Hanri Zeng

Hand, foot and mouth disease in Guangdong, China, in 2013: new trends in the continuing epidemic.

Millions of incidents of hand, foot and mouth disease occur annually in China, with EVA71 and CVA16 as two major causative pathogens. A provincial surveillance system has been implemented in Guangdong for almost 5 years to analyze the aetiological spectrum and epidemic changes. An unusual enterovirus type, CVA6, was identified as the predominant serotype associated with an HFMD epidemic from late 2012 to 2013. In contrast to virus strains isolated before, all CVA6/CHN/2012-2013 strains segregated into one major genetic cluster. This study suggested that one cluster of circulating CVA6 strain had emerged as a new and major cause during a continuing HFMD epidemic in Guangdong, China.

The epidemiological study of Coxsackievirus A6 revealing hand, foot and mouth disease epidemic patterns in Guangdong, China

Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trendsofCVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China.

Seroepidemiology of human enterovirus71 and coxsackievirusA16 among children in Guangdong province, China

BackgroundHand, foot and mouth disease (HFMD) is a common pediatric illness. Mainly induced by the Enterovirus 71 and Coxsackievirus A 16 infections, the frequently occurred HFMD outbreaks have become a serious public health problem in Southeast Asia. Currently,only a few studies have investigated the human immunity to HFMD in China. In this study, we conducted a cohort study in Guangdong province, China.MethodsStored serum samples from children less than 10 years old were analyzed. The levels of EV71 and CA16 specific antibodies before, during and shortly after the 2008 large outbreak of HFMD were evaluated by the microneutralization test. The geometric mean titer (GMT) was calculated and compared. Statistical significance was taken as P < 0.05.ResultsThe seroprevalence data showed a continuous circulation of EV71 and CA16 in Guangdong province China in 2007–2009. The low positive rate in 2009 correlated well with the unprecedented outbreak of HFMD in 2010. Age related increase of seroprevalence was identified in 1–3 years old children for EV71 and in 1–5 years old children for CA16 in Guangdong province. High GMT of EV71 and CA16 antibody titers were also found for these age groups.ConclusionsAll of the above findings indicated common infections for these age groups. And they should clearly be at the top of the priority in periodical seroprevalence survey and future vaccination campaign.

Seroprevalence of Human Enterovirus 71 and Coxsackievirus A16 in Guangdong, China, in Pre- and Post-2010 HFMD Epidemic Period

Background Human Enterovirus 71 and Coxsackie A16 have caused many outbreaks in the last decade in mainland China, resulting in thousands of fatal cases. Seroepidemiology which provides important information to document population immunity is rare in China. Methodology/Principal Findings A cross sectional study of Enterovirus 71 (EV71) and Coxsackie A16 (CA16) seroprevalence was carried out in Guangdong, China, pre- and post- the 2010 hand, foot and mouth disease (HFMD) epidemic period. The levels of EV71 and CA16 specific antibodies were evaluated by a microneutralization test and the geometric mean titer (GMT) was calculated and compared. Our results indicated frequent infection by EV71 and CA16 in Guangdong before the 2010 epidemic. Only EV71 neutralizing antibody but not CA16 seroprevalence was significantly increased after the 2010 HFMD epidemic. Children less than 3 years old especially those aged 2 years showed the lowest positive rates for EV71 and CA16 NA before epidemic and the most significantly increased EV71 seroprevalence after epidemic. CA16 GMT values declined after the 2010 epidemic. Conclusions These results indicate EV71 was the major pathogen of HFMD in Guangdong during the 2010 epidemic. The infection occurs largely in children less than 3 years, who should have first priority to receive an EV71 vaccine.

Population Dynamics and Genetic Diversity of C4 Strains of Human Enterovirus 71 in Mainland China, 1998–2010

Background Since 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD). Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71) belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high. Methodology/Principal Findings To gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010. Conclusions EV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate persistently among the Chinese population.

Association of GII.P16-GII.2 Recombinant Norovirus Strain with Increased Norovirus Outbreaks, Guangdong, China, 2016

An unusual prevalence of recombinant GII.2 noroviruses (GII.P16-GII.2) in Guangdong, China, at the end of 2016 caused a sharp increase in outbreaks of acute gastroenteritis. This event was another non-GII.4 epidemic that emerged after the GII.17 viruses in 2014 and 2015 and warrants global surveillance.

Prevalence of nonpolio enteroviruses in the sewage of Guangzhou city, China, from 2009 to 2012.

ABSTRACT The human-pathogenic viruses in urban sewage have been extensively monitored to obtain information on circulating viruses in human communities. Enteroviruses (EVs) excreted by patients who present with diverse clinical syndromes can remain infectious in the environment for several weeks, and limited data on circulating environmental EVs are available. A 4-year (2009 to 2012) surveillance study was conducted to detect nonpolio enteroviruses (NPEVs) in the urban sewage of Guangzhou city, China. After the viruses in the sewage samples were concentrated and isolated, molecular identification was used to detect and type the NPEVs. During the 4-year study, 17 different NPEV serotypes were identified in the sewage of Guangzhou city. The most common serotypes were echovirus 11 (ECHO11), ECHO6, ECHO7, and ECHO12 and coxsackie group B viruses 5 (CVB5) and CVB3. The predominant serotypes were influenced by spatial and temporal factors and differed each year. CVB5 was commonly detected in 2009 and 2010 but was rarely isolated in 2011 and 2012. In contrast, CVB3 was not observed in 2009 and 2010 but was increasingly detected in 2011 and 2012. Our study provides an overview of the serotype distribution and circulation patterns of NPEVs in the sewage of Guangzhou, China. In the absence of a systematic EV disease surveillance system, the detection and characterization of sewage-borne NPEVs will help us better understand the changes in EV disease trends and the epidemic background of circulating EVs, which could help interpret the EV trends and warn of future outbreaks in this area.

Whole Genomic Sequence and Replication Kinetics of a New Enterovirus C96 Isolated from Guangdong, China with a Different Cell Tropism

Enterovirus 96 (EV-C96) is a newly described serotype within the enterovirus C (EV-C) species, and its biological and pathological characters are largely unknown. In this study, we sequenced the whole genome of a novel EV-C96 strain that was isolated in 2011 from a patient with acute flaccid paralysis (AFP) in Guangdong province, China and characterized the properties of its infection. Sequence analysis revealed the close relationship between the EV-C96 strains isolated from the Guangdong and Shandong provinces of China, and suggested that recombination events occurred both between these EV-C96 strains and with other EV-C viruses. Moreover, the virus replication kinetics showed EV-C96 Guangdong strain replicated at a high rate in RD cells and presented a different cell tropism to other strains isolated from Shandong recently. These findings gave further insight into the evolutionary processes and extensive biodiversity of EV-C96.

Elucidation of Echovirus 30's Origin and Transmission during the 2012 Aseptic Meningitis Outbreak in Guangdong, China, through Continuing Environmental Surveillance

ABSTRACT An aseptic meningitis outbreak occurred in Luoding City of Guangdong, China, in 2012, and echovirus type 30 (ECHO30) was identified as the major causative pathogen. Environmental surveillance indicated that ECHO30 was detected in the sewage of a neighboring city, Guangzhou, from 2010 to 2012 and also in Luoding City sewage samples (6/43, 14%) collected after the outbreak. In order to track the potential origin of the outbreak viral strains, we sequenced the VP1 genes of 29 viral strains from clinical patients and environmental samples. Sequence alignments and phylogenetic analyses based on VP1 gene sequences revealed that virus strains isolated from the sewage of Guangzhou and Luoding cities matched well the clinical strains from the outbreak, with high nucleotide sequence similarity (98.5% to 100%) and similar cluster distribution. Five ECHO30 clinical strains were clustered with the Guangdong environmental strains but diverged from strains from other regions, suggesting that this subcluster of viruses most likely originated from the circulating virus in Guangdong rather than having been more recently imported from other regions. These findings underscore the importance of long-term, continuous environmental surveillance and genetic analysis to monitor circulating enteroviruses.

Evaluating the transmission routes of hand, foot, and mouth disease in Guangdong, China

Although it is an enteroviral infectious disease, recent studies suggest that respiratory transmission might play a role in the transmission of hand, foot, and mouth disease (HFMD). We evaluated the transmission modes (respiratory and fecal-oral transmission) of HFMD among children using a case-control study in Guangdong, China. Our analyses suggested that fecal-oral transmission might be the principal transmission mode of HFMD among children in the study area, and handwashing habits of the children and their parents should be emphasized to control this infection.