PubMed · 692517
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D L Salsbury. 1978. Equidoctorus rex?. https://pubmed.ncbi.nlm.nih.gov/692517/
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INTRODUCTION: Nontyphoidal Salmonella enterica (NTS) is a major zoonotic enteric pathogen. Animal contact-related NTS outbreaks have increased in the United States over the last decade. Geospatial analysis can identify locations with elevated risk of NTS outbreaks where public health authorities can focus their NTS prevention and intervention efforts. METHODS: We analysed NTS outbreak data reported from individual states to the Centers for Disease Control via the National Outbreak Reporting System between 2009 and 2022 across the continental contiguous United States. A geospatial analytical framework that included disease mapping, spatial interpolation, and global and local clustering methods was applied to identify regions with high NTS outbreak rates. Given that the study period (2009-2022) included the COVID-19 pandemic, an interrupted time series negative binomial model was used to assess changes in NTS incidence before and after 2020. RESULTS: A total of 104 NTS single-state outbreaks were reported to the National Outbreak Reporting System (NORS) during the study period. The mean annual incidence rate was 0.02 NTS outbreaks per million person-years. The primary animal contact categories associated with outbreaks were mammals (cattle, pigs, sheep, and horses), birds (backyard chickens, ducklings, and turkeys), and reptiles (turtles and lizards). Exposure settings included farms, fairgrounds, agricultural feed stores, veterinary clinics, dairy/agricultural settings, and residential settings. The local cluster detection methods consistently identified areas with significantly high NTS animal contact-related outbreak rates in the Mountain West, Midwest, and Northeast of the US. The interrupted time series analysis indicated a reduction in incidence following the onset of the COVID-19 pandemic (IRR = 0.03; p = 0.06). CONCLUSION: NTS animal contact-related single-state outbreaks revealed distinct spatial clustering across the United States, with higher risks in the Mountain West, Midwest, and Northeast. Diversity of animal-contact sources and exposure settings depicted complex transmission dynamics of NTS. A decline in reported NTS outbreaks was observed after the COVID-19 pandemic. Focused prevention and control programs are needed in high-risk areas to mitigate the burden of NTS outbreaks.
Defective genes account for ∼80% of the total of more than 7,000 diseases known to date. Gene therapy brings the promise of a one-time treatment option that will fix the errors in patient genetic coding. Recombinant viruses are highly efficient vehicles for in vivo gene delivery. Adeno-associated virus (AAV) vectors offer unique advantages, such as tissue tropism, specificity in transduction, eliciting of a relatively low immune responses, no incorporation into the host chromosome, and long-lasting delivered gene expression, making them the most popular viral gene delivery system in clinical trials, with three AAV-based gene therapy drugs already approved by the US Food and Drug Administration (FDA) or European Medicines Agency (EMA). Despite the success of AAV vectors, their usage in particular scenarios is still limited due to remaining challenges, such as poor transduction efficiency in certain tissues, low organ specificity, pre-existing humoral immunity to AAV capsids, and vector dose-dependent toxicity in patients. In the present review, we address the different approaches to improve AAV vectors for gene therapy with a focus on AAV capsid selection and engineering, strategies to overcome anti-AAV immune response, and vector genome design, ending with a glimpse at vector production methods and the current state of recombinant AAV (rAAV) at the clinical level.
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