Herpes Simplex Virus (HSV)-1 and -2, and Varicella Zoster Virus (VZV)

Abstract

American Journal of TransplantationVolume 4, Issue s10 p. 69-71 Free Access Herpes Simplex Virus (HSV)-1 and -2, and Varicella Zoster Virus (VZV) First published: 21 July 2008 https://doi.org/10.1111/j.1600-6135.2004.t01-2-00697.xCitations: 3AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Epidemiology HSV-1, HSV-2 and VZV belong to the α-herpesvirus family. Seroprevalence rates for HSV vary among different populations, but in the United States is about 62% for HSV-1 and 22% for HSV-2 (1). Seroprevalence rates are lower in children (2). The majority of HSV infections in adult transplant recipients are due to reactivation of endogenous latent virus, although primary infection transmitted from the allograft has been described (3). Seronegative patients, such as children, may also acquire HSV from shedding from close contacts. The most common presentations of HSV are orolabial disease and genital or perianal disease (4). Invasive or disseminated disease may occur and includes esophagitis, hepatitis and pneumonitis (4-6). The latter complication is seen most commonly in lung or heart/lung transplant recipients (5). In the absence of prophylaxis, most cases of HSV disease occur early in the post-transplant period, usually within the first month (1). The incidence of disease due to HSV in patients not receiving prophylaxis ranges from 24% to 34% (4, 7, 8). The seroprevalence of VZV also varies among different populations, but is over 90% in adults in the United States (1). Seroprevalence rates are lower in pediatric transplant recipients. In adults, disease following transplant is usually due to reactivation of latent virus. Infection transmitted with the allograft has been reported but is rare (9). The frequency of herpes zoster is about 2–10% in adult renal and liver transplant patients and 20% for cardiac transplant (1, 4). Zoster may be dermatomal in distribution or generalized, and tends to occur later than HSV infection, with many cases occurring greater than 3 months after transplant (4). Visceral complications including pneumonitis, hepatitis and encephalitis may occur. Primary VZV infection may occur in seronegative patients and is therefore more common in children. Primary chickenpox may be quite severe with higher rates of visceral involvement, more severe skin disease and high morbidity and mortality (10-12). In a retrospective study of pediatric kidney recipients, 19 of 160 (12%) renal transplant recipients developed varicella infection post-transplant of whom 50% had severe disease and one patient died (10). Severe varicella has also been reported in pediatric orthotopic liver transplant recipients. In one review of 67 pediatric liver transplants recipients, varicella developed in 14 patients (21%), two of whom died from varicella-related complications (11). Risk factors Pre-transplant serostatus helps define the risk of infection after transplant. Patients who are seropositive for HSV or VZV prior to transplant are at risk of reactivation post-transplant. Patients who are seronegative for HSV may acquire HSV from shedding from close contacts. Patients who are seronegative for VZV pre-transplant are at risk of primary infection due to exposures in the community. This occurs most commonly in pediatric transplant recipients. Intensity of immunosuppression including use of OKT3 is a risk factor for viral reactivation (4). Newer more potent immunosuppressive agents such as MMF may also increase the risk of reactivation or dissemination (13). Diagnosis Clinical diagnosis is often adequate for typical lesions of HSV or VZV. However, atypical presentations or visceral involvement require laboratory confirmation. Viral culture or DFA assays of lesion scrapings or tissue specimens are commonly used methods (1). Use of nucleic acid detection methods is a promising technique for detecting VZV or HSV DNA in tissue or fluids (1). Serologic testing is generally not useful for diagnosing acute infections. Prevention The use of oral acyclovir has been shown to prevent disease due to HSV and VZV (IB) (14, 15). Disease may occur after discontinuation of the drug. Presumably famciclovir and valacyclovir should be equally effective (BIII). Regimens used for prevention of CMV including oral ganciclovir and high-dose valacyclovir are effective for preventing HSV (IB) and likely also for VZV infections (7, 8). In transplant recipients who are seronegative for VZV, varicella vaccination (live attenuated VZVOKA) should be given pre-transplant to prevent post-transplant primary varicella infection (BII). Since it is a live virus vaccine, a minimal interval of 4–6 weeks from vaccination to transplantation is preferred if possible. Although low response rates may be seen in some patients with end-stage organ failure, clinical benefit may still be gained (16, 17). In a retrospective review of 212 seronegative pediatric renal transplant recipients who received pre-transplant VZV vaccine, the proportion of children with varicella after transplantation was lower among the vaccinated children than among the 49 unimmunized seronegative children (12% vs. 45%) post-transplant (16). Also disease in the vaccinated group was mild while three deaths occurred in the unimmunized group. More recent data suggest that seroconversion rates in patients with organ failure can be improved with two doses of varicella vaccine (18). Since the currently available varicella vaccine is a live viral vaccine, it is not routinely recommended in patients who are immunosuppressed after transplantation. Vaccination of susceptible family members is another method of protecting the high-risk transplant recipient (risk of natural disease may outweigh the low-risk of vaccine related disease acquired from family members). Recently, an investigational heat inactivated vaccine has shown a reduction in zoster infection when given to hematopoietic-cell transplant recipients but has not been tested in solid organ transplant recipients (19). Patients seronegative for VZV with a defined exposure, should receive post-exposure prophylaxis with VZIG (AII) or with oral antiviral agents (CIII) (20). In this setting, it should be noted that post-exposure prophylaxis with VZIG alone may be not be completely protective (21). Also, VZIG prophylaxis must generally be given within 96 h of the exposure (22). Post-exposure prophylaxis with oral antiviral agents (e.g. acyclovir) should be used in patients in whom this window has passed. Treatment Serious disease due to HSV or VZV should be treated with intravenous acyclovir (AII) (23, 24). More limited disease such as orolabial HSV or dermatomal zoster can be treated with oral acyclovir, oral famciclovir (BI) and presumably oral valacyclovir (25). Acyclovir resistance remains relatively uncommon in solid organ transplant recipients and may respond to foscarnet (BIII). Research issues Several potential research issues exist. These include a further elucidation of the effect of newer, more potent immunosuppression on the natural history of these viruses and the optimal timing and dosing schedule of varicella vaccination in seronegative recipients. In addition, varicella vaccination in seropositive patients to boost immune responses prior to transplant, and the use of new varicella vaccines such as the heat inactivated vaccine require further study. References 1 Gnann JW Jr . Herpes simplex and varicella zoster virus infection after hemopoietic stem cell or solid organ transplantation . In : RA Bowden , P Ljungman , CV Paya , eds . Transplant Infections , 2nd Edn . Philadelphia : Lippincott, Williams & Wilkins , 2003 : 350 – 366 . Google Scholar 2 Xu F , Schillinger JA , Sternberg MR et al. . Seroprevalence and coinfection with herpes simplex virus type 1 and type 2 in the United States, 1988–94 . J Infect Dis 2002 ; 185 : 1019 – 1024 . 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DOI: 10.1081/CNV-100000070 CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume4, Issues10October 2004Pages 69-71 AST and ASTS members - please log in via your Society website for full journal access.AST Members >> ASTS Members >> ReferencesRelatedInformation