abstract: Valley Fever (VF), is a potentially lethal fungal pneumonia caused by Coccidioides spp., which is estimated to cause ~15-30% of all community-acquired pneumonias in the highly endemic Greater Phoenix and Tucson areas of Arizona. However, an accurate antigen-based diagnostic is still lacking. In order to identify protein and glycan antigen biomarkers of infection, I used a combination of genomics, proteomics and glycomics analyses to provide evidence of genus-specific proteins and glycosylations. The next goal was to determine if Coccidioides-specific glycans were present in biological samples from VF patients. Urine collected from 77 humans and 63 dogs were enriched for glycans and evaluated by mass spectrometry for Coccidioides-specific glycans and evaluated against a panel of normal donor urines, urines from patients infected with other fungi, and fungal cultures from closely related pneumonia-causing fungi. A combination of 6 glycan biomarkers was 100% sensitive and 100% specific in the diagnosis of human VF subjects, while only 3 glycan biomarkers were needed for 100% sensitivity and 100 specificity in the diagnosis of dog VF subject. Additionally, a blinded trial of 23 human urine samples was correctly able to classify urine samples with 93.3% sensitivity and 100% specificity. The results of this research provides evidence that Coccidioides genus-specific glycosylations have potential as antigens in diagnostic assays. / Dissertation/Thesis / Doctoral Dissertation Microbiology 2019

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / FundaÃÃo de Amparo a CiÃncia e Tecnologia / Coccidioidomicose à uma micose sistÃmica que acomete o homem e outros animais domÃsticos e silvestres, causada pelo fungo dimÃrfico geofÃlico Coccidioides posadasii. Nos Ãltimos anos, a melhoria dos mÃtodos de diagnÃstico micolÃgico e o aumento da ocorrÃncia de doenÃas imunossupressoras causaram grande impacto na incidÃncia das micoses profundas e oportunistas no mundo. Apesar da existÃncia de terapias antifÃngicas eficazes contra a coccidioidomicose, a busca por novas drogas para o tratamento desta doenÃa se faz necessÃria. O objetivo desse estudo foi determinar o efeito inibitÃrio, in vitro, e o mecanismo de aÃÃo dos anÃlogos quÃmicos da isoniazida, isolados e em combinaÃÃo com os antifÃngicos anfotericina B (AMB) e itraconazol (ITC), frente a cepas de Coccidioides posadasii (n=12). Para isso 12 cepas de C.posadasii, foram repicadas em Ãgar dextrose batata e utilizadas na realizaÃÃo dos testes de sensibilidade frente ao agente antituberculose isoniazida (INH) e seus anÃlogos quÃmicos. Os ensaios foram conduzidos por meio do teste de macrodiluiÃÃo em caldo ou definiÃÃo da concentraÃÃo inibitÃria mÃnima (CIM) e o sinergismo foi avaliado pelo mÃtodo do tabuleiro. Os anÃlogos quÃmicos inibiram o crescimento de todas as cepas de C. posadasii testadas isoladamente, com valores de CIM para cada composto que variaram de 100 a 400 Âg/mL, para os anÃlogos P3-[Nâ-(1- (4-methoxifeniletilideno) isonicotinohidrazida] P5- [Nâ- (1-m-tolileilidene) isonicotinohidrazida] e P6- [Nâ-(1-(4-metilfenil) etilideno) isonicotinohidrazida], de 25 a 100 Âg/mL para a PACT- Nâ- (1-feniletilideno) isonicotinohidrazida e de 0,0625 a 0,125 Âg/mL para AMB e 0,125 a 0,5 Âg/mL para ITC. Quanto a combinaÃÃo entre as drogas antifÃngicas e os anÃlogos quÃmicos da droga isoniazida, todos foram capazes de inibir o crescimento in vitro das cepas de C. posadasii. Sinergismo foi detectado em 8 combinaÃÃes nÃo sendo observado nenhum antagonismo em nenhuma delas. Os anÃlogos da isoniazida apresentaram valores de CIM de 2, 4, 8, 16, 32 vezes superior à atividade da droga antituberculose padrÃo. A extraÃÃo dos esterÃis e a permeabilidade da membrana fÃngica foram averiguadas, respectivamente, por saponificaÃÃo com aquecimento e por meio da leitura do sobrenadante da suspensÃo fÃngica em comprimento de onda de 260 e 280 nm. Todos os compostos inibiram o crescimento in vitro das cepas de C. posadasii. Foi observado que os anÃlogos da isoniazida isolados e em combinaÃÃo com antifÃngicos foram capazes de causar reduÃÃo do teor de ergosterol celular; apenas os anÃlogos P3 e P6 foram capazes de alterar a permeabilidade da membrana plasmÃtica nas condiÃÃes testadas. Em conclusÃo, os resultados mostram que os anÃlogos derivados da isoniazida possuem atividade inibitÃria frente a C. posadasii

Central Nervous System (CNS) vasculitis is the most common life-threatening complication of coccidioidal meningitis. It is manifested by cerebral ischemia, hemorrhage, and infarction. We report a case of CNS vasculitis in a patient receiving chemotherapy and review of the literature on coccidioidal meningitis. The patient was treated with combination antifungal therapy and a short course of high dose corticosteroids with a modest improvement in her neurological examination after initiation of steroids.

In the early 1970s, a trial was conducted in Beagles comparing an irradiated spherule vaccine for Valley Fever against a control vaccine. The results did not show a significant difference between the vaccinated and the control dogs. Reactions to the vaccine were significant.

In the early 1970s, a trial was conducted in Beagles comparing an irradiated spherule vaccine for Valley Fever against a control vaccine. The results did not show a significant difference between the vaccinated and the control dogs. Reactions to the vaccine were significant.

In the early 1970s, a trial was conducted in Beagles comparing an irradiated spherule vaccine for Valley Fever against a control vaccine. The results did not show a significant difference between the vaccinated and the control dogs. Reactions to the vaccine were significant.

In the early 1970s, a trial was conducted in Beagles comparing an irradiated spherule vaccine for Valley Fever against a control vaccine. The results did not show a significant difference between the vaccinated and the control dogs. Reactions to the vaccine were significant.

In the early 1970s, a trial was conducted in Beagles comparing an irradiated spherule vaccine for Valley Fever against a control vaccine. The results did not show a significant difference between the vaccinated and the control dogs. Reactions to the vaccine were significant.

Thesis (Ph.D.)--Medical University of Ohio, 2006. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Garry Cole. Includes abstract. Document formatted into pages: ii, 206 p. Title from title page of PDF document. Title at ETD Web site: Evaluation of two homologous Coccidioides posadasii antigens as recombinantly expressed monovalent, divalent, and chimeric vaccine candidates. Bibliography: pages 75-83, 116-120, 165-169, 185-204.