Measles is an acute, highly communicable viral disease that begins with a prodromal fever, conjunctivitis, coryza, cough, and Koplik spots on the buccal mucosa. A characteristic red, blotchy rash appears around the third day of illness, beginning on the face and becoming generalized. Measles is frequently complicated by middle ear infection or diarrhea. The disease can be severe, with bronchopneumonia or brain inflammation (encephalitis) leading to death in approximately 2 of every 1,000 cases in developed countries. In the developing world, case-fatality rates often exceed 150 deaths per 1000 cases.
Prior to widespread immunization, measles was common in childhood, with >90% of infants and children infected by 12 years of age. Since vaccine licensure in 1963, measles elimination efforts in the United States have resulted in record low numbers of reported measles cases. Since 1997, measles has not been endemic in the United States; the measles virus does not circulate in the United States except in limited chains of transmission following importation from other countries. Roughly half of imported measles cases occur in U.S. residents returning from visits to foreign countries. The risk of exposure to measles in the United States is low because of the high population immunity achieved through vaccination.
The incubation period of measles, from exposure to prodrome
averages 10–12 days. From exposure to rash onset averages
14 days (range, 7–18 days).
The prodrome lasts 2–4 days (range 1–7 days). It is characterized
by fever, which increases in stepwise fashion, often
peaking as high as 103°–105°F. This is followed by the onset
of cough, coryza (runny nose), or conjunctivitis.
Koplik spots, a rash (enanthem) present on mucous
membranes, is considered to be pathognomonic for measles.
It occurs 1–2 days before the rash to 1–2 days after the rash,
and appears as punctate blue-white spots on the bright red
background of the buccal mucosa.
The measles rash is a maculopapular eruption that usually
lasts 5–6 days. It begins at the hairline, then involves the
face and upper neck. During the next 3 days, the rash
gradually proceeds downward and outward, reaching the
hands and feet. The maculopapular lesions are generally
discrete, but may become confluent, particularly on the upper
body. Initially, lesions blanch with fingertip pressure. By 3–4
days, most do not blanch with pressure. Fine desquamation
occurs over more severely involved areas. The rash fades in
the same order that it appears, from head to extremities.
Other symptoms of measles include anorexia, diarrhea,
especially in infants, and generalized lymphadenopathy.
Isolation of measles virus is not recommended as a routine
method to diagnose measles. However, virus isolates are
extremely important for molecular epidemiologic surveillance
to help determine the geographic origin of the virus and the
viral strains circulating in the United States.
Measles virus can be isolated from urine, nasopharyngeal
aspirates, heparinized blood, or throat swabs. Specimens for
virus culture should be obtained from every person with a
clinically suspected case of measles and should be shipped
to the state public health laboratory or CDC, at the direction
of the state health department. Clinical specimens for viral
isolation should be collected at the same time as samples
taken for serologic testing. Because the virus is more likely to
be isolated when the specimens are collected within 3 days
of rash onset, collection of specimens for virus isolation
should not be delayed until serologic confirmation is obtained.
Clinical specimens should be obtained within 7 days, and not
more than 10 days, after rash onset.
Serologic testing, most commonly by enzyme-linked immunoassay
(ELISA or EIA), is widely available and may be
diagnostic if done at the appropriate time. Generally, a
previously susceptible person exposed to either vaccine or
wild-type measles virus will first mount an IgM response and
then an IgG response. The IgM response will be transient
(1–2 months), and the IgG response should persist for many
years. Uninfected persons should be IgM negative and will
be either IgG negative or IgG positive, depending upon
their previous infection history.
ELISA for IgM antibody requires only a single serum specimen
and is diagnostic if positive. The preferred reference test
is a capture IgM test developed by CDC. This test should
be used to confirm every case of measles that is reported to
have some other type of laboratory confirmation. IgM capture
tests for measles are often positive on the day of rash onset.
However, in the first 72 hours after rash onset, up to 20%
of tests for IgM may give false-negative results. Tests that
are negative in the first 72 hours after rash onset should be
repeated. IgM is detectable for at least 28 days after rash
onset and frequently longer.
A variety of tests for IgG antibodies to measles are available
and include ELISA, hemagglutination inhibition (HI),
indirect fluorescent antibody tests, microneutralization,
and plaque reduction neutralization. Complement fixation,
while widely used in the past, is no longer recommended.
IgG testing for acute measles requires demonstration of a
rise in titer of antibody against measles virus, so two serum
specimens are always required. The first specimen should be
drawn as soon after rash onset as possible. The second specimen
should be drawn 10–30 days later. The tests for IgG
antibody should be conducted on both specimens at the
same time. The same type of test should be used on both
specimens. The specific criteria for documenting an increase
in titer depend on the test.
Tests for IgG antibody require two serum specimens, and a
confirmed diagnosis cannot be made until the second
specimen is obtained. As a result, IgM tests are generally
preferred to confirm the diagnosis of measles.
Prevention of Spread of Measles Virus
Persons who have a generalized rash and fever and persons who have fever and respiratory symptoms following exposure to a person with measles may be infectious with measles. Persons who are potentially infectious with measles should minimize the risk of spread of the disease by limiting contact with other people who may be susceptible to measles. Contact should be limited until a medical diagnosis has been established excluding measles, or the symptoms resolve completely, or 4 days have passed since the onset of the rash. Persons who are potentially infectious with measles should especially avoid public transportation (including commercial airlines) and crowded indoor areas. Patients who suspect they may have measles should call ahead before visiting a clinic or hospital so that arrangements may be made for the health-care provider to attend to the patient without exposing others in the facility to measles.
Measles vaccine contains live, attenuated measles virus. It is available as a single-antigen preparation or combined with live, attenuated mumps or rubella vaccines, or both. Combined measles, mumps, and rubella (MMR) vaccine is recommended whenever one or more of the individual components are indicated.
Although vaccination against measles, mumps, or rubella is not a requirement for entry into any country (including the United States), persons traveling or living abroad should ensure that they are immune to all three diseases. In general, travelers can be considered immune to measles if they have documentation of physician-diagnosed measles, laboratory evidence of measles immunity, or proof of receipt of two doses of live measles vaccine with the first dose received on or after their first birthday and the second dose at least 28 days later. Most persons born before 1957 have had measles disease and generally need not be considered susceptible. However, measles or MMR vaccine may be given to these persons if there is reason to believe they might be susceptible.
The recommended routine age for measles vaccination of infants in the United States is 12-15 months. A single dose of MMR vaccine induces antibody formation to all three viruses in at least 95% of susceptible persons vaccinated at 12 months of age. A second dose is expected to induce immunity in most vaccinees who do not respond to the first dose. The second dose should be separated from the first by at least 28 days and is routinely administered at 4-6 years of age. Because infants and children traveling internationally are at an increased risk of exposure to measles, earlier vaccination with the first and second doses is recommended.
MMR may be administered simultaneously (but in a different site) with any other live or inactivated vaccine. Inactivated vaccines and typhoid vaccines may be administered at any time before or after live measles-containing vaccine. However, if MMR vaccine and live yellow fever vaccine are not administered simultaneously, they should be separated by an interval of at least 28 days.
Adverse Reactions to Vaccination
Fever and rash, the most common adverse reactions following MMR vaccine, are usually attributable to the measles component. Approximately 5% of vaccinees have fever >39.4°C (>103°F) or a generalized rash. Fever and rash usually occur 7-12 days after vaccination and last 1-2 days. Transient lymphadenopathy sometimes occurs after MMR and is attributable to the rubella component. Parotitis has been reported rarely after MMR receipt and is attributable to the mumps component of the vaccine. Joint symptoms (arthralgia or arthritis or both) are reported in 25% of rubella-susceptible postpubertal women who receive MMR or other rubella-containing vaccine. Joint symptoms are usually mild and transient. Allergic reactions have been reported after MMR vaccine, ranging from mild (urticaria or wheal and flare at the injection site, generalized rash, and pruritis) to severe anaphylactic reactions. Severe allergic reactions are estimated to occur less than once per million doses. Clinically apparent low platelet counts have been reported at a rate of <1 case per 30,000 doses. Central nervous system conditions, including aseptic meningitis, encephalitis, and encephalopathy, have been reported after MMR receipt, but are very uncommon (<1 case per million doses). Reactions following the second dose of MMR (except allergic reactions) are less frequent than reactions following the first dose and occur only primarily among the small proportion of persons who did not respond to the first dose.
Vaccine Precautions and Contraindications
Persons with severe allergy (i.e., 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 should not be vaccinated with MMR except with extreme caution.
In the past, persons with a history of anaphylactic reactions after eating eggs were considered to be at increased risk of serious reactions after receipt of measles- and mumps-containing vaccines, which are produced in chick embryo fibroblasts. However, recent data suggest that anaphylactic reactions to measles- and mumps-containing vaccines are not associated with hypersensitivity to egg antigens, but to other components of the vaccines (such as gelatin). The risk for serious allergic reactions following receipt of these vaccines by egg-allergic persons is extremely low, and skin testing with vaccine is not predictive of allergic reaction to vaccination. MMR may be administered to egg-allergic persons without prior routine skin testing or the use of special protocols.
Pregnancy and Breastfeeding
Pregnant women should not receive MMR vaccine. Pregnancy should be avoided for 1 month after receipt of monovalent measles vaccine and MMR or other rubella-containing vaccines. Close contact with pregnant women is not a contraindication to MMR vaccination. Breastfeeding is not a contraindication to MMR vaccination of either a woman or an infant.
Replication of vaccine viruses can be prolonged in persons who are immunosuppressed or immunodeficient for any reason (e.g., who have congenital immunodeficiency, HIV infection, leukemia, lymphoma, or generalized malignancy, or who are receiving therapy with alkylating agents, antimetabolites, radiation, or large doses of corticosteroids). Evidence based on case reports has linked infection with measles vaccine virus to subsequent death in six severely immunosuppressed persons. For this reason, persons who are severely immunosuppressed for any reason should not be given MMR vaccine. Healthy, susceptible close contacts of severely immunosuppressed persons may be vaccinated.
In general, persons receiving large daily doses of corticosteroids (>2 mg/kg per day or >20 mg/day of prednisone) for 14 days should not receive MMR vaccine because of concern about vaccine safety. MMR and its component vaccines should be avoided for at least 1 month after cessation of high-dose therapy. Persons receiving low-dose or short-course (<14 days) therapy; alternate-day treatment; maintenance physiologic doses; or topical, aerosol, intra-articular, bursal, or tendon injections may be vaccinated. Although persons receiving high doses of systemic corticosteroids daily or on alternate days during an interval of <14 days generally can receive MMR or its component vaccines immediately after cessation of treatment, some experts prefer waiting until 2 weeks after completion of therapy. Persons receiving cancer chemotherapy or radiation who have not received these treatments for at least 3 months may receive MMR or its component vaccines.
Measles disease can be severe in persons with HIV infection. Available data indicate that vaccination with MMR has not been associated with severe or unusual adverse events in HIV-infected persons without evidence of severe immunosuppression, although antibody responses have been variable. MMR vaccine is recommended for all asymptomatic HIV-infected persons and should be considered for symptomatic persons who are not severely immunosuppressed. Asymptomatic persons do not need to be evaluated and tested for HIV infection before MMR or other measles-containing vaccines are administered. A theoretical risk of an increase (probably transient) in HIV viral load after MMR vaccination exists because such an effect has been observed with other vaccines. The clinical significance of such an increase is not known.
MMR and other measles-containing vaccines are not recommended for HIV-infected persons with evidence of severe immunosuppression (e.g., a very low CD4+ T-lymphocyte count), primarily because of the report of a case of measles pneumonitis in a measles vaccine recipient who had an advanced case of AIDS. Refer to the Advisory Committee on Immunization Practices (ACIP) recommendations on MMR for additional details on vaccination of persons with symptomatic HIV infection.
Vaccination of travelers with moderate or severe acute illness should be postponed until their condition has improved. Minor illnesses, such as upper respiratory infections with or without low-grade fever, do not preclude vaccination.
MMR vaccination has no effect on antibiotics or antimalarial drugs, and the drugs do not reduce the immunogenicity of MMR. Persons taking these products should be vaccinated as usual.
Interaction with Immune Globulin or Other Antibody-Containing Blood Products
MMR or its component vaccines should be administered at least 14 days before the administration of antibody-containing blood products, such as immune globulin, because passively acquired antibodies may interfere with the response to the vaccine. Otherwise, MMR vaccination should be delayed until 3 to 11 months after administration of blood products, depending on the type of blood product received.
Tuberculin skin testing is not a prerequisite for vaccination with MMR or other measles-containing vaccine. TB skin testing has no effect on the response to MMR vaccination. However, measles vaccine (and possibly mumps, rubella, and varicella vaccines) can suppress the response to skin testing in a person infected with Mycobacterium tuberculosis. To minimize the risk of a false-negative interpretation, TB skin testing should be done prior to MMR vaccination or at the same time MMR is administered, because the mild immunosuppressive effect of the vaccine will not occur for several days after vaccination. Otherwise, TB skin testing should be delayed for 4-6 weeks after MMR vaccination.
There is no specific antiviral therapy for measles, and the basic treatment consists of providing necessary supportive therapy such as hydration and antipyretics and treating complications such as pneumonia. Multiple studies have shown that vitamin A supplementation improves outcome of measles in communities where vitamin A deficiency is known to occur. Although vitamin A deficiency is not a major problem in the United States, low serum concentrations have been found in children with severe measles. Therefore, the American Academy of Pediatrics recommends vitamin A supplementation be considered for children 6 months of age (limited data are available about the safety of vitamin A for infants <6 months of age) who have any of the following risk factors: immunodeficiency, clinical evidence of vitamin A deficiency, impaired intestinal absorption, moderate to severe malnutrition or recent immigration from areas where high measles mortality rates have been observed. All children 6 months to 2 years of age who are hospitalized with measles should also receive vitamin A. The recommended dosage, administered orally as a capsule, is a single dose of 100,000 IU for children 6-11 months of age or 200,000 IU for children 1 year of age. The dose should be repeated the next week and again 4 weeks later for children with evidence of vitamin A deficiency.