Age-time-specific transmission of hand-foot-and-mouth disease enterovirus serotypes in Vietnam: A catalytic model with maternal immunity.

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013-2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

Molecular epidemiology and clinical characteristics of enteroviruses associated HFMD in Chengdu, China, 2013-2022.

OBJECTIVES: This study aims to investigate molecular epidemiology and clinical characteristics of enterovirus associated hand-foot-mouth disease (HFMD) in Chengdu, China, 2013-2022. Monitoring the molecular epidemiology and clinical features of HFMD for up to 10 years may provide some ideas for future protection and control measures. METHODS: We conducted a retrospective analysis of the medical records of all patients with laboratory-confirmed HFMD-related enterovirus infection at the West China Second University Hospital from January 2013 to December 2022. We described the characteristics in serotype, age, sex distribution and hospitalization of enterovirus infection cases using data analysis and graphic description. RESULTS: A total of 29,861 laboratory-confirmed cases of HFMD-related enterovirus infection were reported from 2013 to 2022. There was a significant reduction in the number and proportion of EV-A71 cases after 2016, from 1713 cases (13.60%) in 2013-2015 to 150 cases (1.83%) in 2017-2019. During the COVID-19 pandemic, EV-A71 cases even disappeared. The proportion of CV-A16 cases decreased from 13.96% in 2013-2015 to 10.84% in 2017-2019 and then to 4.54% in 2020-2022. Other (non-EV-A71 and non-CV-A16) serotypes accounted for 95.45% during 2020-2022, with CV-A6 accounting for 50.39% and CV-A10 accounting for 10.81%. Thus, CV-A6 and CV-A10 became the main prevalent serotypes. Furthermore, There was no significant difference in the enterovirus prevalence rate between males and females. The hospitalization rate of EV-A71 patients was higher that of other serotypes. In general, the proportion of HFMD hospitalizations caused by other pathogens except for EV-A71, CV-A16, CV-A10 and CV-A16 was second only to that caused by EV-A71. The proportion of children over 4 years old infected with enterovirus increased. CONCLUSION: The incidence of HFMD associated with enterovirus infection has decreased significantly and CV-A6 has been the main pathogen of HFMD in Chengdu area in recent years. The potential for additional hospitalizations for other untested enterovirus serotypes suggested that attention should also be paid to the harms of infections with unknown enterovirus serotypes. Children with HFMD were older. The development of new diagnostic reagents and vaccines may play an important role in the prevention and control of enterovirus infection.

Epidemiology of hand, foot and mouth disease and genomic surveillance of coxsackievirus A10 circulating in Zhejiang Province, China during 2017 to 2022.

BACKGROUND: Coxsackievirus A10 (CA10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD). OBJECTIVES: We aimed to perform a retrospective analysis of the molecular epidemiological characteristics and genetic features of HFMD associated with CA10 infections in Zhejiang Province from 2017 to 2022. STUDY DESIGN: Epidemiologic features were summarized. Throat swab specimens were collected and tested. The VP1 regions were sequenced for genotyping. CA10 positive samples were isolated. Whole genomes of CA10 isolations were sequenced. Nucleotide and amino acid changes were characterized. Phylogenetic trees were constructed. RESULTS: The number of HFMD cases fluctuated from 2017 to 2022. Children aged below 3 years accounted for the majority (66.29%) and boys were more frequently affected than girls. Cases peaked in June. The positivity rate of HEV was 62.69%. A total of 90 strains of CA10 were isolated and 53 genomes were obtained. All CA10 in this study could be assigned to two genogroups, C (C2) and F (F1 and F3). CONCLUSION: The clinical manifestations of HFMD associated with HEV are complex and diverse. CA10 infection may be emerging as a new and major cause of HFMD because an upward trend was observed in the proportion of CA10 cases after the use of EV71 vaccines. Different genogroups of CA10 had different geographic distribution patterns. Surveillance should be strengthened and further comprehensive studies should be continued to provide a scientific basis for HFMD prevention and control.

Epidemiology of Hand, Foot, and Mouth Disease and Genetic Evolutionary Characteristics of Coxsackievirus A10 in Taiyuan City, Shanxi Province from 2016 to 2020.

In recent years, the prevalence of hand, foot, and mouth disease (HFMD) caused by enteroviruses other than enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) has gradually increased. The throat swab specimens of 2701 HFMD cases were tested, the VP1 regions of CVA10 RNA were amplified using RT-PCR, and phylogenetic analysis of CVA10 was performed. Children aged 1-5 years accounted for the majority (81.65%) and boys were more than girls. The positivity rates of EV-A71, CVA16, and other EVs were 15.22% (219/1439), 28.77% (414/1439), and 56.01% (806/1439), respectively. CVA10 is one of the important viruses of other EVs. A total of 52 CVA10 strains were used for phylogenetic analysis based on the VP1 region, 31 were from this study, and 21 were downloaded from GenBank. All CVA10 sequences could be assigned to seven genotypes (A, B, C, D, E, F, and G), and genotype C was further divided into C1 and C2 subtypes, only one belonged to subtype C1 and the remaining 30 belonged to C2 in this study. This study emphasized the importance of strengthening the surveillance of HFMD to understand the mechanisms of pathogen variation and evolution, and to provide a scientific basis for HFMD prevention, control, and vaccine development.

The spatial-temporal distribution and etiological characteristics of hand-foot-and-mouth disease before and after EV­A71 vaccination in Kunming, China, 2017-2020.

After vaccination with enterovirus 71 (EV-A71), the prevalence of hand-foot-and-mouth disease (HFMD) remained high, and the spatial-temporal distribution of enteroviruses changed. Therefore, it is essential to define the temporal features, spatial distributions, and epidemiological and etiological characteristics of HFMD in Kunming. Between 2017 and 2020, a total of 36,540 children were diagnosed with HFMD in Kunming, including 32,754 children with enterovirus-positive clinical samples. Demographic, geographical, epidemiological and etiological data of the cases were acquired and analyzed. Other enteroviruses replaced EV-A71, and the incidence of EV-A71 decreased dramatically, whereas coxsackievirus A6 (CV-A6) and coxsackievirus A16 (CV-A16) had substantial outbreaks in 2018 and 2019, respectively. The major and minor peaks all extended for 2-4 months compared to before vaccination with the EV-A71 vaccine. From 2019 to 2020, CV-A6, as the predominant serotype, showed only a single peak. Although a high incidence of HFMD was observed in Guandu, Chenggong and Xishan, the annual incidence of different enterovirus serotypes was different in different regions. In 2017, other enteroviruses were most prevalent in Shilin. In 2018, CV-A16 and CV-A6 were most prevalent in Luquan and Shilin, respectively. In 2019, CV-A16 was most prevalent in Jinning. In 2020, CV-A6 and coxsackievirus A10 (CV-A10) were most prevalent in Luquan and Shilin, respectively. Meanwhile, the epidemic cycle of CV-A6 and CV-A16 was only 1 year, and CV-A10 and other enteroviruses were potential risk pathogens. The spatial and temporal distribution of HFMD varies at different scales, and the incidence of HFMD associated with different pathogens has obvious regional differences and seasonal trends. Therefore, research on multivalent combined vaccines is urgently needed, and proper preventive and protective measures could effectively control the incidence of HFMD-like diseases.

Molecular epidemiology and clinical features of hand, foot and mouth disease requiring hospitalization after the use of enterovirus A71 inactivated vaccine in chengdu, China, 2017-2022: a descriptive study.

Three inactivated enterovirus A71 (EV-A71) vaccines have been widely vaccinated among children in the targeted age group in mainland China since mid-2016. However, comprehensive virological surveillance of hand, foot and mouth disease (HFMD) over multiple years after the use of EV-A71 vaccines has rarely been conducted. Using long-term data extracted from the Public Health and Clinical Center of Chengdu, we described the clinical, aetiological, and epidemiological characteristics of HFMD inpatients after the use of EV-A71 vaccines from 2017 through 2022. A total of 5115 patients were selected for analysis with a male-to-female ratio of 1.63:1 and were mostly under 5 years of age (97.6%). Among these cases, 4.3% presented with severe symptoms, and 4.1% of severe cases experienced significant complications. EV-A71 was no longer the major serotype for laboratory-confirmed HFMD, responsible for 15.6% of severe cases and 1.2% of mild cases. A significant downwards trend of EV-A71 infections was observed after the use of EV-A71 vaccines (P for trend < 0.001). Coxsackievirus A6 was the predominant pathogen, accounting for 63.5% of mild cases and 36.2% of severe cases. Coxsackievirus A10 (CV-A10) and A16 were sporadically detected, and an upwards trend was observed in the proportion of CV-A10 infections. This study provides baseline molecular epidemiology for the evaluation of EV-A71 vaccination impact and potential serotype replacement based on HFMD inpatients. Additional nationwide and population-based epidemiologic and serologic studies are essential to elucidate HFMD dynamics after the use of EV-A71 vaccines, and to inform public health authorities to introduce optimized intervention strategies.

Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai, China, 2016-2020.

Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%-100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.

Drug Repositioning for Hand, Foot, and Mouth Disease.

Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.

Susceptibility and cytokine responses of human neuronal cells to multiple circulating EV-A71 genotypes in India.

Enterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia-Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and G) were isolated in India in recent years, no recognizable outbreak of EV-A71 caused HFMD, Acute Flaccid paralysis (AFP) or encephalitis have been reported so far. It is essential to study the pathogenicity or cell tropism of these Indian isolates in order to understand their tendency to cause disease. We investigated the susceptibility and cytokine responses of indigenous EV-A71 genotypes (D and G) isolated from cases of AFP and genotype C viruses isolated from cases of HFMD and encephalitis, in human cells in-vitro. Although all three EV-A71 genotypes could infect and replicate in human muscle and neuronal cells, the genotype D virus showed a delayed response in human neuronal cells. Quantification of cytokine secretion in response to these isolates followed by confirmation with gene expression assays in human neuronal cells revealed significantly higher secretion of pro-inflammatory cytokines TNF-α IL-8, IL-6, IP-10 (p < 0.001) in G genotype infected cells as compared to pathogenic C genotypes whereas the genotype D virus could not induce any of the inflammatory cytokines. These findings will help to better understand the host response to indigenous EV-A71 genotypes for management of future EV-A71 outbreaks in India, if any.

The surveillance of the epidemiological and serotype characteristics of hand, foot, mouth disease in Neijiang city, China, 2010-2017: A retrospective study.

Hand, foot, and mouth disease (HFMD) is well recognized as one of the major threats to children's health globally. The increasing complexity of the etiology of HFMD still challenges disease control in China. There is little surveillance of the molecular epidemiological characteristics of the enteroviruses (EVs) that cause HFMD in Neijiang city or the Sichuan Basin area in Southwest China. In this study, demographic and epidemiological information for 14,928 probable HFMD cases was extracted and analyzed to describe the epidemic features of HFMD in Neijiang city from Jan 2010 to Dec 2017. The swab samples of select probable HFMD cases from 2012 to 2017 were tested by reverse transcription (RT) real-time PCR to identify the serotype distribution of EVs, and 110 randomly selected RT-real-time PCR positive samples were then amplified and analyzed for the VP1 or VP4 regions of EVs to further analyze the phylogenetic characteristics of the circulating strains in this area. The eight-year average annual incidence was 49.82 per 100,000 in Neijiang. The incidence rates varied between 19.51 and 70.73 per 100,000, demonstrating peaks of incidence in even-number years (2012, 2014 and 2016). The median age of the probable cases was 27 months and the interquartile range (25th to 75th percentile) of ages for the probable HFMD cases was between 14 and 42 months. The male-to-female ratio of the probable HFMD cases was 1.47:1, and scattered children were the major population classification (81.7%). Two epidemic peaks were observed: one major peak between April and July and the other lesser peak between October and December. Of 6513 probable cases tested with RT-real-time PCR, 4015 (61.6%) were positive for enterovirus with the serotype distribution as follows: EV71+, 30.1% (n = 1210); CV-A16+, 28.7% (n = 1154) and a sole pan-enterovirus+, 41.1% (n = 1651). A total of 91 cases (82.7%, 91/110) were successfully amplified and underwent phylogenetic analysis: all EV71+ cases were C4a serotype (n = 23/30); all CV-A16+ cases were B2b serotype (n = 24/30); of 42 sole pan-enterovirus+ samples, 20 were CV-A6, 14 were CV-A10 and the rest within this group were CV-A4 (n = 4), CV-A8 (n = 2), CV-A9 (n = 1) and CV-B3 (n = 1). Our findings provide important evidence that aids the improvement of strategies for vaccination against HFMD and comprehensive disease control in China.

Enfermedad de mano-pie-boca atípica causada por virus Coxsackie A6 en Argentina, 2015 / Atypical hand, foot, and mouth disease caused by Coxsackievirus A6 in Argentina in 2015

We present two groups of cases of atypical hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A6 (CV-A6) detected in Argentina in 2015. The first group involved 14 patients from Chubut province and the second group affected 12 patients from San Luis province. Molecular analysis of the complete VP1 protein gene revealed the circulation of E2 sublineage, the most predominant worldwide. To our knowledge, this is the first report of CV-A6 infections associated with atypical HFMD in Argentina and South America.

Se describen dos grupos de casos de enfermedad de mano-pie-boca (HFMD) atípica causada por el virus Coxsackie A6 (Coxsackievirus A6, CV-A6) detectados en Argentina en el año 2015. El primero de los grupos involucró a 14 pacientes de Chubut y el segundo a 12 pacientes de San Luis. El análisis molecular del gen de la proteína VP1 completa reveló la circulación del sublinaje E2, el predominante a nivel global. Hasta donde sabemos, este es el primer reporte de infecciones CV-A6 asociadas con HFMD atípica en Argentina y Sudamérica.

Clinical characteristics and managements of severe hand, foot and mouth disease caused by enterovirus A71 and coxsackievirus A16 in Shanghai, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a transmissible infectious disease caused by human enteroviruses (EV). Here, we described features of children with severe HFMD caused by EV-A71 or coxsackievirus A16 (CV-A16) in Shanghai, China. METHODS: Severe EV-A71 or CV-A16 caused HFMD children admitted to the Xinhua Hospital from January 2014 and December 2016, were recruited retrospectively to the study. Symptoms and findings at the time of hospitalization, laboratory tests, treatments, length of stay and residual findings at discharge were systematically recorded and analyzed. RESULTS: Of 19,995 children visited clinic service with probable HFMD, 574 children (2.87%) were admitted, 234 children (40.76%) were confirmed with EV-A71 (90/574) or CV-A16 (144/574) disease. Most (91.02%) of the patients were under 5 years. Initial clinical symptoms of EV-A71 and CV-A16 cases were: fever > 39 °C in 81 (90%) and 119 (82.63%), vomiting in 31 (34.44%) and 28 (19.44%), myoclonic twitching in 19 (21.11%) and 11(7.64%), startle in 21 (23.33%) and 20 (13.69%), respectively. Serum levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) were significantly upregulated in severe HFMD subjects. Forty-seven children (20.08%) treated with intravenous gamma globulin (IVIG) showed decreased duration of illness episodes. All children were discharged without complications. CONCLUSIONS: EV-A71 and CV-A16 accounted 40.76% of admitted HFMD during 2014 to 2016 in Xinhua Hospital. IVIG appeared to be beneficial in shortening the duration of illness episodes of severe HFMD.

Molecular characterization of Coxsackievirus A16 strains isolated from children with severe hand, foot, and mouth disease in Yunnan, Southwest China, during 2009-2015.

Coxsackievirus A16 (CV-A16) commonly causes mild symptoms, but severe diseases, such as aseptic meningitis, encephalitis, and even fatal cases, have been reported. Thirteen CV-A16 strains were isolated from patients with severe hand, foot, and mouth disease in Yunnan, Southwest China, from 2009 to 2015. Subgenotype B1a and B1b of CV-A16 were predominantly circulating the region with B1b the predominant strain in recent years. The mean rate of nucleotide substitution based on the VP1 gene sequence was 4.545 × 10 -3 substitution per site per year from 2009 to 2015. These results may help in understanding the genetic diversity of CV-A16 and develop a CV-A16 vaccine.

An update on enterovirus 71 infection and interferon type I response.

Enteroviruses are members of Pichornaviridae family consisting of human enterovirus group A, B, C, and D as well as nonhuman enteroviruses. Hand, foot, and mouth disease (HFMD) is a serious disease which is usually seen in the Asia-Pacific region in children. Enterovirus 71 and coxsackievirus A16 are two important viruses responsible for HFMD which are members of group A enterovirus. IFN α and ß are two cytokines, which have a major activity in the innate immune system against viral infections. Most of the viruses have some weapons against these cytokines. EV71 has two main proteases called 2A and 3C, which are important for polyprotein processing and virus maturation. Several studies have indicated that they have a significant effect on different cellular pathways such as interferon production and signaling pathway. The aim of this study was to investigate the latest findings about the interaction of 2A and 3C protease of EV71 and IFN production/signaling pathway and their inhibitory effects on this pathway.

Seroprevalence of antibodies to enterovirus 71 and coxsackievirus A16 among people of various age groups in a northeast province of Thailand.

BACKGROUND: Hand, foot and mouth disease (HFMD) is endemic among population of young children in Thailand. The disease is mostly caused by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). METHODS: This study conducted serosurveillance for neutralizing (NT) antibodies to EV71 subgenotypes B5 and C4a, and to CA16 subgenotypes B1a and B1b, in 579 subjects of various ages using a microneutralization assay in human rhabdomyosarcoma (RD) cells. These test viruses were the major circulating subgenotypes associated with HFMD in Thailand during the study period. RESULTS: We found that the levels of seropositivity against all 4 study viruses were lowest in the age group of 6-11 months, i.e., 5.5% had antibody to both EV71 subgenotypes, while 14.5% and 16.4% had antibody to CA16 subgenotypes B1a and B1b, respectively. The percentages of subjects with antibodies to these 4 viruses gradually increased with age, but were still less than 50% in children younger than 3 years. These laboratory data were consistent with the epidemiological data collected by the Ministry of Public Health which showed repeatedly that the highest number of HFMD cases was in children aged 1 year. Analyses of amino acid sequences of the test viruses showed 97% identity between the two subgenotypes of EV71, and 99% between the two subgenotypes of CA16. Nevertheless, the levels of seropositivity and antibody titer against the two subgenotypes of EV71 and of CA16 were not significantly different. CONCLUSIONS: This study clearly demonstrated NT antibody activity across EV71-B5 and EV71-C4a subgenotypes, and also across CA16-B1a and CA16-B1b subgenotypes. Moreover, there were no significant differences by gender in the seropositive rates and antibody levels to any of the 4 virus subgenotypes.

Sex differences in common childhood infections in Taiwan.

Sex differences in childhood infections are commonly reported in case-only studies. In this population-based study of 278000 Taiwanese children followed from 3 months to 18 years of age during the period 2000-2012, age-trajectories of monthly numbers of all-cause healthcare visits and monthly rates of infection-specific healthcare visits were compared between boys and girls. For all-cause healthcare visits and for healthcare visits related to conjunctivitis, respiratory tract infections, enteritis, hand, foot, and mouth disease, and herpangina, there was good resemblance of age trajectories between boys and girls. Despite this resemblance, there was evidence of a slightly higher rate in boys than in girls under age 6 years (i.e., a male tendency, or male-to-female ratio >1.0) across all diagnoses except herpangina. For urinary tract infection, where an age-specific sex difference is well reported in case-only studies, this population-based study confirmed that there was a much higher rate of kidney infection among boys than among girls during infancy, and a higher rate of kidney and bladder infection among girls than among boys after this period. The age-specific sex difference in urinary tract infections was so strong that the age trajectories in boys and girls were qualitatively different. This report confirms previously reported sex differences in other countries, whilst placing this in the context of age dynamics in childhood infection.

Características clínico epidemiológicas de pacientes pediátricos con enfermedad boca, mano, pie / Clinical epidemiological characteristics of pediatric patients with mouth, hand and foot disease

Introducción: la enfermedad boca, mano, pie es una enfermedad febril eruptiva provocada por la infección por los virus Coxsackie, consistente en fiebre, exantema pápulo-vesicular en las manos, los pies y un enantema ulceroso en la boca. Objetivos: indagar la etiología viral y describir las características clínico epidemiológicas de la entidad. Métodos: estudio descriptivo prospectivo en 54 pacientes menores de 18 años, diagnosticados con la enfermedad boca, mano, pie, atendidos en el Hospital Pediátrico Docente del Cerro, de septiembre a noviembre de 2017. Se incluyeron aquellos con lesiones vesiculares o pápulas vesiculares, distribuidas en la piel y úlceras en la mucosa oral; y se excluyeron los pacientes con otras entidades exantemáticas o vesiculares. Las variables investigadas resultaron: la edad, el sexo, los signos, los síntomas clínicos de infección, el leucograma y el estudio virológico. La selección de la muestra fue de manera no probabilística consecutiva. Los datos se procesaron por el paquete estadístico XLSTAT con análisis univariado. Resultados: el grupo entre 1-3 años obtuvo 53,7 por ciento, y el sexo masculino el 68,5 por ciento. Las lesiones cutáneas fueron más frecuentes en la cara, las extremidades, los glúteos y el tronco (68,6 por ciento), seguido de la zonas de la cara, las extremidades y el tronco (29,6 por ciento). El enantema fue apreciado en el 48,1 por ciento, la fiebre en el 61,1 por ciento, la fiebre más secreción nasal en el 44,4 por ciento y el prurito en el 70,3 por ciento. El conteo leucocitario alcanzó 11,1 x 109 células. Los polimorfonucleares obtuvieron promedio de 37,9 y los linfocitos 70,3. En 49 de los 54 pacientes se aisló el virus Coxsackie A6. Conclusiones: se describe la enfermedad boca, mano, pie en forma atípica, cuyo cuadro clínico coincide con lo aparecido en la literatura(AU)

Introduction: mouth, hand and foot disease is an eruptive febrile illness caused by the infection of Coxsackie viruses, and it consists in fever, papulo-vesicular exanthema in the hands, feet and an ulcer enanthema in the mouth. Objectives: to investigate the viral etiology and describe the clinical epidemiological characteristics of the entity. Methods: prospective descriptive study in 54 patients under 18 years old diagnosed with mouth, hand and foot disease, and whom were attended at the Pediatric Teaching Hospital of Cerro from September to November 2017. Those with vesicular lesions or vesicular papules distributed in the skin, and ulcers in the oral mucosa were included in the research; and patients with other exanthematic or vesicular entities were excluded. The variables investigated were: age, sex, signs, clinical symptoms of infection, leukogram and virological study. The selection of the sample was consecutive non-probabilistic. The data was processed by the XLSTAT statistical package with univariate analysis. Results: the group from 1 to 3 years old represented the 53.7 percent, and the male sex the 68.5 percent y. Skin lesions were more frequent on the face, extremities, buttocks and trunk (68.6 percent), followed by facial, limbs and trunk areas (29.6 percent). Enanthem was visible in 48.1 percent, and fever appeared in 61.1 percent, fever plus nasal discharge in 44.4 percent and itching in 70.3 percent y The leukocyte count reached 11.1 x 109 cells. Polymorphonuclear cells obtained an average of 37.9 and lymphocytes of 70.3. In 49 of the 54 patients the Coxsackie A6 virus was isolated. Conclusions: mouth, hand, and foot disease is described in an atypical form, whose clinical manifestations coincide with what appeared in the literature(AU)

Genome-wide linear B-cell epitopes of enterovirus 71 in a hand, foot and mouth disease (HFMD) population.

BACKGROUND: Enteroviruses cause hand, foot and mouth disease (HFMD). The host B-cells recognize the viral proteins and provoke humoral responses. Deciphering the B-cell responses to the viral epitopes helps diagnosis and vaccine development. OBJECTIVES: The objective of the present study was to investigate for the first time the landscape of genome-wide linear B-cell epitopes of enterovirus 71 in HFMD population. STUDY DESIGN: The peptides encompassing the entire coding region of EV71 were chemically synthesized and displayed on a microarray. The peptide microarray was used to screen serum samples from an HFMD population, including EV71-, CAV10-, CAV16- and CAV6-infected patients. We identified the dominant epitope-containing-peptides (DECPs) that react with the sera of more than 20% of the HFMD population and the common DECPs that cross-react with the sera from other enteroviruses-infected population. RESULTS: Ten DECPs reacting with IgM and 9 DECPs reacting with IgG antibodies were identified, of which, 6 IgM and 5 IgG common DECPs cross-reacted with the sera from other enteroviruses. Some DECPs preferentially reacted with IgG or IgM antibodies and some epitope-antibody interactions correlated with the severity of HFMD. CONCLUSIONS: We uncovered the DECPs and the common DECPs among a group of enteroviruses in HFMD population and found that some epitope-antibody reactions were associated with the outcome of HFMD. These data may guide developing vaccines against the enteroviruses and help the diagnosis and prognosis of HFMD.

An emerging and expanding clade accounts for the persistent outbreak of Coxsackievirus A6-associated hand, foot, and mouth disease in China since 2013.

Enterovirus (EV)-A71 and Coxsackievirus (CV)-A16 have historically been the major pathogens of hand, foot, and mouth disease (HMFD) in China; however, CV-A6， which had previously received little attention, became the predominant pathogen in 2013, and has remained one of the common pathogens since then. In this work, we conducted a molecular epidemiology study of CV-A6-associated HFMD in Xiamen from 2009 to 2015. The data showed CV-A6 pandemics had a certain periodicity rather than occurring randomly. Evolution analysis based on near-complete VP1 nucleotide sequences showed subgenotype D5 lineage 4 strains account for the persistent outbreak of CV-A6-associated HFMD in China since 2013. Alignment analysis revealed eight candidate amino acid substitutions in VP1, which may provide useful information for the research of CV-A6 virulence enhancement. This study contributed to elucidating the circulation patterns and genetic characteristics of CV-A6 in China; however, further surveillance and intervention in CV-A6 epidemics is recommended.