Aetiology

The aetiological agent for leptospirosis, as the name implies, are spirochetes from the genus Leptospira. Two main classification systems are used for the genus.

The traditional system is based on phenotypic characteristics, classifying the genus into two main species: L 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.[6]

The second classification system is based on DNA-DNA hybridisation, which has identified 35 species in the genus Leptospira.[38] Common pathogenic species in humans include L canicola, L hardjo, L hebdomadis, L autumnalis, and L weilii.[6] According to the WHO, the most common serogroups are Icterohaemorrhagiae, Pomona, Sejroe, Australis, Autumnalis, and Grippotyphosa.[5]

Pathophysiology

The incubation period is generally 7-14 days, but it ranges between 2 and 30 days. Infection most often occurs as a result of direct or indirect contact with urine of infected animals. Other sources of exposure include contact with blood, fluids, or tissues of parturition of infected animals. Leptospira are maintained in nature by chronic renal infection in carrier animals. The animal reservoirs that probably account for the majority of leptospirosis are rats, cattle, dogs, and other peridomestic small mammals.[27] Once infected, the animal will excrete leptospires in its urine for the remainder of its life.

Most cases of leptospirosis are thought to result from percutaneous exposure or mucosal contact with water or soil that is contaminated with leptospires.[34] The risk of developing leptospirosis increases when skin integrity is compromised by wounds.[36][39] Although several factors are likely to affect leptospiral survival in water (e.g., pH, temperature), pathogenic Leptospira can survive and maintain virulence for at least 20 months, even in unfavourable environmental conditions.[27][40] The low density of leptospires in soil and the rapid dilution that occurs in larger bodies of water suggests that many infections result from contact with low-dose exposures.

Dissemination of leptospires within the body probably occurs as a result of the motility of the organism. The virulence of leptospirosis species varies widely among strains, and while studies continue to identify new virulence factors, they are not fully defined or understood mechanistically. Pathogenic leptospires are thought to release haemolysins, sphingomyelinases, and phospholipases. Additional potential virulence factors include toxin production, immune mechanisms, and surface proteins. LipL32, a well-described surface lipoprotein, is present in pathogenic strains.[41] LipL32 is a target of the immune response and is involved in the development of tubulointerstitial nephritis in patients with renal insufficiency.[1][2] Toll-like receptor 2 (TLR2) has an important role in leptospiral protein and lipopolysaccharide recognition.[42] Research also suggests that genetic predisposition and immune-related factors affect the natural history of infection.[43][44]

While most cases of infection are subclinical, patients who develop symptoms may present in two phases: the acute/initial (or septicaemic) phase, characterised by high fevers, malaise, headache, myalgia, and abdominal pain, followed 5-7 days later by the second, immune phase, associated with antibody production and excretion of the organism in urine. During the immune phase, patients can have severe systemic manifestations, including renal failure, hepatic failure, and pulmonary haemorrhages, which can be fatal.

Classification

World Health Organization (WHO): human leptospirosis clinical manifestations[5]

According to the WHO, leptospirosis is classified as follows:

  • Mild, influenza-like or undifferentiated febrile illness

  • Weil syndrome, which is characterised by jaundice, renal failure, haemorrhage, and myocarditis with arrhythmias

  • Meningitis/meningoencephalitis

  • Pulmonary haemorrhage with respiratory failure.

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