July 25, 1997
Infectious Diseases Specialists
The Food and Drug Administration (FDA) is advising physicians that they should not use the result from any one Toxoplasma IgM commercial test kit as the sole determinant of recent Toxoplasma infection when screening a pregnant patient. Because these tests can have false-positive results, reliance on a single test result could lead to misdiagnosis, resulting in unnecessary treatment of the patient and/or termination of the pregnancy.
Anti-Toxoplasma IgM commercial test kits are used to screen pregnant women to determine recent maternal Toxoplasma infection that might place the fetus at risk for toxoplasmosis. The kits contain reagents used to detect antibodies to Toxoplasma gondii in serum, and were cleared by FDA as an aid in the diagnosis of recently acquired infections which are often without signs or symptoms.
FDA has recently become aware of inaccurate test results from clinical reference laboratories, proficiency testing surveys, the Centers for Disease Control and Prevention (CDC), and the scientific literature. As a result, FDA's Microbiology Devices Advisory Panel recommended that the Agency conduct a pilot study to assess the potential inaccuracy of these commercial test kits and alert the medical community if necessary. Results from the pilot study conducted by FDA and CDC clearly indicated that test kit specificity varies greatly and further study is warranted. At present, the feasibility of additional research is being considered and the FDA is working with the manufacturers of the test kits to provide appropriate labeling information.
Physicians are advised to interpret the results of anti-Toxoplasma IgM tests with caution. They should not rely on any single test result as the sole determinant in diagnosing recently acquired infection and deciding on further medical action. If acute infection is suspected, a patient sample should be tested for the presence of Toxoplasma-specific IgG and IgM antibodies. The results should be interpreted using the suggested algorithm for interpretation provided in the accompanying table. The decision to treat or to undertake other medical interventions, including the termination of pregnancy, should be based on clinical evaluation and additional testing performed in reference or research laboratories with experience in the diagnosis of toxoplasmosis.
General Guidelines for Interpretation of Toxoplasma gondii Serology Results
|Igg Result||Igm result||Report/interpretation for all except infants|
|Negative||Negative||No serologic evidence of infection with Toxoplasma gondii.|
|Negative||Equivocal||Possible early acute infection or false-positive IgM reaction. Obtain a new specimen for IgG and IgM testing. If the new specimen result remains the same, the patient is probably not infected with Toxoplasma gondii.|
|Negative||Positive||Possible acute infection or false-positive IgM result. Obtain a new specimen for IgG and IgM testing. If results from the second specimen remain the same, the IgM reaction is probably a false-positive.|
|Equivocal||Negative||Indeterminate: obtain a new specimen for testing or retest this specimen for IgG in a different assay.|
|Equivocal||Equivocal||Indeterminate: obtain a new specimen for both IgG and IgM testing.|
|Equivocal||Positive||Possible acute infection with Toxoplasma gondii. Obtain a new specimen for IgG and IgM testing. If results with the new specimen remain the same or the IgG becomes positive, both specimens should be sent to a reference laboratory with experience in the diagnosis of toxoplasmosis.|
|Positive||Negative||Infected with Toxoplasma gondii for more than one year.|
|Positive||Equivocal||Infected with Toxoplasma gondii for probably more than one year or false-positive IgM reaction. If results from the second specimen remain the same, both specimens should be sent to a reference laboratory with experience in toxoplasmosis.|
|Positive||Positive||Possible recent infection within the last 12 months. Send the specimen to a reference laboratory with experience in the diagnosis of toxoplasmosis.|
NOTE: Spiramycin, which is not FDA approved, is manufactured by Rhone-Poulenc Pharmaceuticals and available via individual investigator IND for treatment of pregnant women with toxoplasmosis. As part of this program the company strongly encourages requesting physicians to submit samples for toxoplasmosis testing to Dr. Jack Remington's laboratory in Palo Alto, California. Information on the Spiramycin program is available by calling the Division of Special Pathogens and Immunologic Drug products at FDA at (301) 827-2335.
NOTE: This table was originally developed at FDA/CDRH and refined in cooperation with Jack Remington, MD of the Palo Alto Medical Foundation and the CDC.
Reporting Adverse Events to FDA
The Safe Medical Devices Act of 1990 (SMDA) requires hospitals and other user facilities to report deaths and serious illnesses and injuries associated with the use of medical devices. Thus, under the law, an erroneous result or any other adverse event from an anti-Toxoplasma commercial test kit resulting in a death or serious illness must be reported. For such mandatory reporting we request that you follow the procedures established by the hospital with which you are affiliated.
Even if a report is not mandatory, it would be helpful to report directly to MedWatch, the FDA's voluntary reporting program. Submit these reports to MedWatch: by telephone at (800) FDA-1088, by FAX at (800) FDA-0178, or by mail to:
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
FDA Medical Device Public Health Notifications are available on the Internet. You can also be notified through email each time a new Public Health Notification is added to our web page. To subscribe, visit: http://service.govdelivery.com/service/subscribe.html?code=USFDA_39.
D. Bruce Burlington, M.D.
Center for Devices and Radiological Health
Food and Drug Administration