United States. Current diagnostic procedures rely on direct stool examination, which is time-consuming, technically difficult, and expensive. An enzyme immunoassay has been developed for serologic diagnosis but is limited in value because it is not able to differentiate between current infections and cured individuals. An effective treatment with phenolics is available, but these drugs are too toxic to use except to treat active infection; thus, there is an urgent need for an improved diagnostic test to differentiate active cases rapidly, accurately, and with minimum cost. Sufficient human samples are readily available to ensure that substantive evaluation of candidate assays will be conducted promptly, with preliminary results likely to be available during 1997.

Project 5: Molecular biological and immunochemical analysis of clinical strains of tuberculosis and mycobacteriosis

Description: This project focuses on characterization of different strains of mycobacteria in Russian patients diagnosed with tuberculosis (TB).

Importance: TB, particularly drug-resistant TB, represents a serious threat to the United States and is increasing in Russia in epidemic proportions. This project is characterizing different strains of mycobacteria isolated from Russian patients diagnosed with TB and is determining the spectrum of drug resistance among them. The relation between strain virulence and the spectrum and degree of drug resistance will be explored by identifying the genes responsible for drug resistance. New antibiotics under development in Russia will be tested for their potency against these clinical strains. This project will help strengthen Russian capability in addressing the emerging TB epidemic in Russia.

Project 6: Investigation of the immunological effectivity of delivery in vivo of the Brucella main outer membrane protein by anthrax toxin components

Description: This project is an initial step toward the eventual goal of producing an effective recombinant protein vaccine or vaccine mixture for veterinary use against Brucella abortus and for protection of occupationally exposed personnel.

Importance: Human brucellosis is a disease caused by species of the bacterium Brucella. In humans it is seriously debilitating but seldom lethal. Its principal reservoirs are cattle, sheep, and swine. Human exposure is principally from direct contact with infected animals and animal products, including consumption of unpasteurized milk and milk products from infected animals. Control of the disease in humans occurs mainly by avoiding the consumption of unpasteurized milk or milk products and contact with infected animals, sacrificing infected animals and herds, and, in areas where brucellosis is endemic, veterinary vaccination. None of the current vaccines against brucellosis is completely satisfactory; their shortcomings include incomplete protection, induction of abortion, and occasional infectivity to humans. This protocol calls for the construction of chimeric genes expressing anthrax lethal factor (LF)- Brucella outer membrane protein (OMP) fusion proteins and testing of the resulting chimeric proteins when administered together with anthrax protective factor for immunological effectiveness against Brucella abortus. The LF-protective antigen (PA) cell delivery system holds great promise for an improved brucellosis vaccine, in particular, and for more effective disease prevention in the United States and Russia generally.

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