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Influenza viruses from avian and porcine sources and their possible role in the origin of human pandemic strains.

Studies on influenza viruses from feral ducks trapped in Canada in August 1976, gave a 26% isolation rate from cloacal samples of juvenile birds. Several different influenza A viruses were isolated, some of which possessed novel hemagglutinin and/or neuraminidase antigens. Influenza A viruses isolated from the rectum of feral ducks replicate in the upper respiratory tract and also in the intestinal tract of feral and domestic ducks. Representative human influenza viruses of the H0N1, H3N2 and Hsw1 N1 subtypes replicate in the upper respiratory tract of ducks but not in the intestinal tract. The A/Hong Kong/68 [H3N2] influenza virus that has not been isolated from man for several years was recently isolated from pigs originating from The People's Republic of China. A/Victoria/3/75-like influenza viruses that are currently circulating in man were also isolated from pigs. Both the A/Hong Kong/68 and the A/Victoria/75-like viruses transmitted readily from pig to pig in experimental studies. The susceptibility of ducks and pigs to infection with human influenza viruses suggests that these animals may play an important role in the ecology of influenza A viruses.

Animals

Multi-scale phylodynamic modelling of rapid punctuated pathogen evolution.

Computational multi-scale pandemic modelling remains a major and timely challenge. Here we identify specific requirements for a new class of models simulating pandemics across three scales: (1) pathogen evolution, often punctuated by the rapid emergence of new variants, (2) human interactions within a heterogeneous population, and (3) public health responses which constrain individual actions to control the disease transmission. We then present a pandemic modelling framework satisfying these requirements and capable of simulating feedback loops between dynamics unfolding at these different scales. The developed framework comprises a stochastic agent-based model of pandemic spread, coupled with a phylodynamic model that incorporates within-host pathogen evolution. It is validated with a case study, modelling the punctuated evolution of SARS-CoV-2, based on global and contemporary genomic surveillance data, which captures a large heterogeneous population. We demonstrate that the model replicates the essential features of the COVID-19 pandemic and virus evolution, while retaining computational tractability and scalability.

SARS-CoV-2

Whole-genome sequencing, strain composition, and predicted antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in England in 2017-20: a prospective national surveillance study.

BACKGROUND: Surveillance of the invasive disease burden caused by Streptococcus pneumoniae in England is performed by the UK Health Security Agency (UKHSA). In 2017, UKHSA switched from phenotypic methods to whole-genome sequencing (WGS) approaches for pneumococcal surveillance. Here, we present the first results of national WGS surveillance, up to the start of the COVID-19 pandemic, with the aim of describing the population genomics of this important pathogen. METHODS: We examined prospective national surveillance data from England, using bacterial isolates from cases of invasive pneumococcal disease (IPD) submitted to the national reference laboratory at UKHSA. A bioinformatic pipeline was developed to quality control WGS data and routinely report species and serotype. We assembled isolate data, assigned global pneumococcal sequencing clusters (GPSCs), and predicted antimicrobial resistance (AMR) profiles for isolates that passed further quality control. We collected additional data on patient outcomes and characteristics using enhanced surveillance questionnaires completed by patients' general practitioners. We used logistic regression analysis to assess the effects of various genomic and patient characteristics on the outcomes of IPD. FINDINGS: In England, between July 1, 2017, and Feb 29, 2020, there were 15 400 cases of IPD. From these cases, 13 749 (89·3%) isolates were sequenced, passed quality control, and were included in analyses. Serotype diversity was high during the study period, with 2751 (20%) isolates serotyped as 13-valent pneumococcal conjugate vaccine (PCV13) types, whereas serotype 8 was the most prevalent serotype (n=3074 [22·4%]) overall. There were 157 GPSCs within the collection, with GSPC3 the most common, encompassing 98·7% (3033 of 3074) of serotype 8 isolates. Most isolates (n=10 198 [74·2%]) did not contain AMR-associated genes. Resistance to co-trimoxazole was the most frequently predicted resistance (n=2331 [17%]), followed by resistance to tetracycline (n=1199 [8·7%]) and β-lactams (n=1149 [8·4%]). Logistic regression analysis found the presence of AMR-associated genes significantly increased the odds of patient death (odds ratio 1·18, 95% CI 1·01-1·38). Some GPSCs were also associated with a significant increase in the odds of patient death, such as GPSC12 (1·88, 1·48-2·38). Isolates from 2018 were associated with a significant increase in the odds of patient death (1·12, 1·00-1·25), whereas younger patient age was significantly associated with a reduction in the odds of patient death compared with being aged 85 years or older. INTERPRETATION: WGS-based surveillance has allowed us to interrogate country-wide population dynamics driving changes in pneumococcal serotype frequency. Here, we observe a stable but diverse population before the COVID-19 pandemic restrictions were enforced in England, with low rates of AMR. These findings will provide the baseline for pandemic and post-pandemic data, to collectively inform implementation and development of the vaccination programme within the country. FUNDING: None.

Streptococcus pneumoniae

RND-mediated efflux couples antimicrobial resistance and hypervirulence in contemporary Vibrio cholerae.

The prevailing view in bacterial pathogenesis is that antimicrobial resistance and virulence are constrained by evolutionary trade-offs, with resistance mechanisms imposing fitness costs that attenuate pathogenic potential. Herein we document that contemporary Vibrio cholerae clinical isolates from the ongoing seventh pandemic have circumvented this paradigm by coupling multidrug resistance with hypervirulence. We examined five geographically diverse Wave 3 isolates collected between 2017 and 2019 and compared them to early pandemic strains. These contemporary isolates exhibited both broad-spectrum antimicrobial resistance and markedly enhanced colonization capacity in the infant mouse model. Phylogenetic analysis of 67 O1 El Tor genomes spanning 1960-2019 confirmed that the isolates cluster within a representative Wave 3 sublineage. We identified the VexB RND efflux pump as a mediator of this coupled phenotype. Elevated vexB expression in the contemporary isolates conferred resistance to multiple antibiotic classes, while vexB inactivation simultaneously impaired resistance and colonization. This dual function was not observed in early pandemic strains, consistent with a recent evolutionary adaptation. VexB-mediated hypervirulence occurred through multiple pathways independent of cholera toxin and toxin-coregulated pilus production levels. VexB deletion impaired bacterial adherence to intestinal epithelial cells, impaired motility, and increased susceptibility to membrane-active antimicrobials. In contrast, laboratory evolution under antibiotic pressure alone generated resistant but avirulent strains, demonstrating that complex selective forces in nature enabled the co-optimization of resistance and virulence. These findings establish VexB as a molecular link between antimicrobial resistance and hypervirulence in pandemic V. cholerae, highlighting efflux pumps as dual-function therapeutic targets whose inhibition could both restore antibiotic activity and attenuate disease.

Animals

The Network of National COVID-19 Data Portals: public health equity through collaboration.

The network of the national COVID-19 Data Portals was developed and linked to the COVID-19 Data Portal (https://www.covid19dataportal.org/)inresponsetothe need for rapid data sharing and analysis during the 2020-2022 SARS-CoV-2 pandemic. Built on open-source code developed by the Swedish COVID-19 Data Portal (now the Swedish Pathogens Portal, www.pathogens.se) the network included 12 national portals addressing demand for local open data sharing and access, across data types and resources. It provides a robust case study of national initiatives for FAIR (Findable, Accessible, Interoperable and Reusable) resources and a foundation for future pandemic preparedness across pathogens globally. In this paper we outline the structure of the origins of the network of National COVID-19 Datal Portals, the technical aspects and code originating from the Swedish Portal and provide an overview of the services and tools offered by each Portal. The paper showcases the process and operation of four Portals: Sweden, Poland, Spain, Norway and The Netherlands. In this study, we observe that pandemic response greatly benefits from an established infrastructure that can be quickly mobilised, developed and extended. Collaborations and preparation built on solid foundations over several years, supported by investment in the form of national and international research grants, is key for sustainability, continuation and readiness to deploy such efforts.

COVID-19

Evolution of Candidaemia and azole resistance in Italy: A multicentre retrospective study.

PURPOSE: Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. METHODS: This retrospective multicentre study (2015-2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. RESULTS: 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020-2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4%), followed by C. parapsilosis (24.7%), C. glabrata (11.8%), and C. tropicalis (11.4%). Echinocandin resistance remained low (<&#x2009;2% for C. albicans and C. glabrata), whereas azole resistance increased markedly, particularly in C. parapsilosis, reaching fluconazole resistance rates of 25.6% in 2022. CONCLUSIONS: Candidaemia increased during the 9-year study period in Italy, particularly in the COVID-19 pandemic, in medical wards and ICU. Emerged a growing azole resistance, underscoring the need for enhanced surveillance and informed empirical treatment strategies.

Candida species etiology

A 4-year longitudinal wastewater surveillance of five gastroenteritis viruses and the correlation with clinical cases in Alberta, Canada.

Viruses are common causes of acute gastroenteritis worldwide. They are detected in large quantities in raw sewage making them amenable to wastewater-based surveillance (WBS). To monitor the prevalence of gastroenteritis viruses in wastewater and assess their correlation with clinical cases, wastewater samples collected between July 2020 and June 2024 from 12 wastewater treatment plants across Alberta, Canada were analyzed for norovirus (NoV) GI & GII, rotavirus (RoV), adenovirus (AdV), sapovirus (SaV) and astrovirus (AsV). Among the 5726 wastewater samples tested, AdV (80.5%) had the highest detection rate followed by NoV GII (75.6%), SaV (63.2%), NoV GI (59.4%), RoV (42.2%) and AsV (20.2%). Winter and spring seasonality was found for NoV and RoV in both wastewater and clinical disease. Public health interventions especially in the 1st year of the COVID-19 pandemic had a significant impact on their burden with marked reduction in wastewater detected viruses and clinical cases. NoV showed a strong correlation between its level in wastewater and the number of clinical cases, while moderate correlation was observed for the other four viruses. Cross-correlation analysis showed that changes of viral RNA concentration in wastewater lagged behind reported gastroenteritis cases by approximately 6&#xa0;days to 3&#xa0;weeks. To our knowledge, this is the longest multi-region WBS study monitoring multiple gastroenteritis viruses spanning both COVID-19 pandemic and post-pandemic periods. The data obtained from this study supported WBS as a complementary tool to track population-based circulation of gastroenteritis viruses, providing actionable public health data.

Clinical cases