Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.
A number of photofunctional molecular compounds have been developed recently. Typical examples of these are phototunable valence tautomeric compounds, which are now attracting great attention. When the charge-transfer bands of some Co valence tautomeric compounds are excited at low temperature, metastable redox isomers can be created after irradiation. The lifetimes of the metastable states can be more than several hours. These transformations can involve changes in the magnetic properties of the compounds, as well as their color. Hence, these compounds can be regarded as novel photomagnetic materials. The photoresponsive behaviors of these valence tautomeric compounds are similar to those of spin-crossover complexes (light-induced excited spin-state trapping effects).
Emerging epidemics of hand-foot-and-mouth disease (HFMD) associated with enterovirus 71 (EV71) has become a serious concern in mainland China. It caused 126 and 353 fatalities in 2008 and 2009, respectively. The epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. To understand the virological evolution of this emerging outbreak, 326 VP1 gene sequences of EV71 detected in China from 1987 to 2009 were collected for genetic analyses. Evidence from both traditional and molecular epidemiology confirmed that the recent HFMD outbreak was an emerging one caused by EV71 of subgenotype C4. This emerging HFMD outbreak is associated with EV71 of subgenotype C4, circulating persistently in mainland China since 1998, but not attributed to the importation of new genotype. Originating from 1992, subgenotype C4 has been the predominant genotype since 1998 in mainland China, with an evolutionary rate of 4.6∼4.8×10−3 nucleotide substitutions/site/year. The phylogenetic analysis revealed that the majority of the virus during this epidemic was the most recent descendant of subgenotype C4 (clade C4a). It suggests that the evolution might be one of the potential reasons for this native virus to cause the emerging outbreak in China. However, strong negative selective pressure on VP1 protein of EV71 suggested that immune escape might not be the evolving strategy of EV71, predicting a light future for vaccine development. Nonetheless, long-term antigenic and genetic surveillance is still necessary for further understanding.
Genetic recombination is a well-known phenomenon for enteroviruses. To investigate the genetic characterization and the potential recombination of enterovirus 71 (EV71) circulating in China, we determined the 16 complete genome sequences of EV71 isolated from Hand Foot Mouth Disease (HFMD) patients during the large scale outbreak and non-outbreak years since 1998 in China. The full length genome sequences of 16 Chinese EV71 in present study were aligned with 186 genome sequences of EV71 available from GenBank, including 104 China mainland and 82 international sequences, covering the time period of 1970–2011. The oldest strains of each subgenotype of EV71 and prototype strains of HEV-A were included to do the phylogenetic and Simplot analysis. Phylogenetic analysis indicated that all Chinese strains were clustered into C4 subgenotype of EV71, except for HuB/CHN/2009 clustered into A and Xiamen/CHN/2009 clustered into B5 subgenotype. Most of C4 EV71 were clustered into 2 predominant evolutionary branches: C4b and C4a evolutionary brunches. Our comprehensive recombination analysis showed the evidence of genome recombination of subgenotype C4 (including C4a and C4b) sequences between structural genes from genotype C EV71 and non-structural genes from the prototype strains of CAV16, 14 and 4, but the evidence of intratypic recombination between C4 strains and B subgenotype was not enough strong. This intertypic recombination C4 viruses were first seen in 1998 and became the predominant endemic viruses circulating in China mainland for at least 14 years. A shift between C4a and C4b evolutionary brunches of C4 recombination viruses were observed, and C4a viruses have been associated with large scale nationwide HFMD outbreak with higher morbidity and mortality since 2007.
The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%–100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China.
Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients’ demography, geographic locations and season of illness in China.
A molecular and morphometric investigation is reported on the species complex of mammalian lungflukes of which Paragonimus skrjabini Chen, 1959 and P. miyazakii Kamo, Nishida, Hatsushika & Tomimura, 1961 are the best-known examples. This species complex (here called the P. skrjabini complex) is shown to be monophyletic using DNA sequences from the nuclear ITS2 region and the mitochondrial cox1 gene. The latter marker permits the discrimination of populations, some previously named as distinct species, from various geographical locations in China and Japan. Morphometric analysis of a number of variables accords remarkably closely with the molecular results. Main findings are that (1) nominal P.skrjabini from Fujian Province in eastern China is phylogenetically very close to P. miyazakii from Japan. It is proposed that both taxa should be referred to the same subspecies as P. krjabini miyazakii. (2) Populations from Guangdong Province, Guangxi Zhuang Autonomous Region, Sichuan and Hubei should be referred to P. skrjabini skrjabini. Specimens of P. skrjabini from the Yangtze basin in Sichuan and Hubei are remarkably similar to one another according to genetic and morphometric data, but are not so different from Guangdong populations that they should be referred to a different subspecies at this stage. Specimens of P. skrjabini from Yunnan have not been assigned to a subspecies at this stage. (3) Partly following earlier studies, we regard the following as synonyms of P. skrjabini: P. miyazakii (reduced to subspecific status); P. szechuanensis Chung & Tsao, 1962 (probably belongs to P. s. skrjabini); and P. hueitungensis Chung, Hsu, Ho, Kao, Shao, Chiu, Pi, Liu, Ouyang, Shen, Yi & Yao, 1975 (probably belongs to P.s.skrjabini ); P. veocularis (Chen & Li, 1979) (specimens from Fujian regarded as belonging to this species should be referred to P.skrjabini miyazakii: the subspecific status of specimens from the type-locality in northern Sichuan is unclear). A number of questions remain unresolved. The name P. hokuoensis Ho & Chung, 1964 was proposed for two individual metacercariae of distinctive appearance from southern Yunnan. DNA sequences from very similar metacercariae from the same locality place this nominal species within, or sister to, the P. skrjabini complex. As yet, nothing is known regarding adult morphology or biology of this taxon and we retain it here as a distinct species. P. heterorchis (Zhou, Pang & Hsiang, 1982) might be a synonym of P. skrjabini: the form of the metacercaria provides evidence against this view and further work is required. P. macrorchis Chen, 1962 has probably been confused with P. skrjabiniin China. Within China, the former probably occurs only on Hainan Island, although P. fukienensis Tang & Tang, 1962 from Fujian Province could be a synonym.
With the implementation of mumps virus (MuV) vaccination in the expanded program on immunization (EPI) in mainland China since 2008, the incidence of mumps has decreased, and the natural epidemic pattern of mumps has slightly changed during 2013–2015. The two epidemic peaks (April-July and November-December) became less obvious than those observed from 2004 to 2012. Children and adolescents younger than 15, particularly in the five-to-nine-year-old age group, remain the target group and should be the focus of high-quality immunization activities in mainland China. However, it was also found that the incidence and reported cases of mumps decreased in each age group during 2013–2015, particularly in the five-to-nine-year-old and ten-to-fourteen-year-old age groups. The proportion of mumps cases among adults in some provinces also increased. Unlike the changes in the epidemiological characteristics of mumps affected by vaccination, the data of MuV virology surveillance indicated that most of the MuV transmission chains have not yet been effectively interrupted, and MuV remains a natural epidemic pattern in mainland China. In the MuV virology surveillance, 194 MuV strains during 2013–2015 were isolated from 10 of 31 provinces in mainland China. Based on the phylogenetic analysis of the small hydrophobic (SH) gene, both genotype (99.0%) and (1.0%) were identified, and genotype was still the predominant genotype continuously circulating in mainland China. Representative genotype and strains isolated in China from 1995 to 2012 were selected for further analysis. The results indicated that there were multiple transmission chains within genotype , with no obvious geographical or time differences. The high genetic diversity of genotype F strains could be a result of the continuous transmission and evolution of the MuV in mainland China. Genotype was also detected in four provinces in mainland China. Because of the limited epidemiological data, it was uncertain whether the genotype MuV strains found in 2011 and 2013 were imported from other countries. Therefore, combined high-quality epidemiological and virological surveillance is necessary for mumps control; it can also be used to observe the changes in epidemiological characteristics and viral transmission of mumps over time after mumps-containing vaccine (MuCV) implementation and to provide a comprehensive epidemiological and genetic baseline for mumps elimination in mainland China.
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