IHMF: Cytomegalovirus and Human Herpesvirus Type 6 Infections in the Immunocompromised (non-HIV) Host
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Management Guidelines Management Guidelines
  Progress with Diagnostic Tests and Vaccines for Alpha-Herpesviruses View Monograph Download Monograph


Background Information
 

The monograph on diagnostic tests and vaccines was published in 1997. Since that time, there have been advances in the areas of type-specific serological testing for herpes simplex virus (HSV) infection and vaccines for controlling genital HSV infection and varicella zoster virus (VZV) infection.

 
Type-specific HSV serological testing

A major problem identified in the monograph was the failure of commercially available tests to accurately distinguish between HSV-1 and HSV-2. Considerable progress has been made in the development of type-specific tests based on HSV glycoprotein G (gG). In the past 3 years, the US Food and Drug Administration (FDA) has approved laboratory-based assays from Focus Technologies that can detect either HSV-1 or HSV-2 antibodies, and point-of -care tests from Diagnology that can identify HSV-2 antibodies. These tests show good performance when compared to the Western blot assay, the gold standard for type-specific serological testing. HSV-1 and HSV-2 type-specific point-of-care tests developed by Quidel also show good performance and the company is seeking FDA approval for the tests. HSV-2 gG tests not approved by the FDA are also available from Roche, Sorin and Centocor. These tests have reasonable performance characteristics but have lower sensitivity than the tests available from Focus Technology or Diagnology. One caveat with regards to the performance of the gG-based tests is that sera from children under 14 years of age exhibit a very high false-positive rate; thus, these tests should probably not be used in evaluating children for HSV-2 infection. More information on type-specific serological tests can be found in a review by Rhoda Ashley.1

 
Varicella zoster virus vaccine back to top

With the recommendation that all US children receive the Oka strain VZV vaccine, more experience has been gained with the product. The effectiveness of the vaccine in clinical practice was evaluated in a 42-month study in the New Haven, Connecticut area. The study found a vaccine effectiveness of 85% against VZV disease and 95% against moderate-to-severe chickenpox.2 Post-marketing safety studies were conducted in the USA. Over a 4-year period 16.1 million doses were distributed and 7963 adverse experiences were reported to the manufacturers for an overall reporting rate of 50 adverse experiences per 100 000 doses distributed.3 Another study using the US Vaccine Adverse Event Reporting System (VAERS) received 6574 reports of adverse experiences for a rate of 67.5 reports per 100 000 doses sold.4 The most common adverse experiences were rashes and injection-site reactions. More serious reactions included: erythema multiforme, Stevens-Johnson syndrome, encephalitis, ataxia, anaphylaxis and thrombocytopaenia. There were reports of breakthrough cases of chickenpox for a reporting rate of 10 cases per 100 000 doses of vaccine sold.3 Some cases of breakthrough varicella required hospitalization. There were also reports of herpes zoster occurring in vaccine recipients. With regards to the issue of reactivation of the vaccine virus, analysis of pre- and post-vaccination serum antibody levels have suggested that large-scale asymptomatic reactivation of VZV Oka might occur in vaccine recipients.5

 
Herpes simplex virus vaccines back to top

Since the publication of the monograph in 1997, trials of two HSV subunit vaccines have been completed. One vaccine developed by Chiron contains HSV-2 glycoprotein B and D combined with the adjuvant MF59, the other,developed by GlaxoSmithKline (GSK), contains HSV-2 glycoprotein D combined with alum and 3-deacylated monophosphoryl lipid A. Both vaccines were shown to be immunogenic and well tolerated in volunteers. The Chiron vaccine afforded a transient protection against acquisition of HSV-2 infection with an overall efficacy of 9% but with greater protection in women (26%) than men (–4%).6 Work on this vaccine has been discontinued. In two studies, the GSK vaccine protected HSV seronegative women from genital herpes disease with a vaccine efficacy of 73% (P=0.01) in study 1 and 74% (P=0.02) in study 2, but afforded no protection to HSV-1 seropositive women or to men.7 Although not statistically significant, the GSK vaccine showed a strong trend towards protection of HSV seronegative women against infection with a vaccine efficacy against HSV infection of 46% in study 1 (P=0.072) and 39% in study 2 (P=0.08).

 
References back to top

1. Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect 2001; 77: 232-237.
2. Vazquez M, LaRussa PS, Gershon AA, Steinberg SP, Freudigman K, Shapiro ED. The effectiveness of the varicella vaccine in clinical practice. N Engl J Med 2001; 344: 955-960.
3. Sharrar RG, LaRussa P, Galea SA, Steinberg SP, Sweet AR, Keatley RM et al. The postmarketing safety profile of varicella vaccine. Vaccine 2000; 19: 916-923.
4. Wise RP, Salive ME, Braun MM, Mootrey GT, Seward JF, Rider LG et al. Postlicensure safety surveillance for varicella vaccine. JAMA 2000; 284: 1271-1279.
5. Krause PR, Klinman DM. Varicella vaccination: evidence for frequent reactivation of the vaccine strain in healthy children. Nat Med 2000; 6: 451-454.
6. Corey L, Langenberg AG, Ashley R, Sekulovich RE, Izu AE, Douglas JM, Jr et al. Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group. JAMA 1999; 282: 331-340.
7. Spruance SL and the SmithKline Beecham (SB) Herpes Vaccine Efficacy Study Group. Gender-specific efficacy of a prophylactic SBAS4-adjuvant gD, subunit vaccine against genital herpes disease (GHD): Results of two clinical efficacy trails. In: Abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy of the American Society for Microbiology, Toronto, Canada 2000.

Lawrence R. Stanberry, University of Texas
Medical Branch, Galveston, Texas, USA

 

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Last Updated : 23/02/2007 15:28:17