Scrub typhus is an acute undifferentiated febrile infectious disease transmitted by a chigger(genus Leptotrombidium)bite carrying Orientia(O.)tsutsugamushi,affecting millions of people annually while more than one bil...Scrub typhus is an acute undifferentiated febrile infectious disease transmitted by a chigger(genus Leptotrombidium)bite carrying Orientia(O.)tsutsugamushi,affecting millions of people annually while more than one billion people are susceptible.Endemic areas are expanding to Africa,Europe,Middle East,and South America which is concerning,as despite best efforts,there is no vaccine to combat the bacteria.There are now three species of Orientia and over 20 strains of O.tsutsugamushi.The past attempts to develop a vaccine have been ineffective as they confer homologous strain-specific immunity.Various immunogenic proteins of O.tsutsugamushi have been identified that interact with the extracellular matrix(fibronectin)or vMLL5 receptor and modify the cytoskeleton of non-phagocytic host cells,which aids in host cell adhesion and invasion.These highly conserved proteins involve type specific antigen 56(TSA56),47 kDa,OmpA,and autotransporter proteins(ScaA,ScaB and ScaC).TSA56 is the most immunogenic and contains four types of hypervariable regions.Out of all autotransporter proteins,ScaA provides the homologous strains specific immunity and when coupled with TSA56 it shows better protective immunity against heterologous strains.The review provides detailed insight into the potential immunogenic proteins of Orientia which can be utilized to develop the vaccine.Furthermore,studies focused on highly antigenic proteins will provide more insight into their roles in developing therapeutics and easy-to-handle rapid diagnostic kits.展开更多
Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types...Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.展开更多
Objective:To evaluate the detection of IgM and IgG antibodies to Orientia tsutsugamushi(O. tsutsugamushi) by rapid diagnostic test(RDT) and microimmunofluorescence assay(ml FA). Methods:RDT using a mixture of recombin...Objective:To evaluate the detection of IgM and IgG antibodies to Orientia tsutsugamushi(O. tsutsugamushi) by rapid diagnostic test(RDT) and microimmunofluorescence assay(ml FA). Methods:RDT using a mixture of recombinant 56-kDa proteins of O.tsutsugamushi and mIFA assay were performed on 20 patients from Fujian and 13 patients from Yunnan Province,and 82 sera samples from healthy farmers in Anhui Province and Beijing City in 2009.Comparison of the RDT and mIFA assay was performed by using X test and the P level of 【0.05 was considered to be significance.Results:Among these 82 normal sera samples,the specificity of RDT was 100%for both IgM and IgG tests.In 33 samples from patients with scrub typhus,5 cases were positively detected earlier by RDT than by mIFA in IgM test,and 2 cases were positive in IgG test.Sensitivities of RDT were 93.9%and 90.9%for IgM and IgG,respectively.The sensitivity of combination lest of IgM and IgG was 100%.Geometric mean titer diluted sera from confirmed cases by IFA and RDT assay were 1:37 vs.1:113(P【0.001) in IgM test and 1:99 vs.1:279 (P【0.05) in IgG test.Conclusions:RDT is more sensitivite than mIFA in the early diagnosis of scrub typhus and it is particularly applicable in rural areas.展开更多
Objective:To predict B cell and T cell epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins.Methods:The sequences of 22-kDa,47-kDa,56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyze...Objective:To predict B cell and T cell epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins.Methods:The sequences of 22-kDa,47-kDa,56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA,DNAstar,Bcepred,ABCpred,NetMHC,NetMHCⅡand IEDB.The 58-kDa tertiary structure model was built by MODELLER9.17.Results:The 22-kDa B-cell epitopes were located at positions 194-200,20-26 and 143-154,whereas the T-cell epitopes were located at positions 154-174,95-107,17-25 and 57-65.The 47-kD a protein B-cell epitopes were at positions 413-434,150-161 and 283-322,whereas the T-cell epitopes were located at positions 129-147,259-267,412-420 and 80-88.The 56-kDa protein B-cell epitopes were at positions 167-173,410-419 and 101-108,whereas the T-cell epitopes were located at positions 88-104,429-439,232-240 and 194-202.The 58-kDa protein B-cell epitopes were at positions 312-317,540-548 and 35-55,whereas the T-cell epitopes were located at positions 415-434,66-84 and 214-230.Conclusions:We identified candidate epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins from Orientia tsutsugamushi.In the case of 58-kDa,the dominant antigen is displayed on tertiary structure by homology modeling.Our findings will help target additional recombinant antigens with strong specificity,high sensitivity,and stable expression and will aid in their isolation and purification.展开更多
What is already known about this topic?Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi that is transmitted primarily through the bite of infected chigger mite larvae.The disease prevalence...What is already known about this topic?Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi that is transmitted primarily through the bite of infected chigger mite larvae.The disease prevalence is closely associated with environments characterized by high moisture levels and abundant vegetation.What is added by this report?This study documents the first confirmed case of scrub typhus in Ningxia Hui Autonomous Region,China.The patient presented with characteristic clinical manifestations,including abnormal biochemical indicators and positive serum-specific IgM antibodies against scrub typhus.Epidemiological evidence suggests local acquisition of the disease.What are the implications for public health practice?Enhanced surveillance and preventive measures for scrub typhus are essential in this region,particularly for individuals residing in or visiting areas where the disease may be endemic.展开更多
Background Scrub typhus,an acute febrile disease caused by Orientia tsutsugamushi,is transmitted to humans through infected chigger mites.We present a case of scrub typhus in a previously healthy man from Shandong Pro...Background Scrub typhus,an acute febrile disease caused by Orientia tsutsugamushi,is transmitted to humans through infected chigger mites.We present a case of scrub typhus in a previously healthy man from Shandong Province diagnosed using next-generation sequencing(NGS)and PCR and review recent literature on NGS for scrub typhus diagnosis.Methods NGS was utilized for testing whole blood collected on admission.Confirmatory testing was done by detecting IgM and IgG antibodies to Orientia in acute and convalescent sera by ELISA.Orientia 47-kDa protein gene TaqMan and standard PCR of the 56-kDa protein gene and Sanger sequencing were performed on eschar scab DNA.Results The NGS diagnosis was confirmed by 47-kDa protein gene TaqMan and sequencing of a fragment of the O.tsutsugamushi 56-kDa protein gene from the eschar scab.Analysis of this sequence and the NGS data indicated O.tsutsugamushi strain Cheeloo2020 is a novel genotype.Mapping of the NGS data against the O.tsutsugamushi Gilliam strain genome sequence identified 304 reads with high similarity.Conclusions NGS is not only useful for multiplex diagnosis of scrub typhus,but also provides insight into the genetic diversity of O.tsutsugamushi.The common failure to submit sequences to databases makes it difficult to determine the minimal quantity and quality of NGS data being used for the positive identification of Orientia DNA in clinical specimens.展开更多
OBJECTIVE: To identify genotype of eight strains of Orientia tsutsugamushi (O. tsutsugamushi) isolated from Nan Peng Lie Islands in China and establish tsutsugamushi disease nature foci for this region. METHODS: The n...OBJECTIVE: To identify genotype of eight strains of Orientia tsutsugamushi (O. tsutsugamushi) isolated from Nan Peng Lie Islands in China and establish tsutsugamushi disease nature foci for this region. METHODS: The nested polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used. Three primers were selected from the DNA sequence of the gene encoding type-specific 56-kDa protein of the Karp strain. The positive products were digested by Hine II and Pst I, meanwhile profiles specific to each strain were analyzed. RESULTS: Three genotypes of O. tsutsugamushi including Karp, Kato and a new strain existed on Nan Peng Lie Islands. CONCLUSION: Nan Peng Lie Islands is tsutsugamushi disease nature foci.展开更多
BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a ...BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.展开更多
Rationale:Longitudinally extensive transverse myelitis(LETM)is a rare inflammatory demyelinating disease predominantly associated with autoimmune and inflammatory disorders.Scrub typhus can cause a variety of neurolog...Rationale:Longitudinally extensive transverse myelitis(LETM)is a rare inflammatory demyelinating disease predominantly associated with autoimmune and inflammatory disorders.Scrub typhus can cause a variety of neurological complications,which may result in poor recovery and long-term disability.This report reveals a rare linkage between LETM and scrub typhus.Patient concerns:A 24-year-old female presented with a history of fever for 10 days associated with progressive quadriparesis.Physical examination revealed bilateral lower limb weakness(grade 0/5)and bilateral upper limb weakness(grade 2/5)with reduced sensation below the T3 dermatome.Diagnosis:Scrub typhus presenting with longitudinally extensive transverse myelitis.Interventions:Steroid pulse therapy with antibiotics supported by early intensive rehabilitation.Outcomes:Complete recovery was achieved.Lessons:This case report highlights the importance of considering scrub typhus as a potential cause of LETM in endemic regions,particularly in patients presenting with febrile illness and neurological symptoms.展开更多
基金funded by Department of Health Research,Government of India,New Delhi,India(grant number:YSS/2020/000116/PRCYSS).
文摘Scrub typhus is an acute undifferentiated febrile infectious disease transmitted by a chigger(genus Leptotrombidium)bite carrying Orientia(O.)tsutsugamushi,affecting millions of people annually while more than one billion people are susceptible.Endemic areas are expanding to Africa,Europe,Middle East,and South America which is concerning,as despite best efforts,there is no vaccine to combat the bacteria.There are now three species of Orientia and over 20 strains of O.tsutsugamushi.The past attempts to develop a vaccine have been ineffective as they confer homologous strain-specific immunity.Various immunogenic proteins of O.tsutsugamushi have been identified that interact with the extracellular matrix(fibronectin)or vMLL5 receptor and modify the cytoskeleton of non-phagocytic host cells,which aids in host cell adhesion and invasion.These highly conserved proteins involve type specific antigen 56(TSA56),47 kDa,OmpA,and autotransporter proteins(ScaA,ScaB and ScaC).TSA56 is the most immunogenic and contains four types of hypervariable regions.Out of all autotransporter proteins,ScaA provides the homologous strains specific immunity and when coupled with TSA56 it shows better protective immunity against heterologous strains.The review provides detailed insight into the potential immunogenic proteins of Orientia which can be utilized to develop the vaccine.Furthermore,studies focused on highly antigenic proteins will provide more insight into their roles in developing therapeutics and easy-to-handle rapid diagnostic kits.
基金supported by the Science and Technology Plan Grant of Guangzhou(grant number 202102080035)the Guangzhou Health and Family Planning Science and Technology Project Western Medicine-general Guidance Project(20221A011067)+2 种基金the Basic Research Project of Key Laboratory of Guangzhou(grant number 202102100001)the Key Project of Medicine Discipline of Guangzhou(grant number 2021-2023-12)the Guangzhou Health Science and Technology Project(grant number 20221A011066).
文摘Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.
基金supported by the National Basil Research Program of China(973 Program) 2010CBS30200(2010CB530206)the grants from the National Key Science and Technolog Projects of China,No.2009ZX10004-203 and 2008ZX10004-008)
文摘Objective:To evaluate the detection of IgM and IgG antibodies to Orientia tsutsugamushi(O. tsutsugamushi) by rapid diagnostic test(RDT) and microimmunofluorescence assay(ml FA). Methods:RDT using a mixture of recombinant 56-kDa proteins of O.tsutsugamushi and mIFA assay were performed on 20 patients from Fujian and 13 patients from Yunnan Province,and 82 sera samples from healthy farmers in Anhui Province and Beijing City in 2009.Comparison of the RDT and mIFA assay was performed by using X test and the P level of 【0.05 was considered to be significance.Results:Among these 82 normal sera samples,the specificity of RDT was 100%for both IgM and IgG tests.In 33 samples from patients with scrub typhus,5 cases were positively detected earlier by RDT than by mIFA in IgM test,and 2 cases were positive in IgG test.Sensitivities of RDT were 93.9%and 90.9%for IgM and IgG,respectively.The sensitivity of combination lest of IgM and IgG was 100%.Geometric mean titer diluted sera from confirmed cases by IFA and RDT assay were 1:37 vs.1:113(P【0.001) in IgM test and 1:99 vs.1:279 (P【0.05) in IgG test.Conclusions:RDT is more sensitivite than mIFA in the early diagnosis of scrub typhus and it is particularly applicable in rural areas.
基金supported by the Finance Science and Technology Project of Hainan Province(ZDYF2018106,ZDXM2014069)the National Natural Science Foundation of China(81860373,51762012,81760376,81460306 and 31160030)+4 种基金the Education Department of Hainan Province(Hnky2019ZD-27)the National Innovation and Entrepreneurship Training Program for College Students(201511810007,201811810024)the Innovation and Entrepreneurship Training Program for College Students of Hainan Province(S201911810034)Innovation and Entrepreneurship Training Program for College Students of Hainan Medical University(HYCX2014013,HYCX2018024)Research Unit of Island Emergency Medicine of Chinese Academy of Medical Sciences(2019RU013).
文摘Objective:To predict B cell and T cell epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins.Methods:The sequences of 22-kDa,47-kDa,56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA,DNAstar,Bcepred,ABCpred,NetMHC,NetMHCⅡand IEDB.The 58-kDa tertiary structure model was built by MODELLER9.17.Results:The 22-kDa B-cell epitopes were located at positions 194-200,20-26 and 143-154,whereas the T-cell epitopes were located at positions 154-174,95-107,17-25 and 57-65.The 47-kD a protein B-cell epitopes were at positions 413-434,150-161 and 283-322,whereas the T-cell epitopes were located at positions 129-147,259-267,412-420 and 80-88.The 56-kDa protein B-cell epitopes were at positions 167-173,410-419 and 101-108,whereas the T-cell epitopes were located at positions 88-104,429-439,232-240 and 194-202.The 58-kDa protein B-cell epitopes were at positions 312-317,540-548 and 35-55,whereas the T-cell epitopes were located at positions 415-434,66-84 and 214-230.Conclusions:We identified candidate epitopes of 22-kDa,47-kDa,56-kDa and 58-kDa proteins from Orientia tsutsugamushi.In the case of 58-kDa,the dominant antigen is displayed on tertiary structure by homology modeling.Our findings will help target additional recombinant antigens with strong specificity,high sensitivity,and stable expression and will aid in their isolation and purification.
基金Supported by the National Key Research and Development Program of China(2022YFC2602203).
文摘What is already known about this topic?Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi that is transmitted primarily through the bite of infected chigger mite larvae.The disease prevalence is closely associated with environments characterized by high moisture levels and abundant vegetation.What is added by this report?This study documents the first confirmed case of scrub typhus in Ningxia Hui Autonomous Region,China.The patient presented with characteristic clinical manifestations,including abnormal biochemical indicators and positive serum-specific IgM antibodies against scrub typhus.Epidemiological evidence suggests local acquisition of the disease.What are the implications for public health practice?Enhanced surveillance and preventive measures for scrub typhus are essential in this region,particularly for individuals residing in or visiting areas where the disease may be endemic.
文摘Background Scrub typhus,an acute febrile disease caused by Orientia tsutsugamushi,is transmitted to humans through infected chigger mites.We present a case of scrub typhus in a previously healthy man from Shandong Province diagnosed using next-generation sequencing(NGS)and PCR and review recent literature on NGS for scrub typhus diagnosis.Methods NGS was utilized for testing whole blood collected on admission.Confirmatory testing was done by detecting IgM and IgG antibodies to Orientia in acute and convalescent sera by ELISA.Orientia 47-kDa protein gene TaqMan and standard PCR of the 56-kDa protein gene and Sanger sequencing were performed on eschar scab DNA.Results The NGS diagnosis was confirmed by 47-kDa protein gene TaqMan and sequencing of a fragment of the O.tsutsugamushi 56-kDa protein gene from the eschar scab.Analysis of this sequence and the NGS data indicated O.tsutsugamushi strain Cheeloo2020 is a novel genotype.Mapping of the NGS data against the O.tsutsugamushi Gilliam strain genome sequence identified 304 reads with high similarity.Conclusions NGS is not only useful for multiplex diagnosis of scrub typhus,but also provides insight into the genetic diversity of O.tsutsugamushi.The common failure to submit sequences to databases makes it difficult to determine the minimal quantity and quality of NGS data being used for the positive identification of Orientia DNA in clinical specimens.
文摘OBJECTIVE: To identify genotype of eight strains of Orientia tsutsugamushi (O. tsutsugamushi) isolated from Nan Peng Lie Islands in China and establish tsutsugamushi disease nature foci for this region. METHODS: The nested polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used. Three primers were selected from the DNA sequence of the gene encoding type-specific 56-kDa protein of the Karp strain. The positive products were digested by Hine II and Pst I, meanwhile profiles specific to each strain were analyzed. RESULTS: Three genotypes of O. tsutsugamushi including Karp, Kato and a new strain existed on Nan Peng Lie Islands. CONCLUSION: Nan Peng Lie Islands is tsutsugamushi disease nature foci.
基金Supported by National Natural Science Foundation of China,No.81800721the Postdoctoral Foundation of China,2020M671387.
文摘BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.
文摘Rationale:Longitudinally extensive transverse myelitis(LETM)is a rare inflammatory demyelinating disease predominantly associated with autoimmune and inflammatory disorders.Scrub typhus can cause a variety of neurological complications,which may result in poor recovery and long-term disability.This report reveals a rare linkage between LETM and scrub typhus.Patient concerns:A 24-year-old female presented with a history of fever for 10 days associated with progressive quadriparesis.Physical examination revealed bilateral lower limb weakness(grade 0/5)and bilateral upper limb weakness(grade 2/5)with reduced sensation below the T3 dermatome.Diagnosis:Scrub typhus presenting with longitudinally extensive transverse myelitis.Interventions:Steroid pulse therapy with antibiotics supported by early intensive rehabilitation.Outcomes:Complete recovery was achieved.Lessons:This case report highlights the importance of considering scrub typhus as a potential cause of LETM in endemic regions,particularly in patients presenting with febrile illness and neurological symptoms.
