Natural Habitat

Leptospires are present in the tubules of mammalian kidneys and are excreted in urine, often for several months. Some serovars may persist in the genital tract of carrier animals. Characteristically, a reservoir or maintenance host shows minimal or no clinical signs. A protracted shedder state is usual in maintenance hosts and they are the main source of environmental contamination. Transmission of infection can then occur to other animal species, termed incidental hosts. Incidental hosts species are less susceptible to infection than maintenance hosts but exhibit more severe disease and are inefficient transmitters of infection to other animals. Nevertheless, protacted shedding of leptospires in urine can occur in animals which have recovered from clinical disease. Significant reservoirs of animal and human leptospirosis are shown in Table 31.4. Indirect exposure depends on wet environmental conditions and a mild climate that favour the survival of leptospires. Streams and ponds can be a source of infection as can aerosols of urine in cowsheds and milk from infected cows. Leptospirosis occurs worldwide.

Pathogenesis

The leptospiral genome is made up of two chromosomes, a larger one of 4400 kb and a smaller one of 350 kb in size. The full genome sequences of two serovars of Leptospira interrogans, two strains of Leptospira borgpetersenii serovar Hardjo and two strains of L. biflexa serovar Patoc have been completed (Ren et al. 2003, Nascimento et al. 2004, Picardeau et al. 2008). Comparative analysis of these genomes provides insight into the physiology and pathogenesis of pathogenic leptospires. However, many of the identified genes have no known function as it appears that the pathogenic mechanisms of leptospires differ from those of most other bacterial pathogens and homologues of these genes have not been identified in other organisms. Leptospires gain entry through mucous membranes or damaged skin as a result of direct or indirect contact. Motility and chemotaxis are essential for penetration of host tissues at this stage of infection. At least 79 motility-associated genes have been identified in the L. interrogans genome, 42 of which are common to Borrelia burgdorferi and Treponema pallidum (Nascimento et al. 2004). Colonization of host tissues is essential in the early stages of infection and afimbrial adhesins of Leptospira serovars have been characterized. After epithelial penetration there is haematogenous spread with localization and proliferation in parenchymatous organs, particularly the liver, kidneys, spleen and sometimes meninges. This phase of infection is likely to be mediated by the secretion of enzymes capable of degrading host cell membranes (Ren et al. 2003). Genes encoding both haemolysins and proteases have been identified. Some of the putative virulence factors of leptospires are given in Table 31.5. The role of some putative virulence attributes in the pathogenesis of disease has been proven through the development of mutagenesis systems for leptospires but many aspects of molecular pathogenesis remain unknown. Penetration and multiplication in the foetus can occur in pregnant animals leading to foetal death and resorption, abortion or weak offspring. The foetus, if infection occurs in the third trimester, can produce specific antibodies and may overcome the infection. Antibody production in infected animals begins a few days after the onset of leptospiraemia aand leptospires are cleared from the circulation by about 10 days after infection. Leptospires are phagocytosed by macrophages in the presence of specific antibody but virulent leptospires can induce apoptosis of macrophages both in vivo and in vitro (Mérien et al. 1997, 1998). Leptospires tend to persist in sites such as renal tubules, eyes and uterus where antibody activity is minimal. In the kidneys the organisms localize in the lumen of the proximal convoluted tubules. The relative ease with which establishment and persistence of infection occurs in maintenance hosts may be explained in part by the down regulation of some outer membrane lipoproteins in vivo and the consequent lack of recognition of infection by the immune response of the host (Haake et al. 1998).

Leptospires damage vascular endothelium resulting in haemorrhages. Serovars in the serogroups Autumnalis, Grippotyphosa, Icterohaemorrhagiae and Pomona produce a haemolysin that is probably responsible for the haemoglobinuria (redwater) in young calves infected with these serovars. The pathogenesis of equine recurrent uveitis is thought to involve the production of antibodies against leptospiral antigens, probably membrane proteins, which cross-react with ocular tissues (Verma et al. 2005). Table 31.6 summarizes the syndromes of leptospirosis in domestic animals. Serological evidence indicates that a variety of leptospiral serovars can infect cats but disease appears to be uncommon in this animal.

Laboratory Diagnosis

Diagnosis of infection with leptospires by demonstration of the organism using conventional methods is problematic. Specimens of body fluids can be examined by dark-field microscopy but this is an insensitive technique as approximately 10⁴ organisms/mL must be present for one leptospire to be visible per field. Culture of blood or urine is a highly specialized technique, requires prolonged incubation times and is performed by few laboratories for veterinary specimens. Diagnosis in animals relies largely on serology although newer immunological and molecular techniques for demonstration of the presence of the organisms are described and may greatly assist with diagnosis in the future.