Unit 3 - Viruses and Transplantation

Question 1

What is Solid Organ Transplantation (SOT)?

What are three groups of viruese that are brought to attention with organ transplantation?

Answer 1

• 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:

1. Herpesviruses (CMV, HSV, EBV)
2. Hepatitis viruses (HBV and HBC)
3. Heterogeneous (respiraotry viruses, BK viruses)

Question 2

What is involved with viral infections in transplant patients?

There are three stages. What are they?

Answer 2

• 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)

Question 3

What is Cytomegalovirus (CMV)?

Answer 3

• 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

Question 4

How does Cytomegalovirus (CMV) relate and is involved in SOT?

Answer 4

• 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

Question 5

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?

Answer 5

• 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

Question 6

What is the drug that is used in CMV and SOT?

Answer 6

• 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

Question 7

What is Epstein-Barr Virus (EBV) and SOT?

Answer 7

• 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

Question 8

What is Hepatitis Virus with SOT?

Answer 8

• 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

Question 9

What are Polyomaviruses?

What are the three species known to infect man?

Answer 9

• 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)

Question 10

What is BK virus?

How do you detect the virus?

Answer 10

• 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

Question 11

How does it become active?

Answer 11

• 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

Question 12

How is the BK virus Treated?

Answer 12

• 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

Question 13

What is the JC virus?

Answer 13

• 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)

Question 14

What is Rabies Virus?

Answer 14

• 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

Question 15

What are some prevention methods used to prevent viral infection in SOT?

Answer 15

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)