![[ Visit Client Website ]](images/banner.jpg)
BACKGROUND: Cryptosporidium is a common cause of sporadic diarrheal disease and outbreaks in the United States. Increasingly, diagnosis using point-of-care immunochromatography-based rapid cartridge assays (RCAs) is providing clinical laboratories with a rapid cryptosporidiosis diagnostic method. The primary commercial RCAs are ImmunoCard STAT! Crypto/Giardia by Meridian Bioscience and Xpect Cryptosporidiumby Remel. A recent report suggested that a large number of false positives were obtained from these RCAs based on public health laboratory retesting of positive samples from clinical laboratories with the gold standard method (i.e., direct fluorescent antibody testing (DFA). Based on these results, CSTE changed the case definition for national notification of cryptosporidiosis cases to exclude RCA-positive samples from being classified as confirmed cases.
METHODS: CDC, APHL, and four state health departments compared RCA-positive samples obtained during routine clinical laboratory Cryptosporidiumtesting. All samples underwent “head to head” re-testing using both RCA and DFA. Log binomial regression was used to identify specimen attributes associated with false positive results from clinical laboratories while accounting for within-laboratory correlation.
RESULTS: Overall, 61.7% of clinical laboratory positive samples were confirmed by DFA at state laboratories. The percentage of RCA-positive samples from clinical laboratories confirmed by DFA varied by manufacturer: 55.0% (171/311) of the Meridian Bioscience RCA positives and 87.0% (67/77) of the Remel RCA positives. The difference in proportion confirmed by DFA differed by age, ranging from 86.4% in persons <20 years of age to 12.5% in persons >60 years of age. In univariable analysis, reporting state and age were significant predictors of false positive results; preservative type approached significance. After adjusting for all other attributes, age and preservative type were the only significant predictors of false-positive results. When RCA testing was repeated at the state laboratory, 86.6% of RCA positives were confirmed by DFA.
CONCLUSIONS: This study documented a high rate of false positive results from RCAs used in clinical laboratories to test for Cryptosporidium, though rates varied by manufacturer. Nearly half of positive results from clinical laboratories could not be confirmed by DFA at the state public health laboratories. Retesting of these samples by RCAs at state public health laboratories revealed better agreement between RCAs and DFA, although an age effect was still observed. Problems with the test device itself or with specimen handling, storage, or testing in clinical laboratories could account for the poor performance of RCAs. The high false-positive rate presents serious problems for understanding the epidemiology of Cryptosporidium in the United States.