Biology subjects

Magstadt, D. R.

Publications and source records attributed to Magstadt, D. R..

4 recordsLinked to original sources

bioRxiv2024

Experimental reproduction of viral replication and disease in dairy calves and lactating cows inoculated with highly pathogenic avian influenza H5N1 clade 2.3.4.4b

Highly pathogenic avian influenza (HPAI) H5N1 of the hemagglutinin clade 2.3.4.4b was detected in the United States in late 2021 and continues to circulate in all four North American flyways to date. In addition to impacting poultry, these HPAI viruses caused mortality events in wild bird species and wild mammals. Transmission in multiple host species raises the concern for mammalian adaptation. On March 25, 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses. Over one hundred positive herds were rapidly identified in Texas and eleven other U.S. states. The case description included reduced feed intake and rumen motility in lactating cows, decreased milk production, and thick yellow milk. The diagnostic investigation revealed detections of viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis, and positive immunoreactivity of glandular epithelium by immunohistochemistry. A single transmission event, likely from avian species to dairy cattle, followed by limited local transmission preceded the onward lateral transmission of H5N1 clade 2.3.4.4b genotype B3.13. We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows. The heifers were inoculated by an aerosol respiratory route and the cows by an intramammary route. Clinical disease was mild in the heifers, but infection was confirmed by virus detection, lesions, and seroconversion. Clinical disease in lactating cows included decreased rumen motility, changes to milk appearance, and production losses consistent with field reports of viral mastitis. Infection was confirmed by high levels of viral RNA detected in milk, virus isolation, lesions in mammary tissue, and seroconversion. This study provides the foundation to investigate additional routes of infection, transmission, and intervention strategies.

microbiology↗

bioRxiv2024

Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations.

microbiology↗

bioRxiv2024

Highly Pathogenic Avian Influenza A (H5N1) clade 2.3.4.4b Virus detected in dairy cattle

The global emergence of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses poses a significant global public health threat. Until March 2024, no outbreaks of this virus clade had occurred in domestic cattle. We genetically characterize HPAI viruses from dairy cattle showing an abrupt drop in milk production. They share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. B3.13 viruses underwent two reassortment events since 2023 and exhibit critical mutations in HA, M1, and NS genes but lack critical mutations in PB2 and PB1 genes, which enhance virulence or adaptation to mammals. The PB2 E627K mutation in a human case underscores the potential for rapid evolution post-infection, highlighting the need for continued surveillance to monitor public health threats.

microbiology↗

bioRxiv2019

Switching between bacteriostatic and bactericidal antimicrobials for retreatment of bovine respiratory disease (BRD) relapses is associated with an increased frequency of resistant pathogen isolation from veterinary diagnostic laboratory submissions

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, studies examining the impact of antimicrobial selection (i.e. bactericidal or bacteriostatic) on retreatment outcomes and the emergence of antimicrobial resistance (AMR) are deficient in the published literature. A survey was conducted to determine the association between antimicrobial class selection for retreatment of BRD relapses on antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis. Original susceptibility testing of these isolates for ceftiofur, danofloxacin, enrofloxacin, florfenicol, oxytetracycline, spectinomycin, tilmicosin, and tulathromycin was performed using Clinical and Laboratory Standards Institute guidelines. Data were analyzed using a Bayesian approach to evaluate whether retreatment with antimicrobials of different mechanistic classes (bactericidal or bacteriostatic) increased the probability of resistant BRD pathogen isolation in calves. The posterior distribution we calculated suggests that an increased number of treatments is associated with a greater probability of isolates resistant to at least one antimicrobial. In addition, the frequency of resistant M. haemolytica isolates was greater with retreatment using antimicrobials of different mechanistic classes than retreatment with the same class. Specifically, treatment protocols using a bacteriostatic drug first followed by retreatment with a bactericidal drug was associated with a higher frequency of resistant BRD pathogen isolation. This effect was more profound with specific treatment combinations; tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant isolates among all antimicrobial combinations. These findings suggest that the selection of antimicrobial mechanistic class for retreatment of BRD should be considered as part of an antimicrobial stewardship program.

microbiology↗