Interlaboratory agreement of coccidioidomycosis enzyme immunoassay from two different manufacturers

Medical Mycology, 2019, 57, 441–446 doi: 10.1093/mmy/myy059 Advance Access Publication Date: 31 July 2018 Original Article Original Article Interlaboratory agreement of coccidioidomycosis enzyme immunoassay from two different manufacturers Soofia Khan1 , Michael A. Saubolle2 , Terry Oubsuntia3 , Arash Heidari4 , Kelly Barbian2 , Kate Goodin5 , Megan Eguchi5 , Orion Z. McCotter6 , Kenneth Komatsu7 , Benjamin J. Park6 , Matthew Casey Geiger4 , Ahmed Mohamed5 , Tom Chiller6 and Rebecca H. Sunenshine5,8,∗ 1 University of Arizona School of Medicine, Phoenix, Arizona, USA, 2 Laboratory Sciences of Arizona/Sonora Quest Laboratories, Banner Health, Phoenix, Arizona, USA, 3 Kern County Public Health Laboratory Services, Bakersfield, California, USA, 4 Kern Medical Center, Bakersfield, California, USA, 5 Maricopa County Department of Public Health, Phoenix, Arizona, USA, 6 Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 7 Arizona Department of Health Services, Phoenix, Arizona, USA and 8 Office of Public Health Preparedness and Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA ∗ To whom correspondence should be addressed. Rebecca H. Sunenshine, MD. Office of Public Health Preparedness and Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. Tel: +602-568-2250; Fax: +602-372-2656; E-mail: Received 5 March 2018; Revised 4 May 2018; Accepted 13 July 2018; Editorial Decision 12 June 2018 Abstract Coccidioidomycosis, a fungal infection endemic to the Southwestern United States, is challenging to diagnose. The coccidioidomycosis enzyme immunoassay (EIA) test is the least expensive and simplest to perform to detect coccidioidomycosis antibodies in the serum. Concerns regarding falsely positive immunoglobulin (Ig) M EIA test results have led to questions about the agreement of commercially available EIA test kits among laboratories. We sought to evaluate the laboratory agreement of the EIA test at three laboratories using both IMMY and Meridian EIA test kits. Sensitivity and specificity of EIA IgM and IgG were calculated as secondary outcomes. The percent agreement of the EIA IgM and IgG test results among all three laboratories was 90% and 89% for IMMY test kits, respectively, and 67% and 80.5% for Meridian test kits, respectively. Agreement between IgM and IgG combined test results was 85.5% and 70.5%, for IMMY and Meridian, respectively. Combined IgM and IgG assays demonstrated a sensitivity of 68% (62.7%–76%) and a specificity of 99.3% (98%–100%) [IMMY] and a sensitivity of 72.4% (57.3%–87.3%) and a specificity of 91.3% (74%–100%) [Meridian]. In summary, results from the IMMY EIA test kit agreed more often across laboratories than Meridian EIA results, especially for the IgM assay. Isolated positive IgM EIA results using the Meridian test kit should be interpreted with caution and consideration of clinical information and test methodology. Further study of the sensitivity and specificity of coccidioidomycosis EIA test kits is warranted. Key words: Coccidioidomycosis, laboratory, enzyme immunoassay, serology. Introduction Coccidioidomycosis, also known as Valley fever, is a fungal infection caused by Coccidioides species and is endemic to Arizona, California, Nevada, New Mexico, Utah, Texas, Washington, and parts of South and Central America.1–3 Coccidioidomycosis is transmitted primarily via the respiratory route by inhalation of airborne spores found in dust, although other transmission routes have been described.4,5 Arizona and California saw an unprecedented increase in the prevalence of reported Valley fever over the last decade during which the rate increased more than 90% and reached its peak in 2011.6,7 The majority of cases continues to be recorded in Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US. 441 442 trols without disease. The secondary objective was to determine the sensitivity and specificity of EIA IgG and IgM combined from each test kit, although the study was not powered specifically for this purpose. Methods Beginning in July 2010, serum samples from 150 patients with laboratory (positive ID tube precipitin [TP], ID IgG, or complement fixation) and clinical evidence of coccidioidomycosis (reviewed by an infectious diseases physician) were stored and frozen by the Kern County Public Health Laboratory. Serum samples were selected from California coccidioidomycosis patients whose specimens were sent for coccidioidomycosis testing at the Kern County Department of Public Health and included both acute and convalescent specimens, depending on when the patient was seen relative to diagnosis. Fifty de-identified serum specimens, presumed negative for coccidioidomycosis, from healthy people in non-endemic areas were purchased from a blood bank by the Centers for Disease Control and Prevention, Mycotic Diseases Branch, frozen, and stored. In February 2013, all 200 specimens were blinded, divided into aliquots, and distributed frozen by the Kern County Department of Public Health for testing among three laboratories: Kern County Public Health Laboratory (Lab A) and two commercial laboratories (Lab B and Lab C). Two EIA test kits from two different manufacturR Coccidioides Enzyme ers (Meridian Biosciences [PREMIER Immunoassay; Cincinnati, OH USA16 ] and IMMY [OMEGA Coccidioides Antibody Enzyme Immunoassay: Norman, OK17 ]) were used by all three laboratories to evaluate the samples for the presence of IgG and IgM as evidence of acute coccidioidomycosis infection. Both test kits are approved by the Food and Drug Administration for the detection of IgM and IgG antibodies to Coccidioides spp. in serum. All EIA test kits were performed and determined to be negative, positive or indeterminate according to the manufacturers’ guidelines in the package insert.16,17 Two laboratories (Labs A and C) did not run Meridian indeterminate results a second time, as recommended by the package insert, because of resource limitations and laboratory standard operating procedures. All test kits from each manufacturer were from the same lot and all three laboratories measured absorbance using a dual wavelength reader. Labs A and B performed the wash step described in the package insert of the Meridian EIA test kit manually, and Lab C performed the wash step using an automated process. Statistical analysis For analysis of the combined IgG and IgM test results, the test set was interpreted as negative if both IgG and IgM results produced from the same kits were below the test manufacturer’s cutoff point for negative. If either IgG or IgM from the same specimen and test kit produced positive results (above the manufacturer’s populous counties in Arizona from which approximately 60% of all national cases are reported.6,8,9 Although th (...truncated)