Laboratory Diagnosis of HSV and Varicella Zoster Virus Infections

Feinan Fan; Stephen Day; Xuedong Lu; Yi-Wei Tang


Future Virology. 2014;9(8):721-731. 

In This Article

Abstract and Introduction


HSV and varicella zoster virus (VZV) are common pathogens of skin and mucous membranes and the CNS. Their rapid and accurate diagnosis is essential for their treatment as well as infection control. Cytological and morphological examination, specific antibody detection methods and virus isolation all have their own limitations in clinical practice. In recent years, molecular methods have become the primary diagnostic methods for the detection and differentiation of HSV1/2 and VZV due to their high sensitivity, specificity, rapid test turnaround time and potential for high throughput and automation. Although molecular assays detect HSV1/2 and VZV more quickly, the clinical significance of positive results may vary in individual patients.


HSV and varicella zoster virus (VZV) are large, dsDNA viruses of the Herpesviridae family. They induce disorders with a wide range of clinical manifestations, including mucocutaneous, genital and neurological diseases, among which mucocutaneous lesions are the most frequently seen.[1] Two serotypes of HSV have been identified – HSV-1 and HSV-2 – with the former predominantly causing orofacial infections via nonsexual contact, whereas the latter are commonly transmitted sexually and are associated with genital diseases, although the artificial demarcation by anatomical site is becoming blurred. Globally, the large majority of HSV-infected cases are caused by HSV-2, although an increasing proportion of genital herpes cases has been attributed to HSV-1 infections.[2] Because mucosal disruption caused by recurrent genital herpes can facilitate HIV entry, there is an increasing awareness that HSV-2 infection is a significant risk factor of HIV acquisition.[3] In addition, perinatal transmission of HSV-2 can result in disseminated infection in newborns with CNS involvement, and possibly neonatal death.[4]

VZV is the causative agent of varicella or chickenpox, which is an acute, highly contagious disease characterized by an itchy, vesicular rash on the face, chest, back and stomach. The virus is primarily transmitted via droplets, aerosol or direct contact, and neonates and immunocompromised individuals are considered to be high-risk populations for infection.[5]

Both HSV and VZV are ubiquitous and important human pathogens. According to a National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004, approximately 57% of US adults are infected with HSV-1 and 17% with HSV-2. There are over 1 million cases of VZV reactivation caused herpes zoster or shingles in the USA each year, with an estimated lifetime attack rate of 30%.[6] Since the clinical courses of primary HSV and VZV infections are usually mild and self-limiting with the exception of neonatal infections, up to 81.1% of infected persons are not diagnosed.[7] Moreover, most HSV-infected individuals are asymptomatic when the virus is transmitted to their partners, or infrequently to their newborns, which further facilitates HSV transmission.[8,9]

Despite the self-limiting characteristics of most herpes infections, growing public attention has been focused on these viruses because HSV and VZV infections are so prevalent and they are associated with rare complications, including encephalitis, hepatitis, pneumonia, esophagitis and keratitis, creating a considerable medical burden in both immunocompetent and immunocompromised populations. Furthermore, the strong synergy between HSV-2 and HIV transmission and the increasing rate of HSV- and VZV-related complications in organ transplant recipients have established the importance of rapid detection methods for HSV and VZV diagnosis and treatment. Nevertheless, since various herpesvirus infections can cause similar symptoms, diagnosis based only on clinical manifestations is unreliable and nonspecific and could lead to improper treatment and increasing mortality.[10–12] Thus, a clinical diagnosis of herpes infection should be confirmed with laboratory tests. In addition, the rapid and accurate laboratory confirmation of diagnosis in cases of HSV-1/2 and VZV infection can be an important clinical resource for guiding the prescription of antiviral therapy. This article summarizes the recent developments in laboratory diagnostic techniques for HSV and VZV infection.