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Purpose: To investigate the clinical features of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) and this work may help early diagnose of atypical HFMD., Methods: From January 2013 to December 2019, a total of 7,208 patients with a clinical diagnosis of HFMD in Xi'an Children's Hospital, Xi'an Central Hospital, and Xi'an Jiaotong University Second Affiliated Hospital, were included in this observational study. The clinical data, specimens and follow-up results were collected. Real-time RT‒PCR was performed for the detection and typing of enterovirus nucleic acids., Results: Of the 7,208 clinically diagnosed HFMD patients, 5,622 were positive for enterovirus nucleic acids, and the positive proportions of CVA6, enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), and other enteroviruses were 31.0% (1,742/5,622), 27.0% (1,518/5,622), 35.0% (1,968/5,622), and 7.0% (394/5,622), respectively. Based on the etiology, patients were divided into CVA6 group, EV-A71group, and CVA16 group. The mean age at onset was significantly higher in the CVA6 group (4.62±2.13 years) than in the EV-A71 group and CVA16 group (3.45±2.25 years and 3.35±2.13 years, respectively; both P < 0.05). The male/female ratio was 1.45 (1,031/711) in the CVA6 group and was not significantly different from the other two groups. The incidence of fever was significantly higher in the CVA6 group [82.5% (1,437/1,742)] than in the EV-A71 group [51.3% (779/1,518)] and the CVA16 group [45.9% (903/1,968)] (P < 0.05). In the CVA6 group, the rashes were more frequently on the trunk and elbows/knees and were significantly different from the other two groups (P < 0.05). The number of patients with two or more rash morphologies was significantly higher in the CVA6 group than in the other two groups (P < 0.05). The incidence of bullous rash in the CVA6 group [20.2%; n = 352] was higher than in the EV-A71 group [0.33%; n = 5] and CVA16 group [0.66%; n = 13] (P < 0.05). The incidence of neurological complications was significantly higher in the EV-A71 group [52.1% (791/1,518)] than in the CVA16 group [5.1% (100/1,968)] and the CVA6 group [0.8% (14/1,742)] (P < 0.05). In the follow-up period, 160 patients (9.2%) with CVA6 HFMD experienced onychomadesis, but no onychomadesis was observed in the EV-A71 and CVA16 groups. The average WBC count was significantly higher in the CVA6 group than in the CVA16 group (P < 0.05). The number of patients with increased CRP was significantly larger in the CVA6 group than in the CVA16 group but was significantly smaller than that in the EV-A71 group (P < 0.05)., Conclusions: CVA6 has become one of the main pathogens of HFMD in the Xi'an area during 2013-2019. The main clinical manifestations were slightly different from those of HFMD caused by EV-A71 or CVA16, with a higher frequency of fever, diverse morphologies and diffuse distribution of rashes, fewer neurological complications and some onychomadesis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: In 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak.Methods: The case definition was that a child with onychomadesis or transverse ridging (Beau's line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes.Results: A total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45 days (ranging from 31 to 58 days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn't (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5-6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range.Conclusion: The results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical characteristics of outpatients with hand, foot and mouth disease (HFMD) caused by different serotypes of enteroviruses. Methods: This was a prospective study. From February 2017 to March 2018, 563 outpatients with HFMD were enrolled by systematic sampling in the Department of Infectious Diseases, Henan Children's Hospital. Throat swabs were collected to determine the serotypes via PCR. Demographic, clinical, and laboratory data were collected by standard questionnaire. All cases were followed up twice at 2 and 9 weeks after the initial outpatient visit through telephone interview. A total of 563 cases were enrolled and 555 (98.6%) cases were positive for human enteroviruses, including 338 (60.9%) males. Analyses were stratified by enterovirus serotypes, Chi square test or Fisher's exact test, Rank sum test was used for comparison among different groups. Results: The age of 555 cases was 24.2 (16.4, 41.3) months. Among them 44.0% (224 cases) were identified as coxsackievirus (CV)-A6, while 189 cases, 35 cases, 14 cases and 73 cases were identified as CV-A16, enterovirus (EV)-A71, CV-A10 and other serotypes, respectively. Fever (≥37.5 ℃) was present in 51.4% (285/555) of laboratory confirmed cases. The proportions of fever in cases of CV-A6 (68.9%(168/244)) and CV-A10 (12/14) were significantly higher than those in cases of CV-A16 (31.7%(60/189),χ(2)=57.344,14.313,both P= 0.000), other serotypes (43.8%(32/73),χ(2)=15.101 and 8.242, P= 0.000 and 0.004) and EV-A71 (37.1%(13/35), χ(2)=13.506 and 9.441, P= 0.000 and 0.002) respectively. There was no significant difference between CV-A6 and CV-A10 in presentation of fever (χ(2)=1.785, P= 0.182). There were 359 cases (64.7%) with eruptions in mouth, hands, feet and buttocks. Cases infected with EV-A71 had the highest proportions (74.3%(26/35)) of rash emerging simultaneously in mouth, hands, feet, and buttocks. The proportion in cases of CV-A16, CV-A6, CVA10 and other serotype were 73.5% (139/189), 61.9% (151/244), 7/14 and 49.3% (36/73), respectively. The proportion of rash on other parts of body, such as face, limbs or torso in cases infected with CV-A6 (16.8% (41/244)) was the higherest and the proportion in cases of CV-A16, EV-A71, CV-A10 or other serotypes were 8.5% (16/189) , 5.7% (2/35) , 1/14, 6.8% (5/73) , respectively. None of these cases developed serious complications. Desquamation occurred in 45.5% (179/393) cases 7.5 (5.0, 9.0) days after disease onset and 13.5% (53/393) cases showed onychomadesis 31.0 (18.0, 33.5) days after disease onset. The proportion of desquamation and onychomadesis associated with CV-A6 (64.2% (95/148) and 31.8% (47/148)) was significantly higher than CV-A16 (31.8% (49/154) and 1.3% (2/154), χ(2)=33.601 and 52.482, both P= 0.000) and other serotypes (38.0%(19/50) and 6.0%(3/50),χ(2)=10.236 and 12.988, P= 0.001 and 0.000). Desquamation appeared more in cases of CV-A6 than in cases of CV-A10 (2/11,χ(2)=9.386, P= 0.002), with the proportion of onychomadesis higher in CV-A6 than in EV-A71 (3.3% (1/30),χ(2)=11.088, P= 0.001). Conclusion: Clinical manifestation such as fever, rash emerging parts, desquamation and onychomadesis are different among outpatient HFMD cases infected with CV-A16, CV-A6, EV-A71, CV-A10 and other enteroviruses.

Background: Coxsackievirus A6 (CVA6) is one of the major agents to cause hand, foot and mouth disease (HFMD) outbreaks globally. The objective of this study is to investigate the epidemiologic and clinical manifestations of CVA6 outbreak, and thus guide the diagnosis and treatment of the disease, as well as disease prevention.Methods: An HFMD outbreak in a kindergarten was reported to Shijingshan District Center for Disease Control and Prevention (SCDC) on November 2, 2015 in Beijing, China. Epidemiological investigation was conducted. We performed a nine-week follow-up study to collect and analyze the clinical manifestations of HFMD cases.Results: The outbreak yield 56 (15.7%) clinical diagnosed HFMD cases out of 357 registered children in the kindergarten with the mean age of 3.5 years old. This outbreak lasted for three days and ceased after initiating infectious disease controlling procedures, including periodical suspension of the kindergarten activities, environmental disinfection, and family health education. Fifty-one cases were followed for nine weeks. The positive rate of clinical manifestations of rash, fever, desquamation, pigmentation and onychomadesis were 100.0%, 84.3%, 68.6%, 17.6% and 43.1%, respectively. Children developed desquamation within the first 4 weeks after disease onset and developed onychomadesis between the 3th and 8th week after disease onset. Children with desquamation had 9.3 (95%CI: 1.836-47.437) times higher odds of developing onychomadesis compared to those without this manifestation. Ten out of 14 collected samples were CVA6 positive, and five positive samples shared a high degree of similarity in the VP1 nucleotide and amino acid sequences (99.9-100.0% and 100%).Conclusion: This HFMD outbreak was caused by CVA6, featured with delayed symptoms. Emerging CVA6-associated HFMD and its delayed symptoms should be paid more attention to reduce outbreaks and provide more information to doctors and parents. [ABSTRACT FROM AUTHOR]