Varicella Zoster Virus in Transplant Recipients

Authors: Maha Assi, M.D., Scott James, M.D., David Kimberlin, M.D.


Varicella-zoster virus (VZV) is a double-stranded DNA virus member of the alphaherpesvirus family. The virus is highly temperature sensitive and depends on the envelope proteins for infectivity. It is spread as a cell-free virus into the susceptible host, but once within the infected host is transmitted by cell-to-cell spread (11).


Primary infection with VZV results in varicella (chickenpox). It is highly transmissible by direct contact with a skin lesion and via respiratory droplets (50). Attack rates range from 30% in a classroom and up to 90% among household contacts (29). After the initial episode, VZV remains latent for life in cranial nerves and dorsal root ganglia and potentially can reactivate up to decades later as zoster (shingles) (23). Zoster is more common with older age and in individuals with decreased cell mediated immunity (27).

Varicella can occur throughout the year, but is more common in the spring (March through May) (50). Prior to the ability to prevent VZV infection by vaccination, chickenpox was a near-universal childhood disease, with 90% of adults in the US having acquired the infection before the age of 13. Since the introduction of the varicella vaccine in 1995, the majority of children and young adults have now been vaccinated (13), significantly altering the natural history of illness in both immunocompetent and immunodeficient populations.

VZV is the second most common viral pathogen in solid organ transplant (SOT) recipients (after cytomegalovirus), with a prevalence of about 29%. Varicella is rare in adult SOT recipients, as the majority is already seropositive (19, 43). On the other hand, zoster occurs in approximately 11% of SOT recipients within four years of transplant due to their required long term immunosuppressive regimens (4, 24). Several reports have linked treatment with mycophenolate mofetil (Cellcept), a commonly used medication for immunosuppression after transplantation, to increased incidence of zoster in SOT recipients (33). Herpes zoster classically occurs in the first 6 months after transplantation in SOT recipients. Recent data points towards increased rates of zoster with increasing time post transplant. This could probably be explained by discontinuation of antiviral prophylaxis, combined with increased length of immunosuppressive treatment (4).

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Primary VZV infection usually manifests initially with fever and malaise, followed by a vesicular pruritic rash. Patients have lesions in different stages of development typically on the face, trunk and extremities (57). Transplant patients are at risk of extensive cutaneous involvement and visceral dissemination, which may lead to pneumonia, hepatitis, encephalitis, and disseminated intravascular coagulopathy. These complications cause a great deal of morbidity and are associated with a high mortality rate (17, 43)


In healthy individuals, herpes zoster is most often unilateral involving one or two adjacent dermatomes. The trigeminal nerve, particularly the ophthalmic branch, is the most frequently affected dermatome, comprising 10-15% of cases. Pain and paresthesia within the involved dermatome usually precede by several days the development of lesions which are identical to those of varicella (37).

In immunocompromised patients, including SOT recipients, herpes zoster infection is often a more severe illness. In adult kidney transplant recipients, up to 8% of zoster cases can present with disseminated disease (4). Skin involvement can be more extensive, affecting several noncontiguous dermatomes and lesions may continue to appear for several weeks. Cutaneous dissemination (defined as more than five vesicular lesions beyond the primary dermatome) is more common in hematopoietic stem cell transplant (HSCT) than SOT recipients. Scabbing can be delayed for more than a month. Lesions can extend into the dermis and become hemorrhagic and necrotic. Visceral dissemination through viremic spread, similar to what is described in primary VZV infection, is also possible in up to 30% of cases, causing increased morbidity and mortality (37). Even in the absence of disseminated visceral disease, viremia often occurs in patients with isolated cutaneous VZV disease (14).

Post herpetic neuralgia is the most common neurologic manifestation of herpes zoster (21). Central nervous system complications have been reported mainly in immunocompetent elderly patients and in immunocompromised patients. In the latter, VZV produces a wide variety of clinical syndromes ranging from diffuse small vessel vasculopathy to meningoencephalitis (20).

There are several neurologic complications of zoster due to cranial nerve (CN) involvement. Herpes zoster ophthalmicus occurs when the ophthalmic division of CN V is affected, and occurs in 9% to 16% of cases of herpes zoster. The clinical manifestations include conjunctivitis, anterior uveitis, keratitis, and ophthalmitis (38). Ramsay Hunt Syndrome is a herpetic infection of the geniculate ganglion of the seventh cranial nerve (CN VII). Patients typically present with acute ear pain that radiates to the pinna. Other symptoms include vertigo, ipsilateral hearing loss, tinnitus and facial paralysis. Physical examination usually reveals peripheral facial nerve paresis with associated blisters in the distribution of the nervus intermedius. However the onset of the rash can be delayed for more than 10 days (35). Other unusual presentations have been described with complete absence of auricular lesions (47).

VZV encephalitis is an uncommon manifestation of varicella zoster infection, affecting only 0.1 to 0.2% of patients with VZV infection (16, 21). Among reported cases, most but not all transplant recipients had zoster rash that preceded or was concomitant with the VZV encephalitis (4, 2).

Acute retinal necrosis manifested by retinal vasculitis, confluent retinal necrosis, and acute vitritis produces devastating visual loss. It is seen in healthy and immunocompromised persons (18, 36). Progressive outer retinal necrosis (PORN) is mostly seen in AIDS patients but has also been described in HSCT recipients (28). It is characterized by early involvement of the outer retina, but paucity of intraocular inflammation (5). Other neurologic complications associated with herpes zoster include peripheral motor paralysis, transverse myelitis, and ascending paralysis. Guillain-Barré syndrome has been reported in 17 cases after reactivation of varicella–zoster virus and occurred few days to two months after the zoster rash (42, 42).

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In the setting of acute infection (both varicella and zoster) rapid diagnosis is required to guide decisions about antiviral therapy in immunocompromised hosts, especially those with atypical presentations. VZV can be isolated in tissue culture, albeit less readily than herpes simplex virus. However, this method is not rapid enough to influence clinical decision making (10). The most practical test to virologically confirm acute VZV disease is detection of VZV antigen using a labeled monoclonal antibody. To perform this test, a scraping is obtained from the base of a vesicle and placed on a slide, from which viral antigens then are identified either by staining with fluorescein-conjugated monoclonal antibodies or with enzyme immunoassay methods (10). Another method is VZV DNA detection by in situ hybridization or polymerase chain reaction (PCR) (49). Several PCR assays are commercially available and can be used on different tissue samples including blood, cerebrospinal fluid (CSF), broncheoalveolar lavage, vesicle fluid, and tissue. A swab can be used to rub the base of an unroofed vesicle and then placed in viral transport media, which is then run for PCR detection of VZV DNA; this diagnostic modality is increasingly being used, and is a good adjunct test to perform in addition to antigen detection. Blood PCR has been used to diagnose disseminated infection in the absence of cutaneous lesions (15). Testing by blood PCR is particularly useful in establishing the diagnosis of a neurologic infection with VZV especially in the absence of a concomitant rash.

Serologic tests traditionally are used to determine immune status prior to transplantation. When positive, such tests confirm previous VZV infection in that individual. However, the sensitivity of serologic tests for VZV can be problematic. Commercially available assays for detection of antibody to VZV include the enzyme immunoassay (EIA) and latex agglutination (LA) test (48, 60). The gpELISA that has been used commonly in clinical studies is not commercially available (41). Commercially available EIA and LA tests are less sensitive and therefore unreliable in detecting immunity among vaccinated people. Additionally, the LA test can yield false positive results(6) . VZV IgG and IgM antibodies develop within three days following infection. However VZV IgM can also be detected in most patients with recurrent infection and therefore may not be useful in clinical practice (8).

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Immunocompromised patients with primary varicella infection should be treated with intravenous (IV) acyclovir at 10 mg/kg every 8 hours (Table 1) (39). Maximum benefit is achieved with early initiation of therapy, especially within 24 h of rash onset. However, treatment should still be given even beyond the initial 24 hours of symptoms onset (40). A switch to oral acyclovir or valacyclovir can be made once the patient is clinically improved. Reduction in immunosuppressive therapy should be considered especially in the severely ill patients. Steroid dosing may need to be maintained or increased to avoid adrenal insufficiency (39).

Localized uncomplicated dermatomal zoster can be treated as an outpatient with oral acyclovir (pediatric dose: 20 mg/kg four times a day; adult dose: 800 mg 5 times a day), valacyclovir (pediatric dose: 20 mg/kg three times a day; adult dose: 1g three times a day), or famciclovir (adult dose: 500 mg three times a day) (31, 39). Intravenous acyclovir (10 mg/kg every 8 hrs) is reserved for patients with disseminated skin infection or organ invasive disease (e.g., pneumonia, hepatitis, encephalitis). SOT recipients with herpes zoster ophthalmicus, Ramsay-Hunt syndrome, or those undergoing treatment for acute rejection should also be preferably treated with IV acyclovir, as above. In addition, patients with Zoster ophthalmicus should have an ophthalmology consult, as they are at risk of losing eyesight (39).

Antivirals are to be given for at least 7 days or until lesions are crusted (39). In SOT recipients, treatment may need to be prolonged as crusting of lesions is usually delayed.

In the rare patient with acyclovir-resistant VZV, the alternative drug is foscarnet 40 mg/kg IV every eight hours for 10 days (44). The major disadvantage associated with foscarnet is the potential for significant metabolic and renal toxicity.

Intravenous immunoglobulin (IVIG) has been used in severely ill patients but there is no evidence of improved outcome (52, 53). The same applies to VZV immunoglobulin and therefore routine use of immunoglobulins is not recommended for treatment of VZV (39).

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VARIVAX (Merck) is a live attenuated Oka VZV vaccine used to prevent chickenpox (34). Pre transplant vaccination is indicated in seronegative individuals, with 2 doses given at least 4 weeks apart (39). Protective varicella titers have been reported in 49 to 100 percent of children on dialysis. Post transplantation, recipients with protective titers developed neither varicella nor herpes zoster (9, 54). However, this would delay transplantation by a minimum of 4 weeks and preferably 3 months to avoid the risk of uncontrolled proliferation of the attenuated strain with high dose immunosuppression. Zostavax (Merck), the herpes zoster vaccine, is not recommended for patients with chronic conditions such as renal failure or end stage liver disease. It has 15 times more plaque forming units of live-virus than the varicella vaccine and therefore could cause disseminated disease in immunosuppressed patients (22, 32). Although two studies have shown no significant adverse effects associated with post transplant administration of a live-virus varicella vaccine in pediatric SOT populations (30, 56) routine post transplant live-virus vaccination is not currently recommended (39).

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Primary Prophylaxis

In the first 3 to 6 months after transplant most patients receive CMV prophylaxis with ganciclovir or valganciclovir, which will also provide protection against VZV reactivation (Table 2) (25). For patients not receiving CMV prophylaxis (or once CMV prophylaxis is discontinued), oral acyclovir or its pro-drug, valacyclovir, used primarily for HSV prophylaxis, will also prevent VZV reactivation in most patients (39). Although transplant recipients are always at greater risk of reactivation due to lifelong immunosuppression, there is no current indication to routinely extend prophylaxis beyond the first 6 months (39).

Secondary Prophylaxis

Exposure to VZV is considered significant with household contact or an indoor non transient face to face contact. If hospitalized, significant exposure includes sharing the same hospital room or face to face contact with an infectious staff member, patient, or visitor (40). Seronegative SOT recipients with such exposures could benefit from immunoglobulin infusions and oral antiviral therapy (39).

Varicella zoster immune globulin (VZIG) was found to be somewhat effective in either preventing infection or lessening the severity of disease in immunosuppressed children with household exposures to varicella (60), but is no longer available. A new varicella zoster immune globulin product, VariZIG (Cangene Corporation, Winnipeg, Canada), is available by expanded access protocol, but its efficacy has not been tested in clinical trials (1). The dose is 125 units/10 kg body weight, with a minimum dose of 125 units (1 vial) and a maximum dose of 625 units (five vials), to be given within 96 hours of exposure ((12, 39). If VariZIG is not administered within this time frame, the Centers for Disease Control and Prevention suggest the use of IVIG (27).

Antiviral therapy has not been well studied for post exposure prophylaxis in immunocompromised patients. Acyclovir has been suggested to be effective as secondary prophylaxis in conjunction with VZV IgG in a small study of high-risk children including five kidney transplant recipients (43). Current recommendations include acyclovir or valacyclovir (for better absorption) for 7 days, beginning 7–10 days after varicella exposure (39). Other regimens suggested by expert opinions include prophylaxis to be given from days 3 to 22 after known exposure or from days 3 to 28 if the patient is given immunoprophylaxis (7, 57).

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Hospitalized patients with varicella, disseminated zoster, and immunocompromised patients with dermatomal zoster should be placed on airborne (negative pressure room) and contact isolation precautions. Patients are to remain in isolation until lesions have crusted, which could be delayed in immunosuppressed individuals (45, 55). Seronegative exposed SOT recipients should receive appropriate secondary prophylaxis and be placed in isolation between days 10 and 21 post exposure, or until day 28 if immunoglobulins are given (39). Household exposure to vaccinated individuals who develop a vaccine associated rash can also potentially transmit varicella (46). Susceptible transplant recipients should be isolated from such contacts to avoid disseminated disease.

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1. A new product (VariZIG) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep 2006;55:209. [PubMed] 

2. Abou Antoun S, Wehbe E, Assi A. Unusual neurologic manifestations of varicella zoster virus infection with the absence of rash in a kidney transplant recipient. Transpl Infect Dis. In Press. [PubMed] 

3. Adour KK. Otological complications of herpes zoster. Ann Neurol 1994;35 Suppl:S62. [PubMed] 

4. Arness T, Pedersen R, Dierkhising R, KremersW, Patel R. Varicella zoster virus-associated disease in adult kidney transplant recipients: Incidence and risk-factor analysis. Transpl Infect Dis 2008;10:260–268. [PubMed] 

5. Austin RB. Progressive outer retinal necrosis syndrome: a comprehensive review of its clinical presentation, relationship to immune system status, and management. Clin Eye Vis Care 2000;12:119-129. [PubMed] 

6. Behrman A, Schmid DS, Crivaro A, Watson B. A cluster of primary varicella cases among healthcare workers with false-positive varicella zoster virus titers. Infect Control Hosp Epidemiol 2003;24(3):202-206. [PubMed] 

7. Boeckh M. Prevention of VZV infection in immunosuppressed patients using antiviral agents. Herpes 2006;13:60–65. [PubMed] 

8. Breuer J, Schmid, DS, Gershon, AA. Use and limitations of varicella-zoster virus-specific serological testing to evaluate breakthrough disease in vaccinees and to screen for susceptibility to varicella. J Infect Dis 2008;197 Suppl 2:S147. [PubMed] 

9. Broyer M, Tete MJ, Guest G, et al. Varicella and zoster in children after kidney transplantation: long-term results of vaccination. Pediatrics 1997;99:35. [PubMed] 

10. Chan EL, Brandt K, Horsman GB. Comparison of Chemicon SimulFluor direct fluorescent antibody staining with cell culture and shell vial direct immunoperoxidase staining for detection of herpes simplex virus and with cytospin direct immunofluorescence staining for detection of varicella-zoster virus. Clin Diagn Lab Immunol 2001;8:909. [PubMed] 

11. Cohen, JI, Straus, SE, Arvin, AM. Varicella-zoster virus. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE, eds. Fields Virology, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2007:2773-2818.[PubMed] 

12. Committee on Infectious Diseases (Kimberlin DW, Bocchini JA Jr, Baltimore RS, Bernstein HH, Bradley JS, Brady MT, Dennehy PH, Fisher MC, Frenck RW Jr, Long SS, McMillan JA, Rubin LG): Prevention of Varicella: Recommendations for Use of Varicella Vaccines in Children, Including a Recommendation for a Routine Two-Dose Varicella Immunization Schedule. Pediatrics 2007;120(1):221-231. [PubMed] 

13. Decline in annual incidence of varicella --- Selected states, 1990--2001. MMWR Morb Mortal Wkly Rep 2003;52:884. [PubMed] 

14. de Jong MD, Weel JF, Schuurman T, Wertheim-van Dillen PM, Boom R. Quantitation of varicella-zoster virus DNA in whole blood, plasma, and serum by PCR and electrochemiluminescence. J Clin Microbiol. 2000;38(7):2568-2573. [PubMed] 

15. de Jong MD, Weel JF, van Oers MH, Boom R, Wertheim-van Dillen PM. Molecular diagnosis of visceral herpes zoster. Lancet. 2001;357(9274):2101-2102. [PubMed] 

16. Espiritu R, Rich M.   Herpes Zoster Encephalitis.  2 Case Reports and Review of Literature. Infect Dis Clin Pract 2007;15:2. [PubMed] 

17. Fehr T, Bossart W, Wahl C, Binswanger U. Disseminated varicella infection in adult renal allograft recipients: Four cases and a review of the literature. Transplantation 2002;73: 608–611. [PubMed] 

18. Garweg J, Bohnke M. Varicella-zoster virus is strongly associated with atypical necrotizing herpetic retinopathies. Clin Infect Dis 1997;24:603. [PubMed] 

19. Geel AL, Landman TS, Kal JA, van Doomum GJ, Weimar W. Varicella zoster virus serostatus before and after kidney transplantation and vaccination of adult kidney transplant candidates. Transplant Proc 2006;38: 3418–3419. [Pued] 

20. Gilden DH, Kleinschmidt-De Masters BK, Laguardia JJ, et al. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med.2000;342:635–645. [PubMed] 

21. Gilden D. Varicella zoster virus and central nervous system syndromes.  Herpes. 2004;11 (suppl 2):89A–94A. [PubMed] 

22. Gilden, DH. Varicella-zoster virus vaccine--grown-ups need it, too. N Engl J Med 2005;352:2344. [PubMed] 

23. Gnann JW Jr, Whitley, RJ. Herpes zoster. N Engl J Med 2002;347:340. [PubMed] 

24. Gourishankar S, McDermid JC, Jhangri GS, Preiksaitis JK. Herpes zoster infection following solid organ transplantation: Incidence, risk factors and outcomes in the current immunosuppressive era. Am J Transplant 2004;4: 108–115. [PubMed] 

25. Humar A. Reactivation of viruses in solid organ transplant patients receiving cytomegalovirus prophylaxis. Transplantation 2006;82:S9–S14. [PubMed] 

26. Hwang EA, Kang MJ, Han SY, Park SB, Kim HC. Viral Infection Following Kidney Transplantation: Long-Term Follow-up in a Single Center. Transplant Proc. 2004 Sep;36(7):2118-2119. [PubMed] 

27. Weinberg JM.  Herpes zoster: Epidemiology, natural history, and common complications. J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S130-S135. [PubMed] 

28. Kalpoe JS, van Dehn CE, Bollemeijer JG, Vaessen N, Claas EC, Barge RM, Willemze R, Kroes AC, Beersma MF. Varicella zoster virus (VZV)-related progressive outer retinal necrosis (PORN) after allogeneic stem cell transplantation. Bone Marrow Transplant 2005;36:467-469. [PubMed] 

29. Kelly PW, Petruccelli BP, Stehr-Green P, et al. The susceptibility of young adult Americans to vaccine-preventable infections: A national serosurvey of US Army recruits. JAMA 1991;266:2724. [PubMed] 

30. Khan S, Erlichman J, Rand EB. Live virus immunization after orthotopic liver transplantation. Pediatr Transplant 2006;10:78– 82. [PubMed] back to top

31. Kimberlin DW, Jacobs RF, Weller S, van der Walt JS, Heitman CK, Man CY, Bradley JS: Pharmacokinetics and safety of extemporaneously compounded valacyclovir oral suspension in pediatric patients from 1 month to 12 years of age. Clin Infect Dis. 2010;50:221-228.  [PubMed]

32. Kimberlin DW, Whitley RJ.  Varicella-zoster virus vaccine for the prevention of herpes zoster. N Engl J Med. 2007;356:1338-1343. [PubMed]

33. Lauzurica R, Bayés B, Frías C, Fontseré N, Hernandez A, Matas L, Jimenez A, Bonet J, Romero R. Disseminated varicella infection in adult renal allograft recipients: role of mycophenolate mofetil. Transplant Proc 2003;35: 1758–1759. [PubMed]

34. Marin M, Güris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56:1. [PubMed]

35. Mortada RA, El Fakih RO, Assi M. Unusual presentation of Ramsay Hunt syndrome in renal transplant patients: case report and literature review. Transpl Infect Dis. 2009 Feb;11(1):72-74. [PubMed]

36. Ormerod LD, Larkin JA, Margo CA, Pavan PR, Menosky MM, Haight DO, Nadler JP, Yangco BG, Friedman SM, Schwartz R, Sinnott JT. Rapidly progressive herpetic retinal necrosis: A blinding disease characteristic of advanced AIDS. Clin Infect Dis 1998;26:34. [PubMed]

37. Oxman, MN. Clinical manifestations of herpes zoster. In: Arvin AM, Gershon AA, eds. Varicella-zoster virus: virology and clinical management. Cambridge, UK: Cambridge University Press, 2000:246-275. [PubMed]

38. Pavan-Langston D. Herpes zoster ophthalmicus. Neurology 1995;45:S50. [PubMed]

39. Pergam SA, Limaye AP, and the AST Infectious Diseases Community of Practice. Varicella Zoster Virus (VZV) in Solid Organ Transplant Recipients. American Journal of Transplantation 2009;9(Suppl 4):S108–S115. [PubMed]

40. Pickering LK, Baker CJ, Kimberlin DW, Long SS (eds). Varicella-Zoster Infections. American Academy of Pediatrics. Red Book: 2009 Report of the Committee on Infectious Diseases, 28th edition, American Academy of Pediatrics (Elk Grove Village, IL) 2009:714-727. [PubMed]

41. Provost PJ, Krah DL, Kuter BJ, Morton DH, Schofield TL, Wasmuth EH, et al. Antibody assays suitable for assessing immune responses to live varicella vaccine. Vaccine 1991;9(2):111-116. [PubMed]

42. Roccatagliata L, Uccelli A, Murialdo A. Guillain–Barré Syndrome after Reactivation of Varicella–Zoster Virus. N Engl J Med 2001;344:65-66. [PubMed]

43. Rodriguez-Moreno A, Sanchez-Fructuoso AI, Calvo N, Ridao N, Conesa J, Marques M, Prats D, Barrientos A. Varicella infection in adult renal allograft recipients: Experience at one center.Transplant Proc 2006; 38: 2416–2418. [PubMed]

44. Safrin S, Berger TG, Gilson I, Wolfe PR, Wofsy CB, Mills J, Biron KK. Foscarnet therapy in five patients with AIDS and acyclovir-resistant varicella-zoster virus infection. Ann Intern Med 1991;115:119. [PubMed]

45. Seigel, JD, Reinhart, E, Jackson, M, Chiarella, L; the Healthcare Infection Control Advisory Committee, 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings, June 2007. http://www.cdc.gove/ncidod/dhqp/pdf/isolation2007.pdf. [PubMed]

46. Seward JF, Zhang JX, Maupin TJ, Mascola L, Jumaan AO. Contagiousness of varicella in vaccinated cases: A household contact study. JAMA 2004;292:704–708. [PubMed]

47. Shapiro BE, Slattery M, Pessin MS. Absence of auricular lesions in Ramsay Hunt syndrome. Neurology 1994;44(4):773-774. [PubMed]

48. Steinberg SP, Gershon AA. Measurement of antibodies to varicella-zoster virus by using a latex agglutination test. J Clin Microbiol 1991;29(7):1527-1529. [PubMed]

49. Stranska R, Schuurman R, de Vos M, van Loon AM. Routine use of a highly automated and internally controlled real-time PCR assay for the diagnosis of herpes simplex and varicella-zoster virus infections. J Clin Virol 2004;30:39. [PubMed]

50. Straus SE, Ostrove JM, Inchauspé G, Felser JM, Freifeld A, Croen KD, Sawyer MH. NIH conference. Varicella-zoster virus infections. Biology, natural history, treatment, and prevention. Ann Intern Med 1988;108:221. [PubMed]

51. Suga S, Yoshikawa T, Ozaki T, Asano Y. Effect of oral acyclovir against primary and secondary viraemia in incubation period of varicella. Arch Dis Child 1993;69:639–642; discussion 642–633. [PubMed]

52. Sulliger JM, Imbach P, Barandun S, Gugler E, Hirt A, Lüthy A, Rossi E, Tönz O, Wagner HP. Varicella and herpes zoster in immunosuppressed children: Preliminary results of treatment with intravenous immunoglobulin. Helv Paediatr Acta 1984;39:63–70. [PubMed]

53. Vales-Albertos LJ, Andrade-Sierra J, Gómez-Navarro B, Monteón-Ramos F, Rodríguez-Pérez M, Torres-Lozano C, Cueto-Manzano AM. Nonspecific immunoglobulin and granulocyte-macrophage colonystimulating factor use in complicated varicella zoster: The first case report in a renal transplant recipient. Transplantation 2006;81:809–810. [PubMed]

54. Webb NJ, Fitzpatrick MM, Hughes DA, Brocklebank TJ, Judd BA, Lewis MA, Postlethwaite RJ, Smith PA, Corbitt G. Immunisation against varicella in end stage and pre-end stage renal failure. Trans-Pennine Paediatric Nephrology Study Group. Arch Dis Child 2000;82:141. [PubMed]

55. Weber DJ, Rutala WA, Hamilton H. Prevention and control of varicella-zoster infections in health care facilities. Infect Control Hosp Epidemiol 1996; 17:694. [PubMed]

56. Weinberg A, Horslen SP, Kaufman SS, Jesser R, Devoll-Zabrocki A, Fleckten BL, Kochanowicz S, Seipel KR, Levin MJ. Safety and immunogenicity of varicella-zoster virus vaccine in pediatric liver and intestine transplant recipients. Am J Transplant 2006;6:565–568. [PubMed]

57. Weinstock DM, Boeckh M, Boulad F, Eagan JA, Fraser VJ, Henderson DK, Perl TM, Yokoe D, Sepkowitz KA. Postexposure prophylaxis against varicella-zoster virus infection among recipients of hematopoietic stem cell transplant: Unresolved issues. Infect Control Hosp Epidemiol 2004;25:603–608. [PubMed]

58. Whitley R. Varicella-Zoster Virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases, 6th ed. Philadelphia, Pennsylvania: Elsevier, 2005:1780-1786. [PubMed]

59. Wreghitt TG, Tedder RS, Nagington J, Ferns RB. Antibody assays for varicella-zoster virus: comparison of competitive enzyme-linked immunosorbent assay (ELISA), competitive radioimmunoassay (RIA), complement fixation, and indirect immunofluorescence assays. J Med Virol 1984;13(4):361-370. [PubMed]

60. Zaia, J. Evaluation of varicella-zoster immune globulin: protection of immunosuppressed children after household exposure to varicella. J Infect Dis 1983;147:737.  [PubMed]

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Table 1. Treatment of Varicella Zoster Virus Infection

Indication Drug and Adult Dose Drug and Pediatric Dose Duration
Primary varicella Acyclovir 10 mg/kg IV Q8h Acyclovir 10 mg/kg IV q8h Antivirals are to be given for at least 7 days or until lesions are custed.
In SOT recipients treatment might need to be prolonged as crusting of lesions is usually delayed or for more invasive disease.


Localized Zoster Acyclovir 800 mg PO 5 times a day

Valacyclovir 1g PO TID

Famciclovir 500 mg PO TID
Acyclovir 20 mg/kg PO 4 times a day
Valacyclovir 20 mg/kg PO TID
Disseminated Zoster Organ invasive disease
Zoster ophthalmicus Ramsey-Hunt Syndrome
Acyclovir 10 mg/kg IV Q8h Acyclovir 10 mg/kg IV Q8h

Table 2. Varicella Zoster Virus Prophylaxis

Indication Drug Adult Dose Duration
Primary prophylaxis Ganciclovir (If CMV prophylaxis indicated) 1 g PO three times a day First 3 months post transplant
Valganciclovir (If CMV prophylaxis indicated) 900 mg PO once a day
Acyclovir 600-1000 mg/day (over 3-5 doses) First 6 months post transplant (if not on CMV prophylaxis)
Valacyclovir 500 mg PO twice a day
Secondary prophylaxis VariZIG 125 units/10 kg IM once (625 units maximum, 125 units minimum) Within 96 hours of exposure
IVIG 400 mg/kg IV once After 96 hours of exposure
Acyclovir 800 mg PO Four times a day For 7 days, starting on day 7-10 post exposure
Valacyclovir 1g PO three times a day

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Bernstein LR. Successful Treatment of Refractory Postherpetic Neuralgia with Topical Gallium Maltolate: Case Report. Pain Med. 2012 Jun 8. [Epub ahead of print]

Simberkoff MS, Arbeit RD, et al. Safety of Herpes Zoster Vaccine in the Shingles Prevention Study: A Randomized Trial. Ann Intern Med. 2010 May 4;152:545-54.

Leung J, et al. Evaluation of Laboratory Methods for Diagnosis of Varicella. Clin Infect Dis. 2010 Jul 1;51:23-32.

Strangfeld A et al. Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Treated with Anti-TNF-Alpha Agents. JAMA. 2009 Feb 18;301(7):737-44.

McDonald, JR, et al. Herpes Zoster Risk Factors in a National Cohort of Veterans with Rheumatoid Arthritis.  Clin Infect Dis 2009;48:1364-1371.

Dworkin RH, Barbano RL, et alA randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster. Pain. 2009 Apr;142:209-17. Epub 2009 Feb 4.

Herpes Zoster: Classic and Unusual Manifestations.  Infections in Medicine 2008;25:506-508.

Ihekwaba UK et al. Clinical Features of Viral Meningitis in Adults: Significant Differences in Cerebrospinal Fluid Findings Among Herpes Simplex Virus, Varicella Zoster Virus, and Enterovirus Infections. Clin Infect Dis. 2008 Sep 15;47(6):783-9.

Nagel MA, et al. The varicella zoster virus vasculopathies. Neurology 2008;70:853-860

Scheinfeld, NS. Skin Disorders in Elderly Persons: Identifying Viral Infections. Infect Med. 2007:479-81



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Klein JO and Hanshaw JB. Thomas H. Weller, 1915-2008: A Remembrance. Clin Infect Dise 2009 April 15; 48:1102-3.


Varicella Zoster Virus in Transplant Recipients