Vaccination News Home Page

http://bmj.com/cgi/content/full/325/7356/147

PDF of this article Email this article to a friend Respond to this article PubMed citation Related articles in PubMed Download to Citation Manager Search Medline for articles by: Best, J. M || Enders, G. Alert me when: New articles cite this article

Collections under which this article appears: Pregnancy Other Infectious Diseases Molecular Medicine Reproductive medicine

BMJ 2002;325:147-148 ( 20 July )

Clinical review

Lesson of the week
 

Interpretation of rubella serology in pregnancypitfalls and problems

Clinical and laboratory expertise is essenrial for evaluating rubella specific IgM test results in pregnancy

Jennifer M Best, reader in virology ^a, Siobhan O'Shea, clinical scientist ^b, Graham Tipples, head of viral exanthemata ^c, Nicholas Davies, specialist registrar ^b, Saleh M Al-Khusaiby, head of department of child health ^d, Amanda Krause, clinical director ^e, Louise M Hesketh, clinical scientist ^f, Li Jin, clinical scientist ^g, Gisela Enders, head of institute ^h. 

^a Guy's, King's and St Thomas's School of Medicine, St Thomas's Hospital, London SE1 7EH, ^b Department of Infection, Guy's and St Thomas's Hospital Trust, London SE1 7EH, ^c Bureau of Microbiology, Laboratory Center for Disease Control, 1015 Arlington Street, Winnipeg, Canada, ^d Royal Hospital, PO Box 1331, Postal Code 111, Sultanate of Oman, ^e Department of Human Genetics, South African Institute for Medical Research and University of the Witwatersrand, PO Box 1038, Johannesburg 2000, South Africa, ^f Public Health Laboratory, Royal Preston Hospital, Fulwood, Preston PR2 9HG, ^g Central Public Health Laboratory, Colindale, London NW9 5HT, ^h Institut für Virologie, Infektologie und Epidemiologie, Rosenbergstrasse 85, D-70193 Stuttgart, Germany

Correspondence to: J M Best jenny.best@kcl.ac.uk

Rubella acquired in the first 12 weeks of pregnancy is associated with a 90% risk of congenital malformations. Although rare in many industrialised countries, because of the success of vaccination programmes, rubella continues to occur where uptake of the vaccine is low and in many developing countries with no vaccination programme. The World Health Organization has therefore encouraged all countries to assess their rubella status and introduce immunisation and surveillance, if appropriate.¹ As the clinical diagnosis of rubella is unreliable, serological tests are needed for a diagnosis, especially when a patient is pregnant or has been in contact with a pregnant woman.² Diagnosis is usually made by detection of rubella specific IgM. Although commercial assays are available, they vary in format, sensitivity, and specificity.³ Furthermore, rubella specific IgM may be present a year or more after natural infection or vaccination and after asymptomatic reinfection.^4-8 False positive results may also be due to cross reacting IgM antibodies or rheumatoid factor.⁹ Consequently, in countries with limited laboratory facilities and expertise, diagnosis of rubella in pregnancy is problematic. It is essential that laboratory results be interpreted in the context of full clinical details, to avoid misinterpretation of results and to minimise anxiety for the patient, especially if termination of pregnancy is considered. Here we discuss six cases referred initially to the Department of Virology at Guy's and St Thomas's Hospital Trust from February to September 2000.

	Case reports

Top Case reports Discussion References

Clinical information on the patients and laboratory test results are shown in the table. Five patients were referred from outside the United Kingdom, four because rubella specific IgM had been detected in the absence of a rash.

Patients 1 to 4 had no history of rash or contact with a rash, and in patients 2, 3, and 4 rubella IgM tests had been conducted without any clear clinical indication. In all of these patients except patient 3 positive rubella IgM results were confirmed, but rubella IgG avidity was high, indicating past rather than recent infection. In addition, detection of IgG antibodies to the E2 glycoprotein of rubella virus by immunoblot in patients 1 and 2 indicated that primary infection occurred more than five months previously, indicating persistence of rubella IgM.¹⁰ Rubella specific IgM was not detected in serum samples from patient 3 when tested in the United Kingdom. Prenatal diagnosis offered to patients 1, 2, and 3 at 18-22 weeks' gestation provided further reassurance that their babies were unlikely to have congenital rubella infection (table). ^{11 12}

Rubella IgM antibodies in case 4 were detected locally using indirect enzyme immunoassays, which are more likely to give non-specific results than antibody capture assays.³ Retesting in two reference laboratories gave negative results in M antibody capture assays but a weak positive result in an indirect assay. This patient was therefore reassured that she had not had primary rubella, as she had a history of rubella vaccination and high avidity rubella specific IgG was detected.

Patient 5 was of particular concern. Rubella specific IgM was not detected locally, but the patient's obstetrician misinterpreted the laboratory results and advised termination of pregnancy.

Patient 6 presented with rash and fever at 33 weeks' gestation. A vesicular scrape was taken and a diagnosis of chickenpox made by immunofluorescence. However, low positive results were obtained in rubella IgM and parvovirus B19 IgM assays. Such false positive IgM results may be explained by cross reacting antibodies known to be induced by some viral infections and autoimmune disease. ^{6 9 13} It is therefore of interest that this patient gave a weak positive result in the Rose Waaler assay and during childhood had suffered from rheumatic fever and required mitral valve replacement.

	Discussion

Top Case reports Discussion References

These cases show that results of rubella IgM assays conducted on serum samples from pregnant women should always be interpreted with caution. Any history of rash or contact with rash, previous rubella testing, and history of vaccination should be taken into consideration.² Tests for rubella IgM are not indicated unless there is a history of rash in a pregnant woman or contact with a rubella-like rash. Unnecessary tests for rubella IgM may lead to problems in interpretation, because the positive predictive value of rubella IgM results has declined in countries where rubella seldom occurs. These cases show that problems may arise as a result of:

• False positive rubella IgM results
• No access to other assays, such as rubella IgG avidity ^{14 15}
• Limited experience of rubella diagnosis and its pitfalls (for example, persistent specific IgM) ^{4 7}
• Misinterpretation of laboratory results.

In our experience results from about 2% of serum samples tested for rubella IgM will be difficult to interpret. In other countries this problem may be more common.⁷ To manage these cases close collaboration between obstetricians and virologists is essential at all stages, to avoid errors and unnecessary terminations and to decide whether prenatal diagnosis is indicated.^2-12

	Acknowledgments

We wish to thank the laboratory staff of all the centres involved.

Contributors: JMB, SO'S, and GE interpreted laboratory results and wrote the paper. ND, SMA-K, and AK investigated patients and provided clinical details. GT provided clinical details and performed laboratory investigations. LMH, LJ, and GE performed laboratory investigations. GE performed tests for prenatal diagnosis. All authors contributed to writing and discussion of the paper.

	Footnotes

Funding: None.

Competing interests: None declared.

	References

Top Case reports Discussion References

(Accepted 12 February 2002)
 

© BMJ 2002
 

PDF of this article Email this article to a friend Respond to this article PubMed citation Related articles in PubMed Download to Citation Manager Search Medline for articles by: Best, J. M || Enders, G. Alert me when: New articles cite this article

Collections under which this article appears: Pregnancy Other Infectious Diseases Molecular Medicine Reproductive medicine

Vaccination News Home Page

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.