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ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen causing subclinical and clinical bovine mastitis. This study examined the molecular properties, biofilm formation, virulence genes, and antimicrobial susceptibility of MRSA isolates from mastitis-infected dairy cow milk in South Korea. Whole-genome sequencing of an ST22-SCCmec IV MRSA strain positive for Panton–Valentine leukocidin (PVL) and toxic shock syndrome toxin-1 (TSST-1) was also performed. Of the 488 S. aureus isolates, 30 (6.1%) were identified as MRSA, harboring the mecA gene. MRSA exhibited the highest resistance to kanamycin (66.7%) among non-beta-lactam antibiotics. Multidrug resistance was observed in 83.3% of MRSA isolates. All MRSA strains had the capacity to form biofilm and harbored biofilm-related genes. The primary virulence genes included hla, hlb, lukED, seg, sei, sem, sen, and seo. The ST72-t324-SCCmec IV genotype was the most prevalent. Of note, three ST22-SCCmec IV isolates were positive for PVL and TSST-1. Our findings suggest that the majority of MRSA isolates from milk obtained from dairy cows with mastitis are multidrug-resistant, capable of forming robust biofilms, and harbor multiple virulence genes. The presence of PVL- and TSST-1-positive ST22-SCCmec IV isolates in mastitis-infected bovine milk highlights the need for persistent monitoring to mitigate possible public health risks.IMPORTANCEThis study reports on the presence and characteristics of methicillin-resistant Staphylococcus aureus strains in milk from mastitis-infected cows. To our knowledge, this is the first report of a Panton–Valentine leukocidin- and toxic shock syndrome toxin-1-positive ST22-SCCmec IV strain in South Korea.

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

Objectives: Changes in the epidemiology of group A streptococcus (GAS) infection is related to emm genotype. We studied the distribution of emm genotypes and their antibiotic susceptibility among Korean children. Methods: Isolates from children with GAS infection between 2012 and 2019 were collected. emm typing and cluster analysis was performed according to the Centers for Disease Control emm cluster classification. Antimicrobial susceptibility was tested using the E-test and resistance genes were analyzed for macrolide resistant phenotypes. Results: Among 169 GAS isolates, 115 were from children with scarlet fever. Among invasive isolates, emm1 (6/22, 27.3%), emm12 (4/22, 18.2%), and emm4 (4/22, 18.2%) were most common. In scarlet fever, although emm4 (38/115, 33.0%) was the most prevalent throughout the study period, emm4 was replaced by emm3 (28/90, 31.1%) during an outbreak in 2017–2018. Among all isolates, only 2 (1.2%) exhibited erythromycin resistance and harbored both ermA and ermB genes. Conclusions: In this analysis of GAS isolated from Korean children, emm1 was the most prevalent in invasive infection. In scarlet fever, emm4 was prevalent throughout the study period, with an increase in emm3 during 2017–2018. GAS isolates during 2012–2019 demonstrated low erythromycin resistance.

Abstract Virus-like particles (VLPs) are recognized as an alternative vaccine platform that provide effective protection against various highly pathogenic avian influenza viruses (HPAIVs). Here, we developed multi-clade VLPs expressing two HAs (a chimera of clade 2.3.2.1c and clade 2.3.4.4c HA) within a single vector. We then compared its protective efficacy with that of a monovalent VLP and evaluated its potency against each homologous strain. Chickens vaccinated with the multi-clade VLP shed less virus and were better protected against challenge than birds receiving monovalent vaccines. Single vaccination with a multi-clade VLP resulted in 100% survival, with no clinical symptoms and high levels of pre-challenge protective immunity (7.6–8.5 log2). Moreover, the multi-clade VLP showed high productivity (128–256 HAU) both in the laboratory and on a large scale, making it cheaper than whole inactivated vaccines produced in eggs. However, the PD50 (protective dose 50%) of the multi-clade VLP against clades 2.3.2.1c and 2.3.4.4c was

Prior to the identification of low pathogenic avian influenza H9N2 viruses belonging to the Y280 lineage in 2020, Y439 lineage viruses had been circulating in the Republic of Korea since 1996. Here, we developed a whole inactivated vaccine (vac564) by multiple passage of Y439 lineage viruses and then evaluated immunogenicity and protective efficacy in specific-pathogen-free chickens. We found that LBM564 could be produced at high yield in eggs (108.4EID50/0.1 mL; 1024 hemagglutinin units) and was immunogenic (8.0 ± 1.2 log2) in chickens. The vaccine showed 100% inhibition of virus in the cecal tonsil with no viral shedding detected in either oropharyngeal or cloacal swabs after challenge with homologous virus. However, it did not induce effective protection against challenge with heterologous virus. An imported commercial G1 lineage vaccine inhibited viral replication against Y280 and Y439 lineage viruses in major tissues, although viral shedding in oropharyngeal and cloacal swabs was observed up until 5 dpi after exposure to both challenge viruses. These results suggest that a single vaccination with vac564 could elicit immune responses, showing it to be capable of protecting chickens against the Y439 lineage virus. Thus, our results suggest the need to prepare suitable vaccines for use against newly emerging and re-emerging H9N2 viruses.

Since 2018, Korea has been building an avian influenza (AI) national antigen bank for emergency preparedness; this antigen bank is updated every 2 years. To update the vaccine strains in the antigen bank, we used reverse genetics technology to develop two vaccine candidates against avian influenza strains belonging to clades 2.3.2.1d and 2.3.4.4h, and then evaluated their immunogenicity and protective efficacy in SPF chickens challenged with H5 viruses. The two vaccine candidates, named rgCA2/2.3.2.1d and rgES3/2.3.4.4h, were highly immunogenic, with hemagglutination inhibition (HI) titers of 8.2–9.3 log2 against the vaccine strain, and 7.1–7.3 log2 against the lethal challenge viruses (in which the HA genes shared 97% and 95.4% homology with that of rgCA2/2.3.2.1d and rgES3/2.3.4.4h, respectively). A full dose of each vaccine candidate provided 100% protection against the challenge viruses, with a reduction in clinical symptoms and virus shedding. A 1/10 dose provided similar levels of protection, whereas a 1/100 dose resulted in mortality and virus shedding by 7 dpi. Moreover, immunity induced by the two vaccines was long lasting, with HI titers of >7 log2 against the vaccine strain remaining after 6 months. Thus, the two vaccine candidates show protective efficacy and can be used to update the AI national antigen bank.

For the development of an optimized Egyptian H9N2 vaccine candidate virus for poultry, various recombinant Egyptian H9N2 viruses generated by a PR8-based reverse genetics system were compared in terms of their productivity and biosafety since Egyptian H9N2 avian influenza viruses already possess mammalian pathogenicity-related mutations in the hemagglutinin (HA), neuraminidase (NA), and PB2 genes. The Egyptian HA and NA genes were more compatible with PR8 than with H9N2 AIV (01310) internal genes, and the 01310-derived recombinant H9N2 strains acquired the L226Q reverse mutation in HA after passages in eggs. Additionally, the introduction of a strong promoter at the 3′-ends of PB2 and PB1 genes induced an additional mutation of P221S. When recombinant Egyptian H9N2 viruses with intact or reverse mutated HA (L226Q and P221S) and NA (prototypic 2SBS) were compared, the virus with HA and NA mutations had high productivity in ECES but was lower in antigenicity when used as an inactivated vaccine due to its high binding affinity into non-specific inhibitors in eggs. Finally, we substituted the PB2 gene of PR8 with 01310 to remove the replication ability in mammalian hosts and successfully generated the best recombinant vaccine candidate in terms of immunogenicity, antigenicity, and biosafety.

PurposeThis study aimed to analyse laboratory values according to fever duration, and evaluate the relationship across these values during the acute phase of Kawasaki disease (KD) to aid in the early diagnosis for early-presenting KD and incomplete KD patients.MethodsClinical and laboratory data of patients with KD (n=615) were evaluated according to duration of fever at presentation, and were compared between patients with and without coronary artery lesions (CALs). For evaluation of the relationships across laboratory indices, patients with a fever duration of 5 days or 6 days were used (n=204).ResultsThe mean fever duration was 6.6±2.3 days, and the proportions of patients with CALs was 19.3% (n=114). C-reactive proteins (CRPs) and neutrophil differential values were highest and hemoglobin, albumin, and lymphocyte differential values were lowest in the 6-day group. Patients with CALs had longer total fever duration, higher CRP and neutrophil differential values and lower hemoglobin and albumin values compared to patients without CALs. CRP, albumin, neutrophil differential, and hemoglobin values at the peak inflammation stage of KD showed positive or negative correlations each other.ConclusionThe severity of systemic inflammation in KD was reflected in the laboratory values including CRP, neutrophil differential, albumin, and hemoglobin. Observing changes in these laboratory parameters by repeated examinations prior to the peak of inflammation in acute KD may aid in diagnosis of early-presenting KD patients.

Purpose This study aimed to evaluate the relationships between 99mTecnicium-dimercaptosuccinic acid (DMSA) scan findings and clinical parameters including age and fever duration. Methods The positive rates for abnormal DMSA scans were analyzed according to the age of patients, fever duration prior to admission, and total fever duration. DMSA scan findings were divided into 3 categories: single defect, multifocal defects, and discrepant defects. We evaluated the detection rates of vesicoureteral reflux according to DMSA scan lesions. Results Among a total 320 cases, 141 (44.1%) had abnormal DMSA scans. The infant group (0-1 year of age) had a shorter total fever duration, and a lower C-reactive protein (CRP) value and DMSA positive rate (39.8% vs. 60.6%, P=0.002) compared to children group (2-15 years of age). Patients with abnormal scans had a longer total fever duration and higher CRP compared to those with normal scans. The positivity rate of abnormal scans did not differ between the patients with a short fever duration prior to admission of ≤2 days and those with longer fever duration of ≥3 days. However, patients with longer total fever duration had a higher rate of abnormal DMSA scans (P=0.02). Among cases with a single defect, multifocal defects, and discrepant defects, vesicoureteral reflux was observed in 22.4%, 60% and 70.6% of cases, respectively (P=0.004). Conclusion Although DMSA scan has limitations in early diagnosis, DMSA scan findings may aid in the prediction of the severity of systemic inflammation and detection of vesicoureteral reflux.

In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus.

An outbreak of highly pathogenic avian influenza, caused by a novel reassortant influenza A (H5N8) virus, occurred among poultry and wild birds in South Korea in 2014. The aim of this study was to evaluate the pathogenesis in and mode of transmission of this virus among domestic and wild ducks. Three of the viruses had similar pathogenicity among infected domestic ducks: the H5N8 viruses were moderately pathogenic (0%–20% mortality rate); in wild mallard ducks, the H5N8 and H5N1 viruses did not cause severe illness or death; viral replication and shedding were greater in H5N8-infected mallards than in H5N1-infected mallards. Identification of H5N8 viruses in birds exposed to infected domestic ducks and mallards indicated that the viruses could spread by contact. We propose active surveillance to support prevention of the spread of this virus among wild birds and poultry, especially domestic ducks.

Starting in late November 2010, the H5N1 highly pathogenic avian influenza (HPAI) virus was isolated from many types of wild ducks and raptors and was subsequently isolated from poultry in Korea. We assessed the genetic and pathogenic properties of the HPAI viruses isolated from a fecal sample from a mandarin duck and a dead Eurasian eagle owl, the most affected wild bird species during the 2010/2011 HPAI outbreak in Korea. These viruses have similar genetic backgrounds and exhibited the highest genetic similarity with recent Eurasian clade 2.3.2.1 HPAI viruses. In animal inoculation experiments, regardless of their originating hosts, the two Korean isolates produced highly pathogenic characteristics in chickens, ducks and mice without pre-adaptation. These results raise concerns about veterinary and public health. Surveillance of wild birds could provide a good early warning signal for possible HPAI infection in poultry as well as in humans.

Highly pathogenic avian influenza (H5N1) among wild birds emerged simultaneously with outbreaks in domestic poultry in South Korea during November 2010–May 2011. Phylogenetic analysis showed that these viruses belonged to clade 2.3.2, as did viruses found in Mongolia, the People’s Republic of China, and Russia in 2009 and 2010.

During surveillance programs in Korea between January 2006 and March 2011, 31 H7 avian influenza viruses were isolated from wild birds and domestic ducks and genetically characterized using large-scale sequence data. All Korean H7 viruses belonged to the Eurasian lineage, which showed substantial genetic diversity, in particular in the wild birds. The Korean H7 viruses from poultry were closely related to those of wild birds. Interestingly, two viruses originating in domestic ducks in our study had the same gene constellations in all segment genes as viruses originating in wild birds. The Korean H7 isolates contained avian-type receptors (Q226 and G228), no NA stalk deletion (positions 69-73), no C-terminal deletion (positions 218-230) in NS1, and no substitutions in PB2-627, PB1-368, and M2-31, compared with H7N9 viruses. In pathogenicity experiments, none of the Korean H7 isolates tested induced clinical signs in domestic ducks or mice. Furthermore, while they replicated poorly, with low titers (10⁰·⁷⁻¹·³ EID₅₀/50 µl) in domestic ducks, all five viruses replicated well (up to 7-10 dpi, 10⁰·⁷⁻⁴·³EID₅₀/50 µl) in the lungs of mice, without prior adaptation. Our results suggest that domestic Korean viruses were transferred directly from wild birds through at least two independent introductions. Our data did not indicate that wild birds carried poultry viruses between Korea and China, but rather, that wild-type H7 viruses were introduced several times into different poultry populations in eastern Asia.

Background: Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. Methods: ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. Results: During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NBACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the blaoxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. Conclusions: In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the blaoxa23 gene. [ABSTRACT FROM AUTHOR]

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanusacellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) bleeding is a rare adverse event of dasatinib, which is known to be caused by dasatinib-induced colitis, severe thrombocytopenia, and platelet dysfunction. We present two cases of pediatric patients who developed hematochezia during treatment with dasatinib after hematopoietic stem cell transplantation (HSCT). A colonic tissue biopsy was performed to differentiate the cause of GI bleeding. Both patients were diagnosed with proven cytomegalovirus (CMV) colitis, but only one was treated with ganciclovir. The patient who did not receive antiviral therapy experienced recurrent GI bleeding during dasatinib administration, leading to multiple treatment interruptions. During dasatinib therapy after HSCT, patients with GI bleeding and confirmed CMV colitis may benefit from antiviral therapy to reduce interruptions in dasatinib therapy. [ABSTRACT FROM AUTHOR]

Research has been conducted on arteminolides B-D, farnesyl protein transferase inhibitors isolated from arteminolide A. Results suggest that these inhibitors can been used as antitumor agents against ras-mutated human cancers.

The human microbiome, which consists of a collective cluster of commensal, symbiotic, and pathogenic microorganisms living in the human body, plays a key role in host health and immunity. The human nasal cavity harbors commensal bacteria that suppress the colonization of opportunistic pathogens. However, dysbiosis of the nasal microbial community is associated with many diseases, such as acute respiratory infections including otitis media, sinusitis and bronchitis and allergic respiratory diseases including asthma. The nasopharyngeal acquisition of pneumococcus, which exists as a pathobiont in the nasal cavity, is the initial step in virtually all pneumococcal diseases. Although the factors influencing nasal colonization and elimination are not fully understood, the adhesion of opportunistic pathogens to nasopharyngeal mucosa receptors and the eliciting of immune responses in the host are implicated in addition to bacterial microbiota properties and colonization resistance dynamics. Probiotics or synbiotic interventions may show promising and effective roles in the adjunctive treatment of dysbiosis; however, more studies are needed to characterize how these interventions can be applied in clinical practice in the future. [ABSTRACT FROM AUTHOR]

After primary infection, varicella zoster virus (VZV) causes prolonged latent infections that may reactivate, depending on the immunologic status of the host. We present a case of VZV reactivation in a 10-year-old male patient that underwent unrelated peripheral blood stem cell transplantation (uPBSCT) for T-lymphoblastic lymphoma with lymphoma cutis lesions. This patient had a history of herpes zoster involving the right L2-5 dermatome and trigeminal V1 dermatome prior to uPBSCT. Three months post-uPBSCT, the patient’s underlying disease relapsed, and the patient presented with lymphoma cutis lesions. A few days after a skin biopsy was performed to pathologically confirm skin relapse, vesicles appeared only involving the skin areas with lymphoma cutis. This case illustrates how decreased areas of epidermal immune mechanisms may cause atypical presentations of varicella infection. [ABSTRACT FROM AUTHOR]

Humanity has been suffering from the global severe acute respiratory syndrome coronavirus 2 pandemic that began late in 2019. In 2020, for the first time in history, new vaccine platforms--including mRNA vaccines and viral vector-based DNA vaccines--have been given emergency use authorization, leading to mass vaccinations. The purpose of this article is to review the currently most widely used coronavirus disease 2019 vaccines, investigate their immunogenicity and efficacy data, and analyze the vaccine safety profiles that have been published, to date. [ABSTRACT FROM AUTHOR]

Background: Understanding the epidemiology and prevalence of febrile urinary tract infection (fUTI) in children is important for risk stratification and selecting appropriate urine sample collection candidates to aid in its diagnosis and treatment. Purpose: This study aimed to analyze the epidemiology, etiology, and changes in antibiotic susceptibility patterns of the first fUTI in children. Methods: This retrospective observational cohort study included children younger than 19 years of age who were diagnosed and treated for their first fUTI in 2006--2016. Electronic medical records were analyzed and radiologic images were evaluated. Results: A total of 359 patients (median age, 5.1 months; interquartile range, 3.0--10.5 months) fit the inclusion criteria; of them, 78.0% (n=280) were younger than 12 months old. The male to female ratio was 5.3:1 for patients aged 0--2 months, 2.1:1 for those 3--5 months, and 1.6:1 for those 6--11 months. Beyond 12 months of age, there was a female predominance. Escherichia coli was the leading cause (83.8%), followed by Enterococcus species (6.7%), and Klebsiella pneumoniae (3.6%). Significant yearly increases in the proportions of multidrugresistant strains (P<0.001) and extendedspectrum betalactamase (ESBL) producers (P<0.001) were observed. In patients with vesicoureteral reflux (VUR), the overall recurrence rate was 53.6% (n=15). A significantly higher recurrence rate was observed when the fUTI was caused by an ESBL versus nonESBL producer (75.0% vs. 30.0%, P=0.03). Conclusion: fUTI was most prevalent in children younger than 12 months of age and showed a female predominance in patients older than 12 months of age. The proportion of ESBL producers causing fUTI is increasing. Carbapenems, rather than noncarbapenems, should be considered for treating fUTI caused by ESBLproducing enteric gramnegative rods to reduce shortterm recurrence rates in children with VUR. [ABSTRACT FROM AUTHOR]

Objective This study was aimed to evaluate epidemiological and clinical relationship between Mycoplasma pneumoniae (MP) infection and childhood recurrent wheezing episode (RWE). Design Retrospective case note review. Setting Paediatric department at a single Korean institution. Participants Consecutive admitted patients with MP pneumonia and RWE (0-15 years of age) between 2003 and 2014. Methods The retrospective medical records of patients with (MP) pneumonia (n=793 for epidemiological analysis and n=501 for clinical analysis) and those with RWE (n=384) from 2003 to 2014 were analysed. Diagnosis of MP pneumonia was made based on two-times titration of IgM antibody during hospitalisation. An RWE patient was defined as one with expiratory wheezing with at least one or more wheezing episodes based on medical records. Results During three MP pneumonia epidemics, there were no corresponding increases of patients with RWE in the epidemic years. In the 501 MP pneumonia patients, 52 (10.4%) had wheezing at presentation and 15 (3%) had RWE. The MP pneumonia patients with wheezing at presentation (n=52) were younger and were more likely to have an allergic disease history than those without wheezing (n=449). Among wheezing patients at presentation, 10 patients had previously RWE history. In a follow-up study, 13 patients (including 5 RWE) with initial wheezing and 25 patients (including 2 RWE) without wheezing had wheezy episodes after discharge. Among the total 501 patients, it was estimated that at least 31 MP pneumonia patients (6.2%) showed recurrent wheezing after initial MP infection. Conclusions A small part of children with MP pneumonia showed recurrent wheezing after MP pneumonia, and patients with RWE had a greater likelihood of experiencing wheezing when they had an initial MP infection. However, there were no increased admitted patients with RWE in MP pneumonia epidemic periods because of rarity of MP reinfection in children including patients with RWE or asthma. [ABSTRACT FROM AUTHOR]

Novel H5N6 highly pathogenic avian influenza viruses (HPAIVs) were isolated from duck farms and migratory bird habitats in South Korea in November to December 2017. Genetic analysis demonstrated that at least two genotypes of H5N6 were generated through reassortment between clade 2.3.4.4 H5N8 HPAIVs and Eurasian low pathogenic avian influenza virus in migratory birds in late 2017, suggesting frequent reassortment of clade 2.3.4.4 H5 HPAIVs and highlighting the need for systematic surveillance in Eurasian breeding grounds. [ABSTRACT FROM AUTHOR]

Background: National surveillance of avian influenza virus (AIV) in South Korea has been annually conducted for the early detection of AIV and responses to the introduction of highly pathogenic avian influenza (HPAI) virus. In this study, we report on a nationwide surveillance study of AIV in domestic poultry and wild birds in South Korea between 2012 and 2014. Methods: During the surveillance programs between 2012 and 2014, 141,560 samples were collected. Of these, 102,199 were from poultry farms, 8215 were from LBMs, and 31,146 were from wild bird habitats. The virus isolation was performed by inoculation of embryonated chicken eggs and AIV isolates were detected using hemagglutination assay. For subtying of AIV, the hemagglutinin and neuraminidase genes were confirmed by sequencing. Phylogenetic analysis of the H5 subtypes was performed using 28 H5 AIV isolates. Results: Between 2012 and 2014, a total of 819 AIV were isolated from 141,560 samples. Virus isolation rates for AIV were 0.6, 0.4, 0.1, and 2.7% in wild birds (n = 202), domestic ducks (n = 387), minor poultry (n = 11), and the live bird market (LBM) (n = 219), respectively. In wild birds, various subtypes were found including H1-H7 and H9-H13. The major subtypes were H5 (n = 48, 23.9%: N3 (n = 4) and N8 (n = 44)), H4 (n = 39, 19.4%), and H1 (n = 29, 14.4%). In domestic poultry, mainly ducks, the H5N8 (n = 275, 59.3%), H3 (n = 30, 17.2%), and H6 (n = 53, 11.4%) subtypes were predominantly found. The most frequently detected subtypes in LBM, primarily Korean native chicken, were H9 (n = 169, 77.2%). H3 (n = 10, 4%) and H6 (n = 30, 13.7%) were also isolated in LBM. Overall, the prevalence of AIV was found to be higher between winter and spring and in western parts of South Korea. The unusual high prevalence of the H5 subtype of AIV was due to the large scale outbreak of H5N8 HPAI in wild birds and domestic poultry in 2014. Conclusions: Enhanced surveillance and application of effective control measures in wild birds and domestic poultry, including LBM, should be implemented to control AI and eradicate HPAI. [ABSTRACT FROM AUTHOR]

In 2014, two genetically distinct H5N8 highly pathogenic avian influenza (HPAI) viruses were isolated from poultry and wild birds in Korea. The intravenous pathogenicity indices for the two representative viruses were both 3.0. Mortality of chickens intranasally inoculated with the two H5N8 viruses was 100% with a mean death times of 2.5 and 4.5 days. Mortality rates of the contact groups for the two H5N8 viruses were 33.3% and 66.6%. Our study showed that transmissibility of the novel H5N8 viruses was different from that of previously identified H5N1 HPAI viruses, possibly due to genetic changes. [ABSTRACT FROM AUTHOR]

In spite of highly pathogenic avian influenza H5N1 vaccination campaigns for domestic poultry, H5N1 viruses continue to circulate in Vietnam. To estimate the prevalence of avian influenza virus in Vietnam, surveillance was conducted between November 2011 and February 2013. Genetic analysis of 312 highly pathogenic avian influenza H5 viruses isolated from poultry in Vietnam was conducted and possible genetic relationships with strains from neighboring countries were investigated. As previously reported, phylogenetic analysis of the avian influenza virus revealed two H5N1 HPAI clades that were circulating in Vietnam. Clade 1.1, related to Cambodian strains, was predominant in the southern provinces, while clade 2.3.2.1 viruses were predominant in the northern and central provinces. Sequence analysis revealed evidence of active genetic evolution. In the gene constellation of clade 2.3.2.1, genotypes A, B, and B(II) existed during the 2011/2012 winter season. In June 2012, new genotype C emerged by reassortment between genotype A and genotype B(II), and this genotype was predominant in 2013 in the northern and central provinces. Interestingly, enzootic Vietnamese clade 2.3.2.1C H5 virus subsequently reassorted with N2, which originated from wild birds, to generate H5N2 highly pathogenic avian influenza, which was isolated from duck in the northeast region. This investigation indicated that H5N1 outbreaks persist in Vietnam and cause genetic reassortment with circulating viruses. It is necessary to strengthen active influenza surveillance to eradicate highly pathogenic avian influenza viruses and sever the link between highly pathogenic avian influenza and other circulating influenza viruses. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide and the single strongest predictor of mortality in patients with diabetes. DKD is a prototypical disease of gene and environmental interactions. Tight glucose control significantly decreases DKD incidence, indicating that hyperglycemia-induced metabolic alterations, including changes in energy utilization and mitochondrial dysfunction, play critical roles in disease initiation. Blood pressure control, especially with medications that inhibit the angiotensin system, is the only effective way to slow disease progression. While DKD is considered a microvascular complication of diabetes, growing evidence indicates that podocyte loss and epithelial dysfunction play important roles. Inflammation, cell hypertrophy, and dedifferentiation by the activation of classic pathways of regeneration further contribute to disease progression. Concerted clinical and basic research efforts will be needed to understand DKD pathogenesis and to identify novel drug targets. [ABSTRACT FROM AUTHOR]

Purpose: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. Methods: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. Results: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1 %) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P=0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P=0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P=0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. Conclusion: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole. [ABSTRACT FROM AUTHOR]

Purpose: To identify the clinical and epidemiological characteristics of human metapneumovirus infections (hMPV) in children compared to respiratory syncytial virus A (RSV A) and B (RSV B). Method: A retrospective review of medical records was performed in 36 patients with hMPV infection, 106 with RSV A infection, and 51 with RSV B infection, from September 2007 to July 2012. Results: The peak incidence of hMPV infection was observed in May, whereas for RSV infections in November and December. hMPV infection occurred in older patients compared to RSV A and B infection (29.9±32.5 months vs. 13.6±15.4 months, P<0.001; 29.9±32.5 months vs. 12.1±13.5 months, P<0.001, respectively). hMPV infection was more often associated with fever compared to RSV A (97.2% vs. 67.9%, P<0.001), while wheezing was less frequent compared to RSV A and B infection (16.7% vs. 47.2%, P=0.001; 16.7% vs. 37.3%, P=0.037, respectively). hMPV infection was more often diagnosed as pneumonia compared to RSV A infection (72.2% vs. 50.0%, P=0.047) while bronchiolitis was less frequent than in RSV A (5.6% vs. 34.9%, P=0.001) or RSV B infection (5.6% vs. 29.4%, P=0.006). In addition, intravenous antibiotic was more often prescribed for patients with hMPV infection than those with RSV A and B (69.4% vs. 39.6%, P=0.002; 69.4% vs. 43.1, P=0.015, respectively). Conclusion: This study identified characteristics of hMPV infection compared to RSV A and B infection. Seasonality in spring, higher age group, and higher proportion of pneumonia in hMPV infections may be a useful guide for management of respiratory viral infections in children. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the outcome of carbapenem versus non-carbapenem antimicrobial therapy for pediatric urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae. Materials and Methods: From 2006 to 2011, 42 episodes of UTI caused by ESBL-producing Enterobacteriaceae were diagnosed at Seoul National University Children's Hospital. Patients were grouped according to the antimicrobials they received into a carbapenem group and a non-carbapenem group. Medical records were retrospectively reviewed to assess treatment outcome, time to defervescence after initiation of treatment, and relapse rate. Results: There were 36 children with 42 episodes of UTI caused by ESBL-producing Enterobacteriaceae. Twenty-seven cases (64%) had an underlying urologic disease, 28 (67%) cases were caused by Escherichia coil, and 14 (33%) cases were caused by Klebsiella pneumoniae. Four (10%) cases were treated with carbapenem, 23 cases (55%) were treated with non-carbapenem, and 15 (36%) cases were treated by switching from a carbapenem to a non-carbapenem and vice versa. There was no treatment failure at the time of antimicrobial discontinuation. Between the carbapenem and the non-carbapenem treatment groups, there were no significant differences in bacterial etiology (P=0.59), time to defervescence after the initiation of antimicrobials (P=0.28), and relapse rate (P=0.50). In vitro susceptibility to non-carbapenem antimicrobials did not affect the time to defervescence after the initiation of antimicrobial treatment, and the relapse rate in the non-carbapenem group. Conclusions: This study found no significant difference in the treatment outcome between pediatric patients treated with carbapenem and those treated with non-carbapenem antimicrobials for UTI caused by ESBL-producing Enterobacteriaceae. Therefore, the initially administered non-carbapenem can be maintained in UTI patients showing clinical improvement. [ABSTRACT FROM AUTHOR]

In Korea, Mycoplasma pneumoniae was detected in 255/2,089 respiratory specimens collected during 2000-2011; 80 isolates carried 23S rRNA gene mutations, and 69/123 culture-positive samples with the mutation were resistant to 5 macrolides. During 2000-2011, prevalence of the mutation increased substantially. These findings have critical implications for the treatment of children with mycoplasma pneumonia. [ABSTRACT FROM AUTHOR]

Starting in late November 2010, the H5N1 highly pathogenic avian influenza (HPAI) virus was isolated from many types of wild ducks and raptors and was subsequently isolated from poultry in Korea. We assessed the genetic and pathogenic properties of the HPAI viruses isolated from a fecal sample from a mandarin duck and a dead Eurasian eagle owl, the most affected wild bird species during the 2010/2011 HPAI outbreak in Korea. These viruses have similar genetic backgrounds and exhibited the highest genetic similarity with recent Eurasian clade 2.3.2.1 HPAI viruses. In animal inoculation experiments, regardless of their originating hosts, the two Korean isolates produced highly pathogenic characteristics in chickens, ducks and mice without pre-adaptation. These results raise concerns about veterinary and public health. Surveillance of wild birds could provide a good early warning signal for possible HPAI infection in poultry as well as in humans. [ABSTRACT FROM AUTHOR]

Background: Virus subtype H13N2, A/mallard/Kr/SH38-45/2010 (H13N2), was first isolated from a mallard fecal sample in South Korea. Results: Phylogenetic analysis of all eight viral genes revealed that this virus emerged by genetic mixing between Eurasian and North American gene pools, and possibly between wild ducks and gulls. The H13 and N2 surface genes clustered together in a group with Eurasian isolates from gulls and wild birds, respectively. The PB2, PA, NP, M and NS segments belonged to the Eurasian lineage, whereas the PB1 gene clustered in the North American lineage. Furthermore, they showed a bird-dependent pattern in phylogenetic analysis: the M gene was similar to subtype H13 viruses within gulls, whereas other segments were similar to avian influenza viruses of other subtypes from wild ducks. Conclusions: The data suggests that the novel reassortant H13N2 virus isolated in South Korea might have emerged by genetic reassortment between intercontinental and interspecies transmission in wild birds. [ABSTRACT FROM AUTHOR]

H1 avian influenza viruses (AIVs) isolated from migratory birds and domestic ducks from 2003 to 2007 were analyzed to determine their genetic relationship. Phylogenic analysis with nucleotide sequences of all eight gene segments showed that 13 H1 AIVs from migratory birds and domestic ducks belonged to Eurasian avian lineages and were closely related to each other. Compared with H1 influenza viruses of swine or human origin in Korea, there was no evidence of reassortment among the human, swine, and avian hosts. Our results show that H1 AIVs isolated in Korea from 2003 to 2007 were genetically stable. However, continued surveillance is needed considering the role of migratory birds and domestic duck as a source of AIVs. [ABSTRACT FROM AUTHOR]

The article offers information on a study which analyzed avian influenza virus (AIV) present in live bird markets (LBM) in Korea during the winter seasons of 2006 to 2008. A brief review of the related literature is presented. Materials and methods used included sampling for virus isolation, virus isolation and subtyping and phylogenetic and molecular analysis. It discusses the findings of the study such as the replication of influenza virus isolates in experimental animals. It concludes that viral gene transfer exists among different animal species in LBM.

The article offers information on a study which described the application of DNA barcoding techniques to avian influenza virus (AIV) surveillance at stopover and breeding sites as well as at major southern wintering sites of migratory waterfowls in Korea. A brief review of the related literature is presented. Materials and methods used included collection of fresh fecal samples from the wintering sites, virus detection and isolation and DNA barcoding for species identification of fecal samples, among others. It discusses the findings of the study, such as the prevalence of AIV in wild bird habitats and differences between observed species and identified species.

Various attempts have been made to develop stem cell-based therapy to alleviate type I diabetes using animal models. However, it has been a question whether human insulin produced from explanted cells is solely responsible for the normoglycemia of diabetic animals. In this study, we isolated neural crest-like stem cells from the human eyelid fat and examined their therapeutic potentials for diabetes. The human eyelid adipose-derived stem cells (HEACs) displayed characteristics of neural crest cells. Using a two-step culture condition combined with nicotinamide, activin, and/or GLP-1, we differentiated HEACs into insulin-secreting cells and examined in vivo effects of differentiated cells by transplantation experiments. Following differentiation in vitro, HEACs released insulin and c-peptide in a glucose-dependent manner. Upon their transplantation under kidney capsules of streptozotocin-treated immunocompetent mice, we observed normalization of hyperglycemia in 10 of 20 recipient mice until sacrifice after 2 months. Only the human, but not the mouse, insulin and c-peptide were detected in the blood of recipient mice. Removal of the kidneys transplanted with HEACs resulted in a sharp increase of blood glucose level. Removed kidney tissues showed distinct expression of various human genes including insulin, and colocalization of the human insulin and the human nuclear protein in many cells. However, they showed diminished or null expression of some immune-related genes. In conclusion, human insulin alone produced from eyelid-derived stem cells following differentiation into insulin-secreting cells and transplantation could normalize type I diabetes in mice. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype have spread since 2003 in poultry and wild birds in Asia, Europe and Africa. In Korea, the highly pathogenic H5N1 avian influenza outbreaks took place in 2003/2004, 2006/2007 and 2008. As the 2006/2007 isolates differ phylogenetically from the 2003/2004 isolates, we assessed the clinical responses of chickens, ducks and quails to intranasal inoculation of the 2006/2007 index case virus, A/chicken/Korea/IS/06. All the chickens and quails died on 3 days and 3-6 days post-inoculation (DPI), respectively, whilst the ducks only showed signs of mild depression. The uninoculated chickens and quails placed soon after with the inoculated flock died on 5.3 and 7.5 DPI, respectively. Both oropharyngeal and cloacal swabs were taken for all three species during various time intervals after inoculation. It was found that oropharyngeal swabs showed higher viral titers than in cloacal swabs applicable to all three avian species. The chickens and quails shed the virus until they died (up to 3 to 6 days after inoculation, respectively) whilst the ducks shed the virus on 2-4 DPI. The postmortem tissues collected from the chickens and quails on day 3 and days 4-5 and from clinically normal ducks that were euthanized on day 4 contained the virus. However, the ducks had significantly lower viral titers than the chickens or quails. Thus, the three avian species varied significantly in their clinical signs, mortality, tissue virus titers, and duration of virus shedding. Our observations suggest that duck and quail farms should be monitored particularly closely for the presence of HPAIV so that further virus transmission to other avian or mammalian hosts can be prevented. [ABSTRACT FROM AUTHOR]

Cells were isolated from four human amniotic membranes, and their biological characteristics analyzed during ex vivoexpansion. Morphologically homogenous populations of fibroblast-like cells were obtained from the second or third passage. Under the appropriate culture conditions, these human amniotic membrane-derived mesenchymal cells (HAM) were shown to differentiate into adipocytes, osteocytes, chondrocytes and neuronal cells, as visualized by Oil Red O, von Kossa, alcian blue, anti-Neu N, and anti-Gal C antibody staining, respectively. Immunophenotype analysis of HAM cells revealed the presence of antigens for SSEA-3, SSEA-4, collagen type-I, -II, -III, -IV, -XII, fibronectin, α-SMA, vimentin, desmin, cytokeratin18 (CK18), HCAM-1, fibroblast surface protein, and human leukocyte antigen (HLA) ABC. ICAM-1 protein was weakly detectable, and proteins of TRA-1-60, VCAM-1, von Willebrand factor, PECAM-1, and HLA DR were not detected. HAM cells reached senescence after 14.5 ± 0.9 passages, over a period of 146.8 ± 8.9 days, and underwent an average of 36.9 4.7 population doublings. RT-PCR analysis showed that all four HAM cell lines consistently expressed genes of Oct-4, Rex-1, SCF, NCAM, nestin, BMP-4, GATA-4, HNF-4α, vimentin, and CK18, regardless of the passage number. The genes of Brachyury, FGF-5, Pax-6, and BMP2 were never expressed. Strikingly, α-fetoprotein (αFP), HLA ABC, and HLA DR genes were expressed in an earlier passage but not expressed in later passages. Telomerase activity of two HAM lines was discernable upon the third passage. These observations strongly suggest that HAM might be immune-privileged and, thus, advantageous as therapeutic cells. [ABSTRACT FROM AUTHOR]

Staphylococcal food poisoning is caused by enterotoxin-producing Staphylococcus aureus. We investigated the prevalence of such organisms in samples of bovine mastitic milk (n = 714), raw meat (n = 139), and vegetables (n = 616). We determined the degrees of relatedness of isolates as indicated by antibiogram, staphylococcal enterotoxin (SE) productivity, and coagulase gene restriction fragment length polymorphism analysis. We examined 297 S. aureus isolates and found SE production in 57 (31.8%), 4 (7.8%), and 49 (73.1%) isolates from raw milk, raw meat, and vegetables, respectively. A high proportion of the isolates obtained from milk produced more than two types of toxins (mainly SEA, SEB, and/or SEC), whereas isolates from raw meat and vegetables primarily produced SEA alone. Most isolates were sensitive to cephalothin (97.6%), gentamicin (80.8%), erythromycin (79.5%), and tetracycline (72.7%), but were resistant to penicillin (90.2%) and ampicillin (88.9%). The proportion of antibiotic-resistant isolates differed according the source of the bacteria: the milk and vegetable isolates were more resistant to penicillin and ampicillin than were the meat isolates (P < 0.05), whereas tetracycline resistance was limited to the milk and vegetables isolates. The coagulase genotypes (I to XII) varied with the source of the organism, and only a few genotypes prevailed in each source: II (42.4%) and IV (24%) types in isolates from milk, IX (35.3%) and XI (45%) from raw meat, and III (40.3%) and XII (32.8%) from vegetables. These findings suggest that remarkable differences exist in antibiogram, SE productivity, and coagulase genotypes, resulting in limited clonal transmission of S. aureus into various food sources. As enterotoxin production only occurs when S. aureus grows to high numbers, staphylococcal food poisoning can be prevented by proper refrigeration. [ABSTRACT FROM AUTHOR]

Abstract Several perinatal factors influence the intestinal microbiome of newborns during the first days of life, whether during delivery or even in utero. These factors may increase the risk of developing necrotizing enterocolitis (NEC) by causing dysbiosis linked to a NEC-associated microbiota, which may also be associated with other gastrointestinal problems. The objective of our study was to evaluate the potential risks associated with microbial shifts in newborns with gastrointestinal symptoms and identify the intestinal microbiota of neonates at risk for NEC.During the study period, 310 preterm and term newborns’ first passed meconium occurring within 72 h of birth were collected, and the microbiome was analyzed. We identified the risk factors in the NEC/FI group. Regarding microbiota, we compared the bacterial abundance between the NEC/FI group at the phylum and genus levels and explored the differences in the microbial composition of the 1st stool samples. A total of 14.8% (n = 46) of the infants were diagnosed with NEC or FI. In univariate analysis, the mean gestational age and birth weight were significantly lower in the NEC/FI group (p 18 h, chorioamnionitis, and histology were significantly higher in the NEC/FI group (p 18 h), and early onset sepsis were consistently associated with an increased risk of NEC/FI. Infants diagnosed with NEC/FI exhibited a significantly lower abundance of Actinobacteria at the phylum level than the control group (p