Search

Summary: Background: International distribution of contaminated foods can be a source of Salmonella infections in people and can contribute to the spread of antimicrobial-resistant bacteria across countries. We report an investigation led by the United States Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and state governmental officials into a multistate outbreak of salmonellosis linked to pig ear pet treats. Methods: Pig ear treats and companion dogs were tested for Salmonella by state officials and the FDA. Products were traced back to the country of origin when possible. Cases were defined as outbreak illnesses in people associated with one of seven Salmonella serotypes genetically related to samples from pig ear pet treats, with isolation dates from June 2015 to September 2019. Whole genome sequencing (WGS) of isolates was used to predict antimicrobial resistance. Findings: The outbreak included 154 human cases in 34 states. Of these, 107 of 122 (88%) patients reported dog contact, and 65 of 97 (67%) reported contact with pig ear pet treats. Salmonella was isolated from 137 pig ear treats, including some imported from Argentina, Brazil, and Colombia, and from four dogs. WGS predicted 77% (105/137) of human and 43% (58/135) of pig ear treat isolates were resistant to ≥3 antimicrobial classes. Interpretation: This was the first documented United States multistate outbreak of Salmonella infections linked to pig ear pet treats. This multidrug-resistant outbreak highlights the interconnectedness of human health and companion animal ownership and the need for zoonotic pathogen surveillance to prevent human illness resulting from internationally transported pet food products. Funding: Animal Feed Regulatory Program Standards award. Animal and product testing conducted by FDA Vet-LIRN was funded by Vet-LIRN infrastructure grants (PAR-22-063).

As the first line of defense, the integumentary system is critical in comprehensively evaluating dolphin morbidity during stranding response. Most published studies on skin lesions in bottlenose dolphins (Tursiops truncatus) lack standardized gross descriptions and methodologies for evaluating lesions. The primary objective of this study was to evaluate the effectiveness of an assessment matrix designed to consistently describe skin lesions based on a set of standardized gross description characteristics. The matrix was implemented by reviewing necropsy reports, histopathology reports, and photographs collected from bottlenose dolphins stranded in Southwest Florida from 2015 through 2019. Of the 32 dolphins that met the inclusion criteria, 19 presented with skin lesions and five reviewers described each of the 46 lesions according to a novel, standardized assessment matrix. The most common descriptor selected, in each of the respective matrix categories, were, by anatomic location, head; distribution, multifocal to coalescing; quantity, moderate (10–30); size,

The Indian River Lagoon (IRL) on Florida’s east coast is a biologically diverse estuary and an important habitat to the threatened Florida manatee (Trichechus manatus latirostris). An unusual mortality event (UME) was declared by the Working Group on Marine Mammal Unusual Mortality Events in 2013 after a marked increase in manatee deaths in the IRL of an unknown cause. This UME followed a dramatic reduction of seagrass coverage in the IRL due to chronic non-toxic phytoplankton blooms, with a resultant ecosystem shift to mixed macroalgal dominance. At least 199 manatee deaths fitting the UME case definition were documented in and adjacent to the IRL during 2012–2019; mortality was highest in 2013, when 111 of these deaths were documented. The case definition included carcasses in good nutritional condition, with multiorgan congestion or wet lungs consistent with drowning without trauma. The gastrointestinal compartments of manatee carcasses were filled with diverse macroalga species, and the contents were notably more fluid than usual. Gross intestinal findings included blebbing to segmental thickening of the wall. Microscopic lesions were primarily intestinal, including necrosis, edema, hemorrhage, mucosa-associated lymphoid changes, and inflammation, sometimes associated with Gram-positive bacterial rods. A multidisciplinary approach of environmental and carcass sampling found no causative evidence through tests for micro- and macroalgal biotoxins, trace metals, general toxin screening, or vitreum biochemistry. Microbiological, cytological, immunohistochemical, and molecular analyses of Clostridiales from intestinal samples identified Clostridioides difficile toxin A, toxins A/B and toxin A gene; Paeniclostridium sordellii lethal gene (and other potential virulence factors from a sequenced strain); and Clostridium perfringens alpha and epsilon toxin genes. The results from this 8 year-long investigation are indicative that the cause of death in this manatee UME was associated with clostridial infection, initiated by a shift to a predominantly macroalgal diet.

We generated two IgG1-like bispecific antibodies (BsAbs) with different molecular formats, symmetrical DVD-Ig and asymmetrical knob-in-hole (KIH), targeting the same antigens, EGFR and PD-L1 (designated as anti-EGFR/PD-L1). We performed the physiochemical and biological characterization of these two formats of anti-EGFR/PD-L1 BsAbs and compared some key quality attributes and biological activities of these two formats of BsAbs. Physiochemical binding characterization data demonstrated that both formats bound EGFR and PD-L1. However, the binding affinity of the KIH format was weaker than the DVD-Ig format in Biacore binding assays. In contrast, both DVD-Ig and KIH BsAbs had similar ELISA and cell surface binding activities, comparable to mAbs. Triple-negative breast cancer (TNBC) cells and a xenograft model were used to test the potency of BsAbs and other biological activities. Results showed that anti-EGFR/PD-L1 BsAbs exhibited in vitro and in vivo antitumor proliferation activity, but there was a difference in the potencies of the respective BsAb formats (DVD-Ig and KIH) when different cells or assays were used. This study provides evidence that the potency of the BsAbs targeting the same antigens can be affected by the respective molecular features, and selection of appropriate cell lines and assays is critically important for the assay development and potency testing of BsAbs.