The prevalence and characteristics of Shiga toxin-producing Escherichia coli isolated by the enteric pathogens active surveillance network (Enter-Net) in the Republic of Korea, 2009-2018.

OBJECTIVE: Shiga toxin-producing Escherichia coli (STEC) is a water- and food-borne pathogenic agent that causes diarrhea, hemorrhagic colitis, hemolytic uremic syndrome (HUS), and end-stage renal disease. As the annual incidence of STEC increases, disease control is also becoming important in Korea. In this study, we aimed to analyze the incidence trends and characteristics of STEC isolated from diarrheal patients over 10 years. METHODS: From 2009 to 2018, STECs were collected by the Enteric Pathogens Active Surveillance Network (Enter-Net) and analyzed according to clinical epidemiological information (month of isolation, age, and sex of patient), O serogroup, and shiga toxin type. Shiga toxin genes (stx1 and stx2) and O serogroups of isolates were determined using multiplex PCR and an agglutination method with the available O antisera, respectively. RESULTS: A total of 418 strains were isolated over 10 years. The isolation rate according to age group and season was highest in children ≤4 years old (38.1%) and in the summer season (June to August). Among the 418 isolates, the major serogroups were divided O157 (20.3%), O103 (13.6%), O26 (7.7%), O111 (5.5%), O91 (4.3%), O108 (2.4%), and O8 (2.2%). The most frequently isolated O157 showed a lower isolation rate compared to that isolated from other developed countries. The profiles of stx genes were distinct among serogroups. In O157 and O91, stx1+stx2 was detected more frequently than either stx1 or stx2 alone. Particularly, most of the O157 (98%) isolates harbored the stx2 gene, which is an important factor in severe diseases, including HUS. In O103, O26, O111, and O108, stx1-only was more frequently present than stx2-only or stx1+stx2. CONCLUSIONS: As a result of analyzing domestic STECs collected through Enter-Net, it was confirmed that patients ≤4 years of age and in the summer months require attention, and that STEC with a serogroup of O157 is highly likely to cause diseases such as HUS. Therefore, the pathogen active surveillance network for characterization and provision of STEC isolates must be operated continuously.

Cohnella cholangitidis sp. nov., a novel species of the genus Cohnella isolated from a clinical specimen in Korea.

A Gram-positive, aerobic, rod-shaped bacterium, designated as strain 1605-214T, was isolated from the blood sample of a patient with cholangitis. Based on its 16S rRNA gene sequence, the strain 1605-214T belonged to the genus Cohnella and exhibited 97.9% sequence identity with Cohnella luojiensis DSM 24270T (GQ214052). DNA-DNA hybridization, digital DNA-DNA hybridization, and average nucleotide identity values between the two species were 23% ± 1.9, 21.1%, and 77.2%, respectively. The cellular fatty acids of strain 1605-214T were mainly comprised of anteiso-C15:0 (36.1%), iso-C16:0 (16.5%), and C16:0 (15.1%). The predominant quinone was menaquinone-7; predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, and aminophospholipid-1. The cell wall peptidoglycan of strain 1605-214T contained meso-diaminopimelic acid. DNA G + C content of strain 1605-214T was 50.6 mol%. 5187 genes out of a total of 5413 (94.6%) were assigned putative functions using eggNOG v5.0. Based on genotypic characteristics and genomic sequence analysis results, strain 1605-214T was confirmed to represent a novel species of genus Cohnella, for which the name Cohnella cholangitidis sp. nov., was proposed.

Serologic Survey and Risk Factors for Coxiella burnetii Infection among Dairy Cattle Farmers in Korea.

BACKGROUND: The zoonotic disease Q fever is caused by Coxiella burnetii and usually affects high-risk human populations. We conducted a serological survey of dairy cattle farmers in Korea to determine seroreactivity and identify risk factors for C. burnetii infection. METHODS: This cross-sectional study included 1,824 of 7,219 dairy cattle farms (25.3%) in the study region. The selected dairy cattle farmers visited the nearest public health centers or branches with completed questionnaires. Serum samples from the farmers were tested using an indirect immunofluorescence assay to detect phase II C. burnetii immunoglobulin (Ig) G or M antibodies. RESULTS: A total of 1,222 dairy cattle farmers from 784 dairy cattle farms (43.0%) participated in this study, and 11.0% (134/1,222) exhibited seroreactivity, defined as a phase II antigen IgG or IgM titer ≥ 1:16. In the multivariate analysis, male sex, residence in Gyeonggi Province, a larger herd size, and ocular/oral contact with birth products during calf delivery were significantly associated with a higher risk of C. burnetii infection. Furthermore, the risk was significantly lower among farmers who always wore protective gloves while cleaning cattle excretion, compared to those who sometimes or rarely wore protective gloves. CONCLUSION: Dairy cattle farmers should exercise caution by avoiding ocular/oral contact with birth products during calf delivery and by using protective equipment (including gloves).

Dermabacter jinjuensis sp. nov., a novel species of the genus Dermabacter isolated from a clinical specimen.

A Gram-stain-positive, catalase-positive, facultatively anaerobic, non-motile, coryneform bacterium, designated strain 32T, was isolated from a closed pus sample from a patient having finger necrosis in Korea. Strain 32T was considered as representing a novel species according to its initial identification by matrix-assisted laser desorption/ionization-time-of-flight MS. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 32T belonged to the genus Dermabacter and was closely related to Dermabacter hominis DSM 7083T (=ATCC 49369T) (98.34 % similarity). Optimal growth was observed at 30-40 °C and pH 7. Growth occurred in the presence of 0-6 % (w/v) NaCl. Menaquinones MK-8, MK-7 and MK-9 were the major respiratory quinones. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, glycolipid and two unknown lipids. The major cellular fatty acids were anteiso-C17 : 0, anteiso-C15 : 0, iso-C16 : 0 and iso-C15 : 0. The DNA G+C content of strain 32T was 62.58 mol%, and the mean level of DNA-DNA relatedness between strain 32T and D. hominis ATCC 49369T was 49±1.6 %. Based on the phenotypic and genotypic characteristics, strain 32T is confirmed to represent a novel species of the genus Dermabacter, for which the name Dermabacter jinjuensis sp. nov. is proposed. The type strain is 32T (=NCCP 16133T=DSM 101003T).

Review: Laboratory diagnosis and surveillance of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a representative human transmissible spongiform encephalopathy associated with central nervous system degeneration. Prions, the causative agents of CJD, are composed of misfolded prion proteins and are able to self-replicate. While CJD is a rare disease affecting only 1-1.5 people per million worldwide annually, it has attracted both scientific and public attention as a threatening disease since an epidemic of variant CJD (vCJD) cases appeared in the mid-1990s. Due to its unconventional transmission and invariable fatality, CJD poses a serious risk to public health. The hundreds of sporadic, genetic, and iatrogenic CJD cases as well as potential zoonotic transmission suggest that CJD is an ongoing concern for the field of medicine. Nevertheless, treatment aimed at clinical prevention and treatment that reverses the course of disease does not exist currently. Active surveillance and effective laboratory diagnosis of CJD are, therefore, critical. In this report, the surveillance systems and laboratory tests used currently to diagnose CJD in different countries are reviewed. The current efforts to improve surveillance and diagnosis for CJD using molecular and biochemical findings are also described.

Emerging high-level ciprofloxacin-resistant Salmonella enterica serovar typhi haplotype H58 in travelers returning to the Republic of Korea from India.

In Korea, typhoid fever is a rare disease due to improved living standards. However, typhoid fever remains a major burden in developing countries and regions, such as India and Southeast Asia. In this study, we isolated Salmonella Typhi (S. Typhi) from eight patients with typhoid fever who were travelers returning from India. The strains isolated were characterized by antimicrobial susceptibility profiling and whole-genome sequencing (WGS) analysis. All strains were resistant to nalidixic acid and azithromycin. Among them, four isolates were highly resistant to ciprofloxacin (MIC ≥32 µg/ml); these strains have not been confirmed in Korea PulseNet DB. According to WGS, the ciprofloxacin-resistant strains belong to the global dominant multidrug-resistant (MDR) haplotype H58 (SNP glpA C1047T, SptP protein Q185* (premature stop codon)) and do not harbor the MDR plasmid. H58-associated SNPs in membrane and metabolism genes, including yhdA, yajI, hyaE, tryE, rlpB and metH, are present. Additionally, phylogenetic analysis assigned the H58 strains to sublineage II, whereas the non-H58 strains are closely related to haplotype H50. The presence of high-level ciprofloxacin-resistant S. Typhi haplotype H58 in Korea was first confirmed as due to influx from overseas via travelers. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.

Intranasal Vaccination with Outer-Membrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

Early Laboratory Preparedness of the Korea Disease Control and Prevention Agency and Response to Unknown Pneumonia Outbreak from Wuhan, China, in January 2020.

We report the response process of the Laboratory Analysis Task Force (LATF) for Unknown Disease Outbreaks (UDOs) at the Korea Disease Control and Prevention Agency (KDCA) during January 2020 to coronavirus disease 2019 (COVID-19), which developed as a UDO in Korea. The advanced preparedness offered by the laboratory diagnostic algorithm for UDOs related to respiratory syndromes was critical for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enabled us to establish and expand the diagnostic capacity for COVID-19 on a national scale in a timely manner.

Traveller-associated high-level ciprofloxacin-resistant Salmonella enterica Serovar Kentucky in the Republic of Korea.

OBJECTIVE: Salmonella enterica serotype Kentucky ST198 (S. Kentucky) is frequently associated with human infections and has been identified in travellers to North Africa, South Asia, Europe, and North America. The antimicrobial resistance of this serotype to multiple drugs, including ciprofloxacin (CIP), is a growing concern. However, little information is available regarding the occurrence and characterization of S. Kentucky in Korea. METHODS: To investigate the characteristics and possible origin of these infections, we characterized highly CIP-resistant S. Kentucky isolates collected through a national surveillance program. Single-nucleotide polymorphisms (SNPs) were identified by whole-genome sequencing (WGS), and genome sequencing was performed to investigate the genetic relationships and resistance mechanisms of the isolates. RESULTS: Ten CIP-resistant S. Kentucky strains were isolated from diarrheal patients in Korea from 2008 to 2017. The travel histories of the patients indicated that seven had returned from Southeast Asia. WGS of all the isolates revealed the presence of Salmonella genomic island 1 (SGI1) and substitutions in the gyrA and parC genes, which are known to confer resistance to CIP. A multilocus sequence type (MLST) analysis revealed that the isolates belonged to ST198, which has been prevalent in Europe and Africa. Furthermore, a phylogenetic analysis showed that all 10 isolates shared close genetic relationships. CONCLUSIONS: We report the identification of S. Kentucky in Korea through long-term surveillance. International travel, especially to Southeast Asia, has been a major risk factor for human infections of CIP-resistant S. Kentucky in Korea.

The role of international travellers in the spread of CTX-M-15-producing Shigella sonnei in the Republic of Korea.

BACKGROUND: Multidrug-resistant Shigella isolates have recently emerged as a serious public health threat worldwide. In particular, overseas travel is a risk factor for acquisition of antimicrobial-resistant Shigella strains. To explore the role of travel in the spread of cefotaxime-resistant Shigella sonnei in Korea, we screened 751 Shigella spp. isolates from 2007 to 2016 through the National Surveillance system, and 28 cephalosporin-resistant S. sonnei isolates were identified. METHODS: For cephalosporin-resistant S. sonnei isolates, epidemiological and molecular analyses (plasmid structure analysis, pulsed-field gel electrophoresis (PFGE) and high-quality single-nucleotide polymorphisms (hqSNPs) based on whole-genome sequencing (WGS)) were conducted to investigate the source of infection and transmission route. RESULTS: Among the 28 cefotaxime-resistant S. sonnei strains, 18 were isolated from travellers returning from Asia, including Vietnam (n=11). Molecular analysis of 18 blaCTX-M-type isolates revealed that 15 contain CTX-M-15; 50% of isolates from domestic patients contain CTX-M-14. Analysis of the genetic environments of the blaCTX-M-14 and blaCTX-M-15 genes revealed different genetic organization surrounding the blaCTX-M genes. Additionally, PFGE and hqSNP results suggested a large phylogenetic distance between the S. sonnei isolates related to overseas travel and those acquired domestically in Korea. CONCLUSION: Our study data demonstrates that two prevalent blaCTX-M genes, blaCTX-M-14 and blaCTX-M-15, have been circulating in S. sonnei in Korea over the last 10 years. Recently, international travellers are at a high risk for acquisition of CTX-M-15-producing S. sonnei in Korea.

Cytokine response in Balb/c mice infected with Francisella tularensis LVS and the Pohang isolate.

We investigated the immune response induced by the Francisella (F.) tularensis live vaccine strain (LVS) and the Pohang isolate. After the Balb/c mice were infected intradermally (i.d) with 2 x 10(4) cfu of F. tularensis LVS and Pohang, respectively, their blood and organs were collected at different times; 0, 3, 6, 24, 72, 96, 120 and 168 h after infection. Using these samples, RT-PCR and ELISA analysis were carried out for the comparative study of the cytokines, including TNF-alpha, INF-gamma, IL-2, IL-4, IL-10 and IL-12. In the Pohang-infected mice at 120 h, the liver showed a 53 times higher level of TNF-alpha and a 42 times higher level of IFN-gamma than the respective levels at the early time points after infection. The levels of TNF-alpha and IFN-gamma induced by LVS were 5 times lower than those induced by the Pohang isolate. Also, the organs from the Pohang-infected mice showed higher levels of TNF-alpha, IFN-gamma, IL-10 and IL-12 than the levels in the LVS-infected mice. The blood from the Pohang-infected mice at 120 h revealed about a 40 times increased level of IFN-gamma, and IL-10 was also increased by 4 times at 96 h compared to an early infection time point, while IL-4 was not induced during the whole infection period. These results suggest that F. tularensis may induce a Th1-mediated immune response to in vivo infection and the Pohang isolate has a higher capacity than the LVS to induce an acute immune response in Blab/c mice.

Seroreactivity and Risk Factors Associated with Coxiella burnetii Infection among Cattle Slaughterhouse Workers in South Korea.

Q fever, caused by Coxiella burnetii, is a zoonotic disease that is an occupational hazard to people who work in close contact with animals or their carcasses. A nationwide serologic study among cattle slaughterhouse workers who were presumed to be at risk of having C. burnetii infection in South Korea was performed to investigate the seroreactivity of C. burnetii infection and identify related risk factors. Out of 1017 cattle slaughterhouse workers in South Korea, 923 (90.8%) participated in this cross-sectional study. Samples were tested for immunoglobulin G (IgG) and M (IgM) antibodies against phase II C. burnetii via indirect immunofluorescence assay. The overall seroreactivity, defined as IgG or IgM antibody titer cutoffs ≥1:16, was 9.1% (84/923). Additionally, a significant association was found between the seroreactivity of C. burnetii infection and performing carcass evisceration work (odds ratio, 2.36; 95% confidence interval, 1.39⁻4.03) in multivariate analysis. To diminish C. burnetii infection, cattle slaughterhouse workers need to take precautions during the evisceration process.

The first case of hand infection caused by Dermabacter jinjuensis in a symmetrical peripheral gangrene patient.

INTRODUCTION: Strains of the genus Dermabacter is a recently established species, recognized as relatively rare opportunistic human pathogen, and is infrequently isolated from clinical specimens, including blood cultures, abscesses, wounds, bone, eye, and skin. PRESENTATION OF CASE: We present a 78-year old female with chronic symmetrical peripheral gangrene and hand infection. The patient underwent surgical debridement with amputation on gangrene with infection of both fingers. At 2 weeks postoperatively, pus discharge was newly observed and the patient underwent reoperation. In the subsequent reinfection, unknown organism has been repeatedly identified, may be the most likely causative agent. On the basis of phenotypic and genotypic distinctness and DNA-DNA hybridization results, new strain should be placed in the genus Dermabacter as representing a novel species, for which the name Dermabacter jinjuensis sp. nov. is proposed. DISCUSSION: We judged the novel species as the causative bacteria. Because of, a novel species called D. jinjuensis was repeatedly identified more than common bacteria. It can be considered as a postoperative nosocomial infection or opportunistic infection. It is not clear how the infection of D. jinjensis occurred. CONCLUSION: This is the first reported case of a human D. jinjuensis infection. We were able to treat patients without any complications by operative treatment and administering appropriate antimicrobial agents according to antibiotics susceptibility test.

Seroreactivity to Q Fever Among Slaughterhouse Workers in South Korea.

OBJECTIVES: Q fever is a zoonotic disease that occurs worldwide; however, little is known about its prevalence in South Korea. We attempted to determine the prevalence of Q fever seroreactivity among Korean slaughterhouse workers and the risk factors for seroreactivity according to the type of work. METHODS: The study was conducted among 1503 workers at a total of 73 slaughterhouses and 62 residual-product disposal plants. During the study period, sites were visited and surveys were administered to employees involved in slaughterhouse work, and serological tests were performed on blood samples by indirect immunofluorescence assays. Serological samples were grouped by job classification into those of slaughter workers, residual-product handlers, inspectors and inspection assistants, and grading testers and testing assistants. Employee risk factors were analyzed according to the type of work. RESULTS: Out of 1481 study subjects who provided a blood sample, 151 (10.2%) showed reactive antibodies. When these results were analyzed in accordance with the type of work, the result of slaughter workers (11.3%) was similar to the result of residual-product handlers (11.4%), and the result of inspectors and assistants (5.3%) was similar to the result of grading testers and assistants (5.4%). Among those who answered in the affirmative to the survey question, "Has there been frequent contact between cattle blood and your mouth while working?" the proportions were 13.4 and 4.6%, respectively, and this was identified as a risk factor that significantly varied between job categories among slaughterhouse workers. CONCLUSIONS: This study found a Q fever seroreactivity rate of 10.2% for slaughterhouse workers, who are known to be a high-risk population. Contact with cattle blood around the mouth while working was the differential risk factor between job categories among slaughterhouse workers.

A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.

We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant. Moreover, the combination of rec47 and CT induced a strong cellular immune response to 47-kDa OMP, as demonstrated by a spleen cell proliferation assay, and also induced Th1- and Th2-type cytokine production, as demonstrated by a cytokine enzyme-linked immunosorbent assay. Intranasal immunization with rec47 plus CT was the most effective method for the induction of humoral and cell-mediated immune responses. Furthermore, relatively strong protection against homologous O. tsutsugamushi strain Boryong challenge was observed in mice immunized with rec47 plus CT. Therefore, 47-kDa OMP is an attractive candidate for developing a prophylactic vaccine against scrub typhus by O. tsutsugamushi infection.

Development and evaluation of an anti-rabies virus phosphoprotein-specific monoclonal antibody for detection of rabies neutralizing antibodies using RFFIT.

BACKGROUND: Rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. The rapid fluorescent focus inhibition test (RFFIT) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. Here, we report the development of a new monoclonal antibody (mAb) designed to react specifically with Rabies virus (RABV) phosphoprotein (P protein), and the evaluation of its applicability to the RFFIT and its effectiveness as a diagnostic reagent for human rabies. METHODOLOGY/PRINCIPAL FINDINGS: The mAb KGH P 16B8 was produced to target the P protein of the Korean KGH RABV strain. An indirect immunofluorescence assay (IFA) was conducted to detect various strains of RABV in various cell lines. Alexa-conjugated KGH P 16B8 (16B8-Alexa) was developed for the RFFIT. The IFA test could detect RABV up to a 1:2,500 dilution, with a detection limit comparable to that of a commercial diagnostic reagent. The sensitivity, specificity, positive predictive value, and negative predictive value of the RFFIT using 16B8-Alexa in 414 clinical specimens were 98.67%, 99.47%, 99.55%, and 98.42%, respectively. The results of the RFFIT with 16B8-Alexa were strongly correlated with those obtained using an existing commercial diagnostic reagent (r = 0.995, p<0.001). CONCLUSIONS/SIGNIFICANCE: The mAb developed in this study shows high sensitivity and specificity, confirming its clinical utility with the RFFIT to measure the rabies neutralizing antibody titer and establish a diagnosis in human. Thus, 16B8-Alexa is expected to serve as an alternative diagnostic reagent that is widely accessible, with potentially broad applications beyond those of the RFFIT in Korea. Further studies with 16B8-Alexa should provide insight into the immunological mechanism of the P protein of Korean RABV.

Alternative application of Tau protein in Creutzfeldt-Jakob disease diagnosis: Improvement for weakly positive 14-3-3 protein in the laboratory.

The 14-3-3 protein has been used as a biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, weakly positive 14-3-3 leads to false positive results and an incorrect diagnosis. We attempted to use quantitative data for tau protein to provide an accurate diagnosis based on weak 14-3-3 protein. Sixty-two patients with sCJD, including pathologically confirmed, clinically definite, and probable cases, and 89 non-CJD patients were investigated based on a Korean population. Among them, 20 sCJD and 14 non-CJD showed weakly positive 14-3-3. The total tau (t-tau) and phosphorylated tau (p-tau) protein levels were measured by ELISA, and the p-tau to t-tau ratio (p/t ratio) was calculated. The combined use of the 14-3-3 protein assay, t-tau levels, and p/t ratio improved the specificity of diagnosis compared with the use of the 14-3-3 protein assay alone (47% for 14-3-3 alone; 85.94% for 14-3-3 combined with t-tau; 90.62% for 14-3-3 combined with the p/t ratio). In addition, 18 of 20 sCJD and 12 of 14 non-CJD who were weakly positive for 14-3-3 were positive for the p/t ratio and negative for the p/t ratio, respectively. When used in combination with the 14-3-3 protein, the tau protein is useful as a biomarker for the precise diagnosis of sCJD.

Epidemiological features and clinical manifestations of Lyme borreliosis in Korea during the period 2005-2012.

Lyme borreliosis is one of the most common tick-borne infections in the northern hemisphere. However, the epidemiological features and clinical manifestations of this disease in Korea are unknown. The present study is the first to investigate the characteristics of Lyme borreliosis in Korea. We traced suspected cases of Lyme borreliosis during the period 2005-2012. Of the 16 identified patients with the disease, 11 had acquired autochthonous infection within Korea, while 5 patients were infected outside Korea. The history of past exposure was investigated in 8 of the 11 patients with autochthonous infection; 5 of these 8 patients (62.5%) were suspected to have acquired the infection in the northeastern alpine region. Clinically, of 11 patients with autochthonous infection, 6 (54.5%) showed early skin manifestations, 4 (36.4%) showed neurological manifestations, and 1 (9.1%) showed acrodermatitis chronica atrophicans. In conclusion, Lyme borreliosis could be endemic in the northeastern alpine region of Korea, and neurological and early skin manifestations are likely to be the major clinical characteristics of autochthonous Lyme borreliosis in Korea.

Metabolic responses to Orientia tsutsugamushi infection in a mouse model.

Tsutsugamushi disease is an infectious disease transmitted to humans through the bite of the Orientia tsutsugamushi-infected chigger mite; however, host-pathogen interactions and the precise mechanisms of damage in O. tsutsugamushi infections have not been fully elucidated. Here, we analyzed the global metabolic effects of O. tsutsugamushi infection on the host using 1H-NMR and UPLC-Q-TOF mass spectroscopy coupled with multivariate statistical analysis. In addition, the effect of O. tsutsugamushi infection on metabolite concentrations over time was analyzed by two-way ANOVAs. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed distinct metabolic patterns between control and O. tsutsugamushi-infected mice in liver, spleen, and serum samples. O. tsutsugamushi infection caused decreased energy production and deficiencies in both remethylation sources and glutathione. In addition, O. tsutsugamushi infection accelerated uncommon energy production pathways (i.e., excess fatty acid and protein oxidation) in host body. Infection resulted in an enlarged spleen with distinct phospholipid and amino acid characteristics. This study suggests that metabolite profiling of multiple organ tissues and serum could provide insight into global metabolic changes and mechanisms of pathology in O. tsutsugamushi-infected hosts.