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This study investigated the infectivity of severe acute respiratory syndrome (SARS-CoV-2) in individuals who re-tested positive for SARS-CoV-2 RNA after recovering from their primary illness. We investigated 295 individuals with re-positive SARS-CoV-2 polymerase chain reaction (PCR) test results and 836 of their close contacts. We attempted virus isolation in individuals with re-positive SARS-CoV-2 PCR test results using cell culture and confirmed the presence of neutralizing antibodies using serological tests. Viral culture was negative in all 108 individuals with re-positive SARS-CoV-2 PCR test results in whom viral culture was performed. Three new cases of SARS-CoV-2 infection were identified among household contacts using PCR. Two of the three new cases had had contact with the index patient during their primary illness, and all three had antibody evidence of past infection. Thus, there was no laboratory evidence of viral shedding and no epidemiological evidence of transmission among individuals with re-positive SARS-CoV-2 PCR test results.

Objectives Chigger mites are vectors for scrub typhus. This study evaluated the annual fluctuations in chigger mite populations and Orientia tsutsugamushi infections in South Korea. Methods During 2006 and 2007, chigger mites were collected monthly from wild rodents in 4 scrub typhus endemic regions of South Korea. The chigger mites were classified based on morphological characteristics, and analyzed using nested PCR for the detection of Orientia tsutsugamushi. Results During the surveillance period, the overall trapping rate for wild rodents was 10.8%. In total, 17,457 chigger mites (representing 5 genera and 15 species) were collected, and the average chigger index (representing the number of chigger mites per rodent), was 31.7. The monthly chigger index was consistently high (> 30) in Spring (March to April) and Autumn (October to November). The mite species included Leptotrombidium pallidum (43.5%), L. orientale (18.9%), L. scutellare (18.1%), L. palpale (10.6%), and L. zetum (3.6%). L. scutellare and L. palpale populations, were relatively higher in Autumn. Monthly O. tsutsugamushi infection rates in wild rodents (average: 4.8%) and chigger mites (average: 0.7%) peaked in Spring and Autumn. Conclusion The findings demonstrated a bimodal pattern of the incidence of O. tsutsugamushi infections. Higher infection rates were observed in both wild rodents and chigger mites, in Spring and Autumn. However, this did not reflect the unimodal incidence of scrub typhus in Autumn. Further studies are needed to identify factors, such as human behavior and harvesting in Autumn that may explain this discordance.

A 56-year-old female goat herder had scrub typhus that persisted after receiving doxycycline for 5 days. Her symptoms continued, prompting us to perform further examinations that revealed coinfection of Q fever and scrub typhus via molecular and serological testing. We also isolated Orientia tsutsugamushi using BALB/c mice and L929 cells.

Scrub typhus is caused by the arthropod-borne bacterium Orientia tsutsugamushi and is an endemic infectious disease in the Asia-Pacific area. This study aimed to investigate the seroprevalence of scrub typhus and identify associated risk and protective factors among forestry workers, a neglected risk group for scrub typhus, in National Park Offices in South Korea. A nationwide cross-sectional serosurvey was carried out on 1945 National Park Office forestry workers (NPOFWs) in South Korea during December 2016. We visited 29 main offices and used a structured questionnaire to collect data regarding general characteristics, work activities, work hygiene-related factors, and other potential risk factors. Serum samples from NPOFWs were tested using indirect immunofluorescence assay to detect O. tsutsugamushi immunoglobulin (Ig) G and M antibodies. Of the 1945 NPOFWs, 718 (36.9%) participated in this cross-sectional study. The seroprevalence, defined as ≥1:256 for IgG and/or ≥1:16 for IgM, was 4.9% (35/718). In multivariate logistic analysis, longer duration of work in national parks (≥15 years, odds ratio (OR), 4.19, 95% confidence interval (CI), 1.71–10.28) and dry field farming (OR, 2.47, 95% CI, 1.12–5.46) were significantly associated with a higher risk of scrub typhus infection. Furthermore, the risk of scrub typhus infection was significantly lower among NPOFWs who washed working clothes daily (OR, 0.37, 95% CI, 0.18–0.75). This study indicated that scrub typhus is an important disease among NPOFWs in South Korea. Work hygiene, especially washing working clothes daily, needs to be emphasized among NPOFWs. Additionally, more precautions are required to diminish the rate of scrub typhus infection among NPOFWs who perform dry field farming.

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.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with

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.

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.

Scrub typhus, caused by infection with Orientia tsutsugamushi, is a mite-borne zoonotic disease endemic to the Asian-Pacific region. In Korea, the incidence of this disease has increased with climate changes, and over 10,000 cases of infection were reported in 2013. Although this infection is treatable with antibiotics such as doxycycline and azithromycin, an effective prophylactic vaccine against O. tsutsugamushi would be more desirable for preventing scrub typhus in endemic areas. In this study, we investigated the 56-kDa type-specific antigen (TSA56), which is a major outer membrane protein of O. tsutsugamushi, as a vaccine candidate. Intranasal immunization of recombinant TSA56 (rec56) induced a higher level of TSA56- specific IgG than that induced by intramuscular immunization of tsa56-expressing DNA (p56). Both types of immunization induced a cell-mediated immune response to TSA56, as demonstrated by the splenic cell proliferation assay. Mice immunized with p56, followed by rec56 plus heat-labile enterotoxin B subunit from E. coli, had a stronger protection from a homologous challenge with the O. tsutsugamushi Boryong strain than with other combinations. Our preliminary results suggest that an effective human vaccine for scrub typhus can include either recombinant TSA56 protein or tsa56-expressing DNA, and provide the basis for further studies to optimize vaccine performance using additional antigens or different adjuvants.

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., Author Summary Scrub typhus is an acute febrile illness caused by attacks of Orientia tsutsugamushi-carrying mites, and is the most prevalent febrile illness in the Asia-Pacific region. If not properly treated with antibiotics, patients often develop severe vasculitis that affects multiple organs, and the mortality rate can reach 30%. To explore the pathogenic mechanisms underlying the host-pathogen interaction, we characterized metabolic changes in various organs and the serum of O. tsutsugamushi-infected hosts. After O. tsutsugamushi infection, the host experienced decreased energy production, as well as a severe deficiency in re-methylation sources and glutathione, which impaired purine synthesis, DNA and protein methylation. In addition, abnormal pathways for phosphatidylcholine (PC) biosynthesis and phosphoethanolamine methylation were utilized in the enlarged spleen of O. tsutsugamushi-infected hosts. These results suggested that metabolic profiling could provide insight into global metabolic changes in O. tsutsugamushi-infected hosts, and increase our understanding of the pathogenic mechanisms of O. tsutsugamushi, as well as providing novel therapeutic targets for scrub typhus.