Chapter 4 Travel-Related Infectious Diseases
Mona Marin, Adriana S. Lopez
Varicella-zoster virus (VZV), a member of the herpesvirus family. Humans are the only reservoir of VZV, and disease occurs only in humans. After primary infection as varicella (chickenpox), VZV remains latent in the sensory-nerve ganglia and can reactivate later, causing herpes zoster (shingles).
Person to person—primarily via the respiratory route—by inhalation of aerosols from vesicular fluid of skin lesions of varicella or herpes zoster; VZV can also spread by direct contact with the vesicular fluid of skin lesions and possibly infected respiratory tract secretions. VZV enters the host through the upper respiratory tract or the conjunctiva. Varicella is a highly contagious viral disease with secondary attack ratios of approximately 85% (range, 61%–100%) in susceptible household contacts; contagiousness after community exposure is lower. Herpes zoster is approximately 20% as infectious as varicella; in susceptible people, contact with herpes zoster rash causes varicella, not herpes zoster.
The period of communicability of patients with varicella 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. This period may be longer in immunocompromised people. Patients with herpes zoster are contagious while they have active, vesicular lesions (usually 7–10 days). In utero infection can also occur due to transplacental passage of the 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; <5% of adults are susceptible to varicella. Disease typically occurs during late winter and early spring. In tropical climates, by contrast, infection tends to be more common later in childhood, with higher susceptibility among adults than in temperate climates, especially in less densely populated areas. The highest incidence of disease in tropical climates occurs during the driest, coolest months.
With the implementation of the childhood varicella vaccination program in the United States in 1996, substantial declines have occurred in disease incidence. Although still endemic, the risk of exposure to VZV is now lower in the United States than in most other parts of the world. As of 2018, 18% of countries have introduced a routine varicella vaccination program, and an additional 6% have varicella vaccination programs for risk groups only.
Because varicella is endemic worldwide, all susceptible travelers are at risk of infection during travel. Additionally, exposure to herpes zoster poses a risk for varicella in susceptible travelers, although localized herpes zoster is much less contagious than varicella. Travelers at highest risk for severe varicella are infants, adults, and immunocompromised people 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-day) prodromal period (fever, malaise), although this may be absent in children, and a 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 the presence of lesions in different stages of development at the same time.
Serious complications can occur, most commonly in infants, adults, and immunocompromised people. Complications include secondary bacterial infections of skin lesions, sometimes resulting in bacteremia/sepsis, pneumonia, cerebellar ataxia, encephalitis, and hemorrhagic conditions; rarely (about 1 in 40,000 varicella cases), these complications may result in death.
Modified varicella, also known as breakthrough varicella, 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 contagious, although less so than varicella, in unvaccinated people.
Often based on an appropriate exposure history and the presence of a generalized maculopapulovesicular rash, the clinical diagnosis of varicella in the United States has become increasingly challenging as a growing proportion of cases now occur in vaccinated people in whom disease is mild, and rash is atypical. Although not routinely recommended, laboratory diagnosis is likely to become increasingly useful.
For laboratory confirmation, skin lesions are the preferred specimen source. Vesicular swabs or scrapings and scabs from crusted lesions can be used to identify varicella-zoster virus DNA by PCR (preferred method, as it is the most sensitive and specific) 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 but are less reliable than PCR or direct fluorescent antibody methods for virus identification. A significant rise in serum varicella IgG titers from acute- and convalescent-phase samples by any standard serologic assay can confirm a diagnosis retrospectively; these antibody tests may not be reliable in immunocompromised people.
Of note, 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. Visit www.cdc.gov/chickenpox/lab-testing/collecting-specimens.html for additional information on specimen collection and testing for varicella. Varicella is a nationally notifiable disease in the United States.
Treatment with antivirals is not recommended routinely for otherwise healthy children with varicella. Consider treatment with oral acyclovir 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; people who are receiving short, intermittent, or aerosolized courses of corticosteroids; and possibly secondary cases among household contacts. Intravenous acyclovir is recommended for immunocompromised people, including patients being treated with high-dose corticosteroids for ≥2 weeks and people with serious, virally mediated complications (such as pneumonia). Therapy initiated within 24 hours of onset maximizes efficacy.
In the United States, all people, including those traveling or living abroad, should be assessed for varicella immunity, and those who do not have evidence of immunity or contraindications to vaccination should receive age-appropriate vaccination. Vaccination against varicella is not a requirement for entry into any country (including the United States), but people who do not have evidence of immunity should be considered at risk for varicella during international travel. Evidence of immunity to varicella includes any of the following:
- Documentation of age-appropriate vaccination
- Preschool-aged children (≥12 months through 3 years of age): 1 dose
- School-aged children (≥4 years of age), 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 verification of a history of varicella
- A health care provider’s diagnosis of herpes zoster or verification of a history of herpes zoster
Varicella vaccine contains live, attenuated VZV. Single-antigen varicella vaccine is licensed for people aged ≥12 months, and the combination measles-mumps-rubella-varicella (MMRV) vaccine is licensed only for children 1–12 years. CDC recommends varicella vaccine for all people aged ≥12 months without evidence of immunity to varicella who do not have contraindications to the vaccine. For children ≥12 months and <13 years: 2 doses of vaccine administered ≥3 months apart. Typically, the first dose is given at 12–15 months and the second at 4–6 years of age. The second dose may be given before age 4 however, provided it has been at least 3 months since the first dose. For people aged ≥13 years: 2 doses of vaccine administered at least 4 weeks apart.
Contraindications to vaccination include allergy to vaccine components, immune-compromising conditions or treatments, and pregnancy. When evidence of immunity is uncertain, a possible history of varicella is not a contraindication to varicella vaccination. Vaccine effectiveness is approximately 80% after 1 dose and 92%–95% after 2 doses.
VACCINE SAFETY AND ADVERSE REACTIONS
The varicella vaccine is generally well tolerated. The most common adverse events after vaccination are self-limited injection-site reactions (pain, soreness, redness, and swelling). Fever or a varicellalike rash, usually consisting of a few lesions at the injection site or generalized rash with a small number of lesions, are reported less frequently.
Compared with use of separate MMR and varicella vaccines at the same visit, use of the combined MMRV vaccine is associated with a higher risk for fever and febrile seizures, approximately 1 additional febrile seizure for every 2,300–2,600 MMRV vaccine doses administered. Fever and febrile seizures typically occur 5–12 days after the first dose of MMRV, with the greatest incidence among children aged 12–23 months. Use of separate MMR and varicella vaccines helps avoid this increased risk. For detailed information regarding the varicella vaccine, visit www.cdc.gov/chickenpox/vaccination.html.
Varicella vaccine is recommended for postexposure administration to 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. However, administration of a second dose is recommended for exposed people to bring them up-to-date on vaccination and for best protection against future exposures.
Varicella Zoster Immune Globulin
People without evidence of immunity who have contraindications to vaccination and who are at risk for severe varicella and complications are recommended to receive postexposure prophylaxis with varicella zoster immune globulin. The varicella zoster immune globulin product licensed in the United States is VariZIG.
People who should receive VariZIG after exposure include immunocompromised people, pregnant women without evidence of immunity, and some neonates and infants. VariZIG provides maximum benefit when administered as soon as possible after exposure but may be effective if administered as late as 10 days after exposure. In the United States, VariZIG can be obtained from specialty distributors (available from https://varizig.com).
If VariZIG is not available, intravenous immune globulin (IVIG) can be considered (also within 10 days of exposure). In the absence of both VariZIG and IVIG, some experts recommend prophylaxis with acyclovir (80 mg/kg/day in 4 divided doses 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. Published data on the benefit of acyclovir as postexposure prophylaxis among immunocompromised people are limited.
CDC website: www.cdc.gov/chickenpox/
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