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In Asia, most reports on the epidemiology of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) are from developed countries, with few data from resource-limited countries, not because of low actual prevalence, but probably because of scarce diagnostic facilities. The rate of MRSA in all community-associated S aureus infections in Asian countries ranges from 2·5% to 39%. Unlike the predominance of USA300-sequence type (ST) 8 staphylococcal cassette chromosome mec (SCCmec) type IV in the USA, the molecular epidemiology of CA-MRSA in Asia is characterised by clonal heterogeneity, similar to that in Europe. The emergence of CA-MRSA is a threat in both community and hospital settings because such strains are now more prevalent than are health-care-associated MRSA (HA-MRSA) strains. Many epidemic clones are in circulation in Asia and with scarce data available, concern has arisen that CA-MRSA could have devastating results if it becomes epidemic in resource-poor regions. The epidemiology of CA-MRSA in Asia is closely linked with the health of both developing and developed countries. The present situation of CA-MRSA in Asia is important not only for local public health, but also to provide a better understanding of the successful epidemic clones of this global pathogen.

During recent 20 years, enterovirus A71 (EV-A71) has emerged as a major concern among pediatric infectious diseases, particularly in the Asia-Pacific region. The clinical manifestations of EV-A71 include uncomplicated hand, foot, and mouth disease, herpanina or febrile illness and central nervous system (CNS) involvement such as aseptic meningitis, myoclonic jerk, polio-like syndrome, encephalitis, encephalomyelitis and cardiopulmonary failure due to severe rhombencephalitis. In follow-up studies of patients with EV-A 71 CNS infection, some still have hypoventilation and need tracheostomy with ventilator support, some have dysphagia and need nasogastric tube or gastrostomy feeding, some have limb weakness/astrophy, cerebellar dysfunction, neurodevelopmental delay, lower cognition, or attention deficiency hyperactivity disorder. Long term sequelae may be related to greater severity of CNS involvement or neuron damage, hypoxia and younger age of onset.

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

Heterologous prime-boost COVID-19 vaccine strategy may facilitate mass COVID-19 immunization. We reported early immunogenicity and safety outcomes of heterologous immunization with a viral vector vaccine (ChAdOx1) and a spike-2P subunit vaccine (MVC-COV1901) in a participant-blinded, randomized, non-inferiority trial (NCT05054621). A total of 100 healthy adults aged 20–70 years having the first dose of ChAdOx1 were 1:1 randomly assigned to receive a booster dose either with ChAdOx1 ( n  = 50) or MVC-COV1901 ( n  = 50) at an interval of 4–6 or 8–10 weeks. At day 28 post-boosting, the neutralizing antibody geometric mean titer against wild-type SARS-CoV-2 in MVC-COV1901 recipients (236 IU/mL) was superior to that in ChAdOx1 recipients (115 IU/mL), with a GMT ratio of 2.1 (95% CI, 1.4 to 2.9). Superiority in the neutralizing antibody titer against Delta variant was also found for heterologous MVC-COV1901 immunization with a GMT ratio of 2.6 (95% CI, 1.8 to 3.8). Both spike-specific antibody-secreting B and T cell responses were substantially enhanced by the heterologous schedule. Heterologous boosting was particularly prominent at a short prime-boost interval. No serious adverse events occurred across all groups. The findings support the use of heterologous prime-boost with ChAdOx1 and protein-based subunit vaccines. Public safety concern of the ChAdOx1 vaccine has led to an alternative immunisation strategy against SARS-CoV-2, with this heterologous schedule widely adopted and officially recommended in many countries. Here, the authors report the immunogenicity and safety outcomes of heterologous prime-boost immunisation with ChAdOx1 and a spike-2P subunit vaccine in a single-blinded, randomised trial.

During infection by positive-sense single-stranded RNA viruses, understanding the mechanisms governing the fate of viral RNA, whether directed towards translation, replication, or virion assembly, remains a significant challenge. In this study, we conducted RNA-interactome analysis using metabolic labeling coupled with quantitative proteomics to investigate the protein composition of temporal ribonucleoprotein complexes (RNPs) during enterovirus A71 (EV-A71) infection. Comparative analysis of RNPs during the early and late infection stages, representing the eclipse and maturation phases, revealed dynamic RNP remodeling over time. This remodeling process involved the exchange of nuclear RNA binding proteins with cytoplasmic membrane-associated proteins. Notably, EV-A71 infection induced the phosphorylation and cytoplasmic re-localization of nuclear serine and arginine-rich (SR) proteins, as determined using pan-SR protein antibodies, with these proteins found to co-localize with viral RNAs. Knockdown of specific SR proteins, including SRSF4, SRSF5, and SRSF6, significantly reduced viral growth, highlighting their critical role in the infection process. Intriguingly, these phosphorylated SR proteins cofractionated with the translation machinery rather than the replication organelles, a phenomenon predominantly observed during the early infection phase and abolished in the late phase. Importantly, inhibition of SR protein phosphorylation using the kinase inhibitors SRPKIN-1 and TG003 significantly impaired IRES-dependent translation and EV-A71 replication. These findings underscore the pivotal role of SR protein phosphoregulation during the eclipse phase of EV-A71 infection in facilitating the formation of translation-competent complexes. Furthermore, they highlight the potential of targeting SR protein phosphorylation as a promising strategy for antiviral development.

Background Methicillin-resistant Staphylococcus aureus (MRSA) ST398 is a livestock associated-bacterium that is most prevalent in Europe. Human-adapted MRSA ST398 was recently reported from China, but there is no data available yet for Taiwan. Methods To identify S. aureus ST398 isolates, we examined 6413  S. aureus isolates (5632 MRSA and 781 susceptible strains) that were collected in Taiwan between 1995 and 2017. If isolates could not be typed by pulsed-field gel electrophoresis upon Sma I digestion, we performed further characterization and complete genome sequencing. Results We identified 18 ST398 S. aureus isolates from 16 subjects (0.28%), including 6 sensitive and 12 resistant strains. Of these, 14 were colonizing isolates, 3 were clinical (infecting) isolates and one isolate was from a pork specimen. All 3 infecting isolates were MSSA strains identified in 2015 from two children with recurrent otitis media or sinusitis. The other 3 MSSA isolates were identified from workers handling pork (2) or pork meat (1) in 2015. The first 5 MRSA colonizing isolates were identified from residents in two nursing homes in 2012. Six MRSA isolates were identified from residents and foreign employees at a nursing home in 2016 and one MRSA from a foreign worker in 2017. Phylogenetic analysis of genome sequences indicated that all 12 local ST398 MRSA strains cluster together, human-adapted and phylogenetically related to a human MRSA strain identified in China in 2002. Two local MSSA isolates could be linked to isolates from livestock. The toxin profiles were similar for the MRSA and MSSA isolates. Conclusions Our results demonstrate that S. aureus ST398 was present in Taiwan in 2012 and potentially earlier. Although some isolates could be linked to livestock, most ST398 S. aureus isolates identified in Taiwan, particularly MRSA, represent human-adapted strains. Local transmission of human-adapted MRSA ST398 strains has occurred in nursing homes in Taiwan, possibly after import from China. Further surveillance is needed.

Enterovirus 71 (EV71)-neutralizing antibodies correlate with protection and have potential as therapeutic agents. We isolate and characterize a panel of plasmablast-derived monoclonal antibodies from an infected child whose antibody response focuses on the plateau epitope near the icosahedral 3-fold axes. Eight of a total of 19 antibodies target this epitope and three of these potently neutralize the virus. Representative neutralizing antibodies 38-1-10A and 38-3-11A both confer effective protection against lethal EV71 challenge in hSCARB2-transgenic mice. The cryo-electron microscopy structures of the EV71 virion in complex with Fab fragments of these potent and protective antibodies reveal the details of a conserved epitope formed by residues in the BC and HI loops of VP2 and the BC and HI loops of VP3 spanning the region around the 3-fold axis. Remarkably, the two antibodies interact with the epitope in quite distinct ways. These plateau-binding antibodies provide templates for promising candidate therapeutics. To date, no therapeutic agents against enterovirus 71, the causative agent of hand, foot and mouth disease, exist. Here, using Cryo-EM Huang et al. characterize two plasmablast-derived plateau-binding neutralizing antibodies conferring effective protection against lethal EV71 challenge in vivo.

Background Rotavirus infection is a leading cause of acute gastroenteritis in children aged < 5 years. However, few studies assessed the spillover effect on caregivers’ health-related quality of life (HRQoL) and out-of-pocket costs associated with rotavirus gastroenteritis (RGE) in Taiwan. Methods This is a prospective, observational, survey-based study conducted in Northern Taiwan between March 2021-September 2023. Caregivers were interviewed during the RGE-hospitalization episode and after patient discharge. One caregiver per child aged ≤ 9 years with clinical presentation of a new RGE hospitalization was enrolled. Outcomes assessed included caregiver HRQoL, emotional state, impact on daily routine, healthcare resource utilization (HCRU), and direct and indirect costs. Results The mean age of inpatients was 3.03 years and 69.0% were male. Rotavirus genotype G3P[8] was detected in 61.2% of patients. Caregivers' mean age was 33.7 years, 79.3% were female, and 65.5% had monthly household income < NT$80,000. Caregivers reported significantly higher health state (EQ visual analog scale) after discharge (86.21) than during RGE hospitalization (74.48) ( p  = 0.049). Among the caregivers, 65.5% and 69.0% experienced disruptions in sleep and leisure activities, respectively. About 45% were worried about complications and 41.4% were concerned about their child’s recovery. The total medical costs associated with hospitalization, reimbursed by National Health Insurance, averaged US$575.56. Additional out-of-pocket costs included US$82.51 for medical visits, US$44.95 for transportation, US$5.47 for medication, and US$90.41 for meals outside the home. The caregivers also reported taking an average of 0.12, 1.18, and 1.82 days of child/parental, paid, and unpaid leave, respectively. The estimated wage loss associated with the days not working was US$246.67. Conclusion RGE poses a significant burden on caregivers’ HRQoL, daily activities, and out-of-pocket costs. Interventions aimed at mitigating the spillover effects of RGE on caregivers are essential to improve family well-being. Clinical trial number Not applicable.

Jer-Yuarn Wu, Fuu-Jen Tsai, Yuan-Tsong Chen and colleagues report a genome-wide association study of Kawasaki disease. They show that common variants near BLK and CD40 influence susceptibility to this acute childhood vasculitis. To find new candidate loci predisposing individuals to Kawasaki disease, an acute vasculitis that affects children, we conducted a genome-wide association study in 622 individuals with Kawasaki disease (cases) and 1,107 controls in a Han Chinese population residing in Taiwan, with replication in an independent Han Chinese sample of 261 cases and 550 controls. We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40 , that are associated with Kawasaki disease at genome-wide significance ( P < 5 × 10 −8 ). Our findings may lead to a better understanding of the role of immune activation and inflammation in Kawasaki disease pathogenesis.

Protective antibody levels are critical for protection from severe enterovirus 71 infection. However, little is known about the specificities and functional properties of the enterovirus 71-specific antibodies induced by natural infection in humans. Here we characterize 191 plasmablast-derived monoclonal antibodies from three enterovirus 71-infected children, each of whom shows a distinct serological response. Of the 84 enterovirus 71-specific antibodies, neutralizing antibodies that target the rims and floor of the capsid canyon exhibit broad and potent activities at the nanogram level against viruses isolated in 1998–2016. We also find a subset of infected children whose enterovirus 71-specific antibodies are focused on the 3- and 2-fold plateau epitopes localized at the margin of pentamers, and this type of antibody response is associated with lower serum titers against recently circulating strains. Our data provide new insights into the enterovirus 71-specific antibodies induced by natural infection at the serological and clonal levels. Enterovirus 71 is a leading cause of hand-foot-and-mouth disease and herpangina. Here, the authors characterize a large panel of plasmablast-derived IgG mAbs that target the capsid of EV71 to identify neutralizing antibodies induced by natural infection.