPTN Ad Hoc Disease Transmission Advisory Committee

Solid Organ Transplant Donors With Central Nervous System Infection

While donor-derived infections (DDI) remain uncommon, multiple reports describe DDI with pathogens that cause central nervous system (CNS) infection resulting in significant recipient disease. The Ad Hoc Disease Transmission Advisory Committee (DTAC) reviewed the records of potential donor-derived disease transmission events (PDDTE) to describe donor characteristics and outcomes associated with DDI from CNS pathogens. All PDDTE reported from January 2008 to September 2010 were reviewed for characteristics suggesting CNS infection in the donor or the recipient. Identified cases were further examined to determine if donor CNS infection resulted in recipient infection. Ninety-one PDDTE cases in which there was concern for CNS infection in the donor or recipient were identified. Further review confirmed CNS infection in 12 donors, six of whom transmitted infection to 10 of 15 exposed recipients with five recipient deaths. Pathogens included Balamuthia mandrillaris, Cryptococcus neoformans, lymphocytic choriomeningitis virus, and West Nile virus. Listed cause of death at procurement for these donors included stroke, anoxia, acute disseminated encephalomyelitis, and meningoencephalitis. Confounding diagnoses were present in 6 of 12 donors that would have allowed them to be considered at low risk of transmitting a CNS pathogen. Of the six donors with no confounding conditions, three exhibited at least two suspicious "DTAC warning criteria" for CNS infection. Careful clinical assessment of donors combined with a high index of suspicion for ambiguous or misleading findings associated with CNS infection can reduce, but not eliminate, DDI with CNS pathogens.

Donor-Derived Tuberculosis (TB) Infection in Lung Transplant Despite Following Recommended Algorithm

Donor-Derived Tuberculosis (TB) Infection in Lung Transplant Despite Following Recommended Algorithm

Update on donor-derived infections in liver transplantation

Advances in surgical techniques, immunosuppressive medications, and robust infectious disease prophylaxis have resulted in liver transplantation becoming the treatment of choice for patients with end-stage liver disease and unresectable hepatocellular carcinoma. Nonetheless, organ transplantation is not without risk. Unexpected donor-derived disease transmission is a newly recognized risk that complicates approximately 0.2% of all organ transplants. We review the epidemiology of donor-derived infectious diseases and methods of risk mitigation with a focus on liver transplantation.

Donor-transmitted diseases

Key Points 1. Donor-derived disease transmission occurs in less than 1% of all transplants. 2. Early recognition and screening of the donor are essential to prevent transmission. Nucleic acid testing, though costly, is more sensitive and accurate than serological testing, and when it is used appropriately, it can effectively identify high-risk donors. 3. Prompt and aggressive treatment of any recipient of donor-derived disease is essential for patient survival. Early removal of the transplanted organ is often necessary. 4. Some instances of malignancy may be acceptable for organ donation. Liver Transpl 16:S40-S44, 2010. © 2010 AASLD.

Donor derived transmission events in the us: a case-based discussion

Donor-derived disease transmission is increasingly recognised as a source of morbidity and mortality among transplant recipients. OPTN Policy 4.0 requires reporting of donor-derived events. In 2009, there were 135 reports of potential donorderived transmission events: 36 reports related to malignancy, 85 reports related to infection, and four reports related to ‘other diseases’. The epidemiology and trends of disease transmission since 2005, when mandatory reporting was initiated in the US, will be discussed as well as lessons learned that may result in a lower risk of donor-derived disease transmission.

Donor-Derived Disease Transmission Events in the United States: Data Reviewed by the OPTN/UNOS Disease Transmission Advisory Committee

Donor-derived disease transmission is increasingly recognized as a source of morbidity and mortality among transplant recipients. Policy 4.7 of the Organ Procurement and Transplantation Network (OPTN) currently requires reporting of donor-derived events. All potential donor-derived transmission events (PDDTE) reported to OPTN/UNOS were reviewed by the Disease Transmission Advisory Committee (DTAC). Summary data from January 1, 2005-December 31, 2007, were prepared for presentation. Reports of PDDTE have increased from 7 in 2005, the first full year data were collected, to 60 in 2006 and to 97 in 2007. More detailed information is available for 2007; a classification system for determining likelihood of donor-derived transmission was utilized. In 2007, there were four proven and one possible donor-derived malignancy transmissions and four proven, two probable and six possible donor-derived infectious diseases transmissions. There were nine reported recipient deaths attributable to proven donor transmissions events arising from eight donors during 2007. Although recognized transmission events resulted in significant morbidity and mortality, transmission was reported in only 0.96% of deceased donor donations overall. Improved reporting, through enhanced recognition and communication, will be critical to better estimate the transmission risk of infection and malignancy through organ transplantation.

Transmission of human immunodeficiency virus and hepatitis C virus through liver transplantation

We are writing in regard to a recently published article by Ahn and Cohen documenting the transmission of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) to a liver recipient, 2 kidney recipients, and 1 heart recipient.1 The authors clearly present the case from their patients' perspective, allowing the transplant community to review many of the facts regarding their care. The authors state in the abstract and in the discussion that the transmission occurred secondary to the donor being within the window period between initial infection and detection of antibodies. This is factually incorrect because it has not been clearly confirmed and hemodilution may have contributed to the lack of detection. To date, confirmatory serologic and molecular testing has been conducted only on residual blood drawn on the donor post-transfusion. Because of legal proceedings, the pretransfusion blood has not had confirmatory serologic or molecular testing. Until this is done, it is impossible to determine whether the negative serologic testing that was reported to the centers at the time of the organ offer represented a true negative because the patient was in the window period or if the blood and fluids that the donor had received prior to specimen collection diluted the sample. Second, an important recommendation from the 1994 Public Health Services Guidelines is not included in the discussion2: the need for posttransplant testing of all recipients of organs from increased-risk donors. This not only is an oversight in the article and in its accompanying editorial1, 3 but also is missing from most discussions on this topic. The guidelines clearly recommend that all recipients of organs from increased-risk donors “be tested for HIV immediately before transplantation and at 3 months following transplantation.” This case demonstrates some key issues to guide the testing of recipients. First, the patient, like the other transplant recipients, acquired HCV infection without seroconversion; as such, posttransplant testing should use both molecular and serologic methods. Second, although we cannot be sure that earlier testing would have affected the overall course of the patient, it is possible that early identification and treatment of the HIV and HCV infection in the recipient may have improved her outcome. Since the transmission event, at our center, we perform baseline serologic testing for HIV, hepatitis B virus, and HCV immediately preoperatively in all recipients of organs from increased-risk donors, and this is followed by serologic and molecular (quantitative polymerase chain reaction) testing for HIV, hepatitis B virus, and HCV, unless there was pretransplant documentation of protection or infection, at 1 and 3 months post-transplant. Such testing is just as important as the consent of recipients of organs from increased-risk donors. Finally, current Organ Procurement and Transplantation Network policy requires reporting of any donor-derived disease transmission if it is recognized to allow appropriate screening and care of other recipients.4 Michael G. Ison*, John J. Friedewald , * Divisions of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, Divisions of Nephrology, and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL.