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Measles

(Rubeola; Morbilli; 9-Day Measles)

by Mary T. Caserta, MD

Measles is a highly contagious viral infection that is most common among children. It is characterized by fever, cough, coryza, conjunctivitis, an enanthem (Koplik spots) on the oral mucosa, and a maculopapular rash that spreads cephalocaudally. Diagnosis is usually clinical. Treatment is supportive. Vaccination is highly effective.

Worldwide, measles infects about 20 million people and causes about 200,000 deaths annually, primarily in children. These numbers can vary dramatically over a short period of time depending on the vaccination status of the population. Measles is rare in the US because of routine childhood vaccination; an average of 63 cases/yr were reported to the Centers for Disease Control and Prevention (CDC) from 2000 to 2007. However, since 2013, cases in the US have been increasing in record numbers, primarily because of imported cases with subsequent spread among unvaccinated groups.

Pathophysiology

Measles is caused by a paramyxovirus and is a human disease with no known animal reservoir or asymptomatic carrier state. It is extremely communicable; the secondary attack rate is > 90% among susceptible people who are exposed.

Measles is spread mainly by secretions from the nose, throat, and mouth during the prodromal or early eruptive stage. Communicability begins several days before and continues until several days after the rash appears. Measles is not communicable once the rash begins to desquamate.

Transmission is typically by large respiratory droplets that are discharged by cough and briefly remain airborne for a short distance. Transmission may also occur by small aerosolized droplets that can remain airborne (and thus can be inhaled) for up to 2 h in closed areas (eg, in an office examination room). Transmission by fomites seems less likely than airborne transmission because the measles virus is thought to survive only for a short time on dry surfaces.

An infant whose mother has immunity to measles (eg, because of previous illness or vaccination) receives antibodies transplacentally; these antibodies are protective for most of the first 6 to 12 mo of life. Lifelong immunity is conferred by infection. In the US, almost all measles cases are imported by travelers or immigrants, with subsequent indigenous transmission occurring primarily among unvaccinated people.

Symptoms and Signs

After a 7- to 14-day incubation period, measles begins with a prodrome of fever, coryza, hacking cough, and tarsal conjunctivitis. Pathognomonic Koplik spots appear during the prodrome, before the onset of rash, usually on the oral mucosa opposite the 1st and 2nd upper molars. The spots resemble grains of white sand surrounded by red areolae. They may be extensive, producing diffuse mottled erythema of the oral mucosa. Sore throat develops.

The rash appears 3 to 5 days after symptom onset, usually 1 to 2 days after Koplik spots appear. It begins on the face in front of and below the ears and on the side of the neck as irregular macules, soon mixed with papules. Within 24 to 48 h, lesions spread to the trunk and extremities (including the palms and soles) as they begin to fade on the face. Petechiae or ecchymoses may occur with severe rashes.

During peak disease severity, a patient’s temperature may exceed 40° C, with periorbital edema, conjunctivitis, photophobia, a hacking cough, extensive rash, prostration, and mild itching. Constitutional symptoms and signs parallel the severity of the eruption and the epidemic. In 3 to 5 days, the fever falls, the patient feels more comfortable, and the rash fades rapidly, leaving a coppery brown discoloration followed by desquamation.

Immunocompromised patients may not have a rash and can develop severe, progressive giant cell pneumonia.

Complications

Complications include

  • Atypical measles syndrome

  • Pneumonia

  • Bacterial superinfection

  • Acute thrombocytopenic purpura

  • Encephalitis

  • Transient hepatitis

  • Subacute sclerosing panencephalitis

Atypical measles syndrome usually occurs in people previously immunized with the original killed-virus measles vaccines, which have been unavailable since 1968. The older vaccines can alter disease expression after infection with wild-type measles. Atypical measles syndrome may begin abruptly, with high fever, prostration, headache, abdominal pain, and cough. The rash may appear 1 to 2 days later, often beginning on the extremities, and may be maculopapular, vesicular, urticarial, or purpuric. Edema of the hands and feet may occur. Pneumonia, pleural effusion, and hilar adenopathy may develop; chest x-ray abnormalities may persist for weeks to months. Symptomatic hypoxemia may occur.

Pneumonia (see Overview of Pneumonia) due to measles virus infection of the lungs occurs in about 5% of patients, even during apparently uncomplicated infection; in infants, it is a common cause of death.

Bacterial superinfections include pneumonia, laryngotracheobronchitis, and otitis media. Measles transiently suppresses delayed hypersensitivity, which can worsen active TB and temporarily prevent reaction to tuberculin and histoplasmin antigens in skin tests. Bacterial superinfection is suggested by pertinent focal signs or a relapse of fever, leukocytosis, or prostration.

Acute thrombocytopenic purpura may occur after infection resolves and cause a mild, self-limited bleeding tendency; occasionally, bleeding is severe.

Encephalitis (see Encephalitis) occurs in 1/1000 to 2000 cases, usually 2 days to 2 wk after onset of the rash, often beginning with recrudescence of high fever, headache, seizures, and coma. CSF usually has a lymphocyte count of 50 to 500/μL and a mildly elevated protein level but may be normal initially. Encephalitis may resolve in about 1 wk or may persist longer, causing morbidity or death.

Transient hepatitis and diarrhea may occur during an acute infection.

Subacute sclerosing panencephalitis (SSPE—see Subacute Sclerosing Panencephalitis (SSPE)) is a rare, progressive, ultimately fatal, late complication of measles.


Diagnosis

  • Clinical evaluation

  • Serologic testing

  • Viral detection via culture or reverse transcription–PCR

Typical measles may be suspected in an exposed patient who has coryza, conjunctivitis, photophobia, and cough but is usually suspected only after the rash appears. Diagnosis is usually clinical, by identifying Koplik spots or the rash. CBC is unnecessary but, if obtained, may show leukopenia with a relative lymphocytosis. Laboratory identification is necessary for public health and outbreak control purposes. It is most easily done by demonstration of the presence of measles IgM antibody in an acute serum specimen or by viral culture or reverse transcription–PCR of throat swabs, blood, nasopharyngeal swabs, or urine samples. A rise in IgG antibody levels between acute and convalescent sera is highly accurate, but obtaining this information delays diagnosis. All cases of suspected measles should be reported to the local health department even before laboratory confirmation.

Differential diagnosis includes rubella (see Rubella), scarlet fever (see Diseases Caused by Streptococci), drug rashes (eg, resulting from phenobarbital or sulfonamides), serum sickness (see Table: Some Causes of Urticaria), roseola infantum (see Roseola Infantum), infectious mononucleosis (see Infectious Mononucleosis), erythema infectiosum (see Erythema Infectiosum), and echovirus and coxsackievirus infections (see Table: Some Respiratory Viruses). Manifestations can also resemble Kawasaki disease (see Kawasaki Disease (KD)) and cause diagnostic confusion in areas where measles is very rare. Atypical measles, because of its greater variability, can simulate even more conditions than typical measles, including Rocky Mountain spotted fever, toxic shock syndromes, and meningococcemia.

Some of these conditions can be distinguished from typical measles as follows:

  • Rubella: A recognizable prodrome is absent, fever and other constitutional symptoms are absent or less severe, postauricular and suboccipital lymph nodes are enlarged (and usually tender), and duration is short.

  • Drug rashes: A drug rash often resembles the measles rash, but a prodrome is absent, there is no cephalocaudal progression or cough, and there is usually a history of recent drug exposure.

  • Roseola infantum: The rash resembles that of measles, but it seldom occurs in children > 3 yr. Initial temperature is usually high, Koplik spots and malaise are absent, and defervescence and rash occur simultaneously.

Prognosis

Mortality is about 2/1000 in the US but is much higher in the developing world. Undernutrition and vitamin A deficiency may predispose to mortality.

Treatment

  • Supportive care

  • For children, vitamin A

Treatment is supportive, including for encephalitis.

Hospitalized patients with measles should be managed with standard contact and airborne precautions. Single-patient airborne infection isolation rooms and N-95 respirators or similar personal protective equipment are recommended. Otherwise healthy outpatients with measles are most contagious for 4 days after the development of the rash and should severely limit contact with others during their illness.

Vitamin A supplementation has been shown to reduce morbidity and mortality due to measles in children in the developing world. Because low serum levels of vitamin A are associated with severe disease due to measles, vitamin A treatment is recommended for all children with measles. The dose is given orally once/day for 2 days and depends on the child’s age:

  • > 1 yr: 200,000 IU

  • 6 to 11 mo: 100,000 IU

  • < 6 mo: 50,000 IU

In children with clinical signs of vitamin A deficiency (see Vitamin A Deficiency), an additional single, age-specific dose of vitamin A is repeated 2 to 4 wk later.

Prevention

A live-attenuated virus vaccine containing measles, mumps, and rubella is routinely given to children in most developed countries (see also Measles, Mumps, and Rubella Vaccine and see Table: Recommended Immunization Schedule for Ages 0–6 yr). Two doses are recommended:

  • The first dose is recommended at age 12 to 15 mo but can be given as young as age 6 mo during a measles outbreak or before international travel.

  • The second is given at age 4 to 6 yr.

Infants immunized at < 1 yr of age still require 2 further doses given after the first birthday. Vaccine provides long-lasting immunity and has decreased measles incidence in the US by 99%. The vaccine causes mild or inapparent, noncommunicable infection. Fever > 38° C occurs 5 to 12 days after inoculation in 5 to 15% of vaccinees and can be followed by a rash. CNS reactions are exceedingly rare; the vaccine does not cause autism.

Contraindications to the vaccine include generalized cancers (eg, leukemia, lymphoma), immunodeficiency, and therapy with immunosuppressants (eg, corticosteroids, irradiation, alkylating agents, antimetabolites). HIV infection is a contraindication only if immunosuppression is severe (CDC immunologic category 3 with CD4 < 15%); if not, the risks of wild measles outweigh the risk of acquiring measles from the live vaccine. Reasons to defer vaccination include pregnancy, serious febrile illness, active untreated TB, or recent administration of antibody (as whole blood, plasma, or any immune globulin). Duration of deferral depends on the type and dose of immune globulin preparation given but may be as long as 11 mo.

Postexposure prophylaxis

Prevention in susceptible contacts is possible by giving the vaccine within 3 days of exposure. If vaccine should be deferred, immune globulin 0.25 mL/kg IM (maximum dose, 15 mL) is given immediately (within 6 days), with vaccination given 5 to 6 mo later if medically appropriate (eg, if the patient is no longer pregnant). An exposed immunodeficient patient with a contraindication to vaccination is given immune globulin 0.5 mL/kg IM (maximum, 15 mL). Immune globulin should not be given simultaneously with vaccine.

In an institutional outbreak (eg, schools), susceptible contacts who refuse or cannot receive vaccination and who also do not receive immune globulin should be excluded from the affected institution until 21 days after onset of rash in the last case. Exposed, susceptible healthcare workers should be excluded from duty from 5 days after their first exposure to 21 days after their last exposure, even if they receive postexposure prophylaxis.


Key Points

  • Incidence of measles is highly variable depending on the vaccination rate in the population.

  • Measles is highly transmissible, developing in > 90% of susceptible contacts.

  • Measles causes about 200,000 deaths annually, primarily in children in the developing world; pneumonia is a common cause, whereas encephalitis is less common.

  • Treatment is mainly supportive, but children should also receive vitamin A supplementation.

  • Universal childhood vaccination is imperative unless contraindicated (eg, by active cancer, use of immunosuppressants, or HIV infection with severe immunosuppression).

  • Give postexposure prophylaxis to susceptible contacts within 3 days of exposure; use vaccine unless contraindicated, in which case give immune globulin.

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