The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing

Introduction: Scrub typhus is a mite-borne infection widespread in Southeast Asia, with clinical symptoms such as fever, chills, skin rash, eschar at the bite site, and other signs of acute febrile illness. The Rickettsia pathogen (Orientia tsutsugamushi) is always difficult to be diagnosed at an ea...

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Main Authors: Xianghong Liu, Ye Zhang, Jun Zhang, Zheng Lou, Han Xia, Zhijuan Lu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2021.755228/full
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author Xianghong Liu
Ye Zhang
Jun Zhang
Zheng Lou
Han Xia
Zhijuan Lu
author_facet Xianghong Liu
Ye Zhang
Jun Zhang
Zheng Lou
Han Xia
Zhijuan Lu
author_sort Xianghong Liu
collection DOAJ
description Introduction: Scrub typhus is a mite-borne infection widespread in Southeast Asia, with clinical symptoms such as fever, chills, skin rash, eschar at the bite site, and other signs of acute febrile illness. The Rickettsia pathogen (Orientia tsutsugamushi) is always difficult to be diagnosed at an early stage by traditional clinical diagnostic methods, especially for patients without typical eschar. This greatly increases the mortality of patients with scrub typhus. A new approach should be introduced to improve its clinical diagnosis.Methods: During May 2018 to March 2021, 13 samples from 10 patients with suspected scrub typhus were collected. Metagenomic next-generation sequencing (mNGS) and other diagnostic methods (including serology using Weil–Felix reaction and indirect immunofluorescence test (IIFT) for scrub typhus and respiratory tract profile IgM as well as culture for routine bacteria) were used to identify the pathogens in this study.Results: The results of mNGS were all positive, with mapped reads of O. tsutsugamushi ranging from 1 to 460. Eight patients (80%) were diagnosed as scrub typhus. The other two were diagnosed as suspected scrub typhus due to the limited number of reads of the pathogen (one and two, respectively). According to clinical evidences, nine of the 10 patients were finally diagnosed as scrub typhus, except for patient 9 (suspected scrub typhus by mNGS with one specific reads of the pathogen) diagnosed as acute exacerbation of chronic obstructive pulmonary disease. For the five scrub typhus patients without typical eschar, mNGS gave all positive results (4–460 specific reads). For other methods, only Weil–Felix reaction of one patient detected the pathogen. In addition, the respiratory tract profile (IgM) detected various pathogens, but all were confirmed to be false positive.Conclusions: mNGS performed better than conventional clinical methods to early diagnose scrub typhus. This approach can be routinely carried out for early and precise diagnosis in clinical infections, especially for those hard to be identified by traditional diagnostic methods.
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spelling doaj.art-f107507d17c142d6a7ee65a549c1cd1b2022-12-21T19:54:56ZengFrontiers Media S.A.Frontiers in Public Health2296-25652021-11-01910.3389/fpubh.2021.755228755228The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation SequencingXianghong Liu0Ye Zhang1Jun Zhang2Zheng Lou3Han Xia4Zhijuan Lu5Department of Neurology, Ganzhou People's Hospital, Ganzhou, ChinaDepartment of Scientific Affairs, Hugobiotech Co., Ltd., Beijing, ChinaEmergency Department, Ganzhou People's Hospital, Ganzhou, ChinaDepartment of Scientific Affairs, Hugobiotech Co., Ltd., Beijing, ChinaDepartment of Scientific Affairs, Hugobiotech Co., Ltd., Beijing, ChinaDepartment of Neurology, Ganzhou People's Hospital, Ganzhou, ChinaIntroduction: Scrub typhus is a mite-borne infection widespread in Southeast Asia, with clinical symptoms such as fever, chills, skin rash, eschar at the bite site, and other signs of acute febrile illness. The Rickettsia pathogen (Orientia tsutsugamushi) is always difficult to be diagnosed at an early stage by traditional clinical diagnostic methods, especially for patients without typical eschar. This greatly increases the mortality of patients with scrub typhus. A new approach should be introduced to improve its clinical diagnosis.Methods: During May 2018 to March 2021, 13 samples from 10 patients with suspected scrub typhus were collected. Metagenomic next-generation sequencing (mNGS) and other diagnostic methods (including serology using Weil–Felix reaction and indirect immunofluorescence test (IIFT) for scrub typhus and respiratory tract profile IgM as well as culture for routine bacteria) were used to identify the pathogens in this study.Results: The results of mNGS were all positive, with mapped reads of O. tsutsugamushi ranging from 1 to 460. Eight patients (80%) were diagnosed as scrub typhus. The other two were diagnosed as suspected scrub typhus due to the limited number of reads of the pathogen (one and two, respectively). According to clinical evidences, nine of the 10 patients were finally diagnosed as scrub typhus, except for patient 9 (suspected scrub typhus by mNGS with one specific reads of the pathogen) diagnosed as acute exacerbation of chronic obstructive pulmonary disease. For the five scrub typhus patients without typical eschar, mNGS gave all positive results (4–460 specific reads). For other methods, only Weil–Felix reaction of one patient detected the pathogen. In addition, the respiratory tract profile (IgM) detected various pathogens, but all were confirmed to be false positive.Conclusions: mNGS performed better than conventional clinical methods to early diagnose scrub typhus. This approach can be routinely carried out for early and precise diagnosis in clinical infections, especially for those hard to be identified by traditional diagnostic methods.https://www.frontiersin.org/articles/10.3389/fpubh.2021.755228/fullscrub typhusOrientia tsutsugamushiearly diagnosismetagenomic next-generation sequencingeschars
spellingShingle Xianghong Liu
Ye Zhang
Jun Zhang
Zheng Lou
Han Xia
Zhijuan Lu
The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
Frontiers in Public Health
scrub typhus
Orientia tsutsugamushi
early diagnosis
metagenomic next-generation sequencing
eschars
title The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
title_full The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
title_fullStr The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
title_full_unstemmed The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
title_short The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
title_sort early diagnosis of scrub typhus by metagenomic next generation sequencing
topic scrub typhus
Orientia tsutsugamushi
early diagnosis
metagenomic next-generation sequencing
eschars
url https://www.frontiersin.org/articles/10.3389/fpubh.2021.755228/full
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