COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays
2020; 40(6): 439-447
Ann Lab Med 2019; 39(3): 317-321
Published online May 1, 2019 https://doi.org/10.3343/alm.2019.39.3.317
Copyright © Korean Society for Laboratory Medicine.
1Department of Laboratory Medicine, Ewha Womans University College of Medicine, Seoul, Korea; 2Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 3Department of Laboratory Medicine, Sanggye Paik Hospital, School of Medicine, Inje University, Seoul, Korea
Correspondence to: Bo-Moon Shin, M.D. https://orcid.org/0000-0001-8432-9556
Department of Laboratory Medicine, Sanggye Paik Hospital, School of Medicine, Inje University, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
In May 2015, we conducted a voluntary online survey on laboratory diagnostic assays for
Keywords: Clostridium difficile infection, Laboratory diagnosis, Toxin AB enzyme immunoassay, Nucleic acid amplification test, Culture, Survey, Korea
Rapid and accurate diagnosis of CDI is crucial for patient care, infection control, and surveillance. Various assays are currently available for diagnosing CDI, including the cell cytotoxicity neutralization assay (CCNA), toxigenic culture (TC), toxin AB enzyme immunoassay (toxin AB EIA), glutamate dehydrogenase (GDH) assay, and nucleic acid amplification tests (NAATs). Algorithmic approaches have also been developed to improve the diagnostic performance, and several guidelines for CDI diagnosis have been established [5,6,7,8]. However, this wide variation in approaches has hindered universal application of these guidelines. Moreover, there is currently no consensus for the best CDI diagnostic assay or strategy to adopt in Korea. As a first step toward standardization of CDI diagnosis in Korea, we conducted a national survey to investigate the diagnostic assays for CDI used in clinical laboratories.
In May 2015, we administered a voluntary online survey on laboratory diagnosis for CDI to health professionals in 120 clinical microbiology laboratories (https://docs.google.com/forms/u/0/). Questions covered the current assays used for CDI diagnosis, including the toxin AB EIA, NAAT,
Responses were obtained from 66 laboratories, including 61 hospitals (number of beds≥1,000, N=11; 500–1,000, N=42; 300–500, N=3; <300, N=5) and five commercial laboratories (CL). The 61 hospitals were located in 6 metropolitan cities (Seoul, N=26; Incheon, N=4; Daegu, N=4; Busan, N=3, Gwangju, N=3; Daejeon, N=1; Ulsan, N=1) and 5 provinces (Gyeonggi, N=12; Chungbuk, N=2; Gyeongnam, N=2; Jeonbuk, N=2; Jeonnam, N=1). Among them, nine laboratories reported having not conducted any CDI assay. All hospitals with ≥1,000 beds performed CDI assays, whereas 88.1% (37/42) of hospitals with 500–1,000 beds and 50.0% (4/8) of hospitals with <500 beds (including the 300–500 and <300 beds categories) performed CDI assays.
The various assay methods used in the participating laboratories are summarized in Table 1. The toxin AB EIA was the most popular assay. Among the 57 laboratories that reported performing CDI assays, 51 (89.5%) used the toxin AB EIA, either alone or in combination with other assays. NAATs and
Table 3 shows the median (range) of examined specimens in one month for the toxin AB EIA, NAATs, and
Toxin AB EIA is more frequently used possibly because of its advantages of short turnaround time and cost-efficiency. However, this assay is often criticized for its poor sensitivity and should therefore no longer be considered as a stand-alone assay for the diagnosis of CDI [1,2,6,7,9,10,11,12]. Therefore, the nine (15.8%) laboratories that use only the toxin AB EIA for CDI diagnosis should reconsider their diagnostic strategy.
Since the clinical guidelines for CDI provided by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) were updated in 2010 , many hospitals in the United States have switched the toxin AB EIA to NAATs for CDI diagnosis. Wong et al.  reported that 84.5% of the hospitals surveyed in Ohio, USA, used NAATs as a stand-alone assay in 2014. However, the proportion of laboratories using NAATs as a stand-alone assay was lower in other countries: only 3% and 6% of small (<500 beds) and large (>500 beds) hospitals in Italy in 2012–2013, respectively , 0.9% of participating laboratories in Spain in 2013 , and 11.1% (2/18) of hospitals in Israel in 2012 . In general, NAATs are more commonly used in combination with other assays, as observed in 16% and 34% of small and large hospitals in Italy in 2012–2013, respectively , 38.2% of participating laboratories in Spain in 2013 , and 38.9% (7/18) of hospitals in Israel in 2012 . In our study, 36 of 57 (63.2%) of the laboratories conducting CDI assays also used NAATs in combination with other assays, except for one laboratory (1.8%) that reported using NAATs as a stand-alone assay.
Approximately 60% (34/57) of the laboratories reported performing
The GDH assay was only recently introduced in the last five years and approved for reimbursement in Korea since 2016. Thus, this assay was not popular at the time of conducting the survey, with only one laboratory reporting its use in combination with the toxin AB EIA. GDH has been reported as a sensitive marker for the detection of
The recently updated clinical guidelines for CDI by IDSA and SHEA recommend using a stool toxin assay as part of a multistep algorithm (i.e., GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than an NAAT alone for all specimens received in the clinical laboratory when there are no pre-agreed institutional criteria for patient stool submission. When there are pre-agreed institutional criteria for patient stool submission, it is recommended to use an NAAT alone or a multistep algorithm for testing . The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) strongly recommends using a two-step algorithm instead of a single assay as a stand-alone assay. The algorithm should start with either the NAAT or GDH assay, and specimens with a positive first assay result should be tested further with the toxin AB EIA. An alternative algorithm is to screen specimens with both the GDH assay and toxin AB EIA .
Although approximately 80% of the laboratories in our study used more than one assay, we did not enquire about the sequences and/or detailed processes used for multiple assays. The diagnostic algorithms applied in Korean hospitals or laboratories are currently not clear; thus, further investigation is necessary to clarify this aspect.
In a survey conducted in Europe in 2014, 24 of the 35 responding countries reported one or more changes in the national/subnational laboratory diagnostics for CDI since 2011 . The main changes included the availability of commercial diagnostic assays, new or revised guidelines for CDI diagnostics, relevant legislation, and reimbursement policies for diagnostic assays. The main barriers to applying appropriate assays according to the guidelines were financial restrictions, along with insufficient reimbursement and trained staff . Although this was not explicitly explored in our survey, a similar situation is expected to be occurring in Korea.
There were several limitations in this study. The number and area of participating laboratories were restricted. As mentioned above, the sequences and/or detailed processes used for multiple assays were not investigated, which are the important issues that need to be addressed in order to develop multistep algorithmic approaches for diagnosis of CDI in Korea.
Despite these limitations, this study represents the first survey on the laboratory diagnosis for CDI conducted in Korea. We found considerable variation in the assays used for CDI diagnosis among laboratories in Korea, and some laboratories were still using inappropriate methods such as the toxin AB EIA as a stand-alone assay. NAATs were more rapidly introduced than expected, utilized in approximately 65% of participating laboratories. These findings suggest the need for establishing optimized guidelines for CDI diagnosis in Korea. Thus, our study can provide valuable basic data on the current situation, as a first step towards standardizing laboratory diagnosis of CDI in Korea.