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Diagnosis by serology of some Cryptococcus gattii infections fails due to low sensitivity

August 22 2016

Latex agglutination tests (LATs) using monoclonal antibodies (mAbs) such as the PastorexTM Crypto plus or the Remel Cryptococcus Antigen Test Kit have insufficient sensitivity to detect 4 out of 10 Cryptococcus gattii infections. Since the distribution of C. gattii is spreading to geographical zones outside of tropical/subtropical areas, Kathrin Tintelnot and colleagues from the Division of Mycology at the Robert Koch Institute, Berlin, recommend the use of an assay with a broad range specificity and sensitivity for C. neoformans and C. gattii in the case of a suspected Cryptococcus infection.

Nine humans and 1 cat diagnosed with C. gattii infection between 1985 and 2014 were used in this study.  Using serum and CSF, antigen detection was performed, using the LATs of IMMY Latex-Crypto test (Immuno-Mycologics, Norman, OK, USA) and Pastorex TM Crypto Plus (BioRad, Marnes-la-Coquette, France). Where both serum and CSF was available the Remel Cryptococcus Antigen Test Kit (Remel, Lenexa, KS, USA) was also used. The dipstick sandwich immunochromatographic assay Cryptococcus Antigen Lateral Flow Assay (CrAg LFA; Immuno-Mycologics) was also used in every sample.

Six out of  10 patients with a proven C. gattii infection had detectable cryptococcal antigens. The Immy assays detected antigens in 4 out of the 10 samples, while no antigens were detected using the LATs by Bio-Rad and Remel. Though the number of patients was limited, the results demonstrated that the detection of CSA (cryptococcal serum antigen) was highly dependent upon the design of the serological test. The Bio-Rad and Remel tests are based on monoclonal Abs, while the IMMY tests are based on the polyclonal antibodies. CSA was not detected with the Pastorex TM­ Crypto Plus test for one isolate because it was not sensitive enough, this was identified as a hybrid species between C. gattii and C. neoformans var. grubii. Originally it had been identified as C. neoformans, since the patient had not travelled outside of Europe, but this case highlights the increasing numbers of endemic zones for C. gattii.

The Bio-Rad and Remel test kits are frequently used in routine laboratories, especially in Europe, which may lead to under-diagnosis and delayed diagnosis of C. gattii, especially in non-endemic areas. If cryptococcosis is suspected, serological screening for cryptococcal antigen should be performed using a test not only able to detect C. neoformans, but one that includes a broader range of specificity and sensitivity for C. gattii and interspecies hybrids. 

Latex Agglutination test for the detection of Cryptococcus

Article in Medical Mycology