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Varicella

U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Prevention Services

Publication date: 12/01/1992


Table of Contents

Varicella
Varicella Zoster Virus
Epidemiology
Pathogenesis and Spread
Clinical Manifestations
Complications
Differential Diagnosis
Laboratory Diagnosis
Current Methods of Control and Prevention
Varicella Vaccine
Varicella-Zoster Immune Globulin: Regional Distribution Centers
Varicella Workshop

For Additional Information

POINT OF CONTACT FOR THIS DOCUMENT:

Tables
Efficacy In Children


Varicella

History --

Varicella (chickenpox) was not reliably distinguished from smallpox until the end of the 19th century. Herpes zoster (shingles) has been recognized since ancient times and was described in the early medical literature. Clinical observations of the relationship between varicella and herpes zoster were made in 1888 by Von Bokay, when susceptible children acquired varicella after contact with herpes zoster. Varicella virus (VZV) was isolated from vesicular fluid of both chickenpox and zoster lesions in cell culture by Weller in 1954. Subsequent laboratory studies of the virus have led to the development of a live attenuated varicella vaccine, Oka strain, in Japan in the 1970s. The vaccine has been shown to be safe and effective in healthy and immunocompromised children, and healthy adults. It will soon be licensed in the U.S., probably for use in healthy children.

Varicella Zoster Virus

VZV is a member of the herpes virus group, (alpha) herpes virus 3. It is a DNA virus. VZV has the capacity to persist as a latent infection in dorsal root or extra medullary cranial ganglia.

Epidemiology

Infectiousness --

  • Varicella is highly contagious (less so than measles, but more so than mumps and rubella), with secondary attack rates in susceptible household contacts of up to 90%.
  • Virtually all persons in the U.S. acquire varicella by adulthood; thus, the number of cases occurring annually should approximate the U.S. birth cohort (3.5 to 4 million).
Epidemiologic Characteristics --

  • Varicella is endemic in the U.S. and has a seasonal fluctuation, with the highest incidence occurring in winter and early spring.
  • Between 150,000 to 200,000 cases of varicella are reported annually to the Centers for Disease Control and Prevention (CDC), representing 4%-6% of all cases.
  • Varicella is notifiable in approximately 33 reporting areas in the U.S.
  • The majority of cases, approximately 90%, occur in children less than 15 years of age. The highest attack rates are in children 5 to 9 years of age, who represent 60% of all cases.
  • By adulthood, 90%-95% of the U.S. population have antibodies to varicella.
  • In the tropics, varicella occurs more often in adults; thus, immigrants from these areas are more likely to be susceptible than the remainder of the population at comparable ages.
Morbidity and Mortality --

  • Normal children usually have a relatively benign course.
  • Complications are most likely to occur in the immunocompromised, newborns whose mothers develop rash close to the time of delivery, and adults.
  • Approximately 40 to 90 deaths due to varicella are reported each year. The majority of these are in normal persons.
Herpes Zoster --

  • Reflects reactivation of latent VZV infection.
  • Reactivation is associated with aging, immunosuppression, in utero exposure to varicella, and postnatal varicella occurring before 18 months of age.
  • Approximately 300,000 cases are estimated to occur annually, and 5% are recurrences. No seasonal variation is known.
  • Herpes zoster is not a notifiable condition.
  • In the immunocompromised, zoster can disseminate, causing generalized skin lesions, and central nervous system (CNS), pulmonary, and hepatic involvement.

Pathogenesis and Spread

Mode of Transmission

  • Person to person - Via direct contact with vesicular fluid or via droplets from respiratory tract secretions.
  • Airborne - Via aerosolized droplet nuclei.
  • Indirect contact - For example, via articles containing fresh discharges of vesicular lesions.
Reservoir: Humans

Incubation Period

  • The average length is 14 to 16 days from exposure, with a range of 10 to 21 days. This may be prolonged in immunocompromised patients and those who have received varicella zoster immune globulin (VZIG). The incubation period may be up to 28 days after VZIG.
Period of Communicability

  • Extends from 1 to 2 days before the onset of rash through the first 5 to 6 days after rash onset. Immunocompromised patients with progressive varicella are probably contagious during the entire period new lesions are appearing. The virus has not been isolated from crusted lesions.
Mild and inapparent infections occur rarely (<5% of infections)

Immunity following primary infection is considered long-lasting

  • However, reexposure may lead to reinfection with boosts in antibody titers, usually without clinically apparent illness or detectable viremia.
Path of entry of the virus into the susceptible host is assumed to be the upper respiratory tract

Clinical Manifestations

  • Prodrome - Adults may have 1 to 2 days of fever and malaise prior to rash onset, but in children the rash is often the first sign of disease.
  • Rash - The rash is generalized, pruritic, and rapidly progresses from macules to papules to vesicular lesions before crusting. Lesions are usually 1 to 4 mm in diameter; the vesicles contain clear fluid on a erythematous base that may rupture or become purulent before they dry and crust. Successive crops appear over several days, with lesions present in several stages of maturity. The rash begins on the scalp, moves to the trunk, and then the extremities. Lesions also can occur on mucous membranes of the oropharynx, respiratory tract, vagina, conjunctiva, and the cornea.
  • Other - The clinical course in normal children is typically benign, with mild malaise, pruritus, and fever up to 102 F for 2 to 3 days. Adults may have more marked systemic symptoms and they have a higher incidence of complications.
  • Zoster - The vesicular eruption of zoster generally occurs unilaterally in the distribution of the dermatomes supplied by a dorsal root or extramedullary cranial nerve sensory ganglion. Most often, this involves the trunk or the area of cranial nerve V. Two to four days prior to the eruption there may be pain and paresthesia in the segment involved. There are few systemic symptoms. Post-herpetic neuralgia is a distressing complication of zoster, with no adequate therapy currently available. Ocular nerve and other organ involvement with zoster can occur, often with severe sequelae. Maternal varicella infection during pregnancy can lead to herpes zoster in the first year of life.

Complications

Varicella in Normal Children

  • Low risk of complications.
  • Accounts for >90% of cases, 75% of all varicella hospitalizations, 70% of cases of encephalitis, 40% to 60% of all deaths, and virtually 100% of Reye Syndrome cases.
  • Most common complication is secondary bacterial infection of cutaneous lesions.
  • CNS Complications:
  • Encephalitis (estimated rate = 1.7/100,000): Cerebellar ataxia is most common, and is associated with a good outcome; diffuse cerebral involvement is less common in children.
  • Reye Syndrome: Recent dramatic decrease in the incidence has occurred, presumably related to decreased use of aspirin in children.
  • Rare: Aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome.
  • Pneumonia: Viral or bacterial, more frequent in adults.
  • Infrequent complications: Thrombocytopenia, hemorrhagic varicella, purpura fulminans, glomerulonephritis, myocarditis, arthritis, orchitis, uveitis, iritis, and clinical hepatitis.
Normal Adults

  • Have a higher risk of complications than normal children.
  • Less than 2% of reported cases are in persons > or equal to 20 years of age, but account for approximately 25% of mortality.
  • Pneumonia: Case fatality rates of up to 30%.
  • Diffuse cerebral encephalitis is more likely to affect adults than children, and has a case fatality rate of up to 37%.
  • Hospitalization rate approximately 14-18/1,000 cases compared with 1-2/1,000 cases in normal children.
Immunocompromised persons (i.e., persons with congenital or acquired immune deficiencies, malignancies, or on immunosuppressive therapy).

  • Immunocompromised persons have a high risk of serious varicella infection.
  • Immunocompromised persons have a high risk of disseminated disease (up to 36% in one report), resulting in multiple organ system involvement, often becoming fulminant and hemorrhagic.
  • Most frequent complications include pneumonia and encephalitis.
  • Increased risk of death; 7% in one report, however, this preceded the widespread use of VZIG and acyclovir and may not reflect current experience.
Congenital Infection

  • Primary varicella infection in the first 16 weeks of gestation is rarely associated with a recognized constellation of abnormalities: low birth weight, hypoplasia of an extremity, cicatricial skin scarring, localized muscular atrophy, encephalitis, cortical atrophy, chorioretinitis, and microcephaly.
  • Risk of congenital birth defects from primary maternal varicella infection during the first trimester is felt to be very low (1%-2%).
  • Rare reports of congenital birth defects following maternal zoster exist; however, virologic confirmation of maternal lesions was lacking.
  • Infection in utero with varicella, particularly after 20 weeks gestation, is associated with zoster in those infants at an earlier age; the exact risk is unknown.
Neonatal Infection Due to Maternal Chickenpox Close to Time of Delivery

  • The onset of maternal varicella from 5 days before to 2 days after delivery may result in severe infection of the neonate (in an estimated 17% to 30%) and an estimated case fatality rate of 31% in the first 5 to 10 days of life.
  • Fetal exposure to varicella virus without protection from sufficient maternal antibody results in severe disease.
  • Infants born to mothers with onset of maternal varicella 5 days or more prior to delivery usually have a benign course, presumably due to passive transfer of sufficient maternal antibody.
Infants After Postnatal Exposure

  • Normal full-term infants with normal birthweight are unlikely to develop serious complications.
  • Premature infants may have medical conditions that put them at increased risk for serious varicella illness and those born before 28 weeks of gestation may not have received adequate maternal antibody.
Pregnancy - There is growing evidence that infection during pregnancy carries increased risk for serious varicella. Further study is needed.

Death

  • Risk in normal children: approximately 1/100,000; in normal infants: approximately 6/100,000.
  • Risk in normal adults: approximately 12/100,000.
  • Risk in leukemics is higher than in normal children and has been reported at 7%.
  • Risk for newborns (who do not receive VZIG) from maternal chickenpox close to time of delivery is estimated at 31%.
  • Majority of deaths occur in normal individuals.

Differential Diagnosis

Chickenpox is associated with a very characteristic vesicular rash illness -- "Your grandmother could diagnose it" (Fehrs, 1990). A history of chickenpox has been shown to be a reliable indicator of immunity; however, a lack of such history is not as reliable and does not always correlate with lack of immunity.

The differential diagnosis for chickenpox includes: Herpes Simplex

  • Disseminated infection in the immunocompromised or neonate.
  • Eczema herpeticum, vesicular lesions occur in the areas of eczematous involvement.
  • Zoster-like lesions.
Enteroviral Infections - Papulovesicular lesions occur on palms and soles, with vesicular lesions on the buccal mucosa; usually self limited.

Impetigo - Erythematous macules progress to vesiculopustular lesions that dry and crust. The infection can spread. Exposed areas such as the face, neck, and limbs are often involved. Skin breaks serve as the portal of entry. Group A Streptococcus is usually the etiologic agent, but superinfection by staphylococci often occurs.

Rickettsialpox

  • Generalized erythematous papulovesicular lesions occur on the palms, soles, and mucous membranes after the bite of a house mouse mite, Liponyssoides sanguineus (the vector).
  • A black scab occurs at the bite.
  • Systemic disease consists of chills, fever, headache, myalgia, photophobia, and adenopathy. It is self-limited, nonfatal, and noncommunicable.

Laboratory Diagnosis

Not routinely required, but useful if confirmation of diagnosis or determination of susceptibility is necessary.

Viral Isolation --

  • Source - Vesicular fluid; difficult to isolate from the respiratory tract.
  • Tissue culture isolation.
  • Vesicular scrapings (Tzanck smear) can identify multi-nucleated giant cells, consistent with VZV and herpes simplex virus (HSV) infection. In some instances, stains of vesicular scrapings may be tested using a fluorescent monoclonal antibody test which is very sensitive and specific.
Serologic Testing --

  • Antibody Tests:
  • Complement fixation (CF): Commercially available, but lacks sensitivity.
  • Neutralization test (NT): Sensitive and specific; time consuming and difficult to perform; not readily available.
  • Immunofluorescence assay for antibody to VZV-induced membrane antigen (FAMA): sensitive, time consuming, not readily available.
  • Immune adherence hemagglutination (IAHA) sensitive; not readily available.
  • Enzyme-linked immunosorbent assay (ELISA): Sensitive, simple, and commercially available; may be useful for routine testing.
  • Cell Mediated Immunity
  • Lymphocyte proliferative response to VZV antigen.
  • Skin test antigen: Not commercially available.
  • In normal individuals, the presence of detectable antibody can be considered evidence of immunity to VZV.
  • Antibody levels in immunocompromised persons may be unreliable predictors of immunity, as they may reflect passively acquired antibody from blood products. Clinical varicella has developed in these persons. Laboratory tests must be interpreted cautiously in this population. History of prior chickenpox may be a more important indicator of immunity.

Current Methods of Control and Prevention

  • VZIG
  • Licensed in 1981.
  • Prepared from plasma of normal blood donors with high antibody titers to VZV.
  • Available from the American Red Cross.
  • If administered within 96 hours of exposure, can modify or prevent clinical varicella and prevent complications or death, especially in susceptible immunocompromised individuals.
  • Indications for use:
    • Individuals with significant exposure: Continuous household contact; playmate contact of over an hour; hospital contact in the same 2- to 4-bed room, or prolonged direct contact; newborn of mother who had onset of varicella 5 days before to 2 days after delivery.
    • Individuals at risk for complications:
      • Immunocompromised children: Those with immune deficiencies, neoplastic disease, or on immunosuppressive therapy.
      • Newborns of mothers with varicella onset 5 days before to 2 days after delivery.
      • Premature infants with postnatal exposure:
      • Those born > or equal to 28 weeks gestation and up to term, and > or equal to 1,000 grams; mother not immune.
      • Those born < 28 weeks or < 1000 grams birth-weight, regardless of maternal history.
    • Immunocompromised adults: If susceptible and have a history of significant exposure.
    • Normal adults and pregnant females: Consider the type of exposure, susceptibility, risks for complications, and cost.
  • No evidence that VZIG will prevent congenital varicella.
  • Dose: 125 units/I0 kg, up to a maximum of 625 units (five vials), IM. Volume 125 units per 1.25 ml (one vial). (Higher doses can be considered for immunosuppressed persons).
  • Should be given within 96 hours of exposure, preferably as soon as possible.
  • The administration of VZIG may prolong the incubation period of varicella to as long as 28 days post-exposure.
Special Varicella Zoster Exposure Situations --

  • Hospital personnel - If susceptible, with significant exposure, workers should be relieved from direct patient contact from day 10 to day 21 after exposure. If workers develop chickenpox, varicella lesions must be crusted before they should return to direct patient contact. Receipt of VZIG does not change this recommendation for reassignment. Since VZIG can prolong the incubation period, the period of removal from direct patient contact should be lengthened to 28 days after exposure.
  • Newborn with maternal rash onset 5 days before to 2 days after delivery
    • Since about 50% of infants who receive VZIG will develop varicella, if these infants remain hospitalized beyond age 10 days, they should be kept in strict isolation until age 21 days.

Antiviral Therapy

  • Acyclovir - The Advisory Committee on Immunization Practices (ACIP) has not set policy concerning acyclovir. The policy of the American Academy of Pediatrics (AAP) includes: Not routinely recommended for uncomplicated varicella in healthy children. Should be considered in individuals at high risk for severe varicella or complications.
  • Healthy nonpregnant individuals 13 years of age or older.
  • Children over 12 months of age with a chronic cutaneous or pulmonary disorder, or salicylate therapy.
  • Children receiving short, intermittent or aerosolized courses of corticosteroids. If immunocompromised, intravenous administration is indicated. Corticosteroids should be discontinued, if possible, after exposure. Dosage: Should be started within the first 24 hours of onset of rash, 20 mg/kg four times a day for 5 days, maximum 800 mg four times per day. Adequate fluid intake should be maintained. Intravenous acyclovir is recommended for primary varicella or recurrent zoster in immunocompromised children and for viral-mediated complications of varicella in normal individuals. Oral acyclovir is not recommended for pregnant women with uncomplicated varicella. Intravenous acyclovir should be considered in pregnant women with serious viral-mediated complications of varicella. Acyclovir should not be used prophylactically in normal children exposed to varicella to prevent infection or illness.
  • Adenine Arabinoside (ara-A).
  • Interferon - Currently under investigation.

Varicella Vaccine

Characteristics --

  • Oka strain.
  • Vaccine virus isolated from vesicular fluid from a healthy child.
  • Attenuated by passage 30 to 33 times in human diploid cells and guinea pig fibroblasts.
  • Live attenuated vaccine developed in Japan in the early 1970s.
  • Licensed for general use in Japan and Korea and in high-risk individuals in a number of European countries.
  • Vaccine has been administered to over 15,000 people in Japan and the U.S., including healthy children, healthy adults, children with acute lymphocytic leukemia (ALL), and other immunocompromised patients.
Table 1; Efficacy in Children

Table 1 Normal Adults

  • Seroconversion only 82% with one dose, 94% with two doses.
  • Effective vaccination may require two doses.
  • Efficacy of two doses only approximately 65%-70% after household exposure.
  • Breakthrough infectious are mild, with few skin lesions, and do not result in dissemination of serious illness.
Adverse Events Following Varicella Vaccination

  • Normal Children/Adults.
  • Rash. (1) 4%-10%. (2) Usually <50 lesions. (3) Often maculopapular rather than vesicular.
  • Injection site lesions, swelling, pain.
  • System reactions rare.
  • Reactivation (zoster).
    1. Adults: 1/302 @ 3 years (wild-type virus isolated).
    2. Normal children:
      1. Six cases reported.
      2. 1.4/10,000 person-years (vs. 8/10,000 following natural disease).
      3. No virus isolated.
  • Children with acute lymphoblastic leukemia (ALL).
  • Rash more frequent.
    1. Occurs in up to 40%.
    2. More frequent in patients:
      1. With recent steroid therapy.
      2. Receiving first dose.
      3. With no suspension of chemotherapy.
  • Reactivation (zoster).
    1. May be less frequent than following natural disease (Hardy I, Gershon AA, Steinberg SP, LaRussa P, Varicella Vaccine Collaborative Study Group. The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. N Engl J Med 1991; 325[22]:1545-50.)
    2. No severe illness or dissemination reported.
    3. More common in those with initial vaccine-related rash.
    4. Vaccine virus isolated.

    Transmission of Varicella Vaccine Virus

    • Transmission from normal recent vaccinees.
    • No secondary clinical illnesses reported.
    • <1% asymptomatic seroconversion documented in susceptible contacts (Weibel).
    • Transmission from children with ALL.
    • Only from recent vaccinees with rash.
    • Transmission rate from those with post-vaccination rash is 9%-28%.
    • Vaccine virus isolated from secondary cases.
    • One case of tertiary transmission.
    • Transmission has been documented from persons who initially seroconverted after vaccination but nevertheless developed mild breakthrough infection later.
    Summary

    • The vaccine appears to be safe and effective.
    • Vaccination prevents illness in normal individuals.
    • Vaccination prevents serious complications in the immunocompromised.
    • Persistent immunity is produced in almost all normal vaccinees.
    • Immunocompromised persons and adults may require two doses of vaccine.
    • The risk for zoster appears to be less than the risk following natural varicella.
    • Antibody levels following simultaneous administration of the vaccine with measles-mumps-rubella (MMR) at 15 months of age are similar to those detected when the vaccines are given alone.
    • Cost/Benefit analysis:
    • Annual cost of caring for normal children estimated to be $400 million; 95% of costs are associated with wages lost when parents must provide home care of an ill child.
    • Vaccine given with MMR at 15 months could reduce costs by 66%; benefit to cost ratio 6.9:1.

    Varicella-Zoster Immune Globulin: Regional Distribution Centers

    Service Area                            Regional Center and
    24-Hour Telephone                   United States and territories
    ------------------------------------------------------------------------
    Alabama                                 American Red Cross Blood Services
    Alabama Region
    (205) 322-5661
    
    Alaska                                  (see Oregon)
    Arizona                                 American Red Cross Blood Services
    Southern Arizona Region
    (602) 623-0541
    
    Arkansas                                (see Missouri)
    California, northern                    American Red Cross Blood Services
    
    L.A.-Orange Counties Region
    (213) 739-5200
    
    Colorado                                (see N. Mexico)
    Connecticut                             American Red Cross Blood Services
    
    Connecticut Region
    (203) 678-2730
    Delaware                                (see Pennsylvania)
    Florida                                 South Florida Blood Service
    
    (305) 326-8888
                                            American Red Cross Blood Services
    Mid-Florida Region
    (904) 255-5444
    
    Georgia                                 American Red Cross Blood Services
    
    Atlanta Region
    (404) 881-9800
    (404) 881-6752 (night)
    
    Hawaii                                  (see California, Southern)
    Idaho                                   American Red Cross Blood Services
    
    Mid-America region
    (312) 440-2222
    Illinois, southern                      (see Missouri)
    Indiana                                 American Red Cross Blood Services
    
    Fort Wayne Region
    (219) 482-3781
    Iowa                                    (see Wisconsin, S.E.)
    Kansas                                  (see Missouri)
    Kentucky                                (see Missouri)
    Louisiana                               (See Texas [Gulf Coast])
    Maine                                   American Red Cross Blood Services
    
    Northeast Region
    (207) 775-2367
    Maryland                                American Red Cross Blood Services
    
    (301) 764-4639
                                            (also see Washington D.C.)
    Massachusetts                           Massachusetts Public Health
    
                                            United States Biologics
                                                Laboratories
    (617) 522-3700
    
    Michigan                                American Red Cross Blood Services
    
    Southeastern Michigan Region
    (313) 494-2715
                                            American Red Cross Blood Services
    Wolverine Region
    (313) 232-1176
                                            American Red Cross Blood Services
    Great Lakes Region
    (517) 484-7461
    
    Minnesota                               American Red Cross Blood Services
    
    St. Paul Region
    (612) 291-6789
    (612) 291 6767 (night)
    
    Mississippi                             (see Alabama)
    Missouri                                American Red Cross Blood Services
    
    (314) 658-2000
    (314) 658-2136 (night)
    Montana                                 (see Oregon)
    Nebraska                                American Red Cross Blood Services
    
    Midwest Region
    (402) 341-2723
    Nevada                                  (see California, northern)
    New Hampshire                           (see Vermont)
    New Jersey, northern                    (see Greater New York Blood
                                                Program)
    New Jersey, southern                    (see Pennsylvania)
    New Mexico                              United Blood Services
    
    (505) 247-9831
    New York                                The Greater New York Blood Program
    
    (212) 468-2106
    (212) 570-3068 (night)
                                            American Red Cross Blood Services
    Northeastern New York region
    (518) 449-5020 or (518)462-7461
    (518) 462-6964 (night)
                                            American Red Cross Blood Services
    Northeastern New York Region
    (518) 449-5020 or (518) 462-7461
    (518) 462-6964 (night)
                                            American Red Cross Blood Services
    Greater Buffalo Chapter
    (716) 886-6866
                                            American Red Cross Blood Services
    Rochester Region
    (716) 461-9800
                                            American Red Cross Blood Services
    Syracuse Region
    (315) 425-1647
    
    North Carolina                          American Red Cross Blood Services
    
    Carolinas Region
    (704) 376-1661
    North Dakota                            (see Wisconsin, S.E.)
    Ohio                                    American Red Cross Blood Services
    
    Northern Ohio Region
    (216) 781-1800
                                            American Red Cross Blood Services
    Central Ohio Region
    (614) 253-7981
    Oklahoma                                (see Texas Gulf Coast)
    Oregon                                  American Red Cross Blood Services
    
    Pacific Northwest Region
    (503) 243-5286
    Puerto Rico                             American Red Cross
    
                                            Servicio de Sangre Capitulo
    (809) 759-7979
    Pennsylvania                            American Red Cross Blood Services
    
    Penn-Jersey Region
    (215) 299-4126
    Rhode Island                            Rhode Island Blood Center
    
    (401) 863-8368
    South Carolina                          American Red Cross Blood Services
    
    South Carolina Region
    (803) 256-2301
    South Dakota                            (see Wisconsin, S.E.)
    Tennessee                               American Red Cross
    
    Nashville Region
    (6154) 327-1931, ext. 315
    Texas                                   Gulf Coast Regional Blood Center
    
    (713) 791-6250
                                            American Red Cross Blood Services
    Central Texas Region
    (817) 776-8754
                                            American Red Cross Blood Services
    Reed River Region
    (817) 322-8686
    
    Utah                                    (see California, northern)
    Vermont                                 American Red Cross Blood Services
    
    Vermont-New Hampshire Region
    (802) 658-6400, ext 217
    Virginia (also see
    Washington, DC)                         American Red Cross Blood Services
    
    Tidewater Region
    (804) 446-7709
                                            Richmond Metropolitan Blood Service
    (804) 359-5100
                                            ARC Blood Services
    Appalachian region
    (703) 985-3595
    Washington                              Puget Sound Blood Center
    
    
    (206) 292-6525
    Washington, DC                          American Red Cross Blood Services
    
    Washington Region
    West Virginia                           (see Washington, DC)
    Wisconsin                               The Blood Center of S.E. Wisconsin
    
    
    (414) 933-5000
                                            American Red Cross Blood Services
    Badger Region
    (608) 255-0021
    Wyoming                                 (see California, northern)
    
    Other countries
    
    Canada                                  Canadian Red Cross
    
                                            Blood Transfusion Service
                                                National Office
    (416) 923-6692
    Central and
    South America                           South Florida Community Blood
                                                Center
    (305) 326-8888
    
    All other countries                     American Red Cross Blood Services
    
    Northeast Region
    (617) 449-0773
    
                                            American Red Cross Blood Services
                                                Blood Services
    (617) 731-2130
    

    Varicella Workshop

    1. Which statement about varicella is not true?
      1. Varicella is highly contagious.
      2. Varicella is a notifiable disease in all states.
      3. Most adults are immune to varicella.
      4. Airborne transmission of vancella can occur.
    2. Which statement about herpes zoster or shingles is not true?
      1. Zoster represents reactivation of latent varicella infection.
      2. About 5% of zoster episodes are recurrences of zoster.
      3. No seasonal variation in zoster is known.
      4. CDC receives reports of herpes zoster from states.
    3. What is the incubation period for chickenpox?
    4. If someone, such as a health care worker, is susceptible to varicella and is exposed to the disease, when should they be considered at risk for developing chickenpox and exposing others?
    5. In the case in question 4, if the exposed person received VZIG, what effect would this treatment have on the incubation period? On recommendations for preventing exposure of high-risk persons to this person?
    6. Which of the following is NOT true regarding vancella?
      1. The period of communicability (for normal persons) extends from 1 to 2 days before onset of the rash through the first 5 to 6 days after rash onset.
      2. Vancella zoster immune globulin (VZIG) is indicated for a healthy full-term infant who is exposed to chickenpox at home at age 2 weeks.
      3. Vancella vaccine is less immunogenic and effective in normal adults than in normal children, although it does prevent serious disease in this group.
      4. Herpes zoster is a reactivation of latent varicella infection.
      5. Normal adults have a higher risk of complications from the disease than do normal children.

      Questions 7-16: Indicate whether the following persons should receive VZIG and why:
    7. The normal newborn whose mother develops a varicella rash on the day of delivery.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    8. The normal newborn whose mother developed a rash 10 days before delivery.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    9. The 1500g infant born at 30 weeks gestation who is exposed in the nursery to chickenpox.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    10. The infant born at 27 weeks gestation who is exposed to chickenpox in the nursery but whose mother is sure she had chickenpox several years ago, when she was in college.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    11. The pregnant woman who is exposed to a household member with chickenpox and whose doctor wants to protect her against the risk of complications of varicella in pregnancy.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    12. The pregnant woman who is exposed in the first trimester to a household member with varicella and who wants VZIG in order to protect her fetus against infection.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    13. The immunocompromised adult who is significantly exposed to varicella.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    14. The normal adult who is exposed to chickenpox and has no memory of ever having had chickenpox.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    15. The high-risk patient who was exposed to varicella 8 days ago.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    16. The susceptible high-risk patient who was exposed to varicella 3 days ago and whose doctor is unsuccessful in reaching CDC to obtain VZIG.
      1. ____ Yes
      2. ____ No
      3. ____ VZIG should be considered
    17. What age group is currently most likely to develop chickenpox?
    18. Name groups which have a higher risk for complications of varicella than do normal children.
    19. For which persons is Merck Sharp & Dohme seeking FDA licensure of varicella vaccine?
    20. Which of the following has not been observed following vaccination in trials of varicella vaccine in normal and immunocompromised children?
      1. Vaccine-associated rash associated with a low rate of transmission of vaccine virus
      2. Vaccine-associated fever
      3. Pain at injection site
      4. Zoster due to reactivation of vaccine virus
      5. Severe complications

    Varicella Workshop Answers --

    1. Which statement about varicella is not true?
      1. Varicella is highly contagious.
      2. Varicella is a notifiable disease in all states.
      3. Most adults are immune to varicella.
      4. Airborne transmission of varicella can occur.

      Answer: B. - Varicella is a notifiable disease in fewer states (less than 70%) than are measles, mumps, or rubella. This fact and the fact that many cases of varicella are mild and never come to medical attention contribute to the low rate of reporting of varicella to the CDC -- only 4%-6% of the estimated annual total of U.S. cases.
    2. Which statement about herpes zoster or shingles is not true?
      1. Zoster represents reactivation of latent varicella infection.
      2. About 5% of zoster episodes are recurrences of zoster.
      3. No seasonal variation in zoster is known.
      4. CDC receives reports of herpes zoster from states.

      Answer: D. - Unlike cases of primary varicella (or chickenpox), cases of herpes zoster are not tracked by the CDC through routine notifiable disease surveillance in States.
    3. What is the incubation period for chickenpox?
      Answer: An average of 14-16 days, with a range of 10-21 days.
    4. If someone, such as a health care worker, is susceptible to varicella and is exposed to the disease, when should they be considered at risk for developing chickenpox and exposing others?
      Answer: During the period of 10-21 days after exposure. This is the period during which they should not be in contact with susceptible persons at high risk for complications from varicella.
    5. In the case in question 4, if the exposed person received VZIG, what effect would this treatment have on the incubation period? On recommendations for preventing exposure of high-risk persons to this person?
      Answer: The incubation period could be lengthened to as long as 28 days. Therefore, the exposed person should not be in contact with susceptible persons at high risk for varicella complications during the period from 10 to 28 days post-exposure.
    6. Which of the following is NOT true regarding varicella?
      1. The period of communicability (for normal persons) extends from 1 to 2 days before onset of the rash through the first 5 to 6 days after rash onset.
      2. Varicella zoster immune globulin (VZIG) is indicated for a healthy full-term infant who is exposed to chickenpox at home at age 2 weeks.
      3. Varicella vaccine is less immunogenic and effective in normal adults than in normal children, although it does prevent serious disease in this group.
      4. Herpes zoster is a reactivation of latent varicella infection.
      5. Normal adults have a higher risk of complications from the disease than do normal children.

      Answer: B. - Use of VZIG for infants and children is reserved primarily for susceptible, immunocompromised children after significant exposure. It is not indicated for healthy, normal-term infants, who are not known to be at any greater risk from complications of chickenpox than older c children.

      Questions 7-16: Indicate whether the following persons should receive VZIG and why:
    7. The normal newborn whose mother develops a varicella rash the day of delivery.
      Answer: A - YES. This infant is likely to develop serious neonatal varicella because it was exposed in utero to varicella virus when the mother was viremic but was born before sufficient maternal antibody could be produced, transferred transplacentally, and moderate disease in the infant.
    8. The normal newborn whose mother developed a rash 10 days before delivery.
      Answer: B - NO. This infant should have received maternal anti-body in utero and should have mild or no disease. Only infants whose mothers develop rash 5 days before to 2 days after delivery are at high-risk for serious varicella.
    9. The 1500g infant born at 30 weeks gestation who is exposed in the nursery to chickenpox.
      Answer: C - VZIG should be considered. Since this infant weighs > or equal to 1000g and was born at > or equal to 28 weeks gestation, VZIG does not need to be given if there is a good maternal history of chickenpox, even though this infant is premature. If the mother does not have a history of chickenpox, VZIG should be given.
    10. The infant born at 27 weeks gestation who is exposed to chickenpox in the nursery but whose mother is sure she had chickenpox several years ago, when she was in college.
      Answer: A - YES. Even though the mother should be immune to chickenpox, since the infant may have been born before maternal antibody was transferred transplacentally, the ACIP and AAP recommend that VZIG be given.
    11. The pregnant woman who is exposed to a household member with chickenpox and whose doctor wants to protect her against the risk of complications varicella in pregnancy.
      Answer: C - VZIG should be considered. It is unclear if pregnant women have a higher risk for complications from varicella than do non- pregnant adults; however, adults do have a higher risk of complications than do children. Some obstetricians will administer VZIG to exposed pregnant women if adequate resources and time are available, especially if the exposure was high, as occurs within households.
    12. The pregnant woman who is exposed in the first trimester to a household member with varicella and who wants VZIG in order to protect her fetus against infection.
      Answer: B - NO. There is no evidence that the administration of VZIG will prevent fetal infection. However, some obstetricians will give VZIG for a different reason (see above). The pregnant exposed women should be reassured that congenital varicella syndrome is rare and results from exposure during the first 16 weeks of pregnancy only.
    13. The immunocompromised adult who is significantly exposed to varicella.
      Answer: C - VZIG should be considered. VZIG should be given if the adult does not have a carefully obtained history of varicella or has serologic evidence of lack of immunity.
    14. The normal adult who is exposed to chickenpox and has no memory of ever having had chickenpox.
      Answer: C - VZIG should be considered. VZIG is expensive and not routinely recommended by the ACIP for such adults. However, since adults do have a higher rate of complications with varicella than do children, some physicians will offer adults the option of receiving VZIG.
    15. The high-risk patient who was exposed to varicella 8 days ago.
      Answer: B - NO. VZIG should be administered within 96 hours of exposure. In this case, the patient would probably be treated with an anti-viral agent, such as acyclovir, at the first sign of illness.
    16. The susceptible high-risk patient who was exposed to varicella 3 days ago and whose doctor is unsuccessful in reaching CDC to obtain VZIG.
      Answer: A - YES. VZIG is obtained from the local American Red Cross, not from CDC.
    17. What age group is currently most likely to develop chickenpox?
      Answer: School-aged children, especially children 5-9 years of age.
    18. Name groups which have a higher risk than do normal children for complications of varicella.
      Answer: - Immunocompromised patients (including persons with AIDS).
      • Adults.
      • Newborns whose mothers develop a varicella rash 5 days before to 2 days after delivery.
      • Premature infants.
      • Normal infants under age 1 year (who have a lower risk than newborns with neonatal exposure but a higher risk than older children).
      • Pregnant women, possibly.
    19. For which persons is Merck Sharp & Dohme seeking FDA licensure of varicella vaccine?
      Answer: Children over 12 months of age and adults.
    20. Which of the following have not been observed following vaccination in trials of varicella vaccine in normal and immunocompromised children?
      1. Vaccine-associated rash associated with a low rate of transmission of vaccine virus?
      2. Vaccine-associated fever.
      3. Pain at injection site.
      4. Zoster due to reactivation of vaccine virus.
      5. Severe complications.

      Answer: E - Severe complications. While a few immunocompromised vaccines have developed extensive rashes similar to wild-type infection, no reports of serious complications or death due to vaccine infection exist.

    For Additional Information

    U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention.

    POINT OF CONTACT FOR THIS DOCUMENT:

    To request a copy of this document or for questions concerning this document, please contact the person or office listed below. If requesting a document, please specify the complete name of the document as well as the address to which you would like it mailed. Note that if a name is listed with the address below, you may wish to contact this person via CDC WONDER/PC e-mail.
    DON H STENHOUSE
    NATIONAL IMMUNIZATION PROGRAM
    Centers for Disease Control
    1600 Clifton Rd MS(E-05)
    Atlanta, GA 30333

    Table 1

                           Table 1 Efficacy In Children
    ===========================================================================
                             Normal Children          Children With ALL
    ___________________________________________________________________________
    1. Immunologic Response
    -------------------------
       Humoral (seroconversion                           One dose: 88%
                rate)                94%-100%            Two doses: 98%
    
       Cellular                       >90%               Data difficult
                                                         to interpret
    
    2. Clinical Efficacy
    _________________________
       Pre-exposure                  85%-95%              85% with 2 doses
    
    3. Duration of Immunity
    _________________________
       Antibody                 >90% (up to 3-10 years)       50%-80%
         Cellular                                          Frequently lost
      (Cell mediated)                  90%                     antibody
         Cellular
    (Positive skin testing)            90%                       90%
    
    4. Breakthrough infections (about 2%/year in first few years post
    vaccination) are generally mild, with few skin lesions, and do not
    result in dissemination or serious illness.
    ===========================================================================
    



This page last reviewed: Wednesday, January 27, 2016
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