Pathology and pathogenesis of human leptospirosis: a commented review

Abstract

Leptospirosis is an acute bacterial septicemic febrile disease caused by pathogenic leptospires, which affect humans and animals in all parts of the world. Transmission can occur by direct contact with infected animals or, more commonly, through indirect contact with water or soil contaminated with urine from infected animals. Leptospires enter the body by penetrating mucous membranes or skin abrasions and disseminate through the hematogenic route. In humans, leptospirosis may cause a wide spectrum of symptoms. Most cases have a biphasic clinical presentation, which begins with the septicemic phase followed by immune manifestations. The severe forms of the disease may be life threatening with multisystem damage including renal failure, hepatic dysfunction, vascular damage, pulmonary hemorrhage and muscle lesions. In this review, we present and discuss the pathogenesis of the human disease and the mechanisms of cell membrane injuries, which occur mainly due to the presence of leptospires and/or their antigen/s in the host tissues.

Figure 1. - Immunohistochemistry and histology analyses. A) Expression of E-cadherin in lobule of normal human liver; B) Areas of diminished and/or absent E-cadherin in liver in human leptospirosis; C) Liver biopsy in human leptospirosis. Hepatic cells show slight variation in size and occasional more marked hyaline cytoplasmatic change. Portal space is unremarkable; D) Human liver biopsy in leptospirosis showing areas of dense reticulin framework. Variations of size and shape of liver cells is more evident with reticulin staining; E) VE-cadherin in normal human lung; F) VE-cadherin in lung in leptospirosis. Marked intra-alveolar hemorrhage. Dilated and discontinuous capillary walls with irregular staining

Figure 2. – Immunohistochemistry and histology analyses. A) VE-cadherin in lung in human leptospirosis. Small openings in the alveolar lining. Areas of intra-alveolar hemorrhage; B) Low view of VE-cadherin in human lung in leptospirosis. Intra-alveolar hemorrhage and diminished and/or absent staining of capillary walls; C) Normal expression of VE cadherin in normal human glomerular capillaries; D) VE-cadherin expression is diminished and/or absent in focal areas of glomerular capillaries in human leptospirosis