Measles (Rubeola)

Infectious Agent

Measles virus is a member of the genus Morbillivirus of the family Paramyxoviridae.

Transmission

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.

Epidemiology

The number of reported measles cases in the United States has declined from nearly 900,000 annually in the early 1940s to 37–667 cases annually from 2001 through 2015. As a result of high vaccination coverage and better measles control in the Americas, in 2000, 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 2002, indigenous measles virus circulation was interrupted in the entire Western Hemisphere. However, measles virus continues to be imported into the region from other parts of the world, and recent outbreaks resulting from measles virus importations highlight the challenges faced in maintaining elimination. Globally, in 2014, the annual reported measles incidence was 40 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, particularly those outside the Western Hemisphere, where measles is endemic or where large outbreaks are occurring. In recent years, measles has been imported into the United States from frequently visited countries, including the United Kingdom, France, Germany, India, and the Philippines, where large outbreaks have been reported. 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. Additional information on global measles control efforts is available on the Measles & Rubella Initiative website at www.measlesrubellainitiative.org.

Clinical Presentation

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. 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), a rare but serious degenerative central nervous system disease caused by a persistent infection with a defective measles virus, is estimated to occur in 4–11 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.

Diagnosis

Laboratory criteria for diagnosis include any of the following: a positive serologic test for measles 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, 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

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.

Prevention

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:

  • 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 or MMRV
    • 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

Vaccine

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 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 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 or MMRV doses separated by ≥28 days.

One dose of MMR or MMRV is approximately 85% effective when administered at age 9 months and 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 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 is approximately 25–33 cases for every 100,000 doses of MMR vaccine administered, but overall, the rate of febrile seizure 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.)

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’s 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.

Contraindications and Precautions

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 MMR or MMRV vaccine, should not be 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 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 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 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 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. 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).
  • Other immunosuppressive therapy: in general, MMR or MMRV vaccine 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.

Precautions

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

Bibliography

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Authors

Paul A. Gastañaduy, James L. Goodson