Varicella Vaccine: Clinical Description

SECTION TWO: Licensed vaccines
37
Varicella vaccine
Anne A. Gershon
Michiaki Takahashi
Jane F. Seward
The varicella-zoster virus (VZV) causes two diseases, vari-

cella (chickenpox) and herpes zoster (HZ, shingles). Infection Clinical description
with VZV (varicella) in temperate climates where vaccina-
tion is not used approaches 100% by the fourth decade of
life. Whereas varicella may be mild in some people, epidemi- Varicella (chickenpox)
ologic studies indicate that there is significant morbidity and
VZV is transmitted by the airborne route.1517 Although less
some mortality with primary infection in previously healthy
readily transmitted than measles, it is highly contagious, with
persons. The live attenuated varicella vaccine (Oka strain)
secondary attack rates in susceptible household contacts rang-
was developed by Takahashi in 1974,1 and it was licensed
ing from 61% to 100%.1821 VZV also can be transmitted to
in Japan in 1986. Varicella vaccine was licensed for routine
susceptible persons from patients with HZ, although studies
use in childhood in the United States in 1995. Monovalent
suggest that the risk of viral transmission is considerably less
varicella vaccines are licensed and available throughout the
from HZ than from varicella. In a household study, 16% of
world for the prevention of infection in healthy children,
71 susceptible children younger than 15 years exposed to HZ
adolescents, and adults. Combination vaccines for the pre-
developed varicella, a risk approximately five times lower than
vention of measles, mumps, rubella, and varicella were
that from varicella.22 In a small day-care study, a 3-year-old with
licensed in the United States in 2005. Progress has been
HZ transmitted varicella to about 30% of susceptible children.23
made in understanding the pathogenesis of HZ, and a large
collaborative clinical trial has demonstrated the effective-
Immunocompetent children and adults
ness of vaccination of the elderly for preventing HZ and its
major complication, postherpetic neuralgia. All VZV vac- Patients with varicella typically have a generalized vesicular rash
cines available worldwide are the Oka strain; the vaccine concentrated on the head and trunk, and fever. In the immu-
used to prevent zoster contains at least 14 times the amount nocompetent person, malaise and fever may occur 1 or 2 days
of virus as the vaccine to prevent varicella.2 This chapter before rash onset, but more commonly these symptoms occur
focuses on varicella vaccine; a later chapter discusses zoster concurrently with the appearance of the rash, a major differenti-
vaccine. ating feature from smallpox (Figure 37-1).2426 The rash appears
in crops; each crop usually progresses within less than 24 hours
from macules to papules, vesicles, pustules, and finally crusts.
New lesions occur in crops over the next few days, with various
Historical aspects stages of healing. The lesions are pruritic and may scar.
The average number of skin vesicles ranges from 250 to
Historically, varicella and smallpox were often confused; in 500 in otherwise healthy children.20,27 The height of the fever
1767, Heberden clinically differentiated them. Numerous stud- usually parallels the extent of rash, and the subject is usually
ies followed in which investigators induced varicella in volun- ill for 5 to 7 days. The rash has a central distribution, with a
teers by inoculation with vesicular fluid or exposure to patients concentration of lesions on the trunk, scalp, and face. Second
with either varicella or HZ. They showed that varicella is an cases of varicella can occur in immunocompetent persons, but
infectious disease (1875),3 the two diseases are caused by the their incidence is unknown.2832 It is hypothesized that the avid-
same agent,46 and HZ is probably the result of reactivation of ity of VZV antibodies is lower in persons who develop second
an agent acquired earlier in life.7 The virus was isolated in cell cases than in those who do not.31 Another possibility is that
culture by Weller and Stoddard in 1952,8 from vesicular fluid VZV temporarily subverts the immune system by immune eva-
from varicella patients. Later studies indicated that the viruses sion.3335 Subclinical reinfection with VZV also occurs.3638
isolated from subjects with varicella and HZ are morpholog- Varicella in otherwise healthy children is usually not severe,
ically and serologically identical, and the virus was named but the disease has a wide variety of infrequent extracutaneous
VZV.911 manifestations or complications.39 These include pneumonia,
Molecular studies showed the restriction endonuclease pat- encephalitis, cerebellar ataxia, arthritis, appendicitis, hepa-
terns of viral genomes from subjects with varicella and subse- titis, glomerulonephritis, pericarditis, and orchitis.4043 The
quent HZ,12 as well from vaccine recipients with subsequent most common complication in children is secondary bacterial
HZ,13,14 to be identical, proving that HZ is caused by reactiva- infection.40,42 Staphylococci or group A beta-hemolytic strepto-
tion of latent VZV. cocci are the usual causative pathogens. Group A streptococcal

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SECTION TWO: Licensed vaccines

The varicella-zoster virus (VZV) causes two diseases, vari-

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