Evaluation of the 50% infectious dose of human norovirus cin-2 in gnotobiotic pigs: a comparison of classical and contemporary methods for endpoint estimation

Human noroviruses (HuNoVs) are the leading causative agents of epidemic and sporadic acute gastroenteritis that affect people of all ages worldwide. However, very few dose?response studies have been carried out to determine the median infectious dose of HuNoVs. In this study, we evaluated the median infectious dose (ID50) and diarrhea dose (DD50) of the GII.4/2003 variant of HuNoV (Cin-2) in the gnotobiotic pig model of HuNoV infection and disease. Using various mathematical approaches (Reed?Muench, Dragstedt?Behrens, Spearman?Karber, exponential, approximate beta-Poisson dose?response models, and area under the curve methods), we estimated the ID50 and DD50 to be between 2400?3400 RNA copies, and 21,000?38,000 RNA copies, respectively. Contemporary dose?response models offer greater flexibility and accuracy in estimating ID50. In contrast to classical methods of endpoint estimation, dose?response modelling allows seamless analyses of data that may include inconsistent dilution factors between doses or numbers of subjects per dose group, or small numbers of subjects. Although this investigation is consistent with state-of-the-art ID50 determinations and offers an advancement in clinical data analysis, it is important to underscore that such analyses remain confounded by pathogen aggregation. Regardless, challenging virus strain ID50 determination is crucial for identifying the true infectiousness of HuNoVs and for the accurate evaluation of protective efficacies in pre-clinical studies of therapeutics, vaccines and other prophylactics using this reliable animal model.Fil: Ramesh, Ashwin K.. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Virología E Innovaciones Tecnológicas; ArgentinaFil: Schmidt, Philip J.. University of Waterloo; CanadáFil: Lei, Shaohua. Virginia-Maryland College of Veterinary Medicine; Estados UnidosFil: Zhong, Weiming. Cincinnati Children’s Hospital Medical Center; Estados UnidosFil: Jiang, Xi. Cincinnati Children’s Hospital Medical Center; Estados UnidosFil: Emelko, Monica B.. University of Waterloo; CanadáFil: Yuan, Lijuan. Virginia-Maryland College of Veterinary Medicine; Estados Unido

ANÁLISE QUANTITATIVA DE RISCO MICROBIOLÓGICO (AQRM): UM ESTUDO APLICADO AOS USOS DAS ÁGUAS DA LAGOA DO PERI - FLORIANÓPOLIS/SC.

TCC(graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. Engenharia Sanitária e Ambiental.Este trabalho avaliou o risco de um indivíduo adquirir uma infecção microbiológica através do contato primário e secundário com um manancial de água superficial contaminado, sendo o rotavírus e o adenovírus os patógenos de referência. Para tal, a metodologia da Análise Quantitativa de Risco Microbiológico (AQRM) foi utilizada e aplicada ao software @risk, o qual, através da Simulação de Monte Carlo, apresentou as curvas de probabilidade de infecção para diferentes cenários de exposição. Os resultados indicaram que o risco de infecção por rotavírus e adenovírus é alto em todos os cenários de exposição, apresentando-se maior para a atividade de nado, com um intervalo de probabilidade de infecção variando entre 65,9% e 88,9% para rotavírus, e 100% para adenovírus. As altas concentrações de adenovírus e rotavírus indicam que houve contaminação fecal no local de análise

Exploring the impact of interventions on the transmission dynamics of infectious diseases: antimicrobial resistant foodborne disease and COVID-19

Antimicrobial resistance (AMR) and coronavirus disease 2019 (COVID-19) currently represent two of the most important threats to human health, with both AMR and COVID-19 resulting in millions of deaths worldwide and severe socioeconomic disruption. It is therefore critical to understand how interventions can be used to mitigate the impact of these two threats to human health. However, there are large gaps in research exploring the range of impacts following the introduction of interventions on the transmission dynamics of AMR and COVID-19. In particular, the influence of livestock antibiotic stewardship on AMR in human populations is poorly understood. This includes antimicrobial resistant foodborne disease caused by human pathogens such as Salmonella. Additionally, during the initial stages of the COVID-19 pandemic in 2020, there was a need to understand the feasibility of so-called “optimal” strategies to best mitigate the impact of outbreaks. In this thesis, I aimed to explore the impact of interventions on the transmission dynamics of AMR and COVID-19. A systematic scoping review identified the literature base for the modelling of AMR transmission/dissemination between livestock/human populations. Mathematical models were also developed to explore the impacts of livestock antibiotic curtailment on antimicrobial resistant human foodborne disease and to optimise the timing, strength and duration of non-pharmaceutical interventions (NPIs) to mitigate COVID-19 outbreaks. Large literature gaps in AMR modelling were identified, with existing models exploring a narrow subset of model structures, interventions, settings, and a general lack of model validation in identified studies. Livestock antibiotic curtailment resulted in increases in the daily incidence of foodborne disease, as well as a decrease in the proportion of antibiotic-resistant human infections. However, increases in foodborne disease could be mitigated by strengthening biosecurity along the farm-to-fork pathway. The efficacy of livestock antibiotic curtailment to control human antibiotic-resistant foodborne disease was disrupted when the influence of AMR contamination on imported food products was also modelled. This was attributable to an increase in antibiotic-sensitive/resistant foodborne disease from imported sources, unalterable through local antibiotic curtailment strategies. Additionally, while optimal NPIs to minimise the attack rate and epidemic peak were identified, they were found to be fragile, with robust, but suboptimal interventions over a broader parameter space for the timing, strength and duration of NPIs being more practical and less prone to implementation error. This work presented in this thesis adds to a growing evidence base quantifying the intended and unintended impacts of interventions on the transmission dynamics of AMR at the one-health interface and COVID-19. This thesis also provides modelling frameworks that can be expanded to explore future AMR and COVID-19 research questions