Measles

Measles: A highly communicable infectious disease caused by the measles virus, characterized by fever, cough, coryza, conjunctivitis, and a maculopapular rash.

Subacute sclerosing panencephalitis (SSPE): A rare neurodegenerative disease marked by behavioral and intellectual decline and seizures, typically developing 7 to 11 years after a wild-type measles virus infection. Children who were infected prior to 2 years of age are at highest risk for developing SSPE.

Measles is one of the most contagious diseases, requiring population immunity of 95% or higher to prevent outbreaks.

Prior to the live measles vaccine being licensed in 1963

• This infection was nearly universal with more than 90% of persons infected by 15 years of age.

• 3 to 4 million people were estimated to be infected annually in the United States, with most cases unreported.

• Among reported cases, 48,000 patients were hospitalized and 1,000 people developed chronic disability from measles-associated acute encephalitis annually.

Today, the incidence of measles in the United States is very low because of routine childhood immunization (incidence: < 1 case per 1 million population).

• In recent years, there has been an increase in measles cases and outbreaks in many states.

• Measles outbreaks in the United States are primarily driven by global measles activity and decreasing measles-mumps-rubella (MMR) vaccination coverage. For a list of recent US outbreaks, please visit https://www.cdc.gov/measles/data-research/index.html.

  • Most cases are linked to importation by unvaccinated international US travelers from countries with measles endemics, including Western Europe. Measles is still a prevalent disease with a devastating effect in resource-limited countries.

  • Internal spread occurs primarily among unimmunized subpopulations, including children who are intentionally unimmunized.

Transmission.

• Measles virus is transmitted via direct contact with infectious droplets or airborne spread.

• It is highly communicable with secondary attack rates of greater than 90% among susceptible individuals in close-contact settings.

• Measles virus from an infected individual can survive in closed airspaces for up to 2 hours.

• Those infected are contagious from 4 days prior to the development of rash and 4 days after.

• Patients who are immunocompromised may have prolonged viral shedding within respiratory secretions.

• Patients with SSPE are not contagious.

Incubation period.

• Average of 11 to 12 days from exposure to prodromal symptoms.

• Average of 14 days from exposure to rash appearance, with a range of 7 to 21 days.

• For SSPE, the mean incubation period for 84 cases reported (1976–1983) was 10.8 years.

Measles is caused by a single-stranded, enveloped RNA virus.

The measles virus of the genus Morbillivirus in the Paramyxoviridae family.

The following groups are at highest risk for complications or death:

• Children 5 years and younger or adults 20 years and older

• Pregnant individuals

• Individuals who are immunocompromised

• Children who are malnourished, including vitamin A deficiency

Even among previously healthy individuals, severe complications may occur.

Vaccination significantly reduces risk of infection and complications.

Prodromal symptoms include

• Fever that can increase in stepwise fashion with temperatures up to 40.6° C (105° F).

• Cough.

• Coryza.

• Conjunctivitis.

• Koplik spots are small spots with white or bluish-white centers on an erythematous base on buccal mucosa, commonly at the level of the upper first and second molar. They typically start 2 to 3 days before rash and fade 1 to 2 days after onset.

  • When present, this is a pathognomonic enanthema.

The characteristic red maculopapular rash typically appears 3 to 7 days after the onset of prodromal symptoms.

• The rash begins on the face and spreads cephalocaudally and centrifugally, lasting 4 to 7 days. The rash typically fades in the order it appears.

• The rash may begin as distinct maculopapular lesions that can coalesce over time, especially on the upper body.

• The lesions may initially blanch with pressure; however, by 3 to 4 days, most areas no longer blanch.

• Severe areas may peel in scales.

• The characteristic rash may not appear among individuals who are immunocompromised.

Measles inclusion body encephalitis (MIBE).

• A rare manifestation that primarily occurs among individuals who are immunocompromised and typically presents within 1 year of initial infection

• Presents with subacute progression of neurological dysfunction over the course of weeks to months

SSPE.

• A rare neurological disease that causes progressive behavioral and cognitive decline along with seizures.

• This usually develops 7 to 11 years after wild-type measles virus infection with the highest risk among children infected before 2 years.

Viral exanthems associated with rubella, adenoviruses, and enteroviruses. These can closely mimic measles and necessitate laboratory confirmation to help differentiate.

• Recent international travel history, contact with a person with a known measles infection, or a local outbreak should raise clinical suspicion for measles testing and isolation, particularly among individuals who are unvaccinated.

Meningococcemia.

• The rash in meningococcemia may begin as maculopapular, similar to measles; however, it progresses to petechial or purpuric within hours. Septicemia presents abruptly with prompt disease progression, particularly when left untreated.

Viral hemorrhagic fever.

• A recent travel history to endemic regions for inciting viruses (eg, Ebola, Marburg, Lassa fever, yellow fever, hantavirus, Rift Valley fever) will keep these on the differential. Presentations may vary, but the resulting coagulopathy typically results in a petechial rash that differs from measles.

Toxic shock syndrome.

• More rapid disease onset with a rash that is described as erythrodermic ("sunburn"), as opposed to maculopapular in measles. Toxic shock syndrome typically presents with symptoms of end-organ damage. The history may include an inciting soft tissue infection, burn, or retained foreign body.

Rickettsial disease (Rocky Mountain spotted fever)

• The rash typically begins on the wrists and ankles before spreading inward. The patient typically lives or has traveled to an area of high endemicity of ticks that transmit Rickettsia rickettsii.

Drug reaction

• Unlike measles, respiratory symptoms are unlikely to be present. Additionally, there should be a history of current drug administration acting as the inciting trigger.

Testing for measles should be considered in any patient presenting with fever and rash with a history of recent international travel (past 21 days), unvaccinated status, exposure to international travel, or exposure to people with measles.

• Initial symptoms may be nonspecific, and a high-level of clinical suspicion is necessary during local outbreaks, especially among individuals who are unvaccinated.

If measles is suspected, diagnostic specimens should be collected, and the case should be discussed promptly with the local health department.

A throat swab for RT-PCR should be paired with a serum specimen for measles virus–specific IgM detection for all suspected measles cases.

Measles virus infection can be confirmed in the following ways (Figure 1):

1. Detection of measles viral RNA via RT-PCR

   • Throat, nasal, posterior nasopharyngeal swabs; bronchial lavage; blood; or urine specimens can be tested.

     • Respiratory specimens are preferred; however, collection of at least 3 different samples from different sources increases the diagnostic yield.

   • RT-PCR is available commercially and at most state public health laboratories through the Association of Public Health Laboratories/Centers for Disease Control and Prevention (CDC) Vaccine Preventable Diseases Reference Centers or the CDC measles laboratory.

   • Measles RNA detection is highest from the first day of rash through 3 days after onset but may still be possible up to 10 to 14 days later.

   • Nasopharyngeal or oropharyngeal swabs should be collected immediately when measles is suspected, as PCR is most sensitive at first contact.

2. Detection of measles virus–specific IgM.

   • The sensitivity of measles IgM assays depends on the timing of specimen collection, the patient's immunization status, and the assay method used.

   • Up to 20% of IgM assays may yield false-negative results within the first 72 hours after rash onset. If a measles IgM result is negative but the patient has a rash lasting longer than 72 hours, the test should be repeated.

   • Measles IgM is detectable for at least 1 month after rash onset in individuals who are unimmunized.

   • IgM may be absent or transient in people immunized with 1 or 2 doses of a measles-containing vaccine.

   • A negative IgM result should not exclude measles diagnosis in individuals who are immunized.

3. A 4-fold increase in measles IgG antibody concentration in paired serum specimens.

4. Isolation of measles virus in cell culture is not recommended for routine confirmation, as isolation can take up to 2 weeks.

Imaging is not routinely recommended for children with measles.

Imaging should be considered if complications such as pneumonia or encephalitis are present, as a means to guide management.

Treatment is primarily supportive. Hospitalization may be required for those with complications who require respiratory or hydration support.

Consultation with the local health department is necessary to guide receipt of specimens, isolation, and contact tracing.

Ensure appropriate isolation measures are implemented among hospitalized patients.

• Airborne precautions should be continued for 4 days after rash onset in healthy children and for the entire duration of illness among children who are immunocompromised.

• Patients requiring airborne precautions should be placed in a single-patient airborne infection isolation room.

• All health care staff must use respiratory protection when entering the room, regardless of their presumptive immunity status.

• Immediately notify the hospital epidemiologist or infection prevention department.

No specific antiviral treatment.

The World Health Organization and most US experts recommend vitamin A supplementation for all children with measles, regardless of country of residence, to prevent associated morbidity and mortality.

• Infants younger than 6 months: 50,000 IU once a day for 2 days.

• Infants 6 to 12 months old: 100,000 IU once a day for 2 days.

• Children 12 months and older: 200,000 IU once a day for 2 days.

• For children with clinical signs and symptoms of vitamin A deficiency, administer a third age-specific dose 2 to 6 weeks following the first round of dosing.

Ribavirin has shown efficacy in vitro but is not US Food and Drug Administration approved for routine treatment.

Admission is required for patients with severe symptoms or complications such as pneumonia, encephalitis, or dehydration, especially those in high-risk groups.

Refer patients who are immunocompromised and those with complications to specialists. Patients with severe or atypical presentations may require specialist evaluation.

Consultation with pediatric subspecialty teams may vary based on the presence of complications and severity of illness but could include infectious diseases, neurology, or intensive care for those who are hospitalized.

Approximately 30% of measles cases in the United States from 1987 to 2000 were reported to have 1 or more complications.

Short-term complications include

• Hospitalization: Approximately 1 in 5 people in the United States with measles who are unvaccinated is hospitalized.

• Otitis media: Occurs in approximately 1 in 10 infected children.

• Diarrhea: Occurs in approximately 1 in 10 infected individuals.

• Pneumonia: Occurs in approximately 1 in 20 children with measles; it is the most common cause of death in young children.

• Encephalitis: Affects approximately 1 in 1,000 children with measles, leading to convulsions, deafness, or intellectual disability.

• Death: 1 to 3 of every 1,000 infected children may die from respiratory or neurological complications.

• Immune amnesia: Infection will result in an increase in measles-specific antibodies at the expense of decreased immunity to all other pathogens. It can take 2 to 3 years before protective memory is restored.

Long-term complications include

• MIBE) is a rare, subacute manifestation of measles infection that occurs among individuals who are immunocompromised, usually within 1 year of measles infection. It presents with progressive neurological dysfunction that develops over the course of weeks to months.

• SSPE is a rare but fatal central nervous system disease linked to earlier measles infection.

Pregnancy complications: Measles can cause preterm birth or babies to be born with low birth weight in pregnant individuals who are unvaccinated.

Routine vaccination with MMR or MMR-varicella (MMRV) vaccine is key. Vaccination schedules start at 12 to 15 months with a second dose at 4 to 6 years.

• One dose of MMR is approximately 93% effective at preventing measles; 2 doses are approximately 97% effective.

PEP with vaccine or immunoglobulin is recommended for susceptible individuals. Detailed guidance regarding PEP is found in Table 1 and Table 2.

For children who require admission, in addition to standard precautions, airborne transmission precautions should be continued for 4 days after rash onset in healthy children and for the entire duration of illness among children who are immunocompromised.

Exposed patients should be placed on airborne precautions for 21 days after their last exposure (or 28 days if they received immunoglobulin as PEP).

Red Book Online (RBO) Measles Resources

RBO Immunization News and Resources

Red Book chapters

• Measles

• International Travel

• Immune Globulin Intramuscular (IGIM)

RBO webinars:

• The Use of Vitamin A in the Management of Measles

• Diagnosing Measles in the Pediatric Setting

• Identifying Measles in the Pediatric Setting

CDC: Measles (Rubeola)

CDC video for physicians on recognizing the signs and symptoms of measles to quickly diagnose infected patients: Measles Clinical Features and Diagnosis (YouTube)

“The Pink Book: Course Textbook—14th Edition (2021).” Chapter 13: Measles. Paul Gastanaduy, MD; Penina Haber, MPH; Paul A. Rota, PhD; and Manisha Patel, MD, MS.