Diagnostic accuracy of a loop-mediated isothermal PCR assay for detection of Orientia tsutsugamushi during acute Scrub Typhus infection.

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.In this study we present the clinical evaluation of loop-mediated isothermal PCR assay (LAMP) in the context...

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Bibliographic Details
Published in:PLoS Neglected Tropical Diseases
Main Authors: Daniel H Paris, Stuart D Blacksell, Pruksa Nawtaisong, Kemajittra Jenjaroen, Achara Teeraratkul, Wirongrong Chierakul, Vanaporn Wuthiekanun, Pacharee Kantipong, Nicholas P J Day
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2011
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Arctic
Chiang
Online Access:https://doi.org/10.1371/journal.pntd.0001307
https://doaj.org/article/8563e15426c24c17ad57d42872d1739e
Description
Summary: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.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%.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.

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