Varicella-Zoster Virus: An Ounce of Prevention Does Not Equal a Cure

The impact of varicella-zoster virus vaccination programs on the US population is not yet clear.

Varicella-zoster virus (VZV), a herpesvirus, is one of the 8 strains of herpesvirus known to infect humans. VZV causes varicella (chickenpox) and herpes zoster (shingles).¹ Despite the relatively recent advent of vaccines for both chickenpox and shingles, the overall incidence of shingles is on the rise.²

Chickenpox

Primary infection with VZV causes the development of chickenpox, which is highly contagious and predominantly affects children. Chickenpox is characterized by a vesicular rash, fever, and malaise. Most children become infected with VZV between 5 and 10 years of age. The rash can develop into as many as 250 to 500 itchy blisters over the entire body, usually lasting for 5 to 7 days. The blisters then crust over and heal with scabs. The rash may spread to the oral cavity or other internal parts of the body; however, the illness is usually benign and not severe.^1,3

Prior to approval of the varicella vaccine (Varivax, Merck & Co, Inc) by the FDA in 1995, there were about 4 million cases of chickenpox per year (incidence rate: 15 cases per 1000 individuals) in the United States. Chickenpox was common. By adulthood, more than 90% of Americans had been infected by VZV.¹

Persons born in the United States prior to 1980 are considered to be immune to VZV infection because prevalence of it was previously so high. Since introduction of the varicella vaccine, the number of yearly chickenpox cases has decreased to only a few hundred. In 1996 and 1999, the Advisory Committee on Immunization Practices (ACIP) initially recommended a single dose of the varicella vaccine for children 12 to 18 months of age and 2 doses for susceptible adults and adolescents who have close contact with persons at high risk for serious complications and/or those at high risk of exposure. These recommendations were updated in 2007 (Online Table 1) and now suggest administration of a first dose of the varicella vaccine in children 12 to 15 months of age, and a second dose at 4 to 6 years of age. Two doses are still recommended for adolescents and adults, now including all patients without evidence of immunity. Although people who receive the varicella vaccine can sometimes develop breakthrough chickenpox, the presentation is usually mild, with 50 or fewer red bumps that rarely evolve to blisters.¹

Table 1: Summary of Recommendations of the Advisory Committee on Immunization Practices for Prevention of Varicella—United States¹

Category

1996 Recommendations

1999 Recommendations

2007 Recommendations

Routine childhood schedules

1 dose recommended at 12—18 mo of age

No change

2 doses recommended:

· first dose at 12—15 mo of age;

· second dose at 4—6 y of age

Adults and adolescents 13 y and older

2 doses, 4—8 wk apart

2 doses, 4—8 wk apart

2 doses, 4—8 wk apart

Recommended for susceptible persons who have close contact with persons at high risk for serious complications:

· health care workers;

family contacts of immunocompromised persons

Should be considered for susceptible persons at high risk for exposure:

· persons who live or work in environments in which transmission of varicella-zoster virus is likely (eg, teachers of young children, child care employees, residents and staff members in institutional settings);

· persons who live and work in environments in which transmission can occur (eg, college students, inmates and staff members of correctional institutions, military personnel);

· nonpregnant women of childbearing age;

· international travelers;

· desirable for other susceptible adolescents

No change

Recommended for all adolescents and adults without evidence of immunity

Shingles

Long after the rash associated with chickenpox disappears or varicella vaccination is received, the VZV lies dormant in the body, hiding in the nerve cells along the spinal cord. The latent virus can reactivate years or decades later, presenting as shingles. This secondary infection is marked by pain and often a blisterlike rash on 1 side of the head, face, limbs, or trunk. Other symptoms can include headache, fever, chills, and upset stomach. The rash and blisters typically scab after 3 to 5 days, but shingles usually lasts for 2 to 4 weeks. Although very painful, most people with shingles recover without serious complications. Very rarely, shingles can lead to pneumonia, hearing loss, bacterial skin infections, scarring, encephalitis, or death. The most common complication is postherpetic neuralgia (PHN), which occurs in about 1 of 5 patients and is associated with severe pain that may last for months or years after the rash has healed.^2,4

Shingles is a fairly common illness that affects about 1 million Americans annually (incidence: 3.2 to 4.1 cases per 1000 individuals), about half of whom are 60 years or older.³ Ninety-five percent of episodes are first occurrences. Although rare, second and third episodes of shingles may develop. It is important to know that shingles cannot be passed from one person to another. However, a person with shingles can infect someone who has not had chickenpox or received the varicella vaccine; these individuals would develop chickenpox rather than shingles.

Only people who were previously infected with the VZV, through either natural chickenpox infection or varicella vaccination, can develop shingles.^2,4

The reasons why the VZV reactivates and causes shingles are not well understood. However, a person’s risk for shingles may increase as the body’s immunity to the VZV declines. This immunity usually wanes with normal aging and with anything that weakens the immune system, such as certain medications, cancers, autoimmune disorders, and infection. Shingles has also been anecdotally linked to stress and trauma.^2,4

The lifetime risk for shingles is about 32%, and it increases to 50% in individuals older than 85 years. Several epidemiologic studies suggest that the overall incidence of herpes zoster is increasing in the United States and elsewhere. This increase appears to be independent of the effect of aging of the population.^2,4 In fact, you may be seeing more young adults contracting shingles. The reasons for this shift are not well understood, but various theories exist.

Reasons for Increased Shingles Incidence

It is thought that the introduction of the varicella vaccine may have altered the dynamics of shingles. More than 90% of American adults have had chickenpox, which generates natural immunity to the VZV.^1,2 After an individual has contracted chickenpox and recovered from it, the individual’s natural immunity also gets asymptomatically “boosted” with age through contact with infected children who are recovering from chickenpox.² Individuals who are repeatedly exposed to chickenpox (eg, health care workers, families with young children) get extra natural immunity, like getting a “booster” vaccination, that helps to extend their protection against shingles. Greater exposure to the VZV lessens the risk for virus reactivation.

Now that the varicella vaccine has eliminated most childhood cases of chickenpox, this natural immunity boost is no longer available. Because younger individuals have been vaccinated, young, unvaccinated adults in their mid-20s and 30s who have had chickenpox are not getting their immunity naturally boosted through exposure to the VZV. This leaves young adults more vulnerable to getting shingles. Because young adults are generally healthy, shingles is typically less severe and has fewer complications than in older individuals. However, gradual waning of natural immunity may allow for a shingles outbreak at an older age.

Vaccines may have, paradoxically, rendered patients more vulnerable. The Centers for Disease Control and Prevention (CDC) reports that there is no consistent evidence supporting the theory that the incidence of shingles in the United States has been increased by the varicella vaccination program. The CDC continues to study the epidemiology of shingles and to monitor the effects of the US varicella and zoster vaccination programs.^2,4

Prevention and Treatment

The zoster vaccine (Zostavax, Merck & Co, Inc) can boost VZV immunity and prevent shingles outbreaks. FDAapproved in May 2006, Zostavax prevents shingles in 50% of vaccinated individuals and reduces the incidence of PHN by 66%. Although vaccinated individuals may still get shingles, they typically experience a milder case. The ACIP recommends that all adults 60 years and older receive 1 dose of the zoster vaccine, including individuals who have already had an episode of shingles.² In March 2011, the FDA approved the use of the zoster vaccine for the prevention of shingles in individuals 50 to 59 years of age; however, ACIP recommendations for this age group have not yet been determined (Online Table 2).⁵

Table 2: Summary of Recommendations of the Advisory Committee on Immunization Practices for Prevention of Herpes Zoster—United States^2,5

Category

2008 Recommendations

2011 Recommendations

Adults 60 y and older

1 dose

No change

Recommended whether or not the patient reported a prior episode of shingles

Primary treatment for shingles is aimed at decreasing viral replication. Oral antiviral therapy (eg, acyclovir, valacyclovir, famciclovir) is the mainstay of treatment and should be initiated within the first 72 hours following diagnosis. These medications help reduce the length and severity of the illness.²

Conclusion

For the first time in history, a generation is growing up vaccinated against chickenpox, a childhood disease that had once affected more than 90% of Americans.¹ Now that US children are routinely vaccinated against varicella, it is becoming less common for adults to receive an immune boost from contact with children infected with chickenpox. Despite various theories, the impact of VZV vaccination programs on the US population is not yet clear, and likely will not be for another 30 to 40 years, when the younger vaccinated population first reaches middle age.

This subject must be brought to light. As a health care provider, you often encounter patients who inquire about the benefits of vaccination. You can confidently inform them that Zostavax is recommended for use in patients 60 years and older to prevent shingles. Zoster vaccination represents the best means of decreasing disease burden from shingles in this older adult population, who are at highest risk for complications.⁴ Even patients who have had shingles can receive Zostavax to help prevent future occurrences of the disease.

Karen Smith received her PharmD from Albany College of Pharmacy in Albany, New York, and completed a primary care specialty residency at Veterans Affairs (VA) Maryland Health Care System in Baltimore, Maryland. Dr. Smith is an active member of American Society of HealthSystem Pharmacists, The American College of Clinical Pharmacy, and the American Society of Consultant Pharmacists and has completed the Geriatrics Scholars Program offered by the VA Geriatric Research, Education & Clinical Center (GRECC). She currently holds certification in geriatric pharmacy and is board certified in ambulatory care pharmacy.Dr. Smith has been a clinical pharmacy specialist at VA Hudson Valley Health Care System for 9 years and currently manages the anticoagulation, diabetes, and primary care clinics at the Castle Point Campus and Goshen, Port Jervis, and Monticello community-based outpatient clinics. She also serves as the PGY1 pharmacy residency and PGY2 ambulatory care residency program director and anticoagulation coordinator, and she precepts pharmacy students from Albany College of Pharmacy and Health Sciences, St. John’s University College of Pharmacy & Allied Health Professions, St. John Fisher College Wegmans School of Pharmacy, and Duquesne University Mylan School of Pharmacy.

References

• Marin M, Güris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(04):1-40.
• Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(05):1-30.
• Centers for Disease Control and Prevention. Update on herpes zoster vaccine: licensure for persons aged 50 through 59 years. MMWR. 2011;60(44):1528.
• CDC website. Shingles clinical overview. www.cdc.gov/shingles/hcp/clinical-overview.html. October 23, 2012. Accessed August 22, 2013.
• National Foundation for Infectious Disease. Facts about chickenpox and shingles for adults. www.nfid.org/publications/factsheets/varicellaadult.pdf. Published August 2009. Accessed August 22, 2013.