Measles & Mumps Notes

Measles

Epidemiology

  • Pre-vaccine era:
    • Major epidemics every 2-3 years.
    • Approximately 2.6 million deaths annually.
  • Post-vaccine era (2023):
    • Approximately 107,500 deaths, mostly in children under 5 years old.
    • Vaccination prevented ~60 million deaths between 2000-2023.

Virology

  • Family: Paramyxoviridae
  • Genus: Morbilivirus
  • Size: 150-300 nm
  • Envelope: Yes
  • RNA: Single-stranded, non-segmented
  • Nucleocapsid: Helical
  • Fusion protein: Present
  • Haemagglutinin: Present
  • Matrix: V
  • Negative-sense ssRNA, non-segmented.
  • Fusion protein (F)
    • Encodes 6 major structural proteins.
    • 2 important transmembrane glycoproteins
  • Haemagglutinin (HA)
  • Strains:
    • Wild strain
    • Vaccine strain
    • Exists as single serotype, but nucleotide sequence analyses have identified distinct lineages.
    • Serotype 1
    • Natural host: Human

Transmission

  • The virus remains active and contagious in the air or on infected surfaces for up to 2 hours.
  • Transmission occurs through contact with infected secretions.
  • Airborne respiratory droplets are a common route.
  • Infectivity period: 4-5 days before rash to 4 days after rash onset.

Contagiousness

  • R_0 (basic reproduction number):
    • Ebola: 2-3
    • Flu: 1-4
    • SARS: 2-5
    • Mumps: 4-7
    • Polio: 5-7
    • Measles: 12-18

Risk Factors

  • No immunization
  • Immunocompromised individuals
  • Malnutrition
  • Crowded living conditions
  • Close contact with infected individuals
  • Low socioeconomic status
  • Very young age

Pathogenesis

  • Viral Attachment: Hemagglutinin (H) protein binds to host cell receptors:
    • CD46 (in non-immune cells)
    • SLAM (in immune cells)
    • nectin-4 (in epithelial cells).
  • Membrane Fusion and Viral Entry: Fusion (F) protein facilitates fusion between the viral envelope and the host cell membrane.
    • Conformational changes upon activation lead to membrane fusion.
    • Enables cell-to-cell fusion, forming syncytia, which contributes to viral spread and immune evasion.
  • The virus multiplies locally in the respiratory tract and then spreads to the regional lymph nodes.
  • Enters the bloodstream through infected monocytes (primary viremia).
  • Further multiplies in reticuloendothelial tissues and spills into the bloodstream (secondary viremia).
  • Disseminates to various sites, predominantly seeding in epithelial surfaces (skin, mucosa, conjunctiva).
  • The skin rash is immune-mediated due to infection of dermal capillary endothelial cells and immune complex formation.
  • Human CD46 molecule (respiratory epithelial cell) has been identified as a cellular receptor for measles virus.
  • Later, immune cells (macrophages, dendritic cells, T & B cells) become the primary target.
  • Infection progresses to affect the alveolar macrophages & dendritic cells that transport the virus to regional lymph nodes where T & B cells become infected.
  • Dissemination to other sites including the spleen, lymphatic tissue, liver, skin, and lungs follows.

Immunity

  • Antibodies raised against either viral haemagglutinin or fusion protein neutralize measles virus in vitro and protect against infection.
  • Both humoral and cellular measles-specific immunity are important for viral clearance.
  • Immunity is thought to be life-long.

Clinical Manifestation

  • Incubation period: 10-14 days (range 7-23 days).
  • Prodrome (4 days): Non-specific symptoms
    • Fever (up to 39°C).
    • Cough, coryza, conjunctivitis.
    • Malaise, vomiting, diarrhea
    • Koplik spots: Pathognomonic of measles; slightly raised, small bluish-white spots in buccal mucosa around first and second lower molar (2-3mm in diameter, erythematous base). "grains of salt on a red background”. Detection improve the accuracy of clinical diagnosis
  • Eruptive/Exanthem (Maculopapular rash):
    • Typically appears at the hairline on the face, then spreads to the upper neck, trunk, arms, and legs (centrifugal pattern).
    • Blanching rash.
    • Lasts for 5-6 days before fading.
    • On average, rash occurs 14 days after exposure.
    • Lymphadenopathy, high fever, pharyngitis, conjunctivitis.
  • Recovery: In uncomplicated measles, the disease improves by the 3rd day after rash onset; fully recovered 7–10 days after the onset of the disease. Cough may persist for one to two weeks after measles. The occurrence of fever beyond the 3rd to 4th day of rash suggests a measles-associated complication.

Clinical Spectrum

  • Classic measles: Immunocompetent individual
  • Atypical measles: Patients immunized with formalin-killed vaccine; rash begins on the extremities and spreads to the trunk and face; pneumonia with nodular pulmonary infiltrates.
  • Modified measles: Mild form of typical measles; pre-existing antibody levels below the protective level.

Diagnosis

  • Clinical diagnosis based on history & findings on physical examination.
  • Laboratory diagnosis:
    • Leukopenia, lymphocytosis.
    • Blood: anti-measles virus IgM antibodies by ELISA.
    • Nasopharyngeal swab, conjunctiva swab, respiratory secretion, and urine: measles virus RNA by RT-PCR or viral culture Spectmen
  • Imaging: Chest X-ray

Complications

  • Approximately 30% of affected patients.
  • More likely in children under 5 years and adults over age 30; also in malnourished children (especially vitamin A deficiency), HIV, etc.
  • Measles itself weakens the immune system.
  • Secondary bacterial infections: Otitis media, pneumonia.
  • Acute laryngotracheobronchitis (croup), severe diarrhoea/dehydration, Giant-cell pneumonitis (Hecht’s pneumonia).
  • Histologic evaluation of conjunctival, nasopharyngeal, or buccal epithelial cells may demonstrate giant cells with inclusions; these cells may also be present in urine.
  • Neurologic complications:
    • Post-infection encephalitis:
      • 1-4 per 1000-2000 cases
      • Occurs 3-14 days after illness onset
      • 15% mortality, 25% survivors develop permanent neurological deficit
    • Acute Disseminated Encephalomyelitis (ADEM):
      • 1 per 1000 cases
      • Post-infectious autoimmune response
      • Occurs during the recovery phase (within 2 weeks of exanthem)
      • 10-20% mortality
    • Subacute Sclerosing Panencephalitis (SSPE):
      • 1 per 10,000-100,000 cases
      • 2-10 years after infection
      • Progressive intellectual, physical, and behavioral deterioration; stuporous and die 6-12 months later

Management

  • No specific antivirals available.
  • Mainly symptomatic treatment & supportive care.
  • Good nutrition, adequate fluid intake.
  • Oral rehydration therapy.
  • Patient isolation is important to prevent further spread of the virus.
  • Increasing population immunity through vaccination is the most effective way to prevent outbreaks.

Prevention

  • Post-exposure prophylaxis to avoid clinical disease:
    • MMR vaccine
    • Measles Immunoglobulin (Ig)
  • Measles vaccine:
    • Live attenuated vaccine
    • Monovalent or combination (e.g., with mumps & rubella vaccine)
    • Given via SC (preferred) or IM (alternative)
    • 93% effective after the 1st dose, 97-99% following the 2nd dose.

Mumps

Virology

  • Family: Paramyxoviridae
  • Genus: Rubulavirus
  • Size: 150-200 nm
  • Envelope: Yes
  • Nucleocapsid: Helical
  • RNA: Single-stranded
  • Pleomorphic virus
  • Important surface glycoproteins:
    • Hemagglutinin-neuraminidase (HN) protein: mediates binding/adsorption of the virus to the host cell
    • Fusion (F) protein: mediates the fusion with lipid membranes, allowing the nucleocapsid to enter the cell
  • Genotype Serotype 1 Natural host Human
  • 12 Small hydrophobic (SH) protein is the most variable part of the genome
  • Sequencing of the SH gene allows genotypic characterization

Epidemiology

  • Pre-vaccine era:
    • Major epidemics every 2–5 years
    • 90% were <15 years old
  • Post-vaccine era:
    • Occurs among school-aged children and college-aged young adults
    • Rare among infants <1 year old due to maternal antibodies

Transmission

  • Spreads rapidly among susceptible individuals living in close quarters (e.g., college dormitories).
  • Contact with infected secretions.
  • Infectivity period: 7 days before swelling of salivary gland to 8 days after swelling.

Pathogenesis

  • Incubation period: 16 - 18 days (range 12- 25 days).
  • The virus replicates in the epithelial lining of the oropharynx.
  • Parotid gland, testes, ovaries, pancreas, and meninges in some cases.

Immunity

  • Antibodies to the HN protein neutralize the infectivity of the virus; lifelong immunity.
  • Maternal antibodies prevent disease during the 1st 6 months of life.

Clinical Manifestation

  • 30% subclinical infection.
  • Prodrome: low-grade fever, fatigue, headache, anorexia, myalgia, ear-ache, ipsilateral parotid swelling & tenderness.
  • Later, difficulty in pronunciation & mastication.
  • Initial unilateral involvement may be followed by contralateral involvement a few days later (90% of cases).
  • Swelling remains for 7 – 10 days.
  • Parotitis may be bilateral or unilateral.
  • Once swelling peaked, recovery is rapid- within a week.
  • Most commonly parotid gland, other salivary glands affected in 10% of cases.
  • Erythematous and enlarged orifice of Stensen's duct.

Differential Diagnosis

  • Bacterial parotitis: S. aureus, S. pyogenes, aerobic & anaerobic oral flora, aerobic gram-negative bacilli
  • Viral parotitis: Enteroviruses, EBV, Parainfluenza virus, Influenza A virus

Diagnosis

  • Most were diagnosed clinically.
  • Leukopenia with lymphocytosis.
  • Elevated serum amylase.
  • Mumps serology- IgM or 4-fold rise in IgG titre indicates recent infection.
  • PCR for mumps virus RNA.

Complications

  • May occur even among vaccinated individuals; may occur in the absence of parotitis.
  • Orchitis: Post-pubertal males
    • Symptoms typically occur 5-10 days after the onset of parotitis.
    • Fever and severe testicular pain accompanied by swelling and erythema of the scrotum.
    • Involvement is unilateral in 60 to 80% of cases.
    • Can lead to infertility or sterility.
  • Neurologic complications: Meningitis, encephalitis, and deafness
    • May occur without parotitis; early onset simultaneously with parotitis; late onset 7 – 10 days later
    • Mostly benign, self-limiting, recover without permanent neurological deficit
  • Others: polyarthritis, pancreatitis, myocarditis, mastitis, and oophoritis.

Management

  • No antivirals
  • Prevention; mumps vaccine
  • Live attenuated
  • Long-lasting immunity.
  • Contraindicated in immunocompromised