Study on the epidemiological characteristics of enterovirus among pediatric patients in Hangzhou, China: A comparison between the pre-COVID-19, COVID-19 pandemic, and post-COVID-19 periods.

Nonpharmaceutical interventions (NPIs) for coronavirus disease 2019 (COVID-19) not only reduce the prevalence of this disease among children but also influence the transmission of other viruses. This retrospective study investigated the impact of NPIs on human enterovirus (HEV) infection in children diagnosed with hand, foot, and mouth disease (HFMD) or herpangina (HA) in Hangzhou, China. We collected and analyzed the laboratory results and clinical data of children diagnosed with HFMD or HA during the following periods: pre-COVID-19 (January 2019 to December 2019), the COVID-19 pandemic (January 2020 to December 2022), and post-COVID-19 (January to December 2023). A total of 41 742 specimens that met the inclusion criteria were obtained, of which 1998 (4.79%) tested positive for enterovirus. In comparison to those in the pre-COVID-19 period, which had 695 (5.63%) HEV-positive specimens, the numbers dramatically decreased to 69 (1.19%), 398 (5.12%), and 112 (1.58%) in 2020, 2021, and 2022, respectively, but significantly increased to 724 (8.27%) in 2023. Seasonal peaks of infections occurred in May, June, July, and August each year, with the total detection rate ranging from 2019 to 2023 being 9.41% in May, 22.47% in June, 28.23% in July, and 12.16% in August, respectively. The difference in the detection rates of HEV infection between males and females was statistically significant (p < 0.005), with 5.11% (1221/23 898) of males and 4.35% (777/17 844) of females testing positive, resulting in a male-to-female positive ratio of 1.57:1. Among the age groups, 11.25% (378/3360) of the children aged 3-5 years had the highest detection rate, which steadily decreased with increasing or decreasing age. The detection of HEV indicated that >95% of the viruses were other types than the previously commonly reported enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16). In conclusion, NPIs for COVID-19 may be effective at reducing the transmission of HEV. However, with the relaxation of NPIs, the detection rate of HEVs increased slowly to a certain extent. Active awareness and surveillance of the epidemiological characteristics of HEV are essential for preventing, controlling, and managing the development of HFMD and HA, as well as contributing to the development of a multivalent HFMD vaccine.

Large-scale resurgence of herpangina in Japan, following the easing of COVID-19 measures.

Objectives: This study examined the rise in herpangina cases and its demographic trends in Japan post-easing of COVID-19 restrictions in the summer of 2023, assessing its potential strain on pediatric healthcare. Methods: Weekly herpangina cases data from the National Institute of Infectious Diseases from 2017 to 2023 were analyzed using difference-in-differences methodology and Poisson regression models, incorporating variables such as time, the COVID-19 pandemic, and the easing of measures. Statistical significance was set at a two-sided P-value of 0.05. Results: A significant increase in herpangina cases was observed from the 19th to the 27th week of 2023, with a notable shift in age distribution compared to that of pre-pandemic years. Poisson regression analysis revealed a positive correlation between the number of herpangina cases and the easing of infection control measures. There was an increase in other respiratory illnesses, including respiratory syncytial virus, particularly in children aged 3 and above. Conclusion: We found a surge in herpangina cases in Japan after the easing of the COVID-19 restrictions during the summer of 2023, along with a noticeable increase in other respiratory illnesses, emphasizing the potential strain on pediatric healthcare and reinforcing the ongoing significance of implementing general infection prevention strategies.

Non-Polio Enterovirus Surveillance in the Ural Federal District and Western Siberia, 2022: Is There a Need for a Vaccine?

Human non-polio enteroviruses (NPEVs) are the etiological agents involved in most cases of hand-foot-and-mouth disease (HFMD), herpangina and aseptic meningitis. Information on the epidemiology profiles of NPEV in the Ural Federal District and Western Siberia is very limited, with no published data available. The aim of this study is to describe NPEV incidence in the Ural Federal District and Western Siberia among patients with different forms of non-polio enterovirus infections (NPEVIs) during 2022, stratified by age and clinical manifestations. A total of 265 samples that tested positive for NPEV using a polymerase chain reaction (PCR) were genotyped by semi-nested PCR for the VP1 gene. The results showed that 21 genotypes were identified among patients in this study. CVA6 was the most common genotype for HFMD. CVA6, along with CVA10, accounted for the majority of herpangina cases, while CVA9 was implicated in most meningitis cases. Sequence and phylogenetic analysis showed that nearly all of the CVA6 strains identified in this study displayed a close genetic relationship to strains identified in other cities in Russia and strains from China. NPEV surveillance allows for monitoring the circulation of clinically relevant genotypes, resulting in continuous data about NPEV epidemiology. This is important for improving case prevention, diagnosis and guiding clinical management.

Phylogenetics and phylogeographic characteristics of coxsackievirus A16 in hand foot and mouth disease and herpangina cases collected in Beijing, China from 2019 to 2021.

Coxsackievirus A16 (CV-A16) is a significant pathogen responsible for causing hand foot and mouth disease (HFMD) and herpangina (HA). This study aimed to investigate the recent evolution and spread of CV-A16 by monitoring HFMD and HA cases in 29 hospitals across 16 districts in Beijing from 2019 to 2021. The first five cases of HFMD and the first five cases of HA each month in each hospital were included in the study. Real-time reverse transcription polymerase chain reaction was used to identify CV-A16, CV-A6, and EV-A71. From each district, two to four CV-A16 positive samples with a relatively long sampling time interval every month were selected for sequencing. A total of 3344 HFMD cases and 2704 HA cases were enrolled in this study, with 76.0% (2541/3344) of HFMD and 45.4% (1227/2704) of HA cases confirmed to be infected by enterovirus. Among the EV-positive samples, CV-A16 virus was detected in 33.61% (854/2541) of HFMD cases and 13.4% (165/1227) of HA cases, with the predominant cluster being B1a. Both B1a and B1b had a co-circulation of local and imported strains, with different origin time (1993 vs. 1995), different global distribution (14 countries vs. 10 countries), and different transmission centers but mainly distributed in the southern and eastern regions of Beijing. Strengthening surveillance of HFMD in southern and eastern regions will improve the prevention and control efficiency of enterovirus infections.

Complete genome comparative analysis of Coxsackievirus A6 causing hand,foot and mouth disease and herpangina in Yunnan Province in 2018 / 中国生物制品学杂志

@#ObjectiveTo analyze the genome-wide characteristics of 17 strains of Coxsackievirus A6(CVA6)that cause hand,foot and mouth disease(HFMD)and herpangina(HA)in Yunnan Province in 2018,and understand the genetic differences between different pathogenic CVA6.MethodsA total of 1 909 stool samples clinically diagnosed as HFMD and HA in Kunming Children′s Hospital in 2018 were randomly selected for detection using enterovirus group A universal primers and screening of CVA6 positive samples. The CVA6 whole genome sequence was amplified with CVA6 whole genome primers,spliced by BioEdit splicting software,and analyzed for the whole genome characteristics by BioEdit,MEGA 7.0,Simplot,Heml 1.0 and Phyre2softwares.ResultsA total of 929 CVA6 positive samples were screened,and 17CVA6 complete gene sequences were obtained(9 of which were clinically diagnosed as HFMD and 8 were clinically diagnosed as HA). All 17 CVA6 strains were in type IV clade on the whole phylogenetic tree. No significant recombination occurred in HA and HFMD representative strains,while mutations occurred in non-structural protein 3D region. HFMD and HA representative strains showed differences in VP1 loci S597T,Q705L and Q663L. Online predictive analysis showed that the secondary structure of VP1 was consistent with that of CVA6 with no change.ConclusionThe 17 CVA6 strains causing HFMD and HA had high genomic homology,as well as nucleotide and amino acid differences,which may affect the replication and adaptability of CVA6.

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020.

Background: The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China. Method: From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes. Result: A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world. Conclusions: The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

The Prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease / 预防医学

Objective@#To establish a prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease, so as to provide insights into analyses of communicable disease epidemics with limited or missing surveillance data.@*Methods@#The incidence of hand, foot and mouth disease in Zhejiang Province during the period from the first week of 2015 through the 39th week of 2021 was retrieved from the China Information System for Disease Control and Prevention, and the Baidu index of hand, foot and mouth disease and herpangina was collected via the Baidu search engine during the same period. The correlation between the Baidu index and time series of hand, foot and mouth disease was examined using wavelet analysis. In addition, a random forest training model was created based on the Baidu index and incidence of hand, foot and mouth disease, and the fitting effectiveness was evaluated using the mean percentage error, while the Baidu index of herpangina was included in the model to predict the epidemic trend of herpangina during the study period.@*Results@#The Baidu index of herpangina and hand, foot and mouth disease, and the Baidu index and incidence of hand, foot and mouth disease all appeared two peaks at the 26th and 52th week. The phase difference was less than 0.1 week between the Baidu index and time series of hand, foot and mouth disease, and the mean percentage error of the training model was 13.07%, with high concordance between the predicted number and actual report number of cases with hand, foot and mouth disease. The numbers of herpangina cases were predicted to be 28 822, 27 341, 28 422, 51 782, 52 457 and 5 691 from 2015 to 2020, and there were totally 48 702 herpangina cases reported until the 39th week of 2021. Like hand, foot and mouth disease, the incidence of herpangina peaked between May and July.@*Conclusion@#The random forest training model based on the Baidu index and incidence of hand, foot and mouth disease is feasible to predict the epidemic trend of herpangina.

Pathogen identification and genotyping of two cluster outbreaks of herpangina in children in Dapeng New District， Shenzhen / 上海预防医学

ObjectiveTo determine the pathogenic characteristics and genotype of two outbreaks of herpangina in children in Dapeng New District， Shenzhen， in May 2021. MethodsA total of five throat swabs from children in the two outbreaks of herpangina were collected and examined for common enteroviruses by real-time PCR. The VP1 region was further amplified by nested RT-PCR. The CLUSTAL W program in MEGA7 software was used to conduct the alignment and reconstruct a phylogenetic tree. ResultsThe pathogen causing the 2 cluster outbreaks of herpangina was coxsackievirus A4 （CVA4）. The sequences of CVA4 VP1 genes revealed that a nucleotide identity of 92% between the strains in the two outbreaks. The three CVA4 strains isolated in kindergarten A had the closest phylogenetic relationship with that isolated in Shenzhen in 2018（MN840533）， with the nucleotide identity of 98.11%. The two strains in kindergarten B had the closest phylogenetic relationship with CVA4 strain isolated in Sichuan in 2018（MW178763）， with the nucleotide identity of 97.88%. The phylogenetic tree showed that all five CVA4 strains in this study belonged to the C2 genotype. ConclusionThe C2 genotype of CVA4 is the causative agent in both outbreaks of herpangina.

[Herpangina. Clinical case]. / Gerpeticheskaya angina ­ aktual'naya problema otorinolaringologicheskoi praktiki.

Enterovirus infections are a group of acute infectious diseases caused by enteroviruses (including Coxsackie A and B viruses, ECHO viruses), which clinically present symptoms of damage to the central nervous system, cardiovascular system, gastrointestinal tract, muscular system, mucous membranes and skin, fever. This article presents a clinical case of patient L., 12 years old, who admitted to an otorhinolaryngologist with clinical manifestations of herpangina. The diagnosis was confirmed by PCR. The patient was prescribed, adequate rehydration, diet with the exclusion of salty, spicy and fried foods, restriction of physical activity, exclusion of thermal procedures, Benzydamine Spray (Oralsept) 0.255 mg/dose, 6 doses 3 times/day, topically, on demand and inosine pranobex (Groprinosin) in a daily dose of 50 mg/kg of body weight: 1 tablet 500 mg 4 times a day for 7 days (at the rate of 1 tablet of 500 mg per 10 kg of body weight; for a patient weighing 41 kg - 4 tablets per day). On the 10th day from the onset of the disease, the docter noted a complete regression of clinical symptoms and the patient was discharged with recovery.

A large-scale outbreak of hand, foot and mouth disease, France, as at 28 September 2021.

We report a large-scale outbreak of hand, foot and mouth disease (HFMD) in France. As at 28 September 2021, 3,403 cases have been reported (47% higher than in 2018-19). We prospectively analysed 210 clinical samples; 190 (90.5%) were enterovirus-positive. Most children presented with atypical HFMD. Coxsackievirus (CV)A6 (49.5%; 94/190) was predominant; no enterovirus A71 was detected. Dermatological and neurological complications of HFMD justify prospective syndromic and virological surveillance for early detection of HFMD outbreaks and identification of associated types.

Molecular Epidemiology and Clinical Features of Enteroviruses-Associated Hand, Foot, and Mouth Disease and Herpangina Outbreak in Zunyi, China, 2019.

Background: Hand, foot and mouth disease (HFMD) and herpangina (HA), two of the most common childhood infectious diseases, are associated with enteroviruses (EVs) infection. The aim of this study was to identify the molecular epidemiology of enterovirus causing HFMD/HA in Zunyi, China, during 2019, and to describe the clinical features of the cases. Methods: We collected the information on demographic and clinical characteristics, laboratory data of laboratory-confirmed EVs associated HFMD/HA cases in Zunyi Medical University Third Affiliated Hospital between March 1 and July 31, 2019. EV types were determined by either one-step real time RT-PCR or partial VP1 gene sequencing and sequence alignment. Phylogenetic analysis of CVA6, CVA2, and CVA5 were established based on the partial VP1 gene sequences by neighbor-joining method. Differences in clinical characteristics and laboratory results of the cases were compared among patients infected with the most prevalent EV types. Results: From 1 March to 31 July 2019, 1,377 EVs associated HFMD/HA inpatients were confirmed. Of them, 4 (0.3%, 4/1,377) were EV-A71-associated cases, 84 (6.1%, 84/1,377) were CVA16-associated cases, and 1,289 (93.6%, 1,289/1,377) were non-EV-A71/CVA16-associated cases. Of the randomly selected 372 non-EV-A71/CVA16 cases, EV types have been successfully determined in 273 cases including 166 HFMD and 107 HA cases. For HFMD cases, the three most common types were CVA6 (80.7%, 134/166), CVA2 (5.4%, 9/166) and CVA5 (3.0%, 5/166); similarly, for HA cases, the three most prevalent serotypes were CVA6 (36.5%, 39/107), CVA2 (21.5%, 23/107) and CVA5 (18.7%, 20/107). Phylogenetic analysis showed that subclade D of CVA5, and subclade E of CVA6 and CVA2 were predominant in Zunyi during the outbreak in 2019. Compared with the cases caused by CVA16, the incidence of high fever and severe infection associated with CVA2, CVA5, and CVA6 was higher. Conclusions: The recent HFMD/HA outbreak in Zunyi is due to a larger incidence of CVA6, CVA2, and CVA5. Novel diagnostic reagents and vaccines against these types would be important to monitor and control EV infections.

Efficacy and safety of interferon α-2b spray for herpangina in children: A randomized, controlled trial.

OBJECTIVES: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. METHODS: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1-7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. RESULTS: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. CONCLUSIONS: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

Caregivers: the potential infection resources for the sustaining epidemic of hand, foot, and mouth disease/herpangina in Guangdong, China?

BACKGROUND: Although several measures have been taken to control hand foot and mouth disease (HFMD) and herpangina (HA), these two diseases have been prevalent in China for 10 years with high incidence. We suspected that adults' inapparent infection might be the cause of the continued prevalence of HFMD/HA infection in mainland China. METHODS: To explore the role of adults (especially caregivers) in the transmission process of HFMD/HA among children, 330 HFMD/HA cases and 330 healthy children (controls) were selected for a case-control study. Then, data were analyzed by logistic regression. RESULTS: Single-variable analyses revealed that caregivers who tested positive for enterovirus was a significant risk factor of HFMD/HA transmission to children (adjusted odds ratio (OR) = 9.22; 95% CI, 1.16 to 73.23). In the final multivariable model, caregiver behavior, such as cooling children's food with mouth (OR = 1.85; 95% CI, 1.11 to 3.08) and feeding children with their own tableware (OR = 2.19; 95% CI, 1.07 to 4.45), significantly increased the risk of transmitting HFMD/HA to children. On the contrary, washing hands before feeding children reduced such risk. CONCLUSIONS: These results implied that the caregivers might be the infectious source or carriers of enterovirus. Therefore, preventing or treating the caregivers' enterovirus infection and improving their hygiene habits, especially when they are in contact with children, could provide a breakthrough for the effective control of HFMD/HA.

Molecular epidemiology and clinical characteristics of herpangina children in Beijing, China: a surveillance study.

BACKGROUND: Herpangina is a highly infectious disease, which is usually prevalent in preschool children. METHODS: This study analyzed the clinical and pathogenic characteristics of herpangina children to demonstrate the epidemiology of herpangina. Clinical manifestations, laboratory indicators and pharyngeal swabs were collected from children with herpangina who were monitored by Tongzhou Center for Disease Control and Prevention in Beijing, 2008. Utilizing pharyngeal swabs, virus extraction and amplification were performed for nucleotide identification and sequencing. The phylogenetic analysis was conducted based on all sequences amplified in this study and strains retrieved from GenBank. RESULTS: Among 190 children with herpangina, 69.0% (131/190) were positive for enterovirus. Eight genotypes were identified, mainly including CV-A6 (39/131), CV-A4 (25/131), CV-A10 (24/131). The phylogenetic analysis showed one CV-A6 strain of Tongzhou was imported from Japan. CV-A10 strains were clustered into five groups (A-E). The dominant cluster of CV-A10 was Group E6 between 2009 and 2013, and converted to Group E5 after 2013. CV-A6 was the predominant pathogen causing herpangina in Tongzhou in 2018, followed by CV-A4 and CV-A10. CONCLUSIONS: The circulation of coxsackievirus had spatiotemporal cluster. In controlling the transmission of herpangina, the surveillance and reporting system should be enhanced.

Weather condition, air pollutants, and epidemics as factors that potentially influence the development of Kawasaki disease.

Environmental factors have been suspected to have effects on the development of Kawasaki disease. However, the associations have been conflicting. The aim of this study was to investigate the effects of air pollution, weather conditions, and epidemic infections on the risks for Kawasaki disease in Japan. The concentrations of air pollutants (nitric oxide, nitrogen dioxide, and sulfur dioxide); ambient weather conditions (temperature, atmospheric pressure, relative air humidity, precipitation, sunshine duration, and wind velocity); and the epidemic conditions of 14 infectious diseases in hospitalized patients with Kawasaki disease were monitored from 2011 to 2018 in Beppu, Japan. The overdispersed generalized additive model was used to evaluate the effects, and a combination model with a distributed lag nonlinear model was used to estimate the cumulative effects. The incidence of Kawasaki disease had positive associations with preceding hot temperature and increased concentrations of nitric oxide and sulfur dioxide and a negative association with epidemic herpangina. The cumulative relative risk of Kawasaki disease at 5 lagged days of increased temperature was 1.76 (95% confidence interval: 1.01-3.07). This city-level observational study suggested that the incidence of Kawasaki disease was associated with air pollution and increased temperature and may be indirectly influenced by epidemic herpangina.

Lack of effective home quarantine: The cause of the continuing prevalence of hand, foot, and mouth disease in China?

BACKGROUND: Home quarantine as a non-pharmaceutical measure is a key strategy for preventing the spread of hand, foot, and mouth disease (HFMD) and herpangina (HA). However, the status of home quarantine remains unclear. This study aimed to provide a theoretical basis for the prevention and control of the HFMD and HA by investigating the situation and determining the factors influencing home quarantine in children with HFMD or HA. METHODS: The convenience sampling method was used in this cross-sectional study involving parents whose children suffered from HFMD or HA in 2019. An online questionnaire tool was used to collect demographic information, socioeconomic status, clinical factors, sources of advice, and details of home quarantine. Logistic regression analysis was used to explore the factors influencing of home quarantine. RESULTS: A total of 3145 parents answered the electronic questionnaire; among them, 317 had children diagnosed with HFMD or HA in 2019. After quality control, 298 questionnaires were included in the analysis. The whole compliance rate of home quarantine for HFMD and HA was 59.1%. Results of multivariate logistic regression analysis indicated that having grandparents as the primary caregiver (OR=2.53, 95% CI: 1.20-5.43) was a risk factor of home-quarantine noncompliance, whereas doctor's notification (OR=0.35, 95% CI: 0.18-0.67) and advice from parents of other infected children (OR=0.53, 95% CI: 0.31-0.91) can increase the compliance with home quarantine. CONCLUSIONS: Home-quarantine measures for HFMD and HA were not well implemented. The caregivers, doctor's notification, and advice from parents of other infected children were associated with home-quarantine compliance. Corresponding measures should be taken to regulate home quarantine.

Comparative Efficacy of Chinese Herbal Injections for the Treatment of Herpangina: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Considering the limitations of broad-spectrum antiviral drugs for the treatment of herpangina and the extensive exploration of Chinese herbal injections (CHIs), systematic evaluation of the efficacy of different CHIs in the treatment of herpangina is a key imperative. In this study, we performed a network meta-analysis to investigate the efficacy of CHIs, including Reduning injection (RDN), Shuanghuanglian injection (SHL), Tanreqing injection (TRQ), Xiyanping injection (XYP), and Yanhuning injection (YHN), in the treatment of herpangina. METHODS: A systematic literature review including studies published before December 17, 2018, was conducted in several databases. The quality of the included studies was assessed using the Cochrane risk of bias tool. Data were analyzed using STATA 13.0 and WinBUGS 1.4.3 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Clustering analysis was performed to compare the effects of CHIs between two different outcomes. RESULTS: A total of 72 eligible randomized controlled trials involving 8,592 patients and five CHIs were included. All patients were under the age of 15 years, and most were under 7 years. The results of the network meta-analysis showed that RDN, XYP, and YHN had significantly better treatment performance than ribavirin. SHL (OR: 0.18; 95% CI: 0.09-0.34) and TRQ (OR: 0.18; 95% CI: 0.10-0.31) were obviously superior to ribavirin with respect to total clinical effectiveness. The results of SUCRA and cluster analysis indicated that RDN is the best intervention with respect to total clinical effectiveness, antipyretic time, and blebs disappearing time. Fifty-four studies described adverse drug reactions/adverse drug events (ADRs/ADEs), and 32 studies reported ADRs/ADEs in detail. CONCLUSIONS: CHIs were found to be superior to ribavirin in terms of treatment performance and may be beneficial for patients with herpangina. RDN had the potential to be the best CHI with respect to all outcome measures. More evidence is needed to assess the safety aspects of CHIs.

Mosaic genome of Human Coxsackievirus A4 associated with herpangina and HFMD in Yancheng, China, 2016 and 2018.

OBJECTIVES: To better understand the spectrums of pathogens causing herpangina and circulation of Coxsackievirus A4 in Yancheng, China. METHODS: Stool samples from herpangina and HFMD cases were collected. Real Time PCR Kits was used to identify Enterovirus 71, CV-A16 and CV-A6, and nested reverse transcription PCR (nRT-PCR) to detect the other enterovirus types. Complete VP1 and genome sequence of CV-A4 were amplified by using nRT-PCR. Genetic, phylogenetic and recombination analysis were performed. RESULTS: Co-circulation of three recombinant CV-A4 groups, including one novel (C2 lineage), was identified in Yancheng, China, 2016 and 2018. One was the major causative agent of herpangina, and another two were responsible for HFMD. Phylogenetic and recombination analysis indicated that the non-structural region of their genome originated from the same ancestry and subsequently adaptation. C2 lineage of CV-A4 group may be introduced from countries outside China and its genome occurred recombination in China. CONCLUSION: Novel recombinant CV-A4 was mainly associated with herpanginain in Yancheng, 2018, China. C2 lineage of CV-A4 group with recombinant non-structural region was also identified in HFMD patients.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Research progress on the correlation between herpangina and hand⁃foot⁃mouth disease / 口腔疾病防治

@# As acute enterovirus⁃induced infections, herpangina(HA) and hand⁃foot⁃mouth disease(HFMD) are simi⁃lar in many aspects. Although these diseases vary with time and region, many studies have shown that the viruses caus⁃ing HA and HFMD are consistent, and there is no notable difference in partial VP1 gene sequences between different vi⁃ruses. HA and HFMD also resemble each other in epidemiological features. Both infections show significant summer⁃time seasonality, have a strong connection with certain environmental conditions and are most prevalent in young chil⁃dren and infants. Herpangina is thought to be a mild disease, defined as vesicular enanthem and then ulcers of the fau⁃ces and soft palate with presentation of feve r, sore throat, and decreased appetite. HFMD, which could lead to severe symptoms, is also characterized by oral ulcers, although they are chiefly on the buccal mucosa and tongue, and typical vesicular rashes, which are most commonly found on the hands, feet, knees and buttocks. While HA is generally be⁃ lieved to be self⁃limited and has a favorable prognosis, HA with certain clinical characteristics, such as diarrhea, vomit⁃ing, limb jitter and sleepiness, can evolve into HFMD, according to some literature in recent years. However, HA is an independent risk factor for HFMD, and severe cases only present with herpes appearing at the isthmus of the fauces at an early stage, which indicates a strong correlation between them. Clinical manifestations of HA should be considered by medical staff to identify potential children with HFMD as early as possible to prevent its further development or transformation.