Molecular surveillance of coxsackievirus A16 in southern China, 2008-2019.

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.

The adsorption characteristics of Cu(II) and Zn(II) on the sediments at the mouth of a typical urban polluted river in Dianchi Lake: taking Xinhe as an example.

This study is to determine the spatial distribution characteristics of Cu and Zn adsorption on the sediments of the estuary of Dianchi Lake, as well as the composite adsorption law of Cu and Zn on combinations of sediment organic matter, metal oxides, and organic-inorganic composites. The relationship between the adsorption contribution of each component of the substance. A static adsorption experiment was applied to the sediments in the estuary of Dianchi Lake. The relationship between adsorption capacity and sediment composition was analyzed through correlation analysis and redundant analysis. The results show that along the direction of the river flow and the vertical depth, the adsorption capacity presents a relatively obvious spatial distribution law; the change trend of sediment component content is not the same as the change trend of Cu and Zn adsorption capacity. The change trend of the sediment component content is not the same as the change trend of the adsorption amount of Cu and Zn, and the compound effect between the components affects the adsorption amount. The adsorption of Cu by the four groups of sediments after different treatments is more in line with the Freundlich isotherm adsorption model; When adsorbing Zn, the untreated and removed organic matter and iron-aluminum oxide group are in good agreement with the Freundlich model, while the organic matter-removed group and the iron-aluminum oxide removal group are more consistent with the Langmuir isotherm adsorption model; The adsorption contribution rate of organic-inorganic composites in sediments is not a simple addition of organic matter and iron-aluminum oxides, but a more complex quantitative relationship.

[The Complete Sequence Analysis of 18 Strains of Coxsackievirus A6 in Guangdong Province of China].

In this study, we examined the complete genome of coxsackievirus A6 (CVA6) from hand, foot, and mouth disease in Guangdong Province from 2013,and explored the genetic similarities and differences in epidemic and non-epidemic stains of CVA6.Eighteen strains of CVA6 were included in complete genome sequencing, and the sequences were subject to phylogenetic analysis,sequence alignment analysis and genetic recombination analysis using the software DNASTAR6.0,MEGA5.2and SimPlot3.5.1.The results showed that the complete genome of 18 Guangdong CVA6strains ranged from 7390bp to 7392bp.No insertions or deletions were detected in the coding region. There were several insertions and deletions in 5'UTR and 3'UTR.Phylogenetic analysis indicated that the nucleotide and amino acid sequence identity between the 18 complete genomes were 90.5%-99.6% and 97.5%-99.9%,respectively.The strains isolated in2013 could be further divided into two clusters, III and IV, while the strains isolated in 2011 were only present in the IV cluster. Genetic recombination analysis revealed that the Guangdong representative strain of CVA6,GD870/2013,had gene recombination in the P2 and P3regions,while the GD839/2013 strain did not show obvious genetic recombination. Genome-wide analysis of CVA6 revealed that there are two possible transmitted chains, III and IV, in epidemic strains from Guangdong Province in 2013.The transmitted chain Ⅲ originated from the strain with genetic recombination in the P2 and P3regions,whichwas completely different from the chain IV. Transmission of chain IV of CVA6 was only observed in the nonepidemic 2011 strain.

[Epidemiology Characteristics and Pathogen Surveillance of Hand, Foot and Mouth Disease in Guangdong Province, China, 2008～2015].

To understand the epidemiological etiology characteristics of hand, foot and mouth disease(HFMD)in Guangdong province, and to explore the risk change trend of the whole province. By using the descriptive epidemiological methods, the whole province's incidence trend, population distribution and pathogenic form of HFMD were analyzed with the HFMD surveillance data,population data and geographic information of Guangdong province from 2008 to 2015.The analysis results show: A total of 2,133,722 cases of HFMD, including 5,066 severe cases and 259 death cases were reported in Guangdong province from 2008 to 2015.All the cities of Guangdong had HFMD cases, especially the Pearl River Delta Regions, which were on high-risk areas. There were two peaks every year, with the main peak of incidence occurred in spring and summer, and the sub peak occurred in autumn.Most cases were children aged<5years old, the proportion of this group in overall infections, the severe and death cases were 90.58%,95.93%and 97.30%,respectively,while the proportion for the children less than 3years old were 77.32% and 81.85%,respectively. The incidence of this disease among men was higher than that of women. Dynamic changes were presented between different years and seasons:CV-A16 was more popular in 2009,and enterovirus that none EV-A71 and none CV-A16 were predominant strains in 2013 and 2015.Especially in 2015,the proportion of other EV ranged as high as 71.97%.Besides,EV-A71 was the absolute predominance pathogen within death cases and was important pathogen in severe cases. This study suggests that HFMD epidemiology and laboratory monitoring in Guangdong Province should be strengthened, and provides scientific data support for further improvement of HFMD prevention and control strategies in Guangdong Province.

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 trends of CVA6 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.

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.

An enterovirus 71 epidemic in Guangdong Province of China, 2008: epidemiological, clinical, and virogenic manifestations.

Enterovirus 71 (EV71) is shown to be a major causative agent in outbreaks of hand, foot, and mouth disease (HFMD) reported in Guangdong (GD) Province of China in 2008. A total of 48,876 HFMD cases (131 severe and 21 fatal) were reported to the GD HFMD web-based surveillance system, which covers 871 clinics. The main causes of death included central nervous system damage, heart failure, and pulmonary edema. The incidence rate was 52 per 100,000, and the epidemic peak appeared in May and June. EV71 was found in 59% and coxsackievirus A16 in 26% of 936 laboratory-confirmed cases. Other viruses are likely to be responsible for the remaining 15% of cases. Of the 185 EV71 cases collected, 62% were mild, 27% were severe, and the remaining 11% were fatal. A total of 17 EV71 isolates were subjected to nucleotide sequencing of the entire VP1 gene. Phylogenetic analysis showed that the GD EV71 strains belonged to the C4 subgenotype and that EV71 circulates at a national rather than a regional level. A Comparison with the VP1 gene from a different clinical case showed that there was no obvious virulence determinant in this locus. Furthermore, this study found that most deaths occurred in rural areas, thereby indicating that delayed diagnosis and incorrect treatment may play an important role.