First detection of multiple cases related to CV-A16 strain of B1c clade in Beijing in 2022.

Coxsackievirus A16 (CV-A16) is a significant etiologic agent of hand, foot, and mouth disease (HFMD) and herpangina (HA), with the capacity to progress to severe complications, including encephalitis, aseptic meningitis, acute flaccid paralysis, myocarditis, and other critical conditions. Beijing's epidemiological surveillance system, established in 2008, encompasses 29 hospitals and 16 district disease control centers. From 2019 to 2021, the circulation of CV-A16 was characterized by the co-circulation of B1a and B1b clades. Multiple cases of HFMD linked to clade B1c has not been reported in Beijing until 2022. This study enrolled 400 HFMD and 493 HA cases. Employing real-time RT-PCR, 368 enterovirus-positive cases were identified, with 180 selected for sequencing. CV-A16 was detected in 18.89% (34/180) of the cases, second only to CV-A6, identified in 63.33% (114/180). Full-length VP1 gene sequences were successfully amplified and sequenced in 22 cases, revealing the presence of clades B1a, B1b, and B1c in 14, 3, and 5 cases, respectively. A cluster of five B1c clade cases occurred between June 29 and July 17, 2022, within a 7-km diameter region in Shunyi District. Phylogenetic analysis of five complete VP1 gene sequences and two full-genome sequences revealed close clustering with the 2018 Indian strain (GenBank accession: MH780757.1) within the B1c India branch, with NCBI BLAST results showing over 98% similarity. Comparative sequence analysis identified three unique amino acid variations (P3S, V25A, and I235V). The 2022 Shunyi District HFMD cases represent the first instances of spatiotemporally correlated CV-A16 B1c clade infections in Beijing, underscoring the necessity for heightened surveillance of B1c clade CV-A16 in HFMD and HA in this region.

Single nucleotide polymorphism in Ag85 genes of Mycobacterium tuberculosis complex: analysis of 178 clinical isolates from China and 13 BCG strains.

Host immune pressure and associated immune evasion of pathogenic bacteria are key features of host-pathogen co-evolution. Human T-cell epitopes of Mycobacterium tuberculosis (M. tuberculosis) were evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. However, in our previous studies, proteins MPT64, PstS1, Rv0309 and Rv2945c all harbored higher numbers of amino acid substitutions in their T cell epitopes, which suggests their roles in ongoing immune evasion. Here, we used the same set of 180 clinical M. tuberculosis complex (MTBC) isolates from China, amplified the genes encoding Ag85 complex, and compared the sequences. The results showed that Ag85 were hyperconserved in T/B cell epitopes and the genes were more likely to be under purifying selection. The divergence of host immune selection on different proteins may result from different function of the proteins. In addition, A312G of Ag85A and T418C of Ag85B may represent special mutations in BCG strains, which may be used to differentiate M.bovis and BCG strains from MTB strains. Also, C714A in Ag85B seems to be a valuable phylogenetic marker for Beijing strains.

The first reported cases of severe fever with thrombocytopenia syndrome virus from domestic sick camel to humans in China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with an increasing annual incidence rate. In this case report, we presented two patients infected with the SFTS virus, suggesting a potential direct transmission route from camels to humans through blood contact. Both patients developed symptoms after engaging in the slaughtering of one sick camel, while their family members living in the same environment or co-diners remained unaffected. Subsequent detection revealed a high viral load of SFTS virus, reaching 1010 viral RNA copies/ml, in the sample obtained from the sick camel. Metagenomic sequencing did not identify any other pathogens. The SFTS virus was successfully isolated from both patient and camel samples. The complete nucleotide sequences obtained from the infected patients demonstrated a remarkable 100% similarity to those found in the camel, and genetic evolution analysis classified the virus as genotype A. Additionally, partial sequences of the SFTS virus were identified in ticks captured from the camel rearing environment, however, these sequences showed only 95.9% similarity to those found in camel and humans. Furthermore, immunoglobulin M and immunoglobulin G antibodies were detected in serum samples collected from the patient. Our findings provide evidence that camel may serve as a competent reservoir for transmitting the SFTS virus to humans. Further in vitro investigations into SFTS virus infections in large animals are warranted to understand their role in viral maintenance and transmission.

Polymorphism of antigen MPT64 in Mycobacterium tuberculosis strains.

We selected 180 clinical isolates of the Mycobacterium tuberculosis complex (MTBC) from patients in China and performed comparative sequence analysis of the mpt64 gene after amplification. From the results, we found that polymorphisms of the mpt64 gene in the MTBC may be the reason for changes in the antigen produced, which may in turn cause alterations of related functions, thereby allowing immune evasion.

19-VNTR loci used in genotyping Chinese clinical Mycobacterium tuberculosis complex strains and in association with spoligotyping.

Recently, tandem repeat typing has emerged as a rapid and easy method for the molecular epidemiology of the Mycobacterium tuberculosis (M. tuberculosis) complex. In this study, a collection of 19 VNTRs incorporating 15 previously described loci and 4 newly evaluated markers were used to genotype 206 Chinese M. tuberculosis isolates and 9 BCG strains. The discriminatory power was evaluated and compared with that obtained by Spoligotyping. It turned out that 15-locus VNTR could be very useful in M. tuberculosis complex strains genotyping in China. The 4 newly evaluated loci were proved informative and could be useful for future epidemiology studies, especially in Beijing family strains. In addition, a unique pattern of the latter 4 loci were found in Chinese BCG strains.

A Retrospective Modeling Study of the Targeted Non-Pharmaceutical Interventions During the Xinfadi Outbreak in the Early Stage of the COVID-19 Pandemic - Beijing, China, 2020.

What is already known about this topic?: China has repeatedly contained multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks through a comprehensive set of targeted non-pharmaceutical interventions (NPIs). However, the effectiveness of such NPIs has not been systematically assessed. What is added by this report?: A multilayer deployment of case isolation, contact tracing, targeted community lockdowns, and mobility restrictions could potentially contain outbreaks caused by the SARS-CoV-2 ancestral strain, without the requirement of city-wide lockdowns. Mass testing could further aid in the efficacy and speed of containment. What are the implications for public health practice?: Pursuing containment in a timely fashion at the beginning of the pandemic, before the virus had the opportunity to spread and undergo extensive adaptive evolution, could help in averting an overall pandemic disease burden and be socioeconomically cost-effective.

Clinical, epidemiological, and virological features of Mpox in Beijing, China - May 31-June 21, 2023.

The first locally acquired case in the Chinese mainland was reported on May 31, 2023, lagging behind other countries. In this study, we aimed to examine the early clinical and epidemiological characteristics of the earliest cases of Mpox in Beijing, China. Additionally, we investigated the sequence and transmission patterns of the Mpox virus (MPXV). We analyzed 37 reported cases of Mpox in Beijing from May 31, 2023 to June 21, 2023. The age range of the subjects was 24-51 years. Thirty-six cases (97.3%) were identified in men who have sex with men (MSM), and 19 cases (51.4%) tested positive for the human immunodeficiency virus. Thirty-three cases were symptomatic, while four were asymptomatic. Skin lesions were observed in 32 cases (97.0%), fever in 26 (78.8%), and swollen lymph nodes in 17 (51.5%). Rash typically appeared in the genital or perianal area 1-3 days before fever onset, with a minimum incubation period of 2 days. For individuals with skin rashes, the skin lesion samples showed 100% positivity and low Ct values. There were high oropharyngeal swab (75.8%) and blood (84.6%) positivity rates. All MPXV strains belonged to the B.1.3 branch of the West African lineage. These strains carried 76-86 nucleotide substitutions compared with the reference human MPXV genome, and genetic diversity was observed. Our findings provide the first insights into the landscape of early transmission of Mpox in Beijing and help inform policy formulation in the Chinese mainland.

SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing.

Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a "Zero-COVID" policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.

Epidemiological Investigation of an Inhalational Anthrax Patient Traveling for Medical Treatment in Beijing Municipality, China, August 2021.

What is already known about this topic?: Inhalational anthrax, also known as pulmonary anthrax, is an infectious disease caused by Bacillus anthracis . The patients are usually infected by inhaling aerosolized B. anthracis spores from dead animals or animal products. Compared to cutaneous anthrax, inhalational anthrax is rare and deadly and few cases in China were reported. What is added by this report?: This report covers all information of clinical features, laboratory testing, and epidemiological characteristics as well as exposure history of a recent primary inhalational anthrax patient who was seeking medical treatment in Beijing Municipality in August 2021. New laboratory techniques, including second-generation sequencing, polymerase chain reaction, and rapid test for serum antibody, played an important role in the process. What are the implications for public health practice?: The information provided in this report, including the correct sample type, epidemiological investigation details, and application of the new diagnostic criteria of anthrax, could assist public health professionals in dealing with anthrax epidemics.

[Epidemiological characteristics and molecular typing of Salmonella in Beijing from 2008 to 2009].

OBJECTIVE: To study the epidemiological characteristics and molecular phenotypes of Salmonella by pulsed-field gel electrophoresis (PFGE) in Beijing from 2008 to 2009. METHODS: A total of one hundred thirty-seven isolates recovered from the WHO Global Salmonella Surveillance system and entero clinic surveillance system were identified by biochemical tests and serotyping. The related epidemiological informations were also analyzed. The isolates were further typed by PFGE. RESULTS: The prevalence of Salmonella from 2008 to 2009 showed obvious seasonal character. High incidence occurred from June to September, and 64.1% (84/131) isolates were recovered in this period. Patients of 18 - 40 year-old were 46.1% (58/128) and 80 patients were male and 40 patients were female with the ratio of 1.57:1. These 137 Salmonella isolates belonged to 20 serotypes, including Enteritidis (46.7%, 64/137) and Typhimurium (17.5%, 24/137) as the dominant serotype. In total, 71 PFGE profiles were identified. Four PFGE patterns of S. Enteritidis isolates (JEGX01.CN0001, JEGX01.CN0003, JEGX01.CN0002, JEGX01.CN0019) and S. Typhimurium pattern of JPXX01.CN0001 were dominant patterns. CONCLUSION: The prevalence of Salmonella from 2008 to 2009 showed distribution characteristics of sex, age and seasons. The numerous PFGE patterns of Salmonella showed diversity of these isolates and different clones existed in Beijing.

Epidemiological Characteristics and Trends of Registered Leprosy Cases in China From 2004 to 2016.

Leprosy is an infectious disease caused by Mycobacterium leprae. China was once one of the countries with severe leprosy epidemics, but its incidence has remained low in recent years. Despite this, there has been no decrease in its incidence more recently, and it is still a public health problem which needs to be controlled. In this study, we analyzed the epidemiological characteristics and trends in the detection rate of new cases of leprosy in China between 2004 and 2016. There were 4,519 cases of leprosy in 28 provinces, municipalities, and autonomous regions between 2004 and 2016, and the total incidence was 0.02815 (per 100,000 individuals) and 21 deaths. The overall incidence of leprosy showed an inverted "V" distribution (i.e., an increase followed by a decrease). Yunnan, Sichuan, Guangdong, Guizhou, and Guangxi were the top five regions with the highest incidence rates, and they accounted for 68.7% of the total cases. There were more male patients than female patients, and peasants accounted for 71.7% of the leprosy cases. The patients with leprosy in China were mainly concentrated in the age-group 15-44 years, as this group accounted for 57.2% of the total cases. The purpose of this study is to explore the epidemiology of leprosy in China. This analysis will be useful for future monitoring of leprosy and establishment of public health measures in China, in keeping with the "Programme for the Elimination of Leprosy in China 2011-2020."

Comparing early outbreak detection algorithms based on their optimized parameter values.

BACKGROUND: Many researchers have evaluated the performance of outbreak detection algorithms with recommended parameter values. However, the influence of parameter values on algorithm performance is often ignored. METHODS: Based on reported case counts of bacillary dysentery from 2005 to 2007 in Beijing, semi-synthetic datasets containing outbreak signals were simulated to evaluate the performance of five outbreak detection algorithms. Parameters' values were optimized prior to the evaluation. RESULTS: Differences in performances were observed as parameter values changed. Of the five algorithms, space-time permutation scan statistics had a specificity of 99.9% and a detection time of less than half a day. The exponential weighted moving average exhibited the shortest detection time of 0.1 day, while the modified C1, C2 and C3 exhibited a detection time of close to one day. CONCLUSION: The performance of these algorithms has a correlation to their parameter values, which may affect the performance evaluation.

Epidemiological characteristics and trends of notifiable infectious diseases in China from 1986 to 2016.

BACKGROUND: Since the 1980s, China has undergone significant social change and the incidence of infectious diseases has also changed considerably. Here, we report the epidemiological features and changes in notifiable infectious diseases in China from 1986 to 2016 to explore the factors contributing to the successful control of infectious diseases and the challenges faced in the prevention and control of infectious diseases. METHODS: The data of notifiable infectious diseases in China from 1986 to 2016 were collected from the monthly analysis report of the National Infectious Disease Surveillance System. Joinpoint regression models were used to examine incidence and mortality trends from 1986 to 2016. IBM SPSS Statistics version 22.0, Excel 2010 and R x64 3.5.2 were used for data analysis. RESULTS: A total of 132 858 005 cases of notifiable infectious diseases were reported over these 31 years, with an average yearly incidence of 342.14/100 000. There were 284 694 deaths with an average yearly mortality rate of 0.73/100 000. The overall incidence and overall mortality of notifiable infectious diseases both showed a "U" distribution (ie, a decrease, stable, an increase, stable again). The top five diseases in terms of incidence were hand, foot and mouth disease, viral hepatitis, tuberculosis, other infectious causes of diarrhea and dysentery, accounting for 78.0% of all reported cases. The top five causes of death were HIV/AIDS, rabies, tuberculosis, viral hepatitis and epidemic encephalitis B, which accounted for 76.07% of all mortalities. The diseases with the top five fatality rates were rabies, H5N1, H7N9, HIV/AIDS and plague, with rates of 91.06%, 66.07%, 38.51%, 25.19% and 10.31%, respectively. CONCLUSIONS: This analysis will benefit the future monitoring of infectious diseases and public health measures in China.

High prevalence of Babesia microti in small mammals in Beijing.

BACKGROUND: Babesiosis is an emerging tick-borne zoonotic infectious disease. Babesia microti is responsible for most cases of human babesiosis globally. It is important to investigate the prevalence of B. microti in the mammalian host population of a specific region in order to elucidate mechanisms of pathogen transmission and to define geographic areas where humans face the greatest risk of exposure. The aim of this study is to understand the prevalence and genotypes of B. microti in the small mammals that are found in Beijing, China. METHODS: We trapped small mammals from all of the 16 urban, suburban, and outer suburban districts of Beijing during the years 2014, 2017 and 2018. Genomic DNA was extracted from the heart tissues individually and the Babesia 18S rRNA gene was detected by PCR. The genotypes of B. microti were identified based on sequence alignments and phylogenetic analysis. The morphology of the parasites was observed under light microscopy. The risk factors were analyzed statistically based on both univariate analyses and multivariate logistic regression. RESULTS: A total of 1391 small mammals were collected. Positive infection of B. microti was detected in 12.1% (168/1391) of small mammals from 15 out of the 16 districts. Both Kobe-type and U.S.-type B. microti, accounting for 9.5% and 2.7%, respectively, were identified. Classic diverse morphologic forms of B. microti were observed. Specific types of ecological habitats including shrub areas, broad-leaved forest, and cropland were revealed to be risk factors associated with B. microti infection. CONCLUSIONS: This study demonstrated the wide prevalence of B. microti infection in eight species of small mammals in Beijing, with Kobe-type more prevalent than U.S.-type. This study provides fundamental information for the development of informed prevention and control measures by public health authorities; the data gathered indicates a need for further monitoring of both clinical diseases in individuals presenting with babesiosis-like symptoms, as well as the infection status of ticks in high risk areas.

Diverse clinical processes of 16 COVID-19 cases who concentrated infection in the same workplace in Beijing, China: An observational study.

ABSTRACT: Since December 2019, an outbreak of COVID-19 sweeping the world. Understanding the clinical and SARS-CoV-2 dynamic changes of mild and ordinary patients of COVID-19, so as to provide basis for the prevention and control of COVID-19.On February 1st, 2020, 16 SARS-CoV-2 RNA positive patients diagnosed in the same site in Beijing. The patients symptoms, signs, medication, and SARS-CoV-2 results were recorded.Of the 16 patients, 12 were female. Although they were infected at the same time in the same workplace, their clinical processes were very different and can be roughly divided into three different types: persistent sputum positive, persistent stool positive and persistent both positive. In 7 patients with mild clinical manifestations, the median days of SARS-CoV-2 RNA negative conversion in sputum samples were significantly later than those with obvious lung injury (27 days [range: 18 to 36]; 17 days, [range 6 to 25], P = .021). The negative conversion of SARS-CoV-2 RNA in stool was significant later than in sputum.There were various clinical manifestations after SARS-CoV-2 infection, even if they were infected by the same source of infection in the same place. The presence of SARS-CoV-2 virus RNA in stool samples was longer than that in respiratory tract.

[Etiological analysis of enteric infectious diseases during Beijing Olympic Games].

OBJECTIVE: To understand pathogen patterns of enteric infectious diseases and its impact on this pattern due to aggregation of a great deal of foreign visitors during Beijing Olympic Games. METHODS: The diarrheal patient's rectal swabs and stool specimens were collected from Olympic stadium and hospitals of four districts, including Dongcheng, Xicheng, Haidian and Chaoyang. Enteric multiple pathogens were detected from the total 45 specimens. The culture method was used for the enteric bacteria, ELISA and RT-PCR for the enteric viruses. Molecular typing of Salmonella Enteritidis isolation was completed by PFGE. RESULTS: It was found that 26 out of 45 cases were positive with 57.8 percent for pathogen detection, and 24 were identified as enteric pathogenic bacteria, including Vibrio parahaemolyticus, Salmonella, diarrheagenic Escherichia coli and Campylobacter jejuni, two as norovirus. There were mixed infections of two pathogenic bacteria for three cases. Ten kinds of pathogens were detected from foreign cases, while five kinds from Chinese cases. A total of 5 PFGE patterns were identified in 10 Salmonella Enteritidis isolates from national and foreign diarrheal cases, which were concentrative in some extent. CONCLUSION: Vibrio parahaemolyticus, Salmonella, diarrheagenic Escherichia coli and Campylobacter jejuni were found to be the primary bacterial pathogens during the Olympic Games. Enteric virus infection existed in summer diarrhea.

Polymorphisms of human T cell epitopes of Mycobacterium tuberculosis indicate divergence of host immune pressure on different categories of proteins.

Mycobacterium tuberculosis is the most successful pathogen with multiple mechanisms to subvert host immune response, resulting in insidious disease. There are few studies on whether the bacteria undergo antigenic variation in response to host immune pressure. Studies on T cell epitopes of M. tuberculosis can help us further understand the mechanism of interaction between the bacteria and host immune system. Here, we selected 180 M. tuberculosis complex in China, amplified 462 experimentally verified human T cell epitopes, sequenced and compared the results to analyze the diversity of those epitopes. It proved that a large majority human T cell epitopes of M. tuberculosis are conserved. However, polymorphisms of T cell epitopes indicated different categories of proteins suffered divergence from host immune pressure. Moreover, Beijing strains are more conservative than non-Beijing strains in T cell epitopes, which might make them easier to transmit than non-Beijing strains.

Genetic diversity of immune-related antigens in Region of Difference 2 of Mycobacterium tuberculosis strains.

Region of Difference 2 (RD2) was lost during the ongoing propagation of BCG between 1927 and 1931, a time that coincides with reports of the ongoing attenuation of the vaccine. Some data demonstrate that RD2 plays a role in mycobacterial virulence, and that its deletion from Mycobacterium tuberculosis leads to a decrease in bacterial growth in both a macrophage and a murine model. Human T-cell epitopes of M. tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. However, two antigens, Rv1986 and MPT64, encoded by RD2 harbored more than one amino acid changes. In this study, we used same set of clinical M. tuberculosis complex (MTBC) isolates from China, amplified the five genes containing T and B cell epitopes other than MPT64 encoded by RD2, and compared the sequences. It turned out that proteins in RD2 region, especially Rv1980c, Rv1985 and Rv1986 may be a special region that undergo antigenic variation in response to host immune pressure and may be involved in ongoing immune evasion. The dN/dS value of all six genes (including MPT64) were 2.33, much higher than 1, which means T cell antigens in RD2 region appeared to be under diversifying selection. Our data support the view that RD2 regions tend to be more variable than we expected to evade host immunity and the immune-related antigens in RD2 were more variable than we expected, especially in T-cell epitope regions.

Detection of yellow fever virus genomes from four imported cases in China.

Yellow fever virus (YFV), as the first proven human-pathogenic virus, is still a major public health problem with a dramatic upsurge in recent years. This is a report on four imported cases of yellow fever virus into China identified by whole genome sequencing. Phylogenetic analysis was performed and the results showed that these four viruses were highly homologous with Angola 71 strains (AY968064). In addition, effective mutations of amino acids were not observed in the E protein domain of four viruses, thus confirming the effectiveness of the YFV-17D vaccine (X03700). Although there is low risk of local transmission in most part of China, the increasing public health risk of YF caused by international exchange should not be ignored.