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Background and Clinical Significance: Kawasaki disease (KD) is an acute febrile vasculitis that primarily affects children and is associated with systemic inflammation, particularly in the coronary arteries. Coxsackievirus A6 (CVA6) has emerged as a significant agent in atypical presentations of hand, foot, and mouth disease (HFMD), raising the possibility of its involvement in KD. Case Presentation: This report presents the case of an 18-month-old Thai boy admitted with symptoms of high fever, sore throat, and ulcerative lesions, initially diagnosed with herpangina. As his condition progressed, additional KD symptoms developed, including conjunctival injection, rash, and elevated inflammatory markers, fulfilling the diagnostic criteria for KD. Notably, throat swab analysis confirmed CVA6 as the causative agent. Phylogenetic analysis revealed that the CVA6 strain closely aligned with Chinese strains from 2023, showing a high nucleotide sequence homology of 98.4%. Conclusions: In conclusion, this case highlights a possible association between CVA6-associated herpangina and KD, suggesting that CVA6 infection may act as a trigger for KD in genetically susceptible children. These findings highlight the need for increased awareness among healthcare providers to promptly identify and manage Kawasaki Disease during peak enterovirus seasons, reducing its impact on children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Childhood viral and bacterial infections may cause oral symptoms that might help early diagnosis and treatment and support the prevention efforts of pediatricians and parents. Oral lesions can clinically mimic malignancy and genetic disorders. The inflammatory changes of oral mucosa during childhood infectious diseases pose some challenges during differential diagnosis, due to the wide range of etiologies. Global migration and gaps in vaccination coverage have allowed viral infections to expand and reemerge. This review highlights the clinical features and treatment recommendations of childhood infections that can be encountered in dental practice, with a short description of the underlying systemic illness. Thorough patient history and physical examination are essential for determining the infectious agent that affects oral cavity. Treatment strategies customized for the pediatric age group are guiding the management of oral and perioral lesions from infancy through adolescence. The clinical features, diagnosis criteria, and treatment algorithms of the most common pediatric infectious diseases are summarized based on their prevalence. Dentists can play an important role in early identification of various childhood infections through soft tissue lesion investigation. Due to the numerous oral complications, vaccination awareness is another important task assigned to dentists

Objective: To explore the efficacy of Qingre Liyan decoction combine with Xiyanping injection in the treatment of children with herpangina and its influence on inflammatory factors and immune function. Methods: 83 children with herpangina who were admitted to Shijiazhuang Traditional Chinese Medicine Hospital from May 2019 to February 2022 were selected, and they were divided into control group (n=41) and study group (n=42) according to the random number table method. On the basis of routine treatment, control group received treatment with Xiyanping injection, and study group received treatment with Qingre Liyan decoction on the basis of control group. The traditional Chinese medicine efficacy, clinical symptom improvement, inflammatory factors, and immune function changes were compared between two groups. Results: The clinical total effective rate in study group was higher than that in control group (P<0.05). The herpes healing time, fever relief time, and pharyngeal pain improvement time in study group were shorter than those in control group (P<0.05). 5 d after treatment, the interleukin-10 (IL-10) increased, γ- interferon (IFN-γ), interleukin-6 (IL-6) and C-reactive protein (CRP) decreased in two groups, and the improvement degree in study group was greater than that in control group (P<0.05). 5 d after treatment, the CD3+, CD4+, CD4+/CD8+, and NK increased in two groups, and the improvement degree in study group was greater than that in control group(P<0.05). Conclusion: Qingre Liyan decoction combine with Xiyanping injection in the treatment of children with herpangina, which can shorten the symptom relief time, reduce the level of inflammatory factors, improve the body's immune function, and improve clinical efficacy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Background: Different Traditional Chinese Medicine (TCM) in the format of granules, such as Kanggan Granules (KangGs), Kouyanqing Granules (KouGs), Lianhua Qingwen Granules (LQGs), Qingkailing Granules (QGs) and Xiao'er Qingjie Granules (XQJGs), collectively named Yinhua-based herbal granules (YH-HGs) have been widely used in the management of pediatric outpatients with herpangina. Few head-to-head randomized controlled trials (RCTs) have compared the efficacy of these agents. This network meta-analysis (NMA) was conducted to indirectly compare the efficacy of YH-HGs. Methods: This systematic review and fixed-effect NMA was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for NMA. RCTs assessing the efficacy and safety of YH-HGs in children that were also receiving ribavirin as the conventional therapy were searched from eight databases and two trial registers up to Jan 13, 2022. The primary outcome was total effectiveness rate (TER). The secondary outcomes were total adverse events (TAEs) and the time to symptom improvement of fever, vesicles, pain and salivation. Relative risk (RR) and weighted mean difference with 95% confidence intervals (CIs) were estimated by direct pairwise meta-analysis (MA) and NMA. Results: A total of 10 RCTs, enrolling 1 017 pediatric patients, were included. YH-HGs were better than no medication (NM) in TER (RR = 1.22, 95%CIs, 1.16 – 1.28) by direct pairwise MA, in which KangGs (RR = 1.24, 95%CIs, 1.05 – 1.47), KouGs (RR = 1.17, 95%CIs, 1.08 – 1.27), LQGs (RR = 1.24, 95%CIs, 1.14 – 1.35), QGs (RR = 1.33, 95%CIs, 1.11 – 1.58) and XQJGs (RR = 1.18, 95%CIs, 1.00 – 1.40) were also more efficient than NM. As for secondary outcomes, YH-HGs was associated with a 103% increased risk of TAEs compared to NM, but no significant differences were found. YH-HGs has a more positive symptom improvement effect than NM in fever, vesicles, pain and salivation. The ranking results showed that QGs (79.2%) had the highest probability ranking first in TER and KangGs (63.6%) ranked as the second, followed by LQGs (52.4%), XQJGs (50.3%), KouGs (49.7%), and NM (4.9%) at last. Conclusions: Our findings support the better efficacy of YH-HGs than NM as regards TER. QGs, KangGs, LQGs, XQJGs, KouGs remain superior to NM and their clinical choice should depend on the patient's conditions to improve symptoms better for the different effects. Given the limitations of NMA, head-to-head RCTs with high-quality are needed.

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.

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.

Abstract 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.

Objectives – to identify the clinical and epidemiological features of enterovirus infection in the adult population in the Oryol region, to track the seasonality of the disease, distribution in different age groups, and to assess the main clinical forms, symptoms, and complications.Objects and methods of research. The object of investigation was 24 medical histories of patients who gave informed consent, with a confirmed diagnosis of “enterovirus infection”, the 2 nd infectious diseases Department of Department of Oryol region “City hospital. S.P. Botkin”.Results. For the period from 2009 to 2019 was gospitalizirovany 24 patients with laboratory-confirmed diagnosis “enterovirus infection”. The most patients with this diagnosis were in 2017 – 33,5 %, the least – in 2012 – 4,1 %. In 2013 and 2019, there were no patients. Women were sick more often than men – 55 % of the total number of subjects. After analyzing statistical data, it was found that young people (aged 20–29 years) were sick more often – 58,3 %. There is a summer-autumn seasonality: 45,8 % and 54,2 %, respectively. 37,5 % of the subjects were in contact with infectious SARS patients. 37,5 % also left the Oryol region the day before.Most often, enterovirus exanthema was observed in patients – 58,3 %.. The onset of the disease in 100 % of cases was acute. All patients had fever, most often subfebrile – 54,2 %. The studied patients complained of body aches – 100 %, headaches of various localization and intensity – 96 %, sore throat – 12,5 %, vesicular-papular rash on the skin of the trunk, limbs, and head – 58,3 %, and enanthema on the oropharyngeal mucosa – 12,5 %. In 100 % of cases, the diagnosis was confirmed by a positive polymerase chain reaction response to the presence of enterovirus RNA.Conclusion. The study revealed that over the past 10 years, enterovirus infection in the Oryol region has a consistently low level. It is more common in young people. The disease is characterized by summer and autumn seasonality. In this area, the more common form is enterovirus exanthema.

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.

BackgroundThe 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.MethodFrom 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.ResultA 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.ConclusionsThe 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.

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.

Sore throats are common! Being able to differentiate low-acuity self-limited infections from those processes that may result in sepsis or life-threatening airway compromise is critical. The author, in this two-part article, reviews the range of pathologies that may present with a sore throat. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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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.

BackgroundConsidering 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.MethodsA 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.ResultsA 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.ConclusionsCHIs 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.

Objective. To reveal the clinical and epidemiological features of еnterovirus meningitis (EVM) in 140 children of Krasnoyarsk in the period of seasonal rise of morbidity in 2017.Materials and methods. For the etiological interpretation of the enterovirus infection (EVI), a molecular biological and virological study of the cerebrospinal fluid, two samples of feces, a swab from the oropharynx, the contents of the vesicles was carried out. Statistical processing of data was carried out using the PASW Statistics 17.0 program.Results. In the Krasnoyarsk Territory, an annual increase in the incidence of EVI is registered, exceeding the average for the country. Serous meningitis is traditionally the main clinical form of EVI. Among the observed patients with EVM, the main group consisted of preschool children (32.9%) and school age (30%), mainly organized in children's groups (84.3%), and the summer-autumn seasonality of the disease remains. Meningitis was observed in 82.8% of patients, meningitis combined with exanthema — in 10%, with herpangina — in 2.1%, with myalgia — in isolated cases . Mediastinal forms of the disease predominated (96.4% — 135 people), severe forms of the EVM were diagnosed only in 3.6% (5 patients). The clinical picture is traditionally represented by three leading syndromes: intoxication, cerebral and meningeal. The implementation of the epidemic process in 2017 was mainly represented by enteroviruses Coxackie B, B1, B2, B4. Despite the relatively favorable course of the EVM, residual events were in 10% of patients (14 people) at the time of discharge.

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Every year, an increase in the incidence of enterovirus infection is registered everywhere, including Coxsackie viruses. Parents of sick children are often very uneasy considering these viruses to be extremely dangerous and the disease to be severe one, with possible adverse consequences. The situation is exacerbated by many mass media that inform about the epidemic of Coxsackie virus, which causes a terrible disease. The article gives main characteristics of microorganisms, modes of infection, clinical manifestations of enterovirus infections as well as measures for prevention and treatment.

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.

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Highlights • Strains in 2001–08 and in 2010–17 were clearly clustered separately. • There were cross-antigenicities among different cluster/subgenotype strains. • Vaccination will be effective, irrespective of genetic cluster/subgenotype. Abstract Although coxsackievirus A6 (CV-A6) is generally recognized as a causative agent of herpangina in children, CV-A6 infections globally emerged as a new and major cause of epidemic hand-foot-and-mouth-diseases (HFMDs) around 2008. To clarify the longitudinal epidemiology of CV-A6, we carried out sequence and phylogenetic analyses for the VP1 and partially for the VP4-3D regions as well as antigenic analysis using 115 CV-A6 isolates and 105 human sera in Yamagata, Japan between 2001 and 2017. Phylogenetic analysis revealed that CV-A6 isolates were clearly divided into two clusters; strains in circulation between 2001 and 2008 and those between 2010 and 2017. Neutralizing antibody titers of two rabbit antisera, which were immunized with Yamagata isolates in 2001 and 2015, respectively, against 28 Yamagata representative strains as well as the prototype Gdula strain were 1:2560–1:5120 and 1:160–1:640, respectively. The neutralizing antibody titers among residents in Yamagata against the above two strains were similar. Our analyses revealed that there were cross-antigenicities among all analyzed CV-A6 strains, although the newly emerged strains were introduced into Yamagata around 2010 and replaced the previous ones. With regard to control measures, these findings suggest that we can prevent CV-A6 infections through the development of a vaccine that effectively induces neutralizing antibodies against CV-A6, irrespective of genetic cluster. [ABSTRACT FROM AUTHOR]

ABSTRACT Enterovirus A71 (EV-A71) infections are one of the main etiological agents of hand, foot and mouth disease (HFMD) and herpangina worldwide. EV-A71 infection is a life-threatening communicable disease and there is an urgent global need for the development of vaccines for its prevention and control. The morbidity rate of EV-A71 infection differs between countries. The pathogen’s genetic lineages are undergoing rapid evolutionary changes. An association between the occurrence of EV-A71 infection and the circulation of different genetic strains of EV-A71 virus has been identified around the world. In this review, we present and discuss the molecular epidemiology and pathogenesis of the human disease caused by EV-A71 infection, as well as current prospects for the development of an EV-A71 vaccine.

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., Competing Interests: The authors have no competing interests to declare., (© 2023 The Authors.)

The article focuses on discovery and structural characterization of a therapeutic antibody against coxsackievirus A10 which emerged as major pathogen of hand, foot, and mouth disease and herpangina in children. It mentions comparisons of the near-atomic cryo–electron microscopy structures of the three forms of CVA10 capsid and their complexes. It also mentions atomic structures of neutralizing antibody of CVA10 inform strategies for designing vaccines and therapeutics against CVA10 infections.

Background: In 2009, a nationwide sentinel surveillance for hand-foot-mouth disease (HFMD) and herpangina (HA) with neurologic complications was initiated in South Korea. We used this surveillance system to investigate the clinical characteristics of patients with either HFMD or HA with neurologic complications, with the aim of determining risk factors for severe neurologic complications. Methods: A retrospective review of medical records was conducted on all cases of HFMD and HA with neurologic complications that were reported in the national system between April 1, 2009 and December 31, 2014. A severe case was defined as having HFMD or HA with encephalitis, polio-like syndrome, or cardiopulmonary failure, and less-severe cases were defined as having HFMD or HA with aseptic meningitis. Results: A total of 138 cases (less-severe: 90/138, 65.2%; severe: 48/138, 24.8%) were included from 28 hospitals; 28 ineligible cases were excluded. Of 48 severe cases, 27 (56.2%) had encephalitis; 14 (29.2%) had polio-like syndrome; and seven (14.6%) had cardiopulmonary syndrome. The median patient age was 36 months (IQR: 18–60) and 63 (45.7%) patients were female. Most patients completely recovered, except for seven cases that were fatal or resulted in long-term symptoms (5.1%, 3 patients with neurologic sequelae and 4 deaths). In a multivariable logistic regression analysis, lethargy (OR = 4.67, 95% CI: 1.37–15.96, P = 0.014), female sex (OR = 3.51, 95% CI: 1.17–10.50, P = 0.025), and enterovirus A71 (OR = 3.55, 95% CI: 1.09–11.57, P = 0.035) were significantly associated with severe neurologic complications in HFMD and HA patients. Conclusion: In patients with HFMD and HA, lethargy, female, and enterovirus A71 may predict severe neurologic complications. [ABSTRACT FROM AUTHOR]