Measles

Measles (Rubeola) is a highly infectious disease that is caused by the measles virus. There are two phases of disease: a catarrhal (prodromal) stage and an exanthem stage. The catarrhal stage is characterized by a fever with conjunctivitis, coryza, cough, and pathognomonic Koplik spots on the buccal mucosa. The sudden development of a high fever, malaise, and exanthem represents the next phase. The exanthem stage is typically characterized by an erythematous maculopapular rash that originates behind the ears and spreads to the rest of the body towards the feet. Infection is usually self-limiting and followed by lifelong immunity. Disease management includes vitamin A supplementation, symptomatic treatment, and possible post-exposure prophylaxis (PEP). Measles causes transient immunosuppression and may lead to serious complications such as encephalitis, otitis, or pneumonia. A rare but lethal late complication of measles is subacute sclerosing panencephalitis (SSPE), which may also affect immunocompetent individuals. The prognosis is good in uncomplicated cases. However, newborns and immunocompromised patients are more likely to suffer from severe complications.
The measles vaccine is a combination vaccine that protects against measles, mumps, and rubella (MMR vaccine); the MMRV vaccine also protects against varicella. Immunization is recommended for all children, in addition to adults without evidence of immunity to measles, mumps, and/or rubella.

• Distribution: Measles typically occurs in regions with low vaccination rates and in resource-limited countries. ^[1]
• Peak incidence: < 12 months of age ^[1]
• Infectivity ^[1]
  • ∼ 90%
  • Highly contagious 4 days before and up to 4 days after the onset of exanthem. .
• Risk factors for measles, mumps, and/or rubella: The following individuals are at increased risk of acquiring or transmitting measles, mumps, and/or rubella. ^[2][3]
  • Individuals with an immunocompromised state
  • Household or close contacts of immunocompromised individuals
  • College students
  • Health care personnel
  • International travelers

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: measles virus (MV), an RNA virus of the Morbillivirus genus belonging to the Paramyxoviridae family
• Route of transmission: direct contact with or inhalation of virus-containing droplets ^[1]

Incubation period

• Duration: ∼ 2 weeks after infection

Prodromal stage (catarrhal stage) ^[4]

• Duration: ∼ 4–7 days
• Presentation
  • Coryza, cough, and conjunctivitis
  • Fever
  • Koplik spots
    • Pathognomonic enanthem of the buccal mucosa
    • Tiny white or bluish-gray spots on an irregular erythematous background that resemble grains of sand
    • Disappear by the second day of the exanthem stage

Exanthem stage ^[4]

• Duration: ∼ 7 days (develops 1–2 days after enanthem)
• Presentation
  • High fever, malaise
  • Generalized lymphadenopathy
  • Erythematous maculopapular, blanching, partially confluent exanthem
    • Begins behind the ears along the hairline
    • Disseminates to the rest of the body towards the feet (palm and sole involvement is rare)
    • Fades after ∼ 5 days of onset, leaving a brown discoloration and desquamation in severely affected areas

Recovery stage

The cough may persist for another week and may be the last remaining symptom.

The most important findings of measles are the 3 Cs and 1 K: Coryza, Cough, Conjunctivitis, and Koplik spots.

Measles should be suspected in a patient with typical clinical findings. Laboratory tests are always necessary to confirm the diagnosis. ^[5]

• CBC: ↓ leukocytes, ↓ platelets
• Serology
  • Gold standard: detection of Measles-specific IgM antibodies
  • IgG antibodies
• Identification of pathogen: direct virus detection via reverse-transcriptase polymerase chain reaction (RT-PCR) possible
• Biopsy: affected lymph nodes show paracortical hyperplasia and Warthin-Finkeldey cells (multinucleated giant cells formed by lymphocytic fusion).

• Symptomatic treatment ^[6]
• Vitamin A supplementation reduces morbidity and mortality (especially in malnourished children). ^[7]
• Isolate patients with confirmed infection. ^[8][9]
  • All patients: Isolate for 4 days from the onset of rash (longer if immunocompromised).
  • Hospitalized patients: Initiate airborne precautions.
• Measles is a nationally notifiable disease; report all cases to the appropriate health departments within 24 hours. ^[1][5]
• See “Prevention” for postexposure prophylaxis for exposed individuals.

Subacute sclerosing panencephalitis (SSPE) ^[1][10][11]

• Definition: a lethal, generalized, demyelinating inflammation of the brain caused by persistent measles virus infection ^[12][13]
• Epidemiology
  • Primarily affects males between 8 and 11 years of age
  • Usually develops ≥ 7 years after measles infection
• Clinical presentation: characterized by four clinical stages
  • Stage I: dementia, personality changes
  • Stage II: epilepsy, myoclonus, autonomic dysfunction
  • Stage III: decerebration, spasticity, extrapyramidal symptoms
  • Stage IV: vegetative state, autonomic failure
• Diagnosis
  • Electroencephalography
    • Paroxysmal delta waves (very slow, 1–3/sec)
    • Periodic sharp and slow wave complexes
  • Cerebrospinal fluid: ↑ anti-measles IgG
• Prognosis: SSPE leads to death within 1–3 years of diagnosis) ^[14]

Other complications ^[1][10]

• Bacterial superinfection
  • Otitis media
  • Pneumonia (most common cause of death)
  • Laryngotracheitis
• Gastroenteritis
• Meningitis
• Acute encephalitis
  • Frequency: ∼ 1:1000 ^[15]
  • Develops within days of infection
  • Acute disseminated encephalomyelitis may develop within weeks.
• Giant cell pneumonia (viral, most commonly seen in immunosuppressed individuals)

Complications are likely to occur when the fever does not subside after a few days after onset of the exanthem.

We list the most important complications. The selection is not exhaustive.

• The prognosis of measles infection is good in uncomplicated cases.
• Fatal courses are more likely in newborns and immunocompromised patients.
• High fatality rate in resource-limited countries due to secondary bacterial infections.

Vaccination ^[2][3][16]

• Available options: live attenuated vaccines that contain multiple antigens
  • Measles, mumps, rubella vaccine (MMR)
  • Measles, mumps, rubella, varicella vaccine (MMRV)
• Indications and schedule: See “ACIP immunization schedule” for details.
• Contraindications ^[17]
  • Any contraindications to live vaccines ^[17][18]
  • History of anaphylaxis from neomycin
• Precautions ^[17]
  • History of thrombocytopenia
  • Tuberculin skin test (TST) within the preceding 4–6 weeks ^[17][19]
  • Personal or family history of epilepsy (MMRV vaccine only) ^[20]

Evidence of immunity ^[9][17]

Indications to test for immunity to measles, mumps, and rubella ^[2][9][17]

The following at-risk groups should be tested for immunity to determine the need for vaccination. ^[1][3][5]

• Pregnant individuals as part of routine prenatal care ^[21]
• Immunosuppressed individuals (e.g., individuals with HIV) ^[18][22]
• Undervaccinated individuals with:
  • Known exposure to measles, mumps, and/or rubella
  • Suspected prior infection that was not confirmed with laboratory testing
• Inadequate or unknown vaccination status in individuals at increased risk of acquiring or transmitting measles, mumps, and/or rubella

Evidence of immunity to measles, mumps, and/or rubella

Any of the following constitutes as evidence of immunity:

• Being born before 1957 (not valid for health care personnel or, for rubella immunity, pregnant individuals)
• Confirmed receipt of MMR vaccine and/or MMRV vaccine ^[17]
  • For mumps and measles immunity: all age-appropriate recommended doses ^[2][3][16]
  • For rubella immunity: 1 dose at ≥ 12 months of age
• Laboratory evidence of either: ^[9]
  • Prior infection: elevated serum IgM antibodies or positive RT-PCR during the infection
  • Immunity: elevated IgG antibody titers

The MMR vaccine is contraindicated during pregnancy. Individuals without evidence of immunity to MMR should receive one dose of MMR after delivery, preferably before discharge from the health care facility. ^[2]

Individuals with HIV and CD4 percentage ≥ 15% and CD4 count ≥ 200 cells/mm³ for ≥ 6 months and no evidence of immunity to MMR should receive a 2-dose series of the MMR vaccine, administered ≥ 4 weeks apart. Live vaccines are contraindicated in individuals with severe immunocompromise (i.e., CD4 percentage < 15% and CD4 count < 200 cells/mm³). ^[2]

Health care personnel with no evidence of immunity to MMR should receive a 2-dose series of MMR vaccine, administered ≥ 4 weeks apart. ^[2]

Postexposure prophylaxis (PEP) for measles ^[9]

• Indication: negative or indeterminate serology
• Methods
  • Active immunization; for immunocompetent individuals after direct exposure
  • Passive immunization; for immunocompromised individuals
• Further measures for exposed individuals: avoidance of communal facilities