Estimation of the Basic Reproduction Number of Enterovirus 71 and Coxsackievirus A16 in Hand, Foot, and Mouth Disease Outbreaks

Ma, Edmond; Fung, Connie; Yip, Steven H. L.; Wong, Christine; Chuang, Shuk-Kwan; Tsang, Thomas

doi:10.1097/inf.0b013e3182116e95

Cited by 62 publications

(53 citation statements)

References 26 publications

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“…The incubation period for EV71 is assumed to be approximately 5 days (d) with the median duration of virus shedding period estimated to be 2 d in close contact group, 18 d in mild HFMD and 25 d for severe HFMD [20]. The median basic reproductive number for EV71 is 5.48, which is approximately two-fold higher than that of coxsackievirus (CV) type A16 infection (2.50 d) [21]. …”

Section: Introductionmentioning

confidence: 99%

Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations

et al. 2014

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BackgroundHuman enterovirus 71 (EV71) is an important pathogen caused large outbreaks in Asian-Pacific region with severe neurological complications and may lead to death in young children. Understanding of the etiological spectrum and epidemic changes of enterovirus and population’s immunity against EV71 are crucial for the implementation of future therapeutic and prophylactic intervention.ResultsA total of 1,182 patients who presented with the symptoms of hand foot and mouth disease (67.3%) or herpangina (HA) (16.7%) and admitted to the hospitals during 2008-2013 were tested for enterovirus using pan-enterovirus PCR targeting 5′-untranslated region and specific PCR for viral capsid protein 1 gene. Overall, 59.7% were pan-enterovirus positive comprising 9.1% EV71 and 31.2% coxsackievirus species A (CV-A) including 70.5% CV-A6, 27.6% CV-A16, 1.1% CV-A10, and 0.8% CV-A5. HFMD and HA occurred endemically during 2008-2011. The number of cases increased dramatically in June 2012 with the percentage of the recently emerged CV-A6 significantly rose to 28.4%. Co-circulation between different EV71 genotypes was observed during the outbreak. Total of 161 sera obtained from healthy individuals were tested for neutralizing antibodies (NAb) against EV71 subgenotype B5 (EV71-B5) using microneutralization assay. The seropositive rate of EV71-B5 was 65.8%. The age-adjusted seroprevalence for individuals was found to be lowest in children aged >6 months to 2 years (42.5%). The seropositive rate remained relatively low in preschool children aged > 2 years to 6 years (48.3%) and thereafter increased sharply to more than 80% in individuals aged > 6 years.ConclusionsThis study describes longitudinal data reflecting changing patterns of enterovirus prevalence over 6 years and demonstrates high seroprevalences of EV71-B5 NAb among Thai individuals. The rate of EV71 seropositive increased with age but without gender-specific significant difference. We identified that relative lower EV71 seropositive rate in early 2012 may demonstrate widely presented of EV71-B5 in the population before account for a large outbreak scale epidemic occurred in 2012 with due to a relatively high susceptibility of the younger population.

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Section: Introductionmentioning

confidence: 99%

Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations

et al. 2014

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“…Studies on molecular epidemiology of CVA16 were reported elsewhere [6-10], the genetic diversity and evolutionary characteristics of this virus has yet to be explored. Previous studies have shown that CVA16 was responsible for the conﬁrmed HFMD cases in China in recent years [11-13]; besides HFMD and herpangina, infection by CVA16 could also cause serious myocarditis and pericarditis, acute heart failure, and even death [14,15]. …”

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology of Coxsackievirus A16: Intratype and Prevalent Intertype Recombination Identified

Chen

Tan

et al. 2013

PLoS ONE

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Coxsackievirus A16 (CVA16) is responsible for nearly 50% of all the conﬁrmed hand, foot, and mouth disease (HFMD) cases in mainland China, sometimes it could also cause severe complications, and even death. To clarify the genetic characteristics and the epidemic patterns of CVA16 in mainland China, comprehensive bioinfomatics analyses were performed by using 35 CVA16 whole genome sequences from 1998 to 2011, 593 complete CVA16 VP1 sequences from 1981 to 2011, and prototype strains of human enterovirus species A (EV-A). Analysis on complete VP1 sequences revealed that subgenotypes B1a and B1b were prevalent strains and have been co-circulating in many Asian countries since 2000, especially in mainland China for at least 13 years. While the prevalence of subgenotype B1c (totally 20 strains) was much limited, only found in Malaysia from 2005 to 2007 and in France in 2010. Genotype B2 only caused epidemic in Japan and Malaysia from 1981 to 2000. Both subgenotypes B1a and B1b were potential recombinant viruses containing sequences from other EV-A donors in the 5’-untranslated region and P2, P3 non-structural protein encoding regions.

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“…An indicator, such as basic reproduction numbers, was estimated from models to evaluate the effectiveness of disease control. 21,22 However, some factors affecting HFMD epidemics at a population level, such as the difference in immunological response at different ages were usually neglected; the relationship between susceptibility to EV71 and age of children was rarely analyzed quantitatively. In this report, 2 models, originating from survey data and from development of the immune system, were used to explore variations between positive rates and age.…”

Section: Discussionmentioning

confidence: 99%

Two models for changes of EV71 immunity in infants and young children

Wang

Zhu

et al. 2015

Human Vaccines & Immunotherapeutics

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Human enterovirus 71 (EV71) has been associated with outbreaks of hand-foot-and-mouth disease (HFMD) in China. Susceptibility to EV71 is associated with age, but few studies have been accomplished to measure such a relationship. A better understanding of the connection between susceptibility and age is necessary to develop strategies for control of HFMD. In 2010, a survey of an epidemic of EV71 was conducted in a northern city of Jiangsu Province in China. Samples were tested serologically to identify the EV71 neutralizing antibody. Two different mathematical models have now been employed to describe how this antibody varied with age, and parameters in the model were estimated from survey data. Both models depicted the variations in EV71-neutralizing antibody. Seroprevalence was high for neonates but decreased to near zero at 5 months of age. Subsequently, the EV71 antibody levels increased and then remained stable after about 36 months. For models 1 and 2, values for the coefficient of determination (R(2)) were 0.9458 and 0.9576, and values for root mean square error (RMSE) were 0.0755 and 0.0752, respectively. Model 2, formulated from the characteristics of development of the immune system, was more reliable than model 1, formulated from survey data, because the impact of the survey on the structure of the model was removed. Moreover, model 2 provided the possibility to define the parameters in a biological sense.

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Estimation of the Basic Reproduction Number of Enterovirus 71 and Coxsackievirus A16 in Hand, Foot, and Mouth Disease Outbreaks

Abstract: The R₀ for EV71 and for Cox A16 was determined using a model which showed that the R₀ for EV71 was higher than that of Cox A16. This finding helps better understand the transmission dynamics of HFMD outbreaks and formulate public health measures for controlling the disease.

Cited by 62 publications

References 26 publications

Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations

Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations

Molecular Epidemiology of Coxsackievirus A16: Intratype and Prevalent Intertype Recombination Identified

Two models for changes of EV71 immunity in infants and young children

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