Donor-derived Infection Research Articles

West Nile Virus Infection in the Immunocompromised Patient.

West Nile virus infection has become the predominant cause of flavivirus-associated encephalitis in the US. While 80% of infected individuals are asymptomatic, 20% develop symptoms including fever, headache, transient rash and gastrointestinal symptoms. Among the immunocompetent population, 1 in 150 develop neuroinvasive disease characterized by acute flaccid paralysis, Parkinsonian cogwheel rigidity, meningitis, encephalitis, meningoencephalitis and asymmetric muscle weakness (Mostashari et al. in Lancet 358:261-264, 2001). In the immunocompromised population such as transplant recipients and HIV-infected and chemotherapy patients, the incidence of neuroinvasive disease may be increased. The largest population studied is recipients of solid organ transplants, with data on both donor-derived and naturally occurring transmissions. The risk of neuroinvasive disease in donor-derived infection is estimated to be between 50% and 75% while in those with mosquito-borne transmission the risk is estimated at 40% of those infected (Kumar et al. in Am J Transplant 4:1883-1888, 2004). With significant morbidity associated with donor transmission, specific pretransplant screening recommendations are reviewed. Treatment includes supportive care and consideration for the use of intravenous immunoglobulin.

Donor-Derived Trypanosoma cruzi Infection in Solid Organ Recipients in the United States, 2001–2011

Although Trypanosoma cruzi, the parasite that causes Chagas disease, can be transmitted via organ transplantation, liver and kidney transplantation from infected donors may be feasible. We describe the outcomes of 32 transplant recipients who received organs from 14 T. cruzi seropositive donors in the United States from 2001 to 2011. Transmission was confirmed in 9 recipients from 6 donors, including 3 of 4 (75%) heart transplant recipients, 2 of 10 (20%) liver recipients and 2 of 15 (13%) kidney recipients. Recommended monitoring posttransplant consisted of regular testing by PCR, hemoculture, and serology. Thirteen recipients had no or incomplete monitoring; transmission was confirmed in five of these recipients. Four of the five recipients had symptomatic disease and all four died although death was directly related to Chagas disease in only one. Nineteen recipients had partial or complete monitoring for T. cruzi infection with weekly testing by PCR, hemoculture and serology; transmission was confirmed in 4 of 19 recipients with no cases of symptomatic disease. Our results suggest that liver and kidney transplantation from T. cruzi seropositive donors may be feasible when the recommended monitoring schedule for T. cruzi infection is followed and prompt therapy with benznidazole can be administered.

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

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

Donor-derived filamentous fungal infections in solid organ transplant recipients

Filamentous fungal infections due to rare opportunistic moulds can be transmitted with an allograft. However, epidemiologic and clinical characteristics of donor-derived filamentous fungal infections (DDFFIs) in transplant recipients are poorly understood. Hence, the aim of this article is to describe donor-related risk factors, clinical presentation, graft and recipient outcomes associated with DDFFIs. To date, 23 cases of donor-derived opportunistic filamentous fungal infections have been reported; a majority (91%) occurred in kidney transplant recipients. Aspergillus spp. was the most common organism (71%). Risk factors for DDFFIs include immunosuppressive state of the donor (transplant recipients serving as organ donors), near-drowning events, and transplant-tourism practices. DDFFIs manifested as vascular complications related to graft vasculature (65%), allograft dysfunction (43%) and unexplained febrile illness (39%) in the recipient. Rates of graft loss and overall mortality were 83 and 17%, respectively. Donor-transmitted filamentous mycoses have a unique spectrum of illness and clinical settings under which transmission occurs. Prompt recognition, early surgical intervention and specific antifungal therapy are necessary for achieving optimal graft and recipient outcomes.

Donor-Derived Infections With Central Nervous System Pathogens After Solid Organ Transplantation

During the past decade, numerous instances have been reportedofdonor-derived infectionamongrecipientsof solidorgan transplants with pathogens associated with central nervous system (CNS) infections.1-7 Many cases have received significant attention both among the transplant community and the laymedia.Notablepathogenshave includedWestNile virus (WNV), Balamuthia mandrillaris, lymphocytic choriomeningitis virus, and rabies virus. In most cases, donorderived infection was suspected only after symptoms developed in recipients and further testing of archived specimens identified a donor source. In some cases, lack of recipient exposure to the pathogenprompted investigation for donor origin of the infection. Recipient outcomes were often poor; in part because even after identification of infection, effective treatment was not available. In this issueof JAMA, Vora andcolleagues8describe a case of donor-derived rabies in a recipient of a kidney transplant. The investigationwas prompted by the death from rabies of a recipient 18 months after transplant in the absence of exposures.Adetailed inquiry ledbyCenters forDiseaseControl and Prevention investigators confirmeddonor origin of the recipient’s infectionwith a raccoon rabies virus. The report contains a number of unexpected clinical features. Despite the immunosuppressed state of all 4 organ recipients, the affected patient remained asymptomatic for 18months after transplantation, and the 3 other patients did not develop rabies. The authors speculate that either a low dose of rabies virus or differential behavioral of the raccoon rabies variant explains these clinical features. Although the epidemiology and pathogenesis considerations are interesting, the most notable aspect of this report surrounds the implications for improving the safety of solid organ transplantation. Combined with previous cases,1-7 this report highlights a pattern of donor-derived infection caused by unidentified (at the time of procurement) donor infection with pathogens associated with CNS infection. Reducing the riskofdonor-derived infection requiresunderstanding thecurrent system of screening potential donors. Policy governing solid organ transplantation is established by the Organ Procurement and Transplantation Network (OPTN). Assessment of deceased donors for the risk of transmissible disease relies on amultipronged approach. The organ procurement organization (OPO)managing the process obtains amedical and social history from individuals familiar with the donor. Information that might reasonably be expected to affect potential recipients (eg, a history of recent intravenous drug usewould increase risk of acute viral hepatitis or human immunodeficiencyvirus [HIV] infection thatmightnotbedetectedon routine serologic donor screening tests) must be communicated to transplant programs.9 Limitations include the availability of friends and family and their familiaritywith thedonor’s exposures and behaviors. In addition, specific laboratory testingmust beperformedonall deceaseddonors. Required tests include serological testing forHIV, hepatitis C virus, hepatitis B virus, syphilis, cytomegalovirus, and Epstein-Barr virus as well as blood and urine cultures. At the time of a potential recipient being offered an organ for transplantation, the accepting transplant center must, in a time-pressured environment, integrate all this information, including the medical urgency of the potential recipient, andmake a decision regarding whether to accept the organs. Accepting centers necessarily rely on the clinical impression of treating physicians. For situations in which an increased riskof transmissible infection is present, specific informed consent must be obtained from the potential recipient.10 As an added safeguard, OPOs are required to report additional information that becomesavailable after transplant (eg, autopsy results) that might affect recipients. Furthermore, transplant centers must report any recipient events suggestive of donor-derived infection, thereby allowing notification of other centers that received organs from the same donor.For example, if a recipientwithnootherknownexposures is newly diagnosedwith hepatitis C after transplantation, the event should be reported to the OPTN. In the case described by Vora and colleagues,8 suspected donor-derived rabieswas reported to theOPTN, allowing rapidnotificationof the transplant centers caring for other recipients andadministrationof postexposure rabiesprophylaxis.AnOPTNcommittee, theDisease Transmission Advisory Committee (DTAC), reviews all such reports anddecideswhether theevent resulted indonorderived disease. Data are aggregated andused to guide policy development and educational efforts within the transplant community. Under the current system, episodes of unexpected donor-derived infection are rare. During 2008-2011, 113 622 patients received solid organ transplants from 57 488 donors.Donor-deriveddisease (infectionandmalignancy)developed in139 recipients (0.1%) resulting in29deaths (0.03%).11 A relevant comparison to make is that, during the same period, 26 852peoplediedwaiting for anorgan transplantation.12 Despite these safeguards, reports of CNS infection transmissionmandate consideration ofwhatmight be done to furRelated article page 398 Opinion

Impaired Direct Priming of CD8 T Cells by Donor-Derived Cytomegalovirus Following Kidney Transplantation

Cytomegalovirus (CMV) infection increases the risk of complications after renal transplantation, but the mechanisms controlling donor-derived infection are not adequately characterized. Here, we assessed the risk of clinically significant CMV disease in donor-seropositive, recipient-seropositive (D+R+) renal transplantation and examined recipients' CMV antigen-specific cellular immune responses primed directly by donor cells. In a retrospective cohort of 569 patients administered standardized basiliximab-tacrolimus-mycophenolate-corticosteroid immunosuppressive therapy, CMV disease rates increased in D+R+ serostatus pairings compared with D-R+ pairings (hazard ratio [HR], 2.61; 95% confidence interval [CI], 1.36 to 5.01; P=0.004) and associated with increased donor-recipient HLA mismatch in the D+R+ group (HR [per class 1 mismatch], 1.43; 95% CI, 1.12 to 1.82]; P=0.02). D+R+ and D+R- transplants in which the donor and recipient differentially expressed at least one HLA class I allele were followed prospectively from the time of transplantation. During the first year after transplantation, four of eight seropositive recipients and one of three seronegative recipients displayed peripheral blood CD8+ T cell responses to CMV presented by recipient-specific HLA. Notably, no recipients mounted responses to CMV presented by donor-specific HLA, despite the detection of CMV antigen expression in all seropositive donor organs examined (n=10), suggesting that the allograft of Class I HLA-mismatched seropositive donors is inaccessible to CD8+ T cell responses. Finally, pretransplant assays of anti-CMV cellular immunity predicted post-transplant CMV replication less accurately in D+R+ pairings than in D-R+ pairings, possibly reflecting in vitro assay specificity for recipient, rather than donor, HLA. These findings are relevant to the clinical management and immunologic understanding of donor-transmitted viral infection.

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-Derived Infections in Solid Organ Transplantation

Summary of potential donor-derived infectious diseasetransmissions reported to the United States organ procurementand transplantation network 2005–2011 (2)Number of Number ofNumber recipients with DDI-attributableInfection of donor confirmed recipienttype reports transmission deathsViruses 1 166 48 16Bacteria 2 118 34 9Fungi 3 75 31 10Mycobacteria 4 53 10 3Parasites 5 35 22 7 1 Viruses: adenovirus, HBV, HCV, HEV, HIV, HTLV, herpes simplex,influenza, LCMV, parainfluenza (PIV)-3, parvovirus B19, rabies,West Nile virus. 2 Bacteria: Acinetobacter, Brucella, Enterococcus (including VRE),Ehrlichiaspp,E.coli,Gram-positivebacteria,Klebsiella,Legionella,Listeria, Borrelia burgdorferi, Nocardia, Pseudomonas, RockyMountain Spotted Fever, Serratia, S. aureus (MRSA), Streptococ-cus spp, Treponema pallidum, Veillonella;bacterialmeningitis&bacterial emboli. 3 Fungi: Aspergillus spp, Candida spp, Coccidioides imitis, Cryp-tococcus neoformans, Histoplasma capsulatum, Scopulariopsis,zygomyces. 4 Mycobacteria: tuberculosis, non-TB mycobacteria.

Endemic Fungal Infections in Solid Organ Transplantation

Endemic Fungal Infections in Solid Organ Transplantation

Transmission of Oriental Tsutsugamichi from a Deceased Donor to Three Organ Transplant Recipients in Thailand

Introduction: Donor-derived infection is rare but growing numbers of cases have increasingly been recognized. We illustrated 3 patients (2 kidneys and 1 liver transplant recipients) who suffered from unexplained clinical symptoms and signs but suggestive of systemic infections following organ transplantation from a common donor. Methods: We performed investigation including detailed medical history of the donor, and examined clinical specimen from the donor and three solid organ recipients using serologic testing and molecular analysis to identify a cause. Results: In February, 2011 two kidney transplant recipients and one liver transplant recipient developed acute high-graded fever 2 weeks after the transplantation. The significant symptoms of kidney recipients also included polyarthralgia and hematuria. Despite an extensive investigation, the cause of their illness remained unknown. Further detailed history showed that the deceased donor was a truck driver who presented to the hospital in comatose from spontaneous intracerebral hemorrhage. However, 3 weeks before his death, his wife reported the history of patient's sub-acute onset of fever which was self-resolved. Following an interview, retrospective analysis of the donor's blood was subsequently analyzed and was positive by IgM and IgG for scrub typhus. Treatment with oral doxycycline resulted in significant clinical improvement of the three cases. Further molecular analysis of the three recipients' blood matched the same strain of Oriental. tsutsugamuchi. Conclusions: We document the first world report of Oriental tsutsugamuchi infection transmitted through organ transplantation.

Donor-Derived Infection: Epidemiology and Outcomes

Over the past decade, the solid organ transplant community has focused increased attention on unexpected transmission of infectious pathogens from organ donor to recipient. While unexpected donor-derived infections are relatively uncommon, recent cases of transmission of human immunodeficiency virus (HIV) and hepatitis C to multiple recipients, as well as transmission of HIV from a living donor, have further increased interest in improving the safety of solid organ transplantation. This article will review the epidemiology and outcomes associated with unexpected donor-derived infection. Furthermore, the reporting and patient safety process will be discussed, as will preventative measures that can reduce the burden of donor-derived infection.

Late primary cytomegalovirus infection presenting with acute inflammatory demyelinating polyneuropathy in a heart transplant recipient: a case report and review of the literature

Cytomegalovirus (CMV) infection is well recognized as a cause of morbidity and mortality in heart transplant recipients. Primary CMV infection can occur early post transplant in at-risk recipients with donor-derived infection, or any time after transplantation in community-acquired infection. We describe a unique case of primary CMV infection occurring 14years after cardiac transplantation. In addition to end-organ CMV disease, this patient developed a post-infectious neurologic phenomenon, acute inflammatory demyelinating polyneuropathy. This entity has rarely been reported in the solid organ transplant population.

Donor-Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation, Infectious Diseases Community of Practice

Donor-derived fungal infections can be associated with serious complications in transplant recipients. Most cases of donor-derived candidiasis have occurred in kidney transplant recipients in whom contaminated preservation fluid is a commonly proposed source. Donors with cryptococcal disease, including those with unrecognized cryptococcal meningoencephalitis may transmit the infection with the allograft. Active histoplasmosis or undiagnosed and presumably asymptomatic infection in the donor that had not resolved by the time of death can result in donor-derived histoplasmosis in the recipient. Potential donors from an endemic area with either active or occult infection can also transmit coccidioidomycosis. Rare instances of aspergillosis and other mycoses, including agents of mucormycosis may also be transmitted from infected donors. Appropriate diagnostic evaluation and prompt initiation of appropriate antifungal therapy are warranted if donor-derived fungal infections are a consideration. This document discusses the characteristics, evaluation and approach to the management of donor-derived fungal infections in organ transplant recipients.

Diagnosis and Management of Tuberculosis in Transplant Donors: A Donor-Derived Infections Consensus Conference Report

Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.

Transmission of Infection With Human Allografts: Essential Considerations in Donor Screening

Transmission of infection via transplantation of allografts including solid organs, eyes, and tissues are uncommon but potentially life-threatening events. Donor-derived infections have been documented following organ, tissue, and ocular transplants. Each year, more than 70000 organs, 100000 corneas, and 2 million human tissue allografts are implanted worldwide. Single donors may provide allografts for >100 organ and tissue recipients; each allograft carries some, largely unquantifiable, risk of disease transmission. Protocols for screening of organ or tissue donors for infectious risk are nonuniform, varying with the type of allograft, national standards, and availability of screening assays. In the absence of routine, active surveillance, coupled with the common failure to recognize or report transmission events, few data are available on the incidence of allograft-associated disease transmission. Research is needed to define the optimal screening assays and the transmissibility of infection with allografts. Approaches are reviewed that may contribute to safety in allograft transplantation.

Highly resistant bacteria and donor‐derived infections: treading in uncharted territory

Transplant Infectious DiseaseVolume 14, Issue 3 p. 223-228 Guest editorial Highly resistant bacteria and donor-derived infections: treading in uncharted territory C.D. Sifri, Corresponding Author C.D. Sifri Division of Infectious Diseases & International Health, University of Virginia, Charlottesville, Virginia, USA Correspondence to: Costi D. Sifri, MD Division of Infectious Diseases & International Health University of Virginia Health System PO Box 800473, Charlottesville, VA 22908-0473 Tel: +1 434 924 0260 Fax: +1 434 924 1225 E-mail: csifri@virginia.edu or Michael G. Ison, MD, MS Divisions of Infectious Diseases and Organ Transplantation Northwestern University Feinberg School of Medicine 645 North Michigan Avenue Suite 900 Chicago, Illinois 60611 Chicago, IL 60611 Tel: +1 312 695 4186 Fax: +1 312 695 5088 E-mail: mgison@northwestern.eduSearch for more papers by this authorM.G. Ison, Corresponding Author M.G. Ison Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA Correspondence to: Costi D. Sifri, MD Division of Infectious Diseases & International Health University of Virginia Health System PO Box 800473, Charlottesville, VA 22908-0473 Tel: +1 434 924 0260 Fax: +1 434 924 1225 E-mail: csifri@virginia.edu or Michael G. Ison, MD, MS Divisions of Infectious Diseases and Organ Transplantation Northwestern University Feinberg School of Medicine 645 North Michigan Avenue Suite 900 Chicago, Illinois 60611 Chicago, IL 60611 Tel: +1 312 695 4186 Fax: +1 312 695 5088 E-mail: mgison@northwestern.eduSearch for more papers by this author C.D. Sifri, Corresponding Author C.D. Sifri Division of Infectious Diseases & International Health, University of Virginia, Charlottesville, Virginia, USA Correspondence to: Costi D. Sifri, MD Division of Infectious Diseases & International Health University of Virginia Health System PO Box 800473, Charlottesville, VA 22908-0473 Tel: +1 434 924 0260 Fax: +1 434 924 1225 E-mail: csifri@virginia.edu or Michael G. Ison, MD, MS Divisions of Infectious Diseases and Organ Transplantation Northwestern University Feinberg School of Medicine 645 North Michigan Avenue Suite 900 Chicago, Illinois 60611 Chicago, IL 60611 Tel: +1 312 695 4186 Fax: +1 312 695 5088 E-mail: mgison@northwestern.eduSearch for more papers by this authorM.G. Ison, Corresponding Author M.G. Ison Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA Correspondence to: Costi D. Sifri, MD Division of Infectious Diseases & International Health University of Virginia Health System PO Box 800473, Charlottesville, VA 22908-0473 Tel: +1 434 924 0260 Fax: +1 434 924 1225 E-mail: csifri@virginia.edu or Michael G. Ison, MD, MS Divisions of Infectious Diseases and Organ Transplantation Northwestern University Feinberg School of Medicine 645 North Michigan Avenue Suite 900 Chicago, Illinois 60611 Chicago, IL 60611 Tel: +1 312 695 4186 Fax: +1 312 695 5088 E-mail: mgison@northwestern.eduSearch for more papers by this author First published: 08 June 2012 https://doi.org/10.1111/j.1399-3062.2012.00752.xCitations: 28Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume14, Issue3June 2012Pages 223-228 RelatedInformation

68 Distinct Microbial Signatures of Healthy and Failing Lung Allografts

Purpose: Donor-derived infections (DDIs) are an adverse consequence of solid-organ transplantation. Potential donor-derived transmission events (PDDTEs) reviewed by the OPTN Disease Transmission Advisory Committee (DTAC) were evaluated to determine the impact of DDIs on lung transplant recipients (LTR). Methods and Materials: PDDTEs reviewed by the DTAC from 1/1/20086/30/2011 were evaluated. The cohort included cases with (i) proven or probable transmission (PPT) of infection to a TR of any organ type and (ii) a lung transplant was performed. Organisms and outcomes with and without transmission to LTR are reported. Results: Of 492 donors with PDDTEs during this era, 337 involved infections and 114 included at least 1 LTR. Of the 114, 18 were determined to have a PPT to at least 1 TR. There were 5386 lung transplant donors during the same period. Eleven of 18 (61%) donors had a PPT to the LTR with 10 of 11 having transmission to the LTR only. In 3/10 at least 1 non-LTR received prophylaxis prior to developing infection, and in 1 other the lung was the only organ transplanted. Organisms transmitted to LTR were bacteria (5: TB in 3, MRSA, Serratia), fungi (4: C. immitis, cryptococcus neoformans, aspergillusin 2) and viruses (2: HBV, LCMV). Four of the 11 infected LTR died. Donor lungs were the source of infection in 7 of 8 cases where the donor source was confirmed. No diagnosis of infection in the donor prior to procurement existed. Of the 7 unaffected LTR, 2 received prophylaxis (AFB, C. Immitis) and did not develop an infection and in the remaining 5 disease was transmitted to a non-LTR only. In 1 case the LTR was seropositive for PPT virus pre-transplant. Organisms transmitted to non-LTR were bacteria (1: Pseudomonas), fungi (3: Aspergillus, C. Albicans, C. immitis), and viruses (1: CMV). All non-LTR were alive at least 1 month post-transplant. Conclusions: Donors associated with a PPT in whom a lung is transplanted have a high frequency of infection which can result in death. Continued efforts must be made to identify infected donors prior to recovery in order to prevent the complications of DDIs in LTR.

67 Donor-Derived Infections in Lung Transplantation

Donor-derived infections (DDIs) are an adverse consequence of solid-organ transplantation. Potential donor-derived transmission events (PDDTEs) reviewed by the OPTN Disease Transmission Advisory Committee (DTAC) were evaluated to determine the impact of DDIs on lung transplant recipients (LTR).

66 Donor-Derived Infections in Heart Transplantation

66 Donor-Derived Infections in Heart Transplantation

Donor Disease Transmission

Donor Disease Transmission