Epidemiological and etiological characteristics of hand, foot, and mouth disease before and after introducing enterovirus 71 vaccines in Sichuan, China: a 6-year retrospective study.
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ABSTRACT:
SUBMITTER: Tong WB
PROVIDER: S-EPMC8710323 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hand, foot and mouth disease (HFMD) is a common illness of infants and young children <10 years of age. It is characterized by fever, ulcers in the oral cavity, and rashes with blisters that appear on the palm and sole. The most common causal agents of HFMD are coxsackievirus A16 (CV-A16) and human enterovirus 71 (HEV71), but other enteroviruses, including CV-A5 and CV-A10, can also cause it. When caused by CV-A16 infection, it is usually a mild disease, and patients normally recover without requiring any special medical attention.
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Project description:We prospectively studied 3,791 children hospitalized during 2011 during a large outbreak of enterovirus 71-associated hand, foot, and mouth disease in Vietnam. Formal assessment of public health interventions, use of intravenous immunoglobulin and other therapies, and factors predisposing for progression of disease is needed to improve clinical management.
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Project description:The Enterovirus A71 (EV-A71) vaccine was introduced in China in December 2015 as a preventive measure against hand, foot, and mouth disease (HFMD) caused by EV-A71. However, the effectiveness of the vaccine (VE) in real-world settings needs to be evaluated. We conducted a test-negative case-control study to assess the effectiveness of EV-A71 vaccines in preventing EV-A71-associated HFMD. Children aged 6-71 months with HFMD were enrolled as participants. The case group comprised those who tested positive for EV-A71, while the control group comprised those who tested negative for EV-A71. To estimate VE, a logistic regression model was employed, adjusting for potential confounders including age, gender, and clinical severity. In total, 3223 children aged 6 to 71 months were included in the study, with 162 in the case group and 3061 in the control group. The proportion of children who received EV-A71 vaccination was significantly lower in the case group compared to the control group (p < .001). The overall VEadj was estimated to be 90.8%. The VEadj estimates for partially and fully vaccinated children were 90.1% and 90.9%, respectively. Stratified by age group, the VEadj estimates were 88.7% for 6 to 35-month-olds and 95.5% for 36 to 71-month-olds. Regarding disease severity, the VEadj estimates were 86.3% for mild cases and 100% for severe cases. Sensitivity analysis showed minimal changes in the VE point estimates, with most changing by no more than 1% point. Our study demonstrates a high level of vaccine effectiveness against EV-A71-HFMD, especially in severe cases. Active promotion of EV-A71 vaccination is an effective strategy in preventing EV-A71 infections.
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Project description:Enterovirus 71 (EV71) is one of the most common intestinal virus that causes hand, foot, and mouth disease (HFMD) in infants and young children (mostly ≤5 years of age). Generally, children with EV71-infected HFMD have mild symptoms that resolve spontaneously within 7-14 days without complications. However, some EV71-infected HFMD cases lead to severe complications such as aseptic meningitis, encephalitis, acute flaccid paralysis, pulmonary edema, cardiorespiratory complication, circulatory disorders, poliomyelitis-like paralysis, myocarditis, meningoencephalitis, neonatal sepsis, and even death. The mechanism of EV71 pathogenesis has been studied extensively, and the regulation of host immune responses is suspected to aggravate EV71-induced severe complications. Recently, several cytokines or chemokines such as TNF-α, IFN-γ, IL-1β, IL-18, IL-33, IL-37, IL-4, IL-13, IL-6, IL-12, IL-23, IL-27, IL-35, IL-10, IL-22, IL-17F, IL-8, IP-10, MCP-1, G-CSF, and HMGB1 have been reported to be associated with severe EV71 infection by numerous research teams, including our own. This review is aimed at summarizing the pathophysiology of the cytokines and chemokines with severe EV71 infection.
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Project description:BackgroundTo clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (HFMD) infected by Enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe HFMD children and 5 healthy children.MethodsThe protein profiles of them were compared using two-dimensional electrophoresis. Differentially expressed proteins were identified using mass spectrometry. Functional classifications of these proteins were based on the PANTHER. The interaction network of the differentially expressed protein was generated with Pathway Studio.ResultsA total of 38 differentially expressed proteins were identified. Functional classifications of these proteins indicated a series of altered cellular processes as a consequence of the severe HFMD. These results provided not only new insights into the pathogenesis of severe HFMD, but also implications of potential therapeutic designs.ConclusionsOur results suggested the possible pathways that could be the potential targets for novel therapy: viral protection, complement system and peroxide elimination.
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Project description:Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth disease (HFMD). There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71) vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs) formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-γ T cells associated with Th1/Th2-balanced IFN-ɣ, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-γ T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and cellular immune responses against CV infection.
| S-EPMC4391779 | biostudies-literature
Project description:Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. HFMD outbreaks and reported cases have sharply increased in China since 2008. Epidemiological and clinical data of HFMD cases reported in Henan Province were collected from 2008 to 2013. Clinical specimens were obtained from a subset of these cases. Descriptive epidemiological methods were used to analyze the time, region and population distribution. The VP1 gene from EV71 and CA16 isolates was amplified, and the sequences were analyzed. 400,264 cases of HFMD were reported in this study, including 22,309 severe and 141 fatal cases. Incidence peaked between April and May. Laboratory confirmation was obtained for 27,692 (6.9%) cases; EV71, CA16, and other enteroviruses accounted for 59.5%, 14.1%, 26.4%, respectively. Phylogenetic analysis revealed that EV71 belonged to the C4a evolution branch of C4 sub-genotype and CA16 belonged to subtype B1a or B1b. The occurrence of HFMD in Henan was closely related to season, age and region distribution. Children under five were the most affected population. The major pathogens causing HFMD and their genotypes have not notably changed in Henan. The data strongly support the importance of EV71 vaccination in a high population density area such as Henan, China.
| S-EPMC4354091 | biostudies-literature
Project description:The aim of the present study was to analyze the sequence of the VP1 gene in enterovirus 71 (EV71) isolates and to explore their genetic evolution, so as to provide a scientific basis for the clinical prevention and treatment of hand, foot and mouth disease. The fecal samples of 590 patients with suspected hand, foot and mouth disease treated at Yan'an Hospital (Kunming, China) between January 2015 and December 2016 were collected and EV71 nucleic acid was detected by fluorescence PCR. The viral RNA of EV71-positive samples was extracted, the VP1 gene was amplified by PCR and the products were sequenced. The VP1 gene sequence was analyzed using DNAMAN and MEGA (version 4.0) software and homologous modeling was performed using Pymol software. A total of 50 EV71-positive samples were identified and the detection rate was 8.47% (50/590 cases). All of the 50 EV71 strains were of the C4 subtype. The genetic distance between the strains detected in the present study and EV71 strains detected in Beijing, Anhui and Malaysia was 0.01-0.03, while that between the strains detected in the present study and Australian strains was 2.11. Homologous modeling indicated that the amino acid sequence of the VP1 gene of the detected strains had a H144Y mutation. There was no significant genetic variation in the EV71 strain within the 2-year period. In conclusion, the EV71 strains detected in the present study was similar to that detected in Beijing, Anhui and Malaysia but different to that from Australia. A point mutation was present in the amino acid sequence of the VP1 gene.
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Project description:Herpangina (HA) and hand, foot, and mouth disease (HFMD) are common infectious diseases caused by human enteroviruses and frequently occurr in young children. Previous published studies have mainly focused on HFMD, while the HA epidemiological and etiological characteristics in mainland China have not been described. From June, 2013 to March, 2014, HA and HFMD patients were monitored in participants from clinical trial of EV-A71 vaccine conducted during 2012-2013. A total of 95 HA patients and 161 HFMD patients were defined. Enteroviruses of HA samples were differentiated into 17 serotypes (EV-A71, CV-A16, CV-A24, E6, CV-B5, CV-A22, CV-A6, CV-A10, CV-B3, E9, CV-A9, CV-B4, CV-B2, E1, E7, E21 and CV-A20), the most common serotypes were EV-A71(10/95,10.5%), CV-A16(4/95,4.2%) and CV-A24(4/95,4.2%); while enteroviruses detected from HFMD samples were classfied into 21 serotypes ( EV-A71, CV-A16, CV-A10, CV-A6, E6, CV-B3, CV-B5, CV-A9, E9, CV-B2, CV-B4, E3, E11, E15, E16, CV-A1, EV-A69, E5, CA22, CA24 and EV99), the most common serotypes were EV-A71(28/161,17.4%), CV-A16(7/161,4.4%) and CV-A10(5/161,3.1%). The first HA epidemic peak occurred in summer and a second smaller peak occurred in January. In HA patients, the body temperature (P < 0.0001) and the incidence of fever (P < 0.05) were significant higher than those in HFMD patients. Between HA and HFMD patients infected with EV-A71, no significant differences were found in age, sex, circulating season, and the viral genome diversity. In summary, we firstly reported the epidemiological and etiological characteristics of HA in mainland China. Developing a multivalent vaccine will be helpful for the control of the HA/HFMD epidemic.
| S-EPMC5404359 | biostudies-literature
Project description:BackgroundTo analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak caused by enterovirus 71 in Linyi City, Shandong Province, China during November 30 to December 28, 2010.MethodsOne hundred and seventy three stool specimens and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak.ResultsAmong the 173 cases reported in December 2010, the male-female ratio was 1.88: 1; 23 cases (13.3%) were severe. The majority of patients were children aged < 5 years (95.4%). Some patients developed respiratory symptoms including runny nose (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight EV71 positive cases were identified based on real time reverse-transcription PCR detection and 107 isolates were sequenced with the VP1 region. Phylogenetic analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they belonged to the C4a cluster of the C4 subgenotype and were divided into 3 lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln for Glu) at position 145 within the VP1 region are more likely to appear in EV71 isolates from severe cases (52.2%) than those recovered from mild cases (8.3%).ConclusionThis outbreak of HMFD was caused by EV71 in an atypical winter. EV71 strains associated with this outbreak represented three separate chains of transmission. Substitution at amino acid position 145 of the VP1 region of EV71 might be an important virulence marker for severe cases. These findings suggest that continued surveillance for EV71 variants has the potential to greatly impact HFMD prevention and control.
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