Rapid diagnostic tests can improve quality of treatment if used appropriately

Issue: November 2008

BOSTON — Currently, more than 50 different commercially-approved rapid diagnostic tests are available for influenza, HIV, group A streptococcus, respiratory syncytial virus and infectious mononucleosis for use in the outpatient setting.

“There are real benefits to making a diagnosis in real time, whether in your office, an outpatient setting or the emergency room to help guide adult education and treatment decisions,” Leonard R. Krilov, MD, chief of pediatric infectious diseases at the Children’s Medical Center, Winthrop University Hospital in Mineola, and professor of Pediatrics at Stony Brook University, both in N.Y., said during a session at the AAP 2008 National Conference and Exhibition.

In 2005, inappropriate diagnosis accounted for 22.6 million out of 44 million antibiotic prescriptions, Krilov said, citing data published in Pediatric Annals. Using rapid diagnostic tests enables physicians to provide prompt therapy, withhold unnecessary therapy, and aptly educate the patient, family members and other members of the medical staff about the actual diagnosis, Krilov told Infectious Diseases in Children.

As use of these relatively new diagnostic tools increases, maintaining safety and quality control may make the difference between potentially delivering and actually delivering improved health care.

Influenza

Several previous studies have quantified the benefits of rapid influenza testing. Emergency department personnel treating children who had confirmed-by-rapid-testing influenza were less likely to order laboratory tests and X-rays, less likely to prescribe antibiotics and more likely to prescribe antivirals compared with physicians who were not aware of their patients’ diagnoses.

Three tests — QuickVue (Quidel), NOW Influenza A and B (Binax) and ZstatFlu (ZymeTx) — for rapid influenza diagnoses are able to detect infection within 30 minutes and are approved for use in the outpatient setting in accordance with the Clinical Laboratory Improvement Amendment (CLIA). These tests offer greater time efficiency than typical virus isolation tests, which can take between five and 10 days, and are easier to read compared with real time polymerase chain reaction assays, which require a higher degree of clinical expertise, according to Krilov. However, both sensitivity and specificity vary depending on the test used:

Median sensitivities are between 70% and 75%, but can vary between 45% and 90%.
Median specificities are between 90% and 95%, but can vary between 60% and 95%.
QuickVue has the best sensitivity (73% to 81%) and specificity (93% to 99%) out of the three tests.

Other factors such as time within the season and at what point in the illness a specimen is collected for testing can affect testing efficacy. Krilov warned that false-positive and true-negative results are more likely to occur at the beginning and end of a given season as disease prevalence is often lower at these times, and he suggested collecting specimens within the first four to five days of the illness to ensure accuracy.

Rapid influenza tests are best for making diagnoses during outbreaks and less useful to differentiate sporadic cases from other respiratory viruses, according to Krilov. He recommends tracking weekly regional influenza reports from the CDC at www.cdc.gov/flu/weekly/fluactivity.htm to determine if rapid testing is appropriate.

Group A streptococcus

Thirty-five CLIA-waived tests are available to physicians to test for group A streptococcus. “Overall, for pediatricians, I think rapid strep testing has had the greatest impact of rapid diagnostics on clinical practice. They allow prompt diagnosis and appropriate use of antibiotic therapy,” Krilov said.

Clinicians using these tests must obtain swabs from the tonsils and posterior pharynx, as they rely on group A carbohydrate antigen nitrous acid extraction. Data indicate that specificity is generally between 85% and 100%. However, the wide variability of sensitivity, ranging from 62% to 95%, requires that back-up throat cultures be performed to confirm diagnoses.

Several factors explain this range in sensitivity, including the quality of throat specimen and the experience of the clinician administering the test. Several newer tests use optical immunoassay or chemiluminescent DNA probes which may be accurate enough to use without a back-up culture, according to Krilov.

Other rapid tests

There is one CLIA-waived rapid test available to detect rapid syncytial virus in high-risk infants — Binax NOW RSV. The test produces results in about 15 minutes with sensitivities between 79% and 88% and specificities between 88% and 100%, depending on specimen quality. These tests are most effective in the communities with high RSV prevalence during the winter months, according to Krilov.

Rapid monospot tests are available to detect infectious mononucleosis. Positive responses are usually detected in 80% to 85% of older children and adolescents with the infection and less frequently in children aged 4 years and younger.

As positive antibodies can generally be detected by the second week of illness but may persist for six months or more, clinicians who suspect infectious mononucleosis in children with a negative monospot should repeat the test again one or two weeks later, according to Krilov, or obtain a specific Epstein-Barr Virus serology.

False-positive results are only a minor concern as the false-positive rate for monospot testing is less than 5%, Krilov said.

Safety tips

As clinical practices continue to use rapid tests, upholding safety should be a primary concern and ensuring that these tests are used properly can determine just how beneficial they may be.

Krilov reminded clinicians to know the indications for performing a given rapid test; be familiar with the concepts of sensitivity, specificity, and positive and negative predictive values; and maintain quality control on all tests performed in the office. – by Nicole Blazek

For more information:

Krilov L. The appropriate use of rapid diagnostic tests for infectious diseases in the outpatient setting. #F2028. Presented at: the AAP 2008 National Conference and Exhibition; Oct. 11-14, 1008; Boston.