Pathology and pathogenesis of human leptospirosis: a commented review

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.

Pathology and pathogenesis of human leptospirosis: a commented review

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.

Human hemorrhagic pulmonary leptospirosis: pathological findings and pathophysiological correlations.

BACKGROUND: Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil's syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease. PRINCIPAL FINDINGS: Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage. CONCLUSIONS: Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease.

Stem cell apoptosis in HIV-1 alopecia.

BACKGROUND: Diffuse alopecia occurs in almost 7% of HIV-1-infected patients. Telogen effluvium is the main pathogenic mechanism involved. Apoptotic keratinocytes in the outer root sheath at bulge level was described as the most characteristic histopathologic finding of this kind of hair loss. METHODS: A case-control study was conducted to investigate the occurrence of apoptosis of follicular stem cells at the bulge in diffuse alopecia of HIV-1 infection. We applied a double-staining procedure to transverse scalp sections from 15 HIV-1-infected patients and 12 controls, with the monoclonal antibody anticytokeratin 19 as stem cell marker and TUNEL technique to identify apoptosis. RESULTS: Eighty percent of cases and 25% of controls presented at least one double-stained follicle. The proportion of positive follicles per section was 48% (+/-7%) for cases and 26% (+/-13%) for controls. CONCLUSION: Our study demonstrated that diffuse alopecia related to HIV-1 infection represents a hair cycle disturbance and that part of the follicular stem cell population become apoptotic in a higher proportion than normal subjects. We found no cytotoxic folliculitis. Owing to its cell-cycle interaction and caspase-induction capacities, we propose HIV-1 viral protein R as a possible follicular stem cell apoptosis inductor.