An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein-Barr virus (HHV-4): New and emerging treatment strategies

Virus Adaptation and Treatment

Volumn 2, Issue 1, 2010, Pages 135-145

  Lerner, A Martin ^a   Beqaj, Safedin H ^b   Gill, Ken ^c   Edington, James ^c   Fitzgerald, James T ^d   Deeter, Robert G ^e  

^a WILLIAM BEAUMONT HOSPITAL   (United States)

^b DCL Medical Laboratories   (United States)

^c The Dr A Martin Lerner   (United States)

^d UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^e AMGEN INC   (United States)

Author keywords

Chronic fatigue syndrome; EIPS; Energy Index Point Score; Epstein Barr virus; Valacyclovir treatment

Indexed keywords

ACICLOVIR; CIMETIDINE; CORTICOSTEROID; FAMCICLOVIR; GANCICLOVIR; IMMUNOGLOBULIN M; METHYLPREDNISOLONE SODIUM SUCCINATE; PENCICLOVIR; PLACEBO; PREDNISONE; PROBENECID; VALACICLOVIR; VALGANCICLOVIR;

ANTIBODY DETECTION; ANTIVIRAL ACTIVITY; B LYMPHOCYTE; CHRONIC FATIGUE SYNDROME; CLINICAL TRIAL; DEMOGRAPHY; DIARRHEA; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG COST; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ERUPTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; ENCEPHALOMYELITIS; EPSTEIN BARR VIRUS; EPSTEIN BARR VIRUS INFECTION; FOOD; FOOD DRUG INTERACTION; GLOMERULUS FILTRATION RATE; HALLUCINATION; HEPATITIS; HOLTER MONITORING; HUMAN; IMMUNOGLOBULIN BLOOD LEVEL; INFECTIOUS MONONUCLEOSIS; LATENT PERIOD; LIVER TOXICITY; LYMPHOCYTE COUNT; MALIGNANT NEOPLASTIC DISEASE; MENINGITIS; MIXED INFECTION; NAUSEA; NEPHROLITHIASIS; NEPHROTOXICITY; NEUROTOXICITY; NEUTROPENIA; ONSET AGE; PERICARDITIS; PERIPHERAL NEUROPATHY; REVIEW; SEROLOGY; T LYMPHOCYTE; THROMBOCYTOPENIA; THYROIDITIS; URTICARIA; VIRUS REPLICATION; VIRUS TITRATION;

EID: 78049365837     PISSN: None     EISSN: 11791624     Source Type: Book Series    
DOI: 10.2147/VAAT.S6749     Document Type: Review

References (76)

1. Pfeifer E, Drüsenfieber J. Kinderheil/Kd. 1889;29:257-264.
2. Sprunt TP, Evans FA. Mononuclear leukocytes reaction to acute infection (in infectious mononucleosis). Bull Johns Hopkins Hosp. 1920;31:410-417.
3. Paul JR, Bunnell WW. The presence of heterophile antibodies in infectious mononucleosis. Am J Med Sci. 1932;183:90-103.
4. Epstein MA, Achong HG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet. 1964;1:702-703.
5. Henle G, Henle W, Diehl V. Relation of Burkitt's tumor associated herpes-type virus to infectious mononucleosis. Proc Natl Assoc Sci U S A. 1968;59:94-101.
6. Miller G, Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leucocytes. Proc Natl Acad Sci U S A. 1973;70:190-194.
7. Niederman JC, Evans AS. Epstein-Barr Virus. In: Evans AS, Kaslow RA, editors. Viral Infections of Humans: Epidemiology and Control. 4th ed. New York, London: Plenum Medical Book Company; 1997:253-284, Chap 10.
8. Klemola E, von Essen R, Henle G, Henle W. Infectious mononucleosislike disease with negative heterophile agglutination test. Clinical features in relation to Epstein-Barr virus and cytomegalovirus antibodies. J Infect Dis. 1970;121:608-614.
9. Roizman B. The family of herpes viridae: a brief introduction. In: Roizman B, Whitley RJ, Lopez C, editors. The Human Herpes Viruses. New York: Raven Press; 1993:1-10.
10. Robertson E, editor. Epstein-Barr Virus. Norfolk, England: Caister Academic Press; 2005:770.
11. Crawford H. Epstein-Barr virus. In: Zuckerman HJ, Banatvala JE, Pattison JR, editors. Principles and Practice of Clinical Virology. 4th ed. John Wiley & Sons Ltd; 2001:117-140.
12. Hadinoto V, Shapiro M, Greenough TC, Sullivan John L, Uzuriaga K, Thorley-Lawson David A. On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis. Blood. 2008;111:1420-1427.
13. Borza CM, Hutt-Fletcher LM. Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat Med. 2002;8:594-599.
14. Tsai CH, Williams MV, Glaser R. Characterization of two monoclonal antibodies to Epstein-Barr virus diffuse study antigen which react to two different epitopes and have different biological function. J Virol Methods. 1991;33(1-2):47-52.
15. Balfour HH Jr, Holman CJ, Hokanson KM, et al. A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J Infect Dis. 2005;192:1505-1512.
16. Cohen JI. Epstein-Barr virus infections, including infectious mononucleosis. In: Kasper DL, Braunwald E, Fauci AS, Longo D, Hauser SL, editors. Harrison's Principles of Internal Medicine. 16th ed. McGraw Hill; 2005:1046-1049.
17. Henle W, Henle G, Harrison FS, et al. Antibody responses to Epstein-Barr virus and cytomegaloviruses after open-heart and other surgery. N Engl J Med. 1968;282:1068-1074.
18. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010;362:1993-1999.
19. Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994;121:953-959.
20. Lerner AM, Zervos M, Dworkin HJ, et al. A unified theory of the cause of the chronic fatigue syndrome. Infect Dis Clin Pract. 1997;63:239-243.
21. Lerner AM, Beqaj SH, Deeter RG, et al. IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with chronic fatigue syndrome. In Vivo. 2004;18:101-106.
22. Tobi M, Morag A, Ravid Z, et al. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet. 1982;1:61-64.
23. Lerner AM, Beqaj S, Fitzgerald JT, et al. Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome. Virus Adapt Treat. 2010;2:1-11.
24. Tynell E, Aurelius E, Brandell A, et al. Acyclovir and prednisone treatment of acute infectious mononucleosis. A multicenter, double-blind, placebo-controlled study. J Infect Dis. 1996;174:324-331.
25. Hoshino Y, Katano H, Zou P, et al. Long-term administration of valacyclovir reduces the number of Epstein-Barr virus (EBV)-infected cells, but not the number of EBV DNA copies per B cell in healthy volunteers. J Virol. 2009;83:11857-11861.
26. Henle W, Henle G, Horwitz CA. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Human Pathol. 1974;5:551-565.
27. Horwitz CA, Henle W, Henle G, et al. Long-term serologic follow-up of patients for Epstein-Barr virus after recovery from infectious mononucleosis. J Infect Dis. 1985;151:1150-1153.
28. Landolfo S, Gariglio G, Lembo D. The human cytomegalovirus. Pharmacol Ther. 2003;98:269-297.
29. Purifoy DJ, Beauchamp LM, de Miranda P, et al. Review of research leading to new anti-herpesvirus agents in clinical development: valacyclovir hydrochloride (256 U, the L-valyl ester of acyclovir) and 882C, a specific agent for varicella zoster virus. J Med Virol. 1993;Suppl 1:139-145.
30. Weller S, Blum MR, Doucette M, et al. Pharmacokinetics of the acyclovir prodrug valacyclovir after escalating single-and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993;54:595-605.
31. Emberg I, Andersson J. Acyclovir efficiently inhibits oropharyngeal excretion of Epstein-Barr virus in patients with acute infectious mononucleosis. J Gen Virol. 1986;67:2267-2272.
32. Pagano JS, Sixby JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother. 1983;12:113-121.
33. Rolan PE, Maillott F, On NT, Posner J. The effects of Cimetidine and probenecid on the conversion of a valacyclovir ester of acyclovir 256U to acyclovir and acyclovir renal clearance in healthy volunteers. Br J Clin Pharmacol. 1993;35:533.
34. Laskin OL. Clinical pharmacokinetics of acyclovir. Clin Pharm. 1983;8:187-201.
35. Laskin OL. Acyclovir pharmacology and clinical experience. Arch Intern Med. 1984;144:1241-1246.
36. Lycke J, Malmestrom C, Stahle L. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003;47:2438-2441.
37. Wagstaff AJ, Faulds D, Goa K Acyclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994;47:153-205.
38. Pagano JS, Data AK. Perspectives on interactions of acyclovir and Epstein-Barr and other herpesviruses. Am J Med. 1982;73:18-26.
39. Lerner AM, Beqaj SH, Deeter RG, et al. A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function. Drugs Today. 2002;38(8):549-561.
40. Datta AK, Colby BM, Shaw JE, Pagano JS. Acyclovir inhibition of Epstein-Barr virus replication. Proc Natl Acad Sci U S A. 1980;77:5163-5166.
41. Colby BM, Shaw JE, Elion GB, Pagano JS. Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication. J Virol. 1980;34:560-568.
42. Colby BM, Furman PA, Shaw JE, Elion GB, Pagano J. Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines. J Virol. 1981;38:606-611.
43. St Clair MH, Furman PA, Lubbers CM, et al. Inhibition of cellular alpha and virally induced deoxyribonucleic acid polymerases by the triphosphates of acyclovir. Antimicrob Agents Chemother. 1980;18:741-745.
44. Furman PA, de Miranda P, St Clair MH, et al. Metabolism of acyclovir in virus-infected and uninfected cells. Antimicrob Agents Chemother. 1981;20:518-524.
45. Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis. 1999;31:543-547.
46. van der Horst C, Joncas J, Ahronheim G, et al. Lack of effect of peroral acyclovir for the treatment of acute infectious mononucleosis. J Infect Dis. 1991;164:788-792.
47. Balfour H Jr, Hokanson KH, Schacherer R, et al. A virologic pilot study of valacyclovir in infectious mononucleosis. J Clin Virol. 2007;39(1):16-21.
48. Vere Hodge RA. Review: antiviral portraits series, number 3. Famciclovir and penciclovir. The mode of action of famciclovir including its conversion to penciclovir. Antivir Chem Chemother. 1993;4:67-84.
49. Boyd MR, Kern ER, Safrin S. Penciclovir: a review of its spectrum of activity, selectivity, and cross-resistance pattern. Antivir Chem Chemother. 1993;4:3-11.
50. Hayden FG. Antiviral drugs other than ante-retrovirals. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Disease. 5th ed. Philadelphia: Churchill Livingstone; 2000. p. 468-469. Penciclovir and Famciclovir.
51. Bacon TH, Boyd MR. Activity of penciclovir against Epstein-Barr virus. Antimicrob Agents Chemother. 1995;39(7):1599-1602.
52. Straus SE. Epstein-Barr virus and human herpesviruses 6 and 7. In: Gallasso GJ, Whitley RJ, Merigan TC, editors. Antiviral Agents and Human Viral Diseases. Lippincott-Rave Publishers; 708. Chap 18.
53. Komaroff AL. Is human herpesvirus-6 a trigger for chronic fatigue syndrome? J Clin Virol. 2006;37:S39-S46.
54. Buchwald D, Cheney PR, Peterson DL, et al. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active herpesvirus type 6 infection. Ann Intern Med. 1992;116:103-113.
55. Agut H, Collandre H, Aubin T, et al. In vitro sensitivity of human herpesvirus-6 to antiviral drugs. Res In Virol. 1989;140:219-228.
56. Lerner AM, Beqaj SH, Fitzgerald JT. Validation of the Energy Index Point Score to serially measure degree of disability in patients with chronic fatigue syndrome. In Vivo. 2008;22:799-802.
57. Lerner AM, Zervos M, Dworkin HJ, et al. A new cardiomyopathy: a pilot study of intravenous ganciclovir in a subset of the chronic fatigue syndrome. In Dis In Clin Prac. 1997;16:110-117.
58. Lerner AM, Dworkin HJ, Sayyed T, et al. Prevalence of abnormal cardiac wall motion in the cardiomyopathy associated with incomplete multiplication of EBV and/or CMV in patients with chronic fatigue syndrome. In Vivo. 2004;18:417-424.
59. Jarisch A. Therapeutische Jersuche bei syphilis. Wien Med Wochenschr. 1895;45:721-742.
60. Herxheimer K, Krause D. Uber eine bei syphilitischen vorkommende quecksilber-reaktion. Deutch Med Wochenschr. 1902;28:895-897.
61. Lerner AM, Lawrie-Hoppen C, Dworkin HJ. Repetitively negative changing T-waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort. Chest. 1993;104:1417-1420.
62. Rowe PC, Bou-Holaigah I, Kan JS, et al. Is neurally medicated hypotension an unrecognized cause of chronic fatigue syndrome? Lancet. 1995;345:623-624.
63. Dworkin HJ, Lawrie-Hoppen C, Bohdiewiez P, et al. Abnormal left ventricular myocardial dynamics in eleven patients with the chronic fatigue syndrome. Clin Nuc Med. 1994;19:657-677.
64. Lerner AM, Goldstein J, Chang CH, et al. Cardiac involvement in patients with the chronic fatigue syndrome as documented with Holter and biopsy data in Birmingham, Michigan. Infect Dis Clin Pract. 1997;6:327-333.
65. Webster BH. Cardiac complications of infectious mononucleosis: a review of the literature and report of five cases. Am J Med Sci. 1957;234:62-70.
66. Tyson AA Jr, Hackshaw BT, Kutcher MA. Acute Epstein-Barr virus myocarditis simulating myocardial infarction with cardiogenic shock. South Med J. 1989;82:1184-1186.
67. Herbert MM, Yu C, Towbin JA, Rogers BB. Fatal Epstein-Barr virus myocarditis in a child with repetitive myocarditis. Fetal Pediatr Pathol. 1995;15:805-812.
68. LeBlanc MH, Boudriau S, Doyle D, et al. Epstein-Barr virus mediated graft rejection in heart transplant patients: implication of the cardiac cytoskeleton. Transplant Proc. 1998;30:918.
69. Lerner AM, Beqaj SH, Deeter RG, et al. IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2 (UL44 and UL 57) are uniquely present in a subset of patients with chronic fatigue syndrome. In Vivo. 2002;16:153-160.
70. Beqaj SH, Lerner AM, Fitzgerald JT. Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome. J Clin Pathol. 2007;61:623-626.
71. Lerner AM, Zervos M, Chang CH, et al. A small randomized placebo controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome. Clin Infect Dis. 2004;32:1657-1658.
72. Lerner AM, Beqaj SH, Deeter RJ, et al. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome with long-term thirty-six month follow-up. In Vivo. 2007;21:707-714.
73. Jason LA, Richman JA, Rademaker AW, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999;159:2129-2137.
74. Straus SE, Tosato G. Persisting illness and phase complete fatigue in adults with evidence of Epstein-Barr virus infections. Ann Intern Med. 1985;102:7-16.
75. Lombardi VC, Ruscette FW, Das Gupta J, et al. Detection of an infectious retrovirus XMRV in blood cells of patients with chronic fatigue syndrome. Science. 2009;326:585-589.
76. Kumar P, Abhik S, Robertson ES. Epstein-Barr virus hijacks cell-cycle machinery. Microbe. 2010;5:251-256.