Evaluation of laboratory methods for diagnosis of varicella

The incidence of varicella disease is declining as a result of vaccination, making clinical diagnosis more challenging, particularly for vaccine-modified cases. We conducted a comprehensive evaluation of laboratory tests and specimen types to assess diagnostic performance and determine what role testing can play after skin lesions have resolved.

We enrolled patients with suspected varicella disease in 2 communities. Enrollees were visited at the time of rash onset and 2 weeks later. Multiple skin lesion, oral, urine, and blood or serum specimens were requested at each visit and tested for varicella zoster virus (VZV) immunoglobulin (Ig) G, IgM, and IgA antibody by enzyme-linked immunoassay; for VZV antigen by direct fluorescent antibody; and/or for VZV DNA by polymerase chain reaction (PCR). Clinical certainty of the diagnosis of varicella disease was scored. PCR results from first-visit vesicles or scab specimens served as the gold standard in assessing test performance.

Of 93 enrollees, 53 were confirmed to have varicella disease. Among 20 unmodified cases, PCR testing was 95%-100% sensitive for macular and/or papular lesions and for oral specimens collected at the first visit; most specimens from the second visit yielded negative results. Among 27 vaccine-modified cases, macular and/or papular lesions collected at the first visit were also 100% sensitive; yields from other specimens were poorer, and few specimens from the second visit tested positive. Clinical diagnosis was 100% and 85% sensitive for diagnosing unmodified and vaccine-modified varicella cases, respectively.

PCR testing of skin lesion specimens remains convenient and accurate for diagnosing varicella disease in vaccinated and unvaccinated persons. PCR of oral specimens can sometimes aid in diagnosis of varicella disease, even after rash resolves.