Rosetting is an adhesion property of malaria parasites whereby infected erythrocytes bind to two or more uninfected erythrocytes, forming a so-called rosette. Rosetting of Plasmodium falciparum is associated with disease severity and high parasitaemia in sub-Saharan Africa, although currently the function of rosetting remains unknown. An early IFNg response elicited from the innate immune system is associated with resolution of malaria infection in mice. Published data suggests that optimal IFNg production may require contact between peripheral blood mononuclear cells and P. falciparum infected erythrocytes. The first part of this thesis investigates the hypothesis that rosetting is an immune evasion strategy to hide infected erythrocytes from detection by innate immune cells. Across five laboratory strains of P. falciparum rosetting was not associated with differential IFNg production when parasites were grown in group O blood. Reappraisal of the data with respect to blood group for one strain found that rosetting significantly reduced the IFNg response to parasites grown in group A blood (P=0.022, Wilcoxon signed-rank test), where it is known that rosettes are bigger and stronger. This is consistent with the hypothesis that rosetting is an immune evasion strategy and the first study to find evidence for a function of rosetting. Further work is needed in order to generalise this finding. The cytokine response to P. falciparum varies between people and this variation may be indicative of disease progression. In mice infected with malaria it is also apparent that parasite strain can determine the cytokine response of the host. It is unclear whether P. falciparum strains vary in their ability to induce cytokines. The second part of this thesis investigates variation in cytokine induction between P. falciparum strains. Across four laboratory strains of P. falciparum, IFNg production was significantly dependent on parasite strain (F3,178= 48.49, P<0.001). Production of GM-CSF, IL-1b, IL-6, IL-10 and TNFa significantly correlated with production of IFNg (P<0.001, Pearson correlation) and followed the same strain-dependent pattern. The ratio of pro-inflammatory cytokines to IL-10 was also dependent on parasite strain. These data provide strong evidence for P. falciparum strain-dependent cytokine responses which may be an important determinant of disease outcome. Phagocytosis by splenic macrophages is proposed to be the principle mechanism of parasitaemia control in malaria infection. CD36 mediated phagocytosis may by an important mechanism of non-opsonic parasite clearance. The final part of this thesis investigates the hypothesis that rosetting is an immune evasion strategy of P. falciparum in order to evade phagocytic clearance, in particular that mediated by CD36. Overall the data obtained were inconsistent. Phagocytosis was significantly reduced in rosetting versus non-rosetting parasites in some strains (e.g. R29; P=0.048, paired T test), whereas others showed no effect (e.g. Muz12; P=0.228, paired T test) or increased versus non-rosetting parasites (e.g. HB3, P=0.004, paired T test). The relationship between CD36 binding and phagocytosis was also unclear, and anti-CD36 antibody did not effectively block phagocytosis, suggesting the involvement of alternative mechanisms. Further experiments are needed to clarify these observations. Data presented in this thesis are suggestive that rosetting in non-group O blood may be an immune evasion strategy with regard to IFNg production by innate immune cells, mechanistically linking rosetting with enhanced parasitaemia and disease severity. Furthermore, parasite strain significantly affects cytokine production and may be a determinant of disease outcome. This thesis demonstrates the importance of continued research into the effect of parasite virulence on the immune response, with particular emphasis on rosetting.

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Forty-two Blarina brevicauda and 50 Sorex cinereus from various locations in Delaware County, Indiana, were examined for helminth parasites. From zero to eight parasites were found in 98 percent of the B. brevicauda. From zero to five parasites were found in 92 percent of the S. cinereus. Longistriata depressa, Porrocaecum americanum, P. encapsulatum, Capillaria blarinae, Protogynella sp., Hymenolepis anthocephalus, Panopistus pricei, Entosiphonus thompsoni, Brachylaima rhomboideus, Trichuris sp., Parastrongyloides winchesi, and a larval spirurid nematode, probably Physaloptera limbata, parasitized B. brevicauda. Larval nematodes, which may be Angiostrongylus michiganensis were abundant in the digestive and respiratory tracts. B. brevicauda also contained a minute, unidentifiable nematode from the small intestine. Tapeworms from four different B. brevicauda were in such poor condition as to make positive identification difficult. These were probably H. blarinae. H. parva; H. serrula; H. faculata; H, longi; two different unidentifiable hymenolepids; P. americanum; P. encapsulatum; A. michiganensis; Pseudophysaloptera formosana soricina; L. depressa; P, pricei; C. rauschi; P. winchesi; larval capillarid nematodes from the liver, probably C. hepatica; and three small unidentifiable nematodes parasitized S. cinereus.First reports include: P. winchesi in an American Sorex sp., Trichuris sp. from the intestine of B. brevicauda, P, pricei in S. cinereus, and larval capillarids, possibly C. hepatica, from the liver of S. cinereus.Possible relationships between the parasites' life cycles and the hosts' habitats were discussed.

A família Trypanosomatidae compreende parasitas obrigatórios de vertebrados, plantas e invertebrados, as espécies exclusivas de insetos infectam principalmente dípteras e hemípteras. Nós revisamos a taxonomia de Herpetomonas e tripanossomatídeos de insetos que abrigam simbionte (SHT), comparando tripanossomatídeos da América do Sul e África. As filogenias revelaram duas novas espécies e possibilitou revalidar os gêneros Strigomonas e Angomonas. As análises filogenéticas revelaram três novas espécies de endossimbiontes proteobacteriano e apoiam a história evolutiva convergente entre hospedeiros e simbiontes. O DNA barcoding de 364 culturas de moscas identificaram 70 culturas (20%) como Angomonas, 71% deles de Calliphoridae. O gênero Herpetomonas compreende agora 13 espécies válidas, incluindo cinco novas espécies. Algumas espécies de Herpetomonas são parasitas generalistas de moscas e parecem ser tão cosmopolita como seus hospedeiros. Os taxon propostos podem ajudar a elaborar critérios mais eficientes para uma classificação melhor dos tripanossomatídeos. / Trypanosomatidae comprises obligate parasites of vertebrates, plants and invertebrates, the species exclusive of insects infect mostly dipterans and hemipterans. We revise the taxonomy of Herpetomonas and Symbiont Harboring Trypanosomatids (SHTs), by comparing trypanosomatids from South America and Africa. The phylogenies disclosed two new species and revalidated the genera Strigomonas and Angomonas. Phylogenetic analyses revealed 3 new species of proteobacterial endosymbionts and support a co-divergent host-symbiont evolutionary history. DNA barcoding of 364 cultures from flies identified 70 cultures (20%) as Angomonas, 71% of them from Calliphoridae. The recent dispersion of calliphorids was important in the dispersal of Angomonas worldwide. The genus Herpetomonas now comprises 13 valid species including 5 new species. Some species of Herpetomonas are generalist parasites of flies and appear to be as cosmopolitan as their hosts. The proposed taxa may help to elaborate more efficient criteria for a better classification of the Trypanosomatidae.