Measles Virus

Virology

  • Member of Paramyxovirus Family (see Paramyxoviruses, [[Paramyxoviruses]])
    • Morbillivirus Genus

Epidemiology

  • Decreased incidence in USA due to vaccination
  • Pre-vaccination era: 3-4 month epidemics occurred q2-5 years in temperate regions (except in isolated areas, most people were infected by age 20/ 90% of cases occurred in children <10 y/o)
  • Post-vaccination era: 98% decrease in incidence in USA (with shift in age distribution: >33% of cases occur in children and adults >15 y/o/ outbreaks in high schools and colleges, unvaccinated preschoolers/ 20% of young adults and 4% of those born before 1957 are seronegative and susceptible/ epidemics in late winter and early spring

Physiology

  • Measles virus infection
  • Measles virus (Morbillivirus, Paramyxoviridae family): structurally similar to RSV and Parainfluenza viruses/ possesses hemagglutinin that attaches it to cells/ only one serotype (although minor antigenic differences seen by monoclonal Ab)/ human is natural host for the measles virus
  • Transmission: highly contagious through airborn transmission (particle aerosols remain stable for several hours at low humidity) and possibly fomites -> invasion through respiratory epithelium and possibly conjunctiva
    • 4% of cases are transmitted in medical settings/ highest infectivity during late prodrome (but virus shed for several days after rash onset)
  • Incubation: 9-14 days (longer in adults)
  • Life cycle: initial viremia infects RES -> second viremia (corresponds to prodrome) -> dissemination to epithelial cells and lymphoid organs
  • Immune suppression (possibly due to direct infection of lymphocyctes/ may last for weeks after rash onset): depressed NK cell function/ decreased cutaneous anergy (measles infection or vaccination may convert PPD to negative for a few weeks/ measles infection may exacerbate active TB but does not appear to increase risk for reactivation)/ leukopenia
  • Risk of pulmonary superinfection: increased due to damaged respiratory epithelium/ virus-related immunosuppression/ Vit. A deficiency

Pathologic Patterns

  • Multinucleated giant cells with intranuclear and intracytoplasmic inclusions (in tonsils, appendix, lymph nodes, respiratory and other epithelium)
  • Lymphoid hyperplasia/ mononuclear cell infiltration
  • Destruction of ciliated respiratory epithelium/ interstitial pneumonia/ epithelial cell hyperplasia/ syncytial cell formation
  • DAD pattern

Diagnosis

  • CXR/Chest CT patterns:
    • Patchy, diffuse reticulonodular, or dense lobar or segmental infiltrates: usually have associated hilar adenopathy/ may have pleural effusion/ hypoxemia/ restriction on PFT’s
      • Residual nodular infiltrates may persist for years (and may calcify)

Conjunctival and respiratory secretions: show multi-nucleated giant cells

Respiratory secretions: measles virus may be recovered during prodrome and up to several days after rash onset

CXR/Chest CT patterns:

ELISA of acute and convalescent samples (collected within days of each during first week): show sero-conversion
-May fail to convert in immunocompromised patients

Anti-measles /IgM: detects specific Ab during acute phase

CBC: leukopenia (leukocyto-sis suggests bacterial superinfec-tion)

Blood and urine: measles virus may be recovered during prodrome and up to several days after rash onset

Urine sediment: show multi-nucleated giant cells

Skin Bx, nasopharyngeal and throat swab, exfoliated urine cells: IF shows measles Ag early in course


Clinical Presentations

  • Interstitial Lung Disease (see [[Interstitial Lung Disease-Etiology]])
  • [[Diffuse Alveolar Damage]] -> [[Acute Lung Injury-ARDS]] or [[Diffuse Alveolar Hemorrhage]]
  • Pleural Effusion (see [[Pleural Effusion-Exudate]]): pleural effusion occurs in cases that have onset post-vaccination with inactivated virus vaccine

Clinical Patterns
1) Typical measles:
-Prodrome (lasts 2-8 days): fever/ cough/ coryza/ malaise/ anorexia/ conjunctivitis/ Koplik’s spots (buccal mucosa)/ leukopenia
-Maculopapular Erythematous Rash (see Exanthems, [[Exanthems]]): begins on face and neck and progresses to extremities and trunk/ disappears in 5-6 days (in same geographic pattern/ symptoms improve several days after rash onset, cough may persist)/ onset correlates with development of host immune response and subsequent termination of virus shedding/ rash also occurs in agammaglobulinemic patients
-Pulmonary complications (4-50% of cases):
a) Bronchitis:
b) Interstitial pneumonia (multilobar reticulonodular infiltrate): pleural effusion and lobar consolidation suggest superimposed bacterial infection
–In 30% of cases with impaired cell-mediated immunity, pneumonia may occur without rash (this is rare in normal persons)
–Measles pneumonia may occur during pregnancy or HIV-associated cases
c) Croup: less common
d) Bronchiolitis: less common
e) SQ or mediastinal emphysema: high incidence in children
f) Bronchiectasis: may follow (sometimes with adenovirus and HSV infection) childhood cases in developing countries
g) Bacterial superinfection (H. Flu/ N. Meningitidis/ Pneumococcus): complicates 30-50% of young adult cases with measles pneumonia/ usually begins 5-10 days after rash onset

-Other organ complications:
a) Otitis media/ sinusitis: complicates 30% of cases
b) Hepatitis/ encephalitis/ keratitis/ mesenteric adenitis/ diarrhea: more common in developing countries

2) Atypical measles (occurs in adults that received the vaccine between 1963-1968 who are exposed to wild type virus/ probably due to destroyed F protein in inactivated Measles virus used in vacccine):
-Abrupt onset of high fever/ headache/ myalgia/ vomiting/ abdominal pain/ coryza/ dry cough/ conjunctivitis/ glossitis with “strawberry tongue”/ absence of Koplik’s spots
-Most of these symptoms resolve within 1-3 weeks
-Recurrences of atypical measles have not been reported
-Serology: shows low titers with rapid rise in early convalescent samples (suggests anamnestic response)
-Polymorphous rash: may include vesicles, petechiae, purpura, urticaria/ begins on distal extremities and spreads proximally over 3-5 days
-Pulmonary complications (occur in most cases):
a) Patchy, diffuse reticulonodular, or dense lobar or segmental infiltrates: usually have associated hilar adenopathy/ may have pleural effusion/ hypoxemia/ restriction on PFT’s
–Residual nodular infiltrates may persist for years (and may calcify)


Treatment

Supportive care: treat bacterial infection, respiratory isolation, etc.
Measles pneumonia: inhaled and IV Ribavirin + IVIG: has been used in some cases
Vit. A: decreases morbidity and mortality in severe measles in children
Measles vaccine (live attenuated): given first dose at 12-15 months, second at school entry
-Confers durable immunity in 90%
-Revaccinate: recipients of inactivated vaccine/ close sequence of inactivated and live attenuated vaccines/ vaccination during IVIG/ vaccination before 1 y/o
-Tolerated but less immunogenic in HIV positive children and post-BMT
-Less immunogenic in infants with colds

Post-exposure IVIG: for close contacts of infectious cases (especially under 1 y/o, pregnant, immuno-compromised)
-Prevents or modifies Measles if given within 6 days of exposure
-Post-exposure vaccine prevents Measles in normal hosts only if given within 72 hrs of exposure


Prognosis

  • Infection induces life-long protection against Measles (although asymptomatic reinfection may occur)
  • Mortality: <0.1% (developed countries), 2% (underdeveloped contries), as high as 25% (some outbreak areas)
    • In hospitalized patients, Measles pneumonia mortality is 70% in oncology and 40% in HIV patients
    • Mortality is due to lung and CNS complications and are related to malnutrition, age, and immunosuppression
  • Poor prognostic factors: leukopenia <2000/mm3