Hamster model of leptospirosis.

Animal inoculation remains essential for many aspects of leptospirosis research. Although pathogenic leptospiral strains may be able to infect a wide variety of animals, the Golden Syrian hamster is the preferred model because its susceptibility to infection and the reproducibility of the results. Common applications include determination of strain infectivity, restoring virulence to culture-attenuated strains, assessing usefulness of potential vaccines or diagnostic antigens, and examining pathology of mammalian infection. In many respects, acute leptospirosis in the hamster reproduces the severe form of human leptospirosis (see Commentary). This unit provides a detailed description of the procedures involved in the hamster model of leptospirosis, including housing and handling of hamsters and intraperitoneal challenge (Basic Protocol 1), and monitoring response to challenge (Basic Protocols 2 and 3, and Alternate Protocol). Methods are provided for demonstrating infection, including culture isolation of leptospires from blood and tissues (Basic Protocol 2) and serologic studies and histopathology (Basic Protocol 3). Quantitative PCR is provided as an alternative detection method (Alternate Protocol). Although leptospires disseminate to many organs, the tissues of the liver and kidney are the primary targets of infection. The liver is heavily infected during the initial stage of hematogenous dissemination. Persistent infection occurs primarily in the kidneys of animals that survive acute disease. Infection of the renal tubules leads to shedding of infectious organisms in the urine, which is the primary mode of transmission in nature. A safety policy memorandum is provided (see Strategic Planning) that should be read and signed by all staff. In the Commentary section, a detailed rationale is presented for use of hamsters as an animal model of leptospirosis. The effects of challenge dose on the hamster model, LD50, in vitro passage of leptospiral strains, and immunological maturity are discussed. Alternative animal models are evaluated with reference to the concept of accidental versus reservoir hosts. The advantages and disadvantages of the hamster model are considered, with reference to use of alternative host animals to address specific research or vaccine-development issues. CAUTION: Pathogenic Leptospira species are Biosafety Level 2 (BSL-2) pathogens. L. interrogans, L. kirschneri, L. noguchii, L. borgpetersenii, L. santarosai, and L. weilii are known to be pathogenic for humans. Certain strains of L. inadai, L. meyeri, L. fainei, and L. alexanderi may also be pathogenic. L. biflexa, L. wolbachii, and L. parva are thought to be nonpathogens. Follow all appropriate guidelines and regulations for the use and handling of pathogenic microorganisms. See UNIT 1A.1 and other pertinent resources (APPENDIX 1B) for more information. CAUTION: Protocols using live animals must first be reviewed and approved by an Institutional Animal Care and Use Committee (IACUC) or must conform to governmental regulations regarding the care and use of laboratory animals. This experiment requires Animal Biosafety Level 2 (ABSL-2) conditions. Follow all appropriate guidelines for the use and handling of infected animals. See UNIT 1A.1 and other pertinent resources (APPENDIX 1B) for more information. Fluids and tissues of infected animals are highly infectious. Numerous laboratory-associated infections, including deaths, have been reported (Miller et al., 1987; Pike, 1976). A safety policy memorandum is provided that should be signed by all staff (see Strategic Planning).