> Table of Contents > Measles (Rubeola)
Measles (Rubeola)
Herbert L. Muncie Jr., MD
image BASICS
DESCRIPTION
  • A highly communicable, acute viral illness characterized by an exanthematous maculopapular rash that begins at the head and spreads inferiorly to the trunk and extremities
  • Rash is preceded by fever and the classic triad of cough, coryza, and conjunctivitis (3 Cs). Koplik spots are pathognomonic lesions of the oral mucosa.
  • Public health problem in the developing world, with significant morbidity and mortality
  • System(s) affected: hematologic; lymphatic; immunologic; pulmonary; skin
  • Synonym(s): rubeola
EPIDEMIOLOGY
  • Transmission: direct contact with infectious droplets; highly contagious; 90% of nonimmune close contacts likely to become infected on exposure.
    • Droplets can remain in the air for hours.
  • Infectivity is greatest during the prodromal phase.
    • Patients are considered contagious from 4 days before symptoms until 4 days after rash appears.
    • Immunocompromised patients are considered contagious for the entire duration of disease.
  • Incubation period: averages 12.5 days from exposure to onset of prodromal symptoms (1)[B]
  • Predominant age: varies based on local vaccine practices and disease incidence. In developing countries, most cases occur in children <2 years.
Incidence
  • United States: no longer considered an endemic disease by the CDC; isolated outbreaks still occur.
  • In the first half of 2015, the CDC reported 159 confirmed cases of measles. Of these cases, 111 (70%) were associated with an outbreak that originated in Disney theme parks in Orange County, California.
    • Many cases were in vaccine-eligible patients who declined due to philosophic or religious beliefs.
    • Children aged 6 to 23 months traveling abroad are at increased risk if unvaccinated.
  • Worldwide: An estimated 20 million measles cases occur each year, with 122,000 measles deaths in
    2012. Over 95% of measles deaths occur in poor countries with limited health infrastructure (2).
ETIOLOGY AND PATHOPHYSIOLOGY
Measles virus enters through the respiratory mucosa and replicates locally. It spreads to regional lymphatic tissues and other reticuloendothelial sites via the bloodstream.
  • Measles virus is a spherical, enveloped, nonsegmented, single-stranded, negative-sense RNA virus of genus Morbillivirus, family Paramyxoviridae.
  • Humans are the only natural host.
RISK FACTORS
  • For developing measles:
    • Lack of adequate vaccination (two doses)
    • Travel to countries where measles is endemic
    • Contact with exposed individuals, travelers, or immigrants
  • For severe measles or measles complications:
    • Immunodeficiency
    • Malnutrition
    • Pregnancy
    • Vitamin A deficiency
    • Age <5 years or >20 years
GENERAL PREVENTION
  • 100% preventable with proper vaccination (3)[A]
  • Measles vaccine (active immunization)
    • Vaccine is usually given in combination with mumps and rubella (MMR) or with added varicella (MMR-V; ProQuad)
    • Primary vaccination requires two doses
      • First dose given at 12 to 15 months of age; 95% develop immunity.
      • Second dose given at time of school entry (4 to 6 years of age) or any time >4 weeks after first measles vaccine; the 5% of initial nonresponders almost always develop immunity after the second dose.
      • Health care workers should have immunity verified and if not immune, should receive the vaccine if not contraindicated.
    • Common adverse reactions to vaccine
      • Fever
      • Febrile seizures are rare (<5%) and occur 6 to 12 days after vaccination. Risk of febrile seizures increases if initial immunization is delayed past age 15 months (4)[B].
      • Transient, mild, measles-like rash 7 to 10 days after vaccination (2%, with decreasing incidence during second vaccination)
      • If hypersensitivity reaction occurs, test for immunity; if immune, second dose is not needed. There is no substantiated link between MMR vaccine and autism (5)[A].
    • Contraindications
      • Live viral vaccines are contraindicated in immunosuppressed patients. For MMR, however, asymptomatic HIV-infected children with adequate CD4 count should be vaccinated.
      • Pregnancy: Live vaccine is contraindicated (theoretical risk of fetal infection).
      • Anaphylactic reaction to gelatin or neomycin; consult allergist before vaccination.
      • Egg anaphylaxis is not considered a contraindication.
COMMONLY ASSOCIATED CONDITIONS
  • Immunosuppression
  • Malnutrition
image DIAGNOSIS
PHYSICAL EXAM
  • Koplik spots
    • Pathognomonic of prodromal measles
    • 2- to 3-mm, gray-white, raised lesions on erythematous base on buccal mucosa
    • Occur ˜48 hours before measles exanthem
  • Exanthematous rash (characteristic but not pathognomonic)
    • Maculopapular blanching rash
    • Begins at ears and hairline and spreads head to toe, reaching hips by day 2
    • Discrete erythematous patches become confluent over time, particularly on the upper body.
    • Clinical improvement usually occurs within 48 hours after rash appears.
    • Rash fades in 3 to 4 days changing to a brownish color, followed by fine desquamation.
  • Lymphadenopathy and pharyngitis may be seen during exanthematous period.
DIFFERENTIAL DIAGNOSIS
  • Drug eruptions
  • Rubella
  • Mycoplasma pneumoniae infection
  • Infectious mononucleosis
  • Parvovirus B19 infection, roseola
  • Enteroviruses
  • Rocky Mountain spotted fever, dengue
  • Toxic shock syndrome
  • Meningococcemia
  • Kawasaki disease
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Obtain serum sample and throat (or nasopharyngeal) swab. Molecular testing of serum and respiratory specimens is the most accurate method to confirm measles infection. IgM assay and measles RNA by real-time polymerase chain reaction (RT-PCR)
  • Measles virus-specific IgM assay from serum and saliva. Antibodies may be undetectable on first day of exanthema but are usually detectable by day 3.
    • Sensitivity: 77% within 72 hours of rash onset; 100% within 4 to 11 days after rash onset. If negative but rash lasts >72 hours, repeat.
    • IgM falls to undetectable levels 4 to 8 weeks after rash onset.
  • Measles virus-specific IgG may be undetectable up to 7 days after exanthem; levels peak 14 days after exanthem.
    • A 4-fold increase in IgG titers 14 days after an initial titer that was measured at least 7 days after rash onset is confirmatory.
  • Viral cultures for measles are not usually performed.
  • Mild neutropenia is common.
  • Liver transaminases and pancreatic amylase may be elevated, particularly in adults.
  • Chest x-ray if concern for secondary pneumonia
P.643

image TREATMENT
GENERAL MEASURES
  • Place all patients with measles in respiratory isolation until 4 days after onset of rash; immunocompromised patients should be isolated for duration of illness.
  • Supportive therapy (i.e., antipyretics, antitussives, humidification, increased oral fluid consumption)
MEDICATION
  • No approved antiviral therapy is available. Immunosuppressed children with severe measles have been treated with IV or aerosolized ribavirin. No controlled trial data exist, and this use is not FDA approved.
  • Vitamin A: WHO recommends daily dosages for two consecutive days:
    • Children <6 months of age 50,000 IU
    • Children 6 to 12 months of age 100,000 IU
    • Children >12 months of age 200,000 IU
  • Antibiotics
    • Reserved for patients with clinical signs of bacterial superinfection (pneumonia, purulent otitis, pharyngitis/tonsillitis) (6)[B]
    • A small randomized, double-blinded trial resulted in an 80% (number needed to treat [NNT] = 7) decrease in measles-associated pneumonia with prophylactic antibiotics; consider antibiotic use prophylactically in patients with a high risk of complications (7)[B].
  • Outbreak control
    • A single case of measles constitutes an outbreak.
    • Immunize contacts (individuals exposed or at risk of having been exposed) within 72 hours.
      • Monovalent vaccine may be given to infants 6 months to 1 year of age, but two further doses of vaccine after 12 months must be given for adequate immunization.
      • Monovalent or combination vaccine may be given to all measles-exposed susceptible individuals age >1 year if not contraindicated.
      • Individuals not immunized within 72 hours of exposure should be excluded from school, child care, and health care settings (social quarantine) until 2 weeks after onset of rash in last case of measles.
    • Immunoglobulin therapy (passive immunity) may be necessary for the following high-risk individuals exposed to measles for whom vaccine is inappropriate:
      • Children age <1 year (infants 6 to 12 months of age may receive MMR vaccine in place of IG if given within 72 hours of exposure)
      • Pregnant women
      • Individuals with severe immunosuppression
      • IM immunoglobulin should be given within 6 days of measles exposure; CDC recommends 0.25 mL/kg to maximum of 15 mL for infants and pregnant women; immunocompromised individuals receive 0.5 mL/kg to a maximum of 15 mL.
INPATIENT CONSIDERATIONS
Outpatient care is appropriate, except where complications develop (e.g., encephalitis, pneumonia).
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Signs of complications needing close follow-up include:
  • Difficulty breathing or noisy breathing
  • Changes in vision
  • Changes in behavior, confusion
  • Chest or abdominal pain
PATIENT EDUCATION
  • Adhere to recommended immunization schedules.
  • Avoid exposure, particularly to unimmunized children and adults, pregnant women, and immunocompromised persons, until 4 days after rash onset.
  • Avoid contact with potential sources of secondary bacterial pathogens until respiratory symptoms resolve.
  • Centers for Disease Control and Prevention. Measles.www.cdc.gov/measles/about/index.html
PROGNOSIS
  • Typically self-limited; prognosis good
  • High fatality rates may be seen among malnourished or immunocompromised children, particularly in developing countries.
REFERENCES
1. Lessler J, Reich NG, Brookmeyer R, et al. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis. 2009;9(5):291-300.
2. Orenstein W, Seib K. Mounting a good offense against measles. N Engl J Med. 2014;371(18): 1661-1663.
3. Althouse BM, Bergstrom TC, Bergstrom CT. Evolution in health and medicine Sackler colloquium: a public choice framework for controlling transmissible and evolving diseases. Proc Natl Acad Sci U S A. 2010;107(Suppl 1):1696-1701.
4. Rowhani-Rahbar A, Fireman B, Lewis E, et al. Effect of age on the risk of fever and seizures following immunization with measles-containing vaccines in children. JAMA Pediatr. 2013;167(12):1111-1117.
5. Demicheli V, Jefferson T, Rivetti A, et al. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2005;(4):CD004407.
6. Kabra SK, Lodha R. Antibiotics for preventing complications in children with measles. Cochrane Database Syst Rev. 2013;(8):CD001477.
7. Garly ML, Balé C, Martins CL, et al. Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau. BMJ. 2006;333(7581):1245.
Additional Reading
&NA;
  • Mulholland EK, Griffiths UK, Biellik R. Measles in the 21st century. N Engl J Med. 2012;366(19):1755-1757.
  • Papania MJ, Wallace GS, Rota PA, et al. Elimination of endemic measles, rubella, and congenital rubella syndrome from the western hemisphere: the US experience. JAMA Pediatr. 2014;168(2):148-155.
Codes
&NA;
ICD10
  • B05.9 Measles without complication
  • B05.2 Measles complicated by pneumonia
  • B05.89 Other measles complications
Clinical Pearls
&NA;
  • There is no substantiated link between MMR vaccine and autism.
  • Measles is a highly communicable viral disease whose natural transmission has been halted in the United States by mass immunization.
  • A single case of measles constitutes an outbreak.
  • Suspected measles cases must be reported to state or local health departments to contain outbreak.
  • Immunization requires two doses: one at 12 to 15 months of age and one at school age (4 to 6 years of age).
  • Presentation includes a prodrome of fever, cough, coryza, and conjunctivitis, followed by a descending maculopapular rash beginning on the face and progressing to the chest and lower body (centrifugal).
  • Consider measles in the differential diagnosis of a febrile rash illness (especially in unvaccinated individuals with recent international travel).
  • Measles-associated pneumonia is the most common cause of mortality.