The epidemic characteristics and spatial autocorrelation analysis of hand, foot and mouth disease from 2010 to 2015 in Shantou, Guangdong, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is the highest incidence of infectious diseases in China. Shantou is one of the most infected cities. Therefore, it is necessary for us to understand the epidemic characteristics and distribution trend of HFMD in Shantou. The purpose of this study is to investigate the spatial epidemiological characteristics of HFMD and analyse its spatial autocorrelation. METHOD: We collated and summarised the data of HFMD in Shantou from 2010 to 2015. SaTScan software and Moran's I were used to analyse the spatial correlation of HFMD, and the results were presented in ArcMap. RESULTS: The distribution of HFMD in Shantou was of a seasonal trend, mainly concentrating during May and June. Children under 5-years-old were the main group of cases of HFMD, accounting for 92.46%. The proportion of infected children, especially those aged zero to 1, was the largest in each year, accounting for 45.62%, meaning that smaller children were more susceptible to HFMD. The number of male patients with HFMD was greater than that of females (1.78:1, male: female). With regard to the potential impact of patients' living style on the incidence rate of HFMD, this study revealed that scattered children were the dominant infected population, accounting for as much 84.49% of cases. The incidence of HFMD was unevenly distributed among streets. The incidence interval of streets was in a range of 13.76/100,000 to 1135.19/100,000. Spatial autocorrelation analysis showed that there was no global spatial correlation in Shantou, except in 2013. The results of local spatial autocorrelation analysis showed that H-H correlation existed in the high incidence local area of Shantou. CONCLUSIONS: The incidence of HFMD across the various streets in Shantou not only varied widely but also represented local autocorrelation. Attention, as well as prevention and control measures, should be focused on those high-incidence areas, such as the Queshi street, Zhuchi street and Xinjin street.

Emerging Enteroviruses Causing Hand, Foot and Mouth Disease, China, 2010-2016.

Coxsackievirus A6 emerged as one of the predominant causative agents of hand, foot and mouth disease epidemics in many provinces of China in 2013 and 2015. This virus strain accounted for 25.9% of mild and 15.2% of severe cases in 2013 and 25.8% of mild and 16.9% of severe cases in 2015.

Epidemiology of Recurrent Hand, Foot and Mouth Disease, China, 2008-2015.

Using China's national surveillance data on hand, foot and mouth disease (HFMD) for 2008-2015, we described the epidemiologic and virologic features of recurrent HFMD. A total of 398,010 patients had HFMD recurrence; 1,767 patients had 1,814 cases of recurrent laboratory-confirmed HFMD: 99 reinfections of enterovirus A71 (EV-A71) with EV-A71, 45 of coxsackievirus A16 (CV-A16) with CV-A16, 364 of other enteroviruses with other enteroviruses, 383 of EV-A71 with CV-A16 and CV-A16 with EV-A71, and 923 of EV-A71 or CV-A16 with other enteroviruses and other enteroviruses with EV-A71 or CV-A16. The probability of HFMD recurrence was 1.9% at 12 months, 3.3% at 24 months, 3.9% at 36 months, and 4.0% at 38.8 months after the primary episode. HFMD severity was not associated with recurrent episodes or time interval between episodes. Elucidation of the mechanism underlying HFMD recurrence with the same enterovirus serotype and confirmation that HFMD recurrence is not associated with disease severity is needed.

Large-scale HFMD epidemics caused by Coxsackievirus A16 in Bangalore, India during 2013 and 2015.

Hand foot and mouth disease (HFMD) is a relatively unreported disease in India. This study was undertaken to characterize the enterovirus type/s associated with two unexpectedly-massive epidemics that occurred in Bangalore, India in 2013 and 2015. Stool samples of 229 children with HFMD living in Northern and Southern areas of Bangalore were tested by RT-PCR; 189 (82.5%) were enterovirus positive. The Indian CV-A16 strains exhibited 98-99% sequence identity with those reported in France and China in the 5' untranslated region. BLAST and phylogenetic analyses of complete genomes of representative Indian isolates revealed that the 2015 epidemic was predominated by an inter-species recombinant between CV-A16 and coxsackievirus B5. The 2013 epidemic was primarily caused by nonrecombinant strains. The CV-A16 strains circulated in India since 2007 and phylogeographic analyses indicated imported cases in France and China. In conclusion, CV-A16-associated HFMD epidemics should be recognized as an emerging public health problem in India.

Epidemiological characteristics of hand, foot, and mouth disease in Shandong, China, 2009-2016.

In the past decade, hand, foot, and mouth disease (HFMD) has posed a serious threat to childhood health in China; however, no epidemiological data from large HFMD epidemics have been described since 2013. In the present study, we described the epidemiological patterns of HFMD in Shandong province during 2009-2016 from a large number of symptomatic cases (n = 839,483), including >370,000 HFMD cases since 2013. Our results revealed that HFMD activity has remained at a high level and continued to cause annual epidemics in Shandong province from 2013 onwards. Although the incidence rate was significantly higher in urban areas than in rural areas, no significantly higher case-severity and case-fatality rates were found in urban areas. Furthermore, the seventeen cities of Shandong province could be classified into three distinct epidemiological groups according to the different peak times from southwest (inland) to northeast (coastal) regions. Notably, a replacement of the predominant HFMD circulating agent was seen and non-EVA71/Coxsackievirus A16 enteroviruses became dominant in 2013 and 2015, causing approximately 30% of the severe cases. Our study sheds light on the latest epidemiological characteristics of HFMD in Shandong province and should prove helpful for the prevention and control of the disease in Shandong and elsewhere.

Ambulatory Pediatric Surveillance of Hand, Foot and Mouth Disease as Signal of an Outbreak of Coxsackievirus A6 Infections, France, 2014-2015.

The clinical impact of enteroviruses associated with hand, foot and mouth disease (HFMD) is unknown outside Asia, and the prevalence of enterovirus A71 (EV-A71) in particular might be underestimated. To investigate the prevalence of enterovirus serotypes and the clinical presentations associated with HFMD in France, we conducted prospective ambulatory clinic-based surveillance of children during April 2014-March 2015. Throat or buccal swabs were collected from children with HFMD and tested for the enterovirus genome. Physical examinations were recorded on a standardized form. An enterovirus infection was detected in 523 (79.3%) of 659 children tested. Two epidemic waves occurred, dominated by coxsackievirus (CV) A6, which was detected in 53.9% of enterovirus-infected children. CV-A6 was more frequently related to atypical HFMD manifestations (eruptions extended to limbs and face). Early awareness and documentation of HFMD outbreaks can be achieved by syndromic surveillance of HFMD by ambulatory pediatricians and rapid enterovirus testing and genotyping.

An outbreak of Kingella kingae infections associated with hand, foot and mouth disease/herpangina virus outbreak in Marseille, France, 2013.

BACKGROUND: Outbreaks of invasive Kingella kingae infections recently emerged as a new public health concern in daycare centers in Europe, USA and Israel. Despite this, no trigger factor has been yet identified, preventing the setting up of rational measures of control and prevention. We report an outbreak of K. kingae infections associated with hand, foot and mouth disease/herpangina outbreak, and we define the research and policy priorities. METHODS: From April 22 to May 07, 2013, 5 toddlers presented successive osteo-articular infections in a daycare center in Marseille, France. Real-time polymerase chain reaction targeting the cpn60 gene of K. kingae was used to investigate suspected cases and the prevalence of oropharyngeal K. kingae carriage of their close contacts. RESULTS: The attack rate of the K. kingae infections outbreak was 23.7% (5/21) with no fatality. Positive real-time polymerase chain reaction targeting the cpn60 gene of K. kingae confirmed the diagnosis in 3 cases and revealed a rate of K. kingae oropharynx carriage in the index classroom of 94.4% (17/18) among daycare attendees not given antibiotic during the previous month, and of 76.9% (10/13) among staff in close contact. The eradication rate of K. kingae was 21.4% (3/14) among classmates after oral administration of rifampicin, and eradication occurred spontaneously in 83.3% (5/6) of the staff. Clinical and epidemiological features of the herpangina outbreak were consistent with that of an emerging European Coxsackievirus-A6 outbreak. CONCLUSIONS: Hand, foot and mouth disease/herpangina virus outbreak enables triggering a K. kingae infections outbreak. Our findings offer support for new guidelines of K. kingae infections outbreaks management and emphasize the need for further research.

Circulation of Coxsackievirus A10 and A6 in hand-foot-mouth disease in China, 2009-2011.

Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5'UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40-5.06; OR = 4.81, 95% CI: 3.07-7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.