Coccidioidomycosis Transmission Through Organ Transplantation: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee.

Donor-derived coccidioidomycosis has caused unexpected morbidity and mortality in transplant recipients. All proven or probable reports of donor-derived coccidioidomycosis to the Disease Transmission Advisory Committee between 2005 and August 2012 were reviewed. Six reports of proven or probable coccidioidomycosis were discovered. In four of six, the infection was first detected at autopsy in the recipient. In two cases it was first identified in the donor. Twenty-one recipients received organs from these six donors. Transmission occurred in 43% at a median of 30 days posttransplant with a mortality rate of 28.5%. Eleven recipients received preemptive antifungals, seven did not receive treatment, and treatment information was not reported for three recipients. Five of seven who did not receive prophylaxis/treatment died and all 11 who received early therapy survived. Six deaths occurred 14 to 55 days after transplant, with a median of 21 days. For exposed recipients, donor-derived coccidioidomycosis is a significant cause of morbidity and mortality. Evidence of infection in one recipient should prompt immediate evaluation for treatment of all other recipients from the same donor as preemptive treatment was effective. Further studies are needed to decide whether all donors from endemic areas should have routine serologic screening.

Successful treatment of a disseminated infection with extensively drug-resistant Klebsiella pneumoniae in a liver transplant recipient with a fosfomycin-based multidrug regimen.

Donor-derived infections with multidrug-resistant gram-negative bacteria are associated with poor outcomes, in part because of limited treatment options. Here, we describe a case of donor-derived, disseminated infection with colistin-resistant, carbapenemase-producing Klebsiella pneumoniae in a liver transplant recipient that was cured with addition of intravenous fosfomycin to a multidrug regimen, in conjunction with aggressive surgical source control. Intravenous fosfomycin represents a promising adjunctive agent for use in treatment of extensively drug-resistant infections in immunocompromised hosts.

Transfusion transmitted infections in solid organ transplantation.

While the risk of infectious disease transmission through blood transfusion has been greatly reduced as a result of improved screening methods, transfusion-transmissible infections remain a concern for transplant recipients, especially those receiving multiple transfusions. Although transfusion and transplant recipients are at risk for similar infections, the current reporting requirements for infections transmitted by transfusions and organ transplantation vary greatly and remain distinctly separate with no communication between reporting systems. This article reviews 23 past reports of transfusion-transmitted infections in organ recipients acquired through transfusions. While cytomegalovirus was a major focus of such reports in the 1980s, more recent reports have focused on West Nile virus transmission. Additionally, this article highlights challenges in determining transfusion-transmitted infection risk in transplant recipients related to the current reporting systems.

Transmission of Hepatitis C Virus From Organ Donors Despite Nucleic Acid Test Screening.

Nucleic acid testing (NAT) for hepatitis C virus (HCV) is recommended for screening of organ donors, yet not all donor infections may be detected. We describe three US clusters of HCV transmission from donors at increased risk for HCV infection. Donor's and recipients' medical records were reviewed. Newly infected recipients were interviewed. Donor-derived HCV infection was considered when infection was newly detected after transplantation in recipients of organs from increased risk donors. Stored donor sera and tissue samples were tested for HCV RNA with high-sensitivity quantitative PCR. Posttransplant and pretransplant recipient sera were tested for HCV RNA. Quasispecies analysis of hypervariable region-1 was used to establish genetic relatedness of recipient HCV variants. Each donor had evidence of injection drug use preceding death. Of 12 recipients, 8 were HCV-infected-6 were newly diagnosed posttransplant. HCV RNA was retrospectively detected in stored samples from donor immunologic tissue collected at organ procurement. Phylogenetic analysis showed two clusters of closely related HCV variants from recipients. These investigations identified the first known HCV transmissions from increased risk organ donors with negative NAT screening, indicating very recent donor infection. Recipient informed consent and posttransplant screening for blood-borne pathogens are essential when considering increased risk donors.

An Assessment of HIV-Infected Patients Dying in Care for Deceased Organ Donation in a United States Urban Center.

Organ transplantation is an acceptable option for human immunodeficiency virus (HIV)-infected patients with end-stage kidney or liver disease. With worse outcomes on the waitlist, HIV-infected patients may actually be disproportionately affected by the organ shortage in the United States. One potential solution is the use of HIV-infected deceased donors (HIVDD), recently legalized by the HIV Organ Policy Equity (HOPE) Act. This is the first analysis of patient-specific data from potential HIVDD, retrospectively examining charts of HIV-infected patients dying in care at six HIV clinics in Philadelphia, Pennsylvania from January 1, 2009 to June 30, 2014. Our data suggest that there are four to five potential HIVDD dying in Philadelphia annually who might yield two to three kidneys and three to five livers for transplant. Extrapolated nationally, this would approximate 356 potential HIVDD yielding 192 kidneys and 247 livers annually. However, several donor risk indices raise concerns about the quality of kidneys that could be recovered from HIVDD as a result of older donor age and comorbidities. On the other hand, livers from these potential HIVDD are of similar quality to HIV-negative donors dying locally, although there is a high prevalence of positive hepatitis C antibody.

Considerations for screening live kidney donors for endemic infections: a viewpoint on the UNOS policy.

In February 2013, the Organ Procurement and Transplantation Network mandated that transplant centers perform screening of living kidney donors prior to transplantation for Strongyloides, Trypanosoma cruzi and West Nile virus (WNV) infection if the donor is from an endemic area. However, specific guidelines for screening were not provided, such as the optimal testing modalities, timing of screening prior to donation and the appropriate selection of donors. In this regard, the American Society of Transplantation Infectious Diseases Community of Practice, together with disease-specific experts, has developed this viewpoint document to provide guidance for the testing of live donors for Strongyloides, T. cruzi and WNV infection, specifically identifying at-risk populations and testing algorithms, including advantages, limitations and interpretation of results.

Risk factors for nontuberculous mycobacterial infections in solid organ transplant recipients: a case-control study.

BACKGROUND: The epidemiology of nontuberculous mycobacteria (NTM) disease in solid organ transplant recipients is poorly defined. METHODS: We identified all solid organ transplant recipients with NTM disease at a single center over a 7.5-year period, and collected data on patient demographics, co-morbidities, immunosuppressive medications, and rejection. We conducted a case-control study to identify risk factors for disease, matching 3 control patients to each case patient by date of transplantation. RESULTS: A total of 34 cases of NTM disease occurred during the study period, involving 6 single lung, 13 bilateral lung, 8 heart, 4 liver, 2 kidney, and 1 pancreas-kidney recipients. Cases were predominantly male (24/34), with a median age of 55 years (interquartile range [IQR]: 46-61 years), and developed after a median of 8 months post transplantation (IQR: 2-87 months). Mycobacterium abscessus and Mycobacterium avium complex were the most common pathogens, and the lung (including pleura) was the most common site of disease. In the adjusted case-control analysis, lung transplant recipients had the highest risk of NTM disease. CONCLUSIONS: Additional studies are needed to evaluate the role of targeted surveillance measures for NTM disease in high-risk patients, particularly lung transplant recipients, and to characterize the mechanisms of disease acquisition.

Optimal testing of the live organ donor for blood-borne viral pathogens: the report of a consensus conference.

In 2011, live donor transmission events involving Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) prompted consideration of changing the process of live donor testing and evaluation in the United States. Following CDC recommendations for screening all live donors with nucleic acid testing for HIV, HCV and Hepatitis B (HBV), a consensus conference was convened to evaluate this recommendation. Workgroups focused on determining whether there was an evidence based rationale for identifying live donors at increased risk for HIV, HBV and HCV, testing options and timing for diagnosing these infections in potential donors and consent issues specific to potential increased risk donor utilization. Strategies for donor assessment were proposed. Based on review of the limited available evidence as well as guidance documents and policies currently in place in the United States and other countries, the conference participants recommended that HIV, HBV and HCV NAT should not be required for live donor evaluation; the optimal timing of live donor testing for these blood borne pathogens has not been determined.

A consolidated biovigilance system for blood, tissue and organs: one size does not fit all.

Biovigilance systems to assess and analyze risks for disease transmission through the transfer of organs, tissue, cells and blood between people is part of administrative oversight and has impact upon clinical practice and policy. In 2009, a formal recommendation by the Public Health Service requested that Health and Human Services fund and support efforts to consolidate national biovigilance efforts. There are differences in the biovigilance issues involved in organ and tissue donation/transplantation. If disease avoidance is made the dominant principle guiding organ donor testing, an unintended consequence may be an increase in deaths on the waiting list. We propose that overall benefit for the organ transplant recipient, tempered by patient informed awareness of limited organ availability and assessment processes, should be the guiding principle of such a system.

Risk factors and clinical outcomes of cytomegalovirus disease occurring more than one year post solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease typically occurs during the first year after solid organ transplantation, after cessation of antiviral prophylaxis. CMV occurring after the first year is uncommon and not well described. METHODS: We conducted a case-control study to identify potential risk factors and a retrospective cohort study to evaluate 1-month mortality in solid organ transplant (SOT) recipients who developed CMV disease after the first year post transplant, or "very late CMV" (VLCMV), compared with those developing CMV within the first year (CMV Y1), adjusting for demographics, donor and recipient CMV serostatus, immunosuppression, rejection, and co-morbidities. RESULTS: We identified 85 SOT recipients with CMV disease at a single transplant center between January 2006 and October 2008: 23 (27%) had VLCMV and 62 (73%) had CMV Y1. Heart transplantation was independently associated with increased risk (adjusted odd ratio [OR] 4.11; 95% confidence interval [CI] 1.34-12.61; P = 0.01) for VLCMV. Patients with VLCMV had increased 1-month mortality (unadjusted OR 5.39; 95% CI 1.06-27.48; P = 0.02). Mortality was uncommonly attributable to CMV. CONCLUSIONS: CMV disease continues to occur after the first year post solid organ transplantation, particularly in heart transplant recipients, and can be associated with poor outcomes. CMV should be suspected in patients with symptoms or laboratory findings consistent with CMV, even if the patients present >1 year post transplant.

Outcomes of transplantation using organs from a donor infected with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae.

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi-organ infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha-1 antitrypsin deficiency and alcohol-related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC-producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living-donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC-producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC-producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed-field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC-producing K. pneumoniae. All transplant recipients had good short-term outcomes. These cases highlight the importance of inter-institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug-resistant organisms.

Influenza vaccination in the organ transplant recipient: review and summary recommendations.

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

Guidance on novel influenza A/H1N1 in solid organ transplant recipients.

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS.

The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients.

Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.

Transplantation of kidneys from donors at increased risk for blood-borne viral infection: recipient outcomes and patterns of organ use.

Kidney transplantation from deceased donors classified as increased risk for viral infection by the Centers for Disease Control (CDC) is controversial. Analyses of Organ Procurement and Transplantation Network (OPTN) data from 7/1/2004 to 7/1/2006 were performed. The primary cohort included 48 054 adults added to the kidney transplant wait list. Compared to receiving a standard criteria donor (SCD) kidney or remaining wait-listed, CDC recipients (HR 0.80, p = 0.18) had no significant difference in mortality. In a secondary cohort of 19 872 kidney recipients at 180 centers, SCD (reference) and CDC (HR 0.91, p = 0.16) recipients had no difference in the combined endpoint of allograft failure or death. Among centers performing >10 kidney transplants during the study period, the median proportion of CDC transplants/total transplants was 7.2% (range 1.1-35.6%). Higher volume transplant centers were more likely to use CDC kidneys compared to low and intermediate volume centers (p < 0.01). An analysis of procured kidneys revealed that 6.8% of SCD versus 7.8% of CDC (p = 0.13) kidneys were discarded. In summary, center use of CDC kidneys varied widely, and recipients had good short-term outcomes. OPTN should collect detailed data about long-term outcomes and recipient viral testing so the potential risks of CDC kidneys can be fully evaluated.

Hepatic involvement in a liver transplant recipient with disseminated cryptococcosis.

Cryptococcosis occurs primarily in immunocompromised patients such as organ transplant recipients. Central nervous system and pulmonary infections are documented most frequently; hepatic involvement is rarely reported. We report a case of early hepatic cryptococcosis in a 54-year-old male liver transplant recipient. Two weeks after orthotopic liver transplant, he was readmitted with fever, malaise, diarrhea, and progressive pulmonary infiltrates. On admission, liver-associated enzymes were decreased from those at discharge after transplantation. Blood and bronchoalveolar lavage cultures were positive for Cryptococcus neoformans. Despite treatment with amphotericin B and flucytosine, the patient developed both marked cholestasis and transaminase elevation. A liver biopsy performed 22 days after admission revealed numerous yeast-like organisms in hepatic sinusoids consistent with C. neoformans. Despite treatment, the patient died 55 days after admission and 66 days after transplantation. Our case illustrates hepatic involvement of cryptococcal infection within the first month following transplantation.