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Recently a US man became the first to receive a pig heart transplant. While this new technology opens many possibilities, it is important to address the pitfalls. Despite numerous safeguards including extensive pathogen screening and protection, the man seems to have acquired a virus from a latent infection in the pig and died. This raises the question, what is a latent infection and what challenges do latent infections present?
Latent Infections
Latent infections occur when a pathogen is in an inactive state and does not multiply or engage in biological activity that might alert the immune system or shed genetic material. Hosts with latent infections generally don’t show symptoms of disease. Serology tests (which look for an immune response) or PCR tests (which look for genetic material) have difficulty capturing latent infections.
Porcine Cytomegalovirus – Pig Heart Transplant
The pig used in a recent human heart transplant was part of a herd kept for specialty medical purposes. The pigs in this herd are sheltered to minimize risks of infection from the environment and tested for pathogens before use. The infection in this pig was presumably latent, as it tested negative for pathogens. Upon further search, the virus was found in its spleen.
The patient first tested positive for porcine cytomegalovirus about 20 days after his transplant. About forty days after his transplant, his health deteriorated and his viral load was much higher. He subsequently died.
Increased contact with animals coupled with emerging diseases increases the risk of contracting a virus or pathogen from an animal. However, this is not the first time a latent infection has gone undetected in a transplant. In these cases, the organs have come from humans who have died. For example, transplant patients have received the West Nile virus from their donors. Reports of West Nile virus transmission may have been underrepresented because transplant care teams may not recognize the emerging disease.
Latent infections, especially from emerging diseases, are a new risk in animal-to-human transplants, and are recognized as a growing risk in blood transfusions and human-to-human transplants. Organizations such as the American Blood Bank Association continually assess risks and testing procedures, and in 2010 the US FDA held a workshop to assess the risk of emerging infectious diseases to blood and transplant safety and produced a report identifying the issues.
Ebola – Immune Privileged Sites
Pathogens can hide in an otherwise healthy human or animal in areas of the body known as “immune privileged sites.” These are sites that can be damaged by inflammation and are protected from inflammatory immune processes. One of these locations is the eyes. Dr. Ian Crozier famously developed a high Ebola viral load in his eye several months after he had otherwise recovered from the disease.
We previously wrote about how immune privileged sites shelter the pathogens that cause Ebola, shingles and Lyme borreliosis.
Dr. Crozier noticed a loss of sight, pain, and discomfort in his eye. The tears and surface of the eye tested negative for the pathogen, which made identifying the infection even more difficult.
Canine Ehrlichiosis – A Latent Infection Invades a Nation
Humans and dogs both get ehrlichiosis but usually from different species. Until 2020, Australia was considered free of Ehrlichia canis, the species that primarily infects dogs. Australia maintained that status through testing and quarantine of traveling animals. But did latent infections slip through the cracks of their screening system?
In 2015, a dog named Ollie was tested for E. canis before traveling to Australia. The dog tested negative. When Ollie arrived in Australia, his tick medication had lapsed by one day, triggering a repeat test. At this point the dog tested positive. Officials wondered how many cases like Ollie’s may have slipped through the cracks because they didn’t have a second test.
No one really knows how E. canis entered Australia, but genetic testing suggests it happened more than one time. It is possible that dogs that tested negative at their origination had a latent infection that developed after they arrived in Australia. The disease now affects domestic and wild dogs in several regions of the country.
HIV – Latent Infection for Good
When HIV spread around the globe in the 1980s, it was impossible to imagine how it would shape the future. HIV is a virus that challenges traditional vaccines and therapeutics. It replicates throughout the body with a high rate of genetic changes. The immune system cannot control the virus or its effects. The evening news showed emaciated, dying people.
After years of research, scientists developed the first HIV treatment. It controlled the replication of the virus enough that people could live longer and in better health. Today, HIV treatments can drive HIV into undetectable levels, that is, into a latent infection. With a latent infection, people do not experience the effects of HIV. They can not transmit the disease through bodily fluids. It’s not a cure for HIV, the treatment must be taken continually and patients experience side effects. If treatment stops, the infection will come back.
Unfortunately, the immune system is unable to fight to destroy the virus when it persists as a latent infection. Experimental treatments have attempted to activate the immune system against the virus that remains in the latent HIV infection. This requires activating the immune system against immune privileged sites including the central nervous system. So far, developing a treatment that does not damage those sites has not been successful.
Conclusion
Latent infections are important to explore as a cause of unexplained relapsing illness and transmittable infections. They pose risks that impact transplant and blood recipients. They also challenge the success of travel testing and quarantine programs. However, driving an infection into latency also carries great promise as a remission status for severe infections that are difficult to eradicate, such as has been accomplished with HIV.
References
Rabin, R. C. (2022, May 5). Signs of an animal virus discovered in man who received a pig’s heart. The New York Times. https://www.nytimes.com/2022/05/05/health/pig-heart-transplant-virus.html
Regalado, A. (2022, May 4). The gene-edited pig heart given to a dying patient was infected with a pig virus. MIT Technology Review. https://www.technologyreview.com/2022/05/04/1051725/xenotransplant-patient-died-received-heart-infected-with-pig-virus/
Greenwald, M. A. et al. (2012). Infectious disease transmission during organ and tissue transplantation. Emerging Infectious Diseases, 18(8), e1. https://doi.org/10.3201/eid1818.120277 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414044/
Clutter, C. (2020, November 30). Conquering latent HIV to end the AIDS pandemic. https://asm.org/Articles/2020/November/Conquering-Latent-HIV-To-End-the-AIDS-Pandemic#:~:text=Latent%20virus%20is%20not%20detectable,be%20expressed%20and%20perpetuate%20infection.&text=In%20light%20of%20these%20challenges,view%20of%20the%20immune%20system.
Neave, M. J. et al. (2022). Comparative genomic analysis of the first Ehrlichia canis detections in Australia. Ticks and Tick-borne Diseases, 13(3), 101909. https://doi.org/10.1016/j.ttbdis.2022.101909 https://www.sciencedirect.com/science/article/pii/S1877959X22000152
Daly, J., & Fowler, C. (2020, July 9). Flawed testing of imported pets could be behind potentially deadly dog disease outbreak. ABC Rural. https://www.abc.net.au/news/rural/2020-07-10/botched-testing-imported-pets-deadly-dog-disease-outbreak/12439812
Grady, D. (2015, May 8). After nearly claiming his life, Ebola lurked in a doctor’s eye. The New York Times. https://www.nytimes.com/2015/05/08/health/weeks-after-his-recovery-ebola-lurked-in-a-doctors-eye.html