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Chapter 3Infectious Diseases Related To Travel
Varicella (Chickenpox)
Kathleen H. Harriman, Gilberto F. Chavez
INFECTIOUS AGENT
Varicella zoster virus is a member of the herpesvirus family. Humans are the only reservoir of the virus, and disease occurs only in humans.
MODE OF TRANSMISSION
Varicella is transmitted from person to person by direct contact, inhalation of aerosols from vesicular fluid of skin lesions of varicella (chickenpox) or herpes zoster (shingles), which is a reactivation of latent varicella, or from infected respiratory tract secretions that might also be aerosolized. The varicella zoster virus enters the host through the upper respiratory tract or the conjunctiva.
In utero infection can also occur as a result of transplacental passage of virus during maternal varicella infection.
EPIDEMIOLOGY
Varicella occurs worldwide. In temperate climates, varicella tends to be a childhood disease, with peak incidence during late winter and early spring. In tropical climates, infection tends to occur at older ages, resulting in higher susceptibility among adults than in temperate climates.
Varicella vaccine is routinely used to vaccinate healthy children in only some countries, including the United States, Australia, Canada, Costa Rica, Dominican Republic, Germany, Mexico, Qatar, Spain, South Korea, Switzerland, United Arab Emirates, and Uruguay. Although varicella is still widely circulating in the United States, the risk of exposure to varicella zoster virus is higher in most other parts of the world than it is currently in the United States. Additionally, exposure to herpes zoster poses a risk for varicella infection in susceptible travelers, although localized herpes zoster has been shown to be much less infectious than varicella. Travelers at highest risk for severe varicella disease are immunocompromised people or pregnant women without a history of varicella disease or vaccination (see below for postexposure prophylaxis recommendations).
CLINICAL PRESENTATION
Varicella is generally a mild disease in children. Infection is often characterized by a short (1 or 2 days) prodromal period (low-grade fever, malaise), although this may be absent, and by pruritic rash consisting of crops of macules, papules, and vesicles (typically 250–500 lesions), which appear in 3 or more successive waves and resolve by crusting. Serious complications are the exception, but they can occur, most commonly in infants, adolescents, and adults. Complications include secondary bacterial infections of skin lesions, pneumonia, cerebellar ataxia, and encephalitis.
The average incubation period for varicella is 14–16 days (range, 10–21 days). The period of communicability is estimated to begin 1–2 days before the onset of rash and end when all lesions are crusted, typically 4–7 days after onset of rash in immunocompetent people, but this period may be longer in immunocompromised people.
Although varicella vaccine is 70%–90% effective in preventing all varicella, modified varicella, also known as breakthrough varicella, can occur in vaccinated people. In breakthrough varicella, which is often mild, the rash is often atypical in appearance with less than 50 vesicles and a predominance of maculopapular lesions; a fever is less common or of shorter duration. Breakthrough varicella is infectious, although less so than varicella in unvaccinated people. People with breakthrough varicella should be isolated for as long as lesions persist.
DIAGNOSIS
Skin lesions are the preferred specimen for laboratory confirmation of varicella disease. Vesicular swabs or scraping and scabs from crusted lesions can be used to identify varicella zoster virus by polymerase chain reaction or direct fluorescent antibody. In the absence of vesicles or scabs, scrapings of maculopapular lesions can be collected for testing.
Serologic tests may also be used to confirm disease:
- In the absence of skin lesions, a significant rise in serum varicella IgG from acute- and convalescent-phase samples by any standard serologic assay can confirm a diagnosis retrospectively but may not be reliable in immunocompromised people.
- Commercially available tests may not be sufficiently sensitive to reliably demonstrate vaccine-induced immunity.
POSTEXPOSURE PROPHYLAXIS
Vaccine
Varicella vaccine is recommended for postexposure administration for healthy unvaccinated people aged ≥12 months without other evidence of immunity. Administration of varicella vaccine to exposed susceptible people aged ≥12 months, as soon as possible within 72 hours and possibly up to 120 hours after exposure, may prevent or modify disease and is recommended, if there are no contraindications to use. In several studies, protective efficacy was reported as ≥90% when children were vaccinated within 3 days of exposure.
Varicella Zoster Immune Globulin
In certain circumstances, postexposure prophylaxis with varicella zoster immune globulin (VZIG) is recommended. People at high risk for severe complications include immunocompromised people, pregnant women without evidence of immunity, and some infants. If the vaccine is contraindicated in a person from one of these groups, he or she may benefit from postexposure prophylaxis with VZIG.
The VZIG product in use in the United States is available under an investigational new drug protocol and can be obtained from the sole authorized US distributor, FFF Enterprises (Temecula, California) at 800-843-7477 or www.fffenterprises.com.
VZIG provides maximum benefit when administered as soon as possible after exposure but may be effective if administered as late as 96 hours after exposure. If VZIG cannot be administered within 96 hours of exposure, administration of immune globulin intravenous should be considered as an alternative (also within 96 hours of exposure).
CDC does not officially recommend using acyclovir as prophylaxis. However, if VZIG is not available or >96 hours have passed since exposure, some experts recommend prophylaxis with acyclovir (80 mg/kg/day, administered 4 times/day for 7 days; maximum dose, 800 mg, 4 times/day) beginning 7–10 days after exposure for immunocompromised people without evidence of immunity. Similarly, a 7-day course of acyclovir also may be given to adults without evidence of immunity if vaccine is contraindicated.
TREATMENT
Oral acyclovir is not recommended for routine use in healthy children with varicella but should be considered for otherwise healthy people at increased risk for moderate to severe disease, such as people aged >12 years, people with chronic cutaneous or pulmonary disorders, people who are receiving long-term salicylate therapy, and people who are receiving short, intermittent, or aerosolized courses of corticosteroids. Intravenous antiviral therapy, when administered within 24 hours of onset of rash, is recommended for immunocompromised people, including patients being treated with chronic corticosteroids.
PREVENTIVE MEASURES FOR TRAVELERS
Vaccine
Indications for Use
Although vaccination against varicella is not a requirement for entry into any country (including the United States), people traveling or living abroad should ensure that they are immune. Evidence of immunity to varicella includes any of the following:
- Documentation of age-appropriate vaccination:
- Preschool-age children aged ≥12 months: 1 dose
- School-age children, adolescents, and adults: 2 doses
- Laboratory evidence of immunity or laboratory confirmation of disease
- Birth in the United States before 1980 (not a criterion for health care personnel, pregnant women, and immunocompromised people)
- A health care provider’s diagnosis of varicella or a health care provider’s verification of a history of varicella disease
- A health care provider’s diagnosis of herpes zoster or a health care provider’s verification of a history of herpes zoster disease
Vaccine Administration
Varicella vaccine contains live, attenuated varicella zoster virus. Two doses of varicella-containing vaccine are now recommended for all people aged ≥12 months without evidence of immunity to varicella who do not have contraindications to the vaccine. The first dose should be administered at age 12–15 months and the second dose at 4–6 years of age. A second catch-up dose of varicella vaccination is recommended for children, adolescents, and adults who have received only 1 dose. The minimum interval between doses for children <13 years is 3 months, and those aged ≥13 years can be vaccinated at an interval of 4–8 weeks. In cases of uncertainty, prior varicella disease is not a contraindication to varicella vaccination.
Vaccine Safety and Adverse Reactions
The 2-dose single-antigen varicella vaccine regimen is generally well tolerated. The most common adverse events after varicella vaccine are self-limited injection site reactions (pain, soreness, redness, and swelling). Fever was reported in uncontrolled trials in 15% of children and 10% of adolescents and adults. A varicella-like rash, usually consisting of a few lesions at the injection site, was reported in 3% and 1% of people receiving the first and second dose, respectively, with generalized rashes with a small number of lesions reported even less frequently.
Contraindications
Allergy
People with severe allergy (hives, swelling of the mouth or throat, difficulty breathing, hypotension, and shock) to gelatin or neomycin or who have had a severe allergic reaction to a prior dose of vaccine should not be vaccinated.
Single-antigen varicella vaccine does not contain egg protein or preservative.
For the combination MMRV vaccine, live measles and live mumps vaccine are produced in chick embryo culture. However, the risk for serious allergic reactions after administration of measles- or mumps-containing vaccines in people who are allergic to eggs is low.
Altered immunity
People with immunosuppression of cellular immune function resulting from leukemia, lymphomas of any type, generalized malignancy, immunodeficiency disease, or immunosuppressive therapy should not be vaccinated. Treatment with low-dose prednisone (<2 mg/kg of body weight per day or <20 mg/day) or aerosolized steroid preparations is not a contraindication to varicella vaccination. People whose immunosuppressive therapy with steroids has been stopped for 1 month (3 months for chemotherapy) may be vaccinated. In addition, people with impaired humoral immunity may be vaccinated. Because HIV-infected children are at greater risk of morbidity from varicella and herpes zoster than healthy children, the Advisory Committee on Immunization Practices recommends considering varicella vaccine for HIV-infected children aged ≥12 months who have CD4+ T-lymphocyte percentages of ≥15% and who do not have evidence of varicella immunity. Eligible children should receive 2 doses of single-antigen varicella vaccine, with a minimum 3-month interval between doses. Vaccination (2 doses, administered 3 months apart) may be considered for HIV-infected older children, adolescents, and adults with CD4+ T-lymphocyte count ≥200 cells/mL, after the risks and benefits are weighed.
Pregnancy
Women who are pregnant or attempting to become pregnant should not receive varicella vaccine. Pregnancy should be avoided for 1 month after varicella vaccination. Breastfeeding is not a contraindication to varicella vaccination.
Precautions
Illness
People who have acute severe illness, including untreated, active tuberculosis, should not be vaccinated until they have recovered.
Recent administration of blood, plasma, or immune globulin
The effect of immune globulin on the response to varicella virus vaccine is unknown. Because passively transferred antibodies may inhibit the antibody response, varicella vaccines should not be administered for 3–11 months, depending on the dose, after administration of blood (except washed red cells), plasma, or immune globulin.
Use of salicylates
No adverse events after varicella vaccination have been reported related to the use of salicylates (such as aspirin). However, the manufacturer recommends that vaccine recipients avoid the use of salicylates for 6 weeks after receiving varicella vaccine because of the association between aspirin use and Reye syndrome after varicella.
BIBLIOGRAPHY
- American Academy of Pediatrics. Varicella. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, editors. Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009. p. 714–27.
- CDC. A new product (VariZIG) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep. 2006 Mar 3;55(8):209–10.
- Gershon AA, Takahasi M, Seward J. Varicella vaccine. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. Philadelphia: Saunders Elsevier; 2008. p. 915–58.
- Guris D, Jumaan AO, Mascola L, Watson BM, Zhang JX, Chaves SS, et al. Changing varicella epidemiology in active surveillance sites—United States, 1995–2005. J Infect Dis. 2008 Mar 1;197 Suppl 2:S71–5.
- Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008 Jun 6;57(RR-5):1–30.
- Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Jun 22;56 (RR-4):1–40.
- World Health Organization. Immunization summary: the 2007 edition. 2007 Feb [cited 2008 Apr 14]. Available from: http://www.unicef.org/publications/files/Immunization_Summary_2007.pdf.
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