This document discusses Varicella-Zoster Virus, which causes chickenpox and shingles. It describes how chickenpox is highly contagious and mainly affects children, while shingles results from reactivation of the virus in nerve ganglia and mainly affects adults and immunocompromised individuals. Complications can be more severe in adults, newborns and immunocompromised patients. Treatment involves antiviral medications like acyclovir to reduce symptoms and duration. Vaccination and immune globulin can help prevent or lessen the disease in high-risk groups following exposure.

2. Varicella-Zoster Virus
Kaveh Haratian,Ph.D.
Medical Virologist
Department of Bacteriology and Virology
School of Medicine
Alborz University of Medical Sciences
Oct 26, 2013

3. Varicella-Zoster Virus
 Varicella (chickenpox)
 acute, highly contagious viral disease with worldwide
distribution
 majority of annual costs*
 80% to 85% of chickenpox : physician visits
 85% to 90% of chickenpox : hospitalization
 most of which are related to productivity losses by
caregivers
 mainly a childhood disease
 5 years of age : infection rate 50%
 12 years of age : infection rate 90%
Health Canada. CCDR 1999;25(S5):1-29.

4. Varicella-Zoster Virus
 mostly a mild disorder in childhood
 tends to be more severe in adults
 It may be fatal
 Neonates
 Immunocompromised persons
 4% to 13% of individuals who had previous varicella
infection : recurrences of varicella-like rash*
 The risk factors
 young age (< 12 months) at first infection
 a milder symptoms at first infection
*Hall S, et al. Pediatrics 2002;109:1068-73.

5. Varicella-Zoster Virus
 Fatality rates for varicella*
 adults 30 deaths/100,000 cases
 infants 7 deaths/100,000 cases
 1-19 yr of age 1-1.5 deaths/ 100,000 cases
 In the United States
 adults account for only 5% of cases but for 55% of
the approximately 100 chickenpox deaths each year
 In Canada, from 1987 to 1996
 70% of the 53 reported chickenpox deaths occurred
in those > 15 years of age.
*Meyer PM, et al. J Infect Dis 2000;182:383-90.
Preblud SR. Pediatrics 1981;68:14-7.

6. The pathogen
 a double-stranded DNA virus
: human herpesvirus-3 subfamily Alphaherpersvirinae
 only one serotype is known
 humans are the only reservoir
 VZV enters the host through the nasopharyngeal
mucosa, and almost invariably produces clinical disease
in susceptible individuals
 Following varicella, the virus persists in sensory nerve
ganglia, from where it may later be reactivated to cause
herpes zoster (Shingles)

7. Transmission
 The virus is transmitted by
 direct contact with the rash
 Airborne respiratory droplets
 vertical transmission (mother to baby) during pregnancy
 can transmit the virus for up to 48 hours before rash
appears and remains contagious until all spots crust over
 little genetic variation
 no animal reservoir
 visceral dissemination of the virus has occurred in 30%
and mortality in 7% to 10% of these patients*
*Feldman S, et al. Pediatrics
1975;56:388.

8. Signs and symptoms
 In healthy children
 the disease is generally mild.
 The illness usually appear 14–16 days after exposure
 Incubation period 10-21 days
 Prodromal symptoms : particularly in older children
 Low-grade fever preceding skin manifestations by 1-2 D
 24-48 hr before rash
 Mild abdominal pain
 Mild cough and runny nose
 Mild headache
 malaise or irritability

9. Signs and symptoms
 red, itchy rash appear first on the scalp, face, trunk
 quickly turn into clear fluid-filled vesicles
 24-48 hr later, clouding and umbilication of lesions
 initial lesions are crusting, new crops form on trunk and
then the extremities
 Characteristics : various stages of evolution
 oropharyngeal, vagina involvement : common
 cornial involvement and serious ocular disease : rare
 the average number of varicella lesion is about 300 lesions
 <10 to >1,500 lesions
 Itching may range from mild to intense

10. Laboratory studies
 unnecessary for diagnosis,
obvious clinically
 Immunohistochemical staining of skin lesion scrapings
can confirm varicella
 A Tzanck smear : multinucleated giant cells
 useful for high-risk patients who require rapid
confirmation
 not sufficiently sensitive or specific for varicella
 more specific immunohistochemical staining of such
scrapings, if available
 Immunoglobulin M tests : not reliable, positive results
indicate current or recent VZV activity
Redbook27th Ed;2006;711-725.

11. Immune response
 Natural infection induces lifelong immunity to clinical
varicella in almost all immunocompetent persons
 Newborn babies of immune mothers are protected by
passively acquired antibodies during their first months of life
 Temporary protection of non-immune individuals can be
obtained by injection of varicella-zoster immune globulin
within 3 days of exposure
 The immunity acquired in the course of varicella prevents
neither the establishment of a latent VZV infection, nor the
possibility of subsequent reactivation as zoster.

12. Immune response
 Antibody assays : indication of previous infection or response
to vaccination
 less reliable as correlates of immunity, particularly to zoster
 failure to detect antibodies against VZV does not
necessarily imply susceptibility, as the corresponding
cell-mediated immunity may still be intact
 20% of persons aged 55–65 show
 no measurable cell-mediated immunity to VZV in spite
of persisting antibodies, and a history of previous varicella
 Zoster is closely correlated to a fall in the level of VZV-
specific T-cells
 an episode of zoster will reactivate the specific T-cell
response

13. High-risk groups
 High risks of complications
 Newborns and infants whose
mothers never had chickenpox
or the vaccine
 Teenagers
 Adults
 Pregnant women
 People whose immune systems are impaired by
another disease or condition
 People who are taking steroid medications for
another disease or condition, such as asthma
 People with the skin inflammation eczema

14. Complications of Varicella
 herpes zoster (shingles)
 lifetime risk 15%-20%
 mainly affecting the
elderly and
immunocompromised
persons
 secondary bacterial skin
and soft tissue infections
 otitis media
 bacteremia, pneumonitis
 osteomyelitis
 septic arthritis
 endocarditis
 necrotizing fasciitis
 toxic shock-like syndrome
 hepatitis
 thrombocytopenia
hemorrhagic varicella
 cerebellar ataxia
 encephalitis
 severe invasive group A
streptococcal infection
increases the risk 40-60 fold*
*Health Canada. CCDR 1999;25(S5):1-29.
Davies HD, et al. N Eng J Med 1996;335:547-54.

15. Complications of Varicella
 When compared with children, adults are
 3 to 18 fold higher risk : admitted to hospital for varicella
 11 to 20 fold higher : higher rates of complications such as
pneumonia
 1.1- to 2.7-fold higher : encephalitis*
 The risk factors identified in adults for varicella pneumonia
 underlying chronic lung disease
 Smoking**
 varicella pneumonia occurring in 3.4% to 9.3% of pregnant
women (no higher than in nonpregnant adults)***
 High mortality
*Choo PW, et al. J Infect Dis 1995;172:706-12
**Ellis ME, et al. Br Med J 1987;294:1002.
***Harger JH, et al. Obstet Gynecol 2002;100(2):260-65.

16. Neonatal varicella
 can be a serious illness, depending upon
the timing of maternal varicella and delivery
 If the mother develops varicella within 5 days before or
2 days after delivery
 acquires the virus transplacentally
 no protective antibodies
 Prophylaxis or treatment is required with varicella-zoster
immune globulin (VZIG) and acyclovir
 Without these drugs, mortality rates 20% - 30%*
 The primary causes of death are severe pneumonia and
fulminant hepatitis
*Derrick CW Jr, et al.South Med J 1998 Nov; 91(11): 1064-6.

17. Neonatal varicella
 Onset of maternal varicella more than 5 days
antepartum
 provides the mother sufficient time to manufacture and
pass on antibodies along with the virus.
 Full-term neonates : usually have mild varicella
 Treatment with VZIG is not recommended, but
acyclovir may be used, depending on individual
circumstances
Derrick CW Jr, et al.South Med J 1998 Nov; 91(11): 1064-6.

18. Congenital varicella syndrome
 gestational varicella : currently no evidence associated
 increase in spontaneous abortion, stillbirth, or prematurity
 transplacental or perinatal infection can have other serious
outcomes.
 0.4% of live births when maternal infection occurred
from conception through the 12th week of gestation
 2% when infection occurred between the 13th and
20th week of gestation*
 A smaller, prospective study of 347 women who had
varicella during pregnancy found an overall congenital
varicella syndrome rate of 0.4%**
*Enders G, et al. Lancet 1994;343:1547-50.
**Harger JH, et al. Obstet Gynecol 2002;100(2):260-65.

19. Congenital varicella syndrome
 maternal infection with chickenpox (maternal varicella
zoster) early during pregnancy (i.e., up to 20 weeks
gestation)
 The range and severity of associated symptoms and
physical findings may vary greatly from case to case
depending upon when maternal varicella zoster infection
occurred during fetal development

20. Stigmata of Varicella-Zoster
Virus Fetopathy
 Damage to Sensory Nerves
 Cicatricial skin lesions
 Hypopigmentation
 Damage to Optic Stalk and
Lens Vesicle
 Microphthalmia
 Cataracts
 Chorioretinitis
 Optic atrophy
 Damage to Brain/Encephalitis
 Microcephaly
 Hydrocephaly
 Calcifications
 Aplasia of brain
 Damage to Cervical or
Lumbosacral Cord
 Hypoplasia of an extremity
 Motor and sensory deficits
 Absent deep tendon reflexes
 Anisocoria
 Horner’s syndrome
 Anal/urinary sphincter dysfunction
Nelson, Textbook of Pediatrics.17th ed;246:973-977.

21. Type of exposure
 Household
 Playmate: face to face, indoor play
 Hospital
 Varicella : same 2-4 bed room, adjacent beds in a large ward
 Zoster : intimate contact with a person deemed contagious
 NB : mother had onset of chickenpox within 5 days
before delivery or within 2 days after delivery
 VariZIG is indicated for susceptible people
Redbook27th Ed;2006;711-725.

22. Postexposure Immunization
 Varicella vaccine
 Susceptible people > 12 mo of age, including adults
 As soon as possible within 72 hr and possibly up to
120 hr after varicella exposure
 To prevent or modify disease
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

23. Chemoprophylaxis
 If VariZIG is not available or > 96 hr after exposure
 Oral Acyclovir (some experts recommend)
 80 mg/kg/day divided 4 times/day for 7 days
 Start on day 7-10 after varicella exposure
if vaccine is contraindicated
 Susceptible immunocompromised adults
 Limited data on acyclovir as postexposure prophylaxis
in healthy children
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

24. Passive immunoprophylaxis
 VZIG : cessation of manufacture,2005
 VariZIG (Varicella-Zoster Immune Globulin)
 125 U/10 kg IM, Maximum dose 625U
 lessen the severity of the disease
 Likelihood that the exposed person is susceptible to varicella
 Probability that a given exposure to varicella or zoster will result in
infection
 Likelihood that complications of varicella will develop if person
is infected
 If VariZIG is not available, choose IGIV (Immune Globulin
Intravenous)
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

25. Passive immunoprophylaxis
 VariZIG should be administered as soon as possible, but
no later than 96 hours after exposure
 Newborns whose mothers have chicken pox five days
prior to two days after delivery
 Children with leukemia or lymphoma who have not
been vaccinated
 Persons with cellular immunodeficiencies or other
immune problems
 Persons receiving drugs, including steroids, that
suppress the immune system
 Pregnant women
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

26. Candidates for Acyclovir or VariZIG
 Immunocompromised children without Hx.of varicella
or varicella immunization
 NB : mother had onset of chickenpox within 5 days
before delivery or within 2 days after delivery
 Hospitalized preterm infants (GA  28 wks) whose
mother lack Hx or serology of varicella
 Hospitalized preterm infants (GA < 28 wks or BW
< 1000gm) regardless Hx of varicella or zoster serostatus
Redbook27th Ed;2006;711-725.

27. Treatment
 Healthy children
 no medical treatment
 antihistamine to relieve itching
 IV Acyclovir (nucleoside analogues)
 < 1 yr 30 mg/kg/day in 3 divided doses for 7-10 days
 > 1 yr 1500 mg/m2/day divided q 8 h for 7-10 days
 Immunocompromised patients
 Patients being treated with chronic corticosteroids
 medications to shorten the duration of the infection
 help reduce the risk of complications
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

28. Treatment
 Oral Acyclovir (Category B drug)
 80 mg/kg/day divided in 4 doses for 5 days, Max dose 3200
mg/day (* some experts recommend)
 Healthy people at increased risk of moderate to severe varicella
 > 12 yr of age
 Chronic cutaneous or pulmpnary disorders
 Receiving long-term salicylate therapy
 Receiving short, intermittent, or aerosonized courses of
corticosteroids
 *Secondary household cases
(disease usually is more severe than in primary case)
 *Pregnancy, especially during the second and third trimesters
 *HIV-infected patients with relatively normal CD4+ T-lymphocytes
 *Leukemia in whom careful follow-up
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

29. Treatment
 Valacyclovir and Famciclovir
 approved for use only in adults
 Complicated cases
 Hospitalization
 skin infections and pneumonia : antibiotics
 encephalitis : antiviral drugs
 Don't give Aspirin : Reye's syndrome.
Recommendations of the Advisory Committee on Immunization Practices.MMWR 2006;55:209-210.

30. Care of Hospital Exposure
 Identify those who are susceptible: both personel and
patients
 immunocompromised patient
 immunocompetent patient who:
< 6 month old without maternal history of chickenpox
> 6 month old with unimmunized/unvaccinated
 All exposed susceptible patients should be discharged
as soon as possible.
 All susceptible patients who cannot be discharged
should be placed in airborne and contact precaution from
day 10-21 after exposure.(28 day who received VariZIG)
Redbook27th Ed;2006;711-725.

31. Care of Hospital Exposure
 All susceptible exposed staff should be furloughed from
day 8-21 post exposure to an infectious patient. (28 day
who received VariZIG)
 Serologic testing for immunity is not necessary for
personel who have been immunized
 Immunizaed health care personel who develop
breakthough infection should be considered infectious
 Varicella immunization is recommended for susceptible
personnel if there are no contraindications to vaccine use
Redbook27th Ed;2006;711-725.

32. A Varicella Zoster outbreak among
Thai healthcare workers
 45 yrs-old, Thai woman, admitted to Thammasart
Hospital ICU because of CAP
 Day 11, she develop chicken pox
Healthcare workers IgG + IgG -
Hx of Varicella + 23 0
Hx of Varicella - 30 47
Sensitivity = 23/53 = 43%
Specificity = 17/17 = 100%
PPV = 23/23 = 100%
NPV = 47/77 = 61%
Sereprevalence
•>90% adults seropositive (in general)
•History of Varicella 97-99% predictive of antibodies
•Negative or uncertain history 79-93% seropositive
Apisarnthanarak A, et al. Infect Control Hosp Epidemio,2007

33. Isolation of the hospitalized patient
 Standard precautions, airborne and contact precaution
 Recommended for patients with varicella for a minimum of 5 days
after onset of rash and until all lesions are crusted
 For exposed susceptible patients
 Airborne and contact precautions from 10-21 days after exposure
to index patient (28 days for those who received VariZIG or IGIV)
 For neonates born to mothers with varicella and, if still
hospitalized, should be continued until 21 or 28 days of
age if they received VariZIG or IGIV
 Airborne and contact precautions
Redbook27th Ed;2006;711-725.

34. Who should get chickenpox vaccine?
 all susceptible children and adults
 A second dose catch-up varicella vaccination
is recommended for
 children, adolescents, and adults who previously had
received only one dose
 exposed to chickenpox may receive varicella vaccine
within 3 days (72 hours) to 5 days (120 hours)
 prevent or diminish the severity of illness
National Foundation for Infectious Diseases.USA. August 2006

35. Who should get chickenpox vaccine?
 special consideration in Adults
 not received the vaccine
 not already had chickenpox
 higher risk for exposure/transmission
 College students
 Household contacts of immunocompromised persons
 Residents and staff in institutional settings
 Inmates and staff of correctional institutions
 International travelers
 Military personnel
 Nonpregnant women of childbearing age
 Teachers and day care workers
 Non-immune persons
National Foundation for Infectious Diseases.USA. August 2006

36. Prevention
 The attack rate in unvaccinated
susceptible children was 88%
 The varicella vaccine is the best way to prevention
 CDC estimate complete protection from the virus for
nearly 90%
 Unvaccinated older children
 7-13 yr
 receive two catch-up doses of the varicella vaccine
 at least 3 mo apart
 > 13 yr
 receive two catch-up doses of the varicella vaccine
 at least 4 wks apart
CDC. MMWR 2005 Jul 29; 54(29): 717-21.

37. Prevention
 Unvaccinated adults who've never had
chickenpox but are at high risk of exposure
 If you don't remember whether you've had chickenpox
or the vaccine, a serum antibody test
 If you've had chickenpox, you don't need the vaccine
CDC. MMWR 2005 Jul 29; 54(29): 717-21.

38. Varicella vaccine
 Oka strain of VZV since 1974
 a single dose of vaccine : seroconversion 95%
 optimal age for varicella vaccination is 12–24 months
 In Japan and several other countries
 one dose of the vaccine : sufficient, regardless of age
 In the United States
 two doses, four to eight weeks apart
 Recommendation for adolescents and adults
 after the first dose : seroconversion 78%
 after the second dose : seroconversion 99%
Hall S, et al. Pediatrics 2002;109:1068-73

39. Asano Y, et al. Biken J 1980;23:157-61.

40. Varicella vaccine
 Varicella outbreak in a day-care center
 efficacy 100% in preventing severe disease
 86% in preventing all disease
 From the Japanese experience
 immunity to varicella following vaccination lasts for
at least 10–20 years
 In the United States : routine vaccination Since 1995
 70%–90% protection against infection
 > 95% protection against severe disease 7–10 years
after immunization*
*Clements DA, et al. Pediatr Infect Dis J 1999;18:1047-50.
Vasquez M, et al. N Eng J Med 2001;344:955-60.
Izurieta H, et al. JAMA 1997;279:1495-99.

41. Varicella vaccine
 In immunocompromised persons, including patients with
advanced HIV infection
 contraindication : fear of disseminated vaccine-induced
disease
 Vaccine safety
 asymptomatic HIV-infected children with CD4 counts
of more than 1,000 cell/μL
 patients with leukaemia in remission or solid tumours
before chemotherapy
 uremic patients waiting for transplantation
 a killed varicella vaccine has been studied in VZV-positive
bone marrow transplant patients where a multiple-dose
schedule has been
 reduce the severity of zoster

42. A Vaccine to prevent Herpes Zoster and
Post-herpetic Neuralgia in older adults
 Randomized, double-blind, placebo-controlled trial of an
investigational live attenuated Oka/Merck VZV vaccine
enrolled 38,546 adults 60 years of age or older
 burden of illness due to herpes zoster, a measure affected by the
incidence, severity, and duration of the associated pain and
discomfort
 secondary end point was the incidence of postherpetic neuralgia
 Results
 > 95 % of the subjects continued in the study to its completion
 a median of 3.12 years of surveillance for herpes zoster.
 A total of 957 confirmed cases of herpes zoster
(315 among vaccine recipients and 642 among placebo
recipients)
NEJM2005;352:2271-2284.

43. A Vaccine to prevent Herpes Zoster and
Post-herpetic Neuralgia in older adults
 107 cases of postherpetic neuralgia (27 among vaccine
recipients and 80 among placebo recipients) were included
in the efficacy analysis.
 zoster vaccine reduced the burden of illness due to herpes
zoster by 61.1% (P<0.001)
 reduced the incidence of postherpetic neuralgia by 66.5%
(P<0.001), and reduced the incidence of herpes zoster by
51.3% (P<0.001)
 Reactions at the injection site were more frequent among
vaccine recipients but were generally mild
 Conclusions
 The zoster vaccine markedly reduced morbidity from
herpes zoster and postherpetic neuralgia among
older adults
NEJM2005;352:2271-2284.

44. Breakthrough Varicella
 Varicella in persons who have received the vaccine
 less severe than the disease in unvaccinated individuals
 3% to 4% per year after varicella vaccination
 5% to 20% after household exposure to wild-type virus.
 The risk that vaccinated individuals with breakthrough
disease will infect others appears to correlate with the
number of lesions that develop.
 > 50 lesions were equally as likely to transmit the
infection to household contacts
 < 50 lesions were only half as likely to transmit the
infection
(J. Seward, Centers for Disease Control and
Prevention, Atlanta: personal communication)
NEJM 2001;344:955-60.
JAMA 1997;279:1495-99.
Pediatrics 1999;104:561-63.

45. Comparison of severity of varicella
symptoms in naturally infected children
and varicella vaccine recipients
Nagai T. Clin Virol 1997;25:271-81.

46. Vaccine associated adverse events
Varilix®
GlaxoSmithKline
In children < 13 years of age In adolescents and adults
Adverse effects local pain, redness and
swelling 11% - 22%
Varicella-like rash 1%
other rash types 10%
Reactions at the injection
site tended to be mild and
transient
Fever 11%
the first and second doses
local symptoms
12% and 16%
fever 29% and 20%
varicella-like rash
0.9% and 1.3%
Product monograph. Varilix®. GlaxoSmithKline, September 12, 2002.

47. Risk of clinical reactions of
Oka strain varicella vaccine
Asano Y. J Infect Dis 1996;174Suppl3:S310-3.

48. Vaccine associated adverse events
 In healthy children
 27% : local swelling and redness at the site of injection
 < 5% : a mild varicella-like disease with rash within 4 wks
 rare occasions of mild zoster following vaccination
 Since licensure and distribution of more than 10 million
doses of vaccine in the United States, the Vaccine Adverse
Event Reporting System (VAERS) reports of
 encephalitis, ataxia
 pneumonia
 thrombocytopenia
 arthropathy and erythema multiforme
 These events may not be causally related and they occur
at much lower rates than following natural disease

49. A tetravalent vaccine with the combined
measles-mumps-rubella vaccine
Immune response
VZV IgG
Varicella vaccine MMRV vaccine
(ProQuad)
6 wks after dose 1 85.7% 91.2%
6 wks after dose 1 and
3 mos between doses
99.6% 99.2%
6 wks after dose 2
at age 4–6 yrs
99.4% 98.9%
1.Kuter B, et al. Pediatr Infect Dis J 2004;23:132–7.
2.Shinefield H, et al. Pediatr Infect Dis J
2005;24:665–9.
3.Reisinger KS, et al. Pediatrics 2006;117:265–72.
Humoral and cellular immune response among children
aged 12 months–12 years measured at 6 weeks postvaccination,
by vaccine type and vaccination schedule — United States, 1988–
2002

50. Contraindications for Varicella vaccine
 a history of anaphylactic reactions to any
component of the vaccine including neomycin
 pregnancy
 due to theoretical risk to the fetus
 pregnancy should be avoided for 4 wks following
vaccination
 ongoing severe illness, and advanced immune disorders
of any type
 except for patients with acute lymphatic leukaemia in
stable remission
 ongoing treatment with systemic steroids
 for adults more than 20 mg/day
 for children more than 1mg/kg/day
American Hospital Formulary Service (AHFS) Drug Information 1997, p.2653-2655.

51. Contraindications for Varicella vaccine
 A history of congenital immune disorders in close family
members is a relative contraindication
 both varicella-zoster immune globulin (VZIG)and antiviral
drugs are available should persons in the
immunocompromised categories receive the vaccine by
mistake
 Administration of blood, plasma or immunoglobulin
 < 5 mo before immunization or
 3 wks afterwards
 reduce the efficacy of the vaccine
 use of salicylates is discouraged for 6 wks following
varicella vaccination : risk of Reye syndrome
American Hospital Formulary Service (AHFS) Drug Information 1997, p.2653-2655.

52.  Between 1995 and 2004 : Researchers from the Centers
for Disease Control and Prevention (CDC) and the Los
Angeles Department of Health Services looked at data
on 350,000 Californians
 > 11,000 people who developed chickenpox, almost
1,100 had been vaccinated
 The study also found that 8- to 12-year-olds who
contracted chickenpox after being vaccinated at least
5 years earlier were twice as likely to have "moderate
or severe" cases than those who had gotten the vaccine
less than 5 years before.
 early on with just one dose may still develop chickenpox
at an older age, when the illness may be more severe
Study : Single Dose of Varicella
Vaccine Not Enough

53. Study : Single Dose of Varicella
Vaccine Not Enough
 Randomized clinical trial : compared the efficacy of
1 dose of vaccine with that of 2 doses
 the cumulative rate of breakthrough varicella during
a 10-year observation period
 was 3.3-fold lower among children who received 2
doses than that among children who received 1 dose
(2.2% and 7.3,respectively; p<0.001)
 Breakthrough cases occurred occasionally in 0.8% of
2-dose vaccine recipients.
Kuter B, et al. Pediatr Infect Dis J 2004;23:132–
7.

54. Study : Single Dose of Varicella
Vaccine Not Enough
 The majority of cases of breakthrough disease occurred
2–5 years
 after vaccination; no cases were reported 7–10 years after
vaccination
 Of 16 children with breakthrough cases, three (19%) had
>50 lesions.
 The proportion of children with >50 lesions did not differ
between the 1-dose and 2-dose regimens (p = 0.5).
 In 2006, the CDC recommended
 First dose at 12 - 15 mo of age
 a booster dose at 4 - 6 yr old
Kuter B, et al. Pediatr Infect Dis J 2004;23:132–
7.

55. Category 1996
recommendations
1999
recommendations
2007
recommendations
Routine
childhood
schedules
1 dose
recommended at
age 12–18months
No change 2 doses recommended
• 1st dose at age 12–
15 months
• 2nd dose at age 4–6
years
Adults and
adolescents
aged >13 years
2 doses, 4–8 weeks
apart
2 doses, 4–8 weeks
apart
No change
Recommended
2 doses, 4–8 weeks
apart
Recommended for all
adolescents and adults
without evidence of
immunity
Catch-up
vaccination
1 dose recommended
for all susceptible
children aged 19
months–12 years
(i.e., those with no
history of varicella or
vaccination)
No change 2nd dose
recommended for all
persons who received
1 dose previously
Recommendations of the Advisory Committee
on Immunization Practices (ACIP):MMWR,June 22, 2007 / Vol. 56 / No. RR-4

56. Category 1996
recommendations
1999
recommendations
2007
recommendations
HIV-infected
persons
Contraindicated 2 doses, 3 months
apart
Considered for
asymptomatic
or CDC N1 or A1
or CD4+ >25%
2 doses, 3 months
apart
Considered for
CD4+ >15%
Outbreak
control
vaccination
None Should be
considered
Recommended 2 dose
vaccination policy
Postexposure
vaccination
Vaccination
requirements
None
None
Recommended
within 3–5 days
Recommended for
children without
evidence of immunity
attending child
care centers and
entering elementary
school
No change
Recommended for
children attending
child care centers,
students in all grade
levels and persons
attending college
Recommendations of the Advisory Committee
on Immunization Practices (ACIP):MMWR,June 22, 2007 / Vol. 56 / No.

57. Herpes Zoster
 rash usually resolves within 14-21 days
 Postherpetic neuralgia
 pain persisting at least 1 month after the rash has healed
 incidence increases dramatically with age
 4% in aged 30-50 years
 50% in older than 80 years
 Immunocompetent host
 all ages : same as Varicella in imunocompromised host
 > 12 yr : Acyclovir 4,000 mg/day in 5 divided doses for 5-7 days
 Immunocompromised children
 < 12 yr : Acyclovir 60 mg/kg/day IV q 8 hr, for 7-10 days
 > 12 yr : Acyclovir 30 mg/kg/day IV q 8 hr, for 7 days
Redbook27th Ed;2006;711-725.

58. Herpes Zoster
 the boosting of cell-mediated
immunity by exposure to
wild-type varicella infection
reduces the risk of zoster in
adults*
 The adults with the most
contact with children had
roughly one-fifth the zoster
risk of those with the least
contact with children**
**Levine MJ, Vaccine 2000;18(25):2915-20.
*Solomon BA, et al. J Am Acad Dermatol 1998;38:763-65.
Thomas SL, et al. Lancet. URL: 2 July, 2002.

59. Infantile zoster
 Infantile zoster usually
manifests within the first yr
 The cause is maternal
varicella infection after
the 20th week of gestation
 commonly involves the
thoracic dermatomes
NEJM1994 Mar 31; 330(13): 901-5.

60. Complications of Herpes Zoster
 Postherpetic neuralgia
 Ocular involvement with facial zoster
 Meningoencephalitis
 Cutaneous dissemination
 Superinfection of skin lesions
 Hepatitis/pneumonitis
 Peripheral motor weakness/segmental myelitis
 Cranial nerve syndromes, particularly ophthalmic and
facial (Ramsay Hunt syndrome)
 Corneal ulceration
 Guillain-Barré syndrome
Ann Neurol 1994; 35 Suppl: S4-8.

61. Isolation of the hospitalized patient
 Immunocompromised patient who have zoster (localized
or disseminated) and immunocompetent patients with
disseminated zoster
 Airborne and contact precautions for the duration of
illness
 For immunocompetent patients with localized zoster
 Contact precautions until all lesions are crusted
Redbook27th Ed;2006;711-725.

62. National Advisory Committee on Immunization. CCDR 2002;28(ACS-3):1-7.

63. National Advisory Committee on Immunization. CCDR 2002;28(ACS-3):1-7.

64. Management of chickenpox in pregnancy

65. Management of significant exposure* to varicella zoster virus (VZV) during pregnancy

66. Immunoglobulin Interval (months)
HBIG
RIG
Measles prophylaxis
standard
immunocompromised
VZIG
Blood transfusion
Washed RBCs
RBCs, adenine saline added
Packed RBCs
Whole blood
Plasma and platelet
Replacement of immune deficiency (IVIG)
ITP
400 mg/kg
1,000 mg/kg
1,600-2,000 mg/kg
Kawasaki disease
3
4
5
6
5
0
3
5
6
7
8
8
10
11
11

68. THANK YOU