Epidemiology And Etiology Of HFMD In Shanghai

Hand, foot and mouth disease (HFMD) is a common illness of infants and children. It is an acute infectious disease characterized by fever, sores in the mouth, and a rash with blisters which are usually located on the tongue, gums, and the inside of the cheeks. But few patients can cause serious complications such as aseptic meningitis, brainstem encephalitis, neurogenic pulmonary edema, acute flaccid paralysis, and myocarditis and so on. Viruses from the group called enteroviruses including echoviruses, coxsackieviruses and enterovirus71(EV71) can cause HFMD, in which coxsackievirus A16and EV71are the most common cause of the disease. EV71can cause serious central neurological complications with high mortality and morbidity and really do great harm to children, so the public pay more attention to EV71infection. HFMD is a global contagious disease. Since1990s, EV71has become the main pathogen of HFMD, numerous outbreaks have occurred in Asia-Pacific region. In2008, the latest large epidemic occurred in Fuyang City, Anhui Province.9446HFMD cases were reported. In response, on2May,2008, HFMD was made a reportable disease, which was included into the notifiable class C infectious diseases category in China, with reporting required within24hours via the surveillance system, or by mail for facilities not covered by the system. The routes of transmission of EV71are so complex that HFMD can spread easily. Everyone is at risk of infection, but not everyone who is infected becomes ill. Children under4years old are more likely to be susceptible to infection. During the EV71epidemic, kindergartens and preschools often cause collective infection. Infection results in immunity to the specific virus, but a second episode may occur following infection with a different member of the enterovirus group. Because EV71is not coated, it has resistance to Ether, deoxycholate, detergents, disinfectants, as well as weak acid. And moreover, organic can protects virus to survive for several months in manure and sewage, resulting in HFMD easily spread from person to person. However, the specific antiviral drugs,treatments and effective vaccine have not been unavailable so far, thus in the HFMD epidemic periods, it is very necessary to take comprehensive measures to prevent EV71transmission, such as popularizing hygiene education, promoting personal hygiene and improving public sanitation.Our study mainly focuses on the epidemic characteristics and etiological agents distribution of severe hand, foot and mouth disease, EV71detection of paired specimens, the complete genome characteristics of EV71isolates from mild and severe HFMD, external survivability of EV71and the effect of comprehensive interventions on blocking HFMD in Shanghai. This research contains five parts as following:1. Epidemic characteristics and pathogen detection of sever HFMD in Shanghai,2011After analyzing the epidemiological data of all hand, foot, and mouth disease cases from the National Disease Supervision Information Management System in Minhang district of Shanghai in2011, a total of364children were reported with severe HFMD, who were concentrated mainly in1-3year-old children accounting for65.93%of the total cases. The number of severe HFMD cases appeared to be most (40.38%) in one year old group, and with age increasing, the number of severe cases had a decreasing trend. The number of severe HFMD cases in scattered children was most, accounting for78.88%.Boys were more affected than girls. The male to female ratio of children accounted for the1.98:1. The occurrence peak was from May to July accounting for46.43%, the second peak was detected in November. Most severe HFMD cases had the suspected epidemiological contact history. All the patients, specimens had been collected for enterovirus testing by RT-PCR assay.335of364(92.03%) severe HFMD cases were found positive for human enterovirus. EV71was the major pathogen which caused severe HFMD accounting for93.43%in the enterovirus-positive HFMD patients. We detected114paired specimens of feces and throat swabs from patients with severe HFMD caused by EV71. The results showed that the detection rate of EV71was higher in feces swabs (98.25%) than in throat swabs (50.00%), and the difference was statistically significant. The detection rate of both feces and throat swabs specimens decreased with time gone, while EV71still could be detected from the two swabs specimens14days after the outbreak.The detection rate of EV71from throat swabs could reach to47.37%in8-14days after the outbreak.In2011, the epidemiologic characteristics of severe HFMD in Minhang district had obvious time and population ditribution. EV71was the dominant pathogen causing severe HFMD. The EV71positive rate of feces swabs was higher than throat swabs, thus it may be more valuable for diagnosing HFMD by feces swabs detection than throat swabs detection. Although EV71mainly spread by parenteral route, the respiratory tract can’t be ignored. 2. The serological studies of EV71in healthy children in Shanghai,2012To investigate nature infectious status and susceptibility to EV71among healthy children with different ages and gender in order to explore EV71serum trends and provide scientific basis for prevention and control of HFMD. We collected total449serum specimens from children ages from0-4years old in June to August2012.EV71antibody was detected by neutralization test method. The results showed that the positive rate of EV71antibody among449serum specimens was43.65%(196/449), the geometric mean titer (GMT) of EV71-specific neutralizing antibody was1:10.43, There were no significant differences of positive rate in gender, while the positive rate had obvious correlation with age. It was decreasing and then increasing with age increasing.0～1month newborns group, EV71antibody level was supreme with100.00%for positive rate and1:60.41for GMT. With age increasing, EV71antibody levels decreased gradually. After5months, EV71antibody levels were significantly decreased. The lowest levels were in two groups (10and11months), only with10.00%for positive rate and1:5.04for GMT. And then, the EV71antibody levels gradually increased. Until48months group, the serum EV71antibody positive rate has been up to66.67%and GMT reached to1:20.87. The research suggested that infants ages from5months to3years are susceptible to EV71infection, it is very necessary to take prevention measures among this age group.3. Full length genome analysis of EV71isolated from severe and mild cases in Shanghai,2011Five EV71strains isolated from sever HFMD cases and five EV71strains from mild cases were chosen. Amplify and sequence the full length genomes of10EV71strains, then compared the sequencing results with that of A, B, C genotype reference EV71strains from GeneBank by amino acid alignment and phylogenetic tree analysis.. The results showed that the full length of10EV71strains was7406bp.The homology. of the nucleotide sequences of5’UTR and3’UTR was96.7%-99.0%and96.2%～100.0%respectively between EV71strains from severe cases and from mild cases in Shanghai. The nucleotide homogeneity of P1、P2and P3region was95.9%-96.9%、95.4%-97.3%and95.1%～97.4%,while the homology of amino acid sequences was99.1%-99.9%、96.5%～100.0%and96.2%-99.7%. The VP1～VP4nucleotide and amino acid sequences of5strains from severe cases shared97.0%-98.5%/99.3%-100.0%、97.7%-98.3%/99.6%-100%、97.3%～98.2%/99.2%-100.0%、96.0%～99.5%/98.5%-100.0%identity with C4, while 5strains from mild cases shared98.2%-98.5%/99.3%～100.0%、97.7%-98.4%/100.0%、97.3%-98.0%/99.6%-100.0%、96.5%-99.0%/100.0%.The10EV71strains were within genotype C subgenogroup C4in the phylogenetic tree. Five EV71strains from severe cases had9significant nucleotide mutations in the non-coding region, while22amino acid mutations in the coding region. Three EV71strains from severe cases had five amino acid variation in VP1region (N282S), the VP4area (T7A), P2area (D85E),3C zone (V56I) and3D (S37N) regions simultaneously.4. Research of EV71survivability on different surfaces under different climateWe used suspension test to observe the survival ability of EV71on different aseptic surface of plastic, rubber, cloth and wood in different temperature and moisture.The results showed that the survival time of EV71on medium surface in different climatic conditions is distinct, the longest survival time of the virus was gained under the condition of20℃the temperature and80%the humidity. Temperature and humidity affect the survival time of EV71on medium surface, which is long in the condition of low temperature and high humidity among four analogue climatic conditions. Under the same climate, the survival time of EV71on different medium surface is distinct.The survival ability of EV71on natural cloth and wood surface is better than which on synthetic plastic surface.5. Preliminary study of prevention and control measures in nurseriesFrom April1to June30in2012, we implemented prevention and control measures including morning check, registering and tracking the absences and blocking the route of transmission at the nurseries in Huacao township of Minhang district in Shanghai, in order to probe an effect mode of HFMD prevention. After analyzing, data showed that during the implementation period of prevention and control measures,3epidemics of HFMD occurred in intervention group, one of which was aggregation epidemic. While7epidemics occurred in control group, two of which were aggregation epidemics. The difference of incidence between control group and intervention group among children under4years old was obvious. In<4years age-group, the incidence of intervention group was3.70%(7/189), which was5.28%(17/322) in control group. Analysis also showed some significant differences on onset time between intervention group and control group. The onset time of HFMD in control group concentrated in April and May, which was earlier than that in intervention group centralizing in May and June. The results demonstrated that prevention and control measures appeared successful at reducing incidence of HFMD and aggregation epidemics.