News & Views — Varicella After 25 Years of Chickenpox Vaccine: Test Yourself

The varicella vaccine was introduced in the U. S. in 1995, but this vaccine was not something that was always a public health priority. Chickenpox was generally considered to be a childhood rite of passage with essentially all children being immune by young adulthood. An estimated 4 million cases occurred annually. Most were not severe, but some were. Each year, varicella caused 10,000 to 14,000 hospitalizations and about 150 deaths.

But it was something other than these hospitalizations and deaths that caused support for a varicella vaccine to grow. By the late 1960s, improvements in the treatment of childhood leukemia led to a group of immune-compromised children who, it became clear, were more susceptible to fatal varicella. While an immune globulin treatment had been developed, its use was limited because it had to be started within 96 hours of exposure, which was not always recognized. It was this realization related to immune-compromised children that caused some to consider a potentially important role for varicella vaccine.

However, it was a researcher in Japan, Dr. Michiaki Takahashi, whose efforts ultimately led to a vaccine. Dr. Takahashi announced that he had developed a chickenpox vaccine in 1974, but his choice to use a live, weakened virus for the vaccine was met with resistance from the scientific and medical communities. Two overarching concerns emerged. First, because the natural virus lingers in nerve cells and later reemerges to cause herpes zoster (shingles), using a live virus in the vaccine could potentially cause the same situation. Second, it was unclear how long protection would last after vaccination. Given that adults are at greater risk of severe disease and complications than children, people worried that protection of short duration could leave people susceptible to infection at a time when they were at risk of more severe disease.

But Dr. Takahashi was not to be deterred, continuing to study his vaccine virus in Japan. Five years later, informed by the findings in Japan, scientists in the U.S. recommended moving forward with plans to develop a chickenpox vaccine in this country. The Collaborative Varicella Vaccine Study Group was formed and several studies completed by the mid-1980s answered some of the most pressing questions, clearing the path for testing the chickenpox vaccine in children in the U.S. and Europe. While it was true that the vaccine virus could also live latently in the central nervous system, reactivation events causing shingle from the vaccine were far less frequent and far less severe.

Within eight years of the vaccine’s introduction (2003), coverage was 85%, and severe disease had been reduced by about 90%. However, declines in disease plateaued and small outbreaks continued to occur, leading to the recommendation for a second dose in 2007. By 2020 (25 years after introduction of the vaccine), rates of chickenpox had decreased by about 97% across the whole population and by 99% in those younger than 20 years of age — individuals who had always lived at a time when chickenpox vaccine was available.

To recognize the impact of this vaccine and to assess where things stand with varicella disease, the Journal of Infectious Diseases (JID) published a dedicated issue on November 1, 2022. We thought it would be fun to provide some trivia questions based on the articles in the issue. If you read the articles, the trivia will be a good opportunity for recall, and if you did not, the questions will offer a chance to find out some of what was covered. Have fun!

Questions

Scroll down for answers.

Q. 1: Who is at greatest risk of suffering complications from varicella?

1. Those who are immune compromised
2. Those who are pregnant
3. Adults
4. Infants less than 1 year of age
5. All of these

Q. 2: Which characteristic of the rash is distinct to varicella (pathognomonic)?

1. Redness at the base of the lesions (erythema)
2. Presence of lesions in varying stages of development
3. Superficial nature of lesions (involving only the epidermis)
4. Lesions of varying size

Q. 3: Which is the preferred testing method for confirming varicella?

1. IgM serology
2. IgG serology
3. Viral culture from skin lesions
4. PCR of fluid or scabs from lesions

Q. 4: How much money (“societal savings”) is it estimated that the varicella vaccine program saved in its first 25 years (1996-2020)?

1. $23 billion
2. $13 billion
3. $3 billion
4. $1 billion

Q. 5: In an analysis of varicella-vaccine-associated VAERS reports submitted between 2006 and 2020, six deaths were attributed to the vaccine. What did these patients have in common?

1. All were infants.
2. All were adults.
3. All were immune compromised.
4. All had received one dose.

Answers

A. 1: The answer is E. Each of these groups (immune-compromised individuals, pregnant people, adults older than 20 years of age and infants less than 1 year of age) is more likely to suffer complications from chickenpox.

A. 2: The answer is B. All four answers are characteristic of varicella rashes. However, the appearance of small blisters in crops over a period of three to seven days leads to a rash that has blisters in varying stages of development, and it is this characteristic that sets the rash apart from those caused by other conditions.

A. 3: The answer is D. PCR of fluid or scabs from the blisters is the preferred method for confirming a varicella infection. IgM serology can be detected not only after primary infection, but also after re-exposure events, including reactivation from latency. IgG serology requires waiting two to three weeks to collect samples, thereby hindering treatment and public health response decisions. Although viral culture takes less time, it is still not as fast as PCR (a week versus a day or two), and it is one of the least sensitive methods of detection, often only about 40% to 50% effective when studied. On the other hand, PCR is fast and can detect as few as two to 10 copies of viral DNA in a sample.

Importantly, commercial PCR tests cannot distinguish between wild-type and vaccine-strain varicella; however, laboratories from the CDC and the Association of Public Health Laboratories are equipped to perform this testing.

A. 4: The answer is A. The varicella vaccine program is estimated to have prevented more than 91 million cases of chickenpox; 238,000 hospitalizations; 1.1 million days of hospitalization and almost 2,000 deaths, resulting in an estimated societal savings of $23.4 billion.

A. 5: The answer is C. The deaths following receipt of varicella vaccine all occurred in individuals who were immune compromised due to disease or treatment, and varicella vaccine would have been contraindicated. Two of the patients were infants, one was a teen, and the remaining three were adults. Five of the patients had received the first dose, and one was reported as having received the second dose.

Between 2006 and 2020, almost 133 million doses of varicella vaccine were distributed. About 41,000 reports of adverse events were reported to VAERS, of which 1,664 were classified as serious. The most common adverse events were injection site reactions (31%), rash (28%), vaccination errors (23%), fever (12%) and itchiness/hives (9%).

The most common vaccine administration errors were incorrect storage (60%), administration of wrong vaccine (12%) and use of expired vaccine (8%). Given that vaccine administration errors accounted for almost a quarter of reported events and that the six deaths were in individuals who should not have received the vaccine due to their immune status, these data are a reminder of the importance of having established protocols and safety checks in place when administering vaccines.

Conclusion and resources

We hope you enjoyed the trivia and learning more about the impact of the varicella vaccine program. The trivia only scratched the surface of what was covered in the dedicated issue. Other topics covered included the vaccine pregnancy registry, nosocomial infections, the impact on herpes zoster and more. To view or download the articles, please check out the special issue of JID, or view a CDC slide deck.