Peter Irwin

Meningoencephalitis is an important cause of neurological signs in dogs and may arise from infectious or noninfectious causes. In this retrospective study, dogs with steroid-responsive meningitis arteritis (SRMA), meningoencephalomyelitis of unknown origin (MUO), and eosinophilic meningoencephalomyelitis (EM), living on the east coast of Australia, were evaluated. Data accessed included signalment, clinical signs, magnetic resonance imaging (MRI) and computed tomography (CT) results. C-reactive protein concentration, complete blood count, cerebrospinal fluid analysis, serological tests, medications, duration of treatment, time to relapse and patient outcomes. Of 89 dogs in total, 45 were classified as SRMA, 24 as MUO and 20 as EM. Cervical pain occurred in all dogs with EM and SRMA, and in 50% of dogs with MUO. Dogs with SRMA were less likely to develop paresis than those with EM and less likely to be ataxic than dogs with MUO. Serum CRP concentrations were significantly higher in SRMA compared with MUO and EM (P < 0.01). Twelve dogs, all with eosinophilic pleocytosis, were diagnosed with CNS infections: angiostrongyliasis (n = 11) and cryptococcus (n = 1). A wide variety of treatment protocols were used, underpinned by immunosuppressive medications, with the duration of treatment not significantly different between groups. The most favourable outcomes for dogs with meningoencephalitides in this study were those with EM, which not only had the shortest treatment durations but also had the longest survival times.

Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms associated with poorly characterised tick-related illnesses, such as debilitating symptom complexes attributed to ticks (DSCATT) in Australia. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events and that the time course of these signals may align with local pathophysiology. As a first step towards testing this hypothesis, we compared molecular signatures in skin biopsies taken from the tick-bite location of human participants, as published in our previous study, together with peripheral blood signatures obtained concurrently. This approach captures differentially expressed molecules across multiple omics datasets derived from peripheral blood (including cellular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our original data revealed that extracellular matrix organisation and platelet degranulation pathways were upregulated in the skin within 72 h of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying longitudinally consistent alterations of biological functions. Despite the limited sample size, these data represent proof-of-concept that molecular events in the skin following a tick bite can be detectable systemically. This underscores the potential value of blood samples, akin to a liquid biopsy, to capture biomarkers reflecting local tissue processes.

Tick-associated diseases present challenges due to tridirectional interactions among host-specific responses, tick toxins and salivary proteins as well as microbes. We aimed to uncover molecular mechanisms in tick-bitten skin samples (cases) and contralateral skin samples (controls) collected simultaneously from the same participants, using spatial transcriptomics. Cases and controls analysed using NanoString GeoMx Digital Spatial Profiler identified 274 upregulated and 840 downregulated differentially expressed genes (DEGs), revealing perturbations in keratinization and immune system regulation. Samples of skin biopsies taken within 72 h post tick-bite DEGs had changes in protein metabolism and viral infection pathways as compared to samples taken 3 months post tick-bite, which instead displayed significant perturbations in several epigenetic regulatory pathways, highlighting the temporal nature of the host response following tick bites. Within-individual signatures distinguished tick-bitten samples from controls and identified between-individual signatures, offering promise for future biomarker discovery to guide prognosis and therapy.

Ticks (Acari: Ixodidae) are major disease vectors globally making it increasingly important to understand how altered vertebrate communities in urban areas shape tick population dynamics. In urban landscapes of Australia, little is known about which native and introduced small mammals maintain tick populations preventing host-targeted tick management and leading to human-wildlife conflict. Here, we determined (1) larval, nymphal, and adult tick burdens on host species and potential drivers, (2) the number of ticks supported by the different host populations, and (3) the proportion of medically significant tick species feeding on the different host species in Northern Sydney. We counted 3551 ticks on 241 mammals at 15 sites and found that long-nosed bandicoots (Perameles nasuta) hosted more ticks of all life stages than other small mammals but introduced black rats (Rattus rattus) were more abundant at most sites (33%-100%) and therefore important in supporting larval and nymphal ticks in our study areas. Black rats and bandicoots hosted a greater proportion of medically significant tick species including Ixodes holocyclus than other hosts. Our results show that an introduced human commensal contributes to maintaining urban tick populations and suggests ticks could be managed by controlling rat populations on urban fringes.

Tick-borne diseases (TBDs) are a growing global health concern. Despite extensive studies, ill-defined tick-associated pathologies remain with unknown aetiologies. Human immunological responses after tick bite, and inter-individual variations of immune-response phenotypes, are not well characterised. Current reductive experimental methodologies limit our understanding of more complex tick-associated illness, which results from the interactions between the host, tick, and microbes. An unbiased, systems-level integration of clinical metadata and biological host data - obtained via transcriptomics, proteomics, and metabolomics - offers to drive the data-informed generation of testable hypotheses in TBDs. Advanced computational tools have rendered meaningful analysis of such large data sets feasible. This review highlights the advantages of integrative system biology approaches as essential for understanding the complex pathobiology of TBDs.

Dirofilaria immitis (the canine heartworm) is widespread in the tropics, with prevalence surpassing 30% in high-risk areas. In addition to the suitable climatic conditions that favour mosquito abundance and filarial larva development, there is low compliance with the recommended year-round use of preventives in these transmission hotspots. This represents a major concern, considering that melarsomine (first-line heartworm adulticide) is unavailable in several tropical countries, resulting in the so-called slow-kill protocol being the only available adulticide treatment option. In this article, the members of TroCCAP (Tropical Council for Companion Animal Parasites) review the current distribution of heartworm in the tropics and the availability of melarsomine, and discuss alternatives for the management of heartworm infections in dogs.

In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia. Our approach focuses on the transmission of potential pathogens and the immunological responses of the patient after a tick bite. The protocol is strengthened by prospective data collection, the recruitment of two external matched control groups, and sophisticated integrative data analysis which, collectively, will allow the robust demonstration of associations between a tick bite and the development of clinical and pathological abnormalities. Various laboratory analyses are performed including metagenomics to investigate the potential transmission of bacteria, protozoa and/or viruses during tick bite. In addition, multi-omics technology is applied to investigate links between host immune responses and potential infectious and non-infectious disease causations. Psychometric profiling is also used to investigate whether psychological attributes influence symptom development. This research will fill important knowledge gaps about tick-borne diseases. Ultimately, we hope the results will promote improved diagnostic outcomes, and inform the safe management and treatment of patients bitten by ticks in Australia.

Large populations of unowned cats constitute an animal welfare, ecological, societal and public health issue worldwide. Their relocation and homing are currently carried out in many parts of the world with the intention of relieving suffering and social problems, while contributing to ethical and humane population control in these cat populations. An understanding of an individual cat’s lifestyle and disease status by veterinary team professionals and those working with cat charities can help to prevent severe cat stress and the spread of feline pathogens, especially vector-borne pathogens, which can be overlooked in cats. In this article, we discuss the issue of relocation and homing of unowned cats from a global perspective. We also review zoonotic and non-zoonotic infectious agents of cats and give a list of practical recommendations for veterinary team professionals dealing with homing cats. Finally, we present a consensus statement consolidated at the 15th Symposium of the Companion Vector-Borne Diseases (CVBD) World Forum in 2020, ultimately to help veterinary team professionals understand the problem and the role they have in helping to prevent and manage vector-borne and other pathogens in relocated cats.

Canine monocytic ehrlichiosis (Ehrlichia canis infection) is a serious tick-transmitted disease of dogs that was considered exotic to Australia until recently. The disease was first reported across northern and central Australia in 2020, with significant canine morbidity and mortalities observed at indigenous communities where dog numbers are high, ticks are superabundant, and tick prevention is scant. The date and location of the incursion are unknown, yet comparative genomic analysis suggest the Australian E. canis may have originated from Asia or the Middle East. Veterinarians nationwide are on alert for this notifiable disease since cases have been reported in southern locations as a consequence of moving infected dogs from endemic areas. Acute infections in dogs respond favourably to doxycycline therapy, however chronic disease results in bone marrow failure and death. Tick prophylaxis is key to preventing canine ehrlichiosis and is best achieved using products that repel and kill ticks before they attach. Although reports exist of E. canis as a zoonosis, there is no evidence that the strain involved in the current Australian outbreak poses risk to humans.

In this expert opinion, two case studies of tick-borne diseases of domestic animals in Australia have been selected to illustrate how climate change can potentially influence the spread of introduced tick species and the pathogens they transmit. The first reports an incursion of canine monocytic ehrlichiosis (CME) into northern regions of Australia in April/June 2020 and the second describes the geographical expansion of bovine anaemia due to Theileria orientalis group (BATOG) across Australia since 2006. The introduction of novel pathogens into ecosystems exposed to climate change provides a unique opportunity to study disease dynamics in real time.