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Correspondence

False Positive Rubeola IgM Tests

N Engl J Med 1995; 332:1103-1104April 20, 1995

Article

To the Editor:

Between June 1 and November 1, 1994, as part of an investigation of an outbreak of rubeola (measles), the Alaska State Health Department studied 57 persons with febrile illness accompanied by a rash. Efforts were made to obtain serum specimens from all persons with these symptoms during the investigation.

Using an enzyme immunoassay kit for rubeola IgM approved by the Food and Drug Administration, and commercially available, the State Public Health Laboratory identified 16 specimens that were positive for rubeola IgM, indicating acute rubeola illness. After noticing that several of the 16 people with IgM-positive specimens did not have the constellation of symptoms or risk factors usually associated with rubeola, we sent all the positive specimens (as well as 10 IgM-negative specimens from persons with febrile illness and a rash) to the Centers for Disease Control and Prevention (CDC) for confirmatory testing with a capture enzyme immunoassay for rubeola IgM.1 The CDC also tested the specimens for human parvovirus B19 (fifth disease) IgM antibodies.

With the CDC test results as the gold standard, the specificity of the rubeola IgM test used by the state laboratory was 55.6 percent. Six of the 18 specimens that were negative for rubeola IgM at the CDC were positive for human parvovirus B19 IgM; 3 of these 6 specimens were from patients with positive rubeola IgM tests at the state laboratory. Of the eight persons with positive tests at the CDC, seven met a clinical case definition for rubeola,2 as compared with only one of the eight persons with positive tests at the state laboratory but negative tests at the CDC (P = 0.01 by two-tailed Fisher's exact test).

Cross-reactions between rubella- and parvovirus-specific IgM tests have been reported previously.3 Our data indicate that a commercially available enzyme immunoassay kit for rubeola IgM used nationwide may yield false positive results, some of which are associated with human parvovirus B19 infection. The CDC had previously notified the directors of state public health laboratories about cross-reactions between specific IgM tests for rubeola and human parvovirus B19. Because of our findings during this investigation, the state laboratory in Alaska now uses a second, more specific capture enzyme immunoassay for rubeola IgM (currently unlicensed), along with the licensed, commercially available test.

The diagnosis of rubeola activates extensive public health efforts, costs parents lost work time, and often leads to the exclusion of unvaccinated children from school and day care. A simple, rapid, and reliable diagnostic test for acute rubeola is needed.

Sue Anne Jenkerson, R.N.C., M.S.N.
Michael Beller, M.D., M.P.H.
John P. Middaugh, M.D.
Alaska Division of Public Health, Anchorage, AK 99524-0249

Dean D. Erdman, Dr.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30333

3 References
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    Hummel KB, Erdman DD, Heath J, Bellini WJ. Baculovirus expression of the nucleoprotein gene of measles virus and utility of the recombinant protein in diagnostic enzyme immunoassays. J Clin Microbiol 1992;30:2874-2880
    Web of Science | Medline

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    Case definitions for public health surveillanceMMWR Morb Mortal Wkly Rep 1990;39:23-23

  3. 3

    Kurtz JB, Anderson MJ. Cross-reactions in rubella and parvovirus specific IgM tests. Lancet 1985;2:1356-1356
    CrossRef | Web of Science | Medline

Citing Articles (5)

Citing Articles

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    A. M. Bispo de Filippis, J. Icenogle, C. R. Matus, J. K. Andrus. (2011) Enhanced Laboratory Surveillance for the Elimination of Rubella and Congenital Rubella Syndrome in the Americas. Journal of Infectious Diseases 204:suppl 2, S652-S658
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  2. 2

    Eden V. Wells, Joel Blostein, Curi Kim, Rachel Potter, Matthew Boulton. (2010) A Measles Cluster in Michigan. Infectious Diseases in Clinical Practice 18:1, 37-40
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  3. 3

    Graham A Tipples, Rasool Hamkar, Talat Mohktari-Azad, Michael Gray, Jennifer Ball, Carol Head, Samuel Ratnam. (2004) Evaluation of rubella IgM enzyme immunoassays. Journal of Clinical Virology 30:3, 233-238
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  4. 4

    William J. Bellini, Rita F. Helfand. (2003) The Challenges and Strategies for Laboratory Diagnosis of Measles in an International Setting. The Journal of Infectious Diseases 187:s1, S283-S290
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  5. 5

    JOHN C. WATSON, STEPHEN C. REDD, PHILIP H. RHODES, STEPHEN C. HADLER. (1998) The interruption of transmission of indigenous measles in the United States during 1993. The Pediatric Infectious Disease Journal 17:5, 363-366
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