What is the best approach to detect rubella infection, particularly in pregnant women?

Detecting Rubella Infection

Confirm acute rubella infection serologically by testing for rubella-specific IgM antibody or demonstrating a significant rise in IgG antibody between acute and convalescent sera, with IgM testing being most reliable when collected between 1-2 weeks after rash onset. 1, 2

Serologic Testing Methods

IgM Antibody Testing (Preferred for Acute Diagnosis)

• Rubella-specific IgM antibody is the primary marker for acute infection and becomes detectable as early as 1-2 days after rash onset, peaks at approximately 7 days, and remains detectable for 4-12 weeks 3
• Collect serum specimen between 1 week and 2 weeks after rash onset for optimal IgM detection 1, 2, 3
• IgM is less likely to be detected if drawn earlier than 1 week or later than 4-5 weeks following rash onset 1
• Beware of false-positive IgM results, especially in low-prevalence settings and pregnant women—interpret results in the context of clinical presentation, timing of specimen collection, and epidemiologic linkage to confirmed cases 3
• False-negative IgM results can also occur even with appropriately timed specimens 1

Paired Sera Testing (IgG Rise)

• Draw acute-phase serum as soon after rash onset as possible, preferably within the first 7 days 1
• Draw convalescent-phase serum 10 or more days after the acute-phase specimen 1
• A fourfold rise in HI antibody titer or significant rise by other assays indicates recent infection 1, 4
• Test both specimens simultaneously in the same laboratory 1
• If acute-phase serum is drawn more than 7 days after rash onset, a significant rise may not be detected by most commonly used tests—consider complement fixation (CF) testing in this scenario, as CF antibodies appear later than HI, EIA, or IFA antibodies 1

Alternative Molecular Testing

• Detection of rubella virus RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) can confirm infection 4

Special Considerations for Pregnant Women

Immediate Testing Protocol

• Obtain serum specimen as soon as possible after suspected exposure or rash onset 2, 3
• Confirmation of rubella infection in pregnant women of unknown immune status following rash illness or exposure is often difficult and serologic results are frequently nonconfirmatory 1
• Retain prenatal screening specimens until delivery to allow retesting if necessary 1, 3

Exposure Without Symptoms

• For subclinical cases following exposure, obtain acute-phase serum as soon as possible after exposure 1
• Draw convalescent-phase specimen 28 or more days after exposure 1
• If paired sera provide inconclusive results, perform rubella-specific IgM antibody testing, but interpret results cautiously and consider expert consultation 1

Prenatal Screening

• Perform routine prenatal serologies to identify susceptible women before exposure occurs—this minimizes diagnostic difficulties later 1
• Any detectable antibody level above the standard positive cutoff value for a licensed assay confirms immunity 1, 3
• A negative rubella IgG test indicates susceptibility to infection 2

Confirmatory Testing Requirements

• Assess epidemiologic linkage to determine if there is known exposure to a confirmed rubella case 3
• Consider confirmatory testing with alternative methods, especially if no clinical symptoms or epidemiologic linkage exists 3
• Report immediately to local health department if IgM positive with compatible clinical presentation 3

Clinical Context for Testing

Symptoms to Assess

• Look for transient erythematous and sometimes pruritic rash 5
• Examine for postauricular or suboccipital lymphadenopathy 5
• Document arthralgia (occurs in up to 70% of adult women) 2, 5
• Check for low-grade fever 5
• Remember that 25-50% of rubella infections are subclinical with no apparent symptoms 5

Differential Diagnosis

• Clinical diagnosis of rubella is unreliable due to variable presentation and similarity to other exanthematous illnesses caused by parvovirus, adenoviruses, and enteroviruses 5
• Laboratory confirmation is essential—never rely on clinical diagnosis alone, especially in pregnant women 6, 4

Common Pitfalls to Avoid

• Do not assume immunity based on history alone—verify with serologic testing 1
• Do not dismiss low-level antibodies detected only by sensitive tests, though their clinical significance requires further study 1
• Do not delay testing in pregnant women—obtain specimens immediately upon exposure or symptom onset 2, 3
• Do not accept IgM results without clinical and epidemiologic correlation, as false positives are problematic 3