Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control. Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, diagnoses, pathogeneses, treatment and control of GINs of horses from Australia. A total of 51 articles published between 1950 to 2018 were included. The main GINs reported in Australian horses were cyathostomins (at least 28 species), Draschia megastoma, Habronema muscae, H. majus, Oxyuris equi, Parascaris equorum, Strongyloides westeri and Trichostrongylus axei across different climatic regions of Queensland, New South Wales, Victoria, and Western Australia. Nematodes are diagnosed based on the traditional McMaster egg counting technique, though molecular markers to characterise common GINs of equines were characterised in 1990s. The use of anthelmintic drugs remains the most widely-used strategy for controlling equine GIN parasites in Australia; however, the threshold of faecal egg count that should trigger treatment in horses, remains controversial. Furthermore, anthelmintic resistance within GIN population of horses is becoming a common problem in Australia. Although GINs infecting Australian horses have been the subject of occasional studies over the past few decades, the effective control of GIN infections is hampered by a generalised lack of knowledge in various disciplines of equine parasitology. Therefore, coordinated and focused research is required to fill our knowledge gaps in these areas to maximise equine health and minimise economic losses associated with the parasitic infections in Australia.

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8⁺ and CD4⁺ T cells, resulting in inhibited growth of transplanted ICB-resistant tumours. Furthermore, ICB treatment of castration-resistant prostate cancer (CRPC) patients results in re-activation of ACK1/pY18-CSK signalling, confirming the involvement of this pathway in ICB insensitivity. An ACK1 small-molecule inhibitor, (R)-9b, recapitulates inhibition of ICB-resistant tumours, which provides evidence for ACK1 enzymatic activity playing a pivotal role in generating ICB resistance. Overall, our study identifies an important mechanism of ICB resistance and holds potential for expanding the scope of ICB therapy to tumours that are currently unresponsive.

Members of the genus Sarcocystis (Apicomplexa: Sarcocystidae) are intracellular protozoan parasites that infect a wide range of domestic and wild animals, resulting in economic losses in production animals worldwide. Sarcocystis spp. have indirect life-cycles where canids and felids serve as main definitive hosts while a range of domestic and wild animals serve as intermediate hosts, including South American camelids (SACs) such as alpacas, llamas and guanacos. These animals primarily occur in South American countries on Andean, elevated plains but in recent years, alpacas and llamas have become emerging animal industries in other parts of the world such as Australia, Europe and the USA due to their high-quality fiber, meat and hides. For instance, alpaca meat is becoming popular in many parts of the world due to its lower cholesterol content than other red meat, thereby it has the potential of a valuable product for both local and international markets. However, SAC meat can be degraded and/or even condemned due to the presence of macroscopic sarcocysts in skeletal muscles, leading to significant economic losses to farmers. The infection is generally asymptomatic, though highly pathogenic or even fatal Sarcocystis infections have also been reported in alpacas and llamas. Despite the economic importance of sarcocystosis in SACs, little is known about the life-cycle of parasites involved, disease transmission, epidemiology, pathogenesis, diagnosis, control and public health significance. This review article provides an in-depth analysis of the existing knowledge on the taxonomy, epidemiology, clinicopathology and diagnosis of Sarcocystis in SACs, highlights knowledge gaps and proposes future areas of research that could contribute to our better understanding of sarcocystosis in these animals.

Accurate and rapid diagnosis is crucial in combating parasitic diseases that cause millions of deaths worldwide. However, the scarcity of specialized diagnostic equipment in low- and middle-income countries is one of the barriers to effective management of parasitic diseases and warrants the need for alternative, inexpensive, point-of-care diagnostic tools. Due to their multiple built-in sensors, smartphones offer cost-effective alternative to expensive diagnostic devices. However, the use of smartphones in parasitic diagnoses remains in its infancy. This minireview describes various smartphone-based devices applied specifically for the diagnosis of parasitic diseases and discusses challenges and potential implications for their use in future.

Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR. The functional relevance of these clinical data was further studied in a mouse model of Citrobacter rodentium–induced colitis. PAR1 expression was significantly upregulated in the inflamed colons of pediatric patients with Crohn's disease, with expression levels directly correlating to disease severity. In patients with severe colitis, PAR1 expression uniquely correlated with Th17-related (IL17A, IL22, and IL23A) cytokines. Infection of PAR1-deficient (PAR1−/−) and wildtype mice with colitogenic C. rodentium revealed that disease severity and colonic pathology were strongly attenuated in mice lacking PAR1. Furthermore, Th17-type immune response was completely abolished in the colons of infected PAR1−/− but not wildtype mice. Finally, PAR1 was shown to be essential for secretion of the Th17-driving cytokine IL-23 by C. rodentium–stimulated macrophages. This study demonstrates a strong link between PAR1 expression, Th17-type immunity, and disease severity in both pediatric patients with Crohn's disease and C. rodentium–induced colitis in mice. The data presented suggest PAR1 exerts a proinflammatory role in colitis in both humans and mice by promoting a Th17-type immune response, potentially by supporting the production of IL-23.