Laboratory diagnosis of herpes zoster

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Abstract

Virological diagnosis of zoster should be rapid when effective antiviral chemotherapy is being considered. In the present study, vesicle specimens of 100 patients with zoster were analysed by detecting viral DNA using polymerase chain reaction (PCR). The findings were compared with those obtained by traditional virological and serological methods. PCR results confirmed the clinical diagnosis of zoster in 95%. Primers selected from varicella-zoster virus (VZV) gene 28 proved to be most sensitive. The sensitivity of virus culture was 20% (specificity 100%), of direct immunofluorescent VZV-specific antigen staining in vesicle samples 82% (specificity 76%), and in 48% there was a serological response to specific IgM and IgA antibodies within 4 days after the onset of rash. These findings suggest that PCR is the method of choice for rapid laboratory diagnosis of zoster.

Introduction

Herpes zoster caused by reactivation of latent varicella-zoster virus (VZV) is usually a clinical diagnosis. Laboratory tests may be helpful in patients with an atypical rash, common in immunosuppression (Schiller et al., 1991). For patients with life-threatening diseases, it is particularly important to achieve a rapid diagnosis, as effective treatment is available. Most laboratories use serological IgM and/or IgA antibody determination and look for a rise in IgG titers. Significant antibody response takes, however, several days and depends on a functioning immune system. Cross-reactions with herpes simplex virus (HSV) antibodies have also been reported (Bernstein et al., 1990). Serological methods have thus become less useful when rapid decision as regards antiviral chemotherapy is necessary.

An early and accurate diagnosis of zoster may be possible by identification of the etiological agent. However, as VZV is extremely labile and cell-associated virus isolation in cell culture cannot been considered a routine method. Further techniques such as electron microscopy and detection of viral antigens have other disadvantages. Molecular virological procedures, particulary polymerase chain reaction (PCR), are becoming increasingly the standard methods for rapid diagnosis of viral diseases.

This study evaluates PCR techniques for diagnosis of zoster using different VZV-specific oligonucleotides. The results are compared with those obtained by conventional virological and serological methods.

Section snippets

Patients

One hundred patients with the clinical diagnosis of zoster were enrolled. Their ages ranged between 6 and 87 years (mean 56 years). An underlying immunosuppressive disease was known in 23 patients. Zoster was localized in dermatomes of the chest (33 cases), head (28 cases), neck (19 cases), waist (nine cases) and pelvis (one case). Disseminated infections were observed in eight immunosuppressed patients. In two cases, the affected dermatomes were not recorded by the physician.

Forty patients

Results

PCR results confirmed the clinical diagnosis of zoster in 95 of 100 cases tested. There were some differences depending on which oligonucleotides and PCR procedure were used. With primers of VZV gene 28 (Fig. 1), viral DNA could be detected in 90% of samples. Using primers of gene 29, 86 patients had positive results including five negative with primers for gene 28, and with primers of gene 4, viral DNA was amplified in 72 cases (Table 2). In the five PCR-negative cases, we also failed to

Discussion

Zoster is caused by endogenous reactivation of VZV latent within sensory ganglia after primary infection. With an increasing elderly population and more patients having immune deficits due to various diseases and/or medication, zoster has become a significant medical problem (Thomsen, 1994). The incidence of zoster increases with advancing age up to 10-fold, and in patients who have malignancies up to 50- or 100-fold (Hope-Simpson, 1965, Balfour, 1988). Zoster is often complicated by

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