- Email: [email protected]
Epstein-Barr virus reactivation
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Michael Sorokin and Peter R Mansfield MS and PRM are both at Healthy Skepticism Inc, Willunga, Australia. MS has been known to enjoy a glass of good South Australian red and a meal at drug company expense but has resolved to cease this practice. In 1996 PRM was funded by Sandoz Ltd for travel to and accommodation at a meeting with that company’s senior staff about marketing of bromocriptine but has since signed the No Free Lunch pledge (www.nofreelunch.org).
Correspondence: Dr M Sorokin, Healthy Skepticism Inc, 34 Methodist St, Willunga, SA 5172, Australia. Email [email protected] References 1
2 3
Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; 3: 148–55. Anon. Revealing all. Lancet Infect Dis 2003; 3: 117. Jureidini JN, Mansfield P. Avoiding competing interests. http://bmj.com/cgi/eletters/325/7377/ 1375#28210 (accessed March 20, 2003).
Epstein-Barr virus reactivation I read with interest the excellent review by Karen F Macsween and Dorothy H Crawford1 of recent advances in Epstein-Barr virus (EBV). The reactivation of EBV is a very important issue, and several factors can contribute to the process. The association with the well-defined “immunocompromised” status of the host (malignancies, HIV infection, etc) is well known,2-5 but increased stress hormone concentrations in astronauts were also considered as a causative factor in the reactivation process as a result of decreased virus-specific T-cell immunity.6 It is likely that similar mechanisms can develop in other conditions leading to the reactivation of EBV. In a previous study7,8 we wanted to estimate the actual EBV serological status in different (adult) patients admitted to the Department of Infectology in our hospital. Singleserum samples were taken from patients with acute gastroenteritis (of different origin), acute viral hepatitis, alcoholic liver disease, and HBsAg carriers, and were screened for viral capsid antigen (VCA)-IgM, IgG, and EBV-associated nuclear antigen (EBNA) antibodies. Rheumatoid-
factor-positive cases were excluded from the study. Heterophil antibodies were detected simultaneously. The results were grouped into serological patterns as seronegative samples, VCA IgM, VCA IgG, and VCA IgG plus EBNA antibody-positive samples. We used negative control groups that comprised healthy blood donors and pregnant women, and a positive control group of infectious mononucleosis cases. The results are summarised in the table. We noted that the incidence rate of anti-VCA IgM seropositivity was significantly higher in patients with alcoholic liver diseases (10·46%) and in HBsAg carriers (11·26%) (p<0·05) than in other disease groups (acute viral hepatitis, gastroenteritis) and in the negative control groups. This finding indicates that the serological signs of reactivation might be seen in such conditions where the actual immunological defence mechanisms of the host are hampered by diseases other than tumours or AIDS, which was not previously suspected (Anthony Epstein, Oxford University, personal communication). Similarly, we also noted a slight increase in VCA IgM antibody in elderly patients.9
I believe that our observations might warrant further, more detailed studies to elucidate EBV reactivation in people. G Ternák GT is at the Department of Infectology, County Hospital, Pécs, Hungary. Correspondence: Dr G Ternák, Department of Infectology, County Hospital, H-7623, Pécs, Rákóczi út 2, Hungary. Email [email protected] References 1 2 3
4
5 6
7
8
9
Crawford DH, Macsween KF. Epstein-Barr virus— recent advances. The Lancet Infect Dis 2003; 3: 131–140. Khan G, Coatest PJ. The role of Epstein-Barr virus in the pathogenesis of Hodgkin’s disease. J Pathol 1994; 174: 141–49. Cinque P, Brytting M, Vago L, et al. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993; 342: 398–401. Hubscher SG, Wiliams A, Davison SM, Young SL, Niedobitek G. Epstein-Barr virus in inflammatory diseases of the liver and liver allografts: an in situ hybridization study. Hepatology 1994; 20: 899–907. Khan G, Coatest PJ. The role of Epstein-Barr virus in the pathogenesis of Hodgkin’s disease. J Pathol 1994; 174: 141–49. Stowe RP, Pierson DL, Barrett AD. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts. Psychosom Med 2001; 63: 891–95. Ternák G, Új M, Szucs Gy, et al. Az Epstein-Barr virus (EBV) aktivitásának szerológiai jelei akut virus hepatitisekben, tünetmentes HBsAg hordozókban és alkoholos eredetu májbetegségekben. Orv Hetil 1996; 137: 851–56. Ternák G, Liszátz M, Új Mária, Szucs György. Az Epstein-Barr vírus (EBV) aktivitásának szerológiai jelei HbsAg hordozókban. Transfuzió 1996; 26: 9–15. Ternák G, Szucs Gy, Új M. The serological signs of the Epstein-Barr virus (EBV) activity in the elderly. Acta Microbiol Immunol Hung 1997; 44: 133–40.
EBV serological status in patients admitted to the department of infectology Diseases
No
Seronegative patients No %
Anti-VCA IgM
Anti-VCA IgG (only)
Anti-VCA IgG + anti-EBNA
No
%
No
No
%
Heterophil antibody positivity No %
Acute viral hepatitis Alcoholic liver disease HbsAg carriers Acute gastroenteritis Healthy blood donors Pregnant women Infectious mononucleosis
346 258 150 539 100 120 126
35 8 4 113 13 3 17
14 27 16 32 3 3 55
4·1 10·5 11·3 5·9 3 2·5 43·7
87 74 74 151 27 14 32
209 149 149 243 56 100 22
60·4 57·8 57·8 45·1 56 83·3 17·5
6 11 3 12 1 0 28
10·1 3·1 2·8 20·9 13 2·5 13·5
THE LANCET Infectious Diseases Vol 3 May 2003
% 25·1 28·7 28·7 28·1 27 11·7 25·4
http://infection.thelancet.com
1·7 4·3 2 2·2 1 0 22·2
271
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Michael Sorokin and Peter R Mansfield MS and PRM are both at Healthy Skepticism Inc, Willunga, Australia. MS has been known to enjoy a glass of good South Australian red and a meal at drug company expense but has resolved to cease this practice. In 1996 PRM was funded by Sandoz Ltd for travel to and accommodation at a meeting with that company’s senior staff about marketing of bromocriptine but has since signed the No Free Lunch pledge (www.nofreelunch.org).
Correspondence: Dr M Sorokin, Healthy Skepticism Inc, 34 Methodist St, Willunga, SA 5172, Australia. Email [email protected] References 1
2 3
Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; 3: 148–55. Anon. Revealing all. Lancet Infect Dis 2003; 3: 117. Jureidini JN, Mansfield P. Avoiding competing interests. http://bmj.com/cgi/eletters/325/7377/ 1375#28210 (accessed March 20, 2003).
Epstein-Barr virus reactivation I read with interest the excellent review by Karen F Macsween and Dorothy H Crawford1 of recent advances in Epstein-Barr virus (EBV). The reactivation of EBV is a very important issue, and several factors can contribute to the process. The association with the well-defined “immunocompromised” status of the host (malignancies, HIV infection, etc) is well known,2-5 but increased stress hormone concentrations in astronauts were also considered as a causative factor in the reactivation process as a result of decreased virus-specific T-cell immunity.6 It is likely that similar mechanisms can develop in other conditions leading to the reactivation of EBV. In a previous study7,8 we wanted to estimate the actual EBV serological status in different (adult) patients admitted to the Department of Infectology in our hospital. Singleserum samples were taken from patients with acute gastroenteritis (of different origin), acute viral hepatitis, alcoholic liver disease, and HBsAg carriers, and were screened for viral capsid antigen (VCA)-IgM, IgG, and EBV-associated nuclear antigen (EBNA) antibodies. Rheumatoid-
factor-positive cases were excluded from the study. Heterophil antibodies were detected simultaneously. The results were grouped into serological patterns as seronegative samples, VCA IgM, VCA IgG, and VCA IgG plus EBNA antibody-positive samples. We used negative control groups that comprised healthy blood donors and pregnant women, and a positive control group of infectious mononucleosis cases. The results are summarised in the table. We noted that the incidence rate of anti-VCA IgM seropositivity was significantly higher in patients with alcoholic liver diseases (10·46%) and in HBsAg carriers (11·26%) (p<0·05) than in other disease groups (acute viral hepatitis, gastroenteritis) and in the negative control groups. This finding indicates that the serological signs of reactivation might be seen in such conditions where the actual immunological defence mechanisms of the host are hampered by diseases other than tumours or AIDS, which was not previously suspected (Anthony Epstein, Oxford University, personal communication). Similarly, we also noted a slight increase in VCA IgM antibody in elderly patients.9
I believe that our observations might warrant further, more detailed studies to elucidate EBV reactivation in people. G Ternák GT is at the Department of Infectology, County Hospital, Pécs, Hungary. Correspondence: Dr G Ternák, Department of Infectology, County Hospital, H-7623, Pécs, Rákóczi út 2, Hungary. Email [email protected] References 1 2 3
4
5 6
7
8
9
Crawford DH, Macsween KF. Epstein-Barr virus— recent advances. The Lancet Infect Dis 2003; 3: 131–140. Khan G, Coatest PJ. The role of Epstein-Barr virus in the pathogenesis of Hodgkin’s disease. J Pathol 1994; 174: 141–49. Cinque P, Brytting M, Vago L, et al. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993; 342: 398–401. Hubscher SG, Wiliams A, Davison SM, Young SL, Niedobitek G. Epstein-Barr virus in inflammatory diseases of the liver and liver allografts: an in situ hybridization study. Hepatology 1994; 20: 899–907. Khan G, Coatest PJ. The role of Epstein-Barr virus in the pathogenesis of Hodgkin’s disease. J Pathol 1994; 174: 141–49. Stowe RP, Pierson DL, Barrett AD. Elevated stress hormone levels relate to Epstein-Barr virus reactivation in astronauts. Psychosom Med 2001; 63: 891–95. Ternák G, Új M, Szucs Gy, et al. Az Epstein-Barr virus (EBV) aktivitásának szerológiai jelei akut virus hepatitisekben, tünetmentes HBsAg hordozókban és alkoholos eredetu májbetegségekben. Orv Hetil 1996; 137: 851–56. Ternák G, Liszátz M, Új Mária, Szucs György. Az Epstein-Barr vírus (EBV) aktivitásának szerológiai jelei HbsAg hordozókban. Transfuzió 1996; 26: 9–15. Ternák G, Szucs Gy, Új M. The serological signs of the Epstein-Barr virus (EBV) activity in the elderly. Acta Microbiol Immunol Hung 1997; 44: 133–40.
EBV serological status in patients admitted to the department of infectology Diseases
No
Seronegative patients No %
Anti-VCA IgM
Anti-VCA IgG (only)
Anti-VCA IgG + anti-EBNA
No
%
No
No
%
Heterophil antibody positivity No %
Acute viral hepatitis Alcoholic liver disease HbsAg carriers Acute gastroenteritis Healthy blood donors Pregnant women Infectious mononucleosis
346 258 150 539 100 120 126
35 8 4 113 13 3 17
14 27 16 32 3 3 55
4·1 10·5 11·3 5·9 3 2·5 43·7
87 74 74 151 27 14 32
209 149 149 243 56 100 22
60·4 57·8 57·8 45·1 56 83·3 17·5
6 11 3 12 1 0 28
10·1 3·1 2·8 20·9 13 2·5 13·5
THE LANCET Infectious Diseases Vol 3 May 2003
% 25·1 28·7 28·7 28·1 27 11·7 25·4
http://infection.thelancet.com
1·7 4·3 2 2·2 1 0 22·2
271
For personal use. Only reproduce with permission from The Lancet Publishing Group.