Two experiments were performed to evaluate effects of amprolium administration at specific times and concentrations in replacement broiler breeders of three genetic lines vaccinated against coccidiosis. Effects on performance parameters including body weight and flock uniformity, and post-vaccination oocyst cycling patterns were evaluated in addition to development of immunity following clinical Eimeria challenge according to gross and microscopic lesion scoring, post-challenge body weight gain (BWG), and total oocyst output. Experiment one was conducted on fresh pine shavings while experiment two was conducted on used litter remaining in treatment pens from the first trial. No significant differences were seen among treatment groups with regard to body weight in either trial. Increased magnitude of oocyst shedding was observed in trial one, Line A with the group receiving amprolium on day 10. Trends in the data indicated increased uniformity in Line A related to amprolium administration following day 21. The group in Line A receiving amprolium at day 10 showed a significantly lower degree of total oocyst output following challenge than the other medicated groups. The group receiving amprolium on day 10 in Line B showed significant reduction in post-vaccination oocyst shedding following treatment in both trials while all shedding was delayed in trial two when compared to the first trial. Effects on uniformity in Line B pullets varied between trials with trends indicating it being advantageous when used litter was a factor. Higher post-challenge BWG was observed in Line B pullets administered the low concentration at day 16 than the controls. Reductions in gross lesion development were seen in Line B pullets in both trials. Line C pullets receiving the highest concentration of amprolium at day 16 showed significantly less uniformity in trial one while the controls appeared to perform better than all medicated groups in trial two. All medicated groups in Line C exhibited delayed and increased magnitudes of oocyst shedding in trial two. These data indicate that the effects of amprolium on performance and immunity development are variable according to genetic strain and indicated that administration may be influenced by litter condition.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / In the first portion of this thesis, epidemiology, clinical signs and distribution of lesions in the brain of thirty one cases of polioencephalomalacia (PEM) in cattle from the Southern (13 cases) and Midwestern (18 cases) Brazil were studied. Morbidity (0.04%-6.66 %), mortality (0.04%-6.66 %), and lethality (50%-100%) rates were similar in both regions studied. Cases occurred mainly in cattle raised at pasture; in the Southern the disease affected mainly young cattle while mainly older cattle were affected in the Midwest. Clinical signs more frequently observed included blindness, incoordination, circling, opisthotonus, recumbence and paddling movements. Clinical course varied from 12 hours to 8 days. In 11 cases no gross changes were observed in the brain. Main gross findings in the brain of remaining cases included congestion with swelling and flattening of gyri, softening and yellow discoloration of cerebral cortex, hemorrhagic foci in the brain stem, cerebellum and telencephalon, and cerebellar herniation. The main histopathological changes were in the cortex of occipital, parietal and frontal telencephalic lobes; however less prominent and less frequently found lesions occurred in the hippocampus, basal nuclei, thalamus, midbrain, and cerebellum. The type of microscopic cortical lesions was consistent in all cases and included segmentar laminar neuronal necrosis, spongiosis, swollen of vascular endothelial nuclei, Alzheimer type II astrocytes and infiltration of gitter cells. In 20% of the cases there was mild lymphohistiocytic cellular infiltrate and in 13% of the cases there was mild infiltrate by neutrophils and eosinophils. Additionally, mild to moderate necro-hemorrhagic lesions were observed in 49% of the cases in the basal nuclei, in 39% of the cases in brain stem and in 26% of the cases in the thalamus. In the cortical laminae of the occipital, parietal and frontal telencephalic lobes, most frequently affected cortical layers both by neuronal necrosis and edema were external and internal granular layers. Both gyri and sulci were equally affected. In the second portion of the thesis, one experimental model for the study of the etiology, pathology, and pathogenesis of polioencephalomalacia in ruminants was established. The condition was induced in five sheep by oral administration of amprolium at daily doses of 500 and 1,000 mg per Kg of live body weight respectively for 28-59 days and for 13-39 days. Clinical course varied from 3 to 7 days. Clinical signs included depression, incoordination, midriasis, grinding of the teeth, blindness, and laying down with opisthotonus and paddling movements. Drooling and a sawhorse stance were observed in one sheep and myoclonus in another one. Main gross lesions were restricted to the central nervous system and included swelling of the brain with flattening of telencephalic gyri, and hemorrhages in the parietal and occipital lobes of the telencephalon. Histologically, there was segmental laminar neuronal necrosis (red neurons) associated with edema, swelling of endothelial cells, hemorrhages and infiltration by foamy macrophages (gitter cells). These changes were more marked in the frontal, parietal and occipital telecephalic lobes and there was sharp demarcation between the lesions and the adjacent normal neuropile. Additionally, similar, but less marked lesions were seen in the mesencephalon, thalamus and hippocampus. Considering the consistent reproducible aspects of polioencephalomalacia in sheep using amprolium, this may be an useful model for the study of the disease. / Na primeira parte dessa tese, foram estudados a epidemiologia, os sinais clínicos e a distribuição das lesões no encéfalo de 31 casos de polioencefalomalacia (PEM) em bovinos do Estado do Rio Grande do Sul (13 casos) e da Região Centro-Oeste do Brasil (18 casos). As taxas de morbidade (0.04%-6.66 %), mortalidade (0.04%-6.66 %) e letalidade (50%-100%) foram semelhantes em ambas as regiões estudadas. Os casos ocorreram principalmente em bovinos criados de forma extensiva em pastagem. Na Região Sul a doença afetou principalmente bovinos jovens, enquanto que principalmente bovinos mais velhos foram afetados no Centro-Oeste. Os sinais clínicos mais freqüentemente observados incluíram cegueira, incoordenação, andar em círculos, opistótono, decúbito e movimentos de pedalagem. A evolução do quadro clínico variou de 12 horas a 8 dias. Em 11 encéfalos não foram observadas alterações macroscópicas; as principais alterações macroscópicas nos outros casos incluíam congestão com tumefação e achatamento das circunvoluções, amolecimento e amarelamento do córtex telencefálico, focos de hemorragia no tronco encefálico, cerebelo e telencéfalo e herniação cerebelar. As principais alterações histológicas ocorreram no córtex dos lobos telencefálicos occipital, parietal e frontal; no entanto, lesões menos acentuadas e menos frequentemente observadas ocorreram no hipocampo, núcleos da base, tálamo, mesencéfalo e cerebelo. O tipo de lesão microscópica cortical era consistente em todos os casos e incluía necrose neuronal laminar segmentar, espongiose, tumefação do núcleo das células endoteliais, astrócitos Alzheimer do tipo II e infiltração por células gitter. Em 20% dos casos havia um leve infiltrado celular linfo-histiocitário e em 13% dos casos havia leve infiltrado de neutrófilos e eosinófilos. Adicionalmente, lesões necro-hemorrágicas leves ou moderadas foram observadas em 49% dos casos nos núcleos da base, em 39% dos casos no tronco encefálico e em 26% dos casos no tálamo. Na substância cinzenta dos telencéfalos frontal, parietal e occipital, as camadas granular externa e interna foram as mais afetadas tanto por neurônios necróticos quanto por edema. Tanto os giros quanto os sulcos foram afetados igualmente. Na segunda parte da tese, foi estabelecido um modelo experimental para o estudo da etiologia, patologia e patogênese da polioencefalomalacia em ruminantes. A condição foi induzida em cinco ovinos pela administração oral de amprólio nas doses diárias de 500 e 1.000 mg/Kg de peso vivo, respectivamente por 28-59 dias e 13-39 dias. O curso clínico foi de 3-7 dias. Os sinais clínicos incluíam depressão, incoordenação, midríase, bruxismo, cegueira e decúbito com opistótono e movimentos de pedalagem. Salivação excessiva e posição de cavalete foi observada em um ovino e mioclonias em um outro. Os principais achados de necropsia restringiam-se ao sistema nervoso central e incluíam tumefação do encéfalo com achatamento dos giros telencefálicos e hemorragias nos lobos parietal e occipital do telencéfalo. Histologicamente, havia necrose segmentar laminar de neurônios associada a edema, tumefação de células endoteliais, hemorragias e infiltração por macrófagos espumosos (células gitter). Essas alterações eram mais marcadas nos lobos frontal, parietal e occipital do telencéfalo e havia uma demarcação abrupta entre as lesões e o neurópilo normal adjacente. Adicionalmente, lesões semelhantes, mas menos acentuadas, eram observadas no mesencéfalo, tálamo e hipocampo. Levando em consideração a reproducibilidade regular dos aspectos da polioencefalomalacia em ovinos pela administração de amprólio, esse modelo pode ser útil para o estudo da doença.