Correspondence
Mucosal Shedding of Human Herpesvirus 8
N Engl J Med 2001; 344:690-692March 1, 2001
- Article
To the Editor:
Transmission of human herpesvirus 8 (HHV-8) remains puzzling, despite the additional insights provided by Pauk et al. (Nov. 9 issue).1 Whereas sexual transmission may occur, we endorse the authors' reasoning that oral transmission may be a more common route, although with a 15 percent frequency of salivary shedding, transmission must be somewhat difficult, since open-mouthed kissing between homosexual men is common. Open-mouthed kissing also is common in the heterosexual community, but the prevalence of HHV-8 in the general population is only 1 to 2 percent in the United States.2,3 Why?
Transmission is probably related not only to the presence of HHV-8 but also to the amount of infectious virus shed. HHV-8 levels could be low in HHV-8–infected persons who are not infected with the human immunodeficiency virus (HIV) and who are immunocompetent. This group would include most heterosexual persons. In the current report, the frequency of shedding in HIV-seropositive homosexual men appeared to be similar to that in HIV-seronegative homosexual men, but the study did not provide data about HHV-8 viral levels in these groups.
A simple rendering of the data in Figure 1 of the article to display viral levels in various body fluids according to HIV status would be of interest. Is HHV-8 prevalence among homosexual men higher because HIV-related immunosuppression has increased the amount of HHV-8 shed and thereby increased its transmission within this community? Such a finding might explain reports4,5 that the prevalence of HHV-8 in the homosexual community has increased in parallel with the rising AIDS epidemic.
5 ReferencesRobert J. Biggar, M.D.
James J. Goedert, M.D.
National Cancer Institute, Bethesda, MD 208521
Pauk J ,Huang ML ,Brodie SJ , et al. Mucosal shedding of human herpesvirus 8 in men. N Engl J Med 2000;343:1369-1377
Full Text | Web of Science | Medline2
Kedes DH ,Operskalski E ,Busch M ,Kohn R ,Flood J ,Ganem D . The seroepidemiology of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission. Nat Med 1996;2:918-924
CrossRef | Web of Science | Medline3
Gao SJ ,Kingsley L ,Li M , et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 1996;2:925-928
CrossRef | Web of Science | Medline4
Melbye M ,Cook PM ,Hjalgrim H , et al. Risk factors for Kaposi's-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1981-1996. Int J Cancer 1998;77:543-548
CrossRef | Web of Science | Medline5
O'Brien TR ,Kedes D ,Gamen D , et al. Evidence for concurrent epidemics of human herpesvirus 8 and human immunodeficiency virus type 1 in US homosexual men: rates, risk factors, and relationship to Kaposi's sarcoma. J Infect Dis 1999;180:1010-1017
CrossRef | Web of Science | Medline
To the Editor:
The frequent detection of HHV-8 in the oropharyngeal samples and saliva of men who have sex with men, as reported by Pauk and colleagues, is an important contribution. However, their study of risk factors has limited value because of its cross-sectional design, which may yield spurious associations.1 The time of infection among their subjects is not known; infection may even have occurred during a period other than that in which sexual practices were investigated. Thus, although deep kissing with HIV-positive partners may appear to be a major risk factor for HHV-8 infection, it may well confound (or be confounded by) many other sex practices or simply the number of HIV-positive sex partners. Even in a study with a prospective design in which the time of infection is known, it is difficult to disentangle the relative contributions of various practices, as the authors noted. With such closely related factors, careful modeling in a prospective setting is required, but this requirement was not met in the study by Pauk et al. Furthermore, the authors give the reader no information about what sexual practices were evaluated and over what period.
Although Pauk et al. clearly demonstrate the presence of HHV-8 in oropharyngeal samples and saliva, the epidemiologic aspect of their study is difficult to interpret and is insufficient to identify deep kissing as the principal mode of HHV-8 transmission. Other modes, such as orogenital sex, may well have an important role.1
1 ReferencesNicole H.T.M. Dukers, M.Sc.
Ronald B. Geskus, Ph.D.
Roel A. Coutinho, M.D., Ph.D.
Municipal Health Service Amsterdam, 1000 CE Amsterdam, the Netherlands1
Dukers NH ,Renwick N ,Prins M , et al. Risk factors for human herpesvirus 8 seropositivity and seroconversion in a cohort of homosexual men. Am J Epidemiol 2000;151:213-224
Web of Science | Medline
To the Editor:
Our studies in a different epidemiologic setting support the conclusions of Pauk et al. about HHV-8 infection. Of 788 patients seen from 1998 through 2000 at our unit for sexually transmitted diseases, 394 consecutive patients (320 of whom were prostitutes) underwent serologic testing for HHV-8. Anti–HHV-8 antibodies were found in 56 (53 from sub-Saharan Africa) of the 320 prostitutes and in 8 (6 from sub-Saharan Africa) of the 74 other patients (Table 1Table 1
Human Herpesvirus 8 (HHV-8) Serologic Status among Prostitutes and Other Patients, According to Their Geographic Origin.). Mantel–Haenszel analysis, with adjustment for geographic origin, and multivariate analysis disclosed no association between prostitution or other indicators of sexual activity and HHV-8 infection, whereas being born in sub-Saharan Africa carried a relative risk of HHV-8 infection of 7.90 (95 percent confidence interval, 3.24 to 19.25; P<0.001).Molecular analysis with the polymerase chain reaction in both salivary and cervical specimens from 34 HHV-8–infected women led to the detection of HHV-8 viral DNA in 32.2 percent of the salivary samples and in none of the cervical specimens.
Our findings from areas where HHV-8 infection is endemic support those of Pauk et al. and further confirm the minor role of sexual contact in HHV-8 transmission. The role of deep kissing cannot be easily extrapolated from that of sexual intercourse; however, the most likely route of HHV-8 spread can be ascertained more clearly when infection with HHV-8 in a population consisting largely of prostitutes is associated only with birth in areas where the infection is highly endemic.1 In such areas, HHV-8 infection is thought to be acquired during infancy, probably through mechanisms similar to those responsible for transmission of the Epstein–Barr virus.2
2 ReferencesAnna Lucchini, M.D.
Ivan Dal Conte, M.D.
Giovanni Di Perri, M.D., D.T.M.&H., Ph.D.
University of Turin, 10149 Turin, Italy1
Olsen SJ ,Chang Y ,Moore PS ,Biggar RJ ,Melbye M . Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985. AIDS 1998;12:1921-1925
CrossRef | Web of Science | Medline2
Sixbey JW ,Nedrud JG ,Raab-Traub N ,Hanes RA ,Pagano JS . Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med 1984;310:1225-1230
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Biggar and Goedert request additional data on the amounts of HHV-8 DNA detected. In our cross-sectional cohort, herpes simplex virus was present in the oral swabs of 5 of 11 HIV-seropositive men and 3 of 16 HIV-seronegative men. The mean amount of HHV-8 DNA present in these samples was 103.1 and 103.8, respectively. Among the participants from whom swabs of the oral mucosa were obtained daily, herpes simplex virus was present in the samples from 9 of 14 HIV-seropositive and 4 of 9 HIV-seronegative men. The mean amount of HHV-8 DNA detected was 104.0 and 103.6, respectively, on the days that HHV-8 was detected (P=0.003 by the Mann–Whitney test). We did not see a correlation between the amount of HHV-8 and the CD4 count; however, the number of people studied was small. There were too few genitourinary samples containing HHV-8 DNA to allow meaningful comparisons.
We agree with Dukers and colleagues that, as stated in our report, deep kissing is a potential but not proven mode of transmission. We hope that our findings will lead to prospective studies designed to obtain data about oral contact as a risk factor for HHV-8 acquisition. In our study, sexual practices that were not related to HHV-8 seropositivity among HIV-seronegative men who had sex with men were the consistent use of condoms, unprotected receptive and insertive anal sex, receptive and insertive oral–anal “rimming,” and receptive and insertive orogenital sex. Because of space constraints, we presented only the final multivariate models in the article. Moreover, our study was designed to evaluate sites of shedding and to estimate shedding rates and patterns; the epidemiologic data reinforce the data on mucosal shedding.
We are gratified to see the data from Italy on the high detection rate of HHV-8 in the saliva of HHV-8–seropositive women. It would be of interest to compare the frequency of detection in HIV-seropositive women with that in HIV-seronegative women. The key goal now is to identify the factors critical to the increased transmission and acquisition of this herpesvirus.
Lawrence Corey, M.D.
John Pauk, M.D.
Anna Wald, M.D.
University of Washington, Seattle, WA 98195- Citing Articles (1)
Citing Articles
1
Marcelo G. Horenstein, Nancy J. Moontasri, Ethel Cesarman. (2008) The pathobiology of Kaposi’s sarcoma: advances since the onset of the AIDS epidemic. Journal of Cutaneous Pathology 35, 40-44
CrossRef
