Clinical Presentation

Figure 2. Figure 2. Manifestations of Measles in Children. Panel A shows an infant with measles conjunctivitis and rash. Patients with measles rash are shown in Panels B, C, and D. In Panel B, pigmentation and desquamation of the measles skin rash (complications that are most often seen in undernourished children) are visible; these signs are evident approximately 5 days after the onset of rash and may continue for weeks. Panel E shows a patient with Koplik spots on the buccal mucosa. Panels A and D were provided by M. Bring of the World Health Organization (WHO), Panel B by the WHO,14 Panel C by U. Sharapov of the Centers for Disease Control and Prevention (CDC), and Panel E by the Office of the Associate Director for Communications, Division of Public Affairs, CDC.

Measles is an acute viral illness that starts with a prodromal phase, lasting 2 to 4 days, of fever and at least one of the “three Cs” (cough, coryza, and conjunctivitis), similar to any upper respiratory tract infection.13 The characteristic measles rash — an erythematous maculopapular exanthem — appears 2 to 4 days after the onset of fever, first on the face and head and then on the trunk and extremities; it may be confluent on the face and upper body (Figure 2). During the ensuing 3 to 5 days, the rash in different parts of the body fades in the order in which it appeared, and full recovery occurs within 7 days after rash onset in uncomplicated cases. Koplik spots, small bluish white plaques on the buccal mucosa, are present in up to 70% of cases and are considered pathognomonic of measles; they may appear 1 to 2 days before the onset of rash and may be present for an additional 1 to 2 days after rash onset (Figure 2).15

Complications associated with measles infection in industrialized countries include otitis media (7 to 9% of patients), pneumonia (1 to 6%), diarrhea (8%), postinfectious encephalitis (approximately 1 per 1000), subacute sclerosing panencephalitis (a progressive degenerative disease with onset usually 5 to 10 years after acute measles; approximately 1 per 10,000), and death (approximately 1 per 1000). The risk of complications is increased among infants, adults older than 20 years of age, pregnant women, undernourished children (particularly those with vitamin A deficiency), and persons with immune suppression (e.g., cancer or human immunodeficiency virus [HIV] infection). An acute progressive encephalitis (measles inclusion-body encephalitis16) and a characteristic giant-cell pneumonia (Hecht’s pneumonia17) are two especially severe complications that may occur in rare cases in persons with immune suppression.

Measles runs a more devastating course in children in developing countries, a phenomenon related to undernutrition, overcrowding, and lack of access to care, with mortality as high as 1 to 15%.18 Measles infection during pregnancy is associated with an increased risk of complications, including miscarriage, preterm birth, neonatal low birth weight, and maternal death.19

Diagnosis

Whereas a typical case of measles is easily recognized during outbreaks, the clinical diagnosis is challenging to many clinicians who have not seen measles and in patients who present before the onset of rash or whose rash is less apparent (e.g., infants with residual maternally acquired antibodies, previous receipt of immunoglobulin, or vaccination after exposure). The typical measles rash may be absent in persons with impaired cell-mediated immunity.20

The differential diagnosis includes rubella, dengue fever, parvovirus B19 infection, human herpesvirus 6 infection, and other infections, as well as reactions to measles vaccine. The measles case definition recommended by the CDC (i.e., generalized maculopapular rash, fever [body temperature, ≥38.3°C], and cough, coryza, or conjunctivitis [or a combination of these symptoms]) has a high sensitivity (75 to 90%) but a low positive predictive value in low-incidence settings, indicating the need for laboratory confirmation.21

The most common laboratory method for confirming measles is detection of measles virus–specific IgM antibodies in a blood specimen (sensitivity, 83 to 89%; specificity, 95 to 99%).22 These antibodies are not detectable in approximately 25% of persons within the first 72 hours after rash onset but are almost always present after 4 days of rash. A real-time polymerase-chain-reaction (PCR) assay for measles virus RNA in urine, blood, oral fluid, or nasopharyngeal specimens can identify infection with a sensitivity of 94% and a specificity of 99%23 before measles IgM antibodies are detectable, and it allows genotyping of the measles virus, which is useful for tracking virus importations and spread.24 All cases of suspected measles should be reported immediately — without waiting for diagnostic test results — to the local or state health department, which can assist with obtaining tests and take actions to minimize spread of virus.

Management

Because there is no specific antiviral medication available, treatment of measles consists of supportive therapy to prevent dehydration and, in some cases, to treat nutritional deficiencies, as well as early detection and treatment of secondary bacterial infections such as pneumonia and otitis media. High doses of vitamin A have been shown to decrease mortality and the risk of complications in young children hospitalized with measles in developing countries.25 In the United States, children with measles have been found to have low levels of serum retinol, and levels tend to be lower among those with more severe illness.26 The American Academy of Pediatrics (AAP) recommends vitamin A administration for all children with severe measles (e.g., requiring hospitalization), with the use of the following age-specific doses: 200,000 IU for children 12 months of age or older; 100,000 IU for infants 6 to 11 months of age; and 50,000 IU for infants younger than 6 months.27 A third age-specific dose should be given 2 to 4 weeks later to children who have clinical signs and symptoms of vitamin A deficiency. In addition, vitamin A therapy should be administered to children with measles who have immunosuppression, have clinical evidence of vitamin A deficiency, or have recently immigrated from areas with a high mortality from measles. Antibiotics, in the absence of pneumonia, sepsis, or other signs of a secondary bacterial complication, are generally not recommended.28 To prevent nosocomial transmission, patients who are suspected to have measles should be triaged in outpatient settings, and hospitalized patients with measles should be isolated with precautions to prevent airborne transmission.27 Patients with measles are infectious from 4 days before to 4 days after the onset of their rash.

Postexposure Prophylaxis

Measles vaccine given within 72 hours after measles exposure, or human immune globulin given up to 6 days after exposure, can prevent or attenuate disease in susceptible persons.29 In household or classroom settings in which the timing of first exposure can be determined, prophylaxis has been shown to be highly effective (up to 90% after vaccine30 and 95% after immune globulin31). Measles-containing vaccine should be considered for all exposed persons who do not have contraindications and who have not been vaccinated or have received only one dose of vaccine.

Administration of immune globulin is particularly critical for patients who are at risk for severe disease, including infants younger than 12 months of age, pregnant women without evidence of measles immunity, and severely immunocompromised persons. The Advisory Committee on Immunization Practices recommends a dose of 0.5 ml per kilogram of body weight administered intramuscularly for persons with a body weight of up to 30 kg and a dose of 400 mg per kilogram intravenously for persons weighing more than 30 kg.29 Because the immunity to measles conferred by administration of immune globulin is temporary, persons who receive immune globulin should subsequently receive MMR vaccine, administered no earlier than 6 months after intramuscular immune globulin or 8 months after intravenous immune globulin.

Severely immunocompromised patients (e.g., bone marrow transplant recipients, as well as persons who have acquired immunodeficiency syndrome or HIV infection with severe immunosuppression and those who have not received MMR vaccine since receiving effective antiretroviral therapy) who are exposed to measles should receive prophylaxis with intravenous immune globulin regardless of their immunologic or vaccination status, because they might not have been protected by vaccination.29

Vaccine Effectiveness

Field studies of the effectiveness of the measles vaccine have found high effectiveness after one dose administered at the age of 12 months or later (median effectiveness, 93%; range, 39 to 100) and even higher effectiveness after two doses (median, 97%; range, 67 to 100).29 The WHO recommends two doses of measles-containing vaccine as the standard of care for the prevention of measles in all countries.2 Two doses are needed to reach herd-immunity thresholds and terminate transmission. Vaccine-induced immunity is probably lifelong in the vast majority of vaccinees.32

Vaccine Safety

Table 1. Table 1. Comparison of the Risk of Complications Associated with Measles and the Risk of Serious Adverse Events after Measles Vaccination.

After 50 years of licensure and with more than 100 million doses administered worldwide each year since 2000, measles-containing vaccines have a well-established safety record. The MMR vaccine has an acceptable side-effect profile. Adverse events include fever (<15% of recipients), transient rashes occurring 7 to 12 days after vaccination (5%), transient lymphadenopathy (5% of children and 20% of adults), parotitis (<1%), and aseptic meningitis (1 to 10 per million).33,34 Serious adverse events are rare and much less common than the risks associated with natural measles infection; these include anaphylaxis (2 to 14 cases per million doses), febrile seizures (1 case per 3000 doses), thrombocytopenic purpura (1 case per 30,000 doses), and measles inclusion-body encephalitis in persons with demonstrated immunodeficiencies (Table 1).35,36 The rubella component of MMR can cause transient arthralgia or arthritis, primarily in susceptible postpubertal female patients.

Antivaccine groups continue to postulate that the MMR vaccine may be a cause of inflammatory bowel disease and autism on the basis of a case series published in 1998 that was later retracted because of falsification of clinical information.37 Subsequent laboratory and epidemiologic studies have not supported an association between the MMR vaccine and these conditions.38,39

General Recommendations for Measles Vaccination

Table 2. Table 2. Summary of Measles Vaccination Recommendations in the United States.

Measles-control programs throughout the world have shown that measles is eliminated if national immunization schedules are fully implemented and high vaccination coverage is achieved and maintained, whereas measles outbreaks occur when populations are not adequately vaccinated. The U.S. recommendations29 are shown in Table 2; schedules for other countries can be found at http://apps.who.int/immunization_monitoring/globalsummary/schedules.

In addition to ongoing vaccination of new birth cohorts, prevention of measles outbreaks requires the identification and vaccination of persons who are at high risk on the basis of exposure or contact frequency (e.g., school-attending children, college students, international travelers, and health care workers) and others who are more likely to have missed both vaccination and natural infection, such as persons from underserved or geographically or socially isolated communities.

Table 3. Table 3. Centers for Disease Control and Prevention Recommendations for Acceptable Evidence of Immunity to Measles in the United States.

In the United States, the only measles-containing vaccines are the MMR vaccine and the combined measles–mumps–rubella–varicella (MMR-V) vaccine. The CDC recommends that the MMR and varicella vaccines be administered separately for the first dose, but they can be given as the MMR-V for the second dose.29 MMR is the vaccine of choice for the prevention of measles in adolescents and adults and in infants 6 to 11 months of age who are at increased risk for exposure (e.g., during outbreaks or international travel) (Table 2). Recommendations regarding acceptable evidence of immunity are available to guide decisions about who should or should not be vaccinated against measles (Table 3).