The etiologic agent for leptospirosis, as the name implies, are spirochetes from the genus Leptospira. Two main classification systems are being used for the genus. The traditional system is based on phenotypic characteristics, classifying the genus into 2 main species: Leptospira interrogans and L biflexa. Specificity of the various serovars within the species serogroups is conferred by lipopolysaccharide (LPS) O-antigens. L interrogans strains are considered pathogenic with over 200 serovars, whereas 60 serovars of L biflexa strains have been identified, which are considered saprophytic.  The second classification system is based on DNA-DNA hybridization, which has identified 20 different species in the genus Leptospira.   Common pathogenic species in humans include L canicola, L hardjo, L hebdomadis, L autumnalis, and L weilii.  According to the WHO, the most common serogroups are Icterohaemorrhagiae, Pomona, Sejroe, Australis, Autumnalis, and Grippotyphosa. 
Infection is initiated through direct or indirect contact with urine of infected animals. Other sources of exposure include contact with blood or fluids, or tissues of parturition of infected animals. Leptospira are maintained in nature by means of chronic renal infection in host animals. Rodents and small mammals are the most common hosts but infection can also be acquired after contact with cattle, pigs, and other domestic and wild animals. Once these animals get infected, they will excrete or shed leptospires in their urine for the remainder of their life. Leptospires penetrate through broken skin, mucous membranes, inhalation of respiratory droplets, and waterlogged contact with intact skin and conjunctivae. The incubation period is generally 7 to 14 days but ranges between 2 and 30 days. Dissemination of leptospires is probably a result of motility of the organism. Virulence factors have not been well described; however, it has been postulated that pathogenic leptospires release hemolysins, sphingomyelinases, and phospholipases. Additional potential virulence factors include toxin production, immune mechanisms, and surface proteins. A well-described major surface lipoprotein is LipL32, which is present in pathogenic strains.  LipL32 is a target of the immune response and is involved in the development of tubulointerstitial nephritis in patients with renal insufficiency.   TLR2 (toll-like receptor 2) has an important role in leptospiral protein and lipopolysaccharide recognition.  Disease presents in 2 phases: the acute/initial (or septicemic) phase characterized by high fevers, malaise, headache, myalgia, and abdominal pain followed 5 to 7 days later by the second, immune phase associated with antibody production and excretion of the organism in urine. During the immune phase, patients suffer from severe systemic manifestations, such as renal failure, hepatic failure, and pulmonary hemorrhages, which can be fatal.