Chapter 4 Travel-Related Infectious Diseases
Paul A. Gastañaduy, James L. Goodson
Measles virus is a member of the genus Morbillivirus of the family Paramyxoviridae.
Measles is transmitted from person to person primarily by the airborne route as aerosolized droplet nuclei. Infected people are usually contagious from 4 days before until 4 days after rash onset. Measles is among the most contagious viral diseases known; secondary attack rates are ≥90% in susceptible household and institutional contacts. Humans are the only natural host for sustaining measles virus transmission, which makes global eradication of measles feasible.
The number of reported measles cases in the United States has declined from nearly 500,000 annually in the decade before the measles vaccine program to 37–667 cases annually from 2001 through 2017. As a result of high vaccination coverage and implementation of measles elimination strategies in the Americas, measles in the United States was declared eliminated (defined as the absence of endemic measles virus transmission in a defined geographic area for ≥12 months in the presence of a well-performing surveillance system) in 2000. In September 2016, the Americas became the first region in the world to be certified as having verified elimination of endemic measles virus transmission. However, measles virus continues to be imported into the region from other parts of the world, and recent prolonged outbreaks resulting from measles virus importations highlight the challenges faced in maintaining elimination.
Globally, in 2016, the annual reported measles incidence was 19 cases per million population. Given the large global incidence and high communicability of the disease, travelers may be exposed to the virus in almost any country they visit where measles is endemic or where large outbreaks are occurring, particularly those outside the Western Hemisphere. Most measles cases imported into the United States have come from unvaccinated US residents who became infected while traveling abroad, became symptomatic after returning to the United States, and in some cases infected others in their communities, causing outbreaks.
Humanitarian emergencies following natural disasters, famine, war, large-scale population movements, and disease outbreaks can disrupt immunization services and create persistent reservoirs for vaccine-preventable diseases and for measles virus, in particular. Protracted armed conflict and absence of a centralized government can cripple efforts to provide basic public health services to local civilian populations, including the delivery of vaccinations to children. Aid workers and volunteers in humanitarian emergencies are thus also at an increased risk of being exposed to measles.
Additional information on global measles elimination efforts is available on the Measles & Rubella Initiative website at www.measlesrubellainitiative.org.
The incubation period ranges from 7 to 21 days from exposure to onset of fever; rash usually appears about 14 days after exposure. Symptoms include prodromal fever that can rise as high as 105°F (40.6°C), conjunctivitis, coryza (runny nose), cough, and small spots with white or bluish-white centers on an erythematous base on the buccal mucosa (Koplik spots). A characteristic red, blotchy (maculopapular) rash appears on the third to seventh day after the onset of prodromal symptoms. The rash begins on the face, becomes generalized, and lasts 4–7 days. Common complications include diarrhea (8%), middle ear infection (7%–9%), and pneumonia (1%–6%). Encephalitis, which can result in permanent brain damage, occurs in approximately 1 per 1,000–2,000 cases of measles. The risk of serious complications and death is highest for children aged ≤5 years and adults aged ≥20 years. It is also higher in populations with poor nutritional status.
Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disorder caused by measles virus that usually presents 5–10 years after recovery from the initial primary measles virus infection. SSPE is manifested by mental and motor deterioration, progressing to coma and death and occurs in approximately 1–2 in 10,000 reported measles cases, with a higher rate among children <5 years of age.
Laboratory criteria for diagnosis include any of the following: a positive serologic test for measles-specific IgM, IgG seroconversion or a significant rise in measles IgG level by any standard serologic assay, isolation of measles virus, or detection of measles virus RNA by RT-PCR.
A clinical case of measles illness is characterized by all of the following:
- Generalized maculopapular rash lasting ≥3 days
- Temperature of ≥101°F (38.3°C)
- Cough, coryza, or conjunctivitis
A confirmed case is one with an acute febrile rash illness with laboratory confirmation or direct epidemiologic linkage to a laboratory-confirmed case. In a laboratory-confirmed case or epidemiologically linked case, the temperature does not need to reach ≥101°F (38.3°C) and the rash does not need to last ≥3 days.
Measles is a nationally notifiable disease.
Treatment is supportive. The World Health Organization recommends vitamin A for all children with acute measles, regardless of their country of residence, to reduce the risk of complications. Vitamin A is administered once a day for 2 days at the following doses:
- 50,000 IU for infants aged <6 months
- 100,000 IU for infants aged 6–11 months
- 200,000 IU for children aged ≥12 months
An additional (third) age-specific dose of vitamin A should be given 2–4 weeks later to children with clinical signs and symptoms of vitamin A deficiency. Parenteral and oral formulations of vitamin A are available in the United States.
Measles has been preventable since 1963 through vaccination. People who do not have evidence of measles immunity should be considered at risk for measles, particularly during international travel. Acceptable presumptive evidence of immunity to measles for international travelers includes meeting any of the following criteria:
- Written documentation of age-appropriate vaccination with a live* measles-containing vaccine (MMR or MMRV):
- For infants aged 6–11 months, documented administration of 1 dose of MMR
- For people aged ≥12 months, 2 doses of MMR or MMRV (the first dose should be administered at age ≥12 months; the second dose should be administered no earlier than 28 days after the first dose)
- Laboratory evidence of immunity
- Laboratory confirmation of disease
- Birth before 1957
Verbal or self-reported history of vaccination is not considered valid presumptive evidence of immunity.
*From 1963 through 1967, a formalin-inactivated measles vaccine was available in the United States and was administered to an estimated 600,000–900,000 people. It was discontinued when it became apparent that the immunity it produced was short-lived. People who received this vaccine should be considered unvaccinated.
Measles vaccine contains live, attenuated measles virus. In the United States, it is available only in combination formulations, such as measles-mumps-rubella (MMR) and measles-mumps-rubella-varicella (MMRV) vaccines. MMRV vaccine is licensed for children aged 12 months through 12 years and may be used in place of MMR vaccine if vaccination for measles, mumps, rubella, and varicella is needed.
International travelers, including people traveling to industrialized countries, who do not have presumptive evidence of measles immunity and who have no contraindications to MMR or MMRV, should receive MMR or MMRV before travel according to the following guidelines:
- Infants aged 6–11 months should receive 1 MMR dose. Infants vaccinated before age 12 months must be revaccinated on or after the first birthday with 2 doses of MMR or MMRV separated by ≥28 days. MMRV is not licensed for children aged <12 months.
- Preschool and school-age children (aged ≥12 months) should be given 2 MMR or MMRV doses separated by ≥28 days.
- Adults born in or after 1957 should be given 2 MMR doses separated by ≥28 days.
One dose of MMR is approximately 85% effective when administered at age 9 months; MMR and MMRV are 93% effective when administered at age ≥1 year. Vaccine effectiveness of 2 doses is 97%.
Measles-containing vaccine and immune globulin (IG) may be effective as postexposure prophylaxis. MMR or MMRV, if administered within 72 hours after initial exposure to measles virus, may provide some protection. If the exposure does not result in infection, the vaccine should induce protection against subsequent measles virus infection. IG can be used to prevent or mitigate measles in a susceptible person when administered within 6 days of exposure. However, any immunity conferred is temporary unless modified or typical measles occurs, and the person should receive MMR or MMRV 6 months after intramuscularly administered IG or 8 months after intravenously administered IG, provided the person is then aged ≥12 months and the vaccine is not otherwise contraindicated.
VACCINE SAFETY AND ADVERSE REACTIONS
In rare circumstances, MMR vaccination has been associated with the following adverse events:
- Anaphylaxis (approximately 3.5–10 occurrences per million doses administered)
- Thrombocytopenia (approximately 1 occurrence per 30,000–40,000 doses during the 6 weeks after immunization)
- Febrile seizures (approximately 1 occurrence per 3,000 doses administered, but overall, the rate of febrile seizures after measles-containing vaccine is much lower than the rate with measles disease)
- Joint symptoms (Arthralgia develops among approximately 25% of nonimmune postpubertal women from the rubella component of the MMR vaccination. Approximately 10% have acute arthritislike signs and symptoms that generally persist for 1 day to 3 weeks and rarely recur. Chronic joint symptoms are rare, if they occur at all.)
There is no evidence to support a causal link between MMR vaccination and hearing loss, retinopathy, optic neuritis, ocular palsies, Guillain-Barré syndrome, cerebellar ataxia, Crohn’s disease, or autism.
CONTRAINDICATIONS AND PRECAUTIONS
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 MMR or MMRV vaccine, should not be vaccinated or revaccinated. MMR or MMRV vaccine may be administered to people who are allergic to eggs without prior routine skin testing or the use of special protocols.
Pregnancy—MMR vaccines should not be administered to pregnant women or to those attempting to become pregnant. Because of the theoretical risk to the fetus when the mother receives a live-virus vaccine, women should be counseled to avoid becoming pregnant for 28 days after receipt of MMR vaccine.
Immunosuppression—Enhanced replication of live vaccine viruses can occur in people who have immune deficiency disorders. Death related to vaccine-associated measles virus infection has been reported among severely immunocompromised people. Therefore, severely immunosuppressed people should not be vaccinated with MMR or MMRV vaccine. For a thorough discussion of recommendations for immunocompromised travelers, see Chapter 5, Immunocompromised Travelers.
- People with leukemia in remission, and off chemotherapy, who were not immune to measles when diagnosed with leukemia, may receive MMR vaccine. At least 3 months should elapse after termination of chemotherapy before administration of the first dose.
- MMR vaccination is recommended for all people aged ≥12 months with HIV infection who do not have evidence of measles, rubella, and mumps immunity or evidence of severe immunosuppression. The assessment of severe immunosuppression can be on the basis of CD4 values (count or percentage); absence of severe immunosuppression is defined as CD4 percentages ≥15% for ≥6 months at any age or CD4 count ≥200 cells/mm3 for ≥6 months for people aged >5 years.
- People who have received high-dose corticosteroid therapy (in general, considered to be ≥20 mg prednisone or equivalent daily for a duration of ≥14 days) should avoid vaccination with MMR or MMRV for ≥1 month after cessation of steroid therapy. Corticosteroid therapy usually is not a contraindication when administration is short-term (<14 days) or a low to moderate dose (<20 mg of prednisone or equivalent per day).
- In general, MMR or MMRV vaccine should be withheld for ≥3 months after cessation of other immunosuppressive therapies and remission of the underlying disease. This interval is based on the assumptions that the immune response will have been restored in 3 months and the underlying disease for which the therapy was given remains in remission.
Thrombocytopenia—The benefits of primary immunization are usually greater than the potential risks of thrombocytopenia. However, avoiding a subsequent dose of MMR or MMRV vaccine may be prudent if an episode of thrombocytopenia occurred within approximately 6 weeks after a previous dose of vaccine.
Personal or family history of seizures of any etiology—Compared with administration of separate MMR and varicella vaccines at the same visit, use of MMRV vaccine is associated with a higher risk for fever and febrile seizures 5–12 days after the first dose among children aged 12–23 months. Approximately 1 additional febrile seizure occurs for every 2,300–2,600 MMRV vaccine doses administered. Use of separate MMR and varicella vaccines avoids this increased risk for fever and febrile seizures.
CDC website: www.cdc.gov/measles
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