Measles

Measles

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Measles It primarily affects children but can infect unvaccinated individuals of any age.

Measles

Key Facts

  • Transmission: Spread via respiratory droplets (coughing, sneezing) or direct contact with infected secretions.
  • Incubation Period: 10–14 days before symptoms appear.
  • Complications: Can be severe, especially in malnourished or immunocompromised individuals.

Symptoms

Symptoms typically occur in two stages:

Prodromal Stage Before Rash

High fever (up to 104°F/40°C)

  • “3 Cs”:
  • Cough
  • Coryza (runny nose)
  • Conjunctivitis (red, watery eyes)
  • KOPLIK’s spots (tiny white spots on the inner cheeks) – a classic sign.

Rash Stage

Rash lasts 5–7 days before fading.

Complications

  • Measles can lead to serious health issues, including:
  • Pneumonia (most common cause of measles-related deaths)
  • Encephalitis (brain inflammation, can cause permanent damage)

Diagnosis

  • Clinical diagnosis based on symptoms and exposure history.
  • Lab tests (if needed):
  • IgM antibody test (acute infection)
  • PCR (viral detection in throat/nose swabs)

Treatment

  • No specific antiviral treatment exists.
  • Supportive care includes:

Hydration

  • Fever control (acetaminophen/ibuprofen)
  • Vitamin A supplementation (reduces complications in children)
  • Antibiotics if secondary bacterial infections (e.g., pneumonia, ear infections) occur.

Prevention

  • Vaccination is the best protection (MMR vaccine: Measles, Mumps, Rubella).
  • Two doses (first at 12–15 months, second at 4–6 years).
  • Effectiveness: ~97% after two doses.
  • Isolation of infected individuals to prevent spread.

Causative Agent

  • Virus: Measles virus (MeV), genus Morbillivirus, family Paramy xoviridae.
  • Genome: Single-stranded, negative-sense RNA.
  • Stability: Dies quickly outside the host (survives <2 hours in air/on surfaces).

Causative Agent

Transmission Dynamics

  • Highly contagious: R₀ (Basic Reproduction Number) = 12–18 (meaning one infected person can spread it to 12–18 unvaccinated people).

Spread via:

  • Airborne respiratory droplets (sneezing/coughing).
  • Direct contact with nasal/throat secretions.
  • High-risk settings: Schools, refugee camps, healthcare facilities.

Pathophysiology How the Virus Affects the Body

  • Entry: Infects respiratory tract → spreads to local lymph nodes.
  • Primary viremia: Virus enters bloodstream → infects immune cells.
  • Secondary viremia: Spreads to skin, lungs, liver, and brain.
  • Immune suppression: Destroys immune memory cells, increasing vulnerability to other infections.

Clinical Features in Detail

  • Prodromal Phase (2–4 days before rash)
  • Fever (often >40°C / 104°F).
  • “3 Cs”:
  • Cough (dry, hacking).
  • Coryza (severe runny nose).
  • Conjunctivitis (red eyes, photophobia).
  • Koplik’s spots (pathognomonic sign):
  • Tiny white lesions on buccal mucosa (appear 1–2 days before rash).
  • Exanthem Phase (Rash Stage)

Rash progression:

  • Starts at hairline/face → spreads downward (trunk, limbs).
  • Maculopapular (flat red spots merging into patches).
  • Fades in 5–7 days (may leave brownish discoloration/peeling).
  • Fever persists until rash fully develops.

Atypical Presentations

  • Modified measles (milder, in partially immune individuals).
  • Hemorrhagic measles (rare, severe bleeding under skin).

Diagnosis Lab & Clinical Confirmation

  • Clinical Diagnosis (WHO Criteria)
  • Fever + generalized rash + cough/coryza/conjunctivitis.
  • Koplik’s spots confirm diagnosis but are often missed.

Laboratory Tests

  • IgM ELISA (detects antibodies 3+ days after rash onset).
  • RT-PCR (nasopharyngeal/throat swab, best in early infection).
  • Viral culture (rarely used, research settings).

Treatment & Management

Supportive Care

  • Hydration (oral rehydration or IV if severe).
  • Fever control (acetaminophen/ibuprofen; avoid aspirin in kids).
  • Vitamin A supplementation (reduces mortality in children):
  • Dosing: 50,000–200,000 IU (depending on age, given for 2 days).

Antibiotics

  • Only for secondary bacterial infections (e.g., otitis media, pneumonia).

Hospitalization Needed If:

  • Severe respiratory distress, encephalitis, or dehydration.

Prevention Strategies

  • Vaccination (MMR or MMRV)
  • MMR Vaccine: Live-attenuated (safe, effective).
  • Dose 1: 12–15 months (~93% effective).
  • Dose 2: 4–6 years (~97% effective).
  • Catch-up vaccination: Unvaccinated adults should get 1–2 doses.
  • Contraindications: Pregnancy, severe immunodeficiency.
  • Post-Exposure Prophylaxis (PEP)
  • Vaccine within 72 HRS(may prevent/modify disease).
  • Immunoglobulin (Ig) within 6 days (for high-risk groups like infants/pregnant women).

Infection Control

  • Isolate cases (4 days before to 4 days after rash).
  • Quarantine unvaccinated contacts for 21 days.

Global Epidemiology & Outbreaks

  • Pre-vaccine era: ~2.6 million deaths/year (mostly children).
  • Current burden: ~136,000 deaths/year (2022, WHO).

Outbreaks in:

  • Low-coverage areas (Africa, Southeast Asia).
  • Vaccine-hesitant communities (e.g., USA, Europe).
  • Elimination status: Some regions (Americas, parts of Europe) have eliminated endemic measles but face imported cases.

Advanced Virology of Measles Virus

Viral Structure:

  • Enveloped virus with H (hemagglutinin) and F (fusion) glycoprotein spikes
  • H protein binds to host receptors (CD150/SLAM on immune cells, nectin-4 on epithelial cells)
  • F protein mediates membrane fusion and cell entry

Replication Cycle:

  • Attachment to CD150+ immune cells (dendritic cells, macrophages)
  • Fusion and release of viral RNA into cytoplasm
  • RNA-dependent RNA polymerase synthesizes mRNA
  • Viral assembly at cell membrane
  • Budding from infected cells (spread via cell-cell fusion)

Host Immune Response

Innate Immunity:

  • TLR7/8 recognize viral RNA → interferon production
  • NK cell activation within 2-3 days of infection

Adaptive Immunity:

  • CD8+ T-cells cause rash through cytotoxic response
  • Neutralizing antibodies target H protein (appear with rash)
  • Lifelong immunity after natural infection

Immune Amnesia:

MeV infects memory B/T cells

  • Causes 11-73% loss of existing antibodies (lasts 2-3 years)
  • Increases mortality from other infections post-measles

Molecular Epidemiology

Genotyping:

  • WHO recognizes 24 genotypes (A, B1-3, C1-2, D1-10, etc.)
  • B3 and D8 currently circulating globally
  • Genotyping helps track transmission chains

Viral Evolution:

  • Mutation rate: ~10^-4 substitutions/site/year
  • H gene most variable (positive selection pressure)

Advanced Clinical Management

High-Risk Groups:

  • HIV+ children: 50% mortality without ART
  • Cancer patients: May develop giant cell pneumonia
  • Malnourished children: 10x higher fatality rate
  • Novel Therapeutics (Experimental):
  • ERDRP-0519 (oral polymerase inhibitor)
  • Ribavirin (for SSPE, investigational)
  • Fusion inhibitor peptides

Outbreak Investigation Protocol

Case Definition:

  • Suspected: Fever + rash + cough/coryza/conjunctivitis
  • Confirmed: Lab verification OR epidemiologic link

Contact Tracing:

  • Identify exposed individuals from 7d before to 21d after rash
  • Classify contacts by vaccination status

Laboratory Network:

  • WHO Measles and Rubella Laboratory Network (800+ labs)
  • Genotyping for outbreak linkage

Vaccine Science

Strain History:

  • Original EDMONSTON strain (1954)
  • Current vaccine: EDMONSTON -Zagreb or MORATEN strains

Correlates of Protection:

  • Neutralizing antibody titer >120 MIU/mL
  • ELISA IgG >200 MIU/mL

Vaccine Failure:

  • Primary (2-5% of recipients don’t respond)
  • Secondary (waning immunity in 1/100,000 after 2 doses)

Historical Impact

  • 9th Century: Persian physician Rhazes distinguishes measles from smallpox
  • 1846: Panum studies Faroe Islands epidemic, proves lifelong immunity
  • 1954: Enders isolates virus (Nobel Prize 1961)
  • 1963: First licensed vaccine (inactivated, later withdrawn)
  • 2000-2020: Vaccines prevent ~31 million deaths globally

Historical Impact

Current Research Frontiers

Transmission Modeling:

  • Super-spreaders cause 80% of transmissions
  • School-age children drive outbreaks (R0=18 in schools)

Eradication Feasibility:

  • Only human reservoir (unlike polio)
  • Challenges: Vaccine hesitancy, cold chain requirements
  • Next target after polio (potential eradication by 2040)

Economic Burden

US Outbreak Costs:

  • $4.6 million per outbreak (median)
  • $20,000 per case (public health response)

Global Costs:

  • $1.5 billion/year in treatment
  • $2.1 billion/year in productivity losses

Special Populations

Healthcare Workers:

  • 5-10% lack immunity (require serologic testing)
  • Highest exposure risk in ER and pediatric units

Adults Born 1963-1989:

  • May have received ineffective early vaccines
  • Need serologic testing/revaccination

Diagnostic Challenges

Atypical Presentations:

  • Vaccine-modified measles (milder, no KOPLIK spots)
  • Immunocompromised: No rash (“black measles” – hemorrhagic)

PCR Pitfalls:

  • False negatives after 5 days of rash
  • Must target N gene (H gene mutations cause false negatives)

 

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