No description available.

This thesis aimed to understand the mechanisms underlying within-host interactions among coinfecting parasites in wild rodents, how they are affected by the host immune response, and how they contribute to shape disease dynamics in nature. Coinfection is ubiquitous in human, domestic and wild animal populations, and can consist of both microparasites (viruses, bacteria and protozoa) and macroparasites (parasitic helminths). Moreover, coinfecting parasites can interact with each other in a number of ways (positive or negative, direct or indirect), which affects disease severity and progression, parasite transmission, the response of target and non-target parasites to treatment and, ultimately, the epidemiology of each coinfecting parasite species. While previous work on laboratory animals has generated detailed knowledge of the cellular components of the host immune response involved during coinfection, we still mostly lack a conceptual understanding of the role of the host immune response in mediating within-host interactions in nature. I used a known within-host interaction between two important intestinal parasites (the nematode Heligmosomoides polygyrus and the protozoan Eimeria hungaryensis) of wild wood mice (Apodemus sylvaticus) to study the underlying causes and consequences of this interaction for both parasite dynamics and host health. I first investigated if specific and total antibody levels can explain natural burdens and infection of H. polygyrus and Eimeria spp. in the context of other parasites and variation in host demography in a cross-sectional field study. I found that H. polygyrus-specific IgG1 and total faecal IgA were the strongest predictors of both H. polygyrus infection and burden and Eimeria spp. infection. Further, Eimeria spp. infection was associated with lower antibody levels, suggesting an interaction between Eimeria spp. and anti-helminth immunity. Next, I tested the causative relationship between antibody levels and parasite infection. Over the course of a longitudinal anthelmintic treatment study in the field, I measured infection and burden of both target and non-target parasites, as wells as specific and general antibody levels. I found that treatment successfully reduced H. polygyrus burden, wild led to a change in both antibody levels and E. hungaryensis dynamics. Further, H. polygyrus-specific IgG1 levels were predicted by pre-treatment H. polygyrus burden, suggesting that helminth infection induces antibody production, rather than vice versa. Following from this, I explored if treatment of single or multiple parasite groups (helminths, coccidia or both) had an effect on host survival. I used data from a longitudinal field study spanning an entire season of A. sylvaticus (April-December), where animals were given either Ivermectin (anthelmintic), Vecoxan (anti-coccidial), a mix of both drugs or water every fortnight. Ivermectin treatment led to a consistent reduction in H. polygyrus prevalence and burden, as well as a steady increase in E. hungaryensis prevalence, whereas Vecoxan treatment failed to show any effect on either target or non-target parasites. Interestingly, anthelmintic treatment led to a reduction in survival at intermediate H. polygyrus burdens, suggesting that anti-parasite treatments might not always be beneficial for the host. By bringing this wild coinfection system into the lab, I examined if the interaction between H. polygyrus and E. hungaryensis could be re-created under controlled laboratory condition, and if the lack of environmental variation had an effect on parasite and/or antibody dynamics. I found that coinfection led to a delay in H. polygyrus expulsion, and decreased E. hungaryensis shedding during chronic helminth infection. However, coinfection did not affect antibody dynamics. This not only demonstrated that the interaction between the two parasites was reciprocal, but also showed that coinfection can significantly affect parasite transmission dynamics. In an ongoing bioinformatic analysis, I investigated the level of genetic diversity in wild Eimeria spp. populations in order to uncover the mechanism underlying a common lack of protective immunity towards Eimeria spp. infections in wild and domestic animal populations. I found that there were multiple genetically distinct strains circulating within all populations tested, but homologous re-infection was not less likely than heterologous reinfection. This suggests that the lack of protective immunity in wild Eimeria spp. Populations cannot solely be explained by high levels of genetic diversity. This thesis provides several important insights into the mechanisms underlying parasite within-host interactions. Importantly, it highlights that, whilst host immunity plays a crucial role in determining the outcome of coinfection, other factors such as host demography have to be taken into account in order to understand the interplay between immunity and coinfection. I further show that anti-parasite treatments in the wild can be successful, but the benefits of such treatments can be context dependent. More broadly, my findings can have important implications for the planning and evaluation of treatment programs targeted at both single and coinfected animals and humans in their natural environment.

No description available.

Bibliography: leaves 113-128 / xii, 128, [63] leaves, [6] leaves of plates : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1984

Bibliography: leaves 218-251.

Bibliography: leaves 111-137.

The research investigated the combined effects of protein deficiency (PD) and a gastrointestinal nematode infection, Heligmosomoides bakeri , on immunopathology and nutritional status in BALB/c mice. The acute phase of a primary infection reduced resting metabolic rate, but PD did not. Early challenge infection led to temporary anorexia and cessation of weight gain in both protein-sufficient (PS) and PD mice. / Among PS mice, a challenge dose of 200 L3 caused more active worm expulsion than infection with 100 L3. Both serum monocyte chemotactic protein-5 and gut fluid leakage were positively correlated with worm expulsion whereas numbers of mucosal mast cells, eosinophils, goblet cells and Paneth cells were unaffected by doses. Among PD mice, worm survival was prolonged and no dose-dependent worm expulsion was observed. In addition, a wide range of Th1 inflammatory cytokines including leptin was elevated in infected PD mice suggesting (1) that PD mice are unable to mount the appropriate Th2 inflammation and (2) that infection in PD mice induces a Th1 inflammation that allows continuing persistence of the parasite. / The shift to Th1 inflammatory responses in PD mice may also explain modifications in mineral distributions in tissues. Despite adequate dietary intakes of minerals in both PD and PS mice, serum iron concentrations were lower after H. bakeri challenge infection. Infection also reduced calcium and iron concentrations as well as the Ca/Zn ratio in the spleen. In contrast, PD resulted in increased iron and calcium concentrations as well as increased Ca/Zn ratio in the spleen and Fe/Zn ratio in the liver, but reduced calcium, zinc, copper and sulfur concentrations, and the Cu/Zn ratio in the liver. / Re-feeding PD mice with a PS diet restored parasite expulsion, regardless of whether the PS diet was provided during the primary or challenge infection. Thus, although PD mice have suppressed Th2 responses and elevated Th1 inflammation, their response to the primary infection is sufficient to ensure that parasite expulsion occurs once protein status is restored. / Together, these studies show that the shift toward Th1 inflammation plays a key role in prolonged parasite survival and mineral redistribution in protein deficient, infected mice.

The aim of this research was to determine the influence of iron deficiency on both the efficacy and metabolic patterns of albendazole in mice infected with Heligmosomoides polygyrus. Anthelmintic efficacy was markedly decreased in iron-deficient mice; the deficiency was also associated with a decrease in body weight, altered hematological parameters and a decreased net egg output; worm establishment in the deficient group was not affected by the deficiency. Although anthelmintic efficacy was significantly decreased by the iron deficiency, plasma concentration profiles of the main metabolites, albendazole sulphoxide and albendazole sulphone, were not changed by the deficiency. Levels of intestinal cytochrome P-450, the main metabolizing enzyme of albendazole however, was significantly depressed in iron-deficient mice. These observations suggest that although pharmacokinetic parameters are not affected by iron deficiency, nutritional status has the potential to influence anthelmintic efficacy and thus warrants further study.

In the past 20 years, boron has been identified as an essential trace element for animals and humans but also as an increasingly important industrial pollutant. We examined first whether boron influenced survival of the gastrointestinal nematode Heligmosomoides bakeri. Female Balb/c mice were fed deficient (0.1 mug B/g), marginal (2.0 mug B/g) or control (12.0 mug B/g) diets, and infected with third-stage larvae. Although liver boron concentrations did not differ among diet groups, dietary boron deficiency impaired survival of the parasite and modulated a broad range of cytokines and chemokines. On the other hand, infection history altered liver mineral concentrations. Second, we examined whether elevated boron concentrations would exert toxic effects on H. bakeri in vitro. Boron toxicity was evidenced by reduced motility, fecundity, infectivity and survival. Feeding stages and free-living stages were more sensitive than non-feeding stages and parasitic stages respectively in a dose-dependent manner.

Bibliography: leaves 218-251 / xviii, [ca. 100] leaves : ill ; 31 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1983