Chapter 3Infectious Diseases Related To Travel
Mona Marin, Stephanie R. Bialek
Varicella-zoster virus, a member of the herpesvirus family. Humans are the only reservoir of the virus, and disease occurs only in humans. After primary infection as varicella (chickenpox), the virus remains dormant in the sensory-nerve ganglia and can reactivate at a later time, causing herpes zoster (shingles).
Varicella-zoster virus is transmitted from person to person by direct contact, inhalation of aerosols from vesicular fluid of skin lesions of varicella or herpes zoster, 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. The period of communicability is estimated to begin 1–2 days before the onset of rash and ends 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. People with varicella should be isolated for as long as lesions persist.
In utero infection can also occur as a result of transplacental passage of virus during maternal varicella infection.
Varicella occurs worldwide. In temperate climates, varicella tends to be a childhood disease, with peak incidence among preschool and school-aged children and during late winter and early spring. In tropical climates, infection tends to occur later during childhood and adolescence, 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, Germany, Greece, Korea, Qatar, Saudi Arabia, Spain, Switzerland, United Arab Emirates, and Uruguay. With the implementation of the varicella vaccination program in the United States, substantial declines have occurred in disease incidence, and although varicella is still endemic, the risk of exposure to varicella zoster virus is higher in most other parts of the world than it is in the United States. Additionally, exposure to herpes zoster poses a risk for varicella in susceptible travelers, although localized herpes zoster is much less infectious than varicella. Travelers at highest risk for severe varicella are infants, immunocompromised people, or pregnant women without evidence of immunity (see criteria for evidence of immunity in “Prevention” below).
Varicella is generally a mild disease in children, and most people recover without serious complications. The average incubation period is 14–16 days (range, 10–21 days). Infection is often characterized by a short (1 or 2 days) prodromal period (fever, malaise), although this may be absent in children, and by pruritic rash consisting of crops of macules, papules, and vesicles (typically 250–500 lesions), which appear in ≥3 successive waves and resolve by crusting. Characteristic for varicella is presence of lesions in different stages of development at the same time. Serious complications can occur, most commonly in infants, adolescents, and adults. Complications include secondary bacterial infections of skin lesions, pneumonia, cerebellar ataxia, encephalitis, and hemorrhagic conditions; rarely (about 1 case in 40,000), these complications may result in death.
Modified varicella, also known as breakthrough, can occur in vaccinated people. Breakthrough varicella is usually mild, with <50 lesions, low or no fever, and shorter duration of rash. The rash may be atypical in appearance with fewer vesicles and predominance of maculopapular lesions. Breakthrough varicella is infectious, although less so than varicella in unvaccinated people.
Varicella is often diagnosed clinically. For laboratory confirmation, skin lesions are the preferred specimen. Vesicular swabs or scrapings and scabs from crusted lesions can be used to identify varicella-zoster virus by PCR 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:
- 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 are not sufficiently sensitive to detect antibody following vaccination, and a 4-fold rise in IgG may not occur in vaccinated people.
- Testing for varicella-zoster IgM by using commercial kits is not recommended, because available methods lack sensitivity and specificity; false-positive IgM results are common in the presence of high IgG levels. A capture assay for varicella-zoster IgM is available at CDC; however, there are limitations for IgM testing: a negative IgM result should not be used to rule out the diagnosis, and a positive IgM in the absence of rash should not be used to confirm a diagnosis.
Treatment with antivirals is not routinely recommended for otherwise healthy children with varicella. Treatment with oral acyclovir should be considered for 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 acyclovir is recommended for immunocompromised people, including patients being treated with chronic (or high-dose) corticosteroids, and people with serious, virally mediated complications (such as pneumonia). Therapy initiated within 24 hours of onset maximizes efficacy.
People traveling or living abroad should ensure that they are immune to varicella. Evidence of immunity to varicella includes any of the following:
- Documentation of age-appropriate vaccination:
- Preschool-aged children aged ≥12 months: 1 dose
- School-aged 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
- A health care provider’s diagnosis of herpes zoster or a health care provider’s verification of a history of herpes zoster
Varicella vaccine contains live, attenuated varicella-zoster virus. Single-antigen varicella vaccine is licensed for people aged ≥12 months, and the combination measles-mumps-rubella-varicella vaccine (MMRV) is licensed only for children 1–12 years. CDC recommends varicella vaccination for all people aged ≥12 months without evidence of immunity to varicella who do not have contraindications to the vaccine: 1 dose for children aged 1–4 years and 2 doses for people aged ≥4 years. The minimum interval between doses is 3 months for children aged <13 years and 4 weeks for people aged ≥13 years. When evidence of immunity is uncertain, a possible history of varicella is not a contraindication to varicella vaccination. For detailed information regarding the varicella vaccine, visit www.cdc.gov/vaccines/vpd-vac/varicella/default.htm.
Varicella vaccine is recommended for postexposure administration for unvaccinated healthy people aged ≥12 months and without other evidence of immunity, to prevent or modify the disease. The vaccine should be administered as soon as possible within 5 days after exposure to rash, if there are no contraindications to use. Among children, protective efficacy was reported as ≥90% when vaccination occurred within 3 days of exposure. No data are available regarding a potential benefit of administering a second dose to 1-dose vaccine recipients after exposure. However, administration of the second dose should be considered for these people to bring them up-to-date on vaccination.
Varicella Zoster Immune Globulin
People without evidence of immunity who have contraindications for vaccination and who are at risk for severe varicella and complications are recommended to receive postexposure prophylaxis with varicella zoster immune globulin (VZIG). People at high risk for severe complications include immunocompromised people, pregnant women without evidence of immunity, and some infants.
The VZIG product used 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) toll-free 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 10 days after exposure.
If VZIG is not available, CDC recommends that administration of intravenous immune globulin be considered as an alternative (also within 10 days of exposure).
Although there are limited published data on the benefit of acyclovir as postexposure prophylaxis, if VZIG is not available some experts recommend prophylaxis with acyclovir (80 mg/kg/day, administered 4 times per day for 7 days; maximum dose, 800 mg, 4 times per day), beginning 7–10 days after exposure for people without evidence of immunity and with contraindications for varicella vaccination.
CDC website: www.cdc.gov/chickenpox
- American Academy of Pediatrics. Varicella-zoster infections. In: Pickering LK, editor. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012. p. 774–89.
- CDC. FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella. MMWR Morb Mortal Wkly Rep. 2012 Mar 30;61(12):212.
- Gershon AA, Takahasi M, Seward JF. Varicella vaccine. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: Saunders Elsevier; 2012. p. 837–69.
- 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, Broder KR, Temte JL, Snider DE, Seward JF. Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 May 7;59(RR-3):1–12.
- 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 2011 edition. Geneva: World Health Organization; 2011 [cited 2012 Sep 21]. Available from: http://www.childinfo.org/files/32775_UNICEF.pdf.
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