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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Autores principales:	Xianghong Liu, Ye Zhang, Jun Zhang, Zheng Lou, Han Xia, Zhijuan Lu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	scrub typhus Orientia tsutsugamushi early diagnosis metagenomic next-generation sequencing eschars Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/f107507d17c142d6a7ee65a549c1cd1b
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spelling	oai:doaj.org-article:f107507d17c142d6a7ee65a549c1cd1b2021-11-11T07:38:29ZThe Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing2296-256510.3389/fpubh.2021.755228https://doaj.org/article/f107507d17c142d6a7ee65a549c1cd1b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fpubh.2021.755228/fullhttps://doaj.org/toc/2296-2565Introduction: 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.Xianghong LiuYe ZhangJun ZhangZheng LouHan XiaZhijuan LuFrontiers Media S.A.articlescrub typhusOrientia tsutsugamushiearly diagnosismetagenomic next-generation sequencingescharsPublic aspects of medicineRA1-1270ENFrontiers in Public Health, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	scrub typhus Orientia tsutsugamushi early diagnosis metagenomic next-generation sequencing eschars Public aspects of medicine RA1-1270
spellingShingle	scrub typhus Orientia tsutsugamushi early diagnosis metagenomic next-generation sequencing eschars Public aspects of medicine RA1-1270 Xianghong Liu Ye Zhang Jun Zhang Zheng Lou Han Xia Zhijuan Lu The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing
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.
format	article
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
title	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_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_sort	early diagnosis of scrub typhus by metagenomic next-generation sequencing
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f107507d17c142d6a7ee65a549c1cd1b
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The Early Diagnosis of Scrub Typhus by Metagenomic Next-Generation Sequencing

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