Human Herpesvirus 8 (HHV-8) as an Emerging Pathogen: Relevance to Semen Donation

1. Human Herpesvirus 8 (HHV-8) as an Emerging Pathogen: Relevance to Semen Donation Michael J. Cannon, Ph.D. Centers for Disease Control and Prevention

2. Issues Relevant to Emerging Pathogens and Donation Deferral Policies • Subsets of donors or potential donors with an elevated prevalence of the pathogen • Assays and assay development • Risk of transmission • Disease burden attributable to donation-related transmission

3. Human Herpesvirus 8 (HHV-8) • Discovered in 1994 (Chang et al., 1994) • Enveloped DNA virus • Closest human herpesvirus relative is Epstein-Barr virus • Strong evidence that HHV-8 has a causal role in: • Kaposi’s sarcoma (KS) • Primary effusion lymphomas • Multicentric Castleman’s disease

4. HHV-8 Seroprevalence in Selected Populations vs. Blood Donors/US Population *Data not shown in article

5. Issue 1—Population Subsets at Risk • HHV-8 is more common in HIV-negative MSM than in blood donors/US population. • There are no data on HHV-8 prevalence in MSM who are negative for HIV, HBV, and HCV. • However, many HIV-negative MSM are also negative for pathogens such as HBV and HCV (Tabet et al., 1998; Ndimbie et al., 1995). • Thus, testing for HIV, HBV, and HCV may not eliminate all MSM donors who are positive for HHV-8.

6. HHV-8 Serologic Assays • Latent antigens targeted • Major latent nuclear antigen encoded by open reading frame 73 • Lytic antigens targeted • Virion glycoprotein encoded by open reading frame K8.1 • Capsid protein encoded by open reading frame 65 • Assay formats • Immunofluorescence assays (IFA) (Gao et al., 1996; Lennette et al., 1996; Smith et al., 1997; Whitby et al., 1998) • Enzyme immunoassays (EIA) (Simpson et al.,1996; Chatlynne et al., 1998; Pau et al., 1998) • Immunoblot assays (Zhu et al., 1999) • No FDA-approved assays

7. HHV-8 Seroprevalence in Different Population Groups in the US

8. HHV-8 Seroprevalence in Blood Donors† †Pellett et al., unpublished data

9. Issue 2—Screening Tests • PCR detection of HHV-8 DNA is not a sensitive testing method. • HHV-8 serological assays are: • Adequate for epidemiologic studies • Not sufficiently reliable for individual testing in low prevalence populations • HHV-8 serologic assays need to be improved and FDA approved.

10. HHV-8 Transmission • In the US, having multiple male homosexual partners carries the highest transmission risk. • Some transmission may occur via heterosexual sex and needle sharing. • In Africa, there is evidence that HHV-8 is transmitted via close, non-sexual contact. • Low HHV-8 seroprevalence in healthy persons suggests that transmission via close, non-sexual contact is rare in the US.

11. Relationship between Male Sex Partners and HHV-8 Seroprevalence† †Martin et al., 1998

12. HHV-8 Transmission via Injection Drug Use† †Cannon et al., 2001

13. HHV-8 Transmission via Heterosexual Sex† †Cannon et al., 2001

14. Prevalence of HHV-8 DNA in US Studies

15. Issue 3—Transmission Risk • In the US the highest risk for HHV-8 transmission is through intimate contact with male homosexual sex partners. • However, HHV-8 is not commonly found in semen. • There are no studies measuring risk of HHV-8 transmission via semen donation. • HHV-8 transmission via donated semen is probably rare but the precise risk is unknown.

16. Estimated Annual Risk of Developing KS • 1 in 1,000,000 in healthy persons (Biggar et al.,1984) • 1 in 80 in organ transplant recipients (Penn, 1997) • 1 in 50 in persons with HIV (Jones et al., 1999) • 1 in 20 in persons seropositive for both HIV and HHV-8 (Martin et al., 1998; Rezza et al., 1998; Jacobson et al., 2000).

17. Issue 4—HHV-8 Disease Burden • HHV-8 is uncommon in semen. • Even if a person becomes infected with HHV-8, additional factors (usually immunosuppression) are required for disease to occur. • Thus, the burden of disease associated with semen-donation acquired HHV-8 is probably very low. • However, the precise burden is unknown.

18. HHV-8 Dichotomies • HHV-8 is more common in HIV-negative MSM than in others. • However, HIV-negative MSM donors could not be screened for HHV-8 because there is no FDA-approved test. • HHV-8 is transmitted through intimate contact between male homosexual sex partners. • However, HHV-8 is rarely detected in semen. • The risk of disease caused by semen donation-acquired HHV-8 is probably very low. • However, the precise risk is unknown, and with blood donation, considerable dollars and effort are spent to lower the already low risks due to HIV, HCV, etc.

19. Conclusions • HHV-8 is an example of an emerging pathogen that can be found in persons negative for HIV, HBV, and HCV. • Screening tests for emerging pathogens need to be developed and approved. • Precise risk of transmission needs to be estimated. • Disease burden attributable to the practice in question needs to be estimated. If steps 2-4 are in place, a scale will exist upon which we can weigh the risks and benefits of different courses of action.

20. References • Chang et al., Science 1994, 266:1865-9 • Simpson et al., Lancet 1996, 348:1133-8 • Lennette et al., Lancet 1996, 348:858-61 • Blackbourn et al., J Infect Dis 1997, 179:237-9 • Martin et al., N Engl J Med 1998, 338:948-54 • Cannon et al., N Engl J Med 2001, 344:637-643 • Tabet et al., AIDS 1998, 12:2041-8 • Ndimbie et al., Clin Diagn Lab Immunol 1995, 2:219-24 • Gao et al., Nat Med 1996, 2:925-8 • Smith et al., J Infect Dis 1997, 176:84-93 • Whitby et al., J Natl Cancer Inst 1998, 90:395-7

21. References (2) • Chatlynne et al., Blood 1998, 92:53-58 • Pau et al., J Clin Microbiol 1998, 36:1574-1577 • Zhu et al., Virology 1999, 256:381-92 • Pellett et al., J Clin Microbiol 1999, 37:1298-1301 • Pauk et al., N Engl J Med 2000, 343:1369-77 • Biggar et al., J Natl Cancer Inst 1984, 73:89-94 • Penn, Transplantation 1997, 64:669-73 • Jones et al., MMWR CDC Surveill Summ 1999, 48(SS-2):1-22 • Rezza et al., Int J Cancer 1998, 77:361-5 • Jacobson et al., J Infect Dis 2000, 181, 1940-9