Leptospirosis

Ralph D. Feigin

Leptospirosis is a disease caused by a single family of organisms that contains multiple serogroups and serotypes. The disease is characterized by a broad spectrum of clinical findings.

EPIDEMIOLOGY

Virtually all mammals can be infected by leptospires (i.e., tightly coiled spirochetes) and can transmit disease caused by this genus of organisms. In various parts of the world, field mice, rats, moles, gerbils, hedgehogs, shrews, foxes, jackels, mongooses, civets, bandicoots, dogs, skunks, raccoons, opossums, and cattle have been implicated as sources of human infection. Leptospires also have been isolated from reptiles and birds. A host species may serve as a reservoir for one or more serotypes of leptospires, and a particular serotype may be hosted by many different animal species. Two or more animal hosts for the same serotype may exist in the same geographic area. Virtually any animal susceptible to infection by leptospires may become a temporary urinary shedder of the organisms.

Transmission of leptospires to humans occurs through contact with urine, blood, tissues, or organs of infected animals or exposure to an environment that has been contaminated by leptospires. Humans generally represent a dead end in the chain of infection, although person-to-person transmission can occur. Human-to-human transmission has been reported through human milk obtained by a breast-fed infant from a lactating mother who was infected with Leptospira interrogans. Leptospires may enter breaks in the skin or may penetrate the mucous membranes of the conjunctiva, nasopharynx, or vagina.

Leptospires may be transmitted from soil or water to humans. A warm climate (warmer than 25°C), moisture, and soil or surface water with pH values between 6.2 and 8.0 are optimal environments for survival of leptospires. These conditions are found commonly in many tropical regions throughout the year and in temperate zones during the late spring, summer, and autumn months.

The role of occupation as a major risk factor in leptospirosis was emphasized in the 1960s. Since then, however, increasing numbers of cases have been reported among children who live in urban areas and who participate in outdoor recreation. In rural areas, leptospires may be acquired from swimming in farm ponds or in contaminated rivers and streams.

Leptospirosis has become increasingly prevalent among children, students, and housewives. Cases from urban and suburban communities have been reported more frequently than have cases from rural areas. The dog has been incriminated increasingly as an important vector and reservoir of this disease.

PATHOPHYSIOLOGY

Leptospires penetrate the skin or mucous membranes and then invade the bloodstream and spread throughout the body to produce a wide variety of manifestations. The organism appears to bore through connective tissue and invade various
tissues, including the anterior chamber of the eye and the subarachnoid space, without eliciting a significant inflammatory response.

Avirulent and virulent strains of leptospires are taken up by fixed phagocytes and reticuloendothelial tissue in vivo. The severity of the lesions produced correlates positively with the number of organisms. Specific resistance apparently is mediated by antibodies, which increase the efficacy of clearance of leptospires from the bloodstream by improving phagocytosis and thereby enhancing opsonization. Polymorphonuclear leukocytes are not an efficient defense factor against pathogenic leptospires in nonimmune hosts. The virulence of leptospires appears to be related to their ability to resist killing by neutrophils and serum components.

Selected clinical and histologic findings in human leptospirosis suggest that pathogenicity may result partially from enzymes, toxins, or other metabolites that are elaborated by or released by lysed leptospires. Endotoxin has been demonstrated in extracts of leptospires, but its precise role in the pathogenesis of leptospirosis remains unknown.

The development of jaundice and hemolytic anemia in patients with leptospirosis suggests that hemolysis may play a role in the pathogenesis of this disease. Hemolysis may persist during leptospirosis, a finding suggesting that circulating hemolysin is adsorbed by erythrocytes early during the course of leptospirosis and that the erythrocytes subsequently lyse despite the development of serum antibody.

In humans, a profound derangement in hepatic function has been associated with leptospirosis. Necrosis of liver cells is an infrequent occurrence, however, and the activity of serum glutamic oxaloacetic and pyruvic transaminases generally is elevated only slightly. The most prominent clinical manifestations of hepatic dysfunction include icterus and impaired production of the clotting factors dependent on vitamin K, decreased serum albumin, and increased serum globulins. These abnormalities have occurred in both icteric and anicteric patients with leptospirosis.

Renal failure is an important cause of death in patients with leptospirosis. In patients who die during the first week of disease, renal changes include cloudy swelling or isolated tubular epithelial cell necrosis. In those who die during the second week of illness, numerous foci of tubular epithelial necrosis are apparent. When patients die after the twelfth day of illness, an inflammatory infiltrate in the kidney is widespread, involving the medulla and the cortex. Impaired renal blood flow appears to constitute a fundamental alteration of the nephropathy associated with leptospirosis. Diminution in renal perfusion is suggested by hypotension, hypovolemia, and circulatory collapse. Reversible oliguria observed during the course of leptospirosis has been attributed to reduced renal blood flow resulting from hypotension, a deficit of extracellular fluid, or both. Rarely, adrenal insufficiency may occur after hemorrhagic infarction of the adrenal glands.

Cardiac dysfunction can lead to hypoperfusion in severe leptospirosis. Focal hemorrhagic myocarditis, pericarditis, and cardiac arrhythmias have been documented. Cardiac malfunction may occur secondary to hypotension, electrolyte imbalance, hypovolemia, or uremia. Other pathologic alterations of leptospirosis include acute hemorrhagic lobar pneumonia and massive hemoptysis, meningitis, meningoencephalitis and encephalitis, radiculitis, myelitis, and peripheral neuritis.

The intraocular fluid provides a protective environment for leptospires. Despite the development of high antibody titers in serum, leptospires may remain viable in the anterior chamber of the eyes for many months. This phenomenon appears to be responsible for the recurrent, chronic, or latent uveitis syndromes of patients with leptospirosis.

Myalgia is a common complaint in patients with all forms of leptospirosis. Myalgia appears to be the result of pathologic changes, including vacuolation of the cytoplasm of the myofibrils.

CLINICAL MANIFESTATIONS

Common Leptospirosis

Leptospirosis is an acute systemic infection characterized by generalized vasculitis. Diminished awareness of this disorder, coupled with the diversity and nonspecificity of its presentation, accounts for the significant number of cases that go unrecognized.

The usual incubation period is 7 to 12 days, but a range of 2 to 20 days has been reported. The variation in incubation periods is not serotype-specific and has no prognostic significance.

The first (septicemic) stage of leptospirosis is characterized by the development of an acute systemic infection with an abrupt onset of symptoms. Fever, myalgia, arthralgia, and conjunctivitis may be noted. This phase terminates in approximately 4 to 7 days, with symptomatic improvement and defervescence. These changes coincide with the disappearance of leptospires from the blood, cerebrospinal fluid (CSF), and all other tissues except the aqueous humor of the eye and renal parenchyma. Antibody titers to leptospires develop rapidly, heralding the onset of the second (immune) stage of the illness. This stage, which lasts 4 to 30 days, may be associated with additional signs and symptoms of central nervous system involvement including stiff neck, photophobia, and irritability. Leptospiruria occurs commonly and continues for 1 week to 1 month. This immune phase of the disease generally is unaffected by antibiotic therapy. Meningitis and hepatic or renal involvement and meningitis reach peak intensity during this stage of disease.

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