Keratouveitis in juvenile dogs and its presumed association with canine adenovirus infection.

OBJECTIVE: We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)-2 vaccinations and assessed the utility of CAV-1 and CAV-2 titers in elucidation of its etiopathogenesis. ANIMALS STUDIED: Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs. PROCEDURES: The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age-matched dogs without corneal edema but with CAV titers were included as controls. RESULTS: Mean CAV-1 and CAV-2 titers were not statistically different between dogs with keratouveitis and controls (p = .16 and p = .76, respectively). Three cases had CAV-1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11-fold increase) suggesting infection with wild-type CAV-1. The six other cases did not appear to be associated with CAV infection or vaccination. CONCLUSION: Keratouveitis continues to occur despite the advent of CAV-2 vaccinations. While this study found no evidence to indicate CAV-2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild-type CAV-1 infection is a possible cause.

A scoping review of risk factors and transmission routes associated with human giardiasis outbreaks in high-income settings.

The flagellated pathogen Giardia duodenalis is one of the leading causes of parasitic gastrointestinal illness worldwide. In many higher income countries, such as the United Kingdom, the disease is often perceived as being travel-related, likely leading to the under-reporting of sporadic cases and outbreaks. A summary of the literature describing outbreaks and risk factors in higher income countries is necessary to improve our understanding of this pathogen and identify existing knowledge gaps. Initial literature searches were carried out in September 2016 and updated at regular intervals until November 2021, using appropriate search terms in Medline, Embase and PubMed databases. A total of 75 papers met the inclusion criteria, revealing that the consumption of contaminated water and contact with young children of diaper-wearing age were the most common transmission routes leading to outbreaks of giardiasis. Of the ten studies where food was primarily associated with outbreaks, food handlers accounted for eight of these. Another reported transmission route was direct contact with fecal material, which was reported in six studies as the primary transmission route. Travel-associated giardiasis was considered the sole transmission route in two studies, whereas multiple transmission routes contributed to giardiasis outbreaks in eleven studies. The evidence around zoonotic transmission was less clear and hampered by the lack of robust and regularly applied parasite molecular typing techniques. This literature review summarizes the findings of Giardia outbreak investigations and epidemiological studies in high-income countries. Transmission routes are identified and discussed to highlight the associated risk factors. These data also indicate gaps in our current knowledge that include the need for robust, in-depth molecular studies and have underscored the importance of water as a transmission route for Giardia cysts. These future molecular studies will improve our understanding of Giardia epidemiology and transmission pathways in higher income countries to prevent spread of this significantly under-reported pathogen.

Identification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells.

As part of an international effort to develop vaccines for Theileria lestoquardi, we undertook a limited screen to test T. lestoquardi orthologues of antigens recognised by CD8+ T lymphocyte responses against T. annulata and T. parva in cattle. Five MHC defined sheep were immunized by live T. lestoquardi infection and their CD8+ T lymphocyte responses determined. Thirteen T. lestoquardi orthologues of T. parva and T. annulata genes, previously shown to be targets of CD8+ T lymphocyte responses of immune cattle, were expressed in autologous fibroblasts and screened for T cell recognition using an IFNγ assay. Genes encoding T. lestoquardi antigens Tl8 (putative cysteine proteinase, 349 aa) or Tl9 (hypothetical secreted protein, 293 aa) were recognise by T cells from one animal that displayed a unique MHC class I genotype. Antigenic 9-mer peptide epitopes of Tl8 and Tl9 were identified through peptide scans using CD8+ T cells from the responding animal. These experiments identify the first T. lestoquardi antigens recognised by CD8+ T cell responses linked to specific MHC class I alleles.

Co-infections determine patterns of mortality in a population exposed to parasite infection.

Many individual hosts are infected with multiple parasite species, and this may increase or decrease the pathogenicity of the infections. This phenomenon is termed heterologous reactivity and is potentially an important determinant of both patterns of morbidity and mortality and of the impact of disease control measures at the population level. Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease. In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection. Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%. Using a mathematical model, we demonstrate that this degree of heterologous protection provides a unifying explanation for apparently disparate epidemiological patterns: variable disease-induced mortality rates, age-mortality profiles, weak correlations between the incidence of infection and disease (known as endemic stability), and poor efficacy of interventions that reduce exposure to multiple parasite species. These findings can be generalized to many other infectious diseases, including human malaria, and illustrate how co-infections can play a key role in determining population-level patterns of morbidity and mortality due to parasite infections.

Exploiting genetic variation to discover genes involved in important disease phenotypes.

Elucidating the underlying genetic determinants of disease pathology is still in the early stages for many pathogenic parasites. There have, however, been a number of advances in which natural genetic diversity has been successfully utilized to untangle the often complex interactions between parasite and host. In this chapter we discuss various methods capable of exploiting this natural genetic variation to determine genes involved in phenotypes of interest, using virulence in the pathogenic parasite Trypanosoma brucei as a case study. This species is an ideal system to benefit from such an approach as there are several well-characterized laboratory strains; the parasite undergoes genetic exchange in both the field and the laboratory, and is amenable to efficient reverse genetics and RNAi.

Molecular approaches to diversity of populations of apicomplexan parasites.

Apicomplexan parasites include many parasites of importance either for livestock or as causative agents of human diseases. The importance of these parasites has been recognised by the European Commission and resulted in support of the COST (Cooperation in Science and Technology) Action 857 'Apicomplexan Biology in the Post-Genomic Era'. In this review we discuss the current understanding in 'Biodiversity and Population Genetics' of the major apicomplexan parasites, namely the Eimeria spp., Cryptosporidium spp., Toxoplasma gondii, Neospora caninum, Theileria spp. and Plasmodium spp. During the past decade molecular tools for characterizing and monitoring parasite populations have been firmly established as an integral part of field studies and intervention trials. Analyses have been conducted for most apicomplexan pathogens to describe the extent of genetic diversity, infection dynamics or population structure. The underlying key question for all parasites is to understand how genetic diversity influences epidemiology and pathogenicity and its implication in therapeutic and vaccination strategies as well as disease control. Similarities in the basic biology and disease or transmission patterns among this order of parasites promote multifaceted discussions and comparison of epidemiological approaches and methodological tools. This fosters mutual learning and has the potential for cross-fertilisation of ideas and technical approaches.