DISSEMINATED RASHES AND VARICELLA VACCINE

Abstract

IN REPLY: Our report stated that “All of 57 vaccinees with breakthrough varicella, clinically diagnosed on the basis of a generalized maculopapular or vesicular rash had wild-type VZV [varicella-zoster virus] infection based on analysis of viral DNA. 1 The Oka vaccine strain of VZV was not identified in any of these cases.” This statement should be amended to say that, “All of 57 vaccinees with breakthrough varicella, clinically diagnosed on the basis of a generalized maculopapular or vesicular rash, in which there was amplifiable DNA had wild-type VZV infection based on analysis of viral DNA.” In fact there were also 36 samples that were VZV PCR-negative and 19 samples that were inadequate. The VZV-negative samples gave negative results by PCR for VZV but were positive for a 268-bp fragment of the human beta-globin gene, indicating that there was amplifiable DNA in the sample. We believe these to be true VZV negatives. The sensitivity of the assay as determined by serial dilution of extracted VZV wild-type and vaccine strain VZV DNA was ≥100. 1 The inadequate samples gave negative results by PCR for both VZV and beta-globin, indicating that there was not even enough DNA to amplify a human gene present in multiple copies in each human cell. We would not agree that assay sensitivity is the problem in these inadequate samples; rather it is the adequacy of sample collection that determines whether there is enough DNA to amplify. If PCR assay sensitivity was the cause of the failure to find the vaccine strain in samples from disseminated rashes in vaccinees, we would have expected even less success in identifying the vaccine strain in samples from zoster lesions which in general are less likely to be vesicular. We were, however, able to identify the vaccine strain in 22 of 32 VZV PCR-positive samples from zoster lesions. In addition even in 9 leukemic children who were vaccinated while receiving chemotherapy and later developed a varicella-like rash, we have only been able to document the wild-type virus as the cause of the rash. Even in these highly immunocompromised children, we were not able to document the vaccine strain as the cause of these rashes. The point of the data presented was that by the most sensitive technique available, we have never been able to find the vaccine strain in a disseminated varicella-like rash in a vaccinee outside of the period when vaccine-associated rash is seen (<42 days postvaccination). Although it is possible that clinical reactivation of the vaccine strain virus could cause disseminated varicella-like rash, we have not been able to document it to date. Philip LaRussa, , M.D. Anne A. Gershon, M.D.