The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteristics and pathological features underlying EV71-associated encephalitis and pulmonary edema remain largely unknown. In this study, we performed a proteomic analysis of fresh brain and lung tissues from EV71-infected mice at 7 days post infection. We detected a perturbed expression of 148 proteins in the brain and 78 proteins in the lung after EV71 expression. Further analysis showed that the dysregulated proteins in the brain are involved in a variety of fundamental biological pathways, including complement and coagulation cascades, innate and adaptive immune responses, platelet activation, and nitrogen metabolism, and those proteins in the lung participate in innate and adaptive immune responses, phagosome, arginine biosynthesis, and hypoxia-inducible factor 1 signaling pathway. Our results suggested that immune activation, complement and coagulation dysfunction, platelet activation, imbalance of nitrogen metabolism, and hypoxia could be involved in the pathogenesis of EV71, which explains the major clinical manifestation of hyperinflammatory status of severe HFMD cases. Our study provides further understanding of the molecular basis of EV71 pathogenesis.

/pdf/pathological-features-of-enterovirus-71-associated-brain-and-4vejc8y5jn.pdf

Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis.

We aimed to quantify the relationship between the outpatient visits of hand, foot, and mouth disease (HFMD) and diurnal temperature range (DTR). The data of daily HFMD outpatient visits and meteorological parameters were obtained. A distributed lag nonlinear model combined with generalized linear model was used to estimate simultaneously nonlinear and delayed effects between DTR and daily HFMD outpatient visits after controlling confounding factors. A total of 15,275 HFMD visits were enrolled. DTR was significantly associated with HFMD outpatient visits in children. High DTR (P75: 11.4 °C) and extreme DTR (P95: 15.3 °C) were compared with 8.5 °C, and HFMD visits increased by a maximum of 3.93% (95% CI: 1.82 to 6.07%) and 4.47% (95% CI: 0.45 to 8.65%) in single-day lag effect, respectively. Furthermore, the extreme DTR effect decreased with the lag time and lasted for 10 days. Cumulative lag effects with markedly increasing percent of visits are over 64.88%. Furthermore, the effects were most pronounced among female children and children aged 0–2 years. Our study suggested that DTR changes were associated with HFMD outpatient visits, and populations of female and aged 0–2 years were more sensitive.

Association between diurnal temperature range and outpatient visits for hand, foot, and mouth disease in Hefei, China: a distributed lag nonlinear analysis.

Transmitted and acquired oseltamivir resistance during the 2018-2019 influenza season

Genomic analysis of a recombinant coxsackievirus A19 identified in Xinxiang, China, in 2019

The waning of vaccine protection may be responsible for outbreaks toward the end of the influenza season. Three of five outbreaks occurred at the beginning of April following an interval of >100 days from the date of vaccination; the reported index case was a nurse or office worker, and >50% of those affected were healthcare workers. The results are consistent with intra-seasonal waning of vaccine immunity that resulted in outbreaks at the end of season.

End-of-season outbreaks of nosocomial influenza caused by waning vaccine immunity.

Emergence of Coxsackie A6 hand-foot-and-mouth disease and comparative severity of Coxsackie B vs. echovirus infections, 2014-2016, UK.

Early seasonal influenza vaccination and delayed influenza peaks - A possible cause of end-of-season outbreaks.

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Emergence of Coxsackie A6 hand-foot-and-mouth disease and comparative severity of Coxsackie B vs. echovirus infections, 2014-2016, UK.

Early seasonal influenza vaccination and delayed influenza peaks - A possible cause of end-of-season outbreaks.