At present, the mechanism of NPE is thought to be caused by specific injury in brainstem or medulla oblongata and inflammatory response [ 32 , 46 , 47 ]. Central nervous system lesions and inflammatory response can increase the intracranial pressure, which causes dysfunction of the optic hypothalamus and medullary solitary tract nucleus and complications such as vomiting, consciousness disorders, Convulsion, excessive sympathetic excitation, etc.
Then the level of serum catecholamine epinephrine, norepinephrine, etc. Blood flow impact may induced vascular endothelial cell damage, vasoactive substances like histamine and bradykinin are released in large quantities, then vascular permeability increased and the plasma extravasation is massive, which intensifying the degree of pulmonary edema. Through the analysis of NPE mechanism, combined with the results of this study, the neurological complications might be the timely predictive factors of poor prognosis, especially consciousness disorders, general weakness, abnormal pupillary light reflex, and some respiratory and circulatory complications are thought to be the warning signal for severe HFMD children, such as white frothy sputum, pink frothy sputum, tachypnea, cyanosis on lips or the whole body; moist rales, tachycardia,arrhythmia, cold limbs, pale complexion, and weakened pulse.
Spatial aggregation of disease means that the risk of disease is significantly higher in some regions than in others. Through analyzing the severe HFMD cases from to in Chongqing, by using space-time scan, found that the clusters were mainly concentrated in Kaixian in , Xiushan in , Fuling and Wanzhou in , and in , mainly concentrated in the Wuxi and Liangping, and it is interesting to note that these areas are mainly concentrated near the Yangtze River basin, which indicates that the prevalence of severe HFMD may be associated with the flow of population, water pollution or other factors related to the river.
From the perspective of overall incidence, the results showed that, the incidence of severe HFMD was relatively high in , and , and significantly decreased in , and , which may be due to the medical and economic conditions in different regions, showing a cyclical change of decrease and increase, and the prevention and control situation is severe.
As an exploratory analysis, the spatial-temporal scanning method objectively demonstrated the spatial and temporal regularity of the severe HFMD, and well evaluated the abnormal increase of HFMD in different time and space.
Through the study, it was found that the incidence of serve HFMD in Chongqing from to was not randomly distributed, and there was obvious spatial and temporal aggregation. The spatial-temporal scanning analysis method makes up for the deficiency of the simple epidemiological morbidity comparison and avoids the artificial high incidence of infectious diseases. The judgment of the incidence area is more convincing than the conventional analysis.
Meanwhile, combined with the geographic information system, the incidence aggregation area is more intuitive and comprehensive, providing a scientific reference for the development of targeted prevention and control measures in the future. In conclusion, the correct and timely diagnosis of HFMD, the timely detection of severe cases, as well as timely intervention, close monitoring, and symptomatic treatment are the keys to avoid or slow down the further development of severe cases and reduce the mortality rate of severe HFMD.
Besides, health education should be carried out before the high incidence period of HFMD and preventive or protective measures should be taken for children according to the temporal, spatial and socio-demographic epidemiological distribution characteristics of HFMD.
Highly sensitive and rapid methods to detect the enterovirus are also needed to be developed [ 50 , 51 ]. The results of this study can be the reference of further clinical and public health practice. In this study, several clinical risk factors and the temporal, spatial and socio-demographic distribution epidemiological characteristics of severe HFMD contribute to the timely diagnosis and intervention of severe HFMD.
Public health or medical staff should take specific measures measures for the children according to the clinical and epidemiological characteristics of severe HFMD, the results of the present study can be the reference of further clinical and public health practice or studies.
Hand, foot, and mouth disease in China, — an epidemiological study. Lancet Infect Dis. Ambulatory pediatric surveillance of hand, foot and mouth disease as signal of an outbreak of Coxsackievirus A6 infections, France, —, Emerging. Infect Dis. Article Google Scholar. Atypical presentations of hand, foot, and mouth disease caused by Coxsackievirus A6 — Minnesota, Virology, epidemiology, pathogenesis, and control of enterovirus PubMed Article Google Scholar.
Enteroviruses associated with hand, foot, and mouth disease in Brazil. J Inf Secur. Google Scholar. Receptors identified for hand, foot and mouth virus. Nat Med. Enterovirus and human Parechovirus surveillance - United States, Samanta GP. A delayed hand-foot-mouth disease model with pulse vaccination strategy. Comp Appl Math. Goksugur N, Goksugur S. Images in clinical medicine. Hand, foot, and mouth disease. N Engl J Med. Esposito S, Principi N. Hand, foot and mouth disease: current knowledge on clinical manifestations, epidemiology, aetiology and prevention.
Clinical features, diagnosis, and management of enterovirus Lancet Neurol. Sharma S, Samanta GP. Analysis of a hand-foot-mouth disease model. Int J Biomathematics. Modelling person-to-person transmission in an enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis. Emerg Microbes Infect.
A guide to clinical management and public health response for hand foot mouth disease HFMD ; Dec Hand, foot, and mouth disease in China: modeling epidemic dynamics of enterovirus serotypes and implications for vaccination. PLoS Med. Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges. J Epidemiol Community Health. Distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications.
Virol J. Epidemiological surveillance of hand, foot and mouth disease in Shanghai in —, prior to the introduction of the enterovirus 71 vaccine. An eight-year study of epidemiologic features of enterovirus 71 infection in Taiwan. Am J Trop Med Hyg. Seiff A. Cambodia unravels cause of mystery illness. Clin Microbiol Infect. Coxsackievirus A6 and enterovirus 71 causing hand, foot and mouth disease in Cuba, — Arch Virol. Epidemiological characteristics and spatial-temporal distribution of hand, foot, and mouth disease in Chongqing, China, — Temporal and spatial clustering characteristics and changes of severe hand, foot, and mouth disease in mainland of China, from to Epidemiological characteristics of hand, foot, and mouth disease in Shandong, China, Sci Rep.
Accessed on 23 June Severe hand, foot and mouth disease in Shenzhen, South China: what matters most? Epidemiol Infect. Spatial clustering of severe hand-foot-mouth disease cases on Hainan Island, China. Jpn J Infect Dis. Risk factors for critical disease and death from hand, foot and mouth disease.
Pediatr Infect Dis J. Risk factors for severe hand foot mouth disease in Singapore: a case control study. BMC Infect Dis. Clinical features and risk factors of pulmonary oedema after enterovirusrelated hand, foot, and mouth disease.
In our study, The proportion and case fatality rate of severe cases in this study were higher than the above study. This is because all children included in this study were hospitalised; mild cases that may have been diagnosed at the outpatient clinic were not included. In addition, our study also included severely ill children who were referred from the primary hospital.
Our study also found that susceptible pathogens and case fatality rates varied between ages. This may be due to two main reasons. Firstly, this may be because children under 1 year of age are mainly breastfed, and breastfeeding is a protective factor against HFMD progression Breast milk may promote the development of the gastrointestinal system of infants and young children which prevents the invasion of foreign viruses.
Furthermore, breast milk contains immune substances, immunomodulators, and inflammatory factors, including some antibodies from the mother 11 , Secondly, older children partake in more activities and have greater contact with the outside world; therefore, they have more opportunities to contact children with latent infection or infected people.
With respect to time distribution, this study showed that the number of cases, the highest proportion of severe disease, and the case fatality rates were highest in However, there were no fatalities in During these five years, the number of HFMD cases increased every other year, and the incidence of complications and mortality between and first increased and then decreased.
Wu et al. These findings support our arguments. These changes may be due to the fact that mixed infections led to genetic recombination of pathogens. This co-infection, which leads to viral gene recombination 12 , could have been responsible for the repeated outbreaks or epidemics of HFMD in China.
Similar results of changes in virus types were also described in different districts in a Japanese study; CV-A6 was the main pathogen of HFMD in and the outbreak occurred once every two years A study in Europe also found a high prevalence of EV-D68 in 14 countries In terms of complications and case fatality rates, our study found that EV-A71 had the highest complication and case fatality rates of Weng et al.
The proportion of EV-A71 infection in children with the mild form of the disease was Disease surveillance data from Shanghai between and showed that From the same surveillance, 5.
According to the national surveillance data, the number of deaths caused by EV-A71, CV-A16, and other enteroviruses in — were , 43, and ; while the mortality rates were 0. This previous mortality rates are similar to the results of this study. Since our study found that EV-A71 infections were concentrated between April and July, we recommend that clinicians should be alert to both EV-A71 and children with severe illnesses during this period in order to implement active intervention measures to reduce the incidence of complications and mortality.
This study had some limitations. The HFMD cases included in this study were drawn from a hospital, and our sample may have been biased.
However, the large sample of HFMD hospitalised cases portrays an accurate representation of hospitalised children; a high proportion of our participants had severe disease and provided information that was beneficial for clinical practice. With regards to the composition of virus types, EV-A71 and CV-A16 infections decreased continuously, as the number of cases caused by other enteroviruses increased each year.
In terms of disease severity, EV-A71 and mixed infections accounted for the high case fatality rates of infections among children with SHFMD, but EV-A71 had the highest incidence of complication and mortality.
The mild form of the disease was mainly caused by other enteroviruses. All the data were fully anonymised. All experiments were performed in accordance with the approved guidelines and regulations. Patients were excluded from this study if they had any of the following characteristics: incomplete documentation of information 37 cases, 0. Finally, cases were included for clinical analysis. Data were obtained from the medical records. Information on children with HFMD, including hospitalisation number, gender, date of birth, date of admission, date of discharge, admission to the department, admission stage, admission diagnosis, and complications during hospitalisation brain encephalitis, pulmonary oedema, pulmonary haemorrhage, circulatory failure , type of virus, mild or severe type, and outcome, was obtained.
According to the expert agreement on clinical treatment of severe cases of enterovirus 71 EV-A71 infection HFMD classification criteria, the disease is divided into five phases: eruption stage, neurological stage, early stage of cardiorespiratory failure, cardiopulmonary failure, and convalescence Evaluation of the severity of disease was performed based on the guidelines for the diagnosis and treatment of SHFMD SHFMD was defined as rapidly progressing with meningitis and encephalitis brainstem encephalitis is the most dangerous , encephalomyelitis, pulmonary oedema, and circulatory disorders which may occur in the first to fifth day of onset.
Meningitis, brainstem encephalitis, encephalitis, pulmonary oedema, pulmonary haemorrhage, and circulatory failure are described as follows. Brainstem encephalitis: frequent spasms, convulsions or acute flaccid paralysis acute emergence of asymmetrical, non-progressive weakness or paralysis in one or more groups of muscle , reduced or absent deep tendon reflexes.
Encephalitis: children with altered level of consciousness, no febrile seizures, or localised neurological deficit defined as the presence of non-reflective limb weakness in the acute phase of the child. Pulmonary haemorrhage: alveolar hyperaemia observed on X-ray and dark red foamy sputum or bloody fluid seen through the tracheal tube.
Circulatory failure: children with respiratory distress, tachycardia, pulmonary oedema, and pulmonary haemorrhage. Primers were designed based on the species specificity and highly conserved segments of the enterovirus.
RNA was extracted according to the experimental procedure provided by the manual, and real-time PCR was performed after reverse transcription. The procedures strictly adhered to the operation standard in the kit. The reference value was set at According to the examination results, children were divided into the EV group, CV-A6 group, and mixed infection group.
Children with negative test results but clinically diagnosed HFMD were defined as other enteroviruses groups. Categorical variables i.
Continuous variables, such as age and length of stay, were summarised as median and inter-quartile ranges IQR if the data were not normally distributed. The Wilcoxon signed rank test was used to compare differences in laboratory indicators between the survivor and non-survivor groups. The dataset generated and analysed in this study are available from the corresponding author on reasonable requests. Liu, B. Tian, H.
Clinical features and management outcomes of severe hand, foot and mouth disease. Article Google Scholar. Weng, Y. Epidemiology and etiology of hand, foot, and mouth disease in Fujian province, — Zhou, Z. This case report aims to describe a fatal case of HFMD with minimal oral and skin manifestations. Case report: A four-year-old girl was brought to a hospital after suddenly becoming unresponsive at home. She had a history of fever and lethargy for three days prior to her demise. The patient, and f ive other children in her neighbourhood had been diagnosed to have HFMD at a local health clinic; the other children had recovered without complications.
Results: Autopsy revealed a few punctate, sub-epidermal vesicles measuring 1 to 2 mm on the palm of her right hand and sole of the right foot, visible only with a magnifying glass.
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