Characterizing the One Health workforce to promote interdisciplinary, multisectoral approaches in global health problem-solving.

BACKGROUND: In recognition of the interconnected nature of complex challenges such as COVID-19, a collaborative, multisectoral, and transdisciplinary approach, referred to as One Health, has been employed to address sustainable development and strengthen global health security. Although significant investments have been made to build global health capacity, characterization of the One Health is absent from the literature. METHODS AND FINDINGS: We collected and analyzed perspectives from students, graduates, workers, and employers in One Health through a multinational online survey across health disciplines and sectors. Respondents were recruited through professional networks. A total of 828 respondents from 66 countries participated, representing governmental and academic institutions and students, among others; 57% were female, and 56% had completed professional health degrees. Interpersonal communication, communication with non-scientific audiences, and the ability to work in transdisciplinary teams were valued in the workplace and were considered essential competencies to build an interdisciplinary health workforce. Employers indicated difficulty recruiting workers, while workers indicated limited availability of positions. Employers identified limited funding and ill-defined career pathways as prominent challenges for retaining One Health workers. CONCLUSIONS: Successful One Health workers use interpersonal skills and scientific knowledge to address complex health challenges. Aligning the definition of One Health will likely improve the matching of job seekers and employers. Encouraging the employment of the One Health approach for a diverse range of positions, even if they do not explicitly include "One Health" in the job title, and clarifying the expectations, roles and responsibilities within a transdisciplinary team will lead to building a stronger workforce. As One Health has evolved to address food insecurity, emerging diseases, and antimicrobial resistance, it holds promise for supporting an interdisciplinary global health workforce that can make substantial progress on Sustainable Development Goals and improve global health security for all.

Strengthening multi-sectoral collaboration on critical health issues: One Health Systems Mapping and Analysis Resource Toolkit (OH-SMART) for operationalizing One Health.

Addressing critical global health issues, such as antimicrobial resistance, infectious disease outbreaks, and natural disasters, requires strong coordination and management across sectors. The One Health approach is the integrative effort of multiple sectors working to attain optimal health for people, animals, and the environment, and is increasingly recognized by experts as a means to address complex challenges. However, practical application of the One Health approach has been challenging. The One Health Systems Mapping and Analysis Resource Toolkit (OH-SMART) introduced in this paper was designed using a multistage prototyping process to support systematic improvement in multi-sectoral coordination and collaboration to better address complex health concerns through an operational, stepwise, and practical One Health approach. To date, OH-SMART has been used to strengthen One Health systems in 17 countries and has been deployed to revise emergency response frameworks, improve antimicrobial resistance national action plans and create multi agency infectious disease collaboration protocols. OH-SMART has proven to be user friendly, robust, and capable of fostering multi-sectoral collaboration and complex system-wide problem solving.

Piloting the One Health Systems Mapping and Analysis Resource Toolkit in Indonesia.

As a global network, countries are being asked to meet goals set forth in the Global Health Security Agenda (GHSA) for a workforce capable of effective and efficient prevention, detection and response to infectious disease threats. There is great need for a cross-sectoral workforce that can innovate and problem-solve. To achieve GHSA goals, countries need a way to visualize their existing system, identify opportunities for improvement, and achieve improved cross-sectoral interactions. The One Health Systems Mapping and Analysis Resource Toolkit (OH-SMART) was successfully piloted in West Sumatra, Indonesia, and was used to enhance multi-agency collaboration around infectious disease outbreaks and proved to be an adaptable, scalable process requiring minimal resources. The authors present OH-SMART as a potential tool to help countries analyze their existing health system and create relevant action steps to improve cross-sectoral collaborations.

Characterization of multiple pathways modulating aggression in the male clouded leopard (Neofelis nebulosa).

Breeding clouded leopards (Neofelis nebulosa) ex situ has been a challenge, primarily due to extreme and often fatal male aggression toward females. This study's aim was to determine the degree to which two possible mechanisms-serotonergic pathways and circulating testosterone levels-affect aggressive behavior. Male clouded leopard behavioral and hormonal data were collected during a series of behavior tests administered before and after treatment with either an anxiety-reducing tricyclic antidepressant (clomipramine) or a GnRH agonist (deslorelin). Results showed that clomipramine treatment decreased "overall activity" (P = 0.054) and increased "lying down" (P = 0.0043) and hiding in a "nest box" (P = 0.0023). Clomipramine treatment also decreased the incidence of "growling" during a mirror image stimulation test, relative to non-test periods (P < 0.0001 pre-drug treatment; P = 0.242 peri-drug treatment), indicating reduced aggression. Suppression of the reproductive axis via deslorelin treatment resulted in significant decreases in circulating androgen (P < 0.0001) and glucocorticoid (P < 0.0001), accompanied by decreased aggressive behaviors, including "swatting" (P = 0.0476), "tail flicking" (P = 0.0409), and "growling" during the behavior reaction tests: mirror image stimulation (P < 0.0001 pre-drug treatment: P = 0.7098 peri-drug treatment) and unfamiliar people test (P < 0.0001 pre-drug treatment: P = 0.2666 peri-drug treatment) relative to non-test periods. Both drug treatments provide evidence that multiple mechanisms modulate aggressive behavior in the male clouded leopard, suggesting that serotonergic modulation coupled with circulating androgens may aid in the formation of successful breeding pairs. Zoo Biol. 35:474-486, 2016. © 2016 Wiley Periodicals, Inc.

Leptospira Seroprevalence and Risk Factors in Health Centre Patients in Hoima District, Western Uganda.

BACKGROUND: The burden of human leptospirosis in Uganda is unknown. We estimated the seroprevalence of Leptospira antibodies, probable acute/recent leptospirosis, and risk factors for seropositivity in humans in rural Western Uganda. METHODOLOGY AND PRINCIPAL FINDINGS: 359 non-pregnant adults visiting the Kikuube and Kigorobya Health Centers were sequentially recruited during March and April 2014. A health history survey and serum were collected from consented participants. Overall, 69% reported having fever in the past year, with 49% reporting malaria, 14% malaria relapse, 6% typhoid fever, 3% brucellosis, and 0% leptospirosis. We tested sera by microscopic agglutination test (MAT) against eight Leptospira serovars representing seven serogroups. Leptospira seroprevalence was 35% (126/359; 95%CI 30.2-40.3%) defined as MAT titer ≥ 1:100 for any serovar. The highest prevalence was against L. borgpetersenii Nigeria (serogroup Pyrogenes) at 19.8% (71/359; 95%CI 15.9-24.4%). The prevalence of probable recent leptospirosis (MAT titer ≥1:800) was 1.9% (95%CI 0.9-4.2%) and uniquely related to serovar Nigeria (serogroup Pyrogenes). Probable recent leptospirosis was associated with having self-reported malaria within the past year (p = 0.048). Higher risk activities included skinning cattle (n = 6) with 12.3 higher odds (95%CI 1.4-108.6; p = 0.024) of Leptospira seropositivity compared with those who had not. Participants living in close proximity to monkeys (n = 229) had 1.92 higher odds (95%CI 1.2-3.1; p = 0.009) of seropositivity compared with participants without monkeys nearby. CONCLUSIONS/SIGNIFICANCE: The 35% prevalence of Leptospira antibodies suggests that exposure to leptospirosis is common in rural Uganda, in particular the Nigeria serovar (Pyrogenes serogroup). Leptospirosis should be a diagnostic consideration in febrile illness and "smear-negative malaria" in rural East Africa.

Description of the Microsporidian Parasite, Heterosporis sutherlandae n. sp., Infecting Fish in the Great Lakes Region, USA.

Heterosporosis is an increasingly important microsporidian disease worldwide, impacting wild and farmed raised fishes in both marine and freshwater environments. A previously undescribed species (Heterosporis sp.), with widespread distribution in the Great Lakes region, was the subject of this study. Three angler-caught fish were submitted to the Minnesota Veterinary Diagnostic Laboratory from 2009-2010 with lesions caused by intracellular proliferation of parasitic spores, resulting in destruction and eventual widespread necrosis of the host skeletal muscles. Mature ovoid (5.8 x 3.5 µm) spores of a microsporidian parasite, consistent with the genus Heterosporis, were observed by light and electron microscopy. Molecular identification was performed using primer walking to obtain a near-complete rRNA gene sequence (~3,600 bp). A unique species of Heterosporis was identified, demonstrating less than 96% sequence identity to other published Heterosporis sp. on the basis of partial rRNA gene sequence analysis. Heterosporis sutherlandae n. sp. (formerly Heterosporis sp.) was identified in yellow perch (Perca flavescens), northern pike (Esox lucius) and walleye (Sander vitreus) from inland lakes in Minnesota and Wisconsin. Previous research suggests this species may be even more widespread in the Great Lakes region and should be reexamined using molecular techniques to better understand the distribution of this novel species.

Disease risk in a dynamic environment: the spread of tick-borne pathogens in Minnesota, USA.

As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease.

Progestin priming before gonadotrophin stimulation and AI improves embryo development and normalises luteal function in the cat.

Exogenous gonadotrophins administered before AI can adversely alter endocrine dynamics and inhibit embryo development in felids. In the present study, we tested the hypothesis that priming the domestic cat ovary with progestin mitigates the negative influence of gonadotrophin therapy by normalising early embryogenesis and luteal function. Queens were given either: (1) progestin pretreatment plus chorionic gonadotrophins (n=8; primed); or (2) gonadotrophins only (n=8; unprimed). Ovulatory response was assessed laparoscopically, and cats with fresh corpora lutea (CL) were inseminated in utero. Ovariohysterectomy was performed 3 days later to recover intra-oviductal embryos for in vitro culture; one ovary was prepared for histology, and CL from the remaining ovary were excised and assessed for progesterone content and targeted gene expression. Of the six primed and seven unprimed queens inseminated, embryo(s) were recovered from five individuals per group. Embryos from progestin-primed donors more closely simulated normal stage in vivo development (P<0.05). No 2- or 4-cell embryos from either group developed beyond 16-cells in vitro; however, 50% of unprimed and 66.7% of primed (P>0.05) 5-16-cell embryos progressed to morulae or blastocysts by Day 4 of culture. Although histological characteristics were unaffected by progestin priming (P>0.05), luteal progesterone was unusually high (P<0.05) in unprimed compared with primed cats (72.4±5.8 vs. 52.2±5.5 ng mg(-1), respectively). Two genes associated with progesterone biosynthesis (luteinising hormone receptor and 3ß-hydroxysteroid dehydrogenase) were upregulated in unprimed versus primed individuals (P=0.05 and P<0.05, respectively), indicating potential mechanistic pathways for the protective influence of pre-emptive progestin treatment. Building on earlier findings that progestin priming prevents spontaneous ovulation, increases ovarian sensitivity to gonadotrophins and ensures a normative endocrine environment, the present study demonstrates that pretreatment with this steroid also benefits embryo development and normalisation of early luteal function.

One Health: Lessons Learned from East Africa.

Africa is faced with many of the most daunting challenges of our time. It comprises roughly 15% of the world's human population, and most of its countries are perpetually ranked "Low" on the United Nations' Human Development Index. On the other hand, Africa has arguably the largest proportion of intact natural ecosystems, biodiversity, and sociocultural capital and the lowest impact on global warming of any continent. Thus, African leaders are faced with competing demands and values among a multitude of complex issues, such as high human population growth, extreme poverty, food insecurity, land use policy, climate change, and biodiversity conservation. In this context, building sustainable national systems for human and/or animal health is one of the grand challenges of this generation. Today's complex global health and development challenges require long-term commitment and a range of approaches that are too broad for any one discipline, institution, or country to implement on its own. The One Health concept recognizes the interconnectedness of global health issues and, as such, promotes the importance of and need for international, interdisciplinary, and cross-sectoral communication and collaboration at local, national, and international levels. By taking advantage of natural cultural tendencies for shared leadership, resource allocation, and community values, African leaders are currently proactively demonstrating the principles of One Health, and thus becoming a model for this global vision. And by focusing on partnerships rather than donor-recipient relationships, they are fostering the development of shared priorities and are increasingly driving their own health agenda to fulfill their own needs.

Oral progestin priming increases ovarian sensitivity to gonadotropin stimulation and improves luteal function in the cat.

As the only domesticated species known to exhibit both induced and spontaneous ovulation, the cat is a model for understanding the nuances of ovarian control. To explore ovarian sensitivity to exogenous gonadotropins and the influence of progestin priming, we conducted a study of queens that were down-regulated with oral progestin or allowed to cycle normally, followed by low or high doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Our metrics included 1) fecal steroid metabolite profiles before and after ovulation induction, 2) laparoscopic examination of ovarian follicles and corpora lutea (CL) on Days 2 and 17 (Day 0 = hCG administration), and 3) ovariohysterectomy (Day 17) to assess CL progesterone concentrations, morphometrics, and histology. Reproductive tracts from time-matched, naturally mated queens (n = 6) served as controls. Every progestin-primed cat (n = 12) produced the desired response of morphologically similar, fresh CL (regardless of eCG/hCG dose) by Day 2, whereas 41.7% of unprimed counterparts (n = 12) failed to ovulate or had variable-aged CL suggestive of prior spontaneous ovulation (P < 0.05). The ovarian response to low, but not high, eCG/hCG was improved (P < 0.05) in primed compared to unprimed cats, indicating increased sensitivity to gonadotropin in the progestin-primed ovary. Progestin priming prevented hyperelevated fecal steroid metabolites and normalized CL progesterone capacity, but only when combined with low eCG/hCG. However, priming failed to prevent ancillary CL formation, smaller CL mass, or abnormal luteal cell density, which were common to all eCG/hCG-treated cats. Thus, the domestic cat exposed to eCG/hCG produces CL with structural and functional aberrations. These anomalies can be partially mitigated by progestin priming, possibly due to a protective effect of progestin associated with enhanced ovarian sensitivity to gonadotropins.

Toxoplasma gondii in feral American minks at the Maullín river, Chile.

American mink (Neovison vison) is a widely distributed invasive species in southern Chile. Thirty four feral minks were trapped at two distinct sites (rural and peri-urban), diet analyzed and Toxoplasma gondii exposure compared using PCR and specific antibodies. Serum samples were evaluated using a commercial latex agglutination test where a titer ≥ 1:32 was considered positive. Of 30 mink analyzed, 21 (70%) were positive to T. gondii antibodies, with titers ranging from 1:32 to 1:2048. As expected, adult mink showed higher seroprevalence of exposure to T. gondii (18/21) than young mink (3/9) (P=0.008). There was not statistically significant difference between sex groups (P=0.687). Differences in seroprevalence were observed between the two sample sites with a higher proportion of positive individuals in the peri-urban area, and therefore, closer to human settlements (35.7% vs. 100%, P=0.0001). Individuals positive to T. gondii using PCR and/or serology showed similar differences by site with higher infected individuals in peri-urban areas (58.8% vs. 100%, P=0.007). Diet of American mink based in fecal composition analyses was mainly based on crustaceans (frequency of occurrence: crustaceans=100%, birds and rodents<7%), suggesting that the high observed prevalence of T. gondii infection might be more associated with its aquatic behavior (e.g. ingestion of oocysts in contaminated fresh water) than with their trophic behavior (e.g. preying over species that can have T. gondii cysts in their tissues). As an invasive species potentially subject to routine culling to maintain population sizes under control, minks could be used as a sentinel species to monitor pathogens of public and wildlife health importance, such as T. gondii, in aquatic environments.

Progestin exposure before gonadotropin stimulation improves embryo development after in vitro fertilization in the domestic cat.

This study investigated the influence of progestin priming and ovarian quiescence on response to exogenous gonadotropin stimulation in the cat. Because a subpopulation of cats routinely ovulated spontaneously, there also was the opportunity to examine the ovary's reaction to the added impact of endogenously secreted progestagen. Queens were given 1) equine chorionic gonadotropin (eCG) plus human chorionic gonadotropin (hCG) only (control; n = 9 cats), 2) GnRH antagonist (antide) injections followed by eCG and hCG (n = 9), and 3) a progestin implant (levonorgestrel) followed by eCG and hCG (n = 9). Laparoscopy was used to assess ovarian activity and aspirate follicular oocytes that were graded on the basis of morphology. In five cats per treatment, half of the high-quality oocytes were assessed for glucose, pyruvate, and lactate metabolism as well as nuclear maturation. Remaining oocytes were inseminated in vitro, cultured, and examined at 72 h after insemination for cleavage. In the remaining four cats per treatment, all oocytes were inseminated in vitro and assessed at 72, 120, and 168 h after insemination for embryo developmental stage. Cats pretreated with progestin had more follicles and produced more embryos per donor (including at the combined morula/blastocyst stage) than controls or females treated with GnRH antagonist (P < 0.05). There were no differences among groups (P > 0.05) in oocyte carbohydrate metabolism, nuclear maturation metrics, or fertilization success, although there was a tendency toward improvements in all three (P < 0.2) in progestin-treated females. Interestingly, cats that spontaneously ovulated within 60 days of treatment onset also produced more embryos per cat than induced-ovulation counterparts (P < 0.05). Results indicate that prior exposure to exogenous progestin (via implant) or endogenous progestagen (via spontaneous ovulation) improves ovarian responsiveness to gonadotropins in the cat through a mechanism that is independent of the induction of ovarian quiescence.

Hematology, serum chemistry, and body mass of free-ranging and captive Canada lynx in Minnesota.

Baseline blood chemistry data could be particularly valuable if reference values from free-ranging populations of rare or endangered species are not available. The Canada lynx (Lynx canadensis) is listed as threatened under the Endangered Species Act in the conterminous United States, even though the species is managed as a furbearer in Alaska and in most provinces of Canada. Body mass, blood chemistry, and hematologic data for free-ranging lynx were collected from 2003 to 2007 and for captive lynx from 1984 to 2007. Up to 2 yr of age, captive lynx were consistently heavier than free-ranging lynx. Body mass of adult free-ranging lynx was similar to body mass of captive adult lynx. Some differences in blood chemistry between free-ranging and captive lynx were statistically significant, but most measured values were within reference ranges for domestic cats. Free-ranging lynx had higher concentrations of aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen than did captive lynx, and these were outside the reference value ranges for domestic cats. Alkaline phosphatase and phosphorus were higher in juveniles (<12 mo when captured) as compared to adults. Free-ranging lynx maintained body mass between serial captures. Hematologic values, blood chemistry values, and body mass of free-ranging Canada lynx provide support for the hypothesis that Canada lynx in Minnesota, at the southern edge of their range, are in normal physical condition.

Priming with progestin, but not GnRH antagonist, induces a consistent endocrine response to exogenous gonadotropins in induced and spontaneously ovulating cats.

Ovarian sensitivity to exogenous gonadotropin stimulation (equine chorionic gonadotropin [eCG] and human chorionic gonadotropin [hCG]) following pre-treatment with a progestin (levonorgestrel) versus GnRH antagonist (antide) was studied in cats known to be induced versus spontaneous ovulators. Queens were assigned to one of three treatments: (1) levonorgestrel implants+eCG/hCG (n=7 cats); (2) antide injections+eCG/hCG (n=7) or (3) eCG/hCG alone (control; n=7). Hormonal metabolites were assessed in fecal samples collected daily for 60 days before and during the 37 days inhibitory pre-treatment and for more than 60 days after eCG/hCG. Fecal metabolites of estradiol and progesterone were measured by radioimmunoassay. Females that maintained baseline progesterone were considered induced ovulators, whereas cats that exhibited a luteal phase before inhibition treatment were classified as spontaneous ovulators. Based on fecal hormone profiles, levonorgestrel thoroughly inhibited ovarian activity, whereas antide synchronized follicular phases but did not induce complete ovarian down-regulation. Both treatments prevented ovulation in spontaneous ovulators, but neither caused regression of existing corpora lutea (CL). Levonorgestrel, but not antide, pre-treatment resulted in a quiescent ovary at the time of eCG injection, yet endocrine responses to eCG/hCG were not different among treatments. Interestingly, spontaneously ovulating females exhibited a prolonged estradiol response to gonadotropin stimulation compared to induced ovulators, and this prolonged estradiol surge was replicated by levonorgestrel pre-treatment. Thus, the progestin levonorgestrel effectively suppresses follicular and luteal activity in the cat, resulting in a more consistent response to gonadotropin stimulation, even in females prone to spontaneous ovulation.

Ovarian control for assisted reproduction in the domestic cat and wild felids.

Of the 37 felid species, all but the domestic cat are classified as threatened with extinction in all or part of their native range. Additionally, the domestic cat is a valuable model for human biomedical research. Propagating some wild felids as well as domestic cat populations serving as human models is a major challenge primarily due to difficulties in transporting animals between facilities to ensure the pairing of genetically matched individuals, behavioral incompatibility between pairs and low fertility. Artificial insemination (AI) and in vitro fertilization/embryo transfer (IVF/ET) are powerful tools for helping manage rare populations. Developing successful assisted reproductive techniques requires knowledge of the female reproductive cycle and precise control of ovarian activity. Successful ovarian stimulation for AI and IVF/ET has been achieved in at least one-third of all cat species. However, sensitivity to a given gonadotropin treatment appears highly species-specific, and poor responses are common, particularly in felid species that exhibit spontaneous ovulations. Furthermore, current gonadotropin regimens have been demonstrated to perturb female reproductive function often leading to reduced fertility. Overall, ovarian response to exogenous hormonal stimulation has been highly variable, and pregnancy success after AI or IVF/ET remains low (<20%) in most species. Therefore, there is an immediate need to develop improved regimens that would allow more predictable ovarian responses in felids. We contend that recent research involving the use of progestins to control the ovary prior to gonadotropin stimulation shows promise for providing consistent ovarian stimulation in felids.

GnRH agonist Lupron (leuprolide acetate) pre-treatments prevent ovulation in response to gonadotropin stimulation in the clouded leopard (Neofelis nebulosa).

In many species, controlling the ovary prior to induction of ovulation improves the success of ovarian response and artificial insemination (AI). We assessed the impact of suppression of estrus with the GnRH agonist, Lupron, on ovarian sensitivity to equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) in the clouded leopard. Seven female clouded leopards were given two injections of Lupron (3.75 mg IM) 23 d apart, followed 44 d later by eCG and hCG. Daily fecal samples were collected from 60 d before Lupron to 60 d after hCG. Fecal metabolites of estrogen (E) and progesterone (P) were measured by radioimmunoassay. Lupron decreased (P < 0.05) the number of E peaks during Lupron treatment compared to pre-Lupron. All females had baseline E and six of seven (86%) had nadir P on day of eCG. Exogenous gonadotropins induced E elevations in all females. However, mean E in the gonadotropin-provoked estrus was decreased (P < 0.05) compared to pre-Lupron estrous periods. Only one of seven (14%) females ovulated after eCG/hCG. In conclusion, estrous cycle control with Lupron resulted in predictable ovarian suppression prior to gonadotropin stimulation but altered ovarian sensitivity by an as yet unknown mechanism so that ovulation was inhibited, even when using a proven exogenous gonadotropin protocol.