Chickenpox laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Michael Maddaleni, B.S.
Overview
- Diagnosis of Chickenpox is usually based upon signs and symptoms of the affected individual.
- Laboratory tests are not routinely used to diagnose active cases of chickenpox and shingles, which are caused by the varicella zoster virus (VZV).
- Children are nowadays vaccinated and most adults generally may have been infected with VZV in their early years.Hence, general population screening is not done usually. Anyhow, testing for VZV or for the antibodies produced in response to VZV infection may be performed in when required for screening purposes.
- Also, screening may be advised for newborns, pregnant women, prior to organ transplantation, and in those with HIV/AIDS.
- Testing may be used to:
- Determine if someone has been previously exposed to VZV either through past infection or
- Vaccination and has developed immunity to the disease
Laboratory Findings
- Laboratory tests can help confirm the diagnosis, if needed. They are:
- Antibody Testing
- Viral detection
- VZV DNA testing
- Direct Fluorescent Antibody (DFA)
- VZV culture
Antibody Testing
- When an individual is exposed to VZV, their immune system responds by producing antibodies to the virus. Laboratory tests detect and measure the level of two classes of VZV antibodies in the blood namely IgM and IgG.
IgM
- First antibodies to be produced in response to the infection.
- Can be detected within a week or two post exposure.
- The levels of IgM antibodies rises for a short period of time and then falls below detectable levels.
- Post-Infection, in the future, the IgM levels rise only when the latent VZV is reactivated.
IgG
- Produced several weeks after the initial exposure.
- IgG levels rise during active infection and then the levels become stable as the VZV infection gets resolves and as the virus gets inactivated.
- Provides Long-Term protection
Viral detection
- Viral detection is done by finding VZV in a blood, vesicle fluid, or tissue sample. Detection done by culturing the virus or by detecting it's genetic material (VZV DNA).
VZV DNA testing
- Performed to detect VZV genetic material in a person's sample. This method is sensitive. It can identify and measure the amount of the virus.
Direct Fluorescent Antibody (DFA)
- DFA test visualizes the presence of VZV in the cells taken from an individuals's skin lesion using a special microscope and labeled antibody. Advantages of DFA test are that it is rapid, but less specific and sensitive than DNA testing.
VZV culture
- Culture is not very reliable for VZV and can lead to false-negative results.
The choice of tests and samples collected depends on the person, their symptoms, and on the healthcare practitioner's clinical findings.
Determining Chickenpox Susceptibility
IgG ELISA
- Whole infected cell (wc) ELISA is the most commonly used test to determine if a person has antibodies to VZV from past varicella disease. Wc ELISA is done on blood samples. It can readily detect seroconversion to a natural infection with VZV. However, it is not sensitive enough to detect all seroconversions after vaccination. The more sensitive purified glycoprotein ELISA (gpELISA) or fluorescent antibody to membrane antigen (FAMA) tests have been used in research settings to detect seroconversion after vaccination. However, these are not available commercially.
IgG Avidity
- IgG avidity has been used in research settings to determine if a person who is IgG positive for VZV was infected with the virus in the past or more recently. Avidity testing can be used to determine if the most recent VZV rash was due to primary infection (varicella) or reactivation (herpes zoster). People infected in the past tend to have antibodies with high affinity for binding to the antigen compared with people with a more recent infection who have a low affinity. As a result, low avidity is an indicator for VZV primary infection. This test is not available commercially.
Laboratory Confirmation of Vaccine-Adverse Event
- PCR genotyping of skin lesions can be used to distinguish rashes due to wild-type VZV from rashes caused by vaccine type (Oka)-strain VZV. Samples of blood, cerebrospinal fluid, or biopsy specimens may also be tested for vaccine-strain VZV to confirm a vaccine-adverse event. VZV-strain-specific testing is not available commercially; it is available at some laboratories, including the CDC National VZV Laboratory. Examples of possible varicella vaccine-adverse events for which PCR genotyping for VZV can be useful include varicella in a vaccinee 7–42 days after vaccination, herpes zoster in a vaccinee >42 days post-vaccination, and suspected secondary vaccine-strain VZV transmission.
Interpretation of Laboratory Findings
Confirmation of Suspected Varicella
- The most sensitive method for confirming a diagnosis of varicella is the use of PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions). Vesicular lesions, if present, are the best for sampling. Adequate collection of specimens from maculopapular lesions in vaccinated persons can be challenging. However a recent study comparing a variety of specimens from the same patients suggests that maculopapular lesions collected with proper technique can be highly reliable specimen types for detecting VZV.
- IgM testing is considerably less sensitive than PCR testing of skin lesions. Commercial IgM assay may not be reliable and false negative IgM results are not uncommon. A positive IgM ELISA result, although suggestive of a primary infection, does not exclude re-infection or reactivation of latent VZV. Careful clinical evaluation may be needed to determine if a rash is varicella or herpes zoster. Nevertheless, IgM testing is readily available and a positive result from a person with a rash is usually interpreted as laboratory confirmation of varicella. A single positive IgG ELISA result cannot be used to confirm a varicella case.
- Paired acute and convalescent sera showing a four-fold rise in IgG antibodies have excellent specificity for varicella, but are not as sensitive as PCR of skin lesions for diagnosing varicella. Persons with prior history of vaccination or disease history may have very high baseline titers, and may not achieve a four-fold increase in the convalescent sera. The usefulness of this method for diagnosing varicella is further limited as it requires two office visits.
Establishing Laboratory Evidence of Immunity to Varicella
- A positive IgG ELISA result indicates that a person has antibodies to VZV either from past varicella disease history or vaccination. This test cannot distinguish whether the antibodies were from a past episode of varicella or vaccination. It is a fairly sensitive and specific assay. However, none of the currently available commercial assays are sufficiently sensitive to detect immunity in all vaccinated persons.