Varicella
The
Misunderstood Vaccine
Introduction/Review
·
Live, attenuated
Varicella virus vaccine
·
Licensed March 1995 >
12 months of age
·
Secondary attack rates
for this virus may reach 90%
·
Systemic infection,
lifetime immunity, clinical illness after reexposure is rare
·
Wild-type varicella
often leads to reinfection that boosts antibody titers
·
Remains dormant in
sensory-nerve ganglia
·
In children 4-5 days and
is characterized by fever, malaise
·
Generalized vesicular
rash, 250-500 lesions, shawl distribution
·
Primary subclinical
infection with VZV is rare
Epidemiology
·
Transmitted
o
direct contact, droplet, or aerosol from vesicular
fluid of skin lesions
o
secretions from the respiratory tract
o
enters the host through the upper-respiratory tract
·
Incubation period for
varicella is 14-16 days (range 10-21)
·
Incubation period for
varicella is 14-16 days
·
Contagiousness: 1-2 days
before the onset of rash until all lesions are crusted
·
Develops in nearly all
persons who live in the United States
·
33% occurred in
preschool-age children (1-4 years)
·
44% occurred in
school-age children (5-9 years)
·
90% of cases in persons
less than 15 years
·
Rate of complications
higher > 15 years and < 1 year
o
Skin lesions (virulent strains of group A
streptococci)
o
Pneumonia, dehydration, encephalitis, hepatitis
o
Reye syndrome unlikely if asa is avoided
·
Decrease in morbidity
o
the substantial reduction in cases of Reye syndrome
o
the availability of acyclovir
o
selective use of VZIG
o
improvements in supportive care
o
the risk for death increases with age
Prenatal
and Perinatal Exposure
·
Intrauterine VZV
infection
o
Congenital Varicella syndrome
o
Clinical newborn Varicella
o
Clinical zoster (infancy/early childhood)
·
Congenital varicella
syndrome
o
13-20 weeks' gestation: low birthweight, cutaneous
scarring, limb hypoplasia, microcephaly, cortical atrophy, chorioretinitis,
cataracts, and other anomalies
·
Clinical newborn
Varicella
o
5 days before to 2 days after delivery
o
infection in an estimated 17%-30%
o
exposed to VZV without sufficient maternal antibody to
lessen the severity
o
risk for death: 31% among infants whose mothers had
onset of rash 0-4 days prepartum
Nosocomial
Transmission
o
Patients @ high risk for severe disease and
complications
o
premature infants born to susceptible mothers
o
infants less than 28 weeks' gestation or less than or
equal to 1,000
o
immunocompromised persons of all
o
Managing Outbreaks
o
Isolating patients and susceptibles
o
controlling air flow
o
using rapid serologic testing
o
furloughing or screening exposed
o
temporarily reassigning susceptible personnel
Herpes
Zoster
o
VZV persists in a latent form in sensory-nerve ganglia
o
latent virus can be reactivated
o
15% of the population will experience herpes zoster
o
immunocompromised persons and the elderly
o
transmission of VZV from herpes zoster is much less
than that from primary Varicella
VARICELLA
ANTIBODY TESTING
o
adults who have negative histories are seropositive
(71%-93%)
o
levels of antibody acquired from vaccination are lower
o
complement fixation (CF) – least sensitive, most
widely used
o
Sensitive but usually impractical for clinical use
§
indirect fluorescent
antibody (IFA)
§
radioimmunoassay (RIA)
§
fluorescent antibody to
membrane antigen (FAMA)
§
neutralization (N)
o
indirect hemagglutination (IHA)
o
immune adherence hemagglutination (IAHA)
o
latex agglutination (LA)
§
not sensitive enough
o
enzyme-linked immunosorbent assay (ELISA)
§
not commercially
available YET
ACYCLOVIR
FOR THE TREATMENT AND PREVENTION OF Varicella
o
synthetic nucleoside analog
o
1992: FDA approved acyclovir for otherwise healthy
children
o
Beneficial clinical effects
o
Decrease in the number of days in which new lesions
appeared
o
The duration of fever
o
The severity of cutaneous and systemic signs and
symptoms
o
Difficult to say if complications were decreased
o
Antibody titers were the same
o
Not enough benefit to justify the cough
o
Primary indication: adolescents in households of infected
children
o
Category C in the FDA use-in-pregnancy rating
o
(risk cannot be ruled out, but potential benefits may
justify the possible risk)
o
Prophylactic use of acyclovir
o
Prevent/modify clinical disease in most cases, some
remained susceptible
LIVE, ATTENUATED
VARICELLA VIRUS VACCINE
o
Oka strain isolated in Japan in the early 1970s
o
Sequential propagation in cultures, a total of 31
passages
o
Licensure was extended to healthy children in 1989
o
Contains: hydrolyzed gelatin, trace amounts of
neomycin and fetal bovine serum, sucrose, and residual components of MRC-5, but
no preservatives
o
Aprox 10,000 volunteers received it in trials
Immunogenicity
o
Seroconversion rate was demonstrated to be 97% (.3 U)
o
76% of these children achieved antibody titers to 5 U
o
Persistence of antibody was consistently high (i.e.,
greater than 90%)
o
7-10 years
post immunization titers: comparable to those in children who had natural
varicella infection 7-10 years earlier
o
20-year follow-up study revealed that antibody levels
were higher than those observed 10 years earlier
o
> 13 years: 78% seroconverted after the 1st
dose and 99% seroconverted after a 2nd
Efficacy
and Breakthrough Infections
o
Efficacy and Breakthrough Infections
o
Breakthrough infections following exposure to wild-type
virus
o
Efficacy among children 1-14 years
o
100% after the first varicella season and
o
96% after the second season
o
9 years Post vaccination: varicella developed in less
than 1%-4.4% of vaccines/year
o
Substantially less severe among vaccinated persons
than unvaccinated persons
o
Usually afebrile and < 50 lesions
o
Rate of disease transmission from vaccinees in whom
varicella develops is low
o
Insufficient data to evaluate the extent of the
protection provided by varicella vaccination against serious complications
o
Current research has not been affected by wide use of
the vaccine
o
The extent to which the protection provided by
vaccination has been increased by boosting from exposure to natural virus is
unknown
o
Whether longer term immunity may wane as the circulation
of natural VZV decreases is unknown
Transmission
of Vaccine Virus
o
immunocompromised and associated with occurrence of
rash
Herpes Zoster Following Vaccination
o
incidence after varicella vaccination: 18 per 100,000
person years
o
incidence after natural varicella infection among
healthy children was 77 per 100,000 person years.
o
2 studies
o
protective efficacy was greater than or equal to 90%
when children were vaccinated within 3 days of exposure.
Cost
Benefit of Vaccine
o
When only direct medical costs were considered, the
benefit-cost ratio was 0.90:1
DISTRIBUTION,
HANDLING, AND STORAGE OF VACCINE
o
Stored frozen at an average temperature of less than
or equal to 5 F
o
Small, dormitory-style refrigerators may not meet
temperature requirements
o
Discarded if not used within 30 minutes after
reconstitution
RECOMMENDATIONS
FOR THE USE OF VARICELLA VIRUS VACCINE
o
Persons less than 13 Years of Age
o
12 months-12 years of age: one 0.5-mL dose of vaccine
subcutaneously
o
Children who have a reliable history of varicella are
considered immune
o
Vaccine is well tolerated in seropositive persons
o
12-18 Months of Age
o
administered to all children at this age, regardless
of history
o
at the same time as measles-mumps-rubella (MMR) vaccine
o
separate sites and with separate syringes
o
Persons greater than or equal to 13 Years of Age
o
two 0.5-mL doses of vaccine, subcutaneously, 4-8 weeks
apart
o
serologic testing before vaccination is likely to be
cost effective for adolescents
VACCINE-ASSOCIATED
ADVERSE EVENTS
o
injection site: only significant adverse
o
pain/soreness, swelling, erythema, rash, pruritus,
hematoma, induration, and stiffness
o
nonlocalized, varicella-like rash
o
Febrile seizures
CONTRAINDICATIONS
AND PRECAUTIONS
o
Neomycin or gelatin allergy
o
Failure to vaccinate children with minor illnesses can
impede vaccination efforts
o
Not recommended for persons who have untreated, active
tuberculosis
o
Malignant condition, including blood dyscrasias,
leukemia, lymphomas of any type, or other malignant neoplasms affecting the
bone marrow or lymphatic systems
o
Primary or acquired immunodeficiency
o
Conditions That Require Steroid Therapy
o
2 mg/kg of body weight or a total of 20 mg/day of
prednisone
o
Withholding steroids for 2-3 weeks following
vaccination when possible
o
Administration of immune globulin (IG) on the response
to varicella virus vaccine is unknown
o
immunocompromised person is inadvertently exposed to a
person who has a vaccine-related rash, VZIG need not be administered
o
Avoid using salicylates for 6 weeks
o
Nonpregnant women who are vaccinated should avoid
becoming pregnant for 1 month
o
Varicella virus vaccine may be considered for a
nursing mother
Chickenpox
The Misunderstood Vaccine
Varicella (chickenpox or VZ) is a disease that
has a mild reputation that it does not deserve. Yuppies and Generations
X-ers have had “chickenpox parties” to intentionally expose their children to
an infected child “to get it over with”. True enough, the disease is
generally mild and self-limited. Chickenpox is not the scourge of the modern
age.
However, VZ is a herpes virus and is a successful and complex organism, which modulates the immune system. This decreases the body’s ability to fight infections normally for a variable period of time. It is not unusual to have lesions on all mucosal surfaces (i.e. eye, mouth, nose, ear, rectum, and vagina) and to have secondary bacterial infections. Dehydration, pneumonia, infection of the brain tissue and balance organs is also common. The skin lesions can develop into disfiguring scars. 50 -100 deaths per year occur in the US in normal children secondary to VZ. The annual cost of caring for children of normal health who contract chickenpox was $918 million in1993 (mostly missed work). You do not want to hear about the uncommon complications.
On
the other hand, Varicella vaccine is an immunization that has a bad reputation
it doesn’t deserve. The urban myth surrounding the vaccine actually
carries within it a kernel of truth. It is true varicella is a disease process
that is worse in individuals less than one year of age greater than 15
years. Avoidance of vaccination is based on the idea that if the immunity
from vaccination wanes he/she will acquire more severe disease as an adult than
he/she would as a child.
The
vaccine has been used in Japan and Korea since 1988 with excellent
success. The studies in the U.S on duration of response to the vaccine
are ongoing. However, these studies indicate immunity appears to be long
lasting and is probably permanent in the majority of patients. A booster may be
required but that is being discovered that may be true for many vaccines. As to
complications, the rule of thumb throughout all the literature is that the vaccine
organism is much less likely to cause problems than the wild or “natural”
infection.
The CDC and the American Academy of Pediatrics recommend it. Some
physicians hesitate to give it because it means more injections.
Financially and scientifically this is the best advice we can give you for your
child at this time.
To restate the case above: the bug has a good reputation it does not deserve,
the vaccine has a bad reputation it does not deserve. Talk to your doctor about
the chickenpox vaccine.
|
Northeast Indiana Pediatric Specialists, PC |
|
Dr. Michael Dick & Dr. Todd Dillon nips@med-web.com |