Dataset Information

Hand, Foot, and Mouth Disease in China: Critical Community Size and Spatial Vaccination Strategies.

ABSTRACT: Hand Foot and Mouth Disease (HFMD) constitutes a considerable burden for health care systems across China. Yet this burden displays important geographic heterogeneity that directly affects the local persistence and the dynamics of the disease, and thus the ability to control it through vaccination campaigns. Here, we use detailed geographic surveillance data and epidemic models to estimate the critical community size (CCS) of HFMD associated enterovirus serotypes CV-A16 and EV-A71 and we explore what spatial vaccination strategies may best reduce the burden of HFMD. We found CCS ranging from 336,979 (±225,866) to 722,372 (±150,562) with the lowest estimates associated with EV-A71 in the southern region of China where multiple transmission seasons have previously been identified. Our results suggest the existence of a regional immigration-recolonization dynamic driven by urban centers. If EV-A71 vaccines doses are limited, these would be optimally deployed in highly populated urban centers and in high-prevalence areas. If HFMD vaccines are included in China's National Immunization Program in order to achieve high coverage rates (>85%), routine vaccination of newborns largely outperforms strategies in which the equivalent number of doses is equally divided between routine vaccination of newborns and pulse vaccination of the community at large.

SUBMITTER: Van Boeckel TP

PROVIDER: S-EPMC4850478 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Hand, Foot, and Mouth Disease in China: Critical Community Size and Spatial Vaccination Strategies.

Van Boeckel Thomas P TP Takahashi Saki S Liao Qiaohong Q Xing Weijia W Lai Shengjie S Hsiao Victor V Liu Fengfeng F Zheng Yaming Y Chang Zhaorui Z Yuan Chen C Metcalf C Jessica E CJ Yu Hongjie H Grenfell Bryan T BT

Scientific reports 20160429

Hand Foot and Mouth Disease (HFMD) constitutes a considerable burden for health care systems across China. Yet this burden displays important geographic heterogeneity that directly affects the local persistence and the dynamics of the disease, and thus the ability to control it through vaccination campaigns. Here, we use detailed geographic surveillance data and epidemic models to estimate the critical community size (CCS) of HFMD associated enterovirus serotypes CV-A16 and EV-A71 and we explore ...[more]

PMID: 27125917

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Project description:BackgroundHand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus.Methods and findingsWeekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16.ConclusionsThe ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden.

Project description:BackgroundHand, Foot, and Mouth Disease (HFMD) is most frequently caused by Enterovirus71 (EV-A71) or Coxsackie virus A16 (CV-A16), infants and young children are at greatest risk. Describing the epidemiology of HFMD can help develop and better target interventions, including the use of pediatric EV-A71 vaccination.MethodsWe obtained data from the national surveillance system for HFMD cases with onset dates from 2009 to 2015. We defined probable cases as patient with skin papular or vesicular rashes on the hands, feet, mouth, or buttocks and confirmed cases as patients with the above symptoms along with laboratory-based enterovirus detection. We generated overall and age-specific annual incidence rates and described the temporal variability and seasonality of HFMD in Qinghai Province. We identified spatial clustering of HFMD incidence at the county level using the Local Indicator of Spatial Associationand an alpha level of 0.05.ResultsDuring the study period, 14,480 HFMD probable or confirmed cases were reported in Qinghai Province. Of the 2158 (14.9%) with laboratory confirmation, 924 (42.6%) were caused by CV-A16 and 830 (38.2%) were caused by EV-A71. The majority (89%) of all case-patients were???5?years of age and male (61.5%). The overall mean annual HFMD incidence rate was 36.4 cases per 100,000 populations, while the incidence rate for children ?5?years of age was 379.5 cases per 100,000. Case reports peaked during the months of May through July. HFMD was predominantly caused by EV-A71, except in 2010 and 2014 when CV-A16 was the predominant causative agent. High incidence rates of HFMD were clustered (Moran's I?=?0.59, P?< 0.05) in the eastern region of the province.ConclusionHFMD remains an important cause of childhood disease in Qinghai Province, occurring in an acyclical pattern of increased incidence, primarily due to CV-A16 circulation every three years. Incidence is also seasonal and tends to spatially cluster in the eastern region of the province. Since approximately 40% of confirmed HFMD cases were due to EV-A71, EV-A71 vaccination is likely to have a positive impact on the HFMD disease burden. Routine analysis of local surveillance data is crucial for describing disease occurrence and changes in etiology.

Project description:Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008-2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen's serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens' serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008-2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children. Furthermore, literature summary for 26 seroprevalence studies during 1997-2015 confirmed that 0-5 years group showed lowest level of EV71 seroprevalence (29.1% on average) compared to the elder children (6-10 years group: 54.6%; 11-20 years group: 61.8%). Global positive spatial autocorrelation patterns (Moran's Is>0.25, P<0.05) were discovered not only for mild cases but also for severe cases, and local positive spatial autocorrelation patterns were revealed for counties from the eastern coastal and southern regions. The retrospective space-time cluster analysis also confirmed these patterns. Risk factors analyses implied that more EV71 and less sunshine were associated with the clusters of HFMD in Zhejiang Province. Our study confirmed that Zhejiang Province was one of the highly epidemic provinces in China and that the epidemiological characteristics of HFMD were similar to other provinces. Occult infection in elder children and adults was one of the important reasons why most HFMD cases were children aged under-five. Combining the results of spatial autocorrelation analysis and the space-time cluster analysis, the major spatial-temporal clusters were from the eastern coastal and southern regions. The distribution of pathogens' serotypes and the level of sunshine could be risk factors for, and serve as an early warning of, the outbreak of HFMD in Zhejiang Province.

Dataset Information

Hand, Foot, and Mouth Disease in China: Critical Community Size and Spatial Vaccination Strategies.

Publications

Hand, Foot, and Mouth Disease in China: Critical Community Size and Spatial Vaccination Strategies.

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