Infectious disease risks in xenotransplantation

A search for confirmatory and more recent data revealed that, although the average lifespan of most domestic pigs is 15-27 years, [4][5][6] approximately 90% of pigs are slaughtered between 4.5 and 6 months of age as sources of food. 7,8 Hence, relatively little is known about malignancies occurring in older pigs. However, by the age of 6 months or before, the source pigs (if not miniature swine) will be of a sufficient size eg, 90 kg, for their kidneys to be transplanted into adult human recipients. As pigs will therefore likely be used as sources of organs for clinical transplantation during the first year of life, it is important to review the data on malignancies that develop in young pigs. AbstractThere is an increased incidence of certain tumors and other neoplastic disease in organ allotransplant recipients receiving immunosuppressive therapy. Following clinical pig organ xenotransplantation, will there be a risk of the development of neoplasia in the pig graft or in other tissues transplanted with it, eg, lymph nodes? The incidence of neoplasia in young slaughterhouse pigs is very low (<0.005%), but in older pigs is largely unknown (as most pigs are killed within the first six months of life). However, lymphosarcoma, nephroblastoma, and melanoma have been reported in pigs. These tumors should be readily identified by ultrasound or direct inspection and palpation before an organ is excised for clinical xenotransplantation, and so transfer to the human recipient should be unlikely. Post-transplant lymphoproliferative disorder (PTLD) has been reported in pigs receiving intensive immunomodulatory therapy, particularly if this includes whole body irradiation, in an effort to induce mixed hematopoietic chimerism and immunological tolerance. However, the pigs used as sources of organs in xenotransplantation should be free of the porcine lymphotropic herpesvirus that is a key causative factor for PTLD in pigs, and so donorderived PTLD should not occur. We conclude that the risk of a malignant tumor developing in a transplanted organ from a young pig is small. K E Y W O R D Sneoplasia, pigs, post-transplant lymphoproliferative disorder, tumors, xenotransplantation

Section: Commentmentioning

confidence: 99%

Will donor‐derived neoplasia be problematic after clinical pig organ or cell xenotransplantation?

Jagdale

Iwase

Klein

et al. 2018

“…A real concern in xenotransplanation is the presence of asymptomatic viral swine infections, which are not part of routine pig veterinary screening. Viruses of pigs which are of potential risk in xenotransplantation have been widely researched and reviewed . Some of these viruses cause overt infections, others such as porcine lymphotropic herpesvirus 1 (PLHV‐1), PLHV‐2, and PLHV‐3 may cause latent infections thereby complicating any screening processes.…”

Section: Pig Selection For Xenotransplantationmentioning

confidence: 99%

“…However, pigs are known to be a reservoir of viruses that are pathogenic to humans such as Japanese encephalitis virus, Nipah virus, swine influenza A virus, Menangle virus, and Hepatitis E virus . In addition to these viruses, porcine cytomegalovirus and vesicular stomatitis virus are also known to have zoonotic potential …”

Section: Introductionmentioning

confidence: 99%

Possible risks posed by single‐stranded DNA viruses of pigs associated with xenotransplantation

Karuppannan

Opriessnig

2018

Routine large‐scale xenotransplantation from pigs to humans is getting closer to clinical reality owing to several state‐of‐the‐art technologies, especially the ability to rapidly engineer genetically defined pigs. However, using pig organs in humans poses risks including unwanted cross‐species transfer of viruses and adaption of these pig viruses to the human organ recipient. Recent developments in the field of virology, including the advent of metagenomic techniques to characterize entire viromes, have led to the identification of a plethora of viruses in many niches. Single‐stranded DNA (ssDNA) viruses are the largest group prevalent in virome studies in mammals. Specifically, the ssDNA viral genomes are characterized by a high rate of nucleotide substitution, which confers a proclivity to adapt to new hosts and cross‐species barriers. Pig‐associated ssDNA viruses include torque teno sus viruses (TTSuV) in the Anelloviridae family, porcine parvoviruses (PPV), and porcine bocaviruses (PBoV) both in the family of Parvoviridae, and porcine circoviruses (PCV) in the Circoviridae family, some of which have been confirmed to be pathogenic to pigs. The risks of these viruses for the human recipient during xenotransplantation procedures are relatively unknown. Based on the scant knowledge available on the prevalence, predilection, and pathogenicity of pig‐associated ssDNA viruses, careful screening and monitoring are required. In the case of positive identification, risk assessments and strategies to eliminate these viruses in xenotransplantation pig stock may be needed.

“…Technological advances such as the development of alpha‐1,3‐galactosyltransferase gene knockout pigs, genomewide inactivation of porcine endogenous retrovirus (PERV), and the establishment of successful immunosuppression strategies for nonhuman primates (NHP) have increased the feasibility of xenotransplantation clinical trials . The infection risks related to donor‐derived pathogens and host‐derived opportunistic pathogens under immunosuppression remain a significant challenge to devising clinical trials in xenotransplantation…”

Section: Introductionmentioning

confidence: 99%

“…Given that the possibility of transmission is independent of the value of the NHP model, the possibility of the transmission remains to be established . To exclude other potentially transmissible organisms, “designated pathogen‐free (DPF)” breeding pigs are used to minimize the risk . Importantly, systemic immunosuppressive therapy may not only increase donor‐derived, but also host‐derived infections.…”

Section: Introductionmentioning

confidence: 99%

Long‐term safety outcome of systemic immunosuppression in pig‐to‐nonhuman primate corneal xenotransplantation

Choi

Yoon

Lee

et al. 2018

Costimulatory blockade-based and anti-CD20 antibody/tacrolimus-based immunosuppressive therapies seem to be comparably safe with steroid therapy in nonhuman primates receiving corneal xenotransplantation, as they did not reactivate Rhesus Cytomegalovirus and maintained manageable systemic status. Although reactivation is rare, antiviral prophylaxis for simian varicella virus should be considered in immunocompromised hosts.