Rubella Laboratory Diagnosis

PATHCHAT Edition No. 86
Published: September 2023
Please contact your local Ampath pathologist for more information.

Author:

• Dr. Marieke Brauer

Key Messages

✅ Rubella IgG testing is recommended before a planned pregnancy

• Determines protective immunity against rubella.
• Ensures early identification of susceptible individuals.

✅ Rubella IgM testing should be used selectively during pregnancy

• Best suited for symptomatic individuals or those with known exposure.
• Routine screening in asymptomatic pregnant women is discouraged due to low predictive value.

✅ Rubella IgM remains the first-line test for diagnosing acute rubella

• Confirmed cases should be verified using rubella PCR on throat swabs or urine.
• PCR testing is necessary due to rubella's short viraemic phase.

📌 Appropriate testing strategies are crucial to prevent unnecessary anxiety and ensure accurate diagnosis.

Introduction to Rubella

✅ What is Rubella?

• A viral infection commonly known as German measles.
• Usually mild in children but may cause severe complications in pregnancy.
• Transmission occurs via aerosolized respiratory droplets.
• Individuals are contagious from 7 days before symptom onset to 7 days after.

✅ Clinical Presentation of Rubella

• Incubation period: 14–18 days post-exposure.
• Symptoms include:
  • Mild fever.
  • Fine maculopapular rash (starting on the face and spreading to the trunk).
  • Postauricular and posterior cervical lymphadenopathy.
  • Polyarthralgia/arthritis (in ~70% of adolescent and adult cases).
• 25–50% of cases are asymptomatic.

📌 Rubella is a mild illness in most cases, but maternal infection during pregnancy can lead to severe foetal complications.

Congenital Rubella Infection (CRI) and Congenital Rubella Syndrome (CRS)

✅ Foetal Transmission Risk by Pregnancy Stage

• First trimester: 80–90% risk, with a high likelihood of congenital defects.
• Second trimester (weeks 14–26): 25% risk, declining towards mid-pregnancy.
• Late second to early third trimester (weeks 27–30): 35% risk.
• After week 36: Nearly 100% risk of foetal transmission, but low congenital malformation risk.

✅ Congenital Rubella Syndrome (CRS) Features

• Classic triad:
  • Cataracts.
  • Sensorineural deafness.
  • Congenital heart defects (e.g., peripheral pulmonary artery stenosis, patent ductus arteriosus, ventricular septal defect).
• Additional signs:
  • Congenital glaucoma.
  • Purpura ("blueberry muffin" rash).
  • Splenomegaly.
  • Microcephaly.
  • Developmental delays.

✅ Reinfection During Pregnancy

• Foetal transmission risk in maternal reinfection: 5–8% (first 16 weeks).
• No CRS cases reported in reinfections after 12 weeks.

📌 Maternal rubella infection before 17 weeks poses the highest risk for congenital malformations.

Rubella Vaccination & Changing Epidemiology

✅ Global Impact of Vaccination

• Rubella vaccines were introduced in 1969, reducing global rubella incidence.
• Live attenuated rubella vaccines (RA27/3 strain) provide 99.3% protection.

✅ Rubella Vaccination in South Africa

• Only available in combination with measles and mumps (MMR) or with measles, mumps, and varicella (MMRV).
• Not included in the public sector Expanded Programme on Immunisation (SA-EPI).
• Available in the private sector and administered at 6 and 12 months (aligned with measles schedule).

✅ Challenges of Rubella Vaccine Introduction in South Africa

• Paradoxical CRS risk:
  • If vaccine coverage is insufficient (<80%), immunity gaps in childbearing women may increase CRS risk.
  • WHO advises introducing rubella vaccination only if high routine measles vaccine coverage is sustained.

📌 Rubella vaccine implementation requires careful planning to prevent unintended increases in CRS cases.

Laboratory Diagnosis of Rubella

✅ Diagnostic Testing Methods

1. Antibody Testing (First-Line):
   • Rubella IgM (detects recent infection).
   • Rubella IgG (determines immunity).
   • Rubella IgG avidity (distinguishes recent vs. past infections).
2. Molecular Testing (Confirmatory in Acute Cases):
   • Rubella PCR on throat swab, urine, or amniotic fluid.

✅ Key Considerations for IgM Testing

• IgM positivity does not distinguish between natural infection and vaccine response.
• False positives may occur due to:
  • Cross-reactivity (e.g., parvovirus B19, EBV, rheumatoid factor).
  • Persistent IgM responses after vaccination.
• Low positive predictive value in low-prevalence settings.

✅ Rubella PCR for Confirming Acute Infection

• Best sample: Throat swab.
• Detection window: 2 days before to 4 days after rash onset.
• Serum PCR has limited utility due to short viraemic phase.

📌 Rubella IgM should be cautiously interpreted, especially in routine antenatal screening.

Diagnostic Approach to Congenital Rubella Infection (CRS)

✅ Prenatal Testing

• Maternal IgM and IgG testing.
• Rubella PCR on amniotic fluid (optimal after 20 weeks).
• Foetal blood IgM (less reliable before third trimester).
• Counselling is essential regarding prenatal test limitations.

✅ Postnatal Testing for CRS

• Rubella IgM in infants (first 3 months of life).
• Confirm with rubella PCR on nasopharyngeal swab or urine.
• Persistent or rising IgG titres in infants (before rubella vaccination) also suggest CRS.

📌 Laboratory confirmation of CRS is crucial for early intervention and monitoring.

Key Takeaways for Clinicians

✅ Rubella IgG testing before pregnancy is essential to confirm immunity.
✅ Routine rubella IgM screening in asymptomatic pregnant women is discouraged due to false positives.
✅ PCR testing is the preferred confirmatory method for acute rubella infection.
✅ Congenital rubella syndrome risk is highest with maternal infection before 17 weeks.
✅ Rubella vaccination is highly effective but should be introduced strategically to avoid paradoxical increases in CRS.

📌 Accurate rubella testing and vaccination strategies are critical for reducing congenital rubella syndrome worldwide.