Biosafety and Health最新文献

Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8⁺ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8⁺ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8⁺ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8⁺ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8⁺ T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2⁺ and HLA-A24⁺ donors, providing a novel method for SARS-CoV-2 infected case tracing.

Ceftazidime-avibactam (CZA) is a recently approved combination synthetic β-lactamase inhibitor used in human clinical medicine. Cases of CZA resistance in humans have already been reported, but limited research has investigated CZA resistance in pets. This study explored the prevalence and transmission of CZA-resistant Escherichia coli (CZAREC) among pets, their owners, veterinarians, and the environment in animal hospitals. A total of 5,419 clinical samples were collected from dogs and cats, along with samples from the environment (n = 5,843), veterinarians (n = 557), and pet owners (n = 368) in animal hospitals. From these samples, 760 Escherichia coli (E. coli) isolates were obtained, out of which 60 were identified as CZAREC. These included 34 isolates from the environment (9.14 %, n = 372), three from veterinarians (8.11 %, n = 37), and 23 from animals (6.82 %, n = 337). No CZAREC isolates were found in pet owners. The predominant sequence types of CZARECs were ST156 (n = 20), ST410 (n = 19) and ST101 (n = 7). Bayesian analysis revealed six clusters comprising 47 isolates from the hospital environment, pets, and veterinaries, displaying genetic relatedness of less than 100 core genome single nucleotide polymorphisms (cgSNPs) between any two isolates in each cluster. Some CZAREC isolates with high genetic similarity persisted in the same animal hospital for four to six months. Moreover, discriminant analysis of principal components indicated that most isolates from different hosts shared a genetic source in the human/dog/cat merged cluster. Overall, evidence of CZARECs transmission was found among pets, the environment, and veterinarians in animal hospitals. The findings emphasize the importance of monitoring CZARECs in the veterinary clinical setting to ensure the health of both pets and humans.

Mpox is a zoonotic infectious disease caused by the mpox virus (MPXV). Historically, the majority of mpox cases have been documented in Central Africa. However, since May 2022, there has been a notable rise in reported cases from regions beyond Africa. Currently, over 110 countries spanning Europe, North America, South America, Asia, and other territories have reported mpox infections. This report details a case involving a patient who identifies as a man who has sex with men (MSM) and is concurrently infected with MPXV, human immunodeficiency virus type 1 (HIV-1), Pneumocystis jiroveci, as well as extensively drug-resistant tuberculosis (XDR-TB). This patient had also received a vaccination for smallpox in the past. Additionally, we provide photographic documentation charting the progression of dermatological manifestations associated with mpox. This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox. The rapid and widespread dissemination of the MPXV across various regions, especially among MSM communities, underscores the importance of enhancing preventive education efforts targeted at high-risk populations.

Chicken is an important food animal worldwide and plays an important role in human life by providing meat and eggs. Despite recent significant advances in gut microbiome studies, a comprehensive study of chicken gut bacterial, archaeal, and viral genomes remains unavailable. In this study, we constructed a chicken multi-kingdom microbiome catalog (CMKMC), including 18,201 bacterial, 225 archaeal, and 33,411 viral genomes, and annotated over 6,076,006 protein-coding genes by integrating 135 chicken gut metagenomes and publicly available metagenome-assembled genomes (MAGs) from ten countries. We found that 812 and 240 MAGs in our dataset were putative novel species and genera, respectively, far beyond what was previously reported. The newly unclassified MAGs were predominant in Phyla Firmicutes_A (n = 263), followed by Firmicutes (n = 126), Bacteroidota (n = 121), and Proteobacteria (n = 87). Most of the classified species-level viral operational taxonomic units belong to Caudovirales. Approximately, 63.24 % of chicken gut viromes are predicted to infect two or more hosts, including complete circular viruses. Moreover, we found that diverse auxiliary metabolic genes and antibiotic resistance genes were carried by viruses. Together, our CMKMC provides the largest integrated MAGs and viral genomes from the chicken gut to date, functional insights into the chicken gastrointestinal tract microbiota, and paves the way for microbial interventions for better chicken health and productivity.

In response to problems of poor sampling quality, low sensitivity, and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) oropharyngeal (OP) swab sampling used in China, we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests (NAATs) in China. The results showed that, using nasopharyngeal (NP) swab results as the gold standard, the overall sensitivities for saliva specimens and OP swabs were 93.3 % and 85.0 %, the specificities were 92.6 % and 93.8 %, respectively. The results of an acceptability survey showed that the scores for saliva, OP, and NP samples were 9.46 ± 1.69, 8.11 ± 2.42, and 4.58 ± 3.82 out of 10, respectively, with significant differences among the three groups (P < 0.05). With higher sensitivity, comparable specificity, and strong public preference, saliva-based NAATs represent a convenient and effective method for detecting SARS-CoV-2 in future epidemics.

Uganda has been implementing the Global Health Security Agenda (GHSA) since 2015 to build its capacity according to World Health Organization (WHO) Benchmarks on International Health Regulations Capacities. The country remains prone to outbreaks, with more than 20 disease outbreaks reported in the past five years, including Ebola virus disease, Crimean-Congo haemorrhagic fever, Marburg haemorrhagic fever, measles, yellow fever, coronavirus disease 2019 (COVID-19), and cholera. Antimicrobial resistance (AMR) is an ongoing challenge. Uganda scored capacity level 3 on infection prevention and control (IPC) and antimicrobial stewardship (AMS) in the 2017 Joint External Evaluation (JEE) assessment. Identified gaps were being addressed after a self-assessment in 2021. This paper describes the technical assistance approaches provided to Uganda by the Medicines, Technologies, and Pharmaceutical Services Program, funded by the United States (U.S.) Agency for International Development, and implemented by Management Sciences for Health. The program, through a One Health approach, supported systematic capacity strengthening based on the JEE’s capacity advancement framework for global health security, specifically relating to AMR. The program’s interventions impacted 32 WHO benchmark actions (7 for AMR multisectoral coordination, 16 for IPC, and 9 for AMS), contributing to Uganda’s strengthened GHSA capacity. Leveraging success built on the AMR platform, the program trained 745 health workers in IPC for the Ebola virus and provided support for simulation exercises by eight district IPC teams. The program also worked with the Ministry of Health to coordinate IPC for the COVID-19 response in five health regions, covering 45 districts and reaching 5,452 health workers at 858 health facilities.

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5.2 or BF.7 in China in the winter of 2022, which is suspected to contribute substantially to the overloaded severe cases, needs to be investigated. We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing. We found that 317 (82.3 %) patients were coinfected with at least one additional pathogen(s), including bacteria (58.7 %), fungi (27.1 %) and viruses (73.5 %). Pseudomonas aeruginosa (P. aeruginosa) (24.2 %), Staphylococcus aureus (S. aureus) (14.0 %), and Klebsiella pneumoniae (K. pneumonia) (13.4 %) ranked as the top three coinfected bacteria. Aspergillus fumigatus (A. fumigatus) (39.5 %), Pneumocystis jirovecii (P. jirovecii) (24.4 %) and Canidia albicans (C. albicans) (22.1 %) were the top three coinfected fungi. Epstein-Barr virus (EBV) (63.1 %), Human herpesvirus 7 (HHV-7) (34.8 %), and Herpes simplex virus 1 (HSV-1) (32.6 %) were the top three coinfected viruses. Of note, the detection of multiple coinfections of potential pathogenic bacteria, fungi, and viruses, despite lacking consistent patterns, highlighted a complicated synergistic contribution to disease severity. Our study presents the most comprehensive spectrum of bacterial, fungal, and viral coinfections in Omicron-associated severe coronavirus disease 2019 (COVID-19), implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

The emerging viruses within the genus Henipavirus in the family Paramyxoviridae pose a great threat to public biosafety. To develop a quadruple real-time fluorescence-based quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay is pivotal for the early warning of the potential of zoonotic infectious diseases. Specific primers and probes were designed for the relatively conserved regions based on whole genome sequences of Langya virus (LayV), Mojiang virus (MojV), Nipah virus (NiV), and Cedar virus (CedV), followed by the establishment of a quadruple real-time fluorescence-based qRT-PCR detection method. No cross-reactivity was observed with other viral nucleic acids. The optimal linear detection range for LayV, MojV, NiV, and CedV was 10¹-10⁸ copies/μL, and the lower limit of detection was 10 copies/μL. Three different DNA concentrations of LayV, MojV, NiV, and CedV (10⁴, 10⁵, and 10⁶ copies/μL) were tested 14 times, achieving good repeatability. The standard deviation of the cycle threshold values for each concentration was <0.5 and the coefficient of variation was <3 %. Furthermore, the amplification efficiency of quadruple real-time fluorescence-based qRT-PCR was >90 %, and the correlation coefficient was >0.99. The established quadruple real-time fluorescence-based qRT-PCR assay for the detection of LayV, MojV, NiV, and CedV exhibits good sensitivity, specificity, and repeatability. Therefore, it can be used to detect Henipavirus and other related clinical specimens.

Human adenoviruses (HAdVs) are major respiratory pathogens. Specifically, human adenovirus type 4 (HAdV4) and human adenovirus type 7 (HAdV7) are known for causing fever and pneumonia, with documented cases of fatalities among the population. In recent years, HAdV4/HAdV7 has been implicated in causing substantial outbreaks, leading to increased morbidity in multiple countries. Most HAdV4 and HAdV7 infections have been reported in North America, Asia, Europe, Africa, South America, Oceania, and the Middle East. Most fatalities occurred in North America (the United States) and Asia (China and Singapore). Engineered recombinant adenoviruses have played a crucial role as vaccine vectors. In this study, we constructed a recombinant adenovirus, Ad4ITRmut-Ad7E3, and evaluated it in vitro and in vivo. We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain, indicating that the mutation of inverted terminal repeats (ITRs) weakened the replication ability of HAdV4. Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain, administered by intraperitoneal injection and oral gavage, resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdV7. This finding not only provides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vaccine candidate against HAdV4 and HAdV7 but also against other prevalent adenovirus serotypes such as HAdV3, HAdV11, HAdV14, and HAdV55, from various regions.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted public health. In 2022, the Omicron variant of SARS-CoV-2 rapidly became the dominant circulating variant in the local COVID-19 outbreaks in Tianjin Municipality, China. To gain a deeper understanding of the genetic variations of the Omicron variant in Tianjin, specimens from individuals who tested positive for SARS-CoV-2 between December 2021 and November 2022 were used for virus whole genome sequencing and phylogenetic analysis. A total of 1,674 high-quality Omicron sequences were obtained, consisting of 1,339 sequences from local cases belonging to 20 Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages and 335 sequences from imported cases belonging to 70 lineages. Tianjin experienced five waves of local outbreaks, accompanied by multiple substitutions among subvariants, ranging from the initial BA.1.1 lineage to the subsequent BA.2, BF.7, and BA.5.2 lineages. The evolutionary rate of local strains, estimated to be 28.999 substitutions per year, and the evolutionary rate of imported strains, estimated to be 24.946 substitutions per year, were lower than that of the strains circulating globally. The additional substitutions and deletions of local strains have been used to identify and disrupt the virus transmission chains. The subvariants such as BA.5.2.48, BA.5.2.49, BF.7.14, and XBB.1 circulating in the fifth epidemic wave presented criterial immune escape mutations including S: R346T, S: L452R and S: F486V. It is essential to implement genomic surveillance strategies to investigate further the development of genomic mutation characteristics in the SARS-CoV-2 variant. This ongoing monitoring will contribute to a better understanding of the virus's genetic changes and aid in effective control measures.