Abstract
Here we estimated the accuracy of the InBios Scrub Typhus Detect™ immunoglobulin M (IgM) ELISA to determine the optimal optical density (OD) cut-off values for the diagnosis of scrub typhus. Patients with undifferentiated febrile illness from Chittagong, Bangladesh, provided samples for reference testing using (i) qPCR using the Orientia spp. 47-kDa htra gene, (ii) IFA ≥1:3200 on admission, (iii) immunofluorescence assay (IFA) ≥1:3200 on admission or 4-fold rise to ≥3200, and (iv) combination of PCR and IFA positivity. For sero-epidemiological purposes (ELISA vs. IFA ≥1:3200 on admission or 4-fold rise to ≥3200), the OD cut-off for admission samples was ≥1.25, resulting in a sensitivity (Sn) of 91.5 (95% confidence interval (95% CI: 96.8–82.5) and a specificity (Sp) of 92.4 (95% CI: 95.0–89.0), while for convalescent samples the OD cut-off was ≥1.50 with Sn of 66.0 (95% CI: 78.5–51.7) and Sp of 96.0 (95% CI: 98.3–92.3). Comparisons against comparator reference tests (ELISA vs. all tests including PCR) indicated the most appropriate cut-off OD to be within the range of 0.75–1.25. For admission samples, the best Sn/Sp compromise was at 1.25 OD (Sn 91.5%, Sp 92.4%) and for convalescent samples at 0.75 OD (Sn 69.8%, Sp 89.5%). A relatively high (stringent) diagnostic cut-off value provides increased diagnostic accuracy with high sensitivity and specificity in the majority of cases, while lowering the cut-off runs the risk of false positivity. This study underlines the need for regional assessment of new diagnostic tests according to the level of endemicity of the disease given the high levels of residual or cross-reacting antibodies in the general population.
Highlights
Scrub typhus, caused by Orientia tsutsugamushi, remains a significant acute febrile illness in most of Asia and northern Australasia, recent studies indicate that its geographical range is expanding [1,2]
This study evaluated the commercial InBios Scrub Typhus DetectTM immunoglobulin M (IgM) ELISA using a mixture of recombinant p56 kDa type-specific-antigens for the detection of O. tsutsugamushi IgM antibodies, to determine (a) its relationship to the current gold standard serological assay immunofluorescence assay (IFA), and (b) suitable diagnostic positivity cut-off levels for acute diagnostic and (c) for sero-epidemiology purposes based on a single serum admission sample at the scrub typhus-endemic locality of Chittagong, Bangladesh
We estimated the accuracy of the InBios Scrub Typhus DetectTM IgM ELISA
Summary
Scrub typhus, caused by Orientia tsutsugamushi, remains a significant acute febrile illness in most of Asia and northern Australasia, recent studies indicate that its geographical range is expanding [1,2]. The delayed treatment of patients with febrile illnesses may result in complications leading to death [3]. The most accurate diagnosis relies on the combination of a method to detect the infectious agent such as a polymerase chain reaction (PCR) test, coupled with well-validated serological techniques [4]. PCR is generally considered to be the most reliable diagnostic test upon admission; it requires significant levels of infrastructure and costly reagents, and despite improving the lower limits of detection, a positive result is only likely during the rickettsaemic phase of the infection [5]. Combining PCR with antibody-based techniques may improve the possibility of detection
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