Emerging Microbes & Infections最新文献

Coronaviruses (CoVs) pose a significant threat to public health, causing a wide spectrum of clinical manifestations and outcomes. Beyond precipitating global outbreaks, Human CoVs (HCoVs) are frequently found among patients with respiratory infections. To date, limited attention has been directed towards alphacoronaviruses due to their low prevalence and fatality rates. Nasal swab and serum samples were collected from a paediatric patient, and an epidemiological survey was conducted. Retrospective surveillance investigated the molecular prevalence of CoV in 880 rodents collected in the Republic of Korea (ROK) from 2018 to 2022. Next-generation sequencing (NGS) and phylogenetic analyses characterized the novel HCoV and closely related CoVs harboured by Apodemus spp. On 15 December 2022, a 103-day-old infant was admitted with fever, cough, sputum production, and rhinorrhea, diagnosed with human parainfluenza virus 1 (HPIV-1) and rhinovirus co-infection. Elevated AST/ALT levels indicated transient liver dysfunction on the fourth day of hospitalization. Metagenomic NGS (mNGS) identified a novel HCoV in nasal swab and serum samples. Retrospective rodent surveillance and phylogenetic analyses showed the novel HCoV was closely related to alphacoronaviruses carried by Apodemus spp. in the ROK and China. This case highlights the potential of mNGS to identify emerging pathogens and raises awareness of possible extra-respiratory manifestations, such as transient liver dysfunction, associated with novel HCoVs. While the liver injury in this case may be attributable to the novel HCoV, further research is necessary to elucidate its clinical significance, epidemiological prevalence, and zoonotic origins.

During our surveillance of avian influenza viruses (AIVs) in wild birds across China, H10Nx viruses were isolated from diverse migratory flyways between 2022 and 2024. We identified one wild-bird H10N5 strain that shared a common ancestor with the human H10N5 virus in multiple gene segments. Phylogenetic and molecular dating revealed the origin and evolution of H10N5, highlighting the need for continued monitoring.

Antimicrobial resistance has recently increased due to emerging carbapenem-resistant Klebsiella pneumoniae and extended-spectrum β-lactamase (ESBL)-producing strains of K. pneumoniae, especially among hypermucoviscous K. pneumoniae (hmKp) strains. To evaluate the prevalence of ESBL-producing and carbapenem-resistant strains in hmKp and non-hmKp clinical isolates through a systematic review and meta-analysis. We searched PubMed, Scopus, and Cochrane Library databases from January 2000 to June 2023. Clinical and in vivo/in vitro studies involving confirmed K. pneumoniae clinical isolates differentiated into hmKP and non-hmKP strains based on string test results. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on the number of individuals in each target group. Forest plots were used to visualize the effect sizes and 95% CIs of individual studies estimated using the inverse variance and DerSimonian - Laird methods with fixed - and random-effects models, respectively. Heterogeneity was assessed using Cochran's Q test (I² ≥ 50%). Fifteen studies comprising 2049 clinical isolates of K. pneumoniae met the inclusion criteria. Meta-analysis revealed that hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains (pooled OR: 0.26, 95% CI: 0.11-0.63, P = 0.003) and a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR: 0.63, 95% CI: 0.40-0.97, P = 0.038). hmKp strains exhibited lower and slightly lower prevalence of ESBL production and carbapenem resistance, respectively, than non-hmKp strains. However, given the rising prevalence of ESBL-producing and carbapenem-resistant hmKp strains, patients infected by string-test-positive K. pneumoniae must be managed prudently, considering the potential for highly resistant strains.

Buruli ulcer (BU) is a chronic and debilitating skin disease caused by the environmental pathogen, Mycobacterium ulcerans (MU). The primary virulence determinant is mycolactone, a cytotoxic lipid compound unique to MU and its other mycolactone producing mycobacteria (MPM) ecological variants. Although BU prevalence is highest in West Africa and Australia, little is known about MU and other MPM distribution in non-endemic regions such as the Southeastern United States (US). In this study, environmental samples (water filtrand, plant biofilm, soil, aquatic invertebrates) were collected from nine freshwater sites across Louisiana, Mississippi and Alabama over three sampling periods (August 2020, November 2020, March 2021). Samples were screened for MU and MPM presence and abundance by PCR and genotyped using variable number tandem repeat (VNTR) profiling. All nine sites were positive for MU or other MPM DNA in at least one substrate, except invertebrates. Overall, mean concentrations were 4.3 × 10⁴ genome units (GU)/sample in August 2020, 1.26 GU/sample in November 2020, and 55.5 GU/sample in March 2021. Profiling by VNTR identified four MU (designated A-D) and one M. liflandii genotype(s), among environmental samples, with genotype frequencies varying by site and sampling time. Detection of MU and M. liflandii genotypes in Southeastern US aquatic environments, matching those from BU endemic regions, provides rationale for ongoing surveillance. Our findings broaden the known geographic range of MU and MPMs and offer baseline data to help predict and prevent and predict the possibility of zoonotic transmission in Southeastern US.

Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints - providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses - two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines.Trial registration: ClinicalTrials.gov identifier: NCT01799954..Trial registration: ClinicalTrials.gov identifier: NCT02109354..Trial registration: ClinicalTrials.gov identifier: NCT02404311..Trial registration: ClinicalTrials.gov identifier: NCT02207920..Trial registration: ClinicalTrials.gov identifier: NCT02296541..Trial registration: ClinicalTrials.gov identifier: NCT03284710..Trial registration: ClinicalTrials.gov identifier: NCT02915016..Trial registration: ClinicalTrials.gov identifier: NCT02997969..Trial registration: ClinicalTrials.gov identifier: NCT03122223..Trial registration: ClinicalTrials.gov identifier: NCT03409276..Trial registration: ClinicalTrials.gov identifier: NCT02968849..Trial registration: ClinicalTrials.gov identifier: NCT03060629..Trial registration: ClinicalTrials.gov identifier: NCT00223080..

The multiple epidemics of Zika virus (ZIKV) posed a substantial threat to public health. Clinical evidence suggests that ZIKV could break through the blood-brain, blood-placenta, and blood-testis barriers, leading to severe outcomes such as congenital malformations in newborns and Guillain-Barré syndrome in adults. Currently, there are no specific treatments for ZIKV infection. To address the antibody-dependent enhancement (ADE) of dengue virus (DENV) infection induced by ZIKV vaccination, we designed two modified prM-E RNAs (ZA and ZB) with specific mutations either shielding or disrupting the conserved fusion-loop epitope in the E protein. Then, we chose the mRNA-LNP vaccine platform to evaluate the safety and efficacy. After prime-boost immunization, ZA vaccine could induce high levels of T cells secreting IFN-γ and exhibit limited neutralizing ability against Asian-lineage and African-lineage ZIKV. After ZIKV challenge, ZA vaccine could provide complete protection in immunocompromised AG129 mice at low levels of neutralizing antibodies, preventing viral dissemination to the brain, uterus, and testes. Importantly, the ZA vaccine also reduced the ADE effect of DENV infection. Although ZB vaccine exhibited good immunogenicity, it could not achieve complete viral clearance in AG29 mice. Our findings suggested that the ZA vaccine could prevent both lethal ZIKV infection and DENV ADE induced by infection or vaccination.

In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.4.4b infection. The viral genome sequences are closely related to recent SD cattle H5N1 sequences. Cat H5N1 genomes had unique mutations, including T143A in haemagglutinin, known to affect infectivity and immune evasion, and two novel mutations in PA protein (F314L, L342Q) that may affect polymerase activity and virulence, suggesting potential virus adaptation. Dead cats showed systemic infection with lesions and viral antigens in multiple organs. Higher viral RNA and antigen in the brain indicated pronounced neurotropism. Lectin-histochemistry revealed widespread co-expression of sialic acid α-2,6 and α-2,3 receptors, suggesting cats could serve as mixing vessels for reassortment of avian and mammalian influenza viruses. No differences in clade 2.2 or 2.3.4.4b H5 pseudoviruses binding to cat lung/brain tissues indicated the neurotropism is unlikely mediated by receptor binding affinity.

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants. Via analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.