Measles virus

• Highly contagious virus that causes a triad of cough, coryza, and conjunctivitis

Background

Microbiology

• Enveloped RNA Morbillivirus in the Paramyxoviridae family
  • Family includes parainfluenza, RSV, measles, mumps
• Eight structural proteins: F, C, H (haemagglutination), L (large), M (matrix), N (nucleoprotein), P (phosphopolymerase), and V
  • N, P, and L complex with RNA
  • C and V interact with cellular proteins and regulate replication
  • M, H, and F are viral envelope proteins
  • H helps with host cell attachment, and F helps with spread between cells

Pathophysiology

• Airborne droplets can remain in the air up to 2 hours after a person with measles has coughed
  • It is droplet, but just very small droplet
• Innoculated through respiratory mucosa, enters lymphoid cells via SLAM receptor
  • SLAM (CDw150) is present on lymphocytes and antigen-presenting cells
• Spreads to entire respiratory systems, as well as intestines, bladder, skin, and spleen, lymph nodes, liver, conjunctiva, and brain
• Propagates within T and B lymphocytes and monocytes, but also endothelial, epithelial, and dendritic cells
• Host response success causes disappearance of serology and appearance of rash
  • Possibly the rash represents a hypersensitivity reaction to the virus mediated by cellular immunity

Epidemiology

• Infection confers lifelong immunity, though vaccination may not
• Worldwide distribution
• Prior to vaccination, there were epidemics every 2 to 5 years lasting 3 to 4 months
• Vaccine hesitancy is becoming more common
  • Parts of Europe

Clinical Manifestations

• Incubation period 10 to 14 days (range up to 21 days), followed by several days of prodrome that includes fever, anorexia, cough, coryza, and conjunctivitis
  • Can be mistaken for common cold or for Kawasaki disease
  • Koplik spots appear at end of prodrome
    • Bluish gray specks on a red base in the oral mucosa ("like grains of sand")
• Rash follows Koplik spots
  • Spreads from face to body, including palms and soles
  • Fevers resolve soon after rash appears
  • Rash is erythematous and maculopapular, and my desquamate as it begins to heal
  • Usually lasts 5 days, clearing in the same pattern that it appeared
• The rash disappears about 7 to 10 days after late prodromal period, with cough being the last symptom to disappear

Complications

• Respiratory involvement, either as primary infection of with bacterial superinfection
  • Otitis media, pneumonia (on CXR, even if uncomplicated)
• Acute encephalitis in 1 in 1000-2000 patients, with new fevers, headaches, seizures, and altered level of consciousness
  • Likely from hypersensitivity to virus in the brain rather than from direct infection
  • Sequelae include blindness, corneal scarring
• Chronic encephalitis, also called subacute sclerosing panencephalitis
• Hepatitis
• Complications are more common in adults who are infected

Subacute Sclerosing Panencephalitis (SSPE)

• Degenerative neurological condition caused by persistent CNS infection despite immune response
• 5-10 years after infection
• Higher risk if infection before age 2 years
• Inevitably ends in death

Special Populations

Modified Measles

• Patients with passive immunity to measles may present with a milder form
  • Babies with mom's immunoglobulin, or patients who have received immune globulin
• The prodrome, Koplik spots, and rash are often absent, and it is sometimes subclinical

Atypical Measles

• Patients with prior immunization with killed vaccine (no longer on market, since 1960s) may have an atypical presentation
• Prodrome of fever and pain for 1 to 2 days
• Rash follows, but moves peripherally to centrally, and have varied form (urticarial, maculopapular, hemorrhagic, vesicular)
  • Can mimic varicella, RMSF, HSP, drug eruption, or toxic shock syndrome
• Fever continues, with edema, interstitial pneumonia, hepatitis, and occasionally pleural effusion
• More prolonged course, with very high antibody titres

Immunocompromised

• Chemotherapy, transplantation, AIDS, and congenital cellular immunodefieciency are all risk factors for severe measles
  • Possibly also malnutrition
• Can develop giant cell pneumonia, without rash, as well as a chronic encephalitis
  • Can detect measles RNA in brain tissue

Pregnancy

• Can be severe
• Can cause spontaneous abortion and premature delivery
• Newborn can be infected; they should get immune globulin at birth

Differential Diagnosis

• Rubella
• Kawasaki syndrome
• Scarlet fever
• Roseola
• Infectious mononucleosis
• Rickettsioses
• Enteroviral infections
• Adenoviral infections

Diagnosis

• Typically diagnosed clinically; CBC may show leukopenia
• If uncertain of the diagnosis, can use serology or molecular tests to confirm
  • NP swab PCR within 7 days of rash onset
  • Urine PCR within 14 days of rash onset
  • ELISA IgG serology, repeated after 1 week; fourfold titre increase is diagnostic
    • Or IgM, if available, to diagnose on one sample
    • IgM can persist for up to a month
  • Viral culture is also possible
• For SSPE, can demonstrate high titres in serum and CSF

Management

• Most infectious just before rash; quickly becomes non-infectious after end of prodrome
• Supportive care
• Vitamin A can be given, especially if the child is deficien
  • In children >1 year, vitamin A 200,000 IU daily for 2 days
  • If 6-12 months old, use 100,000 IU for 2 days
  • Less than 6 months, use 50,000 IU
  • If deficient, give another dose at 2 to 4 weeks
• Ribavirin unhelpful but sometimes given

Prevention

Infection Control

• Infectious period is 5 days prior to until 4 days after onset of rash
• Need to do contact tracing, including people up to two hours after any room they were in
• All contacts should be quarantined at home regardless of symptoms
  • Susceptible contacts should be placed in airborne precautions from 5 days after first exposure to 21 days after last exposure

Post-Exposure Prophylaxis (PEP)

• Use either MMR vaccine or immune globulin in susceptible people
• Immunization
  • Should be offered to all susceptible, immunocompetent people age 6 months and older
  • Give within 72 hours of exposure
  • Can shorten the time to rash, suggesting a shorter period of infectiousness
• Immunoglobulin can provide short-term protection to certain susceptible, immunocompromised people
  • Given to people with high risk for severe or fatal measles and are susceptible:
    • Susceptible pregnant women
    • Susceptible immunocompromised people
      • Regardless of prior vaccination, should also be considered in advanced HIV
      • Regardless of prior vaccination, should also be consider in all patients with hematopoietic stem cell transplantation until they have been revaccinated post-transplant with confirmed adequate antibody titres
    • Susceptible infants <6 months of age
    • Susceptible immunocompetent infants from 6 to 11 months of age who present after 72 hours
  • Give within 6 days of exposure

Population	Time since measles exposure
	≤72 hours	73 hours to 6 days
Susceptible infants <6 months old	IMIg 0.5 mL/kg
Susceptible immunocompetent infants 6-12 months old	MMR	IMIg 0.5 mL/kg
Susceptible immunocompetent people ≥12 months old	MMR
Susceptible pregnant people	IVIg 400 mg/kg (preferred) or IMIg 0.5 mL/kg
Immunocompromised individuals	IVIg 400 mg/kg (preferred) or IMIg 0.5 mL/kg
People with confirmed immunity	None

Vaccination

• Live vaccine (given in MMR or MMRV) at 12-15 months, with a booster later in childhood between 18 months and school entry
  • Wait at least 5-6 months after receiving immunoglobulin
  • Wait at least 4 weeks from a dose given before 12 months for post-exposure prophylaxis
• No adverse effects of revaccination
• Rates need to be >95% to prevent imported cases from causing outbreaks
• Rates less than 80% allow endemic transmission with cyclical outbreaks every 3-5 years
• Vaccination is contraindicated in advanced HIV, other cell-mediated immunodeficiency, and in pregnancy
  • Wait 3 months after chemotherapy
  • Don't use MMRV, since no safety data are available
• Can be associated with anaphylaxis in patients with true egg allergy

Vaccine Failure

• Improper storage >4º C
• Failure to use proper diluent for lyophilized vaccine
• Exposure to light or heat
• Vaccination in the presence of passive antibody

Catch-Up

• 2 doses of MMR at least 4 weeks apart

Further Reading

• Measles vaccine: Canadian Immunization Guide. Public Health Agency of Canada.