The New South Wales Mouse Plague 2020-2021: A One Health description.

A mouse plague occurred in Eastern Australia from spring 2020 to winter 2021, impacting an area of around 180,000 km2. It harmed human physical and psychological health, damaged the natural and built environment, and endangered farmed, domestic and native animals. However, the mouse plague was overshadowed by the COVID-19 pandemic, especially as the end of the plague coincided with the arrival and surge of the COVID-19 delta strain in rural New South Wales (NSW). In this article, we systematically overview the multiple impacts of the plague and highlight their complex interactions. Using a One Health framework, we comprehensively review the i) human, ii) animal and iii) environmental impacts including economic dimensions. Given the damage that the mouse plague caused to infrastructure, we consider the environment from two perspectives: the natural and the built environment. This One Health description of the 2020-2021 mouse plague identifies priorities for preparedness, response and recovery at local, regional land levels to inform response and management of future mouse plague events in Australia. It also highlights the need for ongoing collaboration between researchers and practitioners in the human, animal and environmental health sectors.

Exploring patterns of female house mouse spatial organisation among outbreaking and stable populations.

The size and distribution of home ranges reflect how individuals within a population use, defend, and share space and resources, and may thus be an important predictor of population-level dynamics. Eruptive species, such as the house mouse in Australian grain-growing regions, are an ideal species in which to investigate variations in space use and home range overlap between stable and outbreaking populations. In this study, we use spatially explicit capture-recapture models to explore if space use and home range overlap among female mice could serve as indicators of changes in population density leading into summer. Additionally, we assess the sensitivity of space use and home range estimates to reduced recapture rates. Our analysis did not reveal variations in the spring spatial organisation of female mice based on existing capture-mark-recapture data. However, our study highlights the need to balance monitoring efforts within regions, emphasising the importance of exploring studies that can improve spatial recaptures by optimising trapping efforts. This is particularly important in Australian agricultural systems, where varying farm management practices may drive differences in population dynamics.

From chip to SNP: Rapid development and evaluation of a targeted capture genotyping-by-sequencing approach to support research and management of a plaguing rodent.

The management of invasive species has been greatly enhanced by population genetic analyses of multilocus single-nucleotide polymorphism (SNP) datasets that provide critical information regarding pest population structure, invasion pathways, and reproductive biology. For many applications there is a need for protocols that offer rapid, robust and efficient genotyping on the order of hundreds to thousands of SNPs, that can be tailored to specific study populations and that are scalable for long-term monitoring schemes. Despite its status as a model laboratory species, there are few existing resources for studying wild populations of house mice (Mus musculus spp.) that strike this balance between data density and laboratory efficiency. Here we evaluate the utility of a custom targeted capture genotyping-by-sequencing approach to support research on plaguing house mouse populations in Australia. This approach utilizes 3,651 hybridization capture probes targeting genome-wide SNPs identified from a sample of mice collected in grain-producing regions of southeastern Australia genotyped using a commercially available microarray platform. To assess performance of the custom panel, we genotyped wild caught mice (N = 320) from two adjoining farms and demonstrate the ability to correctly assign individuals to source populations with high confidence (mean >95%), as well as robust kinship inference within sites. We discuss these results in the context of proposed applications for future genetic monitoring of house mice in Australia.

Effects of harvesting and stubble management on abundance of pest rodents (Mus musculus) in a conservation agriculture system.

BACKGROUND: The shift to more environmentally sensitive agricultural practices over the last several decades has changed farmland landscapes worldwide. Changes including no-till and retaining high biomass mulch has been coincident with an increase in rodent pests in South Africa, India, South America and Europe, indicating a possible conflict between conservation agriculture (CA) and rodent pest management. Research on effects of various crop management practices associated with CA on pest rodent population dynamics is needed to anticipate and develop CA-relevant management strategies. RESULTS: During the Australian 2020-2021 mouse plague, farmers used postharvest stubble management practices, including flattening and/or cutting, to reduce stubble cover in paddocks to lessen habitat suitability for pest house mice. We used this opportunity to assess the effects of both harvest and stubble management on the movement and abundance of mice in paddocks using mouse trapping and radio tracking. We found that most tracked mice remained resident in paddocks throughout harvest, and that mouse population abundance was generally unaffected by stubble management. CONCLUSION: Recent conversions to CA practices have changed how pest house mice use cropped land. Management practices that reduce postharvest habitat complexity do not appear to reduce the attractiveness of paddocks to mice, and further research into new management strategies in addition to toxic bait use is required as part of an integrated pest management approach. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Acute oral toxicity of zinc phosphide: an assessment for wild house mice (Mus musculus).

Irregular plagues of house mice, Mus musculus, incur major economic impacts on agricultural production in Australia. The efficacy of zinc phosphide (ZnP), the only registered broadacre control agent for mice, is reported as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study, the sensitivity of mice (wild caught; outbred laboratory strain) was assessed using oral gavage of a range of ZnP concentrations. The estimated LD50 values (72-79 mg ZnP/kg body weight) were similar for each mouse group but are significantly higher than previously reported. The willingness of mice to consume ZnP-coated grains was determined. ZnP-coated grains (50 g ZnP/kg grain) presented in the absence of alternative food were consumed and 94% of wild mice died. Mice provided with alternative food and ZnP-coated wheat grains (either 25 or 50 g ZnP/kg grain) consumed toxic and non-toxic grains, and mortality was lower (33-55%). If a sublethal amount of ZnP-coated grain was consumed, aversion occurred, mostly when alternative food was present. The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions, ZnP-coated grains coated with a new higher dose (50 g ZnP/kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. Our unambiguous findings for house mice indicate a re-assessment of the ZnP loading for baits used for control of many rodents around the world may be warranted.

Electromyography of the Multifidus Muscle in Horses Trotting During Therapeutic Exercises.

Thoracolumbar pain has been identified in both human and equine patients. Rehabilitation and conditioning programs have focused specifically on improving trunk and abdominal muscle function (1-5). Equine exercise programs routinely incorporate ground poles and training devices for the similar goals of increasing spinal and core stability and strength (6-8). The multifidus muscle has been an area of focus due to atrophy associated with disease (9). To date, there have been no reports on the activity of the multifidus muscle in horses in relation to therapeutic exercises. Our objectives were to use electromyography to determine the average work performed and peak muscle activity of the multifidus in horses trotting, trotting over ground poles, trotting while wearing a resistance band-based training device and trotting while wearing the training device over ground poles. We hypothesized that ground poles and the training device would each increase average work performed and peak multifidus muscle activity. Right and left cranial thoracic locations showed significant increased muscle work and peak activation when horses were trotted over ground poles versus without. The peak activation was significantly greater in horses trotting over poles in both lumbar regions, but there was no significant change in peak activation in either location due to the training device. When the influence of the training device was investigated without ground poles, left caudal thoracic muscle work and peak activity, and right lumbar muscle work were significantly lower when using the training device, as compared to without. When the training device was combined with trotting over ground poles, both left and right caudal thoracic regions showed significantly lower muscle work and peak activity when the device was used. There was no significant difference between with and without the device in either left or right lumbar muscle work. In conclusion, implementing ground poles can be an effective strategy to increase the activation of the multifidus muscle, however, caution should be taken when incorporating the use of a resistance band training device as muscle work and peak activation were significantly reduced in most locations. Further study should be performed in regards to the training device to determine its effects on epaxial musculature.

Sensitivity of the stripe-faced dunnart, Sminthopsis macroura (Gould 1845), to the insecticide, fipronil; implications for pesticide risk assessments in Australia.

A lack of toxicity data quantifying responses of Australian native mammals to agricultural pesticides prompted an investigation into the sensitivity of the stripe-faced dunnart, Sminthopsis macroura (Gould 1845) to the insecticide, fipronil (5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinyl pyrazole, CAS No. 120068-37-3). Using the Up-And-Down method for determining acute oral toxicity in mammals (OECD) median lethal dose estimates of 990 mg kg-1 (95% confidence interval (CI) = 580.7-4770.0 mg kg-1) and 270.4 mg kg-1 (95% CI = 0.0->20,000.0 mg kg-1) were resolved for male and female S. macroura, respectively. The difference between median lethal dose estimates for males and females may have been influenced by the older ages of two female dunnarts. Consequently, further modelling of female responses to fipronil doses used the following assumptions: (a) death at 2000 mg kg-1, (b) survival at 500 mg kg-1 and (c) a differential response (both survival and death) at 990 mg kg-1. This modelling revealed median lethal dose estimates for female S. macroura of 669.1 mg kg-1 (95% CI = 550-990 mg kg-1; assuming death at 990 mg kg-1) and 990 mg kg-1 (95% CI = 544.7-1470 mg kg-1; assuming survival at 990 mg kg-1). These median lethal dose estimates are 3-10-fold higher than available LD50 values of 94 mg kg-1 for a similarly sized eutherian mammal, Mus musculus (L. 1758) and 97 mg kg-1 for Rattus norvegicus (Birkenhout 1769). Implications for pesticide risk assessments in Australia are discussed.

Effects of background food on alternative grain uptake and zinc phosphide efficacy in wild house mice.

BACKGROUND: House mice (Mus musculus) cause significant, ongoing losses to grain crops in Australia, particularly during mouse plagues. Zinc phosphide (ZnP) coated grain is used for control, but with variable success. In a laboratory setting, we tested if mice would (i) switch from consumption of one grain type to another when presented with an alternative and (ii) consume ZnP-treated grains when presented as a choice with a different grain. RESULTS: Mice readily switched from their background grain to an alternative grain, preferring cereals (wheat or barley) over lentils. Mice readily consumed ZnP-coated barley grains. Their mortality rate was significantly higher (86%, n = 30) in the presence of a less-favoured grain (lentils) compared to their mortality rate (47%, n = 29; 53%, n = 30) in the presence of a more-favoured grain (wheat and barley, respectively). Mice died between 4 and 112 h (median = 18 h) after consuming one or more toxic grains. Independent analysis of ZnP-coated grains showed variable toxin loading indicating that consumption of a single grain would not guarantee intake of a lethal dose. There was also a strong and rapid behavioural aversion if mice did not consume a lethal dose on the first night. CONCLUSIONS: The registered dose rate of 25 g of ZnP/kg wheat (~1 mg of ZnP/grain) in Australia needs to be re-evaluated to determine what factors may be contributing to variation in efficacy. Further field research is also required to understand the complex association between ZnP dose, and quantity and quality of background food on efficacy of ZnP baits.

Postweaning mortality in commercial swine production II: review of infectious contributing factors.

Postweaning mortality is extremely complex with a multitude of noninfectious and infectious contributing factors. In the current review, our objective is to describe the current state of knowledge regarding infectious causes of postweaning mortality, focusing on estimates of frequency and magnitude of effect where available. While infectious mortality is often categorized by physiologic body system affected, we believe the complex multifactorial nature is better understood by an alternative stratification dependent on intervention type. This category method subjectively combines disease pathogenesis knowledge, epidemiology, and economic consequences. These intervention categories included depopulation of affected cohorts of animals, elimination protocols using knowledge of immunity and epidemiology, or less aggressive interventions. The most aggressive approach to control infectious etiologies is through herd depopulation and repopulation. Historically, these protocols were successful for Actinobacillus pleuropneumoniae and swine dysentery among others. Additionally, this aggressive measure likely would be used to minimize disease spread if either a foreign animal disease was introduced or pseudorabies virus was reintroduced into domestic swine populations. Elimination practices have been successful for Mycoplasma hyopneumoniae, porcine reproductive and respiratory syndrome virus, coronaviruses, including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus, swine influenza virus, nondysentery Brachyspira spp., and others. Porcine circovirus type 2 can have a significant impact on morbidity and mortality; however, it is often adequately controlled through immunization. Many other infectious etiologies present in swine production have not elicited these aggressive control measures. This may be because less aggressive control measures, such as vaccination, management, and therapeutics, are effective, their impact on mortality or productivity is not great enough to warrant, or there is inadequate understanding to employ control procedures efficaciously and efficiently. Since there are many infectious agents and noninfectious contributors, emphasis should continue to be placed on those infectious agents with the greatest impact to minimize postweaning mortality.

Postweaning mortality in commercial swine production. I: review of non-infectious contributing factors.

Postweaning mortality is a complex causal matrix involving animal, environment, and infectious etiologic factors. Despite advances in swine productivity such as total pigs born, growth rate, feed intake, and efficiency, there have been modest to no improvements in postweaning mortality rates over the last several years. Industry averages for postweaning mortality range from four to eight percent for each the nursery, grow-finish, or wean-finish stages. Retrospective mortality causal analyses of individual databases have been performed. However, little information derived from meta-analysis, systematic review, or comprehensive literature reviews are available. In order to develop and evaluate strategies to comprehensively manage and reduce postweaning mortality, addressing the complexity and range of impact that factors have on mortality is necessary to identify and prioritize such contributing factors. Our objective is to describe the current state of knowledge regarding non-infectious causes of postweaning mortality, focusing on estimates of frequency and magnitude of effect where available. Postweaning mortality can be generalized into non-infectious and infectious causes, with non-infectious factors further classified into anatomic abnormalities, toxicity, animal factors, facility factors, nutritional inadequacies, season, and management factors. Important non-infectious factors that have been identified through review of literature include birth weight, pre-weaning management, weaning age and weight, and season. Additionally, reasons for mortality with a low incidence but a high magnitude include abdominal organ torsion/volvulus, sodium ion or ionophore toxicosis, or dietary imbalance due to feed formulation or manufacture error. Many interactive effects are present between and among infectious and non-infectious factors, but an important trend is the impact that non-infectious factors have on the incidence, severity, and resolution of infectious disease. Strategies to reduce postweaning mortality must consider the dynamic, complex state that forms the causal web. Control of postweaning mortality through understanding of the complexity, evaluation of mortality reduction strategies through rigorous scientific evaluation, and implementation remains an area of opportunity for continued growth and development in the global swine industry.

A bipedal mammalian model for spinal cord injury research: The tammar wallaby.

Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropuseugenii), because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P) days (P7-60) tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180), the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions relevant to humans.

Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR.

MicroRNAs (miRNAs) regulate many aspects of human biology. They target mRNAs for translational repression or degradation through base pairing with 3' untranslated regions, primarily via seed sequences (nucleotides 2 to 8 in the mature miRNA sequence). A number of individual miRNAs and miRNA families share seed sequences and targets, but differ in the sequences outside of the seed. miRNAs have been implicated in the etiology of a wide variety of human diseases and therefore represent promising therapeutic targets. However, potential redundancy of different miRNAs sharing the same seed sequence and the challenge of simultaneously targeting miRNAs that differ significantly in nonseed sequences complicate therapeutic targeting approaches. We recently demonstrated effective inhibition of entire miRNA families using seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiRs in short-term experiments in mammalian cells and in mice. However, the long-term efficacy and safety of this approach in higher organisms, such as humans and nonhuman primates, have not been determined. We show that pharmacological inhibition of the miR-33 family, key regulators of cholesterol/lipid homeostasis, by a subcutaneously delivered 8-mer LNA-modified antimiR in obese and insulin-resistant nonhuman primates results in derepression of miR-33 targets, such as ABCA1, increases circulating high-density lipoprotein cholesterol, and is well tolerated over 108 days of treatment. These findings demonstrate the efficacy and safety of an 8-mer LNA-antimiR against an miRNA family in a nonhuman primate metabolic disease model, suggesting that this could be a feasible approach for therapeutic targeting of miRNA families sharing the same seed sequence in human diseases.