Fungi can cause a number of diseases ranking from localized mild infections to deep-seated mycoses. Invasive fungal infections are more prevalent due to the increasing number of high-risk patients, with different degrees of immunosuppression. Nowadays, the diagnosis of fungal infections remains a significant problem. The clinical presentation is difficult to interpret, and the findings of noninvasive methods (computed tomographic scanning and X ray) are not specific. Culture results are available at the earliest in 2 to 3 days, and blood and deep-tissue sample cultures from infections with focal lesions are frequently negative. Direct microscopy and histopathological examination are rapid, but they do not always allow identification of the infecting agent to the species level. In contrast, even though the latest generation of monoclonal antibody-based enzyme-linked immunosorbent assays (ELISAs) for circulating Aspergillus and Candida antigens are specific, they lack sensitivity. Thus, rapid methods that are sensitive and specific are needed. In this Doctoral Thesis a sensitive and specific PCR method and dot immunobinding assay to detect very low levels of fungi components in blood samples have been successfully developed. On the other hand, despite efforts during the last few years to elucidate the cause of AZOOR, multifocal choroiditis, serpiginous choroiditis and some neurodegenerative diseases like multiple sclerosis, this has not been achieved. Intensive research for an infectious agent that may directly provoke or trigger these diseases has been carried out in many laboratories. A number of viruses, mostly from the herpesvirus group, have been pointed out as the culprit. In the present PhD Thesis we have study the possibility that AZOOR, multifocal choroiditis, serpiginous choroiditis and multiple sclerosis may have a fungal origin. Our results provide evidence that in most of the patients studied there are signs of fungal infection. A high percentage of these patients contain fungal genomes and fungal antigens in blood. Thus, some of these patients exhibit high antibody titers against several Candida spp. and several of them contain significant amounts of β-1,3 glucan in serum. Anyway, to distinguish if fungal infections are the cause or a consequence of these diseases, it must be necessary to extend this study with a higher number of patients and to carry out clinical trials with antifungal compounds.

El trabajo presentado en esta Tesis Doctoral ha sido realizado en el Centro de Biología Molecular “Severo Ochoa”, bajo la dirección del Dr. Luis Carrasco Llamas. Nuestro grupo de investigación agradece a la Organización Nacional de Ciegos Españoles (ONCE) su colaboración en la financiación del proyecto de investigación que ha permitido llevar a cabo la presente Tesis Doctoral.

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura 23-03-2007

Peer reviewed