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JUNE 13th, 2006 NOVITEC product Newsletter!
Serological determination of the Human Herpes Virus type 1 (HHV-1) and Human Herpes Virus type 2 (HHV-2) by means of NOVITEC enzyme immuno assays (ELISA) and DotBlot.
Description:
HHV-1/2 formerly Herpes Simplex Virus type 1/2 (HSV-1/2)
Pathogen:
Family: Herpesviridae
Distribution:
worldwide, sero prevalence HHV-1/2 75-95% for HHV-1, HHV-2 ca. 10-30% but increasing (Ron Ballard, 2001)
Reservoir:
Human
Route of infection:
Droplet infection, smear infection, barely via blood cells in transplantation, sexual, oral, genital secretion
Incubation period:
2-12 days
Clinical picture:
Gingivostomatitis, Herpes labialis, Herpetic Cerato-conjungtivitis, Herpes genitalis (HHV-2) with aseptic meningitis as complication, hardly as sporadic hemorrhagic Herpes-Simplex-Encephalitis (primary or secondary). Herpes neonatorum (perinatal infection).
Form of infection:
from initially lytic productive to latent (non-productive) to reactive lytic productive to latent (multiple cycles during life after primary infection).
Differential diagnosis:
CMV, EBV, VZV, measles, mumps, rubella, HPV, Adenovirus...
Diagnosis:
Virusisolation, PCR1, Serology: IFA2, ELISA3,
Therapy:
Aciclovir, Valaciclovir, Foscarnet, Famciclovir
Prevention:
no vaccine available but post-exposition prophylaxis of perinatal infection with Aciclovir
Immunity:
basically immunity to HHV-1 and HHV-2, but 10-30% double positive. Problem: reactivation especially under immunosuppression
INTRODUCTION
In most cases pimary infection with HHV-1 and often also with HHV-2 is inapparent.While HHV-1 infections mostly cause herpes labialis, gingivostomatitis, eccema herpeticum or conjunctivitis, the HHV-2 infections are mostly restricted to the genital area and may cause lesions and blisters. Sexual behaviour enables reciproke distribution of HHV-1 versus HHV-2 viruses. Nevertheless, many infections despite of symptoms remain undetected, while asymptomatic genital shedding of viruses dramatically contribute to virus transmission (Preiser and Doerr). The epidemiological problem of these herpesviruses is due to the reactivation pocesses. HHV-1 or HHV-2 reactivation may either be symptomatic or non-symptomatic (60%!). These episodes of non-symptomatic reactivation are the major cause of efficient virus transmission. The HHV-1/2 non-symptomatic reactivation and sero negative pregnant women are of iatrogenic risk to acquire HHV-1/2 either post partum or through perinatal exposition of HHV-1/2 to transmit the virus to the newborn baby, which ultimately leads to “herpes neonatorum” (Enders, 2003). Within the last 20 years the HHV-2 sero prevalence has increased by 30%, while HHV-2 incidence can be found in teenagers in contrast to earlier observations where HHV-2 sero positivity was restricted to elderly (Ashley & Wald, 1999).
Indications for a serologic diagnosis:
The classical approach to test for HHV-1 or HHV-2 is to isolate the virus from clinical specimens. Today, the molecular methods such as the PCR and the HHV-1/2-type-specific sero diagnosis are favoured. Indications for serological diagnosis are discordant couples, examination of the risk for Herpes neonatorum during pregnancy but also sero epidemiological studies (Preiser and Doerr). Epitope mapping in the glycoprotein G has enabled the production of HHV-1 and HHV-2-specific ELISAs, DotBlots and Western Blots
(Liljeqvist et al., 1998).Type-specific sero diagnosis allows the determination of the HHV-1/2 carrier status (latent HHV-1/2 infection) even if virus isolation or PCR are negative (Ashley & Wald, 1999). Thus, HHV-1/2-type-specific sero diagnosis is an effective screening tool. The impact of serology in herpes infections excludes HHV-1 through differential diagnosis excludes, while the detection of anti-HHV-2 antibodies are of epidemiological interest (Buxbaum et al. 2004).
The NOVITEC ELISAs Herpes Simplex Virus (HSV) Type 1 rekombinant protein G IgG-Test und Herpes Simplex Virus (HSV) Type 2 rekombinant protein G IgGTest use rekombinant HSV-1 gG and HSV-2 gG-proteins, respectively and provide higher specificities as compared to whole lysate formulations. While three different whole lysate ELISAs provided averaged sensitivities of 96% and specificities of 93%, the NOVITEC ELISAs with the recombinant antigens resulted in sensitivities of 93% (HSV-1) and 94% (HSV-2), and in specificities of 96% (HSV-1) and 98% (HSV-2), respectively (US study, data not shown). World wide –although still ongoing - studies do confirm those data. The comparison of affinity purified gG-specific antigens used in ELISAs proofed to be equivalent to whole virus lysate antigen ELISAs, while ELISAs using the recombinant gG proteins proofed to be superior.
The NOVITEC Dot Blots do have the advantage, that in addition to whole virus (HHV-1 and HHV-2) lysate antigens also recombinant gG proteins are used. Thus, the DotBlot enables a direct side-by-side comparison on the same dip stick. One dip stick allows the determination of IgM antibodies, while the other allows the determination of IgG antibodies. The use of these dip sticks allows the discrimination of an acute and a reactivated reaction, respectively.
Table 1 illustrates the performance characteristics (specimens used were identical to those tested for The NOVITEC ELISAs).
Table 1: Performance characteristics of the NOVITEC Herpes Simplex Dot Blot IgG Test
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Interpretation
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relative sensitivity
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relative specificity
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negative
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100% (15/15)
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100% (15/15)
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HSV-1
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95% (56/59)
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100% (15/15)
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HSV-2
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94% (31/33)
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100% (15/15)
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References
Preiser und Doerr: Hauptvorlesung Medizinische Virologie: Herpesviren. Am Institut für Medizinische Virologie der Johann Wolfgang von Goethe Unversität zu Frankfurt/Main; download von www.kgu.de/zhyg/virologie/handout19.pdf
Ron Ballard, 2001: The role serological screening in the management of genital herpes download von www.mediscover.net.
Liljeqvist J-A, Trybala E, Svennerholm B, Jeansson S, Sjögren-Jansson E, Bergström T. 1998. Localization of type-specific epitopes of Herpes Simplex Virus type 2 glycoprotein G recognized by human and mouse antibodies. J Gen Virol 79: 1215-1224.
Enders G. 2003. Infektionsgefährdung : Mutterschutz im Krankenhaus. Arbeitsmed. Sozialmed. Umweltmed. 38: 324-335.
Ashley RL, Wald A, 1999. Genital Herpes: Review of the epidemic and potential use of type-specific serology. Clin Microbiol Reviews 12: 1-8.
Buxbaum S, Ludwig B, Doerr HW. 2004. Diagnostik und Therapie vpn Herpes-simplex virus (HSV)-Infektionen: Immunologische Methoden im Vergleich. Abstracts Deutsches Herpes Management Formum 2003, Chemotherapie Journal, 13. Jahrgang Heft 1/2004, Seite 28-29.
PRODUCTS
NOVITEC ELISA:
Herpes Simplex Virus (HSV) Type 1, recombinant gG-protein. Cat.No.: 703580 96 determinations
Herpes Simplex Virus (HSV) Type 2, recombinant gG-protein. Cat.No.: 703590 96 determinations
NOVITEC DotBlot:
Herpes Simplex Virus- dip sticks with: positive control, HSV-1-ysate HSV-2-lysate, HSV-1-gG, HSV-2-gG, negative control, IgG: Cat.No.: 703595, 25 strips, IgM: Cat.No.: 703596, 25 strips
Responsible for the content: Ralf D. Hess, PhD; Comments exclusively reflect the author`s [au] opinion. e-mail for correspondence: rdhess@novitec.org
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