Leptospirosis 

Leptospirosis is a disease that is caused by pathogenic spirochetes of the genus Leptospira. It is considered the most common zoonosis in the world. Leptospirosis has recently been recognized as a re-emerging infectious disease among animals and humans^[1] and has the potential to become even more prevalent with anticipated global warming. Leptospirosis is distributed worldwide (sparing the polar regions) but is most common in the tropics.

Humans and a wide range of animals, including mammals, birds, amphibians, and reptiles can develop Leptospira infection. However, humans are rarely chronic carriers and are therefore considered accidental hosts. Leptospirosis is transmitted via direct contact with the body fluid of an acutely infected animal or by exposure to soil or fresh water contaminated with the urine of an animal that is a chronic carrier.

Human leptospirosis is often acquired via contact with fresh water contaminated by bovine, rat, or canine urine as part of occupational contact with these animals. The disease is also acquired during adventure travel or vacations that involve water sports or hiking, or even as a consequence of flooding.

The burgeoning exotic-pet trade further increases the likelihood of transmission. In 2005, leptospirosis was transmitted from southern flying squirrels imported from Miami, Florida, to two Japanese animal handlers employed by an importer of exotic pets. Endemic canine leptospirosis is becoming more common in the United States, and California has seen a re-emergence of disease since 2000.

Leptospirosis in humans is characterized by an acute febrile illness followed by mild self-limiting sequelae or an even more severe, and often fatal, multiorgan involvement. The disease was first described by Larrey in 1812 of fièvre jaune among Napoleon's troops at the siege of Cairo. It was initially believed to be related to the plague but not as contagious. Throughout the remainder of the 19th century, the illness was known in Europe as bilious typhoid.

A little over 100 years ago, Adolph Weil published his historic paper describing the most severe form of infection that would be later known as Weil disease.

In 1907, special staining techniques were used to confirm that a spirochete was responsible for this illness. A postmortem examination of the kidney of a person with Weil disease contained a spiral organism with hooked ends, which was first named Spirochaeta interrogans.

The leptospires are thin, coiled, gram-negative, aerobic organisms 6-20 µm in length. They are motile, with hooked ends and paired axial flagella (one on each end), enabling them to burrow into tissue. Motion is marked by continual spinning on the long axis. They are unique among the spirochetes in that they can be isolated on artificial media.

Leptospires belong to the order Spirochaetales and the family Leptospiraceae. Traditionally, the organisms are classified based on antigenic differences in the lipopolysaccharide envelopes that surround the cell wall. Serologic detection of these differences, therefore, is based on identifying serovars within each species. Based on this system, the genus Leptospira contains two species—the pathogenic Leptospira interrogans, with at least 218 serovars, and the nonpathogenic, free-living, saprophytic Leptospira biflexa, which has at least 60 serovars.

Current studies that classify the organisms based on DNA relatedness identify at least 7 pathogenic species of leptospires. However, organisms that are identical serologically may be different genetically, and organisms with the same genetic makeup may differ serologically. Therefore, some authors feel that the traditional serologic system is the most useful from a diagnostic and epidemiologic standpoint.

Although not fully understood, leptospires are believed to enter the host through abrasions in healthy skin, through sodden and waterlogged skin, directly through intact mucus membranes or conjunctiva, through the nasal mucosa and cribriform plate, through the lungs (after inhalation of aerosolized body fluid), or through the placenta during pregnancy. Virulent organisms in a susceptible host gain rapid access to the bloodstream through the lymphatics, resulting in leptospiremia and spread to all organs. The incubation period is usually 5-14 days but has been described from 72 hours to a month or more.

If the host survives the acute infection, septicemia and multiplication of the organism persist until the development of opsonizing immunoglobulin in the plasma, followed by rapid immune clearance. However, after clearance from the blood, leptospires remain in immunologically privileged sites, including the renal tubules, brain, and anterior chamber of the eye, for weeks to months. In humans, leptospires in the renal tubules and resulting leptospiruria rarely persist longer than 60 days.

During acute infection, leptospires are thought to multiply in the small blood vessel endothelium, resulting in damage and vasculitis. The major clinical manifestations of the disease are believed to be secondary to this mechanism, which can affect nearly any organ system.

• In the kidneys, interstitial nephritis, tubular necrosis, and impaired capillary permeability, as well as the associated hypovolemia, result in renal failure.
• Liver involvement is marked by centrilobular necrosis and Kupffer cell proliferation, with hepatocellular dysfunction.
• Pulmonary involvement is secondary to alveolar and interstitial vascular damage resulting in hemorrhage. This complication is considered to be the major cause of leptospirosis-associated death.
• The skin is affected by epithelial vascular insult.
• Skeletal muscle involvement is secondary to edema, myofibril vacuolization, and vessel damage.
• The damage to the vascular system as a whole can result in capillary leakage, hypovolemia, and shock. Many patients with leptospirosis may develop disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and vasculitis. Thrombocytopenia indicates severe disease and should raise suspicion for a risk of bleeding.^{[2, 3]}

Clinical manifestations of leptospirosis after the acute infection are the result of the inflammatory response, as well as action of the remaining organisms in the aqueous humor.

Frequency

United States

Leptospirosis is a ubiquitous disease found throughout the world. Leptospirosis is no longer a reportable disease in the United States; however, numerous states, including Hawaii, continue to report. An estimated 100-200 cases are identified annually in the United States, with about 50% of cases occurring in Hawaii. The state of Hawaii is affected more than any other state.

Over the past 20 years, epidemiology has begun to shift from primarily recreational water exposures to an increasing number of occupational exposures related to farm and agricultural activities.^[4]

Because most cases are self-limiting and unreported, underreported, or even misdiagnosed, the true incidence is difficult to determine.

International

Up to 80% of individuals in tropical areas are estimated to have positive seroconversion rates, indicating either past or present infection.

Mortality/Morbidity

The mortality rate in severe leptospirosis has been described as ranging from 5-40%. The mild form of the illness is rarely fatal, and an estimated 90% of cases fall into this category. Elderly and immunocompromised people are at the highest risk of mortality overall.

Subclinical infection is controversial. Evidence from limited population studies during epidemics have indicated agglutination titers are elevated in more people than are clinically infected with the disease.

Sex

Although leptospirosis is rare in pregnancy, acute infection without fever may mimic the clinical pattern of HELLP (hemolytic anemia, elevated liver enzymes, low platelet count) syndrome or acute fatty liver of pregnancy, and the diagnosis may be a challenge.^[5]

Age

No evidence suggests that leptospirosis affects persons of various races, ages, or sexes differently. However, because occupational exposure constitutes a major risk for development of disease, a disproportionate number of working-aged males seem to be affected.

In addition, immunosuppressed patients may develop a fulminant course of leptospirosis. Two cases of Weil syndrome in transplant patients have been described.^[6]