Chapter 3Infectious Diseases Related To Travel
Amy Parker Fiebelkorn, James L. Goodson
Measles virus is a member of the genus Morbillivirus of the family Paramyxoviridae.
Measles is transmitted primarily from person to person by large respiratory droplets but can also spread 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 one of 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 900,000 annually in the early 1940s to an average of 83 cases annually from 2001 through 2011. As a result of high vaccination coverage and better measles control in the Americas, in 2000, measles was declared eliminated (no disease transmission for at least 12 months) in the United States. Indigenous measles virus circulation was interrupted in 2002 in the rest of the Western Hemisphere. However, measles virus continues to be imported into the United States from other parts of the world. Globally, an estimated 20 million measles cases occur each year. Given the large global incidence and high communicability of the disease, travelers may be exposed to the virus in almost any country they visit, particularly those outside the Western Hemisphere, where measles is endemic or where large outbreaks are occurring. Of the 222 reported measles cases in the United States in 2011, 200 (90%) were associated with importations from other countries, including 72 direct importations (52 among US residents traveling abroad and 20 among foreign visitors). The largest percentage of importations (46%) was among people who acquired the disease in Europe. However, importations consistently occur from other countries and regions, including India and the Philippines. Additional information on global measles control efforts is available on the Measles Initiative website at www.measlesinitiative.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 prodromal symptoms appear. 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.
Subacute sclerosing panencephalitis (SSPE), a rare but serious degenerative central nervous system disease caused by a persistent infection with a defective measles virus, is estimated to occur in 1 per 100,000 cases. However, among people who became infected with measles during the 1989–1991 measles resurgence in the United States, the estimated risk of SSPE was 22 per 100,000 reported measles cases. SSPE is manifested by mental and motor deterioration that starts an average of 7–10 years after measles virus infection (most frequently in children who were infected at age <2 years), progressing to coma and death. 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.
Laboratory criteria for diagnosis include any of the following: a positive serologic test for measles IgM, IgG seroconversion, a significant rise in measles IgG level by any standard serologic assay, isolation of measles virus, or identification by PCR of measles virus RNA from a clinical specimen.
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 that is either laboratory-confirmed or that meets the clinical case definition and is epidemiologically linked to a confirmed case. A laboratory-confirmed case does not need to meet the clinical case definition.
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 during international travel. Acceptable presumptive evidence of immunity to measles for international travelers includes meeting any of the following criteria:
- For infants aged 6–11 months, documented administration of 1 dose of live measles-containing vaccine (MCV) and for people aged ≥12 months, 2 doses of MCV ≥28 days apart, on or after the first birthday
- Laboratory evidence of immunity
- Birth before 1957
- Documented physician-diagnosed measles
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) vaccine. MMRV vaccine is licensed for children aged 12 months to 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 MCV, should receive MCV before travel according to the following guidelines:
- Infants aged 6–11 months should receive 1 MCV dose. Infants vaccinated before age 12 months must be revaccinated on or after the first birthday with 2 doses of MCV 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 MCV doses separated by ≥28 days.
- Adults born in or after 1957 should be given 2 MCV doses separated by ≥28 days.
One dose of MCV is approximately 85% effective if administered at age 9 months and up to 95% effective if administered at age ≥1 year. More than 99% of people who receive 2 doses of MCV develop serologic evidence of measles immunity.
MCV and immune globulin (IG) may be effective as postexposure prophylaxis. MCV, 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 MCV 5–6 months after IG administration.
Vaccine Safety and Adverse Reactions
In rare circumstances, MMR vaccination has been associated with the following adverse events:
- Anaphylaxis (approximately 1–3.5 occurrences per million doses administered)
- Thrombocytopenia (a rate of 1 case in every 25,000 doses during the 6 weeks after immunization)
- Febrile seizures (The risk of febrile seizures increases approximately 3-fold 8–14 days after receipt of MMR vaccine, but overall, the rate of febrile seizure after MCV is much lower than the rate after measles disease.)
- Joint symptoms (Arthralgia develops among approximately 25% of susceptible 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.)
Evidence does not support a causal link between MMR vaccination and any of the following: hearing loss, retinopathy, optic neuritis, ocular palsies, Guillain-Barré syndrome, cerebellar ataxia, Crohn disease, or autism. A published report on MMR vaccination and inflammatory bowel disease and pervasive developmental disorders (such as autism) has never been replicated by other studies, and has subsequently been widely discredited and retracted by the journal.
Compared with use of 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, and approximately 1 additional febrile seizure 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.
Precautions and Contraindications
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 revaccinated. MMR or MMRV vaccines may be administered to people who are allergic to eggs without prior routine skin testing or the use of special protocols.
Enhanced replication of 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 vaccines (for a thorough discussion of recommendations for immunocompromised travelers, see Chapter 8, 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 asymptomatic HIV-infected people who do not have evidence of severe immunosuppression (age-specific CD4 T-lymphocyte percentages of ≥15% of total) and for whom measles vaccination would otherwise be indicated. MMR vaccination should also be considered for all symptomatic HIV-infected people who do not have evidence of severe immunosuppression.
- People who have received high-dose corticosteroid therapy (in general, considered to be >20 mg prednisone or equivalent daily or on alternate days for an interval of ≥14 days) should avoid vaccination with MMR or MMRV for ≥1 month after cessation of steroid therapy.
- People who have received high-dose corticosteroid therapy daily or on alternate days for an interval of <14 days generally can be vaccinated with MMR or MMRV immediately after cessation of treatment, although some experts prefer waiting until 2 weeks after completion of therapy.
- Other immunosuppressive therapy: in general, MMR or MMRV vaccines should be withheld for ≥3 months after cessation of the immunosuppressive therapy 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.
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.
CDC website: www.cdc.gov/measles
- American Academy of Pediatrics. Measles. 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. 489–99.
- Bellini WJ, Rota JS, Lowe LE, Katz RS, Dyken PR, Zaki SR, et al. Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis. 2005 Nov 15;192(10):1686–93.
- CDC. General recommendations on immunization—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(2):1–64.
- CDC. Measles—United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Apr 20;61:253–7.
- CDC. Public health reporting and national notification for measles. Atlanta: CDC; 2009 [updated 2010 Jun 10; cited 2012 Sep 21]. Available from: www.cste.org/resource/resmgr/PS/09-ID-48.pdf.
- CDC. Recommended adult immunization schedule—United States, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(04):1–7.
- CDC. Recommended immunization schedules for persons aged 0 through 18 Years—United States, 2012. MMWR Morb Mortal Wkly Rep. 2012 Feb 10;61(5):1–4.
- European Centre for Disease Prevention and Control. European monthly measles monitoring (EMMO). Surveillance Report [Internet]. 2012 Feb 21 [cited 2012 Sep 21](8). Available from: http://ecdc.europa.eu/en/publications/Publications/SUR_EMMO_European-monthly-measles-monitoring-February-2012.pdf.
- King GE, Markowitz LE, Patriarca PA, Dales LG. Clinical efficacy of measles vaccine during the 1990 measles epidemic. Pediatr Infect Dis J. 1991 Dec;10(12):883–8.
- 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.
- MeaslesRubellaInitiative.org [Internet]. Washington, DC: American National Red Cross; 2012 [cited 2012 Sep 21]. Available from: http://www.measlesrubellainitiative.org/mi/.
- Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis. 2004 May 1;189 Suppl 1:S4–16.
- Strebel PM, Papania MJ, Fiebelkorn AP, Halsey NA. Measles vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: Saunders Elsevier; 2012. p. 352–87.
- Sudfeld CR, Navar AM, Halsey NA. Effectiveness of measles vaccination and vitamin A treatment. Int J Epidemiol. 2010 Apr;39 Suppl 1:i48–55.
- Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998 May 22;47 (RR-8):1–57.
- Watson JC, Pearson JA, Markowitz LE, Baughman AL, Erdman DD, Bellini WJ, et al. An evaluation of measles revaccination among school-entry-aged children. Pediatrics. 1996 May;97(5):613–8.
- World Health Organization. Measles [fact sheet no. 286]. Geneva: World Health Organization; 2012 [cited 2012 Sep 21]. Available from: http://www.who.int/mediacentre/factsheets/fs286/en/index.html.
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