Hand, Foot, and Mouth Disease (HFMD) is an outbreak infectious disease that can easily spread among children under the age of five. The most common causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but infection caused by EV71 is more associated with fatalities due to severe neurological disorders. The present diagnosis methods rely on physical examinations by the doctors and further confirmation by laboratories detection methods such as viral culture and polymerase chain reaction. Clinical signs of HFMD infection and other childhood diseases such as chicken pox, and allergies are similar, yet the genetics and pathogenicity of the viruses are substantially different. Thus, there is an urgent need for an early screening of HFMD using an inexpensive and user-friendly device that can directly detect the causative agents of the disease. This paper reviews current HFMD diagnostic methods based on various target types, such as nucleic acid, protein, and whole virus. This was followed by a thorough discussion on the emerging sensing technologies for HFMD detection, including surface plasmon resonance, electrochemical sensor, and surface enhanced Raman spectroscopy. Lastly, optical absorption spectroscopic method was critically discussed and proposed as a promising technology for HFMD screening and detection.

BACKGROUND: Hand-foot-mouth disease (HFMD) is a common childhood infectious disease. Atypical skin findings of HFMD, often associated with coxsackievirus A6 (CVA6), were first reported in 2008, with increasing reports worldwide since. Atypical lesions of HFMD often involve sites beyond the palms and soles and tend to have unusual, polymorphic morphology.
METHODS: A systematic review was conducted on clinical features and outcomes of pediatric HFMD with atypical cutaneous manifestations.
RESULTS: Eighty-five studies were included, representing 1359 cases with mean age 2.4 years and a male predominance of 61%. The most reported morphologies were vesicles (53%), papules (49%), and bullae (36%). Other morphologies included eczema herpeticum-like (19%), purpuric/petechial (7%), and Gianotti Crosti-like (4%). Common atypical sites included the arms and/or legs (47%), face (45%), and trunk (27%). CVA6 was identified in 63% of cases. Symptoms resolved in a mean of 10 days. Overall, 16% of cases received treatment, most commonly with acyclovir, intravenous antibiotics, or topical steroids. The most common complications were nail changes (21%) and desquamation (4%) which occurred a mean of 3 and 2 weeks after symptoms, respectively.
CONCLUSIONS: Due to unusual morphologies resembling other conditions, HFMD with atypical cutaneous findings may be misdiagnosed, leading to inappropriate and unnecessary investigations, hospitalization, and treatment. Greater awareness of atypical presentations of HFMD is warranted to improve patient care and counseling on infection control precautions.

Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has gradually become the dominant pathogen of HFMD in recent years. This study was conducted mainly to assess the serological prevalence of EV-A71 and CVA6 antibodies in people of different ages, sexes, and regions through a systematic review and meta-analysis. A comprehensive study was performed based on the EV-A71 and CVA6 serological literature published before May 2022. Heterogeneity analysis (Cochrane\'s Q test and the I2 statistic) and random effect models were adopted. Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity in the data, and all analysis was performed using STATA version 16.0. This study included 71 studies involving 55,176 people from 13 countries that met the inclusion criteria. The serological prevalence of EV-A71 antibody in different studies was 4.31-88.8%, and that of CVA6 antibody was 40.8-80.9%. Meta-analysis results showed that the serum positive rate for EV-A71 antibody was 45.9% (95% CI: 37.6-54.1%). The rate in the Chinese population was 47.8% (95% CI: 42.4-53.2%), and in the other countries, it was 38% (95% CI: 23-55%). The serum positive rate for CVA6 antibody was 58.3% (95% CI: 46.5-70.2%). The rate in the Chinese population was 49.1% (95% CI: 38.3-59.9%), and in the other countries, it was 68% (95% CI: 51-83%). Subgroup analysis was also conducted. The seroprevalence of EV-A71 and CVA6 antibodies is related to age rather than gender or region. The rates of EV-A71 and CVA6 seropositivity are considerably lower in children younger than five years of age. However, the rates gradually increase with age. The findings of this study suggest that children under five years of age may be susceptible to EV-A71 and CVA6. Thus, safety education and vaccination should be strengthened accordingly. This study provides a basis for understanding the risk factors for EV-A71 and CVA6 infection in China and for deciding how to formulate standard preventive measures to prevent the spread of the virus.

OBJECTIVE: The purpose of this study is to study laboratory indicators for the identification of hand, foot, and mouth disease (HFMD) severity.
METHODS: We searched PubMed, Embase, and the Web of Science for literature that was published before May 2022. The main results are presented as forest plots. Subgroup analyses, sensitivity analyses, and publication bias were also performed.
RESULTS: Our study indicated that white blood cells (WBC) (95%CI: 0.205-0.778), blood glucose (95%CI: 0.505-0.778), lymphocytes (95%CI: 0.072-0.239), creatinine (95%CI: 0.024-0.228), interleukin (IL)-2 (95%CI: 0.192-1.642), IL-6 (95%CI: 0.289-0.776), IL-8 (95%CI: 0.499-0.867), IL-10 (95%CI: 0.226-0.930), interferon-γ (IFN-γ) (95%CI: 0.193-2.584), tumor necrosis factor-α (TNF-α) (95%CI: 1.078-2.715), and creatine kinase MB isoenzyme (CK-MB) (95%CI: 0.571-1.459) were associated with an increased risk of HFMD severity, and the results of the sensitivity analysis of these indicators were stable and free of publication bias.
CONCLUSIONS: Our results suggest that various deleterious immune and metabolic changes can increase the risk of HFMD severity, which can provide a basis for predicting the prognosis and useful evidence for clinicians to manage patients efficiently.

BACKGROUND: Hand, foot, and mouth disease is a common viral disease in childhood. Because the disease has the potential to reach epidemic levels and mortality is high in some countries, early recognition of this disease is of paramount importance.
OBJECTIVE: This purpose of this article is to familiarize pediatricians with the clinical manifestations and management of hand, foot, and mouth disease.
METHODS: A search was conducted in February 2022 in PubMed Clinical Queries using the key term \"hand, foot, and mouth disease\". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in English were included in this review.
RESULTS: Hand, foot, and mouth disease is characterized by a painful oral enanthem and asymptomatic exanthem on the palms and soles. Children younger than 5 years are most commonly affected. Hand, foot, and mouth disease caused by enterovirus A71 is more severe and has a higher rate of complications than that attributed to other viruses such as coxsackievirus A16. Circulatory failure secondary to myocardial impairment and neurogenic pulmonary edema secondary to brainstem damage are the main causes of death. Fortunately, the disease is usually benign and resolves in 7 to10 days without sequelae. Given the self-limited nature of most cases, treatment is mainly symptomatic and supportive. Intravenous immunoglobulin should be considered for the treatment of severe/complicated hand, foot, and mouth disease and has been recommended by several national and international guideline committees. Currently, there are no specific antiviral agents approved for the treatment of the disease. Drugs such as ribavirin, suramin, mulberroside C, aminothiazole analogs, and sertraline have emerged as potential candidates for the treatment of hand, foot, and mouth disease. Vaccination of susceptible individuals in high-risk areas and good personal hygiene are important preventative measures to combat the disease.
CONCLUSIONS: Familiarity of the disease including its atypical manifestations is crucial so that a correct diagnosis can be made, and appropriate treatment initiated. A timely diagnosis can help avoid contact with the affected individual and decrease the risk of an outbreak.

For the past few years, only a few monovalent EV71 vaccines have been developed, while other enterovirus vaccines are in short supply. We conducted a quantitative meta-analysis to explore the epidemiological characteristics, routine laboratory diagnosis, clinical signs and risk factors for hand, foot and mouth disease (HFMD).
PubMed, Embase and the Web of Science were searched for eligible reports published before April 16, 2021, with no publication time or language restrictions. The primary outcome was the odds ratio of the epidemiological characteristics, routine laboratory diagnosis, and clinical signs associated with HFMD severity and death.
After screening 10522 records, we included 32 articles comprising 781903 cases of hand, foot and mouth disease. Patients with severe illness developed some clinical signs (hypersomnia (OR = 21.97, 95% CI: 4.13 to 116.74), convulsion (OR = 16.18, 95% CI: 5.30 to 49.39), limb shaking (OR = 47.96, 95% CI: 15.17 to 151.67), and breathlessness (OR = 7.48, 95% CI: 1.90 to 29.40)) and had some changes in laboratory parameters (interleukin-6 levels standardized mean difference (SMD) = 1.57, 95%CI: 0.55 to 2.60), an increased neutrophils ratio (SMD = 0.55, 95%CI: 0.17 to 0.93), cluster of differentiation 4 (CD4+) (SMD = -1.38, 95%CI: -2.33 to -0.43) and a reduced lymphocytes ratio (SMD = -0.48, 95%CI: -0.93 to -0.33)) compared with patients with mild illness. The risk factors for death included cyanosis (OR = 5.82, 95% CI: 2.29 to 14.81), a fast heart rate (OR = 3.22, 95% CI: 1.65 to 6.30), vomiting (OR = 2.70, 95% CI: 1.33 to 5.49) and an increased WBC count (SMD = 0.60, 95% CI: 0.27 to 0.93).
China has the highest incidence of HFMD. Our meta-analyses revealed important risk factors that are associated with the severity and mortality of HFMD.

BACKGROUND: Hand-foot-mouth is a viral infectious disease characterized by fever, hand foot rash and oral mucosal herpes caused by a variety of enteroviruses. It is often found in preschool children, and its immune system is not well developed, so it is very susceptible to infection by pathogens and epidemics, resulting in rapid progress of the disease. At present, the commonly used Chinese patent medicine oral liquid in our country has good clinical efficacy of antiviral, antibacterial, antiphlogistic and improving immunity, but there is no evidence to compare the clinical efficacy and safety of a variety of oral liquid of Chinese patent medicine. Therefore, this study is aim to use the network meta-analysis to integrate the clinical relevant evidence of direct and indirect comparative relationship, and to conduct quantitative comprehensive statistical analysis and sequencing after the aggregation of different Chinese patent medicine oral liquid with the same evidence body, and then the best clinical medication scheme is selected, which can provide reference value and evidence-based theoretical evidence for clinical optimization of drug selection.
METHODS: Comprehensive retrieval of CNKI, VIP, CBM, and WANFANG database and the Cochrane Library, PubMed, Web of Science and EMBASE database. Search and publish the clinical RCT of these 7 kinds of oral liquid of Chinese patent medicine compared with ribavirin or oral liquid of Chinese patent medicine. The retrieval time is from the establishment of the database to October 31st, 2021. The 2 first authors will screen the literatures that meets the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane manual standard. Data merging and network meta-analysis were carried out with R programming software to evaluate the ranking probability of all interventions.
RESULTS: This network meta-analysis and probability ranking will identify the best Chinese patent medicine oral liquid treatment for Hand-foot-mouth.
CONCLUSIONS: This study will provide systematic evidence-based medicine evidence for Chinese patent medicine oral liquid treatment for Hand-foot-mouth, and help clinicians, patients with poststroke depression and decision-makers to make more effective, safer and economic optimal treatment plan in the decision-making process.
BACKGROUND: INPLASY202210032. The protocol for this systematic review was registered on INPLASY and is available in full on the inplasy.com (https://inplasy.com/inplasy-2022-1-0032/).

BACKGROUND: Previous reports have described hypogonadism associated with virus infection such as hantavirus, human immunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). However, to our best knowledge there has been no case report of secondary hypogonadism following hand, foot, and mouth disease (HFMD).
METHODS: A previously healthy 28-year-old man with no history of major physical and psychological trauma, presented with bilateral gynecomastia and erectile dysfunction 2 weeks after HFMD. Laboratory testament showed the level of gonadotropin hormones declined. Imaging examination demonstrated no major abnormal change in pituitary or reproductive system. The diagnosis of hypogonadism was established. Then the patient was ordered to maintain mental health outward of hospital without drug intervention. One month after presentation, his gonadotropin hormone level and sexual desire had recovered, while bilateral gynecomastia and erectile dysfunction symptoms disappeared.
CONCLUSIONS: Physicians should notice the possibility for hypogonadism in adult patients with a recent history of HFMD.

UNASSIGNED: This study reports a systematic review of association between meteorological parameters and hand, foot and mouth disease (HFMD) in mainland China.
UNASSIGNED: Using predefined study eligibility criteria, three electronic databases (PubMed, Web of Science, and Embase) were searched for relevant articles. Using a combination of search terms, including \"Hand foot and mouth disease,\" \"HFMD,\" \"Meteorological,\" \"Climate,\" and \"China,\" After removal of duplicates, our initial search generated 2435 studies published from 1990 to December 31, 2019. From this cohort 51 full-text articles were reviewed for eligibility assessment. The meta-analysis was devised in accordance with the published guidelines of the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Effect sizes, heterogeneity estimates and publication bias were computed using R software and Review Manager Software.
UNASSIGNED: The meta-analysis of 18 eligible studies showed that the meteorological parameters played an important role in the prevalence of HFMD. Lower air pressure may be the main risk factor for the incidence of HFMD in Chinese mainland, and three meteorological parameters (mean temperature, rainfall and relative humidity) have a significant association with the incidence of HFMD in subtropical regions.
UNASSIGNED: Lower air pressure might be the main risk factor for the incidence of HFMD in Chinese mainland. The influence of meteorological parameters on the prevalence of HFMD is mainly through changing virus viability in aerosols, which may be different in different climate regions. In an environment with low air pressure, wearing a mask that filters the aerosol outdoors may help prevent HFMD infection.

BACKGROUND: Hand-Foot-and-Mouth disease (HFMD) is a viral illness commonly seen in young children, characterized by fever, vomiting, ulcerative lesions in oral mucosa, and vesicles on hands and feet. The early symptoms resolve but sometimes, it leads to more harsh neurological complications and even death. Therefore, the objective of this review was set to provide an overview of the symptoms, pathogenic agents, and treatment of neurological complications associated with HFMD.
METHODS: We reviewed literature from PubMed and Science Direct covering at least one of our objectives from inception to 4th March 2018.
RESULTS: This review represents 6 countries including China, Vietnam, Cambodia, South Korea, Taiwan, and Australia. Fifteen studies with a total of 1043 patients were included. The majority of HFMD cases with neurological complications were reported in China, predominance in boys as compared to girls, with 97% cases under 15 years of age. Meningoencephalitis and brainstem encephalitis contributed 70% of all neurological complications related to HFMD. Human Enterovirus71 genotype C, especially C4a was a causative agent associated with severe complications. Among symptoms, fever, vomiting, myoclonic jerks or seizure, headache, convulsion, and rashes were reported in almost all neurological complications. The common and supportive treatments were the administration of intravenous immunoglobulin and glucocorticoid therapies.
CONCLUSIONS: Early detection and appropriate treatment of severe neurological complications can minimize the risk of adverse health outcomes. Evidence based clinical practice guidelines for early detection and treatment would be significant in the management of these devastating neurological complications.