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Objective: The clinical implications of SARS-CoV-2 RNA viremia in blood (RNAemia) remain uncertain despite gaining more prognostic implications for coronavirus disease 2019 (COVID-19). However, the clinical relevance of SARS-CoV-2 RNAemia has not been well documented. Methods: We conducted a cohort study on 95 confirmed COVID-19 patients and explored the prospects with evidence of SARS-CoV-2 RNAemia in association with various clinical characteristics. We performed reverse transcription-polymerase chain reaction and studied the risk factors of SARS-CoV-2 RNAemia using logistic regression analysis. Results: The presence of SARS-CoV-2 RNAemia in critical or fatal cases was the highest (66.7%), followed by severe (12.5%) and mild to moderate (1.7%) in admission samples. SARS-CoV-2 viral RNAemia was detected on admission and 1st week samples; however, RNAemia was not detected on the samples collected on the second week post-symptom onset. Multiple regression analysis showed that the severity of the disease was an independent predictor of RNAemia (p < 0.021), and the Kaplan–Meier survival curve estimated an increased mortality rate in SARS-CoV-2 RNAemia cases (p < 0.001). Conclusions: Our study demonstrated that SARS-CoV-2 RNAemia is a predictive risk factor for clinical severity in COVID-19 patients. Hence, we showed that blood RNAemia might be a critical marker for disease severity and mortality. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with SARS-CoV-2. Both hrACE2 and hrACE2-Fd inhibited SARS-CoV-2 by 50% at concentrations below the maximum plasma concentration, with EC50 of 5.8 μg/mL and 6.2 μg/mL, respectively. The hrACE2 and hrACE2-Fd injection groups showed a tendency for decreased viral titers in nasal turbinate tissues on day 3 after virus inoculation; however, this decrease was not detectable in lung tissues. Histopathological examination on day 9 after virus inoculation showed continued inflammation in the SARS-CoV-2 infection group, whereas decreased inflammation was observed in both the hrACE2 and hrACE2-Fd injection groups. No significant changes were observed at other time points. In conclusion, the potential therapeutic efficacy of plant-based proteins, hrACE2 and hrACE2-Fd, against COVID-19 was confirmed in a SARS-CoV-2-inoculated Golden Syrian hamster model. Further preclinical studies on primates and humans are necessary to obtain additional evidence and determine the effectiveness of these therapies. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile disease caused by bites from ticks infected with the SFTS virus. In Korea, SFTS patients are observed nationwide, including Jeju Island, but there are currently no data regarding the national prevalence of SFTS, including that of residents of 16 cities and provinces. This study aimed to investigate the seroprevalence of SFTS in Korea. Methodology/Principal findings: A total of 1500 participants were selected through random sampling from the 2014–2015 Korea National Health and Nutrition Examination Survey (KNHANES). An indirect immunofluorescence antibody assay (IFA) was performed to assess immunoglobulin (Ig) G and IgM antibody titers against SFTS virus. Results: Of the 1500 participants, 55 (3.7%) tested positive for IgG and 1 (0.1%) tested positive for IgM, with antibody titer of ≥ 1:32. Approximately 3.9% and 2.5% of participants in urban and rural areas, respectively, had a positive titer of ≥ 1:32. There was a significant correlation between SFTS incidence per 100,000 population and seroprevalence using an IgG titer ≥ 1:64 as the cut-off value. Conclusion: This is the first study to investigate national SFTS seroprevalence in all 16 cities and provinces representing Korea. Our study will also provide useful guidelines for the development of preventive measures against SFTS. Author summary: Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile disease caused by a bite from a tick carrying the SFTS virus. This new infectious disease is observed mainly in Korea, China, and Japan. In Korea, SFTS incidence reported in Korea Disease Control and Prevention Agency is an average of 233 cases between 2016 and 2020, with 39 deaths and a fatality rate of 16.68%. SFTS patients are observed nationwide, including Jeju Island, but there are currently no data regarding the national prevalence of SFTS, including that of residents of 16 cities and provinces. In the present study, we aimed to investigate the seroprevalence of SFTS in Korea. A total of 1500 participants were selected through random sampling from the 2014–2015 Korea National Health and Nutrition Examination Survey. An indirect immunofluorescence antibody assay was performed to assess immunoglobulin (Ig) G and IgM antibody titers against SFTS virus. Of the 1500 participants, 55 (3.7%) tested positive for IgG and 1 (0.1%) tested positive for IgM, with antibody titer of ≥ 1:32. Approximately 3.9% and 2.5% of participants in urban and rural areas, respectively, had a positive titer of ≥ 1:32. There was a significant correlation between SFTS incidence per 100,000 population and seroprevalence using an IgG titer ≥ 1:64 as the cut-off value. This is the first study to investigate national SFTS seroprevalence across all 16 cities and provinces representing Korea; furthermore, our study will also provide useful guidelines for the development of preventive measures against SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic tick-borne infectious disease caused by the SFTS virus (SFTSV). Few studies have assessed SFTS seroprevalence among veterinary hospital staff and their awareness of SFTS. From January to May 2021, serum samples from 103 veterinary hospital staff were tested for SFTS using an enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay, and a 50% plaque reduction neutralization antibody test, which yielded positive results in four (3.9%), three (2.9%), and two (1.9%) participants, respectively. A questionnaire was used for an epidemiological investigation. ELISA positivity was higher among those who lacked awareness of possible animal-to-human SFTS transmission (p = 0.029). SFTS awareness was significantly lower among veterinary hospital staff than among the veterinarians (p < 0.001). Providing staff with training concerning standard precautions and the use of appropriate personal protective equipment is important. [ABSTRACT FROM AUTHOR]

Adjuvant use of geraniol, a plant essential oil component, is known to increase the efficacy of antibiotics by acting as a potent inhibitor of efflux mechanisms. In this study, we assessed the effect of a geraniol–antibiotic combination in 21 Acinetobacter baumannii clinical isolates consisting of high efflux (HE) and low efflux (LE) activity groups. We determined the MIC for geraniol and the four antibiotics and evaluated the adjuvant antimicrobial activity and resensitization efficacy of adjuvant geraniol. Geraniol–antibiotic combinations significantly reduced the MIC of all four antibiotics (P < 0.0001), and the fold change in MIC decreased by 4 to >256-fold for tigecycline, >16 to >4,096-fold for ceftazidime, 1 to >4,096-fold for cefepime, and >2 to >4096-fold for ciprofloxacin. Importantly, geraniol showed adjuvant antimicrobial activity and resensitization efficacy when used in combination with antibiotics in 21 A. baumannii clinical isolates. However, there was no statistically significant difference between the HE and LE groups. Low concentrations (0.125% and 0.0625%) of geraniol showed no cytotoxic or hemolytic activity. Our study shows that geraniol, acting as an antibiotic adjuvant, is a good candidate for in vivo studies of combination therapy for the treatment of MDR/XDR A. baumannii infections. [ABSTRACT FROM AUTHOR]

To investigate the specific genomic features and mutation pattern, whole and near-complete SARS-CoV-2 genome sequences were analyzed. Clinical samples were collected from 18 COVID-19–positive patients and subjected to nucleic acid purification. Cell culture was performed to extract various SARS-CoV-2 isolates. Whole-genome analysis was performed using next-generation sequencing, and phylogenetic analyses were conducted to determine genetic diversity of the various SARS-CoV-2 isolates. The next-generation sequencing data identified 8 protein-coding regions with 17 mutated proteins. We identified 51 missense point mutations and deletions in 5′ and 3′ untranslated regions. The phylogenetic analysis revealed that V and GH are the dominant clades of SARS-CoV-2 circulating in the Gwangju region of South Korea. Moreover, statistical analysis confirmed a significant difference between viral load (P < 0.001) and number of mutations (P < 0.0001) in 2 mutually exclusive SARS-CoV-2 clades which indicates frequent genomic alterations in SARS-CoV-2 in patients with high viral load. Our results provide an in-depth analysis of SARS-COV-2 whole genome which we believe, can shed light in the understanding of SARS-COV-2 pathogenesis and mutation pattern which can aid in the development of prevention methods as well as future research into the pathogenesis of SARS-CoV-2 and therapeutic development. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses is a frequently reported acute hemorrhagic fever in South Korea. These viruses are transmitted by various rodent species such as Apodemus agrarius. Methodology/Principal findings: To investigate hantavirus infection and seroprevalence in rodents, wild rodents were captured from two districts in the suburbs of Gwangju Metropolitan City from January 2016 to December 2018. Nested reverse-transcription polymerase chain reaction (RT-PCR) targeting the hantavirus-specific L segment and indirect immunofluorescence antibody (IFA) assay using Hantaan virus antigen slides were performed. A total of 585 wild rodents were captured—512 A. agrarius, 49 Crocidura lasiura, and 24 Myodes regulus. Nested RT-PCR was performed to examine the rate of hantavirus infection in wild rodents, and 1.88% (11/585) of all rodents, 1.17% (6/512) of A. agrarius, 6.12% (3/49) of C. lasiura, and 8.33% (2/24) of M. regulus tested positive. The nucleotide sequence analysis of the eleven PCR-positive products revealed that six PCR products showed over 85% sequence similarity with the Jeju virus, four showed over 99.7% similarity with the Hantaan virus, and one showed over 95.3% homology with the Imjin virus. Moreover, IgG antibodies against the Hantaan virus were detected in 6.15% (36/585) of all rodents, 6.8% (35/512) of A. agrarius, and 4.17% (1/24) of M. regulus. IgG antibodies were not detected in C. lasiura. Conclusions/Significance: Hantaviruses were detected in all three wild rodent species of A. agrarius, C. lasiura, and M. regulus captured in the suburbs of Gwangju Metropolitan City, South Korea, and it was demonstrated that they were various strains of hantaviruses such as the Hantaan, Jeju, and Imjin viruses. Author summary: Hantaviruses (family Hantaviridae, genus Hantavirus) are rodent viruses that can cause two fatal human diseases—hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. These viruses are transmitted by various rodent species such as Apodemus agrarius. In the present study, wild rodents captured in the suburbs of Gwangju Metropolitan City were analyzed by nested reverse-transcription polymerase chain reaction targeting the hantavirus-specific L segment and indirect immunofluorescence antibody assay using Hantaan virus antigen slides. A total of 585 wild rodents were captured and 1.88% (11/585) of all rodents, 1.17% (6/512) of A. agrarius, 6.12% (3/49) of Crocidura lasiura, and 8.33% (2/24) of Myodes regulus were PCR-positive. Of the eleven PCR-positive wild rodents, six PCR products showed over 85% sequence similarity with the Jeju virus, four showed over 99.7% similarity with the Hantaan virus, and one showed over 95.3% homology with the Imjin virus. Moreover, IgG antibodies against the Hantaan virus were detected in 6.15% (36/585) of all rodents, 6.8% (35/512) of A. agrarius, and 4.17% (1/24) of M. regulus. IgG antibodies were not detected in C. lasiura. When we examined the detection rate of hantavirus genes in different seasons, hantaviruses were most commonly detected in fall (seven cases [5.69%]) and winter (four cases [2.76%]). No hantaviruses were detected in spring or summer. However, the seasonal prevalence of IgG antibodies was higher in spring and summer (12 [7.32%] and 11 [7.10%] cases, respectively) than in fall and winter (seven [5.69%] and six [4.14%] cases, respectively). This study was performed on a monthly basis throughout a three-year period, and thus, it provides reliable data that may provide insight into preventive measures against HFRS. Our results suggest that various types of hantaviruses, including Hantaan, Jeju, and Imjin viruses, are distributed throughout Gwangju Metropolitan City, South Korea. Data regarding the rate of Hantaan virus infection in rodents in Gwangju and knowledge of the hantavirus seroprevalence, species, and genotypes circulating in these domestic rodent species will provide useful information for developing vaccines and diagnostic testing using sequence data. These will help increase preparedness for the emergence of new species. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease caused by the SFTS virus (SFTSV). SFTS can be considered a life-threatening notifiable infectious disease. The unavailability of specific therapeutics encourages the investigation of potential efficacy of existing drugs against this infection. Drug repurposing was done by performing virtual screening of already established drug molecules followed by 100 ns molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area–based binding-energy calculation by targeting the SFTS L protein. On the basis of binding energy and protein–ligand interactions, top 10 promising hits were identified, showing stable binding with SFTS L protein. Further 100 ns atomistic MD simulation refined the hits from top 10 to top 4 with docking-based binding energy lesser than −8.0 kcal/mol toward the SFTS L protein and engaged in π–π interactions with pivotal amino acid residues. Various parameters and binding affinity of top 4 ligands towards L protein was computed. Ligand zaltoprofen exhibited best binding energy −220.095 kJ/mol. The present work is the first in silico study to assess bromfenac, cinchophen, elliptinium, and zaltoprofen; four promising hits against SFTS. Nonetheless, further proper biological evaluation is necessary to determine their efficacy against SFTS. [ABSTRACT FROM AUTHOR]

Lyme disease is a tick-borne infectious disease caused by the Borrelia burgdorferi sensu lato complex. However, the distribution of Borrelia genospecies and the tissue detection rate of Borrelia in wild rodents have rarely been investigated. Here, we studied 27 wild rodents (Apodemus agrarius) captured in October and November 2016 in Gwangju, South Korea, and performed nested polymerase chain reaction targeting pyrG and ospA to confirm Borrelia infection. Eight rodents (29.6%) tested positive for Borrelia infection. The heart showed the highest infection rate (7/27; 25.9%), followed by the spleen (4/27; 14.8%), kidney (2/27; 7.4%), and lungs (1/27; 3.7%). The B. afzelii infection rate was 25.9%, with the highest rate observed in the heart (7/27; 25.9%), followed by that in the kidney and spleen (both 2/27; 7.4%). B. garinii and B. burgdorferi sensu stricto were detected only in the spleen (1/27; 3.7%). This is the first report of B. burgdorferi sensu stricto infection in wild rodents in South Korea. The rodent hearts showed a high B. afzelii infection rate, whereas the rodent spleens showed high B. garinii and B. burgdorferi sensu stricto infection rates. Besides B. garinii and B. afzelii, B. burgdorferi sensu stricto may cause Lyme disease in South Korea. [ABSTRACT FROM AUTHOR]

Background: Mosquito-borne flaviviruses are prime pathogens and have been a major hazard to humans and animals. They comprise several arthropod-borne viruses, including dengue virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus. Culex flavivirus (CxFV) is a member of the insect-specific flavivirus (ISF) group belonging to the genus Flavivirus, which is widely distributed in a variety of mosquito populations. Methods: Viral nucleic acid was extracted from adult mosquito pools and subjected to reverse transcriptase nested polymerase chain reaction (PCR) using target-specific primers for detecting CxFV nonstructural protein 5 (NS5). The PCR-positive samples were then sequenced, and a phylogenetic tree was constructed, including reference sequences obtained from GenBank. Results: 21 pools, belonging to Culex pipiens pallens (Cx. p. pallens) were found to be positive for the CxFV RNA sequence, with a minimum infection rate of 14.5/1000 mosquitoes. The phylogenetic analysis of the NS5 protein sequences indicated that the detected sequences were closely related to strains identified in China, with 95–98% sequence similarities. Conclusion: Our findings highlight the presence of CxFV in Cx. p. pallens mosquito species in Jeju province, Republic of Korea. This is the first study reporting the prevalence of CxFV in Culex Pipiens (Cx. pipiens) host in the Jeju province, which can create possible interaction with other flaviviruses causing human and animal diseases. Although, mosquito-borne disease causing viruses were not identified properly, more detailed surveillance and investigation of both the host and viruses are essential to understand the prevalence, evolutionary relationship and genetic characteristic with other species. [ABSTRACT FROM AUTHOR]

In this study, we investigated the presence of tick-borne pathogens in ticks removed from tick-bitten humans in the southwestern provinces of the Republic of Korea (ROK). We identified 33 ticks from three tick species, namely Amblyomma testudinarium (60.6%), Haemaphysalis longicornis (27.3%), and Ixodes nipponensis (12.1%) in order of occurrence via morphology and 16S rDNA-targeting polymerase chain reaction (PCR). Tick-borne pathogens were detected in 16 ticks using pathogen-specific PCR. From the results, 12 ticks (36.4%) tested positive for spotted fever group (SFG) Rickettsia: Rickettsia monacensis (1/12), R. tamurae (8/12), and Candidatus Rickettsia jingxinensis (3/12). Three ticks (9.1%) were positive for Anaplasma phagocytophilum. In addition, three ticks (9.1%) tested positive for Babesia gibsoni (1/3) and B. microti (2/3). In conclusion, we identified three tick species; the most common species was A. testudinarium, followed by H. longicornis and I. nipponensis. SFG Rickettsia, A. phagocytophilum, and Babesia spp. were the most frequently detected pathogens in ticks removed from tick-bitten humans. To our knowledge, this is the first report of R. tamurae and Ca. R. jingxinensis detection in Korea. The present results will contribute to the understanding of tick-borne infections in animals and humans in the ROK. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Few follow-up studies have assessed antibody titers using serologic tests from various commercial laboratories and the Korea Centers for Disease Control and Prevention (KCDC).Methods: A prospective study to assess the antibody titers in patients with scrub typhus and seroprevalence in individuals undergoing health checkups was conducted using results of immunofluorescence antibody assays (IFAs) and serologic tests, used by the KCDC and commercial laboratories, respectively. The following tests were performed simultaneously: (i) indirect IFA used by the KCDC to detect immunoglobulin (Ig) M and IgG, (ii) IFA used by a commercial laboratory to detect total Ig, and (iii) antibody tests using two commercially available kits.Results: When the IgM and IgG cutoff values (≥1:16 and ≥1:256, respectively) used in the IFA and the total IgG cutoff values (≥1:40) were used in prospective follow-up investigations, the antibody positivity rates of 102 patients with scrub typhus were 44.1, 35.3, and 57.6%, respectively, within 5 days of symptom onset. Among 91 individuals who recovered from scrub typhus, the follow-up IgM, IgG, and total Ig positivity rates for 13 years were 37.4% (34/91), 22.0% (20/91), and 76.9% (70/91), respectively. Among 216 individuals undergoing health checkups, the seroprevalence of IgM was 4.2% (9/216); no seroprevalence of IgG was observed.Conclusions: IFAs used by the KCDC and the commercial laboratory and rapid commercial kits could not distinguish between patients who had recovered from scrub typhus and those who are currently infected with O. tsutsugamushi. In South Korea and other countries, where low antibody cutoff values are used, upward adjustments of cutoff values may be necessary. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS is caused by the SFTS virus, a novel phlebovirus, and is spread by ticks. Methods: A 50-year-old man was admitted to our hospital with the chief complaint of fever and was diagnosed with confirmed SFTS. An epidemiological investigation was conducted, and immunofluorescent antibody assays (IFAs) were performed to determine the role of the patient's three dogs in the transmission. PCR assays were performed using ticks that were collected with the dragging and flagging method from the patient's dogs and home. Results: PCR results were positive, and IFA confirmed an increased antibody titer. Although the reverse transcription PCR results of the three dogs were negative for SFTS virus, one dog had an elevated SFTS IFA immunoglobulin G (IgG) titer of 1:1,024. Moreover, a number of ticks were observed in the area surrounding the dog cages. Based on the findings of the patient interview, the patient was likely to have acquired SFTS by blood splash because he removed or burst ticks from the dogs with his bare hands. Although no tick bites were reported, tick transmission could not be ruled out. Studies have shown that only one in three individuals with a diagnosis of SFTS recalls a tick bite; thus, a definite exclusion of tick transmission in this case was not possible. Conclusions: The epidemiological findings of our case suggest a possible relationship between tick infestation in domestic dogs and SFTS virus transmission to humans. However, there is no direct evidence supporting this viral transmission route. Future studies are needed to further investigate a potential route of SFTS transmission by exposure to engorged tick blood or pet dogs. [ABSTRACT FROM AUTHOR]

Background: Tick-borne lymphadenopathy (TIBOLA) is an infectious disease, mainly caused by species from the spotted fever group rickettsiae and is characterized by enlarged lymph nodes following a tick bite. Among cases of TIBOLA, a case of scalp eschar and neck lymphadenopathy after tick bite (SENLAT) is diagnosed when an eschar is present on the scalp, accompanied by peripheral lymphadenopathy (LAP). Only a few cases of SENLAT caused by Bartonella henselae have been reported.Case Presentation: A 58-year-old male sought medical advice while suffering from high fever and diarrhea. Three weeks before the visit, he had been hunting a water deer, and upon bringing the deer home discovered a tick on his scalp area. Symptoms occurred one week after hunting, and a lump was palpated on the right neck area 6 days after the onset of symptoms. Physical examination upon presentation confirmed an eschar-like lesion on the right scalp area, and cervical palpation revealed that the lymph nodes on the right side were non-painful and enlarged at 2.5 × 1.5 cm. Fine needle aspiration of the enlarged lymph nodes was performed, and results of nested PCR for the Bartonella internal transcribed spacer (ITS) confirmed B. henselae as the causative agent.Conclusion: With an isolated case of SENLAT and a confirmation of B. henselae in Korea, it is pertinent to raise awareness to physicians in other Asian countries that B. henselae could be a causative agent for SENLAT. [ABSTRACT FROM AUTHOR]

This study investigated the prevalence of Orientia tsutsugamushi, Anaplasma phagocytophilum, and Leptospira interrogans in wild rodents through molecular detection using organ samples and through serological assay using blood samples of mice collected from two distinct sites in Gwangju Metropolitan City, Republic of Korea (ROK). A total of 47 wild rodents, identified as Apodemus agrarius (A. agrarius), were captured from June to August 2016. The seroprevalence of antibodies against bacterial pathogens in A. agrarius sera was analyzed; 17.4% (8/46) were identified as O. tsutsugamushi through indirect immunofluorescence assay and 2.2% (1/46) were identified as Leptospira species through passive hemagglutination assay. Using polymerase chain reaction, the spleen, kidney and blood samples were investigated for the presence of O. tsutsugamushi, A. phagocytophilum, and L. interrogans. Out of the 47 A. agrarius, 19.1% (9/47) were positive for A. phagocytophilum and 6.4% (3/47) were positive for L. interrogans, while none were positive for O. tsutsugamushi. Four out of 46 (8.7%) blood samples, six out of 45 (13.3%) spleen samples, and one out of 47 (2.1%) kidney samples were positive for A. phagocytophilum. Three out of 47 (6.4%) kidney samples were positive for L. interrogans. The sequencing results of PCR positive samples demonstrated > 99% similarity with A. phagocytophilum and L. interrogans sequences. A. phagocytophilum was mostly detected in the spleen, whereas L. interrogans was mostly detected in the kidneys. Notably, A. phagocytophilum and L. interrogans were detected in A. agrarius living in close proximity to humans in the metropolitan suburban areas. The results of this study indicate that rodent-borne bacteria may be present in wild rodents in the metropolitan suburban areas of ROK. [ABSTRACT FROM AUTHOR]

Background: This study investigated Borrelia species prevalence in ticks from vegetation, through a molecular method, in Gwangju Metropolitan City, South Korea. Methodology/Principal findings: A total of 484 ticks were collected through flagging and dragging in a suburban area of Gwangju Metropolitan City, South Korea, in 2014. These ticks were morphologically identified and subjected to nested PCR, targeting Borrelia–specific CTP synthase (pyrG), outer surface protein A (ospA) and flagellin (flaB) genes. Molecular biological species identification of Borrelia-positive ticks was conducted via 16S rRNA PCR assays. Of the 484 ticks collected, 417 (86.2%) were identified as Haemaphysalis longicornis, 42 (8.7%) as H. flava, and 25 (5.2%) as Ixodes nipponensis. All the ixodid ticks containing Borrelia species bacteria were confirmed to be I. nipponensis adults, by both morphological and molecular methods. Of the 25 I. nipponensis ticks collected, four (16%) were positive for Borrelia species, three of which were B. afzelii and one B. miyamotoi. Conclusions/Significance: Our study has shown the harboring of B. miyamotoi by I. nipponensis in South Korea. Morphological and molecular genetic analyses revealed that, in South Korea, I. nipponensis could potentially transmit B. miyamotoi to humans. [ABSTRACT FROM AUTHOR]

Candidatus Neoehrlichia mikurensis (Ca. N. mikurensis; family Anaplasmataceae) is an emerging tick-borne pathogen that causes a systemic inflammatory syndrome with thrombotic complications. We report here the first identification of Ca. N. mikurensis in organ samples from small mammals captured in southwest South Korea. Nested PCR of groEL and 16S rRNA genes was used to confirm the identity of the bacteria present, and successfully amplified fragments were sequenced. All captured animals were identified as striped field mice (Apodemus agrarius), approximately 28.6% (4/14) and 21.4% (3/14) of which were found to be PCR-positive for Ca. N. mikurensis and Anaplasma phagocytophilum, respectively. The detection of Ca. N. mikurensis in these animals represents the first evidence of this pathogen in South Korea. Carriage of this bacterium by rodents highlights the need for more detailed investigation of their role in its transmission to humans. [ABSTRACT FROM AUTHOR]

Vibrio vulnificus is a causative agent of fatal septicemia and necrotic wound infection and the pathogen infection became an important public health problem in many counties. Vibrio vulnificus causes RtxA1 toxin-induced acute cell death. We tried to identify natural products that inhibit the acute cytotoxicity of V. vulnificus using a lactate hydrogenase assay. A polyphenol pyrogallol protected HeLa cells from V. vulnificus-induced cytotoxicity. Pyrogallol also decreased the growth of V. vulnificus; this inhibitory effect was more significant during log phase than stationary phase. To further elucidate the inhibitory mechanism, pyrogallol-induced toxicity was compared between a V. vulnificus catalase-peroxidase mutant (katG−) and the isogenic wild-type MO6-24/O strains. No growth was observed for the katG− mutant in the presence of pyrogallol (50 μg/mL) even after 24 h, whereas the wild-type strain demonstrated growth recovery following a prolonged lag phase. Pyrogallol-mediated growth inhibition of the katG− mutant strain was partially rescued by exogenous catalase treatment. These results indicate that the mechanism by which pyrogallol inhibits the growth and cytotoxicity of V. vulnificus likely involves polyphenol-induced prooxidant damage. Taken together, these results suggest that pyrogallol has potential for development as a new paradigm drug to treat infectious diseases. [ABSTRACT FROM AUTHOR]

Enterobacter aerogenes is recognized as an important bacterial pathogen in hospital-acquired infections. This report describes two unusual cases of septicemia caused by E. aerogenes in immunocompetent healthcare workers. E. aerogenes was isolated from blood cultures of the two patients experiencing septicemia. The clinical isolates were initially identified as E. aerogenes using a VITEK II automated system and 16S rRNA sequence analysis, and; both isolates involved in the outbreak shared a common pulse-field gel electrophoresis pattern. The similarities between the two cases included the simultaneous development of gastroenteritis symptoms, severe sepsis and thrombocytopenia after taking intravenous injections of ketorolac tromethamine. A common source of normal saline, a 100 mL bottle, was used for diluting the analgesic in both cases. In addition to the general population, healthcare workers, especially those who are also intravenous drug abusers, should be considered subjects that could cause a transmission of Enterobacter infection. [ABSTRACT FROM AUTHOR]

Upon entering the human body, Vibrio vulnificus, a gram-negative marine bacterium, must withstand a temperature change (TC) from 25 to 37 °C. This bacterium acquires iron mainly via the vulnibactin receptor (VuuA)-mediated iron uptake system (IUS), which is under the positive control of cyclic AMP receptor protein (CRP), a global regulator responsible for catabolite repression. In this study, we examined the effect of TC on the expression of vuuA and crp, and the reciprocal relation between VuuA-mediated IUS and CRP under iron-limited conditions. Iron limitation increased vuuA expression but decreased crp expression. TC resulted in increased vuuA and crp expression. A crp or vuuA mutation reciprocally decreased vuuA or crp expression. TC could increase vuuA or crp expression even in a crp- or vuuA-mutated background. These results indicate that TC increases the expression of both vuuA and crp by facilitating metabolism under iron-limited conditions, and that CRP and VuuA-mediated IUS interact coordinately toward optimal metabolism in V. vulnificus. [ABSTRACT FROM AUTHOR]

• Hantaan virus showing geographical clustering in the Republic of Korea. • Geographical variation presenting genetic divergence of Hantaan virus. • Genetic divergence indicates the emergence of new Hantavirus strains. • High hantavirus prevalence and seasonal variation in A. agrarius captured from Jeju. Several studies on hantavirus evolution have shown that genetic reassortment plays an important role in the evolution and epidemiology of this disease. To understand the genetic epidemiology of human hantaviruses, samples from rodent reservoirs were subjected to reverse-transcription nested polymerase chain reaction (RT-N-PCR) targeting the L - and S-segments of the hantavirus genome. Positive isolates from Gwangju, Boseong-gun (Jeollanam-do Province), and Jeju Island were confirmed as Hantaan virus using DNA sequencing. Phylogenetic analysis showed that all isolates grouped together as Hantaan virus but with each region forming a distinct cluster. In addition, these three clusters were distinct from other Hantaan isolates reported in previous studies from Korea and its neighboring countries China and Russia. This suggests Hantaan viruses exhibit a considerable degree of geographical clustering, and there may be a novel Hantaan genotype in southwestern ROK. This study helps expand our knowledge regarding the emergence of new hantavirus strains and their degree of geographical variation. Hantaan virus, a pathogenic prototype hantavirus carried by Apodemus agrarius , is found throughout China, Russia, and Korea. Here, we examined the genetic diversity of hantaviruses to expand our knowledge regarding the emergence of new hantavirus strains and their degree of geographical variation. We found that hantaan viruses show a considerable degree of geographical clustering, which may allude to the development of a new genotype variant in the southwestern region of the ROK. [ABSTRACT FROM AUTHOR]

This study was undertaken to determine whether cyclic AMP (cAMP) or cAMP-receptor protein (CRP) modulates the activity of the autoinducer (AI)-2-mediated quorum sensing (QS) system in response to glucose availability in Vibrio vulnificus. A mutation in crp impaired V. vulnificus growth, decreased AI-2 production, and repressed the expression of smcR encoding the master regulator SmcR (a Vibrio harveyi LuxR homolog) of the AI-2-QS system, and these changes were prevented by in trans complementation of wild-type crp. Furthermore, glucose repressed smcR expression in the presence of CRP but not in its absence. A mutation in cyaA encoding adenylate cyclase, which is required for cAMP synthesis, also impaired V. vulnificus growth and repressed smcR expression, and these changes were recovered by in trans complementation of wild-type cyaA. These results indicate that cAMP or CRP modulates the AI-2-QS system in response to glucose availability in V. vulnificus, demonstrating the presence of a connection between catabolite repression and quorum sensing in V. vulnificus. [ABSTRACT FROM AUTHOR]

Abstract: In Vibrio vulnificus, cAMP-receptor protein (CRP) and the quorum-sensing regulator SmcR are simultaneously and cooperatively required for the metalloprotease vvpE gene expression, rather than sequentially in a regulatory cascade. However, this study shows a new temporal and functional sequence between the two factors in regulating vvpE expression. A crp mutation inhibited vvpE expression with growth impairment from early stage. In contrast, a smcR mutation inhibited vvpE expression only at the late stage with no effect on growth. A crp–smcR double mutation severely inhibited vvpE expression with growth impairment from early stage. The inhibited vvpE expression was restored only at the early stage by a crp single complementation, but not at all by a smcR complementation. These results indicate that CRP functions as an essential activator, whereas SmcR functions in the presence of CRP for full vvpE expression. [ABSTRACT FROM AUTHOR]

The non-typhoidal bacterium Salmonella enterica subspecies enterica serovar Othmarschen ( Salmonella Othmarschen) is a rare human pathogen. Abscess formation due to non-typhoidal Salmonella infections is a very rare complication in this antibiotic era. We report the first case of iliacus abscess after a short period of gastroenteritis which was caused by non-typhoidal Salmonella enterica belonging to group C1, serovar Othmarschen in a patient without any underlying conditions. A young female presented in our hospital complaining of pain in right hip joint area. She gave a history of watery diarrhea 3 days before the onset of pain. On examination the patient was ill-looking and there was tenderness in the right hip joint area. S. enterica was identified using 16S rRNA gene amplification by PCR and serotyped to be serovar Othmarschen from the pus sample of iliacus abscess. This is the first reported case of iliacus abscess due to Salmonella serover Othmarschen infection. Our case suggests that S. enterica serovar Othmarschen can cause severe focal infections associated with gastroenteritis. The literature on the rare association of Salmonella enterica and abscess formation is reviewed. [ABSTRACT FROM AUTHOR]

Reference 1 Chatterjee S. Molecular detection and identification of Culex flavivirus in mosquito species from Jeju, Republic of Korea. Shilpa Chatterjee and HyeonJe Song equally contributed to this work Correction to: Virol J (2021) 18:150 https://doi.org/10.1186/s12985-021-01618-9 Following publication of the original article [[1]], the authors realised that a few minor but necessary edits were needed to the text. [Extracted from the article]

Abstract: Recent studies have demonstrated that expression of the vvpE gene begins during the early growth phase albeit at low levels. However, we found that the traditional protease assay method that is used to measure caseinolytic activity in culture supernatants is not suitable for the measurement of extracellular VvpE that is produced at low levels during the early growth phase. By using gelatin-zymography in place of the protease assay, we could specifically detect only VvpE of several proteases produced by Vibrio vulnificus. Moreover, we could sensitively measure VvpE produced at low levels during the early growth phase, which was consistent with transcription of the vvpE gene. The extracellular production of VvpE was reduced or delayed by mutation of the pilD gene which encodes for the type IV leader peptidase/N-methyltransferase associated with the type II general secretion system; the delayed production of VvpE was recovered by in trans complementation of the wild-type pilD gene. These results indicate that VvpE begins to be produced during the early growth phase via the PilD-mediated type II general secretion system, and that the use of gelatin-zymography is recommended as a simple method for the sensitive and specific detection of VvpE production. [Copyright &y& Elsevier]

Bacterial swarming constitutes a good in vitro model for surface adherence and colonization, and is accompanied by expressions of virulence factors related to invasiveness. In this study, it was determined that Vibrio vulnificus swarming was abolished by mutation of the vvpE gene encoding a metalloprotease VvpE and this swarming defect was recovered by complementation of the vvpE gene. Expression of the vvpE gene began simultaneously with the beginning of swarming and increased along with expression of the luxS gene encoding the synthase of the precursor of quorum-sensing signal molecule autoinducer 2, and this increased vvpE expression was decreased by mutation of the luxS gene. Moreover, VvpE destroyed IgA and lactoferrins, which are responsible for mucosal immunity. These results suggest that VvpE may play important roles in the surface adherence and colonization of V. vulnificus by facilitating swarming and in the mucosal invasion of V. vulnificus by destroying IgA and lactoferrin. [ABSTRACT FROM AUTHOR]

Background Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. There have been few follow-up studies assessing antibody titers using serologic tests from various commercial labs. Methods A prospective investigation to assess antibody titers of scrub typhus patients and seroprevalence for health checkup individuals were evaluated. The antibody titers of former patients diagnosed with scrub typhus at least 1 year and a maximum of 13 years were also investigated. The following tests were performed simultaneously: (i) immunofluorescence antibody assays (IFAs) that detect immunoglobulin(Ig) M and IgG, (ii) IFA that detects total Ig by a commercial lab, (iii) antibody tests using two commercially available kits. Results In prospective analyses with cutoff values set to ≥1:16 for IgM, ≥1:256 for IgG based on the KCDC's criteria, and ≥1:40 for total Ig. The antibody positive rates of 102 confirmed scrub typhus patients were 44%, 35.3%, and 57.6%, respectively, in the first week after symptom onset. Among 91 former patients recovered, the follow-up IgM, IgG, and total Ig positivity rates were 38.5% (35/91), 22% (20/91), and 76.9% (70/91), respectively. In overall cohort of 216 health checkup subjects, 4.2% (9/216) IgM and 0% (0/216) IgG seroprevalence was observed. Conclusion The IFA from KCDC and commercial lab, and rapid commercial kits cannot differentiate between former patients recovered from scrub typhus and current scrub typhus. In Korea and other countries where low antibody cut-off titer values have been used as criteria for diagnosing and reporting scrub typhus, upward adjustments of cut-off values may be necessary. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

High incidences of haemorrhagic fever with renal syndrome (HFRS) have been reported in the southern Republic of Korea (ROK). A distinct southern genotype of Orthohantavirus hantanense (HTNV) was identified in Apodemus agrarius chejuensis on Jeju Island. However, its association with HFRS cases in southern ROK remains elusive. We investigated the potential of the southern HTNV genotype as an etiological agent of HFRS. Samples from 22 patients with HFRS and 193 small mammals were collected in the southern ROK. The clinical characteristics of patients infected with the southern HTNV genotype were analysed. Amplicon-based MinION sequencing was employed for southern HTNV from patients and rodents, facilitating subsequent analyses involving phylogenetics and genetic reassortment. High-throughput sequencing of HTNV exhibited higher coverage with a cycle of threshold value below 32, acquiring nearly whole-genome sequences from six patients with HFRS and seven A. agrarius samples. The phylogenetic pattern of patient-derived HTNV demonstrated genetic clustering with HTNV from Apodemus species on Jeju Island and the southern Korean peninsula, revealing genetic reassortment in a single clinical sample between the M and S segments. These findings imply that the southern HTNV genotype has the potential to induce HFRS in humans. The phylogenetic inference demonstrates the diverse and dynamic characteristics of the southern HTNV tripartite genomes. Therefore, this study highlights the significance of active surveillance and amplicon sequencing for detecting orthohantavirus infections. It also raises awareness and caution for physicians regarding the emergence of a southern HTNV genotype as a cause of HFRS in the ROK. [ABSTRACT FROM AUTHOR]

• The numbers of O. tsutsugamushi DNA copies in surviving and non-surviving patients were significantly different (p <0.001). • Our finding demonstrates the relationship between O. tsutsugamushi DNA copy load and fatality in patients with scrub typhus. • Our study demonstrated that the disease severity was associated with the genotypes and bacterial load in patients infected with O. tsutsugamushi. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi and is endemic to many parts of the Asia-Pacific region. We investigated whether the genotype of O. tsutsugamushi or the DNA load would be a useful marker of disease severity in scrub typhus patients. We evaluated the clinical features, genotypes and bacterial DNA load in the blood of 118 patients, including 114 surviving and 4 non-surviving patients, admitted at Chosun University Hospital. Four patients infected with the Pajoo, Yonchon, Youngworl and Boryong genotypes died. In the 114 survivors, 100 Boryong and 2 Taguchi genotypes were identified. The genotypes involved showed significant differences between the surviving and non-surviving patients (p <0.001). The median number of O. tsutsugamushi DNA copies was 78 copies /μL (range 3,960) in surviving patients, whereas 83,800 copies/μL (range 244,600) in the non-surviving patients. We found that the genotype and DNA load in the patient's blood are useful markers of disease severity in scrub typhus. [ABSTRACT FROM AUTHOR]

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset. [ABSTRACT FROM AUTHOR]

Examines Vibro vulnificus strains that have either opaque or translucent colonies, focusing on microbiology. Methodology used in the examination; Results from the examination; Relationship of metaphotypes with physiological properties.

Background: Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum, an obligate intracellular granulocytotropic bacterium.Case Presentation: A 70-year-old female patient was admitted with the clinical signs of fever and an altered state of consciousness 1 week after experiencing a tick bite while planting lawn grass. Magnetic resonance imaging, performed at the time of admission, indicated cerebral infarction in the left basal ganglia, whereas increasing immunofluorescence assay antibody titers for A. phagocytophilum were also documented. A. phagocytophilum was identified using groEL and ankA targeted polymerase chain reaction and sequencing. Because of severe thrombocytopenia, only doxycycline was administered, without any antiplatelet agents. Subsequently, the symptoms improved without any focal neurologic sequela.Conclusion: This is the first reported case of cerebral infarction occurrence in an anaplasmosis patient. [ABSTRACT FROM AUTHOR]

Background: Severe fever thrombocytopenia syndrome virus (SFTSV) is the causative agent of severe fever thrombocytopenia syndrome (SFTS). SFTS is an emerging infectious disease, characterized by high fever, gastrointestinal symptoms, leukopenia, thrombocytopenia, and a high mortality rate. Until now, little importance has been given to the association of SFTS with leukocytosis and bacterial co-infection.Case Presentation: A 51-year old man visited our hospital with fever and low blood pressure. He was a farmer by occupation and often worked outdoors. He had a Foley catheter inserted due to severe BPH. Laboratory tests revealed thrombocytopenia, elevated liver function, and elevated CRP levels. He had marked leukocytosis, proteinuria, hematuria, and conjunctival hemorrhage. Initially, we thought that the patient was suffering from hemorrhagic fever with renal syndrome (HFRS). However, we confirmed SFTS through PCR and increasing antibody titer. However, his blood culture also indicated E. coli infection.Conclusion: SFTS displays characteristics of fever, thrombocytopenia, elevated liver function, and leukocytopenia. We described a case of SFTS with leukocytosis due to coinfection with E. coli. Since patients with SFTS usually have leukocytopenia, SFTS patients with leukocytosis are necessarily evaluated for other causes of leukocytosis. Here, we report the first case of an SFTS with concurrent E. coli bacteremia. [ABSTRACT FROM AUTHOR]

Background: Anaplasmosis is an emerging acute febrile disease that is caused by a bite of an Anaplasma phagocytophilum-infected hard tick. As for healthy patients, reports on asymptomatic anaplasmosis resulting from such tick bites are rare.Case Presentation: A 55-year-old female patient visited the hospital with a tick bite in the right infraclavicular region. The tick was suspected to have been on the patient for more than 10 days. PCR and an indirect immunofluorescence assay (IFA) were performed to identify tick-borne infectious diseases. The blood sample collected at admission yielded a positive result in nested PCR targeting Ehrlichia- or Anaplasma-specific genes groEL and ankA. Subsequent sequencing confirmed the presence of A. phagocytophilum, and seroconversion was confirmed by the IFA involving an A. phagocytophilum antigen slide. PCR detected no Rickettsia-specific genes [outer membrane protein A (ompA) or surface cell antigen 1 (sca1)], but seroconversion of spotted fever group (SFG) rickettsiosis was confirmed by an IFA.Conclusions: This study genetically and serologically confirmed an asymptomatic A. phagocytophilum infection. Although SFG rickettsiosis was not detected genetically, it was detected serologically. These findings indicate the possibility of an asymptomatic coinfection: anaplasmosis plus SFG rickettsiosis. It is, therefore, crucial for clinicians to be aware of potential asymptomatic anaplasmosis following a tick bite. [ABSTRACT FROM AUTHOR]

Many pathogens causing hemorrhagic fevers of medical and veterinary importance have been identified and isolated from rodents in the Republic of Korea (ROK). We investigated the occurrence of emerging viruses causing hemorrhagic fevers, such as hemorrhagic fever with renal syndrome (HFRS), severe fever with thrombocytopenia syndrome (SFTS), and flaviviruses, from wild rodents. Striped field mice, Apodemus agrarius (n = 39), were captured during 2014–2015 in the south-west of ROK. Using molecular methods, lung samples were evaluated for SFTS virus, hantavirus, and flavivirus, and seropositivity was evaluated in the blood. A high positive rate of hantavirus (46.2%) was detected in A. agrarius lungs by reverse transcription-nested polymerase chain reaction (RT-N-PCR). The monthly occurrence of hantavirus was 16.7% in October, 86.7% in November, and 25% in August of the following year (p < 0.001). Moreover, 17.9% of blood samples were serologically positive for hantavirus antibodies. The most prevalent strain in A. agrarius was Hantaan virus. All samples were positive for neither SFTS virus nor flavivirus. Hantaan virus was detected in 86.7% of A. agrarius in November (autumn), and thus, virus shedding from A. agrarius can increase the risk of humans contracting HFRS. These findings may help to predict and prevent disease outbreaks in ROK. [ABSTRACT FROM AUTHOR]

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0–4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949–0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases. [ABSTRACT FROM AUTHOR]

The clinical characteristics and the effect of viral RNA loads on fatality in 56 patients with severe fever with thrombocytopenia syndrome (SFTS) were analyzed. The non-survival group (12 patients) demonstrated a significantly higher mean age (77 years) than the survival group (44 patients, 65 years) (p = 0.003). The survival rates were 91.7% and 8.3% in patients with Ct values ≥30 and differed significantly (p = 0.001) in the survival and non-survival groups, respectively. The survival rates were 52.4% and 47.6% in patients with viral copy numbers ≥10,000 and 94.3% and 5.7% in patients with viral copy numbers <10,000 in the survival and non-survival groups, respectively (p = 0.001). In a multivariate analysis, viral copy numbers and initial Acute Psychologic Assessment and Chronic Health Evaluation II (APACHE II) scores were identified as the factors affecting fatality (p = 0.015 and 0.011, respectively). SFTS viral RNA loads can be useful markers for the clinical prediction of mortality and survival. [ABSTRACT FROM AUTHOR]

Background: Rickettsial diseases associated with the spotted fever group constitute a growing number of newly identified Rickettsia pathogens and their tick vectors in various parts of the world. At least 15 distinct tick species belonging to six genera have shown the presence of Rickettsia raoultii. Herein, we report the detection of R. raoultii in ticks from the Republic of Korea (ROK). Methods: Thirty-five ticks were collected from 29 patients with tick bites in Gwangju Metropolitan City, Jeollanam Province, ROK. The ticks were identified using molecular, morphological, and taxonomic characteristics. All samples were screened for presence of Rickettsia species using nested polymerase chain reactions of their outer membrane protein (ompA) and citrate synthase (gltA) genes. The amplified products were sequenced for subsequent phylogenetic analyses. Results: Sequencing data showed the DNA sequences of R. raoultii in three Haemaphysalis longicornis ticks. All three tick samples were 99.4–100% similar to previously reported partial sequences of ompA of R. raoultii strains CP019435 and MF002523, which formed a single clade with the reference strains. Conclusions: We provide the first description and molecular identification of R. raoultii detected in H. longicornis ticks in the ROK. This observation extends the geographical distribution of R. raoultii. Screening of human samples for this pathogen will provide information about the prevalence of rickettsial infections in this region. [ABSTRACT FROM AUTHOR]

Background: Rickettsial diseases associated with the spotted fever group constitute a growing number of newly identified Rickettsia pathogens and their tick vectors in various parts of the world. At least 15 distinct tick species belonging to six genera have shown the presence of Rickettsia raoultii. Herein, we report the detection of R. raoultii in ticks from the Republic of Korea (ROK). Methods: Thirty-five ticks were collected from 29 patients with tick bites in Gwangju Metropolitan City, Jeollanam Province, ROK. The ticks were identified using molecular, morphological, and taxonomic characteristics. All samples were screened for presence of Rickettsia species using nested polymerase chain reactions of their outer membrane protein (ompA) and citrate synthase (gltA) genes. The amplified products were sequenced for subsequent phylogenetic analyses. Results: Sequencing data showed the DNA sequences of R. raoultii in three Haemaphysalis longicornis ticks. All three tick samples were 99.4–100% similar to previously reported partial sequences of ompA of R. raoultii strains CP019435 and MF002523, which formed a single clade with the reference strains. Conclusions: We provide the first description and molecular identification of R. raoultii detected in H. longicornis ticks in the ROK. This observation extends the geographical distribution of R. raoultii. Screening of human samples for this pathogen will provide information about the prevalence of rickettsial infections in this region. [ABSTRACT FROM AUTHOR]

Background Scrub typhus, anaplasmosis, and leptospirosis are well-known diseases that are considered common, widespread rodent-borne infectious diseases Methods This study investigated the prevalence of Orientia tsutsugamushi , Anaplasma phagocytophilum , and Leptospira interrogans in wild rodents through molecular detection using organ samples and through serological assay using blood samples of mice collected from two distinct sites in Gwangju Metropolitan City, Republic of Korea (ROK). Results A total of 47 wild rodents, identified as Apodemus agrarius (A. agrarius), were captured from June to August 2016. The seroprevalence of antibodies against bacterial pathogens in A. agrarius sera was analyzed; 17.4% (8/46) were identified as O. tsutsugamushi through indirect immunofluorescence assay and 2.2% (1/46) were identified as Leptospira species through passive hemagglutination assay. Using polymerase chain reaction, the spleen, kidney and blood samples were investigated for the presence of O. tsutsugamushi, A. phagocytophilum , and L. interrogans. Out of the 47 A. agrarius , 19.1% (9/47) were positive for A. phagocytophilum and 6.4% (3/47) were positive for L. interrogans , while none were positive for O. tsutsugamushi. Four out of 46 (8.7%) blood samples, six out of 45 (13.3%) spleen samples, and one out of 47 (2.1%) kidney samples were positive for A. phagocytophilum. Three out of 47 (6.4%) kidney samples were positive for L. interrogans. The sequencing results of PCR positive samples demonstrated >99% similarity with A. phagocytophilum and L. interrogans sequences Conclusion A. phagocytophilum was mostly detected in the spleen, whereas L. interrogans was mostly detected in the kidneys. Notably, A. phagocytophilum and L. interrogans were detected in A. agrarius living in close proximity to humans in the metropolitan suburbans. The results of this study indicate that rodent-borne bacteria may be present in wild rodents in the metropolitan suburban areas of ROK Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Abstract: Vibrio vulnificus, a halophilic estuarine bacterium, causes a fatal septicemia and necrotizing wound infection. To investigate the role of cAMP in V. vulnificus virulence regulation, an in-frame deletion mutant of the cya gene encoding adenylate cyclase was constructed. The cya null mutation resulted in a pleiotropic change of virulence phenotypes. The production of hemolysin and protease, the motility, and the cytotoxicity were decreased by the cya mutation. The defects in the cya mutant were functionally complemented in trans by a plasmid carrying the wild type cya allele. The V. vulnificus cya mutant exhibited a 100-fold increase in LD50 to mice. The result indicates that cAMP plays an essential role in the global regulation of V. vulnificus virulence. [Copyright &y& Elsevier]

To date, only a few studies have analyzed the clinical characteristics and genetic features of human granulocytic anaplasmosis (HGA) in South Korea. Thus, in this study, we investigated the clinical characteristics of HGA and methods used for clinical diagnosis. The clinical characteristics of patients with HGA were studied retrospectively. We reviewed the medical charts of 21 confirmed patients with HGA admitted to the Chosun University Hospital, located in Gwangju, South Korea. Twenty-one HGA patients visited the hospital 2–30 days (median 7 days) after the onset of symptoms. Fourteen patients (66.7%) had fever, which was alleviated 2 h (range 0–12.75 h) after starting treatment with doxycycline. Of the 18 patients who underwent peripheral blood (PB) smear test, only one (5.6%) had morulae. Additionally, only 4/17 patients (23.5%) had morulae in the PB smear reconducted after the confirmation of anaplasmosis. All 21 patients recovered without significant complications. As per results of the blood tests conducted at the time of admission, 7/21 (33.3%) and 5/21 (23.8%) patients showed at least 1:16 and 1:80 of IgM and IgG titers, respectively. Most HGA patients in Korea recovered without significant complications. The indirect immunofluorescence antibody diagnosis or morulae identification for HGA in this study had low sensitivity in the early stage of the disease. [ABSTRACT FROM AUTHOR]

Background: Rickettsial diseases associated with the spotted fever group constitute a growing number of newly identified Rickettsia pathogens and their tick vectors in various parts of the world. At least 15 distinct tick species belonging to six genera have shown the presence of Rickettsia raoultii. Herein, we report the detection of R. raoultii in ticks from the Republic of Korea (ROK). Methods: Thirty-five ticks were collected from 29 patients with tick bites in Gwangju Metropolitan City, Jeollanam Province, ROK. The ticks were identified using molecular, morphological, and taxonomic characteristics. All samples were screened for presence of Rickettsia species using nested polymerase chain reactions of their outer membrane protein (ompA) and citrate synthase (gltA) genes. The amplified products were sequenced for subsequent phylogenetic analyses. Results: Sequencing data showed the DNA sequences of R. raoultii in three Haemaphysalis longicornis ticks. All three tick samples were 99.4–100% similar to previously reported partial sequences of ompA of R. raoultii strains CP019435 and MF002523, which formed a single clade with the reference strains. Conclusions: We provide the first description and molecular identification of R. raoultii detected in H. longicornis ticks in the ROK. This observation extends the geographical distribution of R. raoultii. Screening of human samples for this pathogen will provide information about the prevalence of rickettsial infections in this region. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. Methods: A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. Results: Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P <.001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70–30.73] vs. 24.9 (95% CI 21.21–28.53], P =.022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P =.005). Conclusions: After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14). Author summary: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. In patients with SFTS, steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14). [ABSTRACT FROM AUTHOR]

Background: Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum. To date, there have been no reported cases of A. phagocytophilum infection found in both the biting tick and the patient following a tick bite.Case Presentation: An 81-year-old woman presented with fever following a tick bite, with the tick still intact on her body. The patient was diagnosed with HGA. The tick was identified as Ixodes nipponensis by morphological and molecular biological detection methods targeting the 16S rRNA gene. The patient's blood was cultured after inoculation into the human promyelocytic leukemia cell line HL-60. A. phagocytophilum growth was confirmed via culture and isolation. A. phagocytophilum was identified in both the tick and the patient's blood by Anaplasma-specific groEL- and ankA-based nested polymerase chain reaction followed by sequencing. Moreover, a four-fold elevation in antibodies was observed in the patient's blood.Conclusion: We report a case of a patient diagnosed with HGA following admission for fever due to a tick bite. A. phagocytophilum was identified in both the tick and the patient, and A. phagocytophilum was successfully cultured. The present study suggests the need to investigate the possible incrimination of I. nipponensis as a vector for HGA in Korea. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is an acute disease, characterized by symptoms of fever, which occurs due to infection by Orientia tsutsugamushi. In most cases, patients recover from the disease with appropriate treatment, but serious and fatal complications may occur. The present study examined laboratory findings and tumor necrosis factor-alpha (TNF-α) levels of scrub typhus patients to identify the prognostic predictors of disease severity.Method: Patients whose scrub typhus diagnosis was confirmed by elevated indirect fluorescent antibody (IFA) levels and positive polymerase chain reaction (PCR) results were classified according to disease severity into one of three groups; i.e., deceased (n = 7), severe (n = 15), and mild (n = 15) retrospectively registered. Additionally, the usefulness of modified Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein (CRP) level, white blood cell (WBC) count, and TNF-α level as prognostic predictors were examined.Result: The mean TNF-α levels of the deceased, severe, and mild groups were 53.5 (range: 7.8-147.8), 26.0 (1.7-64.4), and 8.8 pg/mL (4.6-16.0), respectively. The results of Kruskal-Wallis tests showed statistically significant differences between the deceased and severe groups versus the mild group (p = 0.005). CRP level and Modified APACHE II score also differed significantly among the groups (p = 0.046 and 0.007, respectively); however, WBC count did not (p = 0.196).Conclusion: An elevated serum TNF-α level in patients with scrub typhus could predict a severe condition or death and may be useful in predicting patient prognosis. [ABSTRACT FROM AUTHOR]

Background Doxycycline is currently the most frequently used treatment in patients with scrub typhus. However, doxycycline-resistant strains have been found, necessitating the development of a new treatment. Rifampin is known to be effective even for such strains. Our aim in this study was to compare the effects of rifampin and doxycycline treatment in patients with scrub typhus in areas in which resistance to doxycycline has not been reported. Methods Patients admitted to Chosun University Hospital and regional network hospitals between 2007 and 2009 with a body temperature ≥37.5°C and suspected to have scrub typhus were randomly assigned to 1 of 2 treatment groups: a group administered doxycycline 100 mg twice daily for 5 days and a group administered rifampin 600 mg once daily for 5 days. For treatment outcomes, fever, headache, muscle ache, and rash clearance times were compared between the groups. Results The rifampin and doxycycline groups showed equivalence in all treatment outcomes evaluated. The proportions of patients with fever clearance within 48 hours were similar between groups. Furthermore, there was no significant difference in the occurrence of side effects following drug administration between groups. Conclusions On the basis of the finding that equivalent treatment effects and safety were found in patient groups that received 600 mg of rifampin and 200 mg of doxycycline, respectively, for 5 days to treat scrub typhus, rifampin may be considered an alternative treatment to doxycycline. Clinical Trials Registration NCT00568711. [ABSTRACT FROM AUTHOR]

Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal. [ABSTRACT FROM AUTHOR]

Background: Scedosporium apiospermum, which can usually be isolated from soil, polluted stream water and decaying vegetation, is increasingly recognized as an opportunistic dematiaceous fungus. The mortality rate of infection in immunocompromised hosts is over 50%. S. apiospermum is commonly responsible for dermal and epidermal infections (i.e., mycetoma) after traumatic penetration.Case Presentation: A 73-year-old woman was admitted to our hospital complaining of painful swelling and tenderness on the dorsum of the proximal left wrist and hand. The symptoms had persisted for approximately 2 months. A physical examination revealed a 4 x 3 cm, poorly defined, erythematous papule, which was fluctuant, with pustules and crusts on the dorsum of the left hand.Conclusions: We report a very rare case of tenosynovitis caused by S. apiospermum infection. We identified the infectious agent via molecular DNA sequencing. The infectious agent was initially misidentified as an Alternaria species by microscopic examination with lactophenol cotton blue (LPCB) staining. The infection was successfully treated with debridement and adjuvant fluconazole therapy. [ABSTRACT FROM AUTHOR]