What are the etiology, pathogenesis, clinical presentation, diagnostic investigations, management, complications, post‑exposure precautions, and prevention strategies for measles?

Measles: Comprehensive Clinical Overview

Etiology

Measles (rubeola) is caused by measles virus, a single-stranded RNA virus belonging to the genus Morbillivirus in the Paramyxoviridae family. 1, 2, 3 The virus is strictly human with no animal reservoirs, having evolved from rinderpest virus around the 6th century BCE. 1

Pathogenesis

The virus spreads via respiratory aerosols through human-to-human contact, with an extraordinarily high R0 of 15-20, making it one of the most contagious infectious diseases. 1, 4

• The incubation period averages 10-12 days from exposure to prodrome and 14 days from exposure to rash (range: 7-18 days). 5, 6
• Patients are infectious from 4 days before rash onset through 4 days after rash appearance. 5, 7, 6
• The virus causes profound immune suppression, predisposing to secondary bacterial infections. 4
• Immunocompromised persons may shed virus for several weeks after acute illness and may present without typical rash. 5, 6

Clinical Features

Symptoms and Signs

The disease begins with a prodrome of fever (≥38.3°C/101°F), cough, coryza (runny nose), and conjunctivitis ("the three Cs"), followed by a characteristic maculopapular rash. 5, 6, 3

Prodromal Phase:

• Fever, cough, coryza, and conjunctivitis develop first. 6, 3
• Koplik spots (small white spots on red background inside the mouth) appear during prodrome and are pathognomonic for measles. 6, 3

Exanthem Phase:

• Generalized erythematous maculopapular rash lasting ≥3 days. 5, 3
• Rash begins on the face and spreads cephalocaudally (downward) to trunk and extremities, becoming more confluent as it spreads. 6, 2, 3

Investigations

Laboratory Diagnosis

Blood for measles-specific IgM antibody testing should be collected during the first clinical encounter, even before results return, as control activities must not be delayed. 5, 7, 8

Serologic Testing:

• If IgM is negative within the first 72 hours of rash onset, obtain a second specimen at least 72 hours after rash onset, as IgM may not be detectable early with some assays. 5, 7
• IgM peaks approximately 10 days after rash onset and remains detectable for at least 1 month. 5, 7
• A four-fold or greater rise in measles-specific IgG between acute and convalescent sera confirms diagnosis. 3

Viral Detection:

• Collect urine or nasopharyngeal specimens for viral isolation and genetic characterization as close to rash onset as possible. 5
• RT-PCR detection of measles virus RNA provides confirmation. 6, 3

Important Caveat: False positive IgM results can occur, particularly with parvovirus infection; confirmatory testing with direct-capture IgM EIA should be considered when no epidemiologic linkage exists. 5

Management

Immediate Actions

Isolate the patient immediately for at least 4 days after rash onset using airborne precautions (negative pressure room, N95 respirators for all staff regardless of immunity status). 5, 7, 8

Contact the local or state health department immediately—one confirmed measles case constitutes an urgent public health situation requiring prompt investigation. 5, 7

Essential Treatment: Vitamin A Supplementation

All children with clinical measles must receive vitamin A supplementation on day 1—this is the only evidence-based intervention proven to reduce measles mortality. 7, 8, 6

Dosing Protocol:

• Children ≥12 months: 200,000 IU orally on day 1. 7, 8, 6
• Children <12 months: 100,000 IU orally on day 1. 7, 8, 6
• For complicated measles: Repeat identical dose on day 2. 7, 8
• Additional dose 1-4 weeks later for vitamin A deficiency with eye symptoms. 8, 6

Supportive Care

Treatment is primarily supportive with aggressive management of complications. 7, 8

• Treat secondary bacterial infections with appropriate antibiotics (pneumonia, otitis media). 7, 8, 6
• Oral rehydration therapy for diarrhea. 7, 8, 6
• Monitor nutritional status and enroll in feeding programs if indicated. 8

Complications

Diarrhea is the most frequent complication, followed by otitis media and bronchopneumonia. 5, 6

Serious Complications:

• Encephalitis occurs in approximately 1 per 1,000 cases; survivors often have permanent brain damage and mental retardation. 5, 6
• Death occurs in 1-2 per 1,000 reported cases in the United States; the case-fatality rate can reach 25% in developing countries. 5, 6
• Pneumonia and acute encephalitis are the most common causes of death. 5

Special Populations at Higher Risk:

• Infants, young children, and adults have greater risk for death and complications than older children and adolescents. 5, 6
• Pregnant women: increased rates of premature labor, spontaneous abortion, and low birth weight. 5, 6
• Immunocompromised persons: severe, prolonged infection, sometimes without typical rash. 5, 6

Late Complication:

• Subacute sclerosing panencephalitis (SSPE) is a rare but fatal degenerative CNS disease appearing years after infection; widespread vaccination has essentially eliminated SSPE from the United States. 5, 6

Precautions (Post-Exposure Prophylaxis)

For Exposed Contacts Without Immunity

MMR vaccine administered within 72 hours of exposure may provide protection or modify disease severity. 7, 8, 6

Healthcare personnel without evidence of immunity must be excluded from work days 5-21 following exposure, even if they receive post-exposure IG. 5, 8

Immune Globulin (IG) Administration

For persons with contraindications to measles vaccination requiring immediate protection:

• Standard dose: 0.25 mL/kg IM (maximum 15 mL) within 6 days of exposure. 5, 7, 8
• Immunocompromised persons: 0.5 mL/kg IM (maximum 15 mL) within 6 days of exposure. 5, 7, 8
• Pregnant women: 0.25 mL/kg (maximum 15 mL) within 6 days of exposure. 7, 8

Critical Timing: Live measles vaccine should be given 3 months after IG administration, as passive antibodies interfere with vaccine response. 5

Prevention

Vaccination Strategy

Vaccination with MMR is the cornerstone of measles prevention and the only effective strategy to prevent SSPE. 6, 4

Routine Immunization Schedule:

• First dose: 12-15 months of age. 6, 4, 3
• Second dose: 4-6 years of age. 6, 3
• Seroconversion at 9 months is approximately 85%; at 12 months approximately 95%. 4

Two-Dose Requirement Rationale:

• Interruption of endemic transmission requires >95% population immunity; a second dose is necessary to achieve this level. 4
• Persons should receive two doses at least 28 days apart. 5

Special Vaccination Considerations

High-Risk Groups Requiring Enhanced Protection:

• College students and healthcare workers: two documented doses required. 5
• International travelers: ensure two doses before departure. 5

Outbreak Control:

• Infants aged 6-11 months may receive measles vaccine during outbreaks; they must be revaccinated at 12-15 months and again before school entry. 5
• Persons without acceptable evidence of immunity should be vaccinated or excluded from outbreak settings until 21 days after rash onset in the last case. 5, 7

HIV-Infected Persons:

• HIV-infected children without severe immunosuppression should receive MMR at 12 months, with consideration for second dose as early as 28 days later. 6
• Children with severe immunosuppression should NOT receive measles vaccination due to risk of vaccine-associated disease. 6

Important Note: Undernutrition is not a contraindication but rather a strong indication for vaccination. 6

Contraindications

Absolute Contraindications:

• Pregnancy (theoretical risk to fetus). 5
• Severe immunocompromise from immune deficiency diseases, leukemia, lymphoma, generalized malignancy, or immunosuppressive therapy. 5
• High-dose corticosteroids (≥20 mg/day prednisone for >2 weeks). 6

Vaccine Timing:

• Administer 14 days before—or defer for at least 6 weeks and preferably 3 months after—receipt of IG, whole blood, or other antibody-containing blood products. 5