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Background To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993–2021 were analyzed. Methods Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993–2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. Results With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020–2021 (average 0.5 per million). During 1993–2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. Conclusions The evidence of low incidence during 2020–2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.

Measles is one of the most infectious diseases of humans. It is caused by measles virus (MeV) and can lead to serious illness, lifelong complications and even death. Whole-genome sequencing (WGS) is now available to study molecular epidemiology and identify MeV transmission pathways. In the present study, WGS of 23 MeV strains of genotype H1, collected in Mainland China between 2006 and 2018, were generated and compared to 31 WGSs from the public domain in order to analyze genomic characteristics, evolutionary rates and date of emergence of H1 genotype. The non-coding region between M and F protein genes (M/F NCR) was the most variable region throughout the genome. Whereas the nucleotide substitution rate of H1 WGS was around 0.75×10-3 substitution per site per year, the M/F NCR had an evolutionary rate 3 times higher, with 2.44×10-3 substitution per site per year. Phylogenetic analysis identified 3 distinct genetic groups. The Time of the Most Recent Common Ancestor (TMRCA) of H1 genotype was estimated at approximately 1988, while the first genetic group appeared around 1995 followed by 2 other genetic groups in 1999-2002. Bayesian skyline plot showed that the genetic diversity of H1 genotype remained stable even though the number of MeV cases decreased 50 times between 2014 (52,628) and 2020 (993). The current COVID-19 pandemic might have some effect on measles epidemic and further studies will be necessary to assess genetic diversity of H1 genotype in a post COVID area. This article is protected by copyright. All rights reserved.

Oral fluids (OFs) have been broadly used as non-invasive samples for evaluating protective IgG antibodies from natural infection or vaccination, especially in pediatric populations.Paired OF and serum were collected from both individuals who received a booster dose of the inactive coronavirus disease 2019 (COVID-19) vaccine as well as those who did not have a history of COVID-19 vaccination and infection (as the control group). The total human IgG antibody (HIgG) content was evaluated as a marker of OF sampling quality. An in-house adapted magnetic particle-based chemiluminescence immunoassay was used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody detection in the OF. The SARS-CoV-2 IgG antibody in the serum samples was detected using a commercial immunoassay.In total, 579 paired OF and serum samples were collected. An additional 172 OF samples were collected from preschool children. The results indicated that the HIgG concentration in qualified OF samples should be higher than 0.3 µg/mL. Compared to the serum assay, the in-house OF immunoassay for detecting IgG antibodies against SARS-CoV-2 had 95.06% accuracy, 95.03% sensitivity, and 100% specificity.Overall, the in-house immunoassay for detecting SARS-CoV-2 IgG antibodies in OF showed high potential for application towards serological surveillance and immunization effect assessment after large-scale, inactive COVID-19 vaccination in China.

What is known about this topic? Few major outbreaks of coronavirus disease 2019 (COVID-19) have occurred in China after major non-pharmaceutical interventions and vaccines have been deployed and implemented. However, sporadic outbreaks that had high possibility to be linked to cold chain products were reported in several cities of China.. What is added by this report? In July 2020, a COVID-19 outbreak occurred in Dalian, China. The investigations of this outbreak strongly suggested that the infection source was from COVID-19 virus-contaminated packaging of frozen seafood during inbound unloading personnel contact. What are the implications for public health practice? Virus contaminated paper surfaces could maintain infectivity for at least 17–24 days at -25 ℃. Exposure to COVID-19 virus-contaminated surfaces is a potential route for introducing the virus to a susceptible population. Countries with no domestic transmission of COVID-19 should consider introducing prevention strategies for both inbound travellers and imported goods. Several measures to prevent the introduction of the virus via cold-chain goods can be implemented.

What is already known about this topic? Though coronavirus disease 2019 (COVID-19) has largely been controlled in China, several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products. Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated on the outer packaging of cold chain products, live virus has not been obtained. What is added by this report? In September 2020, two dock workers were detected as having asymptomatic SARS-CoV-2 infection using throat swabs during routine screening in Qingdao, China. Epidemiological information showed that the two dock workers were infected after contact with contaminated outer packaging, which was confirmed by genomic sequencing. Compared to the Wuhan reference strain, the sequences from the dock workers and the package materials differed by 12–14 nucleotides. Furthermore, infectious virus from the cold chain products was isolated by cell culture, and typical SARS-CoV-2 particles were observed under electron microscopy. What are the implications for public health practice? The international community should pay close attention to SARS-CoV-2 transmission mode through cold chain, build international cooperative efforts in response, share relevant data, and call on all countries to take effective prevention and control measures to prevent virus contamination in cold-chain food production, marine fishing and processing, transportation, and other operations.

BACKGROUND Measles is a highly infectious illness requiring herd immunity of 95% to interrupt transmission. China has not reached elimination goals despite high vaccination coverage. We estimated the population susceptibility against measles in Tianjin, China and to tailor awareness raising activities in the measles elimination plan. METHODS Age-specific measles seroprevalence was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) on 12,164 individual aged 0-44 years in 2009-2018. Measles IgG avidity testing was performed to confirm the relationship of the waning immunity after vaccination and secondary vaccination failures (SVF) on 324 confirmed measles cases in 2013-2018. RESULTS 11,108 samples (91.32%) tested positive for measles IgG, 239 (1.96%) tested as equivocal and 817 (6.72%) were negative. The age distribution of measles cases in Tianjin followed a U-shaped curve and was highest for those at

During 2017–2018, Nasopharyngeal aspirates (NPAs) from 627 hospitalized patients with SARI at Luohe Center Hospital were tested by RT-PCR for human parainfluenza virus 4(HPIV-4). 14 (2.2%) of 627 samples were positive for HPIV-4. The complete nucleotide sequence of the HN gene from 9 positive samples was amplified and sequenced successfully. Genetic analysis showed that the HPIV-4 strains circulating in Luohe city are more closely related to HPIV-4A. Our study indicated that there were multiple lineages of HPIV-4 circulating in Henan Province in China during the study period, which will improve our understanding of the epidemiological and clinical characteristics of HPIV-4.

During 2017–2018, nasopharyngeal aspirates (NPAs) from 627 hospitalized patients with severe acute respiratory infection at Luohe Center Hospital were tested by RT-PCR for human parainfluenza virus 4 (HPIV-4). Fourteen (2.2%) of the 627 samples were positive for HPIV-4. The complete HN gene was amplified from nine positive samples and sequenced. Sequence comparisons showed that the HPIV-4 strains circulating in the city of Luohe are closely related to HPIV-4A strains. Our study indicated that there were multiple lineages of HPIV-4 circulating in Henan Province in China during the study period. This will improve our understanding of the epidemiological and clinical characteristics of HPIV-4. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05154-3.

Hand, foot and mouth disease (HFMD) was reported in May 2, 2008 to be the 38th legally notifiable disease in China's National Notifiable Disease Reporting and Surveillance System. In order to solve the infection, an extensive three-level HFMD surveillance laboratory network was established. In this study, the framework of that network is assessed and the incidence of HFMD in China from 2008 to 2017 is reported using a descriptive epidemiologic method. During these 10 years, a series of techniques have been widely applied in all the network laboratories. Using information and material obtained from the network, a virus bank and database containing 18,238 viruses were established. Nationally, 18,184,834 HFMD cases, including 152,436 severe cases and 3633 fatal cases, were reported in mainland of China. The average annual incidence in the population was 133.99/100,000 people, with a maximum incidence of 205.06/100,000 people in 2014. The incidence and mortality rates of HFMD were the highest in children aged 1–2 years. The numbers of reported cases fluctuated, with a high incidence observed every 2 years. An overall increase in the number of reported cases was also observed throughout the study period. Despite this, the incidence of severe cases and the mortality rate have been decreasing. High-risk regions are located in southern, eastern, and central China. Two peaks of HFMD infection cases were observed annually except for Northeast China. Different proportions of enterovirus serotypes were observed during the studied years. The predominant enterovirus varies from year to year, but the disease severity is always closely related to the specific serotype. EV-A71 is the dominant serotype associated with severe and fatal cases, with constituent ratios of 70.03% and 92.23%, respectively. The studied highly sensitive and efficient surveillance network provides information that is critical for prevention and control of the disease. It is extremely necessary and important to continuously conduct extensive virological surveillance for HFMD. Key words: Hand, Foot and Mouth Disease; Laboratory network; Surveillance, Epidemiological characteristics; Pathogen spectrum

This study aims at analyzing all publicly available HAdV-C whole genome sequences (WGSs) and describes the genetic relationships between these genomes as well as identifies potential hotspots for recombination throughout the viral genome. In addition to the 4 prototypical genomic sequences, this analysis identified 20 HAdV-C WGSs which should be relevant for future recombination analysis of HAdV-C. This report confirmed the recombinogenic property of HAdV-C genomes and identified two main regions for breakpoints, within the hexon gene and around the fiber genomic region. No obvious recombination was detected between HAdV-Cs and non-human mastadenoviruses or non-C HAdVs. Finally, it highlighted the need for a surveillance of HAdVs in order to detect novel recombinant types that might represent health risks and develop possible prevention measures. Genetic analyses of recombination between recently collected HAdV-Cs and the assessment of their potential virulence are necessary steps towards the establishment of a surveillance of HAdVs in the future.

Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the characteristics of VARI, 101 VARI cases confirmed by measles virus genotyping in 2011 to 2018 were analyzed in this study. With the decrease in measles incidence, the detection rate of VARI cases increased among the cases confirmed by genotyping. Compared with genotype H1 wild-type measles, VARI occurred throughout the year, without obvious seasonal distribution. Infants and children of ages 8 to 23 months were the main population of VARI. VARI mainly occurred within 14 days after measles vaccination. The number of VARI cases peaked on the 8th day after measles vaccination, which was later than that of genotype H1 wild-type measles cases with a measles vaccination history. VARI presents clinical symptoms similar to those of measles. The frequencies of the “3Cs” (cough, coryza, and conjunctivitis), Koplik spots, and complications in VARI cases were significantly lower than those in wild-type measles cases. In total, 94.06% of sequences from VARI cases were identical to measles vaccine strain S191 in the C-terminal 450-nucleotide sequence of the nucleoprotein (N-450) gene. A few substitutions were found in N-450 sequences of the VARI cases. The confirmation of VARI has become an emerging issue in the process of measles elimination. Rapid confirmation of VARI is critical for measles surveillance and will help to determine the response measures for measles, especially in measles preelimination and elimination settings. The suspected measles cases with measles-containing vaccine (MCV) vaccination were recommended to be tested by the laboratory to identify wild-type measles or VARI.

What is already known about this topic? Coronavirus disease 2019 (COVID-19) has become a global pandemic, while the profile of antibody response against the COVID-19 virus has not been well clarified. What is added by this report? In this study, 210 serum samples from 160 confirmed COVID-19 cases with different disease severities were recruited. The IgM, IgA, IgG, and neutralizing antibodies (NAb) against COVID-19 virus were determined. Our findings indicated that four antibodies could be detectable at low levels within 2 weeks of disease onset, then rapidly increasing and peaking from the 3rd to 5th Weeks. NAb decreased between 5th and 9th Weeks, and a higher IgM/IgA level was observed in the groups with mild/moderate severity within 2 weeks (p

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

Measles incidence has decreased dramatically in China due to the implement of measles-containing vaccine (MCV). However, a measles epidemic caused resurgence recently, even among vaccinated individuals. To evaluate the effectiveness of current immunization programs and discuss initiatives for the next step in measles elimination in mainland China, the characteristics of 121,969 laboratory-confirmed measles cases reported in the measles surveillance system (MSS) during 2014–2018 were analyzed according to the vaccination status of the cases in this study. Children under 2 years of age without MCV vaccination (44,424, 36.42% of all cases) and adults over 20 years of age with an unknown vaccination history (37,564, 30.80% of all cases) accounted for the majority of measles cases from 2014 to 2018. 42,425 (34.78%) of the 77,384 cases with available vaccination information were categorized as programmatically preventable. 38,840 (91.55%) of the 42,425 cases were aged ≥8 months without the MCV vaccination history. 34,959 (28.66%) cases were categorized as programmatically non-preventable, of whom 22,611 (64.68%) were too young to receive their first MCV dose, 6857 (19.61%) received their first dose and were too young to receive their second dose, 5491 (15.71%) received at least two doses of MCV. 15,933 (13.06%) of the 121,969 cases had a history of MCV vaccination. Measles virus infection in cases with an MCV vaccination history mainly occurred within the first month after MCV vaccination, especially in those who received a one-dose measles vaccination. MCV vaccination could reduce the frequencies of clinical symptoms and complications of measles cases. Our study confirmed that the current measles immunization programs used in mainland China is effective in reducing the measles incidence in China. Unvaccinated infants/children aged 8–23 months and high risk susceptible adults over 20 years of age with unknown vaccination histories should be the focus groups of measles immunization activities in China in the future.

[This corrects the article DOI: 10.1371/journal.pone.0232092.].

Background: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic After the first epidemic wave, we conducted population-based serological surveys to determine extent of infection, risk factors for infection, and neutralization antibody levels to assess the real infections in the random sampled population Methods: We used a multistage, stratified cluster random sampling strategy to conduct serological surveys in three areas - Wuhan, Hubei Province outside Wuhan, and six provinces selected on COVID-19 incidence and containment strategy Participants were consenting individuals >1 year old who resided in the survey area >14 days during the epidemic Provinces screened sera for SARS-CoV-2-specific IgM, IgG, and total antibody by two lateral flow immunoassays and one magnetic chemiluminescence enzyme immunoassay;positive samples were verified by micro-neutralization assay Findings: We enrolled 34,857 participants (overall response rate, 92%);427 were positive by micro-neutralization assay Wuhan had the highest weighted seroprevalence (4*43%, 95% confidence interval [95%CI]=3*48%-5*62%), followed by Hubei-ex-Wuhan (0*44%, 95%CI=0*26%-0*76%), and the other provinces (

Coxsackievirus A16 (CV-A16) is one of the main causative agents of hand, foot and mouth disease (HFMD) in young children and has become prevalent in the Asia-Pacific region in recent years. However, no approved vaccines or drugs are available for CV-A16 infection. CV-A16 virus-like particles (VLPs) are a potential vaccine candidate; however, whether the intranasal route of immunization is suitable for inducing immune responses against CV-A16 infection has not been clarified. In this study, the comprehensive immunogenicity and protective efficacy of the CV-A16 VLP vaccine were evaluated by multiple methods in a mouse model. In mice, a high neutralizing antibody (NTAb) titre could be elicited by intranasal immunization with CV-A16 VLPs, which produced NTAb levels similar to those induced by intranasal immunization with inactivated CV-A16. Passive immunity with NTAbs provided very good protection, as the survival rate of the immunized neonatal mice was 100% after challenges with CV-A16 at a dose of 1000 LD50. Passive protective effects were transferred to the neonates via the mother, thus protecting all the pups against challenges with the homologous or heterologous strains of CV-A16 at a dose of 1000 LD50. In addition, intranasal immunization with CV-A16 VLPs also induced the production of mucosal secretory IgA (s-IgA) antibodies, which may inhibit CV-A16 virus invasion. This study provides valuable supplemental information to facilitate our understanding of the specific protective efficacy of CV-A16 VLPs and has significance for development of the candidate vaccine into a safe and effective vaccine.

We wished to study the dynamic change in variation of rubella viruses circulating during 1999-2015 in mainland China at the molecular level. Molecular evolution of Chinese rubella viruses collected during 1999 ~ 2015 was analyzed according to a surveillance database of measles/rubella laboratory networks in China. A total of 1737 rubella viruses were obtained from 20 of 31 provinces (except Xinjiang and Tibet) during 1999 ~ 2015. Four genotypes (1E, IF, 2A, 2B) were detected. The genotype-1E rubella virus was detected first in 2001. Subsequently, genotype 1E became the predominant genotype circulating during 2001~2013, and could be divided into two closely related clusters (A (2004-2015) and B (2001-2009)). However, the detection rate of the genotype-1E rubella virus decreased year-by-year from 2011, and reached the lowest level (1. 3%) in 2015. The genotype-1F rubella virus was restricted geographically to China, and no longer found after 2002; presumably its circulation in China was interrupted. All genotype-2A rubella viruses were derived from vaccine-related cases. At least four genotypes of 2B rubella viruses (lineage 1 ~ 4) circulated in mainland China during 2000 ~ 2015. The genotype-2B rubella virus was detected sporadically and was in a weak position until 2010. However, the detection rate of imported genotype-2B rubella viruses (lineage 3) was increased and became the predominant genotype during 2014~2015. Through the study of 16 consecutive years in mainland China, the evolution and epidemic situation of the rubella virus was obtained to aid virology surveillance for rubella control in China.

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.

The human mastadenovirus C (HAdV-C) cause respiratory infections in children. Homologous recombination was clearly involved in the molecular evolution of HAdV-A, B, and D, but little is known about the molecular evolution of HAdV-C. From 2000 to 2016, 201 HAdV-C strains were collected from nine provinces covering six administrative regions of mainland of China via 3 existing surveillance programs, namely the febrile respiratory syndrome surveillance, the acute flaccid paralysis surveillance, and the hand, foot, and mouth disease surveillance system. The genes coding for the capsid protein (penton base, hexon, and fiber) of 201 HAdV-C strains were sequenced and compared with representative sequences publicly available. In addition, the whole genome sequence of 24 representative strains of HAdV-C was generated for further recombination analysis. Phylogenetic analysis of the penton base sequences of HAdV-C revealed six genetic groups (labelled as Px1-6), which showed that the penton base had more variation than previously thought. Based on the penton base, hexon, and fiber gene sequences, 16 new genetic patterns of HAdV-C circulating in mainland of China were identified in this study. Whole genome sequence analysis revealed frequent recombination events among HAdV-C genomes. This study is highly beneficial for case classification, tracking the transmission chain, and further epidemiological exploration of HAdV-C-related severe clinical diseases in the near future. Our data demonstrated that multiple newly divergent HAdV-C co-circulated across mainland China during the research period.

To clarify the protective effect of one-dose mumps-containing vaccines (MuCV) in mainland China, the antigenic variations of HN gene and cross-neutralization capacities between MuCV and wild type genotype F MuVs were studied. In total, 70 HN gene sequences of genotype F MuV representative strains obtained from 2001 to 2015, two types of MuCV strains, 139 pairs of pre- and post-vaccination serum samples from infants receiving one dose of MuCV vaccination were analyzed. Genotype-specific amino acid variations were observed in the potential antigenic epitopes between MuCV and wild-type genotype F MuVs circulating in mainland China. The mumps neutralization antibody titers induced by one-dose MuCV were found to be generally low. Moreover, significant differences in neutralization titers were observed between vaccine and wild-type strains. It could be concluded that one-dose MuCV had a cross-protective effect against the wild-type genotype F MuVs, but its effectiveness was limited, which might be caused by insufficient doses of MuCV vaccination and the genotype-specific antigenic differences between vaccine and wild-type MuVs as well. In addition, a poor linear correlation between mumps-specific IgG concentrations and neutralization titers was observed in this study, indicating the concentration of MuV-specific IgG could not fully reflect the neutralizing antibody titer in serum. Therefore, it is highly recommended to provide a second dose of MuCV to preschool children to increase MuV neutralizing antibody titers and use MuV cross-neutralization test as preferred tool for assessment of mumps-containing vaccine effectiveness on wild-type MuVs. This is the first report to assess the effectiveness of one-dose Chinese MuCV against wild-type genotype F MuVs, which would be benefit for the development of mumps vaccination strategy.

Human mastadenovirus species C (HAdV-C) are the most common etiologic agents of respiratory disease in young children and are frequently detected worldwide including China. Two recombinant HAdV-C strains (BJ04 and BJ09) were isolated from infants with acute respiratory infection (ARI) in Beijing in 2012–2013. The whole genome sequences (WGS) of BJ04 and BJ09 were generated and compared to other 35 HAdV-C WGSs publicly available. Phylogenetic analyses showed that the BJ04 strain might be the result of three homologous recombination events involving the parental strains JX173086 (HAdV-1), NC_001405 (HAdV-2) and LC068718 (HAdV-6), whereas BJ09 viral genome might be made of genetic elements from JX173083 (HAdV-1), KF268199 (HAdV-5), and KR699642 (strain CBJ113). Despite intratypic recombination, amino acid analysis showed that the gene repertoire of BJ04 and BJ09 were similar to type 2 viruses. Finally, this analysis revealed that at least three lineages of HAdV-C have been identified in China, represented by BJ04 related to NC_001405, BJ09 related to CBJ113, and KF951595 (strain DD28) related to virus isolated in Japan. This study showed that the frequent recombination played an important driving force for complexity of the HAdV-C epidemic in Beijing, thereby demonstrating the necessity for epidemiological and virological surveillance for HAdV-C in China.

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 F (99.0%) and G (1.0%) were identified, and genotype F was still the predominant genotype continuously circulating in mainland China. Representative genotype F and G strains isolated in China from 1995 to 2012 were selected for further analysis. The results indicated that there were multiple transmission chains within genotype F, 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 G was also detected in four provinces in mainland China. Because of the limited epidemiological data, it was uncertain whether the genotype G 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.

To characterize the genetic properties of coxsackievirus A12 (CVA12) strains isolated from hand, foot and mouth disease (HFMD) patients in Qingdao during 2008-2011, the complete genome and VP1 coding region were sequenced and analyzed. Phylogenetic analysis showed that all strains from China clustered into three different branches, suggesting multiple lineages of CVA12 co-circulating in Asia. Sequence analysis indicated a monophyletic group only when the P1 region was examined, indicating possible recombination between CVA12 and other HEV-A serotypes. The emergence of CVA12 involved in an HFMD outbreak in China is a public-health issue.

We wished to understand the genetic characteristics of enteric cytopathic human orphan (ECHO) virus type 6 (ECHO6) circulating in China. First, the partial VP1 coding region of six strains of the ECH-O6 virus isolated from cases of hand, foot and mouth diseases during routine surveillance in Hunan Province (China) from 2009 to 2014 were sequenced. Those sequences were analyzed along with 138 sequences of ECHO viruses covering five provinces of China and countries outside China retrieved from the GenBank database. A phylogenetic tree based on partial VPI was constructed, and it indicated that Chinese strains of the ECHO virus could form two distinct evolutionary branches: branch 1 and branch 2. All isolates of the ECHO virus from Hunan Province belonged to the 2c subranch, which revealed that they may share a common evolutionary origin. ECHO strains in branch 2 may be the predominant strains in China due to their wide geographic distribution and long period of circulation. We used nucleotide differences of30%o as the basis of cluster division. ECHO, viruses could be divided into four clusters (A-D). Cluster D could be divided further into ten subclusters on the basis of nucleotide differences of 15%-30%. All ECHO6 isolates from Hunan Province belonged to the D7 subcluster. These data showed that the ECHO6 strains that circulated in Hunan Province in 2009-2014 were closely related to each other, and probably shared a common evolutionary origin. In addition, at least four distinct lineages of ECHO viruses have circulated in China.

An outbreak of acute respiratory tract infection occurred in Shanxi Province, China, from March to April 2006. Of the 254 patients affected by this outbreak, 247 patients were students of a senior high school; 1 of these patients died during the outbreak. Serological tests and blood culture revealed no evidence of bacterial infection. The results of direct reverse transcription-PCR or PCR performed with clinical specimens collected from the patients, including the sole patient who died, were positive for human adenoviruses (HAdVs) but negative for influenza virus, measles virus, rubella virus, mumps virus, parainfluenza virus, respiratory syncytial virus, and human enteroviruses. These findings were confirmed by enzyme-linked immunosorbent assay for HAdV immunoglobulin A, the conventional neutralization test, and viral isolation and identification. Sequencing of the entire hexon gene revealed that HdAV type 11a (HAdV-11a) belonging to the B2 species of HAdV was the etiological agent responsible for the outbreak. However, both the analysis of the phylogenetic relationship and the similarity plot indicated that the sequence of the 3′ end of the hexon gene outside the hypervariable regions the HAdV-11a strain isolated in this outbreak may be a recombinant with the sequence of the HAdV-14 strain of species B2. Although isolates of HAdV species B2 seldom cause respiratory infections, they may pose a new global challenge with regard to acute respiratory diseases; this possibility cannot be overlooked and should be carefully considered. Hence, the need to establish and improve both epidemiological and virological surveillance of HAdV infections in China should be emphasized.

Virologic surveillance is a critical component of measles management. One of the criteria for verification of elimination of endemic measles is genetic analysis of wild-type viruses to demonstrate lack of an indigenous genotype. Measles is yet to be eliminated in China, and genotype H1 has been detected continuously since virologic surveillance was initiated in 1993. Virologic surveillance has been very active in China, providing a unique opportunity to conduct a detailed study of the evolution of a single, endemic genotype over a timespan of nearly two decades. Phylogenetic analysis performed on the 450 nt coding sequence for the C-terminal 150 amino acids of the nucleoprotein (N-450), fusion (F) gene and haemagglutinin (H) gene confirmed the continued circulation of genotype H1 viruses for 19 years. No evidence of selective pressure for the H protein was found. The substitution rates ranged from 0.75×10−3 substitutions site−1 year−1 for H to 1.65×10−3 substitutions site−1 year−1 for N-450. The time of most recent common ancestor (TMRCA) for genotype H1 was estimated as approximately 1985 (95 % highest probability density, 1979–1989). Finally, the overall diversity of measles sequences from China decreased from 2005 to 2012, coincident with a substantial decrease in measles cases. The results suggest that detailed evolutionary analyses should facilitate the documentation of eventual measles elimination in China. Moreover, the molecular approaches used in this study can be applied in other countries approaching measles elimination.

The authors would like to provide some additional relevant information about this study that was not included in the published article: The author Wenbo Xu is an inventor for a patent on the methodology employed for the detection of the viruses tested in the study (application number: 201110168721.X). This methodology employed for the analyses followed the protocol described in the BMC Infectious Diseases article below: BMC Infect Dis. 2012 Aug 14;12:189. doi: 10.1186/1471-2334-12-189. The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes. Li J, Mao NY, Zhang C, Yang MJ, Wang M, Xu WB, Ma XJ. This reference should have been cited in the article and the authors apologize for this omission. The authors originally developed a method for the detection of viruses as described in the Bing Du Xue Bao article cited as reference 33. The original method used the GeXP strategy (chimeric primers) to detect 12 respiratory viruses. The protocol reported in the BMC Infectious Diseases article constitutes an improvement over the approach described in the Bing Du Xue Bao article as it combined the GeXP and Temperature Switch PCR strategies to detect 16 respiratory viruses. The Temperature Switch PCR method had been originally described in the publication below, which should also have been cited in the article: BMC Genomics. 2009 Dec 3;10:580. doi: 10.1186/1471-2164-10-580. Temperature switch PCR (TSP): Robust assay design for reliable amplification and genotyping of SNPs. Tabone T, Mather DE, Hayden MJ.

Background Acute respiratory infections (ARIs) are the leading cause of children and their leading killer. ARIs are responsible for at least six percent of the world's disability and death. Viruses are one of the most common agents causing ARIs. Few studies on the viral etiology and clinical characteristics of ARIs have been performed in the northwest region of China, including Gansu Province. Methods Clinical and demographic information and throat swabs were collected from 279 patients from January 1st to December 30st, 2011. Multiplex RT-PCR was performed to detect 16 respiratory viral pathogens. Results 279 patients were admitted for ARIs. The patients aged from 1 month to 12 years, with the median age of 2 years. Of which, 105 (37.6%) were positive for at least one pathogen. A total of 136 respiratory viral pathogens were identified from the 105 patients. Respiratory syncytial virus (RSV) was the most frequently detected pathogen (26.5%, 36/136), followed by parainfluenza virus (PIV) 1–3 (22.1%, 30/136), human rhinovirus (HRV) (21.3%, 29/136), human coronavirus (CoV) (10.3%, 14/136) and human adenovirus (HAdV) (9.6%, 13/136). Influenza A (Flu A), human metapneumovirus (hMPV) and human bocavirus (BoCA) were found 4.4%, 3.7% and 2.2%, respectively. Influenza B (Flu B) and seasonal influenza A H1N1(sH1N1) were not detected. Single-infections were detected in 30.5% (85/279) of cases. RSV was the most common pathogens in patients under 1 year and showed seasonal variation with peaks during winter and spring. Conclusions This paper presents data on the epidemiology of viral pathogens associated with ARIs among children in Gansu Province, China. RSV is most frequently detected in our study. The findings could serve as a reference for local CDC in drawing up further plans to prevent and control ARIs.

Coxsackievirus A16 (CVA16) is responsible for nearly 50% of all the confirmed hand, foot, and mouth disease (HFMD) cases in mainland China, sometimes it could also cause severe complications, and even death. To clarify the genetic characteristics and the epidemic patterns of CVA16 in mainland China, comprehensive bioinfomatics analyses were performed by using 35 CVA16 whole genome sequences from 1998 to 2011, 593 complete CVA16 VP1 sequences from 1981 to 2011, and prototype strains of human enterovirus species A (EV-A). Analysis on complete VP1 sequences revealed that subgenotypes B1a and B1b were prevalent strains and have been co-circulating in many Asian countries since 2000, especially in mainland China for at least 13 years. While the prevalence of subgenotype B1c (totally 20 strains) was much limited, only found in Malaysia from 2005 to 2007 and in France in 2010. Genotype B2 only caused epidemic in Japan and Malaysia from 1981 to 2000. Both subgenotypes B1a and B1b were potential recombinant viruses containing sequences from other EV-A donors in the 5’-untranslated region and P2, P3 non-structural protein encoding regions.