Seroprevalence of HHV-6 and HHV-8 among blood donors in Greece
- Marianna Politou1,
- Dimitrios Koutras2,
- Georgios Kaparos2,
- Serena Valsami1,
- Theodoros Pittaras1,
- Emmanouil Logothetis2,
- George Panayiotakopoulos3Email author and
- Evangelia Kouskouni2
© Politou et al.; licensee BioMed Central Ltd. 2014
Received: 20 June 2014
Accepted: 18 August 2014
Published: 27 August 2014
Herpes viruses infection transmitted through healthy but infected blood donors pose a danger to herpes-naive immunocompromised recipients. The risk of transfusion-related HHV-8 transmission is different in endemic and not endemic areas. HHV-6 and HHV-8 seroprevalence and viral load among blood donors have been reported from different countries. The aim of our study was to assess the seroprevalence of HHV-8 and HHV-6 in volunteer blood donors from Greece which is unknown.
Serum samples from 179 healthy blood donors were tested for the presence of IgG antibodies against HHV-6 and HHV-8 with ELISA. None of the 179 donors of Greek origin tested was positive for HHV-8. HHV-6 seropositivity was assessed in 160 blood donors’ samples and was found to be 78.75% (126/160). The HHV-6 seroprevalence did not differ either between males and females or among different decade age groups.
The fact, that no blood donor was positive for HHV-8 IgG antibodies indicates that the risk for transfusion related HHV-8 transmission in Greece, if any, is negligible and does not warrant broad testing for HHV-8. Definitely further studies are needed, in order to clarify the potential risk of HHV-6 transmission.
KeywordsHHV-6 seroprevalence HHV-8 seroprevalence Blood donors Greece
Herpes viruses 6 and 8 (HHV-6 and HHV-8) are enveloped ds-DNA viruses that can remain latent in the host cells for a long time. They can re-enter a lytic cycle and thus cause reactivation of the viral infection. Herpes viruses i transmitted from healthy but infected blood donors pose the danger of primary infection to herpes-naive immunocompromised recipients. HHV-8 seroprevalence has been assessed in several countries and it is found that the risk of transfusion-related HHV-8 transmission is different in endemic and not endemic areas . I HHV-6 seroprevalence among blood donors has also been reported from different countries . The aim of the present study was to assess the prevalence of anti- HHV-8 and anti-HHV-6 antibodies in volunteer blood donors in Greece, which is unknown.
Materials and methods
We analyzed 179 blood donor samples collected from January 2012 to May 2012 in the Blood Bank of Aretaieion University Hospital, in Athens. All donors completed the blood donor screening questionnaire and were eligible for blood donation. Serum samples were stored at -20°C prior to being tested. The study was approved by the Scientific and Ethics Committee of our Hospital, and informed consent was obtained from all participants.
All donors underwent the routine Blood Bank screening that includes HBsAg testing, antibodies against HIV 1/2, HCV and HTLV1/2, VDRL (Venereal Disease Research Laboratory) test, along with Nucleic Acid Testing (NAT) for HBV, HCV, and HIV. We analyzed the data only from blood donors, who tested negative for the full above screening.
The anti-HHV-8 and anti-HHV-6 lytic IgG antibodies were analysed in serum samples using commercially available ELISA kits (Advanced Biotechnologies Inc HHV-8 IgG., Columbia, MD, USA and PANBIO HHV-6 IgG Inverness Medical Innovations Australia), according to the manufacturer’s instructions.
All statistical analysis was performed using SPSS v.22.0 (IBM Corp, Armonk, NY, USA) P values were considered as significant when P < 0.05.
The study group comprised of 179 volunteers blood donors, 136 males and 43 females with a mean age of 38 years (range 19–64 years). All tested negative for HBV, HCV, HIV1/2, HTLV1/2 and VDRL.
None of the 179 donors of Greek origin tested was positive for HHV-8. There was only one additional sample which tested positive for anti-HHV-8 antibodies from one Greek male donor, who tested positive for HIV (both with Elisa and NAT) and thus was excluded from the study.
HHV-6 seroprevalence (sex and age distribution)*
Age groups (years)
A: 19-30 N = 46
B: 31-40 N = 44
C: 41-50 N = 43
D: 51-64 N = 27
p = 0.657
p = 0.526
p = 0.668
p = 0.126
P = 0.802
Epidemiological data for HHV-6 and HHV-8 in blood donor in Greece is poor. HHV-8 is the etiological agent for Kaposi sarcoma, Castelmann’ disease and primaty effusion lymphoma. Kaposi Sarcoma unrelated to HIV infection is more common in countries of Mediterranean “basin” such as Greece and Italy than in Northern Europe and the USA .
The seroprevalence of HHV-8 in blood donors in Southern Europe ranges from 4.5% (9/200) in Spain Basque country to 20% and 25% in Sicily and Sardinia respectively. Interestingly, a seroprevalence of 2.4% was reported recently in Eastern Sicily . However, the seroprevelance in blood donors in the U.K. (2.7%) and the United States (1.4%) is significantly lower [5, 6].
Since HHV-8 modes of transmission are elusive and the HHV-8 transmission through blood transfusion differs in endemic and non endemic areas, assessing HHV-8 seroprevalence among blood donors in Greece would help us identify the putative danger of transfusion related HHV-8 transmission in Greece. We have also previously found that 48% of the HIV-1-positive and 56% of the HEPS subjects in Greece tested positive for anti-HHV-8 antibodies, a prevalence which is higher than that reported in other countries of Western Europe . All the above mentioned data triggered the study of the seroprevalence of HHV-8 in healthy blood donors in Greece. It has been previously reported that the prevalence of HHV-8 in the general population in Greece is 7.6% and that the seropositivity for HHV-8 was associated with a history of endoscopic procedures and HBsAg positivity . Nevertheless, we found no blood donor tested positive for HHV-8 IgG antibodies. We have used an ELISA with similar sensitivity detecting HHV-8 IgG antibodies  with the previous study and thus the discrepancy between the two studies could be attributed either to the relatively small size of our study or the differences between the general population and the blood donors population. We cannot overlook the fact that with the help of the donor screening questionnaire we practically exclude candidate donors with risk factors for HHV-8 transmission. Endoscopic procedures in the 6 months preceding blood donation, HBsAg seropositivity, and high-risk sexual behaviour are exclusion criteria for a blood donor.
In terms of HHV-6, the seroprevalence of HHV-6 in blood donors in Greece is unknown. Existing literature deals only with the detection of HHV-6 in the sera or tissue from patients with certain disease entities [10–14]. We detected HHV-6 IgG antibodies in 78.75% of blood donors, a seroprevalence similar to the one reported from other countries. Furthermore, the distribution between sexes and among age groups confirms the fact that infection with HHV-6 occurs early in life and that the IgG antibodies persist for a long time.
Blood transfusion–related transmission of herpesviruses from chronically infected donors to previously uninfected or immunocompromised recipients has been a subject of investigation for several years. The possibility of transfusion-related transmission of herpesviruses from healthy adult blood donors is moderately high for HHV-6, while it seems to be very low for HHV-8 .
A number of studies have shown that even in blood donors, who tested positive for HHV-8, HHV-8 DNA was rarely detected. Moreover, it has been suggested that leukoreduction could efficiently remove HHV-8 from blood donations, although some authors argue that this is true only in terms of the viral cellular counterpart. Cell-free HHV-8 was still present in a ranging percentage in 42% of subjects after filtration, as 1% to 20% of the total virus was not removed . Furthermore, it seems that transfusion with fresh blood from HHV-8 positive blood donors can be associated with an increased risk of death . But the fact, that no blood donor was positive for anti-HHV-8 IgG antibodies indicates that the risk for HHV-8 transmission with transfusion in Greece, if any, is negligible and does not warrant broad testing for HHV-8.
Regarding HHV-6 transmission with transfusion, the natural course of transfused WBCs carrying latent integrated HHV-6 in a immunocompetent recipient is the elimination of infected donor cells. However, in immunodeficient patients, especially those who receive stem cell transplants, there is an existing possibility that the integrated virus in the transplanted hematopoietic cells can be reactivated and lead to acute infection .
Although HHV-6 seropositivity reported from several studies is high, HHV-6 DNA is detected only in a small proportion of seropositive subjects. The possibility of HHV-6 transmission from a healthy blood donor with high HHV-6 viral load to an immunocompromised recipient cannot be excluded but it does not warrant broad testing for HHV-6. Further studies are needed, to clarify the potential risk of HHV-6 transmission from seropositive donors especially with high HHV-6 viral load but after the adoption of a common accredited detection method .
In our study no blood donor tested positive for HHV-8 antibodies and the HHV-8 seroprevalence in the general population in Greece is not confirmed in our blood donor population. This may reflect, the usefulness of the donor screening questionnaire that tends to exclude donors with risk factors and/or behaviour which are related to HHV-8 transmission. Accordingly the risk for HHV-8 transmission related to transfusion in Greece, if any, is substantially low and does not warrant broad testing for HHV-8. Further studies are needed, in order to clarify the potential risk of HHV-6 transmission.
- Vamvakas EC: Is human herpesvirus-8 transmitted by transfusion? Transfus Med Rev 2009, 24:1–14.View Article
- Braun DK, Dominguez G, Pellett PE: Human herpesvirus 6. Clin Microbiol Rev 1997, 10:521–567.PubMedPubMed Central
- Dourmishev LA, Dourmishev AL, Palmeri D, Schwartz RA, Lukac DM: Molecular Genetics of Kaposi’s Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol Mol Biol Rev 2003, 67:175–212. 10.1128/MMBR.67.2.175-212.2003PubMedView ArticlePubMed Central
- Larocca L, Leto D, Celesta BM, Maccarone S, Mazza C, Cacopardo B, Nigro L: Prevalence of antibodies to HHV-8 in the general population and in individuals at risk for sexually transmitted and blood-borne infections in Catania, Eastern Sicily. Infez Med 2005, 13:79–85.PubMed
- 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. 10.1038/nm0896-918PubMedView Article
- Simpson GR, Schulz TF, Whitby D, Cook PM, Boshoff C, Rainbow L, Howard MR, Gao SJ, Bohenzky RA, Simmonds P, Lee C, de Ruiter A, Hatzakis A, Tedder RS, Weller IV, Weiss RA, Moore PS: Prevalence of Kaposi’s sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 1996, 348:1133–1138. 10.1016/S0140-6736(96)07560-5PubMedView Article
- Panayiotakopoulos GD, Mavroyianni D, Politou M, Aroni K, Kosmopoulou O, Kontos AN, Choremi-Papadopoulou H, Pediaditis J, Kordossis T: Human herpesvirus-8 seropositivity and clinical correlations in HIV-1-positive and highly exposed, persistently HIV-seronegative individuals in Greece. AIDS Patient Care STDS 2005, 19:375–383. 10.1089/apc.2005.19.375PubMedView Article
- Zavitsanou A, Sypsa V, Petrodaskalaki M, Kalapothaki V, Whitby D, Hatzakis A: Human herpesvirus 8 (HHV-8) infection in healthy urban employees from Greece: Seroprevalence and associated factors. J Med Virol 2007, 79:591–596. 10.1002/jmv.20812PubMedView Article
- Chatlynne LG, Lapps W, Handy M, Huang YQ, Masood R, Hamilton AS, Said JW, Koeffler HP, Kaplan MH, Friedman-Kien A, Gill PS, Whitman JE, Ablashi DV: Detection and titration of human herpesvirus-8-specific antibodies in sera from blood donors, acquired immunodeficiency syndrome patients, and Kaposi’s sarcoma patients using a whole virus enzyme-linked immunosorbent assay. Blood 1998, 92:53–58.PubMed
- Laina I, Syriopoulou VP, Daikos GL, Roma ES, Papageorgiou F, Kakourou T, Theodoridou M: Febrile seizures and primary human herpesvirus 6 infection. Pediatr Neurol 2010, 42:28–31. 10.1016/j.pediatrneurol.2009.07.016PubMedView Article
- Zaravinos A, Bizakis J, Spandidos DA: Prevalence of human papilloma virus and human herpes virus types 1–7 in human nasal polyposis. J Med Virol 2009, 81:1613–1619. 10.1002/jmv.21534PubMedView Article
- Katzoli P, Sakellaris G, Ergazaki M, Charissis G, Spandidos DA, Sourvinos G: Detection of herpes viruses in children with acute appendicitis. J Clin Virol 2009, 44:282–286. 10.1016/j.jcv.2009.01.013PubMedView Article
- Neofytou E, Sourvinos G, Asmarianaki M, Spandidos DA, Makrigiannakis A: Prevalence of human herpes virus types 1–7 in the semen of men attending an infertility clinic and correlation with semen parameters. Fertil Steril 2009, 91:2487–2494. 10.1016/j.fertnstert.2008.03.074PubMedView Article
- Thomas D, Karachaliou F, Kallergi K, Vlachopapadopoulou E, Antonaki G, Chatzimarkou F, Fotinou A, Kaldrymides P, Michalacos S: Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease. Endocrine 2008, 33:171–175. 10.1007/s12020-008-9068-8PubMedView Article
- Dollard SC, Roback JD, Gunthel C, Amin MM, Barclay S, Patrick E, Kuehnert MJ: Measurements of human herpesvirus 8 viral load in blood before and after leukoreduction filtration. Transfusion 2013, 53:2164–2167.PubMed
- Hladik W, Pellett PE, Hancock J, Downing R, Gao H, Packel L, Mimbe D, Nzaro E, Mermin J: Association between transfusion with human herpesvirus 8 antibody-positive blood and subsequent mortality. J Infect Dis 2012, 206:1497–1503. 10.1093/infdis/jis543PubMedView Article
- Hudnall SD, Chen T, Allison P, Tyring SK, Heath A: Herpesvirus prevalence and viral load in healthy blood donors by quantitative real-time polymerase chain reaction. Transfusion 2008, 48:1180–1187. 10.1111/j.1537-2995.2008.01685.xPubMedView Article
- Wilborn F, Schmidt CA, Zimmermann R, Brinkmann V, Neipel F, Siegert W: Detection of herpesvirus type 6 by polymerase chain reaction in blood donors: random tests and prospective longitudinal studies. Br J Haematol 1994, 88:187–192. 10.1111/j.1365-2141.1994.tb04995.xPubMedView Article
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.