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Protecting Your Transplant Patient From Varicella Zoster in 2012:
What Can You Do?


Fernanda P Silveira, MD, MS
University of Pittsburgh


silveirafd@upmc.edu


fernanda silveiraThoracic transplant recipients have the highest incidence of varicella zoster virus (VZV) infection among all transplant recipients. Primary VZV infection causes varicella, also known as chickenpox, and reactivation of VZV causes herpes zoster (HZ), which can be complicated by post-herpetic neuralgia, a significant cause of morbidity. Less common but severe complications include disseminated cutaneous disease and visceral involvement, such as pneumonitis.

Almost all adults in Europe and North America have evidence of prior VZV infection, so adult transplant recipients are generally at risk for HZ. In a study of adult lung transplant recipients, HZ occurred in 12.1% of the recipients.1 Well established risk factors for HZ following transplantation are not known. As seen in the general population, older age increases the risk. Transmission of VZV occurs from individuals with active infection through aerosol particles and direct skin contact.

Prevention of VZV infection post-transplant starts in the pre-transplant evaluation. VZV serology must be checked and susceptible individuals should be given the live attenuated Oka strain vaccine (Varilrix®, GlaxoSmithKline, Belgium or Varivax®, Merck & Co., Inc., USA). The standard two doses should be given prior to transplantation with a minimal interval of 6 weeks. Vaccination should occur at least 2-4 weeks prior to transplantation. Some small studies have shown that varicella vaccine may be safe post-transplant, particularly in pediatric transplant recipients who are clinically stable and not in the early post-transplant phase; however, until larger and controlled trials are available varicella vaccine is not recommended post-transplant.

A live attenuated zoster vaccine (Zostavax®, Merck & Co., Inc., USA), which contains approximately 15 times more live virus than the varicella vaccine is available for individuals ≥ 50 years old. In a large, randomized trial in adults >60 years old, the vaccine showed a > 50% reduction in the incidence of HZ and post-herpetic neuralgia.2 The vaccine has not been studied in patients with end-organ disease or in pre-transplant patients. Further study is needed to determine if it will be efficacious in preventing post-transplant HZ when administered to VZV seropositive transplant candidates. The zoster vaccine is not recommended for post-transplant patients.

Antiviral therapy used for cytomegalovirus (CMV) prevention will prevent VZV reactivation and additional prophylaxis for VZV is not needed. Short-term herpes simplex prophylaxis with acyclovir or valacyclovir given to transplant recipients who do not receive CMV prophylaxis will be effective against VZV. Because VZV infection can occur at any point after transplantation, long-term VZV prophylaxis is not recommended.

Post-exposure prophylaxis should be offered to every seronegative transplant recipient after a significant exposure, due to the risk of developing varicella. Significant exposure includes household contact; contact in the same room, such as a classroom or a 2- to 4-bed hospital room for a significant period of time (usually 1 hour or more); and face to face contact with an infectious staff member or patient. VZV infection can be spread from a person with varicella or HZ. Passive immunoprophylaxis with varicella zoster immune globulin (VariZIG™, Cangene Corporation, Canada) should be given as soon as possible. VariZIG is available in the United States through an investigational new drug application expanded access protocol.

In May 2011, the US Food and Drug Administration (FDA) approved an extended period for administering VariZIG. VariZIG can now be administered up to 10 days after exposure.3 It was previously approved for administration only up to 4 days after exposure. FDA's decision was based on limited data showing a comparable incidence of varicella among persons who received varicella zoster immune globulin within 4 days of exposure and those who received it up to 10 days after exposure. Disease attenuation is achieved with administration up to 10 days post-exposure.

Post-exposure prophylaxis with antiviral agents can be given as adjunctive therapy or to transplant recipients who were not able to receive varicella zoster immune globulin within 10 days of exposure. Valacyclovir is preferred over acyclovir due to better bioavailability. Antiviral prophylaxis should be given for 7 days, starting 7-10 days after exposure.

Transplant patients with varicella or HZ who require hospitalization should be placed on airborne and contact isolation until lesions are crusted. Exposed susceptible transplant recipients should be placed on airborne and contact isolation from day 10 to 21 after exposure. Those who received varicella immune globulin should remain in precautions until day 28. HZ lesions should be covered to decrease the risk of transmission.

Lastly, we must create a circle of protection around our transplant patients. Their close contacts and family members 12 months or older should receive the varicella vaccine if they have no history of varicella or HZ, were never immunized and have no contraindications to vaccination. Close contacts and family members 50 years or older may receive the zoster vaccine if they have no contraindications to vaccination.


Disclosure Statement: The author has no conflicts of interest related to this topic.

References:

  1. Manuel O, Kumar D, Singer LG, Cobos I, Humar A. Incidence and clinical characteristics of herpes zoster after lung transplantation. J Heart Lung Transplant. 2008 Jan;27(1):11-6.
  2. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84.
  3. FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella. MMWR Morb Mortal Wkly Rep. 2012 Mar 30;61(12):212.