Diagnostic Accuracy of the InBios Scrub Typhus Detect™ ELISA for the Detection of IgM Antibodies in Chittagong, Bangladesh

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.

[1]  R. Maude,et al.  Rickettsial Illnesses as Important Causes of Febrile Illness in Chittagong, Bangladesh , 2018, Emerging infectious diseases.

[2]  D. Mathai,et al.  Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy , 2017, BMC Infectious Diseases.

[3]  S. Dittrich,et al.  Endemic Scrub Typhus in South America. , 2016, The New England journal of medicine.

[4]  J. Dumler,et al.  State of the art of diagnosis of rickettsial diseases: the use of blood specimens for diagnosis of scrub typhus, spotted fever group rickettsiosis, and murine typhus , 2016, Current opinion in infectious diseases.

[5]  R. Chaudhry,et al.  Determination of Cutoff of ELISA and Immunofluorescence Assay for Scrub Typhus , 2016, Journal of global infectious diseases.

[6]  Derek J. Smith,et al.  Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand , 2016, PLoS neglected tropical diseases.

[7]  N. Day,et al.  Diagnostic Accuracy of the InBios Scrub Typhus Detect Enzyme-Linked Immunoassay for the Detection of IgM Antibodies in Northern Thailand , 2015, Clinical and Vaccine Immunology.

[8]  N. Day,et al.  Optimal Cutoff Titers for Indirect Immunofluorescence Assay for Diagnosis of Scrub Typhus , 2015, Journal of Clinical Microbiology.

[9]  N. Day,et al.  Comparative Accuracy of the InBios Scrub Typhus Detect IgM Rapid Test for the Detection of IgM Antibodies by Using Conventional Serology , 2015, Clinical and Vaccine Immunology.

[10]  P. Newton,et al.  A Systematic Review of Mortality from Untreated Scrub Typhus (Orientia tsutsugamushi) , 2015, PLoS neglected tropical diseases.

[11]  M. Varma,et al.  Diagnostic validation of selected serological tests for detecting scrub typhus , 2015, Microbiology and immunology.

[12]  B. Cooper,et al.  How to Determine the Accuracy of an Alternative Diagnostic Test when It Is Actually Better than the Reference Tests: A Re-Evaluation of Diagnostic Tests for Scrub Typhus Using Bayesian LCMs , 2015, PloS one.

[13]  P. Newton,et al.  Rickettsia felis Infections and Comorbid Conditions, Laos, 2003-2011 , 2014, Emerging infectious diseases.

[14]  X. de Lamballerie,et al.  Causes of non-malarial fever in Laos: a prospective study , 2013, The Lancet. Global health.

[15]  N. Day,et al.  Diagnostic Accuracy of a Loop-Mediated Isothermal PCR Assay for Detection of Orientia tsutsugamushi during Acute Scrub Typhus Infection , 2011, PLoS neglected tropical diseases.

[16]  N. Day,et al.  Isolation of a Novel Orientia Species (O. chuto sp. nov.) from a Patient Infected in Dubai , 2010, Journal of Clinical Microbiology.

[17]  P. Newton,et al.  Diagnosis of Scrub Typhus , 2010, The American journal of tropical medicine and hygiene.

[18]  N. Day,et al.  Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: a lack of consensus leads to a lot of confusion. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  J. Sattabongkot,et al.  Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand. , 2002, The American journal of tropical medicine and hygiene.