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