From simple beginnings, when only one host was required, numerous parasitic organisms have evolved complex life-cycles involving two or more host species. For example, trematode parasites reproduce in vertebrates, their definitive host, but their current life cycle also typically involves two intermediate hosts that were added during the course of evolution. Vertebrates are often considered to be the ancestral hosts of trematodes although other scenarios exist. While multi-host life cycles are observed in distantly related groups of parasites, their evolution remains largely unexplored. In trematodes, while recent phylogenetic studies have shed light on the sequence along which the different hosts were incorporated in the cycle, conditions that favoured the evolution of such complex life cycles can only be hypothesized. However, one opportunity to understand the force shaping the evolution of complex life cycles is provided by the few trematode species in which the classical three-host cycle facultatively reverts to a shorter cycle (i.e. life cycle abbreviation). In this study, the effects of different environmental factors on the life history strategy of the trematode Coitocaecum parvum were investigated using laboratory and field studies. C. parvum is able to abbreviate its life cycle from three to two hosts by maturing early (i.e. progenesis) and producing eggs inside the second intermediate host; both life history strategies occur simultaneously in C. parvum populations. Environmental factors such as predator densities should strongly influence parasite life history strategies. In fact, this study shows that laboratory reared Coitocaecum parvum adopt preferentially the normal three-host cycle when chemical cues from the definitive host are added to their environment, while the shorter cycle is favoured when these cues are absent. However, in nature, multiple environmental factors are likely to be perceived by parasites. Consequently, C. parvum�s ability to adapt its developmental strategy to definitive host densities may be confounded by the complex combination of various environmental parameters. Within-host competition between parasites sharing a common host is also likely to influence individual life history strategies. Parasites could then use alternative life strategies to adaptively respond to intraspecific and interspecific competition. Indeed, this study found that C. parvum preferentially adopts the abbreviated cycle in the presence of competitors. However, in interspecific competition, C. parvum�s strategy also depends upon the competitor species, possibly influenced by the other species� transmission route. Furthermore, intensity of intraspecific competition proved to constrain C. parvum�s ability to use the abbreviated life cycle. Finally, genetic relatedness between co-infecting C. parvum individuals seems to affect parasite life strategy through kin selection: closely related individuals are more likely to adopt the same developmental strategy, when they share a host, than unrelated ones. C. parvum individuals adopting the abbreviated cycle are enclosed within a cyst in their intermediate host and must produce eggs by self-fertilization, the most severe case of inbreeding. It was hypothesized that their offspring would have reduced fitness due to inbreeding depression, therefore selecting against the shorter cycle. However, this study found no difference in the survival and infection success of offspring produced through the abbreviated and normal cycles. Furthermore, no evidence for a genetic basis of life cycle abbreviation was detected: the same proportion of offspring from both reproductive strategies adopted the shorter life cycle. The work in this thesis provides evidence that although life cycle abbreviation provides Coitocaecum parvum with a viable alternative life strategy, numerous factors promote or restrict the adoption of this strategy. While this life history strategy has no detectable effect on parasite fitness, both environmental parameters and within-host competition affect C. parvum life-history strategies, alternatively selecting for either the shorter or normal life cycle. Overall, the complexity of the parasite environment could maintain both developmental strategies in C. parvum populations and, on a broader scale, could have influenced the evolution of complex life cycles in parasites.

Some ill. mounted. / Bibliography: leaves [473]-504. / xxxvi, 505 leaves : ill. (some col.) ; 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 Pathology, 1984

Severe population bottlenecks and the small size of many remnant habitats may render many bird populations prone to extinction from disease outbreaks. Bottlenecks may increase inbreeding which in turn may result in a low diversity of resistance and an immune system that is impaired or defective. Thus, bottlenecked populations may be less immunocompetent and more vulnerable to microbiological and parasitic perturbations. Few studies have assessed the effect of bottlenecks on the immunocompetence of birds. In this study, I used twelve saddleback (Philesturnus carunculatus) and two New Zealand robin (Petroica a. australis) populations, to determine if the severe bottlenecks reduce the immunocompetence of birds. When I experimentally challenged the immune system of two robin populations I found that despite the two populations having similar parasite loads, robins from the severely bottlenecked Motuara Island population exhibited a significantly lower T-cell mediated immune response than the source population (Nukuwaiata Island) suggesting that birds passing through severe population bottlenecks have a compromised immunocompetence. In the saddleback, severe bottlenecks, as well as high population densities and small island size, lead to individuals exhibiting higher stress levels and feather mite loads and lower immune function, as was evident by lower lymphocyte counts. I did not find levels of fluctuating asymmetry of saddlebacks to be directly influenced by bottleneck size. However, I did find that individuals with higher levels of fluctuating asymmetry had higher loads of hippoboscid flies and lower loads of coccidia suggesting a possible trade-off between growth and immune function. In contrast to previous studies looking at behavioural secondary sexual traits, I found no effect of founder number on the size of wattles in saddleback. I did however demonstrate that wattle size reflected the level of immune function in females as well as males, suggesting that females play a far greater role in offspring fitness than has been appreciated in traditional theories of sexual selection. Overall, my results indicate that severe bottlenecks can lead to reductions in immunocompetence in the resulting populations, especially in those populations that pass through the most severe bottlenecks. Based on the evidence from my thesis, I recommend conservation managers should aim to use at least 90 individuals to found new populations in order to reduce the deleterious effects of bottlenecks on immune function. If the costs of population bottlenecks and inbreeding are to be avoided, conservationists must adequately address the role of genetic factors in susceptibility to disease, and work towards minimising the risk of severe population bottlenecks in the management of endangered birds

I investigated parasitic infection and immunocompetence in populations of introduced bird species in New Zealand (NZ) that had experienced a range of population bottlenecks (11-808 individuals), and compared these parameters to non-bottlenecked conspecifics in the United Kingdom (UK). My aims were two-fold; firstly to assess if population bottlenecks are linked to increased parasite loads and/or decreased immunocompetence, and secondly, to assess at what severity of bottleneck these effects become evident. I found that ectoparasite load (chewing lice, Order: Phthiraptera, Sub-Orders: Amblycera & Ischnocera) was significantly higher in the more severely bottlenecked species in NZ than in the UK, whilst this difference became non-significant at more moderate bottlenecks. The difference was mainly driven by the Sub-Order Amblycera. The prevalence of avian malaria (Plasmodium spp.) was significantly negatively correlated to bottleneck size within NZ, after controlling for body mass. Total leucocyte and differential lymphocyte counts were elevated in the less bottlenecked species that were infected with malaria, whilst the populations at the more severe end of the bottleneck spectrum did not exhibit such a response. Furthermore, heterophil/lymphocyte (HL) ratio (a parameter used as an indicator of environmental and/or immunological stress), was significantly raised in the more bottlenecked species when compared to their UK counterparts, and this difference was correlated with the size of the bottleneck. Immunocompetence was further assessed by the experimental challenge of six introduced birds species in NZ with the mitogen phytohaemagglutinin (PHA). Immune response to PHA was significantly correlated to bottleneck size, but in the opposite direction to that predicted; immune response was greater in the more bottlenecked species. However, this may be an indication of increased investment in immunity, due to increased parasite and pathogen pressure or differential investment in varying components of the immune system. Finally, the immune response to PHA was compared in nestlings of two species that had experienced very different bottlenecks (70 vs. 653). After controlling for ectoparasitic infestation, I found no difference between the two species; however, this finding may be confounded by interspecific competition. Overall, my findings suggest that more severe population bottlenecks may result in increased susceptibility to pathogens, and impact on the immune system. This has a number of implications for the development of conservation protocols, and future avenues of research are suggested.

The purpose of the present study was to evaluate the potential usefulness of tubulin inhibitors when complexed with hydroxypropyl-â-cyclodextrin (ÇPâCD) against a range of protozoan parasites. This approach involved investigations into the complexation of these drugs with ÇPâCD, and subsequent investigations of these drugs and their complexes in regard to cytotoxicity, pharmacokinetics, in vitro efficacy against Giardia, Cryptosporidium and rodent malaria (Plasmodium chabaudi), and their in vivo efficacy against Giardia and malaria. Albendazole (ABZ) is a benzimidazole carbamate with a broad anti-parasite spectrum, while the dinitroanilines trifluralin (TF) and oryzalin (OZ) have recently been found to exhibit activity against certain parasites. All three compounds are microtubule antagonists in either nematodes or weeds and have poor aqueous solubility, with the solubility of ABZ and OZ dependent on pH. Cyclodextrins (CD) have a hydrophobic cavity that allows them to form inclusion complexes with hydrophobic drugs, resulting in increased drug aqueous solubility, and often, improved drug dissolution and bioavailability. Thus the complexation of these drugs with ÇPâCD was investigated. All three compounds exhibited type AL phase solubility diagrams with ÇPâCD complexation, with additional increases in ABZ and OZ solubility achieved through the manipulation of temperature and pH. OZ displayed a stronger interaction with ÇPâCD when ionised over its neutral form. However, insufficient concentrations of the TF/ÇPâCD complex were achieved for drug efficacy studies. The cytotoxicity of the drugs and their complexes was assessed using the assay kit Cytotox 96 with human carcinoma cells. This is a colourimetric assay that measures lactate dehydrogenase release as a consequence of compromised cellular and membrane integrity. Both ABZ and OZ are cytotoxic to rapidly proliferating and differentiating cells but are not cytotoxic to cells in the stationary phase. Complexation did not affect drug cytotoxicity. In pharmacokinetic studies, complexation improved ABZ (and metabolites) bioavailability, but had no significant affect on OZ bioavailability. In vitro drug assessment studies found ABZ to be highly effective against Giardia, and effectiveagainst Cryptosporidium and malaria. OZ on the other hand exhibited no activity against Giardia, but was effective against Cryptosporidium and malaria. Complexation did not improve the antiprotozoal efficacy of either ABZ or OZ. In particular, excess ÇPâCD decreased the antigiardial effects of ABZ, possibly due to competitive complex formation. In addition, complexation did not improve the antiprotozoal effects of ABZ in vivo. However, the cytotoxic effect of the ABZ/ÇPâCD complex was more evident in the treatment of malaria in vivo, resulting in increased anaemia and suppression in weight gain, due to the improved bioavailability of ABZ and metabolites. ÇPâCD alone was found to be cytotoxic at greater than 2.5%, and inhibited Giardia both in vitro and in vivo at greater than 1% and 2% respectively. This was attributed to membrane disruption caused by the dissolution and removal of membrane components. In comparison, malaria grew better in the presence of ÇPâCD in vitro, with no detrimental effect observed at up to 8% ÇPâCD. This was attributed to either the increased solubilization of a necessary media component, or the complexation and removal of an inhibitory compound from the cultivation medium. Therefore ÇPâCD complexation did not improve the antiprotozoal activity of the tubulin antagonists ABZ and OZ. However, the results of the pharmacokinetic studies suggest that anthelmintic activity of ABZ, particularly against systemic infections, may be improved with oral administration of the ABZ/ÇPâCD complex. In addition, the antiparasitic activity of ÇPâCD alone may be promising, especially against intestinal infections. Finally, the improved in vitro cultivation of P. chabaudi in the presence of ÇPâCD presents a promising approach to its potential long term cultivation.

Diss. (sammanfattning) Stockholm : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Sveriges lantbruksuniversitet, 2005. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Univ., 2006. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Missouri - Columbia, 1996. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.