MS

thesisThe early detection of infectious disease outbreaks is key to their management and initiation of mitigation strategies. This is true whether the disease is naturally occurring or due to intentional release as an act of terrorism. In recent times, this has become evident with the anthrax bioterrorism attacks of October 2001, the occurrence of emerging infections such as West Nile Virus and Severe Acute Respiratory Syndrome of the concern for a new pandemic of influenza based on H5N1 avian influenza. Public health surveillance efforts at the University of Utah have been place for several years and came to the forefront during the 2002 Winter Olympic Games. At that time, an electronic medical record-based system was developed and deployed to perform daily surveillance of patients visiting the clinics and emergency department of the University of Utah Health Care System. This effort was then followed by a detailed validation of the computer rules used in the surveillance system, with special emphasis on the early detection of central nervous system (CNS) syndromes such as meningitis and encephalitis. These syndromes are of importance to both emerging infections such as West Nile Virus and for NIH/CDC Category B threat agents such as Eastern and Western Equine Encephalitis. True CNS syndromes caused by infectious agents represent a small proportion of patients seen at the emergency department of a large tertiary hospital. "Reason for visit" chief complaint data were poor predictors for the early detection of CNS syndromes. Orders and early results from the laboratory testing of cerebro-spinal fluid were useful for the early detection of meningitis and encephalitis. Overall, computer-based surveillance methods have a role to play in the early detection of infectious diseases. In particular, this project has contributed to public health surveillance by moving the field beyond complaint data and has shown the validity of suing computer-based rules for the detection of meningitis and encephalitis

Characterization of a filarial retinol-binding protein

Filarial parasites are a major public health problem in a number of third world countries, where there are an estimated 120,000,000 cases of lymphatic filariasis and 20,000,000 cases of onchocerciasis. In an attempt to generate a recombinant DNA based subunit vaccine for this disease, our laboratory has focused on aspects of the parasite\u27s metabolism that are unique to it and distinct from that of the host. One function that appears to be critical in parasite physiology is the accumulation of retinoids. Considerable evidence in the literature suggests that filarial parasites sequester retinoids by synthesizing high affinity retinol binding proteins (RBP). The current work is based on the hypothesis that an immune response against parasite RBP should prevent the sequestration of retinoids by filarial parasites and thereby prevent their growth in the mammalian host. Using a combination of ion-exchange and size separation chromatography, we have purified a retinol-binding protein from the dog heartworm Dirofilaria immitis, and obtained the N-terminal amino acid sequence of the protein. The 37 amino acid sequence does not match any of the RBP\u27s catalogued in GenBank, which are all of vertebrate origin. The sequence does, however, show almost complete identity with a sequence previously reported by Tremholme, et al, to be that of a highly immunogenic antigen derived from the human filarial parasite, Onchocerca volvulus. The published sequence of this antigen (Ov20/11) was used to synthesize oligonucleotide primers for PCR amplification and several recombinant expression clones were generated. Detailed analyses of these clones showed that the recombinant clones also exhibited retinol binding activity. This thesis describes the characterization of a filarial retinol-binding protein and discusses it\u27s potential as a vaccine candidate in filarial disease.