Unit 3 - Viruses and Transplantation Flashcards
What is Solid Organ Transplantation (SOT)?
What are three groups of viruese that are brought to attention with organ transplantation?
- Accepted form of treatment for end-stage kidney, liver, heart and pancreatic diseases
- In 2011 there were 28,535 organ transplants (an average of 79 transplants per day)
- Besides rejection, viral pathogens have emerged as the most important microbial agents compicating solid organ transplant
Adverse effects on allograft survival
Adverse effects on patient survival
- Three groups of viruses merit attention:
- Herpesviruses (CMV, HSV, EBV)
- Hepatitis viruses (HBV and HBC)
- Heterogeneous (respiraotry viruses, BK viruses)
What is involved with viral infections in transplant patients?
There are three stages. What are they?
- Viral pathogens cause 30% of all post-transplantation infections (mostly herpesviruses)
- Month 1 (early): The immune system is usually most suppressed in the first month after transplant; most infections during this time period are nosocomial or iatrogenic.
- Months 2-6: Transplant recipient at risk for opportunistic infections and at highest risk for reactivation of certain latent viruses
- > 6 months (late): most recipients do well; risk for community acquired infections (e.g. influenza)
What is Cytomegalovirus (CMV)?
- Member oof the Herpesviridae family of viruses (Human herpesvirus-5)
- Transmitted via close, intimiate contact with person who is excreting virus in saliva, urine, other body fluids
- Characteristic ability to remain latent within the body over long periods (asymptomatic infection in healthy individuals)
- Encodes multiple proteins that interfere with MHC class I presentation of viral antigens
How does Cytomegalovirus (CMV) relate and is involved in SOT?
- CMV is the single most important viral infection in solid organ transplant recipients
=40-80% of adults in U.S. have been exposed (seropositive)
=20% to 60% of all transplant recipients develop symptomatic CMV infection
=Sources of infection in recipients include latent reactivation, donor-transmitted virus, & virus present in donor WBCs
=Highest risk is with CMV-seropositive donor and CMV-seronegative recipient
-primary infection; severe manifestations
With CMV and SOT, what are some of the characteristics of diseases that develop during the first few months?
What are the diagnostic methods used?
- Disease develops during the first few months after transplantation and is associated iwth clinical infectious disease (ranging from mild to life-threatening)
***episodic fever spikes
***fatigue, pneumonia, abdominal pain, diarrhea, hepatitis
***viral dissemination
***acute/chronic graft injury and dysfunction
***increased risk for fungal and other opportunistic infection
The diagnosis methods are: PCR, serology, shell vial culture technique
- pre0empitve drug therapy if recipient is positive
What is the drug that is used in CMV and SOT?
- Ganciclovir (IV or oral) is the most commonly used agent for the prevention of CMV infection/disease in recipients (prophylaxis and preemptive therapy)
- Viral load is an optimal parameter to use for monitoring response to antiviral therapy
—- Drug given until viral replication is no longer evident (PCR negative)
- Incidence of ganciclovir-resistant CMV infection is 2.1%
==Diagnosis made if virus is not cleared after 14-21 days of IV ganciclovir therapy
===Valganciclovir; a prodrug of ganciclovir
What is Epstein-Barr Virus (EBV) and SOT?
- Also called Human herpesvirus 4 (HHV-4)
- >90% of adults in developed countries are seropositive
- cause of infectious mononucleosis
- Severe T cell immunosuppression in recipients can cause EBV-infected B cells to expand unchecked resulting in malignancy
- Post-transplant lymphoproliferative disorders (PTLD)
- Primary EBV infection is the greatest risk factor for the development of PTLD (recipient is EBV seronegative)
- PTLD most common among intestine and lung transplant recipients
What is Hepatitis Virus with SOT?
- Transmitted by infected blood and body fluids; also perinatally
- Chronic HBV infection confers 25-40% lifetime risk for death due to liver failure or carcinoma
- Common indication for liver transplantation
- Recurrence of active HBV disease occurs after liver transplantation in >90% of cases
- Immunosupression
- HBV-infected blood cells, spleen, other organs
- Passive immunization with HBV Ig
- Antiviral agents
What are Polyomaviruses?
What are the three species known to infect man?
- DNA viruses that are ubiquitous in nature
- Up to 90% of humans have been exposed to polyomavirus by adulthood
- Initial infection is usually asymptomatic and probably occurs via the respiratory route or as a blood-borne infection
- Three species known to infect man: BK virus, JC virus, and a simian virus 40 (SV40)
What is BK virus?
How do you detect the virus?
- Virus first isolated in 1971 from the urine of a renal transplant patient (initials B.K.)
- Rarely causes disease since many people who are infected with this virus are asymptomatic or mild (respiratory symptoms, fever)
- Virus disseminates to kidneys and urinary tract
- 82% of healthy blood donors contains a latent form of this virus
- BKV DNA quantification in plasma is used as an important diagnotic tool and is detected in 15 to 30% of renal transplant recipients during the first posttransplantation year
- Urine test for “decoy cells”
== virally infected epithial cells
== strong resemblance to cancer cells; misdiagnosis
How does it become active?
- Immunosupression (during kidney transplant) results reactivation and severe disease.
- 1-10% of renal transplant patients progress to BK virus nephropathy
- 80% of these patients are reported to have lost their grafts
How is the BK virus Treated?
- Therapy is reduction in immunopression
- Discontinuation of a single immunopression agent, antimetabolite (MMF or azathioprine), upon recognition of viremia has been used successfully to clear viremia
- Cidofovir is nephrotoxic and its use must be weighed against the possible risk for further worsening of renal function
- Probably because of its latency in the kidney, BK rarely affects nonrenal transplant recipients
![](https://s3.amazonaws.com/brainscape-prod/system/cm/028/587/566/a_image_thumb.png?1659404296)
What is the JC virus?
- 75% sequence similarity to BK virus
- Infects 70-90% of the general population
- Acquired in childhood
- Tonsils or GI tract are the initial sites of infection
- Crosses blood–brain barrier into the central nervous system, where it infects oligodendrocytes and astrocytes
- Immunodeficiency or immunosuppression allows JCV to reactivate
- progressive multifocal leukoencephalopathy (PML)
What is Rabies Virus?
- Four organ recipients died in Texas in 2004 after contracting rabies from donor organs
- Donor exhibited encephalitis
- Maryland man died of rabies last month; received a kidney from an infected donor in 2011
- Donor exhibited encephalitis; doctors suspected a food-borne toxin rather than rabies
- Other recipients have shown no symptoms but are ongoing post-exposure vaccination (anti-rabies Ig plus rabies vaccine)
- New guidelines established in 2012 urge caution when considering donors with encephalitis
- Risk of dying without an organ is still much greater than the risk of dying due to a transmitted disease
What are some prevention methods used to prevent viral infection in SOT?
Methods of prevention include:
- Avoidance (screening; lifestyle changes)
- Active immunization (vaccines, if available)
- Passive immunization (virus-specific Ig)
- Immunomodulation (interferons)
- Chemoprophylaxis (anti-virals)
Prophylaxis (entire population)
Pre-emptive (evidence of active infection)