Long-Term Outcomes of Pediatric Enterovirus Infection in Taiwan: A Population-Based Cohort Study
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Background The major burden of diseases in childhood has shifted from infectious diseases to chronic health conditions in recent decades. Although the rates of infectious diseases have decreased, the incidence of chronic diseases stemming from infectious agents continues to grow. Enterovirus is a major infectious disease of childhood and has been linked to numerous chronic diseases. We analyzed population-based data from Taiwan’s National Health Insurance Research Database (NHIRD) to investigate the correlations between enterovirus infection and major chronic health conditions in children. Methods Children diagnosed with enterovirus (EV) infection during 1999-2003 were identified from the Longitudinal Health Insurance Database 2000 (LHID 2000), a subdataset of Taiwan’s National Health Insurance Research Database (NHIRD). A total of 14,168 patients were selected after excluding patients with existing chronic diseases and missing data. Another 14,168 patients matched by age and sex were selected as the control group. Five primary outcomes, including attention deficit and hyperactivity disorder (ADHD), epilepsy, asthma, allergic rhinitis, and atopic dermatitis, were recorded. Results The risks of ADHD, asthma, allergic rhinitis, and epilepsy were significantly increased in the EV group compared with the control group. The risk of atopic dermatitis was significantly increased in the crude model. However, there were no significant differences in the adjusted model. The risks of ADHD, asthma, allergic rhinitis, and epilepsy were also significantly increased in patients with severe EV infection compared with patients with non-severe EV infection. [Is this what you mean? If you are just comparing patients with and without EV infection, you have already mentioned this finding in the first sentence of the results.] Conclusion Chronic diseases, such as ADHD, epilepsy, and allergic diseases were shown to be associated with enterovirus infection during childhood. EV infection during early childhood might have long-term public health implications and thus prevention strategies should be implemented.Keywords:
Enterovirus 71
To study the clinical and epidemiologic characteristics and the serum types of enterovirus of hand, foot and mouth disease (HFMD) in children.The RT-nPCR method was established with universal primers within 5' untranslated region of enterovirus and VP1 region of Coxsackievirus A16 (CAV16) and enterovirus 71 (EV 71). Enteroviruses were detected with RT-nPCR in 237 children with HFMD. Clinical and epidemiologic characteristics and serum types of enterovirus of the patients with HFMD were studied.The patients'age ranged from 7 months to 11 years (mean 4.2 +/- 0.5 years). The majority (94.5%) were less than 6 years old. HFMD was mostly seen in spring and winter (67.9%). Oral mucosal pox or ulcer as well as hand and foot rashes were observed in all 237 patients. Fever occurred in 141 patients (59.5%). Of the 237 patients, 133 (56.1%) were RT-nPCR positive. Of the 133 cases, 38 were positive for EV71, 64 were positive for CAV16, and 31 were negative for both EV71 and CAV16. The patients infected by different types of enteroviruses had similar clinical characteristics. Gene colon and sequence analysis for 12 strains of enteroviruses PCR positive products presented as EV71 (n=5), CAV16 (n=5), ECHO13 (n=1), and CAV5 (n=1).HFMD tends to occur in younger children less than 6 years old. The majority are affected in spring and winter. EV71 and CAV16 are common pathogens of HFMD. There is no relationship between clinical characteristics and serum types of enteroviruses in HFMD patients.
Enterovirus 71
Hand-foot-and-mouth disease
Foot (prosody)
Coxsackievirus
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Objective To investigate the pathogen distribution of patients with hand, foot and mouth diseases (HFMD) hospitalized in division of pediatrics, Beijing Ditan Hospital, Capital Medical University, in 2010. Methods Real-time fluorescence quantitative RT-PCR kits with three reagents: universal enterovirus primer, Coxsackievirus A16 (CA16) primer and enterovirus 71 (EV71) primer were used to detect the samples. Results The enterovirus-positive rate was 63.20% (213/337).Among this, the positive rates of enterovirus 71, Coxsackievirus A-16 and other types of enterovirus were 40.36% (136/337), 5.46%(19/337) and 17.21%(58/337), respectively. Conclusions In 2010, the etiology of children with hand, foot and mouth disease hospitalized in our hospital was dominated by enterovirus 71(EV71). The infection rates of enterovirus except enterovirus 71 and Coxsackievirus A16 are main pathogens. Non-CA16, non-EV71 virus infection were significant higher than Coxsackievirus A16 infection.
Enterovirus 71
Coxsackievirus
Hand-foot-and-mouth disease
Etiology
Primer (cosmetics)
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The recent, ongoing epidemic of hand, foot, and mouth disease (HFMD), which is caused by enterovirus infection, has affected millions of children and resulted in thousands of deaths in China. Enterovirus 71 (EV71) and coxsackie A16 (CA16) are the two major distinct pathogens for HFMD. However, EV71 is more commonly associated with neurologic complications and even fatalities. Therefore, simultaneously detecting and differentiating EV71 and CA16 specifically from other enteroviruses for diagnosing HFMD is important. Here, we developed a one-step, triplex, real-time RT-PCR assay for the simultaneous detection of EV71, CA16, and pan-enterovirus (EVs) in a single tube with an internal amplification control. The detection results for the serially diluted viruses indicate that the lower limit of detection for this assay is 0.001-0.04 TCID50/ml, 0.02 TCID50/ml, and 0.001 TCID50/ml for EVs, EV71, and CA16, respectively. After evaluating known HFMD virus stocks of 17 strains of 16 different serotypes, this assay showed a favorable detection spectrum and no obvious cross-reactivity. The results for 141 clinical throat swabs from HFMD-suspected patients demonstrated sensitivities of 98.4%, 98.7%, and 100% for EVs, EV71, and CA16, respectively, and 100% specificity for each virus. The application of this one-step, triplex, real-time RT-PCR assay in clinical units will contribute to HFMD surveillance and help to identify causative pathogen in patients with suspected HFMD.
Enterovirus 71
Throat
Hand-foot-and-mouth disease
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To investigate the epidemic characteristics of etiological agents in children with hand, foot and mouth disease (HFMD) and analyze the differences between the severe and mild cases with HFMD seen from 2008 to 2009 in the Children's Hospital.A total of 154 patients with HFMD were enrolled from May 2008 to September 2008 and from May 2009 to September 2009, including 28 severe HFMD patients. Data from 80 cases with suspected herpangina were collected as control. Enterovirus universal type, enterovirus type 71 (EV71) and coxsackie virus group A 16 (CA16) were detected by real-time RT-PCR respectively.The positive rate of enterovirus universal type in the 154 patients with HFMD was 81.82%(126/154). EV71 positive rate in these 126 patients with enterovirus universal type infection was 57.14%(72/126). The positive rate of enterovirus universal type in the 80 cases with suspected herpangina was 68.75%(55/80). There was no EV71 infection in these 80 cases with suspected herpangina. EV71 infection was mainly popular in 2008. Both EV71 and CA16 were prevalent in 2009. The epidemic characteristics of enterovirus infection with HFMD between 2008 and 2009 had significant differences (χ(2) = 23.50, P = 0.000) (P < 0.01). The epidemic characteristics of enterovirus infection between severe and mild HFMD patients also had significant differences (χ(2) = 29.85, P < 0.01). There were 28 cases with severe HFMD, in whom the EV71 positive rate was 92.86% (26/28). EV71 positive rate in the mild HFMD was 36.51% (46/126) (χ(2) = 29.22, P < 0.01). There was no significant difference in the gender (χ(2) = 0.135, P = 0.714) and virus load (t = 0.141, P = 0.889) between the mild and severe HFMD cases. But the age of mild and severe HFMD showed a significant difference (t = 2.926, P = 0.009). Patients who were less than 2 years of age had a proportion of 88.89% (8/9) with severe HFMD. The mean age of mild HFMD patients was 3.19 years.HFMD showed different epidemic characteristics at different times of enterovirus infection. There was no significant difference in the gender and virus load between the mild and severe cases with HFMD. Children under 3 years of age with EV71 infection were at high risk for severe HFMD.
Enterovirus 71
Etiology
Hand-foot-and-mouth disease
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Citations (8)
Enterovirus 71
Coxsackievirus
Hand-foot-and-mouth disease
Medical microbiology
Enterovirus Infections
Isolation
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Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in Jiangsu Province from 2012 to 2013. Fifty-nine infants were randomly selected from 522 non-EV-A71/CV-A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT-PCR was used to amplify 5'-UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty-one non-EV-A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non-EV-A71/CV-A enteroviruses among infants were CV-B3, CV-A10, CV-A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co-infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co-infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD.
Enterovirus 71
Etiology
Throat
Picornavirus
Rhinovirus
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Citations (22)
Objectives To understand the difference of clinical features of hand-foot-mouth disease(HFMD) caused by enterovirus 71 and other enterovirus types.Methods A total of 106 children with HFMD were included and divided into three groups according to etiology: group 1(enterovirus 71 infection,n = 63),group 2(Coxsackievirus A16 infection,n = 16) and group 3(other enterovirus types infection,n = 27).The information of fever,rash and clinical manifestations of nervous system,respiratory and circulatory systems,and the laboratory data were summarized and analyzed among the three groups.Results The patients in group 1 had higher incidence of central nervous system infection than that of group 2 and group 3.The patients in group 1 had higher peak temperature,longer fever time and more frequent limb tremor and irritation than that in group 2(P 0.05).The patients of CA16 had higher incidence of headache,vomiting,convulsion than that in group 1(P 0.05).Conclusions Patients with EV71 infection had higher peak temperature,longer fever time,higher incidence of central nervous system infection,more frequent limb tremor and irritation than other enterovirus types infection.These characteristics may help pediatricians to identify the type of enterovirus.
Enterovirus 71
Etiology
Coxsackievirus
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Citations (1)
Objective
To analyze the epidemic characteristics of enterovirus infection in Yueqing city from 2010 to 2018, and to provide reference for the prevention and control of hand, foot and mouth disease (HFMD) caused by enterovirus.
Methods
Clinical data of HFMD cases caused by enterovirus infection during 2010 to 2018 were derived from the disease monitoring information report management system of Yueqing city. Descriptive epidemiological study was performed to analyze the characteristics of enterovirus infection by season, age, gender and region and the features of pathogens.
Results
There were 53 178 patients with HFMD in total, including 75 severe cases and six deaths. Enterovirus infection occurred in every month of the years and peaked from April to July. Most of the cases were scattered children and nursery children under five years old and the incidence was higher in males than in females. From 2010 to 2018, the characteristics of enterovirus in Yueqing city had changed significantly. Enterovirus 71 (EV71) was the predominant pathogen during 2010 to 2014, but its detection rate had gradually decreased since 2013. In recent years, the incidence of HFMD caused by non-EV71 and non-coxsackievirus A16 (non-CVA16) enteroviruses significantly increased.
Conclusions
Enterovirus infection in Yueqing city was featured by significant seasonality and population-specific variation. Etiological detection should be strengthened. Comprehensive prevention and control measures should be taken to prevent the outbreak of HFMD during April to July.
Key words:
Enterovirus; Epidemiology; Hand, foot and mouth disease; Child
Enterovirus 71
Etiology
Coxsackievirus
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Citations (0)
Few studies have investigated the viral isolation characteristics for severe complicated enterovirus infection (SCEI). This study evaluated the seasonality and contribution of circulated viruses to the chronologic trend and weekly reported SCEI epidemic.Enterovirus infection surveillance and virology laboratory data in 2000 to 2008 obtained from the Centers for Disease Control in Taiwan were analyzed. We measured the monthly and weekly virology isolation rates by viral types. The virus-specific and the season-specific relative risks for SCEI and 95% confidence intervals (CI) associated with the isolated circulating viruses and weather status was evaluated.Among 1539 virology confirmed SCEI cases, the mean annual incidence rates ranged from 0.72/100,000 to 32.5/100,000 in children aged 5 years and less; rates were higher in warm months with cases peaking in June (12.6%). The untypeable nonpolio enterovirus was the most frequently isolated type among the monitored specimens (6.07%), followed by coxsackievirus A (3.99%), EV71 (1.77%), coxsackievirus B (1.56%), and echovirus (1.23%). However, these SCEI cases had very strong associations with the isolation of EV71 and coxsackievirus A and B. The corresponding relative risks were 1.14 (95% CI, 1.11-1.17), 1.03 (95% CI, 1.01-1.04), and 1.09 (95% CI, 1.07-1.12), respectively, for 1% increase in weekly isolation rate.Isolation rates for EV71 and coxsackieviruses A and B can predict the development of SCEI cases, particularly in warm months.
Enterovirus 71
Enterovirus Infections
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Citations (10)
A rapid expansion of hand, foot, and mouth disease (HFMD) outbreaks has occurred and caused deaths in China in recent years, but little is known about the other etiologic agents except enterovirus 71 (EV71) and coxsackievirus A 16 (CA16). The objective of this study is to determine the genotype compositions of enterovirus causing HFMD in Shanghai and identify any associations between enterovirus types and clinical manifestations. Stool specimens were collected from patients hospitalized for treatment of HFMD, from May 2010 to April 2011. Enterovirus was detected by reverse transcription PCR and directly genotyped by sequencing the PCR products. Phylogenetic analysis was based on the VP1 partial gene. Of 290 specimens, 277 (95.5%) tested positive for enterovirus. The major genotypes were EV71 (63.8%), CA10 (9.0%), CA6 (8.3%), CA16 (6.9%), CA12 (2.4%), and CA4 (1.4%). The EV71 strains belonged to the C4a subtype and CA16 belonged to the B subtype. CA6 was closely related to strains detected in Japan, Taiwan and China, and CA10, CA12 and CA4 were phylogenetically similar to other strains circulating in China. Mean hospital stays and the prevalence of complications in patients with EV71 infection were higher than those in patients in CA6, CA10 or CA16 infection (P < 0.05 for all comparisons). Children with CA12 infection were the youngest, and most likely have the highest risk of complications when compared to the other non-EV71 infection groups. This study demonstrated a diversified pathogen compositions attributing to HFMD and clinical symptoms differing in enterovirus genotypes. It deserves our attention as early identification of enterovirus genotypes is important for diagnosis and treatment of HFMD patients.
Enterovirus 71
Coxsackievirus
Medical microbiology
Hand-foot-and-mouth disease
Molecular Epidemiology
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Citations (51)