Leptospirosis in Emergency Medicine 

Leptospirosis, an infectious disease that affects humans and animals, is considered the most common zoonosis in the world.^[1] Leptospirosis is often referred to as swineherd's disease, swamp fever, or mud fever. The organism enters the body when mucous membranes or abraded skin come in contact with contaminated environmental sources.

The infection causes a systemic illness that often leads to renal and hepatic dysfunction. The disease was first recognized as an occupational disease of sewer workers in 1883. In 1886, Weil described the clinical manifestations in 4 men who had severe jaundice, fever, and hemorrhage with renal involvement. Inada et al identified the causal agent in Japan in 1916.^[2]

Occupational exposure probably accounts for 30-50% of human cases. The main occupational groups at risk include farm workers, veterinarians, pet shop owners, field agricultural workers, abattoir workers, plumbers, meat handlers and slaughterhouse workers, coal miners, workers in the fishing industry, military troops, milkers, and sewer workers.

Studies in sewer workers show greater prevalence of leptospira antibodies than in controls. Infected rats may contaminate sewer water. Partial or total immersion in mud and water plays a role in facilitating infection in sewer workers and rice field workers.

Milkers may be splattered in the face, causing subsequent infection via the conjunctivae. Infection of military troops occurs as a result of direct exposure to infected urine or indirect contact with contaminated soil and water. Seroprevalence surveys of livestock workers have shown ranges of positive antibody titers at 8-29%.

Although leptospirosis continues to be predominantly an occupational disease since 1970, it has also increasingly been recognized as a disease of recreation. Recreational activities that present some risk include traveling to tropical areas, canoeing, hiking, kayaking, fishing, windsurfing, swimming, waterskiing, wading, riding trail-bikes through puddles, white-water rafting, and other outdoor sports played in contaminated water. Camping by and traveling to endemic areas also add some risk.

An outbreak of an acute febrile illness occurred among athletes competing in the Eco-Challenge-Sabah 2000 in Malaysia; 44% of those who reported feeling ill met the case definition of leptospirosis.^[3] Significant risk factors included kayaking and swimming in and swallowing water from the Segama River. In 1998, athletes who participated in a triathlon in Springfield, Illinois, and who swam in Lake Springfield developed leptospirosis.^[4] Other athletes who participated in the same event, although asymptomatic, were found to have laboratory evidence of the disease. Prolonged water exposure, in the form of a 1.5-mile swim in Lake Springfield, was the epidemiologic association among the sick athletes. In 1997, US travelers who visited Costa Rica and engaged in white-water rafting contracted the disease.^[5]

Leptospirosis may be spread epidemically in large populations in conditions of widespread flooding, as occurred in Nicaragua in 1995.^[6] In Brazil, the highest incidence of leptospirosis occurs during the summer months when heavy rains and floods occur in urban areas. Flooding in the Philippines in 2009 led to more than 2000 cases of leptospirosis infection, resulting in more than 100 deaths. Flooding on a smaller scale may also lead to individuals contracting the disease. For example, in 2004, a stream overflowed and caused flooding on the University of Hawaii campus.^[7] Leptospirosis cases were found among those involved in the clean-up process.

Urban dwellers are also at increased risk because these residents may be sporadically exposed to rat urine as inner cities deteriorate. The incidence is increasing in urban children. However, human disease remains mainly related to occupation. The prevalence is higher in males because they tend to be engaged in outdoor work more frequently than females.

Leptospirosis is caused by pathogenic spiral bacteria that belong to the genus Leptospira, the family Leptospiraceae, and the order Spirochaetales. These spirochetes are finely coiled, thin, motile, obligate, slow-growing anaerobes.

Their flagella allow them to burrow into tissue. The genus Leptospira was originally thought to comprise only 2 species: L interrogans, which is pathogenic, and L biflexa, which is saprophytic. More recent work has identified 7 distinct species of pathogenic leptospires, which appear as more than 250 serologic variants (serovars).

Most leptospiral serovars have their primary reservoir in wild mammals, which continually reinfect domestic populations. The organism affects at least 160 mammalian species and has been recovered from rats, swine, dogs, cats, raccoons, cattle, and other animals. The most important reservoirs are rodents, and rats are the most common source worldwide. In the United States, important leptospiral sources include dogs, livestock, rodents, wild animals, and cats. Many serovars are associated with particular animals. For example, L pomona and L interrogans are seen in cattle and pigs; L grippotyphosa is seen in cattle, sheep, goats, and voles; L ballum and L icterohaemorrhagiae are associated with rats and mice; and L canicola is associated with dogs. Other important serotypes include autumnalis, hebdomidis, and australis.

Urinary shedding of organisms from infected animals is the most important source of these bacterial pathogens. Contact with the organism via infected urine or urine-contaminated media results in human infection. Such media include animal bedding, soil, mud, and aborted tissue. The organism enters the body via abraded skin or mucous membranes, such as the conjunctiva or alimentary tract. Occasionally, the organism may even enter the body through intact skin. Infection has occurred after animal and rodent bites, after contact with abortion products of infected animals, and after ingestion of contaminated food and water. The latter route of infection is believed to occur via the mucosa of the mouth and the esophagus because leptospires cannot survive in an acidic environment.

Leptospirosis in animals is often subclinical. Leptospires may persist for long periods in the renal tubules of animals by establishing a symbiotic relationship with no evidence of disease or pathological changes in the kidney. As a result, animals that serve as reservoirs of host-adapted serovars can shed high concentrations of the organism in their urine without showing clinical evidence of disease.

This leptospiruria in animals often occurs for months after the initial infection. Leptospiruria also has been found to occur in healthy immunized dogs. Leptospiruria in humans is more transient, rarely lasting more than 60 days. Humans and nonadapted animals are incidental hosts. With rare exceptions, man represents a dead end in the chain of infection because person-to-person spread of the disease is rare.

Most cases occur in the warm season and in rural areas because leptospires can persist in water for many month. The leptospires from infected animals contaminate the warm lake water. They survive best in freshwater, damp alkaline soil, vegetation, and mud with temperatures higher than 22°C.

Mucous surfaces of the mouth, pharynx, and esophagus may be crossed easily by pathogenic leptospires, as are mucous membranes of the bronchial tree and lung alveoli. A waterborne outbreak occurred in Italy in the summer of 1984 when a contaminated water fountain was used as a source of drinking water.^[8]

Transmission via laboratory accidents may occur but is rare.

After the organism gains entry via intact skin or mucosa, it multiplies in blood and tissue. The resulting leptospiremia can spread to any part of the body but particularly affects the liver and kidney.

After the organism gains access to the kidney, it migrates to the interstitium, renal tubules, and tubular lumen, causing interstitial nephritis and tubular necrosis. When renal failure develops, it is usually due to tubular damage, but hypovolemia from dehydration and from altered capillary permeability can also contribute to renal failure.

Liver involvement is seen as centrilobular necrosis with proliferation of Kupffer cells. Jaundice may occur as a result of hepatocellular dysfunction.

Leptospires may also invade skeletal muscle, causing edema, vacuolization of myofibrils, and focal necrosis. Muscular microcirculation is impaired and capillary permeability is increased, with resultant fluid leakage and circulatory hypovolemia.

In severe disease, a disseminated vasculitic syndrome may result from damage to the capillary endothelium.

Leptospires may invade the aqueous humor of the eye, where they may persist for many months, occasionally leading to chronic or recurrent uveitis.

Despite the possibility of severe complications, the disease is most often self-limited and nonfatal. Over time, a systemic immune response may eliminate the organism from the body but may also lead to a symptomatic inflammatory reaction that can produce secondary end-organ injury.

Frequency

United States

Leptospirosis is a zoonosis with worldwide distribution. Specific serovars vary with locality. The incidence varies from sporadic in temperate zones to endemic in a few tropical countries.

The disease has a seasonal incidence. Most cases occur during the rainy season in the tropics and during the late summer or early fall in Western countries, when the soil is moist and alkaline.

The incidence of leptospirosis within the United States steadily increased during the first decades of the 20th century but has remained stable more recently. From 1987-1993, 43-93 cases were reported annually. Leptospirosis is generally underdiagnosed and underreported because many cases are asymptomatic or mildly symptomatic, self-limited, and nonfatal.

In 1995, the Council of State and Territorial Epidemiologists and the US Centers for Disease Control and Prevention (CDC) removed leptospirosis from the US list of notifiable diseases. Because reliable diagnostic testing was not readily available and organized reporting had not resulted in implementation of methods to control the disease, many states stopped reporting leptospirosis.

International

Leptospirosis is generally associated with tropical countries and heavy rainfall, but most cases actually occur in temperate climates, probably because of underreporting in some countries.

Sex

Most cases occur in middle-aged men, probably because they are employed in at-risk occupations. However, with the change in social roles and the increased exposure during leisure activities, more cases are now reported in women.