APPENDIX 2 Herpes Viruses (Other Than CMV, EBV, Common Human Exposure Routes: and HHV-8) • Contact with infected human secretions (saliva, semen) most common; aerosols also possible Disease Agent: Likelihood of Secondary Transmission: • Herpes simplex viruses 1 and 2 (HSV-1,2) • Varicella-zoster virus (VZV) • Moderate • Human herpesviruses-6,7 (HHV-6,7) At-Risk Populations: Disease Agent Characteristics: • All populations at risk for infection for most of these • Family: Herpesviridae; Subfamilies: Alphaherpesviri- agents nae (HSV-1,2; VZV), betaherpesvirinae (HHV-6,7); • Typically greater risk of disease in immunocompro- Genus: Simplexvirus (HSV-1,2); Varicellovirus (VZV); mised hosts or following bone marrow or solid organ Roseolovirus (HHV-6,7) transplantation • Virion morphology and size: Enveloped; icosadelta- hedral nucleocapsid symmetry, spherical to pleomor- Vector and Reservoir Involved: phic particles, 160-200 nm in diameter. Between the • Infected humans capsid and the envelope is an amorphous layer of proteins termed the tegument. Blood Phase: • Nucleic acid: Linear, double-stranded DNA about • HSV and VZV viremia in symptomatic neonates, and 125-170 kbp in length immuncompromised hosts is well described. • Physicochemical properties: Nonionic detergents • Viremia in immunocompetent hosts occurs with both solubilize the envelope; virus stable when frozen, primary and recurrent HSV and VZV infection, but for especially at -80°C or below; virus inactivated by UV short intervals and at relatively low levels light, gamma-irradiation, standard disinfectants, and • HHV-6,7 circulates as latent virus in lymphocytes over heating. Herpes viruses do not, in general, survive for the long-term (lifelong) and can reactivate later in life long periods outside the host. and in association with immunosuppression. • Herpesviridae cause primary infection followed by lifelong latency with the opportunity for reactivation Survival/Persistence in Blood Products: of productive infection. ᭺ HSV-1,2 and varicella are latent in nerve cells. • Unknown ᭺ HHV-6,7 are latent in lymphocytes. Transmission by Blood Transfusion: Disease Name: • While the lymphocyte association of HHV-6,7 sug- • Multiple, including oropharyngeal and genital herpes gests the possibility of transfusion transmission, well- (HSV-1,2); varicella (chickenpox), herpes zoster, or documented case reports or series are not available. shingles (VZV); and exanthem subitum or roseola • Case reports of HHV-6 transmission by peripheral infantum (HHV-6,7) blood stem cells have used molecular methods to detect integrated donor HHV-6 DNA in the chromo- Priority Level somes of engrafted donor cells. This appears to be • Scientific/Epidemiologic evidence regarding blood transmission of latent infection rather than of active safety: Theoretical infection. Furthermore, transplant recipients may • Public perception and/or regulatory concern regard- reactivate preexisting HHV-6 infection, thereby con- ing blood safety: Absent founding the evaluation of potential transfusion • Public concern regarding disease agent: Absent transmission. • Although viremia occurs during both primary and Background: reactivation infections with HSV and VZV, transmis- • Primary infections are followed by lifelong latency of sion by blood has never been reported for HSV-1, this family of viruses, which raises the issue of reacti- HSV-2, and VZV. vation syndromes in both healthy and immuno- Cases/Frequency in Population: compromised hosts. • Rates of infection are stable in US population, except • HSV: 50-80% adults seropositive for a marked decrease in the incidence of primary • VZV: Up to 95% seropositive VZV infection with introduction of universal • HHV-6: >90% seropositive immunization. • HHV-7: 70-90% seropositive 96S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 Incubation Period: any of these viruses in the immune compromised host can cause severe disease. • HSV-1,2: 2-12 days • VZV: 10-21 days Mortality: • HHV-6,7: 5-15 days • Rare, except in immunocompromised patients Likelihood of Clinical Disease: Chronic Carriage: • HSV: Mucocutaneous disease (orolabial and genital • Yes; lifetime latency is typical. herpes) common. Severe disease is rare in immuno- competent hosts, but, if it occurs, it can be deadly Treatment Available/Efficacious: (e.g., severe encephalitis). • VZV: Varicella (chickenpox) was previously very • There are a variety of nucleoside analog drugs used to common (about 4 million cases/year in the US before treat herpes virus infections, including acyclogua- recommendations for universal vaccination), but nosine (acyclovir), famciclovir, valacyclovir, ganciclo- rates have fallen 75-85% and continue to decline; vir and valgancylovir, cidofovir, and foscarnet. All of herpes zoster due to reactivation of latent virus con- these drugs suffer from the selection of resistant tinues to increase after age 60 years with lifetime risk herpes mutants. As with HSV, acyclovir (or other ~50% among persons who survive to 85 years (1.7 nucleoside analogs) can be useful, particularly in pre- cases/1000 population in the US) venting VZV disease, and varicella immunoglobulin • HHV-6,7: High in children; prevalent in febrile chil- also can be used. Unlike herpes simplex virus and dren if sought VZV, there are no drugs proven effective for HHV-6 or 7, although there is uncontrolled evidence suggesting Primary Disease Symptoms: that several of the above drugs have promise for • HSV-1 and -2 HHV-6 infections. ᭺ Gingivostomatitis and orolabial ulcers (cold Agent-Specific Screening Question(s): sores) primarily from HSV-1 ᭺ Genital herpes primarily with HSV-2 • No specific question is in use. ᭺ Aseptic meningitis (sometimes recurrent) • Not indicated because transfusion transmission has ᭺ Encephalitis and disseminated infections seen in not been definitively demonstrated neonates and immunocompromised hosts • No sensitive or specific question is feasible. Most • VZV infections are aquired during childhood, and the pre- ᭺ Disseminated rash (chickenpox or varicella) and velance of latent infections is so high as to make ques- dermatomal rash (zoster) tions impractical. ᭺ Widespread visceral dissemination in immuno- compromised hosts Laboratory Test(s) Available: • HHV-6,7 • No FDA-licensed blood donor screening test exists. ᭺ Exanthem subitum (or roseola infantum) is a very common self-limited, benign childhood • Serology, NAT, and cultivation of viruses rash. Nonspecific febrile illness is also frequently Currently Recommended Donor Deferral Period: observed. ᭺ Reactivation of latent HHV-6,7 in immuncom- • No FDA Guidance or AABB Standard exists. promised hosts can result in disseminated infec- • Persons with symptomatic primary genital or orola- tion of multiple organs and is assocatiated with bial HSV may not feel well on the day of donation and poor clinical outcomes, especially in recipients of would often be deferred. hematopoetic transplantation. • Deferral practices for recurrent HSV infection, if reported by the donor, vary by collection facility. Severity of Clinical Disease: • Prudent practice would be to defer prospective donors with primary (chickenpox) or recurrent • Primary infections in well hosts are generally self- (shingles/zoster) varicella until signs and symptoms limited with full recovery. Reactivation of latent infec- are gone. tions with HSV-1 and 2 causes self-limited illness. Reactivation of VZV as shingles generally heals with Impact on Blood Availability: few sequelae but can cause relatively severe disability because of postherpetic neuralgia. HHV-6,7 infec- • Agent-specific screening question(s): Not applicable tions in children are usually benign. Reactivation of • Laboratory test(s) available: Not applicable Volume 49, August 2009 Supplement TRANSFUSION 97S APPENDIX 2 Impact on Blood Safety: 4. Hambleton S. Chickenpox. Curr Opin Infect Dis 2005; 18:235-40. • Agent-specific screening question(s): Not applicable 5. Harel L, Smetana Z, Prais D, Book M, Alkin M, Supaev • Laboratory test(s) available: Not applicable E, Mendelson E, Amir J. Presence of viremia in patients with primary herpetic gingivostomatitis. Clin Leukoreduction Efficacy: Infect Dis 2004;39:636-40. 6. Hellstrom B, Vahlquist B. Experimental inoculation of • Viruses that have a blood phase (HHV-6,7) are typi- roseola infantum. Acta Paediatr 1951;40:189-97. cally present within WBCs; therefore, leukoreduction 7. Kempe C. Show EB, Jackson JR, Silver HK. Studies on is likely to be effective by analogy to human cytome- the etiology of exanthema subitum (roseola infan- galovirus. However, cell-free virus also has been tum). J Pediatr 1950;37:561-8. detected in cases of primary infection in children. 8. Mainka C, Fuss B, Geiger H, Höfelmayr H, Wolff MH. Pathogen Reduction Efficacy for Plasma Derivatives: Characterization of viremia at different stages of varicella-zoster virus infection. J Med Virol, 1998;56: • These viruses are primarily WBC associated, but 91-8. plasma viremia may be present. Because these 9. Naraqui S, Jackson GG, Jonasson OM. Viremia with viruses are lipid enveloped and relatively labile, any herpes simplex type 1 in adults. Four non-fatal cases, free virus in plasma should be sensitive to the many one with features of chickenpox. Ann Int Med. 1976; measures used in the fractionation process. 85:165-9. 10. Pellett PE, Roizman B. The family Herpesviridae:a Other Prevention Measures: brief introduction. In: Knipe DM, Howley PM, editors. Fields virology, 5th ed. Philadelphia: Lippincott • None Williams