3C protease of enterovirus 71 cleaves promyelocytic leukemia protein and impairs PML-NBs production

Background Enterovirus 71 (EV71) usually infects infants causing hand-foot-mouth disease (HFMD), even fatal neurological disease like aseptic meningitis. Effective drug for preventing and treating EV71 infection is unavailable currently. EV71 3C mediated the cleavage of many proteins and played an important role in viral inhibiting host innate immunity. Promyelocytic leukemia (PML) protein, the primary organizer of PML nuclear bodies (PML-NBs), can be induced by interferon and is involved in antiviral activity. PML inhibits EV71 replication, and EV71 infection reduces PML expression, but the molecular mechanism is unclear. Methods The cleavage of PMLIII and IV was confirmed by co-transfection of EV71 3C protease and PML. The detailed cleavage sites were evaluated further by constructing the Q to A mutant of PML. PML knockout cells were infected with EV71 to identify the effect of cleavage on EV71 replication. Immunofluorescence analysis to examine the interference of EV71 3C on the formation of PML-NBs. Results EV71 3C directly cleaved PMLIII and IV. Furthermore, 3C cleaved PMLIV at the sites of Q430–A431 and Q444–S445 through its protease activity. Overexpression of PMLIV Q430A/Q444A variant exhibited stronger antiviral potential than the wild type. PMLIV Q430A/Q444A formed normal nuclear bodies that were not affected by 3C, suggesting that 3C may impair PML-NBs production via PMLIV cleavage and counter its antiviral activities. PML, especially PMLIV, which sequesters viral proteins in PML-NBs and inhibits viral production, is a novel target of EV71 3C cleavage. Conclusions EV71 3C cleaves PMLIV at Q430–A431 and Q444–S445. Cleavage reduces the antiviral function of PML and decomposes the formation of PML-NBs, which is conducive to virus replication.

Atypical hand foot mouth disease presenting as vesiculobullous lesion

Hand, food, and mouth disease (HFMD) is a highly contagious disease caused by enteroviruses affecting young children under 5 years. Among enteroviruses (EVs), the main pathogens of HFMD are coxsackievirus A16 (CV-A16) and EV-A71 (EV-71).1 The clinical features include a prodromal phase which has low-grade fever, malaise and sore throat. This initial phase is usually followed by enanthem and erythematous papular skin lesions, predominantly affecting palms and soles. The dorsal surface of hands, feet, and perioral skin are rarely affected. Atypical HFMD presents as a widely distributed rash with varying morphology that makes clinical diagnosis and treatment challenging.2 Our objective is to present atypical cutaneous manifestations of HFMD caused by CA6.

Risk Factors for Severe Hand-Foot-Mouth Disease in China: A Systematic Review and Meta-Analysis

Background: This study aimed to identify potential risk factors for severe hand-foot-mouth disease (HFMD).Methods: The PubMed, Embase, the Cochrane Library, Sinomed, WanFang, CNKI, and VIP databases were searched (up to August 2021).Results: Twenty-nine studies (9,241 and 927,355 patients with severe HFMD and controls, respectively; all from China) were included. EV71 was associated with higher odds of severe HFMD compared with other agents (OR = 4.44, 95%CI: 3.12–6.33, p < 0.001). Being home-raised (OR = 1.99, 95%CI: 1.59–2.50, p < 0.001), higher number of children in the family (OR = 2.09, 95%CI: 1.93–2.27, p < 0.001), poor hand hygiene (OR = 2.74, 95%CI: 1.78–4.23, p < 0.001), and no breastfeeding (OR = 2.01, 95%CI: 1.45–2.79, p < 0.001) were risk factors for severe HFMD. First consulting to a district-level or above hospital (OR = 0.34, 95%CI: 0.25–0.45, p < 0.001) and diagnosis of HFMD at baseline (OR = 0.17, 95%CI: 0.13–0.24, p < 0.001) were protective factors against severe HFMD. Fever, long fever duration, vomiting, lethargy, leukocytosis, tic, and convulsions were each associated with severe HFMD (all p < 0.05), while rash was not.Conclusions: EV71, lifestyle habits, frequent hospital visits, and symptoms are risk factors for severe HFMD in children in China, while early diagnosis and admission to higher-level hospitals are protective factors.

Application Effect of Medical Care Integration Combined with Family Intervention under the Evidence-Based Nursing Mode on Child Patients with Severe Hand-Foot-Mouth Disease and Its Influence on Intestinal Function

Objective. To explore the application effect of medical care integration combined with family intervention under the evidence-based nursing mode on child patients with severe hand-foot-mouth disease (HFMD) and its influence on intestinal function. Methods. 120 child patients with severe HFMD admitted to Qilu Children’s Hospital of Shandong University from January 2019 to January 2020 were selected as the research object and randomly divided into group A and group B, with 60 cases each. Conventional nursing was performed on patients in group B, and medical care integration combined with family intervention under the evidence-based nursing mode was performed on patients in group A. Patients were assessed after the intervention using the hospital-made treatment adherence scale, PedsQLTM 4.0 (Pediatric Quality of Life Inventory Version 4.0) scale, and the faces pain scale-revised (FPS-R). The levels of gastrointestinal function indicators such as serum endotoxin (ET), diamine oxidase (DAO), and d-lactic acid (D-LA) were measured before and after the intervention, and recovery such as time to clear fever and time to relief of oral pain were recorded in both groups. Results. Children in group A had significantly higher compliance in diet, behaviour, exercise, and medication than group B ( P < 0.05 ); the time to clear fever, time to relief of oral pain, time to healing of oral ulcers, time to relief of skin herpes, time to hospitalization, and time to eating were shorter in group A than those in group B ( P < 0.001 ); all scores on the PedsQLTM 4.0 scale were higher in group A than those in group B after the intervention ( P < 0.001 ); ET, DAO, and D-LA levels decreased in both groups after the intervention, with group A having lower levels than group B ( P < 0.001 ), in addition, group A had lower eating pain scores after the intervention ( P < 0.05 ). Conclusion. Medical care integration combined with family intervention under the evidence-based nursing mode can effectively improve the treatment compliance of child patients with severe HFMD, accelerate their recovery progress, ensure a better prognostic quality of life and gastrointestinal tract function, and reduce the eating pain, indicating that such comprehensive nursing intervention mode should be promoted in practice.

Effectiveness of Educational Communication in Knowledge, Attitude, and Practice to Hand-Foot-Mouth Disease Prevention of Mother Having Children Under 5 Years Old

Background: Hand-foot-mouth disease (HFMD) is an infectious disease that mainly occurs in children under five years old. Vietnam is a developing country with high prevalence of the disease outbreak every year. Can Tho City, Co Do District had the highest incidence of children under five years old acquired HFMD. Objective: 1) To determine the factors correlating with knowledge, attitude, and practice in HFMD prevention of mothers having children under five years old, and 2) to evaluate the alteration in knowledge, attitude, and practice in prevention HFMD of mothers having children under five years old after intervention with health educational communication. Materials and Methods: Community intervention study was done in 420 subjects. At first, all the participants would do the questionnaire and practicing assessment. Then, the participants were divided into two groups, the intervened group for educational communication, and the control group with no intervention. The intervention included three steps, 1) training knowledge and skills for medical staffs and collaborators, 2) providing information about HFMD for the mothers, 3) broadcasting information leaflets to the subjects’ house every month. The assessment in awareness, attitude, and practice would be performed again after one month. The present study staff achieved approval from the Science and Educating Council of Can Tho University of Medicine and Pharmacy. In addition, the present study also received the agreement from The People’s Committee of Co Do District. Results: The present study results shows that 23.3% of mothers had the right knowledge, 50.5% of mothers had the right attitude, and 17.4% of mothers with children under five years of age had the right disease prevention practice. There was an association between education level of mothers with children under five years of age with knowledge, attitude, and practice in disease prevention. After intervention, knowledge of the mothers in the intervened group improved more than 2.79 times, right attitude more than 2.84 times, and practice improvement more than 1.83 times in compared with the control group. Conclusion: Educational communication plays an important role in HFMD disease prevention through increasing the awareness, opinion, and disease prevention of the mothers who directly take care of the under five years old children. Keywords: Hand-foot-mouth disease; Knowledge; Attitudes; Practices; Effective intervention

Nail Changes following Hand-Foot-Mouth Disease in North India

: Hand-foot-mouth disease (HFMD) is common, but nail changes have not been well described. We described nail changes in HFMD. Nail changes following (HFMD) in two outpatient clinics were assessed over two years. Out of 524 cases of HFMD, 40 patients (7.6%) presented with nail problems, 29 cases had onychomadesis, and 11 cases had Beau’s lines. The median age of the subjects was 36 (15 - 126) months, and slight male preponderance (23:17) was seen. HFMD is a common disease having delayed nail changes also. So identification of and preventive strategies are required to limit complications.