Diagnostic accuracy of a loop-mediated isothermal PCR assay for detection of Orientia tsutsugamushi during acute scrub typhus infection

Background: there is an urgent need to develop rapid and accurate point-of-care (poc) technologies for acute scrub typhus diagnosis in low-resource,primary health care settings to guide clinical therapy. methodology/principal findings: in this study we present the clinical evaluation of loop-mediated isothermal pcr assay (lamp) in the context of a prospective fever study,including 161 patients from scrub typhus-endemic chiang rai,northern thailand. a robust reference comparator set comprising following 'scrub typhus infection criteria' (stic) was used: a) positive cell culture isolate and/or b) an admission igm titer ≥1:12,800 using the 'gold standard' indirect immunofluorescence assay (ifa) and/or c) a 4-fold rising ifa igm titer and/or d) a positive result in at least two out of three pcr assays. compared to the stic criteria,all pcr assays (including lamp) demonstrated high specificity ranging from 96-99%,with sensitivities varying from 40% to 56%,similar to the antibody based rapid test,which had a sensitivity of 47% and a specificity of 95%. conclusions/significance: the diagnostic accuracy of the lamp assay was similar to realtime and nested conventional pcr assays,but superior to the antibody-based rapid test in the early disease course. the combination of dna- and antibody-based detection methods increased sensitivity with minimal reduction of specificity,and expanded the timeframe of adequate diagnostic coverage throughout the acute phase of scrub typhus. © 2011 paris et al.