What are the diagnostic criteria and treatment options for a child or unvaccinated adult presenting with symptoms of measles, including high fever, cough, runny nose, and a characteristic rash?

Diagnosis of Measles

Diagnose measles clinically when a patient presents with fever ≥38.3°C (≥101°F), generalized rash lasting ≥3 days, plus at least one of cough, coryza, or conjunctivitis, and immediately confirm with serum measles-specific IgM antibody testing using the direct-capture IgM EIA method. 1, 2

Clinical Diagnostic Criteria

A clinical case of measles requires all three of the following components 3, 1:

• Generalized rash lasting ≥3 days that typically begins on the face and spreads cephalocaudally 3, 4
• Temperature ≥38.3°C (≥101°F) 3, 1
• At least one of the "three C's": cough, coryza (runny nose), or conjunctivitis 3, 1

Key Clinical Features to Identify

• Prodromal phase: Fever combined with cough, coryza, and conjunctivitis appear first, before the rash 5, 4, 6
• Koplik spots: Small white spots on the buccal mucosa that may appear 2-3 days before the rash, providing diagnostic opportunity before rash emergence 6, 7
• Rash characteristics: Erythematous, maculopapular rash that starts on the face and behind the ears, then spreads downward to the trunk and extremities, becoming more confluent as it spreads 4, 8, 7
• Rash timing: Typically appears 3-4 days after fever onset, coinciding with peak symptoms 6

Laboratory Confirmation

The primary diagnostic test is serum measles-specific IgM antibody using the direct-capture IgM EIA method, which is the most sensitive and specific assay available. 3, 1, 2

Specimen Collection Algorithm

1. Collect blood during the first clinical encounter with any suspected measles case 3, 1
2. Optimal timing: IgM is most reliable when collected 6-14 days after symptom onset, with seropositivity rates of 92-100% 1, 2
3. Early collection caveat: IgM may not be detectable in the first 72 hours after rash onset with some assays 3, 1
4. If initial test is negative within 72 hours: Obtain a second specimen ≥72 hours after rash onset 3, 1

IgM Antibody Kinetics

• Becomes detectable: At the time of rash onset or 1-2 days after 3
• Peaks: Approximately 7-10 days after rash onset 3, 1
• Becomes undetectable: Within 30-60 days after rash onset in uncomplicated acute measles 3

Alternative Laboratory Criteria

A confirmed case can also be established by 3:

• Significant rise in measles antibody level by any standard serologic assay (four-fold or greater increase between acute and convalescent sera) 7
• Isolation of measles virus from a clinical specimen (throat/nasopharyngeal swabs, urine, or oral fluid) 4, 7
• Detection of measles virus RNA by reverse transcriptase-polymerase chain reaction 4, 7

Case Classification System

Suspected Case

• Definition: Any febrile illness accompanied by rash 3, 1
• Action: Report immediately to local or state health department 3, 1

Probable Case

A case that 3, 1:

• Meets the clinical case definition (fever ≥38.3°C, rash ≥3 days, plus cough/coryza/conjunctivitis)
• Is not epidemiologically linked to a confirmed case
• Has not been serologically/virologically tested or has noncontributory results

Confirmed Case

A case that meets either 3, 1:

• Laboratory criteria for measles (positive IgM, significant antibody rise, or virus isolation/detection)
• Clinical case definition and is epidemiologically linked to a confirmed case

Critical Diagnostic Pitfalls

False-Negative IgM Results

• Specimen collected too early: Within first 72 hours of rash onset 1, 2
• Solution: Repeat testing ≥72 hours after rash onset if clinical suspicion remains high 3, 1

False-Positive IgM Results

• Causes: Parvovirus infection, other viral infections, rheumatoid factor positivity 2
• Context: As measles becomes rare, the likelihood of false-positive results increases significantly in low-prevalence settings 2
• Solution: Use confirmatory testing with the highly specific direct-capture IgM EIA method when IgM is detected without epidemiologic linkage to a confirmed case 2

Reinfection in Previously Vaccinated Individuals

• Presentation: Vaccinated individuals can have milder or even no symptoms 4
• Laboratory pattern: High-avidity measles IgG with IgM positivity 9
• Key distinction: Normal CSF/serum index in reinfection, unlike SSPE which shows extremely high titers with elevated CSF/serum index ≥1.5 9

Immediate Public Health Actions

Do not delay reporting, investigation, or implementation of control activities while awaiting laboratory results. 3

• Report immediately: All suspected and known cases to local or state health department 3, 1
• Urgent investigation: One confirmed case constitutes an urgent public health situation requiring rapid investigation 1
• Purpose: Classify the case, identify source of exposure, and prevent further spread 3

Treatment Considerations

Vitamin A Supplementation

The World Health Organization recommends vitamin A supplementation for all children with clinical measles 1:

• Children ≥12 months: 200,000 IU orally on day 1 1
• Children <12 months: 100,000 IU orally on day 1 1

Supportive Care and Complications Management

• Bacterial superinfections: Treat with appropriate antibiotics 1, 7
• Diarrhea: Oral rehydration therapy 1
• Acute lower respiratory infections: Standard antibiotic treatment 1
• Pneumonia: One of the most lethal complications requiring aggressive management 6

Special Populations Requiring Aggressive Management

Patients who are pregnant, immunocompromised, or unvaccinated may require 5:

• Measles vaccine (if eligible)
• Intravenous immunoglobulin
• Vitamin A supplementation
• Potentially ribavirin in severe cases

Infection Control Measures

• Patient isolation: Airborne infection isolation room 5
• Healthcare worker protection: N-95 masks required 5
• Outbreak control: Vaccinate or exclude susceptible persons from outbreak settings until 21 days after rash onset in last case 1