Varicella Immunity and History of Infection

1. Varicella Immunity and History of Infection Maryellen E. Gusic MD Assistant Professor of Pediatrics Penn State Children’s Hospital

2. Introduction • Immunization against varicella is recommended for susceptible, immunocompetant children over the age of 12 months. • A reliable history of naturally occurring infection is considered to be evidence of immunity.

3. Introduction continued • Infection rarely occurs without the development of characteristic skin lesions. • Parents are usually able to report a history of varicella infection in their child.

4. Introduction continued • Varicella immunity requires • development of specific antibodies • stimulation of cell mediated immunity • Immune status of a child can be determined by measuring specific IgG immunoglobulin levels.

5. Introduction continued • Varicella in infants • A modified specific antibody and cell mediated immune response has been described. • mild infection • effect of transplacentally acquired antibodies

6. Introduction continued • Natural infection is thought to provide life long immunity. • Reinfections are observed in healthy children. • inaccurate diagnoses? • modified antibody and/or cell mediated immune response?

7. Our Study • Hypotheses • Children infected with varicella early in life may have a modified immune response to infection and remain susceptible to reinfection. • Children whose infection was clinically mild, may not have developed protective antibody titers and thus also remain susceptible to reinfection.

8. Objectives • To identify children with a history of natural infection whose illness occurred before 1 year of age • To identify children whose infection would be classified as mild or moderate by determining the number of skin lesions present during the illness

9. Objectives continued • To determine if children with a history of natural infection before 1 year of age or with mild or moderate infection have protective antibody titers • To determine if further questions to describe the skin lesions present aid in supporting the “reliability” of the history of infection

10. Methods • Children with a history of varicella infection identified by chart review and by parental questioning at clinic visits were included. • Children with a known immunodeficiency were excluded. • A varicella questionnaire was completed.

11. Methods continued • Varicella questionnaire • patient’s current age • age at which varicella infection occurred • infection diagnosed by parent or health care professional • description of illness • vesicular, itchy, number of lesions

12. Methods continued • Finger stick blood samples were obtained for those children whose infection occurred before one year of age or who had less than 250 lesions during their infection. • Serologic testing for anti-VZV IgG antibodies was performed by the National VZV Lab at the CDC.

13. Methods continued • Serologic testing • ELISA assay for anti-VZV IgG antibodies • Results recorded as mean adjusted OD reading and by objective rating • 0.166 and above positive • Equivocal results retested at lower serum dilution

14. Methods continued • Odds ratios were determined and a Chi square analysis was performed on the data. • Research was approved by the Institutional Review Board of the Hershey Medical Center and the Penn State University College of Medicine.

15. Results • 32 patients were enrolled in the study • 11 children had <50 lesions • 21 children had moderate infection • 17 children were infected before 1 year of age • 5 children whose infection occurred before 1 year of age had mild infection • No child whose infection occurred before 1 year of age had >250 lesions

16. Results continued • 30 patients underwent serologic testing • 4 patients had negative antibody titers • 6 patients had equivocal serologic results

19. Conclusions • Children with a history of mild varicella infection should be evaluated to determine if they have protective antibody titers. • An immunocompetant child aged 12 months or older who has negative antibody titers should be immunized against varicella zoster virus.

20. Conclusions continued • Determining if the rash associated with the infection was itchy may further support the reliability of the diagnosis. • Both parents and health care professionals may incorrectly identify an illness as varicella.

21. Limitations of this Study • Power of study limited by the small number of patients enrolled • Results dependent upon parental reporting of age of infection, symptoms of disease • Negative serologic titers may be result of inaccurate diagnoses

22. Implications for Future Research • Studies are needed to determine the factors that may interfere with the development of life long protective immunity to varicella infection. • Further studies identifying the clinical signs and symptoms that ensure the accuracy of diagnosing varicella have important public health considerations.

23. A Special Thanks to... • Dr. Scott Schmid and the National VZV lab at the CDC • Beth Anne Nagy, MS II, Penn State College of Medicine • David Mauger, PhD, Department of Health Evaluation Sciences, Penn State College of Medicine