While the epidemiology and clinical presentation of varicella disease have changed dramatically post-vaccine implementation,1
our results suggest that management of varicella cases in the outpatient setting is still mostly based on clinical judgment, at least in our area. After implementation of the second dose of the varicella vaccine, further declines in varicella incidence were reported.17
However, elimination is not expected, and outbreaks have occurred in populations with high two-dose coverage.14
Pockets of susceptible individuals in the population remain for various reasons, including limitations on administration of live-virus vaccines to some immunocompromised individuals, erroneous perception of varicella being a relatively benign disease, religious or philosophical objections to vaccination, and residence in institutional facilities from a young age.18
We advocate for increased awareness regarding the use of available laboratory tests for varicella. An effort to educate physicians on the importance of laboratory confirmation of potential breakthrough varicella cases is crucial as, frequently, its nonspecific appearance can be confused with other rashes of noncommunicable diseases.6,9,10
As with other exanthematous vaccine-preventable diseases (e.g., measles and rubella) that are now rare in the United States and with clinical presentation modified by immunization, we believe that clinical identification alone for breakthrough varicella is not reliable. We suspect that the diagnostic challenge is even greater for younger physicians who train in the post-vaccine era and rely mostly on textbook descriptions of vaccine-preventable viral exanthems. Our study shows that physicians practicing for #5 years are not as likely to test for breakthrough varicella as physicians with .5 years of practice, even when an exposure to varicella is provided in the history. Although one could expect that younger physicians would have less trust in their clinical judgment in making the diagnosis and be more prone to test, we speculate that many might have a low index of suspicion for breakthrough varicella.
Survey participants were not alerted to a diagnosis of VZV by the description of the rash as maculopapular even though a lack of vesicles and predominance of maculopapular lesions have been described with breakthrough varicella in both clinical trials and post-varicella vaccine licensure studies.3,4,6,8,9
While a clear exposure history to VZV prompted most HCPs to consider breakthrough varicella, it is doubtful that exposure information would be available in daily practice, as most source cases would also have a modified clinical appearance and may not be recognized as varicella. The contagiousness of breakthrough varicella is lower than varicella in unvaccinated individuals, depending also on the number and type of lesions, but can still be spread to close contacts.19
In addition, exposure to herpes zoster may go under recognized because there is only moderate awareness that herpes zoster is contagious via airborne droplets and not only from direct contact with skin lesions.18,20–22
There is no doubt that various causes of maculopapular rashes exist and some of them are noninfectious. While it is not feasible to test every patient with a maculopapular rash for a variety of reasons, we believe that once varicella is suspected, one should test to confirm the diagnosis, because of the related public health implications.
The survey results indicate that there is uncertainty about which test should be selected for laboratory confirmation of breakthrough varicella. Three different tests were equally popular among clinicians for this purpose (): direct fluorescent antibody (DFA), polymerase chain reaction (PCR), and serology (comparison of acute and convalescent immunoglobulin G [IgG] titers). DFA has been used to diagnose varicella and differentiate it from herpes simplex-related rashes, but its performance relies on adequate specimen collection, and it is also less sensitive than PCR.23
PCR is both highly sensitive and specific and has recently been recognized as the test of choice for diagnosing breakthrough varicella.23,24
Measurement of serum IgG antibody against varicella is only useful to provide proof of immunity to natural infection and does not have adequate sensitivity to detect change in IgG antibody titer of vaccinated individuals after breakthrough varicella.25
The limited availability of the PCR test for varicella may explain in part the fact that many HCPs did not select PCR as their first-choice test. We believe that PCR for varicella should be made readily available so that HCPs are encouraged and empowered to laboratory confirm suspected cases, as it is taught with other vaccine-preventable diseases and diseases with public health consequences. As a component of their bioterrorism preparedness programs, state public health laboratories were given the capability to test for varicella along with the necessary training, as varicella is the first diagnosis in the differential for smallpox.26
Although a specific funding mechanism will be needed to support the continued use of VZV laboratory services, having these public health laboratories process specimens collected to rule out breakthrough varicella may provide a solution and facilitate diagnosis and management. Use of these laboratory services on a regular basis could also help the technicians in these laboratories maintain skills related to testing for orthopoxviruses. While PCR is a relatively costly test, control of outbreaks resulting from missed diagnoses is also very labor- and resource-intensive. A cost-benefit analysis was outside the scope of this study but should shed some light on the use of PCR as a confirmatory test in the future.
Notably, 28% of the clinicians would not advise a patient's family on school attendance when a child has an exanthematous illness. The reluctance of the survey participants to weigh in on school attendance is corroborated by the fact that most would not report a possible case of varicella to a public health agency and would not notify the school. Physicians' underreporting of communicable diseases to public health agencies has been documented previously.27
We believe there is significant lack of recognition on the important role primary HCPs can play in protecting and promoting public health. By notifying public health agencies, outbreaks can be prevented and contained, and individuals at greater risk for morbidity and mortality can be protected. We advocate that suspicion of breakthrough varicella should prompt physicians to report their suspicion to public health, conduct a confirmatory test, and offer counseling on containment strategies until the test rules in/out the diagnosis, as is the case for other vaccine-preventable diseases (e.g., measles and pertussis).
Our study had certain limitations. We surveyed a small subset of HCPs in Philadelphia, and results may not be generalizable to other areas. Because West Philadelphia has been an active surveillance site for varicella and zoster for several years, we would have expected greater awareness and knowledge about optimal management of breakthrough varicella cases than would be found in other locations. While the responses provided by HCPs in the survey might not reflect their actual actions in daily practice, the testing history and the survey responses of these practices seem consistent. We performed analysis on HCP responses without controlling for the effect of providers working in the same practice. A cost analysis to determine cost-effectiveness of the use of PCR as the confirmatory test for suspected varicella cases was beyond the scope of this study.