Author(s): Paul Gastañaduy, James Goodson

Infectious Agent

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

Transmission

Measles is transmitted from person to person via respiratory droplets and 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% among susceptible household and institutional contacts. Humans are the only natural host for sustaining measles virus transmission, which makes global eradication of measles feasible.

Epidemiology

Measles 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) from the United States in 2000. Measles virus continues to be imported into the country from other parts of the world, however, and recent prolonged outbreaks in the United States resulting from measles virus importations highlight the challenges faced in maintaining measles elimination.

Given the large global measles burden and high communicability of the disease, travelers could be exposed to the virus in any country they visit where measles remains endemic or where large outbreaks are occurring. Most measles cases imported into the United States occur in unvaccinated US residents who become infected while traveling abroad, often to the World Health Organization (WHO)–defined Western Pacific and European regions. These travelers become symptomatic after returning to the United States and sometimes infect others in their communities, causing outbreaks.

Nearly 90% of imported measles cases are considered preventable by vaccination (i.e., the travelers lacked recommended age- and travel-appropriate vaccination). Furthermore, observational studies in travel clinics in the United States have shown that 59% of pediatric and 53% of adult travelers eligible for measles-mumps-rubella (MMR) vaccine at the time of pretravel consultation were not vaccinated at the visit, highlighting a missed opportunity to reduce the likelihood of measles introductions and subsequent spread. Encourage all eligible travelers to receive appropriate MMR vaccination. Outbreak investigations are costly and resource intensive, and infected people—in addition to productivity losses—can incur direct costs for the management of their illness, including treatment, quarantine, and caregiving.

Clinical Presentation

The incubation period averages 11–12 days from exposure to onset of prodrome; rash usually appears ≈14 days after exposure. Symptoms include fever, with temperature ≤105°F (≤40.6°C); conjunctivitis; coryza (runny nose); cough; and small spots with white or bluish-white centers on an erythematous base appearing on the buccal mucosa (Koplik spots). A characteristic red, blotchy (maculopapular) rash appears 3–7 days after onset of prodromal symptoms. The rash begins on the face, becomes generalized, and lasts 4–7 days.

Common measles complications include diarrhea (8%), middle ear infection (7%–9%), and pneumonia (1%–6%). Encephalitis, which can result in permanent brain damage, occurs in ≈1 per 1,000–2,000 cases of measles. The risk for serious complications or death is highest for children aged ≤5 years, adults aged ≥20 years, and in populations with poor nutritional status or that lack access to health care.

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 manifests as mental and motor deterioration, which can progress to coma and death. SSPE occurs in ≈1 of every 5,000 reported measles cases; rates are higher among children <5 years of age.

Diagnosis

Measles is a nationally notifiable disease. Laboratory criteria for diagnosis include 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 reverse transcription PCR (RT-PCR) testing. The Centers for Disease Control and Prevention’s Measles Virus Laboratory is the national reference laboratory; it provides serologic and molecular testing for measles and technical assistance to state public health laboratories for the collection and shipment of clinical samples for molecular diagnostics and genetic analysis. See detailed information on diagnostic support.

A clinical case of measles illness is characterized by generalized maculopapular rash lasting ≥3 days; temperature ≥101°F (38.3°C); and 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 or epidemiologically linked case, the patient’s temperature does not need to reach ≥101°F (38.3°C) and the rash does not need to last ≥3 days.

Treatment

Treatment is supportive. The WHO recommends vitamin A for all children with acute measles, regardless of their country of residence, to reduce the risk for complications. Administer vitamin A as follows: for infants <6 months old, give 50,000 IU, once a day for 2 days; for infants 6 months old and older, but younger than 12 months, give 100,000 IU once a day for 2 days; for children ≥12 months old give 200,000 IU once a day for 2 days. For children with clinical signs and symptoms of vitamin A deficiency, administer an additional (i.e., a third) age-specific dose of vitamin A 2–4 weeks following the first round of dosing.

Prevention

Measles has been preventable through vaccination since a vaccine was licensed in 1963. 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 includes birth before 1957; laboratory confirmation of disease; laboratory evidence of immunity; or written documentation of age-appropriate vaccination with a licensed, live attenuated measles-containing vaccine¹, namely, MMR or measles-mumps-rubella-varicella (MMRV). For infants 6 months old and older, but younger than 12 months, this includes documented administration of 1 dose of MMR; for people aged ≥12 months, documentation should include 2 doses of MMR or MMRV (the first dose administered at age ≥12 months and the second dose administered no earlier than 28 days after the first dose). Verbal or self-reported history of vaccination is not considered valid presumptive evidence of immunity.

¹From 1963–1967, a formalin-inactivated measles vaccine was available in the United States and was administered to ≈600,000–900,000 people. It was discontinued when it became apparent that the immunity it produced was short-lived. Consider people who received this vaccine unvaccinated.

Vaccination

Measles vaccine contains live, attenuated measles virus, which in the United States is available only in combination formulations (e.g., MMR and MMRV vaccines). MMRV vaccine is licensed for children aged 12 months–12 years and can be used in place of MMR vaccine if vaccination for measles, mumps, rubella, and varicella is needed.

International travelers, including people traveling to high-income 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 per the following schedule.

Infants (6 months old and older, but younger than 12 months): 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.

Children (aged ≥12 months): 2 doses of MMR or MMRV separated by ≥28 days.

Adults born in or after 1957: 2 doses of MMR separated by ≥28 days.

One dose of MMR is ≈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%.

Adverse Reactions

In rare circumstances, MMR vaccination has been associated with anaphylaxis (≈2–14 occurrences per million doses administered); febrile seizures (≈1 occurrence per 3,000–4,000 doses administered, but overall, the rate of febrile seizures after measles-containing vaccine is much lower than the rate with measles disease); thrombocytopenia (≈1 occurrence per 40,000 doses during the 6 weeks after immunization); or joint symptoms (arthralgia develops among ≈25% of nonimmune postpubertal females from the rubella component of the MMR vaccination, and ≈10% have acute arthritis-like signs and symptoms that generally persist for 1–21 days and rarely recur; chronic joint symptoms are rare, if they occur at all). No evidence supports a causal link between MMR vaccination and autism, type 1 diabetes mellitus, or inflammatory bowel disease.

Contraindications

Allergy

People who experienced a severe allergic reaction (difficulty breathing, hives, hypotension, shock, swelling of the mouth or throat) following a prior dose of MMR or MMRV vaccine, or who had an anaphylactic reaction to topically or systemically administered neomycin, should not be vaccinated or revaccinated. People who are allergic to eggs can receive MMR or MMRV vaccine without prior routine skin testing or the use of special protocols.

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; thus, severely immunosuppressed people should not be vaccinated with MMR or MMRV vaccine. For a thorough discussion of recommendations for immunocompromised travelers, see Sec. 3, Ch. 1, Immunocompromised Travelers.

HIV

MMR vaccination is recommended for all people with HIV infection aged ≥12 months who do not have evidence of measles, mumps, and rubella immunity, and who do not have evidence of severe immunosuppression. The assessment of severe immunosuppression can be based on CD4 values (count or percentage); absence of severe immunosuppression is defined as CD4 ≥15% for ≥6 months for children aged ≤5 years, or CD4 ≥15% and CD4 count ≥200 cells/mL for ≥6 months for people aged >5 years.

Leukemia

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 administering the first dose of vaccine.

Steroids & Other Immunosuppressive Therapies

Avoid vaccinating people who have received high-dose corticosteroid therapy (in general, considered to be ≥20 mg or 2 mg/kg body weight of prednisone, or its equivalent, daily for ≥14 days) 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, withhold MMR or MMRV vaccine for ≥3 months after cessation of other immunosuppressive therapies and remission of the underlying disease. See Sec. 3, Ch. 1, Immunocompromised Travelers, for more details.

Pregnancy

MMR vaccines should not be administered to pregnant people or people attempting to become pregnant. Because of the theoretical risk to the fetus, people should be counseled to avoid becoming pregnant for 28 days after receiving a live-virus (e.g., MMR) vaccine.

Precautions

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.

Thrombocytopenia

The benefits of primary immunization are usually greater than the potential risks for vaccine- associated thrombocytopenia. Avoid giving subsequent doses of MMR or MMRV vaccine, however, if an episode of thrombocytopenia occurred ≤6 weeks after a previous dose of vaccine.

Postexposure Prophylaxis

Measles-containing vaccine or immune globulin (IG) can be effective as postexposure prophylaxis. MMR or MMRV administered ≤72 hours after initial exposure to measles virus might provide some protection. If the exposure does not result in infection, the vaccine should induce protection against subsequent measles virus infection.

When administered ≤6 days of exposure, IG can be used to confer temporary immunity in a susceptible person. If the exposure does not result in modified or typical measles, vaccination with MMR or MMRV is still necessary to provide long-lasting protection. Six months after receiving intramuscularly administered IG, or 8 months after receiving intravenously administered IG, administer MMR or MMRV vaccine, provided the patient is aged ≥12 months and the vaccine is not otherwise contraindicated.

CDC website: Measles