Gender Analysis for One Health: Theoretical Perspectives and Recommendations for Practice.

One health emphasizes the interdependent health of humans, animals, and their shared environments and shows promise as an integrated, equitable transdisciplinary approach to important ecohealth issues. Notably, research or programming explicitly examining the intersection of gender and one health is limited, although females represent half of the human population and play important roles in human and animal health around the world. Recognizing these gaps, scholars from the University of Wisconsin-Madison in collaboration with United States Department of Agriculture convened a consultative workshop, "Women and One Health," in 2016. This paper outlines the workshop methods and highlights outcomes toward shared terminology and integration of frameworks from one health, gender analysis, and women in agriculture. Further, recommendations for education, policy, and service delivery at the intersection of women's empowerment and one health are offered as important efforts toward the dual goals of gender equality and sustainable health of humans, animals, and their shared ecosystems.

Students' perception of case-based continuous assessment and multiple-choice assessment in a small animal surgery course for veterinary medical students.

OBJECTIVE: To determine the relationship between students' perceptions of 2 assessment methods and academic performance. STUDY DESIGN: A 2-year prospective survey study in a 4-year Doctor of Veterinary Medicine (DVM) curriculum. SAMPLE POPULATION: Year 3 DVM students (n = 44). METHODS: An assessment of learning gain questionnaire was used to investigate students' perceptions regarding multiple-choice examination (MCE) versus take-home case-based continuous assessment (CA) in a 3rd year small animal surgery lecture course. Academic performance and student assessment of learning gain in the 2 course components were compared. Relationships between student perceptions and academic performance were examined. A follow-up survey was conducted during clinical rotations in 4th year to determine change in student perceptions over time. RESULTS: Academic performance in 3rd year was significantly enhanced by use of CA, particularly for students with weaker grades. Academic performance in 4th year clinical rotations was not closely related to 3rd year performance. Many students preferred an instructional approach with provision of comprehensive notes and assessment with multiple-choice questions based on the notes. However, students recognized that feedback on work submitted for CA grading significantly facilitated learning. Student assessment of learning gain was correlated with academic performance in the 3rd year course component examined by CA, but not the component assessed using MCE. CONCLUSION: Our data suggest that perceptions of learning gain, academic accomplishment, and clinical performance in 4th year are weakly correlated. Teachers should better explain to veterinary students that learning to be a clinician is more than replication of knowledge.

Differentiated swine airway epithelial cell cultures for the investigation of influenza A virus infection and replication.

BACKGROUND: Differentiated human airway epithelial cell cultures have been utilized to investigate cystic fibrosis, wound healing, and characteristics of viral infections. These cultures, grown at an air-liquid interface (ALI) in media with defined hormones and growth factors, recapitulate many aspects of the in vivo respiratory tract and allow for experimental studies at the cellular level. OBJECTIVES: To optimize growth conditions for differentiated swine airway epithelial cultures and to use these cultures to examine influenza virus infection and replication. METHODS: Primary swine respiratory epithelial cells were grown at an air-liquid interface with varying amounts of retinoic acid and epidermal growth factor. Cells grown with optimized concentrations of these factors for 4 weeks differentiated into multilayer epithelial cell cultures resembling the lining of the swine respiratory tract. Influenza virus infection and replication were examined in these cultures. RESULTS/CONCLUSIONS: Retinoic acid promoted ciliogenesis, whereas epidermal growth factor controlled the thickness of the pseudoepithelium. The optimal concentrations for differentiated swine cell cultures were 1·5 ng/ml epidermal growth factor and 100nm retinoic acid. Influenza A viruses infected and productively replicated in these cultures in the absence of exogenous trypsin, suggesting that the cultures express a protease capable of activating influenza virus hemagglutinin. Differences in virus infection and replication characteristics found previously in pigs in vivo were recapitulated in the swine cultures. This system could be a useful tool for a range of applications, including investigating influenza virus species specificity, defining cell tropism of influenza viruses in the swine respiratory epithelium, and studying other swine respiratory diseases.

History of Swine influenza.

Swine influenza is a continual problem for the Swine industry and can pose a public health threat as evidenced by the 2009 H1N1 influenza virus pandemic. Given its importance, it is not surprising to find papers describing the disease from the early 20th century. In this chapter, we discuss the history of Swine influenza, the important role swine influenza virus has played in our understanding of influenza virus pathogenesis and virology, and its impact on public health worldwide.

Infectivity phenotypes of H3N2 influenza A viruses in primary swine respiratory epithelial cells are controlled by sialic acid binding.

BACKGROUND: In the late 1990s, triple reassortant H3N2 influenza A viruses emerged and spread widely in the US swine population. We have shown previously that an isolate representative of this virus-lineage, A/Swine/Minnesota/593/99 (Sw/MN), exhibits phenotypic differences compared to a wholly human-lineage H3N2 virus isolated during the same time period, A/Swine/Ontario/00130/97 (Sw/ONT). Specifically, Sw/MN was more infectious for pigs and infected a significantly higher proportion of cultured primary swine respiratory epithelial cells (SRECs). In addition, reverse genetics-generated Sw/MN × Sw/ONT reassortant and point mutant viruses demonstrated that the infectivity phenotypes in SRECs were strongly dependent on three amino acids within the hemagglutinin (HA) gene. OBJECTIVES: To determine the mechanism by which Sw/MN attains higher infectivity than Sw/ONT in SRECs. METHODS: A/Swine/Minnesota/593/99, Sw/ONT, and mutant (reverse genetics-generated HA reassortant and point mutant) viruses were compared at various HA-mediated stages of infection: initial sialic acid binding, virus entry, and the pH of virus-endosome fusion. RESULTS/CONCLUSIONS: Sialic acid binding was the sole stage where virus differences directly paralleled infectivity phenotypes in SRECs, indicating that binding is the primary mechanism responsible for differences in the infectivity levels of Sw/MN and Sw/ONT.

Cross-protection between antigenically distinct H1N1 swine influenza viruses from Europe and North America.

BACKGROUND: An avian-like H1N1 swine influenza virus (SIV) is enzootic in swine populations of Western Europe. The virus is antigenically distinct from H1N1 SIVs in North America that have a classical swine virus-lineage H1 hemagglutinin, as does the pandemic (H1N1) 2009 virus. However, the significance of this antigenic difference for cross-protection among pigs remains unknown. OBJECTIVES: We examined protection against infection with a North American triple reassortant H1N1 SIV [A/swine/Iowa/H04YS2/04 (sw/IA/04)] in pigs infected with a European avian-like SIV [A/swine/Belgium/1/98 (sw/B/98)] 4 weeks earlier. We also examined the genetic relationships and serologic cross-reactivity between both SIVs and with a pandemic (H1N1) 2009 virus [A/California/04/09 (Calif/09)]. RESULTS: After intranasal inoculation with sw/IA/04, all previously uninfected control pigs showed nasal virus excretion, high virus titers in the entire respiratory tract at 4 days post-challenge (DPCh) and macroscopic lung lesions. Most pigs previously infected with sw/B/98 tested negative for sw/IA/04 in nasal swabs and respiratory tissues, and none had lung lesions. At challenge, these pigs had low levels of cross-reactive virus neutralizing and neuraminidase inhibiting (NI) antibodies to sw/IA/04, but no hemagglutination-inhibiting antibodies. They showed similar antibody profiles when tested against Calif/09, but NI antibody titers were higher against Calif/09 than sw/IA/04, reflecting the higher genetic homology of the sw/B/98 neuraminidase with Calif/09. CONCLUSIONS: Our data indicate that immunity induced by infection with European avian-like H1N1 SIV affords protection for pigs against North American H1N1 SIVs with a classical H1, and they suggest cross-protection against the pandemic (H1N1) 2009 virus.

Transmission of influenza A viruses between pigs and people, Iowa, 2002-2004.

BACKGROUND: Triple-reassortant (tr) viruses of human, avian, and swine origin, including H1N1, H1N2, and H3N2 subtypes, emerged in North American swine herds in 1998 and have become predominant. While sporadic human infections with classical influenza A (H1N1) and with tr-swine influenza viruses have been reported, relatively few have been documented in occupationally exposed swine workers (SW). METHODS: We conducted a 2-year (2002-2004) prospective cohort study of transmission of influenza viruses between pigs and SW from a single pork production company in Iowa. Respiratory samples were collected and tested for influenza viruses from SW and from pigs under their care through surveillance for influenza-like illnesses (ILI). Serial blood samples from study participants were tested by hemagglutination inhibition (HI) for antibody seroconversion against human and swine influenza viruses (SIV), and antibody seroprevalence was compared to age-matched urban Iowa blood donors. RESULTS: During the first year, 15 of 88 SW had ILI and were sampled; all were culture-negative for influenza. During the second year, 11 of 76 SW had ILI and were sampled; one was culture-positive for a human seasonal H3N2 virus. Among 20 swine herd ILI outbreaks sampled, influenza A virus was detected by rRT-PCR from 17 with 11 trH1N1 and five trH3N2 virus isolates cultured. During both years, HI geometric mean titers were significantly higher among SW compared to blood donor controls for three SIV: classical swine Sw/WI/238/97 (H1N1), tr Sw/IN/9K035/99 (H1N2), and trSw/IA/H02NJ56371/02 (H1N1)] (P < 0·0001). CONCLUSIONS: SW had serologic evidence for infection with both swine and human influenza viruses and were exposed to diverse influenza virus strains circulating in pigs. Influenza virus surveillance among pigs and SW should be encouraged to better understand cross-species transmission and diversity of influenza viruses at the human-swine interface.

Glycan analysis and influenza A virus infection of primary swine respiratory epithelial cells: the importance of NeuAc{alpha}2-6 glycans.

To better understand influenza virus infection of pigs, we examined primary swine respiratory epithelial cells (SRECs, the primary target cells of influenza viruses in vivo), as a model system. Glycomic profiling of SRECs by mass spectrometry revealed a diverse range of glycans terminating in sialic acid or GalαGal. In terms of sialylation, α2-6 linkage was more abundant than α2-3, and NeuAc was more abundant than NeuGc. Virus binding and infection experiments were conducted to determine functionally important glycans for influenza virus infection, with a focus on recently emerged swine viruses. Infection of SRECs with swine and human viruses resulted in different infectivity levels. Glycan microarray analysis with a high infectivity "triple reassortant" virus ((A/Swine/MN/593/99 (H3N2)) that spread widely throughout the North American swine population and a lower infectivity human virus isolated from a single pig (A/Swine/ONT/00130/97 (H3N2)) showed that both viruses bound exclusively to glycans containing NeuAcα2-6, with strong binding to sialylated polylactosamine and sialylated N-glycans. Treatment with mannosamine precursors of sialic acid (to alter NeuAc/NeuGc abundances) and linkage-specific sialidases prior to infection indicated that the influenza viruses tested preferentially utilize NeuAcα2-6-sialylated glycans to infect SRECs. Our data indicate that NeuAcα2-6-terminated polylactosamine and sialylated N-glycans are important determinants for influenza viruses to infect SRECs. As NeuAcα2-6 polylactosamine glycans play major roles in human virus infection, the importance of these receptor components in virus infection of swine cells has implications for transmission of viruses between humans and pigs and for pigs as possible adaptation hosts of novel human influenza viruses.

Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey.

BACKGROUND: Maternal infection with influenza and other pathogens during pregnancy has been associated with increased risk for schizophrenia and neurodevelopmental disorders. In rodent studies, maternal inflammatory responses to influenza affect fetal brain development. However, to verify the relevance of these findings to humans, research is needed in a primate species with more advanced prenatal corticogenesis. METHODS: Twelve pregnant rhesus monkeys were infected with influenza, A/Sydney/5/97 (H3N2), 1 month before term (early third trimester) and compared with 7 control pregnancies. Nasal swabs and blood samples confirmed viral shedding and immune activation. Structural magnetic resonance imaging was conducted at 1 year; behavioral development and cortisol reactivity were also assessed. RESULTS: Maternal infections were mild and self-limiting. At birth, maternally derived influenza-specific immunoglobulin G was present in the neonate, but there was no evidence of direct viral exposure. Birth weight and gestation length were not affected, nor were infant neuromotor, behavioral, and endocrine responses. However, magnetic resonance imaging analyses revealed significant reductions in cortical gray matter in flu-exposed animals. Regional analyses indicated the largest gray matter reductions occurred bilaterally in cingulate and parietal areas; white matter was also reduced significantly in the parietal lobe. CONCLUSIONS: Influenza infection during pregnancy affects neural development in the monkey, reducing gray matter throughout most of the cortex and decreasing white matter in parietal cortex. These brain alterations are likely to be permanent, given that they were still present at the monkey-equivalent of older childhood and thus might increase the likelihood of later behavioral pathology.

Serologic cross-reactivity with pandemic (H1N1) 2009 virus in pigs, Europe.

We tested serum samples from pigs infected or vaccinated with European swine influenza viruses (SIVs) in hemagglutination-inhibition assays against pandemic (H1N1) 2009 virus and related North American SIVs. We found more serologic cross-reaction than expected. Data suggest pigs in Europe may have partial immunity to pandemic (H1N1) 2009 virus.

Influenza: pigs, people and public health

Text about the influenza A virus, its subtypes and interspecies transmission. Document from 2004.

The dual DVM/MPH degree at the University of Wisconsin--Madison: a uniquely interdisciplinary collaboration.

The University of Wisconsin-Madison (UWM) launched a new Master of Public Health (MPH) degree program in 2005. This 42-credit MPH degree consists of 18 core and 14 elective course credits, two seminar credits, and eight field project/culminating experience credits. Unique strengths of the program include its strongly interdisciplinary philosophy, encompassing both health science (human medicine, veterinary medicine, pharmacy, nursing) and social science units on campus, and its emphasis on service learning through instructional and field project ties to the public-health community of the state and beyond. To date, the program has admitted 87 students, including full-time students as well as part-time students who continue to work in the health care and/or public-health sectors. The program is currently proceeding with the process for accreditation through the Council for Education in Public Health. In 2007, a formal dual DVM/MPH program was approved to allow students to integrate DVM and MPH training and complete both degrees in a total of five years. Nine MPH students over the first three years of admissions have been individuals affiliated with veterinary medicine (five DVM students and four post-graduate veterinarians).

Amino acid 226 in the hemagglutinin of H4N6 influenza virus determines binding affinity for alpha2,6-linked sialic acid and infectivity levels in primary swine and human respiratory epithelial cells.

Avian lineage H4N6 influenza viruses previously isolated from pigs differ at hemagglutinin amino acids 226 and 228 from H4 subtype viruses isolated from birds. Using a parental H4N6 swine isolate and hemagglutinin mutant viruses (at residues 226 and/or 228), we determined that viruses which contain L226 had a higher affinity for sialic acid alpha2,6 galactose (SAalpha2,6Gal) and a higher infectivity level for primary swine and human respiratory epithelial cells, whereas viruses which contain Q226 had lower SAalpha2,6Gal affinity and lower infectivity levels for both types of cells. Using specific neuraminidases, we found that irrespective of their relative binding preferences, all of the influenza viruses examined utilized SAalpha2,6Gal to infect swine and human cells.

Identification of amino acids in the HA of H3 influenza viruses that determine infectivity levels in primary swine respiratory epithelial cells.

In the late 1990s, triple reassortant H3N2 influenza A viruses emerged and spread widely within the swine population of the United States. We have shown previously that an isolate representative of this lineage of viruses, A/Swine/Minnesota/593/99 (Sw/MN), has higher infectivity and accelerated replication kinetics in pigs, compared to a human-lineage H3N2 virus isolated from a pig during the same time period, A/Swine/Ontario/00130/97 (Sw/ONT [Landolt, G.A., Karasin, A.I., Phillips, L., Olsen, C.W., 2003. Comparison of the pathogenesis of two genetically different H3N2 influenza A viruses in pigs. J. Clin. Microbiol. 41, 1936-1941]). Additional in vivo experiments using reverse genetics-generated reassortant viruses demonstrated that these phenotypes are dependent upon the HA and/or NA genes (Landolt, G.A., Karasin, A.I., Schutten, M.M., Olsen, C.W., 2006. Restricted infectivity of a human-lineage H3N2 influenza A virus in pigs is hemagglutinin and neuraminidase gene dependent. J. Clin. Microbiol. 44, 297-301). To further study the infectivity of influenza viruses for pigs, we developed a primary swine respiratory epithelial cell (SREC) culture model. In SRECs, Sw/MN infects a significantly higher number of cells compared to Sw/ONT. Using reverse genetics-generated Sw/MN x Sw/ONT reassortant viruses we demonstrate that the infectivity phenotypes of these viruses in SRECs are strongly dependent upon the HA gene. Using chimeras and point directed mutations within the HA genes, we have identified amino acids that, either alone or in combination with other amino acids, impact infectivity. In particular, amino acid 138 is the dominant factor in determining infectivity levels in SRECs.

Creating a center for global health at the University of Wisconsin-Madison.

Globalization, migration, and widespread health disparities call for interdisciplinary approaches to improve health care at home and abroad. Health professions students are pursuing study abroad in increasing numbers, and universities are responding with programs to address these needs. The University of Wisconsin (UW)-Madison schools of medicine and public health, nursing, pharmacy, veterinary medicine, and the division of international studies have created an interdisciplinary center for global health (CGH). The CGH provides health professions and graduate students with courses, field experiences, and a new Certificate in Global Health. Educational programs have catalyzed a network of enthusiastic UW global health scholars. Partnerships with colleagues in less economically developed countries provide the foundation for education, research, and service programs. Participants have collaborated to improve the education of health professionals and nutrition in Uganda; explore the interplay between culture, community development, and health in Ecuador; improve animal health and address domestic violence in Mexico; and examine successful public health efforts in Thailand. These programs supply students with opportunities to understand the complex determinants of health and structure of health systems, develop adaptability and cross-cultural communication skills, experience learning and working in interdisciplinary teams, and promote equity and reduce health disparities at home and abroad. Based on the principles of equity, sustainability, and reciprocity, the CGH provides a strong foundation to address global health challenges through networking and collaboration among students, staff, and faculty within the UW and beyond.

Up to new tricks - a review of cross-species transmission of influenza A viruses.

Influenza is a highly contagious disease that has burdened both humans and animals since ancient times. In humans, the most dramatic consequences of influenza are associated with periodically occurring pandemics. Pandemics require the emergence of an antigenically novel virus to which the majority of the population lacks protective immunity. Historically, influenza A viruses from animals have contributed to the generation of human pandemic viruses and they may do so again in the future. It is, therefore, critical to understand the epidemiological and molecular mechanisms that allow influenza A viruses to cross species barriers. This review summarizes the current knowledge of influenza ecology, and the viral factors that are thought to determine influenza A virus species specificity.

Cases of swine influenza in humans: a review of the literature.

As the threat of a pandemic looms, improvement in our understanding of interspecies transmission of influenza is necessary. Using the search terms "swine," "influenza," and "human," we searched the PubMed database in April 2006 to identify publications describing symptomatic infections of humans with influenza viruses of swine origin. From these reports, we extracted data regarding demographic characteristics, epidemiological investigations, and laboratory results. We found 50 cases of apparent zoonotic swine influenza virus infection, 37 of which involved civilians and 13 of which involved military personnel, with a case-fatality rate of 14% (7 of 50 persons). Most civilian subjects (61%) reported exposure to swine. Although sporadic clinical cases of swine influenza occur in humans, the true incidence of zoonotic swine influenza virus infection is unknown. Because prior studies have shown that persons who work with swine are at increased risk of zoonotic influenza virus infection, it is prudent to include them in pandemic planning efforts.

Swine workers and swine influenza virus infections.

In 2004, 803 rural Iowans from the Agricultural Health Study were enrolled in a 2-year prospective study of zoonotic influenza transmission. Demographic and occupational exposure data from enrollment, 12-month, and 24-month follow-up encounters were examined for association with evidence of previous and incident influenza virus infections. When proportional odds modeling with multivariable adjustment was used, upon enrollment, swine-exposed participants (odds ratio [OR] 54.9, 95% confidence interval [CI] 13.0-232.6) and their nonswine-exposed spouses (OR 28.2, 95% CI 6.1-130.1) were found to have an increased odds of elevated antibody level to swine influenza (H1N1) virus compared with 79 nonexposed University of Iowa personnel. Further evidence of occupational swine influenza virus infections was observed through self-reported influenza-like illness data, comparisons of enrollment and follow-up serum samples, and the isolation of a reassortant swine influenza (H1N1) virus from an ill swine farmer. Study data suggest that swine workers and their nonswine-exposed spouses are at increased risk of zoonotic influenza virus infections.

Triple reassortant H3N2 influenza A viruses, Canada, 2005.

Since January 2005, H3N2 influenza viruses have been isolated from pigs and turkeys throughout Canada and from a swine farmer and pigs on the same farm in Ontario. These are human/classical swine/avian reassortants similar to viruses that emerged in US pigs in 1998 but with a distinct human-lineage neuraminidase gene.