Impact of public health measures and new introducing variants on Respiratory syncytial virus recrudescence in Taiwan during the COVID-19 pandemic.

OBJECTIVES: Respiratory syncytial virus (RSV) causes clinically significant distress in children and adults. Non-pharmaceutical interventions against SARS-CoV-2 have affected the seasonal activity of common respiratory pathogens. This seems exceptionally true regarding RSV's seasonal circulation, hence we have investigated the changes in the epidemiology of RSV in Taiwan during the pandemic. MATERIALS: A prospective surveillance of RSV among hospitalized children was carried out between 2020 and 2022 in central Taiwan. Of all PCR-detected RSV, genotype and evolutionary analysis were further investigated. Demographics and clinical features were compared between each outbreak. RESULTS: Throughout the consecutive three years of the SARS-CoV-2 pandemic, RSV outbreaks took place in Taiwan first in 2020 and a second time in 2022. We enrolled 80 and 105 hospitalized child cases, in each surge respectively. The RSV G protein genomic analysis revealed that RSV ON1 and RSV BA9 were separately contributing to these two outbreaks, and evolutionary evidence indicated these RSV variants are new to Taiwan, with their own featured sets of mutations. Clinically, a shift in age of RSV infected children was found, but the clinical severity was not worse and remained independent of RSV genotype. CONCLUSIONS: There were two delayed RSV surges after the relaxation of public measures during the pandemic in Taiwan, and both outbreaks were driven by new RSV genetic variants rather than cryptic circulation of the previous genetic clusters in Taiwan. These findings highlight the importance of continued surveillance on the trend and evolution of RSV after the COVID-19 pandemic.

Clinical characteristics and differential cytokine expression in hospitalized Taiwanese children with respiratory syncytial virus and rhinovirus bronchiolitis.

BACKGROUND: Viral bronchiolitis presents a heterogeneous spectrum. In this study, we investigated the clinical characteristics and the cytokines/chemokines profiles among respiratory syncytial virus (RSV), rhinovirus (RV), and their dual infection in Taiwanese children with viral bronchiolitis. METHOD: This study was conducted between October 2014 and June 2017. Viral etiology was identified using a Luminex respiratory virus panel and blood cytokines were evaluated using a MILLIPLEX MAP Human Cytokine/Chemokine Panel. Cytokine/Chemokine expressions were compared by clinical severity, steroid treatment, and viral entities. RESULTS: A total of 184 patients were evaluated; at least one respiratory virus was identified in 163 (88.6%) patients. RSV and RV were the two leading viral etiologies, with 25.5% and 17.3%, respectively. RV bronchiolitis has a comparable severity to RSV but is more common in children of an older age with a history of recurrent wheezing and blood eosinophilia. Decreased tumor necrosis factor-alpha (TNF-α) and interferon gamma (INF-γ) levels were correlated with clinical severity. Patients infected with RV exhibited higher levels of Interleukin (IL)-22, IL-23, IL-25, IL-31, and IL-33 (p < 0.05), whereas those with RSV had higher levels of TNF-α, INF-γ, and IL-10 (p < 0.05). Systemic steroid treatment was associated with higher expressions of IL-4, IL-8, IL-13, and MIP-1α levels (p < 0.05). Cluster analysis revealed a high correlation of IL-33 and IL-31(R2 = 0.9731, p < 0.0001). CONCLUSION: Different viral infections elicited the characteristic clinical presentation and immune profiles in bronchiolitis. Our findings also highlight the role of the IL-33/IL-31 axis in the immunopathogenesis of bronchiolitis.

Delayed respiratory syncytial virus outbreak in 2020 in Taiwan was correlated with two novel RSV-A genotype ON1 variants.

BACKGROUND: Human respiratory syncytial virus (RSV) is a leading pathogen of acute respiratory tract disease among infants and young children. Compared with previous seasons, RSV outbreaks in Taiwan during the 2020-2021 season were delayed because of COVID-19 mitigation measures. We conducted this study to determine the association of viral factors with clinical characteristics of preschool children with RSV infection. METHODS: We performed a molecular epidemiology analysis of RSV among inpatient preschool children in Taiwan. In 80 nasopharyngeal samples positive for RSV, we sequenced and analyzed viral genotypes according to patient data. Patients' clinical data were obtained from medical files, and their clinical profiles were compared with those of RSV cases recorded during the 2014-2017 seasons. RESULTS: Phylogenetic analysis revealed that among the RSV-positive samples, all RSV strains identified during the 2020-2021 season belonged to the ON1 genotype. Most of the Taiwan ON1 strains were categorized into two well-supported clusters with distinct G protein amino acid substitution patterns that had never been demonstrated previously. Furthermore, the proportion of cases among children aged >24 months increased (P < 0.001). Compared with patients infected during the 2014-2017 seasons, patients infected during the 2020-2021 season were hospitalized for shorter days from hospital admission to dereference (P = 0.004) and had a greater need for oxygen supplements (P = 0.021) and systemic steroid therapy (P = 0.026). CONCLUSION: The delayed 2020-2021 RSV outbreak in Taiwan was caused by two novel RSV ON1.1 variants. How the change in RSV epidemiology affects future RSV outbreaks warrants exploration.

Sequence types 8, 59, and 45 methicillin resistant Staphylococcus aureus as the predominant strains causing skin and soft tissue infections in Taiwan's prisons and jails.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the predominant cause of skin and soft tissue infections (SSTIs), which is a problem in prisons and jails. We conducted this study to understand MRSA molecular characteristics among inmates with SSTIs, and we chose MRSA isolates from a community hospital as a comparison. METHODS: A total of 219 MRSA isolates from three custodial facilities and 134 isolates from a community hospital in Taiwan were collected in the 2017 calendar year. MRSA isolates were investigated molecularly by staphylococcal chromosome cassette mec (SCCmec) type, mupirocin, and chlorhexidine genotypical resistance, and multi-locus sequence typing (ST). RESULTS: Of the 219 MRSA isolates from custodial facilities, SCCmec IV was the most prevalent type (65.3%), followed by type VT (32.4%) and type V (1.8%). Regarding sequence types, ST59 (36.4%), 8 (35.3%), and 45 (17.9%) were the leading three predominant types out of 184 selected MRSA isolates, and ST45 MRSA was more prevalent in custodial facilities (p = 0.019). The antimicrobial resistance rates varied for different MRSA strains, with ST45 MRSA having the lowest rates of resistance to most antimicrobials. Overall, 91.5% of isolates carried mupA gene and 25.8% were positive for qacA/B gene, this was independent of the MRSA sequence types. CONCLUSIONS: ST59, ST8, and ST45 MRSA are the leading three MRSA strains causing SSTIs in Taiwan, 2017, but the molecular distribution varied distinctly between the custodial facilities and hospital settings. The genotypical mupirocin resistance rate is quite high in this study. The frequency of chlorhexidine resistance gene is relatively low, especially in MRSA isolates from custodial facilities.

Macrolide Resistance, Clinical Features, and Cytokine Profiles in Taiwanese Children With Mycoplasma pneumoniae Infection.

BACKGROUND: The factors that predict the progression of Mycoplasma pneumoniae infection remain inconclusive. Therefore, we investigated macrolide resistance prevalence, M pneumoniae genotype, and clinical characteristics of childhood M pneumoniae respiratory tract infections in Taiwan. METHODS: A total of 295 children hospitalized with respiratory tract infections with positive serological M pneumoniae immunoglobulin M test results were enrolled in this 3-year prospective study. Oropharyngeal swabs were obtained for M pneumoniae cultures and polymerase chain reaction tests. All M pneumoniae specimens were further characterized by P1 typing, multilocus variable-number tandem-repeat analysis (MLVA), and macrolide resistance genotyping. The clinical characteristics and blood cytokine profiles were analyzed accordingly. RESULTS: Of 138 M pneumoniae specimens, type I P1 was the predominant (136 of 138, 98.6%). The MLVA type P (4-4-5-7-2) was the leading strain (42 of 138, 30.4%), followed by type J, U, A, and X. The overall macrolide-resistant rate was 38.4% (53 of 138); the resistance rate increased dramatically yearly: 10.6% in 2017, 47.5% in 2018, and 62.5% in 2019 (P < .001). All macrolide-resistant M pneumoniae (MRMP) harbored the A2063G mutation and were MLVA type 4-5-7-2 (49 of 53, 92.5%), especially type U and X. No significant differences in clinical symptoms, duration of hospital stay, and radiographic findings were identified among patients between MRMP and macrolide-sensitive M pneumoniae (MSMP) groups. Patients with MRMP infection had more febrile days before and during hospitalization and higher interleukin (IL)-13 and IL-33 levels than patients with MSMP infection (P < .05). CONCLUSIONS: Macrolide-resistant M pneumoniae surged in Taiwan throughout the study period, but macrolide resistance was not a determinant factor of clinical severity.

Genetic Diversity and Molecular Epidemiology of Circulating Respiratory Syncytial Virus in Central Taiwan, 2008-2017.

In this study, we investigated the molecular evolution and phylodynamics of respiratory syncytial virus (RSV) over 10 consecutive seasons (2008-2017) and the genetic variability of the RSV genotypes ON1 and BA in central Taiwan. The ectodomain region of the G gene was sequenced for genotyping. The nucleotide and deduced amino acid sequences of the second hypervariable region of the G protein in RSV ON1 and BA were analyzed. A total of 132 RSV-A and 81 RSV-B isolates were obtained. Phylogenetic analysis revealed that the NA1, ON1, and BA9 genotypes were responsible for the RSV epidemics in central Taiwan in the study period. For RSV-A, the NA1 genotype predominated during the 2008-2011 seasons. The ON1 genotype was first detected in 2011 and replaced NA1 after 2012. For RSV-B, the BA9 and BA10 genotypes cocirculated from 2008 to 2010, but the BA9 genotype has predominated since 2012. Amino acid sequence alignments revealed the continuous evolution of the G gene in the ectodomain region. The predicted N-glycosylation sites were relatively conserved in the ON1 (site 237 and 318) and BA9 (site 296 and 310) genotype strains. Our results contribute to the understanding and prediction of the temporal evolution of RSV at the local level.

Prevalence of cytomegalovirus DNAemia and genotypic distribution among childbearing mothers and neonates in Taiwan.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading cause of neurologic disabilities and sensorineural hearing loss in children. However, in Taiwan, there is limited information on the genotypic diversity and prevalence of perinatal CMV infection in both mothers and neonates. The aim of this study was to screen samples from both mothers and umbilical cord blood for CMV at the time of delivery and to determine the CMV genotypic distribution. METHODS: Between June 2012 and July 2015, residual maternal and umbilical cord blood samples were collected from consenting participants admitted to the Chang Bing Show Chwan Memorial Hospital in central Taiwan. The blood samples were screened for CMV DNA using real-time PCR assay, and the genotypic classification of the CMV UL55, UL144, and US28 genes was determined by sequencing and phylogenetic analysis. RESULTS: A total of 1282 mother-neonate paired samples were enrolled in the study, 95.3% of whom were Taiwanese. CMV DNA was detectable in 6.2% of the maternal blood samples, with a significantly higher rate noted in non-Taiwanese mothers (11.7%,p=0.027). For the 1,282 umbilical cord blood samples, CMV DNA was detectable in 5.3% of the samples. The presence of CMV DNA in maternal blood was positively associated with the presence of CMV DNA in umbilical cord blood (p=0.01). In addition, the UL55, UL144, and US28 genotypic distribution was similar between mothers and neonates. CONCLUSION: The prevalence of CMV DNAemia in childbearing mothers and neonates is similar and their genotypic distribution implies potential CMV infection during pregnancy.

Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus among nasal carriage strains isolated from emergency department patients and healthcare workers in central Taiwan.

BACKGROUND AND OBJECTIVE: Screening and identification of methicillin-resistant Staphylococcus aureus (MRSA) carriage are helpful for controlling MRSA dissemination in hospitals. The aim of our study was to determine the prevalence of nasal carriages and diversity of MRSA among patients and healthcare workers (HCWs) at two regional hospitals in Taiwan. METHODS: Nasal swabs were obtained prospectively from 204 patients visiting the emergency department (ED) and 326 HCWs in two regional hospitals in Changhua, Taiwan, between February 2015 and June 2015. All the MRSA isolates were further molecularly characterized. RESULTS: Of the 204 participating patients, the nasal carriage rates of S. aureus and MRSA were 22.1% and 7.8%, respectively. For HCWs, the S. aureus and MRSA carriage rates were 26.1% and 6.1%, respectively. There was no statistically significant difference in MRSA carriage rate between patients and HCWs (P = 0.447). Patients receiving hemodialysis were significantly associated with MRSA colonization (P = 0.012). The leading three sequence types (ST) were ST59 (16, 44.4%), ST45 (11, 30.6%), and ST239 (3, 8.3%) for all 36 MRSA isolates. ST59/SCCmec IV/t437/PVL-negative and ST45/SCCmec V/t1081/PVL-negative were the predominant clones among HCWs (30%) and participating patients (19%), respectively. CONCLUSION: Overall, a substantial proportion of patients visiting the ED and HCWs harbored CA-MRSA, mostly ST59 strains, in their nares. It is noteworthy that MRSA ST45 strains supplanted ST239 as the second leading nasal MRSA colonization strain in our study.

Comparison of molecular epidemiology of bloodstream methicillin-resistant Staphylococcus aureus isolates between a new and an old hospital in central Taiwan.

OBJECTIVE: To compare the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolates between an old, urban hospital and a new, rural hospital over the same time period. METHODS: The molecular characteristics of 398 MRSA bloodstream isolates collected between 2007 and 2013 from two hospitals in Taiwan were analyzed retrospectively; 202 isolates were from the old hospital and 196 from the new hospital (opened in 2007). RESULTS: The rate of resistance to multiple antibiotics was significantly higher in the old hospital (93%) than in the new hospital (81%) (p<0.001). Genetic community-associated MRSA carrying staphylococcal cassette chromosome (SCC) type IV or V accounted for 58% of all MRSA isolates in the new hospital, significantly higher than the rate in the old hospital (p=0.018). The rate of spa t037-SCCmec III MRSA was significantly lower in the new hospital than in the old hospital (p=0.02). A significant decreasing trend in spa t002-SCCmec II MRSA isolates was observed in the old hospital (p=0.006), while the proportion of spa t037-SCCmec III MRSA decreased significantly in the new hospital (41.7% to 26.1%, p=0.022). CONCLUSIONS: The rate of multiple antibiotic resistance and the molecular characteristics of MRSA differed significantly between the old and new hospitals and changed over time.

Oxonium picrate.

The title compound, H(3)O(+)·C(6)H(2)N(3)O(7) (-), consists of one picrate anion and one oxonium cation. The oxonium cation is located on a crystallographic twofold axis and both its H atoms are disordered, each over two symmetry-equivalent positions with occupancy ratios of 0.75. The picrate anions are also located on twofold axes bis-ecting the phenolate and p-nitro groups. π-π inter-actions between the rings of the picrates [centroid-to-centroid distances of 3.324 (2) Å] connect the anions to form stacks along the a-axis direction. The stacks are further joined together by the protonated water mol-ecules through hydrogen bonds to form two-dimensional sheets extending parallel to the ab plane. The sheets are stacked on top of each other along the c-axis direction and connected through C-H⋯O inter-actions between the CH groups of the benzene rings and the picrate nitro groups, with C⋯O distances of 3.450 (2) Å.