Abstract
BackgroundThe indirect immunofluorescence assay (IFA) is considered a reference test for scrub typhus. Recently, the Scrub Typhus Infection Criteria (STIC; a combination of culture, PCR assays and IFA IgM) were proposed as a reference standard for evaluating alternative diagnostic tests. Here, we use Bayesian latent class models (LCMs) to estimate the true accuracy of each diagnostic test, and of STIC, for diagnosing scrub typhus.Methods/Principal FindingsData from 161 patients with undifferentiated fever were re-evaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar, and tested with blood culture for Orientia tsutsugamushi, three different PCR assays, IFA IgM, and the Panbio IgM immunochromatographic test (ICT). True sensitivity and specificity of culture (24.4% and 100%), 56kDa PCR assay (56.8% and 98.4%), 47kDa PCR assay (63.2% and 96.1%), groEL PCR assay (71.4% and 93.0%), IFA IgM (70.0% and 83.8%), PanBio IgM ICT (72.8% and 96.8%), presence of eschar (42.7% and 98.9%) and STIC (90.5% and 82.5%) estimated by Bayesian LCM were considerably different from those obtained when using STIC as a reference standard. The IgM ICT had comparable sensitivity and significantly higher specificity compared to IFA (p=0.34 and p<0.001, respectively).ConclusionsThe low specificity of STIC was caused by the low specificity of IFA IgM. Neither STIC nor IFA IgM can be used as reference standards against which to evaluate alternative diagnostic tests. Further evaluation of new diagnostic tests should be done with a carefully selected set of diagnostic tests and appropriate statistical models.
Highlights
Scrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is endemic in South, East and Southeast Asia, as well as some areas in northern Australia [1,2]
Neither Scrub Typhus Infection Criteria (STIC) nor immunofluorescence assay (IFA) IgM can be used as reference standards against which to evaluate alternative diagnostic tests
We recently proposed the Scrub Typhus Infection Criteria (STIC), a combination of culture, polymerase chain reaction (PCR) assays, and IFA IgM, as a reference standard for scrub typhus diagnosis [17,18]
Summary
A bacterial infection caused by Orientia tsutsugamushi, is endemic in South, East and Southeast Asia, as well as some areas in northern Australia [1,2]. Patients with scrub typhus often come to hospital with undifferentiated fever and symptoms that are similar to other endemic infections such as leptospirosis, malaria and dengue. An eschar is not observed in every scrub typhus patient, and similar lesions can be observed in patients with other diseases such as spider bites, spotted fever group rickettsioses, and cutaneous lesions caused by tuberculosis, leishmaniasis and anthrax [6,7]. The indirect immunofluorescence assay (IFA) is considered a reference test for scrub typhus. The Scrub Typhus Infection Criteria (STIC; a combination of culture, PCR assays and IFA IgM) were proposed as a reference standard for evaluating alternative diagnostic tests. We use Bayesian latent class models (LCMs) to estimate the true accuracy of each diagnostic test, and of STIC, for diagnosing scrub typhus
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