Rubella, Measles and Mumps Serology

Serology for rubella, measles and mumps detects IgG (immunity from infection or vaccination) and IgM (acute or recent infection) by enzyme immunoassay or chemiluminescence, usually reported together as a panel. IgG avidity is used for rubella in pregnancy. PCR of throat swab, urine, oral fluid or CSF is the preferred test for acute measles, mumps and rubella, and virus genotyping supports outbreak investigation.

These infections are vaccine preventable but have resurged where coverage has fallen. Measles remains a leading cause of child death in low income settings (over 100 000 deaths each year), with outbreaks in under vaccinated communities worldwide.

Congenital rubella syndrome (cataracts, sensorineural deafness, congenital heart disease, microcephaly, learning difficulty) follows maternal infection in the first 16 weeks, with foetal infection rates of 80 to 90% in the first 12 weeks. Mumps causes parotitis, orchitis (15 to 30% of post-pubertal males), meningitis and deafness.

Measles complicates with otitis, pneumonia, encephalitis (1 in 1000) and subacute sclerosing panencephalitis years later.

Components.

• Rubella IgG. Protective level 10 to 15 IU/mL (negative under 10 IU/mL). Confirms immunity from vaccination or past infection.
• Rubella IgM. Indicates recent infection (from rash onset, peaking at 1 to 2 weeks, persisting for 6 to 8 weeks or longer), reinfection or false positive. Avidity of rubella IgG (low avidity under 30 to 40% suggests infection within 2 to 3 months) helps distinguish.
• Measles IgG. Protective level over the laboratory cut off (often over 150 to 200 mIU/mL). Negative indicates susceptibility.
• Measles IgM. Positive from 3 days after rash onset, peak at 1 to 2 weeks, gone by 6 to 8 weeks. A sample before day 3 may be falsely negative, so repeat if the first is negative with a compatible illness.
• Mumps IgG. Indicates immunity from infection or vaccination, although assays are less sensitive for vaccine induced antibody.
• Mumps IgM. Positive in about 70% of unvaccinated patients with mumps but often negative in vaccinated patients with breakthrough infection, so PCR of buccal swab or oral fluid is preferred.

Indications. Antenatal screening for rubella immunity. Rash and fever in pregnancy or contact with a rash illness. Suspected measles (fever, cough, coryza, conjunctivitis, Koplik spots, maculopapular rash), suspected mumps (parotitis, orchitis, meningitis) or rubella. Newborn with cataract, deafness or heart defect (congenital rubella).

Healthcare workers, students, military recruits and travellers to document immunity. Contact tracing in outbreaks. Immunocompromised patients and before transplant.

Specimen. Serum 1 mL, no fasting. Stable for days at 2 to 8 °C. Throat swab, oral fluid, urine (measles, rubella) and buccal or parotid duct swab (mumps) in viral transport medium for PCR within 7 days of rash or swelling onset.

Reference values (assay dependent).

• Rubella IgG: under 10 IU/mL non-immune, 10 to 15 IU/mL low or equivocal, over 15 IU/mL immune.
• Rubella IgM, measles IgM, mumps IgM: negative (index under 0.8 or under 0.9), equivocal, positive.
• Measles IgG and mumps IgG: negative under laboratory cut off, positive indicates immunity.

Pattern interpretation.

• A rising IgG titre (four fold or more) in paired sera taken 10 to 14 days apart confirms acute infection.
• Rubella in pregnancy: positive IgM with low avidity IgG in the first 16 weeks indicates high risk, and foetal infection is confirmed by amniocentesis PCR from 18 weeks or foetal blood. Counselling is specialised.
• Immune status in pregnancy: IgG over 10 IU/mL is considered protective, and women with levels under 10 IU/mL are vaccinated after delivery.
• Measles IgM positive in a person with rash, fever and cough: confirms measles, and a notification is made to public health authorities.
• Mumps IgM or PCR positive: confirms mumps, with PCR more reliable in vaccinated people.
• Subacute sclerosing panencephalitis: very high measles IgG in serum and CSF with intrathecal synthesis.

Critical values and findings needing immediate action.

• Pregnant woman with rash, fever or contact with rubella and low or negative IgG: urgent paired serology and IgM, avidity, specialist counselling, and isolation.
• Suspected measles: airborne isolation immediately, notification to public health, and PCR with IgM. Vitamin A in children and supportive care. Susceptible contacts are offered vaccine within 72 hours or immunoglobulin within 6 days (infants, pregnant women and immunocompromised).
• Measles with pneumonia, encephalitis, dehydration or immunosuppression: admission and intensive care as needed.
• Mumps with severe headache, vomiting, stiff neck (meningitis), testicular swelling (orchitis) or acute hearing loss: admission, analgesia and audiology.
• Newborn with suspected congenital rubella: isolation (viral shedding for up to a year), PCR of urine, throat and CSF, and referral for ophthalmology, cardiology and audiology.

Interferences and pitfalls.

• IgM false positives are frequent in rubella, measles and mumps, with cross-reactions from parvovirus B19, Epstein-Barr virus, cytomegalovirus, rheumatoid factor and polyclonal B-cell stimulation. A positive IgM in a pregnant woman without symptoms or contact needs IgG avidity and a second sample before action.
• Measles and mumps IgM may be negative in the first 3 days of rash and in vaccinated patients with breakthrough disease, so PCR and repeat serology are required.
• Vaccine induced antibody may be lower than natural infection and missed by some assays, so documented vaccination is accepted as evidence of immunity.
• Passive antibody after immunoglobulin or blood products can give false positive IgG.
• Rubella antibody levels fall over years in some vaccinated women, and revaccination is needed if under 10 IU/mL.
• Live vaccines (measles, mumps, rubella) are not given in pregnancy or severe immunosuppression, and pregnancy is avoided for 4 weeks after vaccination.
• Rash illnesses with similar appearance (parvovirus B19, enteroviruses, dengue, HHV-6 roseola, scarlet fever, drug rash) are excluded.
• Notification of suspected measles, mumps and rubella to public health authorities is required in most countries.

Special groups.

• Children: the combined vaccine is given at 9 to 12 months and a second dose at school entry or 15 to 18 months. Measles under 12 months is severe, and maternal antibody wanes by 6 to 9 months.
• Pregnancy: rubella and varicella immunity checked at the first antenatal visit. Non-immune women are vaccinated after delivery.
• Healthcare workers and students: evidence of two documented doses or positive IgG is required.
• Immunocompromised and malnourished patients: prolonged, severe measles with atypical presentation.
• Older adults born before routine vaccination (before 1957 in some countries): presumed immune from natural infection.
• Regions: measles outbreaks follow vaccine hesitancy and conflict. In low income countries measles mortality is high in malnourished children and vitamin A deficiency, and rubella vaccination coverage is incomplete.

Follow up tests. PCR for measles, mumps and rubella (throat, oral fluid, urine), genotyping, rubella IgG avidity, paired sera for IgG rise, parvovirus B19 IgM, Epstein-Barr virus and cytomegalovirus serology for differential diagnosis, HIV test, amniocentesis PCR in pregnancy, foetal ultrasound, newborn urine and throat PCR, audiology, ophthalmology, CSF analysis in encephalitis or panencephalitis, and testicular ultrasound in orchitis.