Background: Leptospirosis, an infectious disease that affects humans and animals, is considered the most common zoonosis in the world. Leptospirosis often is 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. 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 increasingly been also recognized as a disease of recreation. Recreational activities presenting 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. Forty-four percent of those who reported feeling ill met the case definition of leptospirosis. Significant risk factors were kayaking and swimming in and swallowing water from the Segama River. In 1998, athletes who participated in a triathlon in Springfield, Illinois, and swam in Lake Springfield developed leptospirosis. 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 visiting Costa Rica who engaged in white-water rafting contracted the disease. Leptospirosis may be spread epidemically in large populations in conditions of widespread flooding, as occurred in Nicaragua in 1995. In Brazil, the highest incidence of leptospirosis occurs during the summer months when heavy rains and floods occur in urban areas. Urban dwellers are also at increased risk because these residents may become exposed sporadically 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 as they tend to be engaged in outdoor work more frequently than females. Leptospirosis is caused by pathogenic spiral bacteria belonging 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 re-infect 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 US, 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 are 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, as person-to-person spread of the disease is rare. The majority of cases occur in the warm season and in rural areas because leptospires can persist in water for many months. They survive best in fresh water, 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. Transmission via laboratory accidents may occur, but it is rare. Pathophysiology: 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 usually is due to tubular damage, but hypovolemia from dehydration and from altered capillary permeability also can 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 also may 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 it also may lead to a symptomatic inflammatory reaction that can produce secondary end-organ injury. Frequency:
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 being seen in women.
History: Leptospirosis infection has protean manifestations. As a result, it is frequently misdiagnosed. Approximately 15-40% of exposed patients who do not become ill show serologic evidence of past infection. This statistic includes 15% of abattoir workers, packinghouse workers, and veterinarians. - During this stage, which lasts about 4-7 days, the patient develops a nonspecific flulike illness of varying severity.
- It is characterized by fever, chills, weakness, and myalgias, primarily affecting the calves, back, and abdomen.
- Other symptoms are sore throat, cough, chest pain, hemoptysis, rash, frontal headache, photophobia, mental confusion, and other symptoms of meningitis.
Physical: Lab Studies:
- Only specialized labs carry out serologic tests; hence, the decision to treat should not be delayed while awaiting the results of testing.
- Other tests include an indirect hemagglutination test, a microcapsule agglutination test, an immunoglobulin M (IgM) enzyme-linked immunoabsorbent assay (ELISA), and a dark-field examination of blood or urine. More recently, rapid commercial tests have been made available, such as the Dip-S-Ticks (PanBio, Inc, Baltimore, Maryland), which detects leptospira antibodies.
Imaging Studies:
Other Tests:
- Electrocardiographic (ECG) abnormalities are common during the leptospiremic phase of Weil syndrome; in severe cases, congestive heart failure and cardiogenic shock may occur.
- Emergency Department Care:
- Supportive therapy and careful management of renal, hepatic, hematologic, and CNS complications are important
Mild leptospirosis is treated with doxycycline, ampicillin, or amoxicillin. For severe leptospirosis, the primary therapy is penicillin G, which is used widely in clinical practice. Alternative regimens are ampicillin, amoxicillin, or erythromycin. Several other antibiotics, including cephalosporins, may be useful, but clinical experience with these is more limited.
Drug Category: Antibiotics -- Therapy must cover all likely pathogens in the context of the clinical setting. Drug Name
| Doxycycline (Bio-Tab, Doryx, Vibramycin) -- Should be considered for treatment of mild cases. Hepatobiliary and renally excreted. | | Adult Dose | 100 mg PO bid |
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| Pediatric Dose | <8 years: Not recommended
>8 years: 2 mg/lb PO divided bid on first day, followed by 1 mg/lb/d qd or divided bid on subsequent days |
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| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
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| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can increase hypoprothrombinemic effects of anticoagulants; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy |
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| Pregnancy | D - Unsafe in pregnancy |
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| Precautions | Adverse effects include GI distress, tooth discoloration in children and fetuses, hypersensitivity reactions, erosive esophagitis, dose-related increase in BUN, nephrotoxicity, and hepatotoxicity; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
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Drug Name
| Ampicillin (Omnipen, Marcillin) -- Some ampicillin metabolized by liver, although primarily renally excreted. |
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| Adult Dose | 500-750 mg PO qid; 1 g if severe |
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| Pediatric Dose | 50 mg/kg/d PO divided qid |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
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| Precautions | Adverse effects include GI discomfort, rash, anaphylactic reaction, and allergic interstitial nephritis; adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction |
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Drug Name
| Amoxicillin (Amoxil, Polymox, Trimox) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible bacteria. |
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| Adult Dose | 500 mg PO qid; 1 g IV if severe |
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| Pediatric Dose | 20-40 mg/kg/d PO divided qid |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Reduces efficacy of oral contraceptives |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
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| Precautions | Adverse effects include GI discomfort, diarrhea, abdominal cramps, rash, anaphylactic reactions, and allergic interstitial nephritis; adjust dose in renal impairment; may enhance chance of candidiasis |
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Drug Name
| Penicillin G (Pfizerpen) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. |
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| Adult Dose | 20-24 million U/d IM divided q4-6h |
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| Pediatric Dose | <30 lb: 600,000 U IM
30-50 lb: 900,000-1.2 million U IM
>50 lb: Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Probenecid can increase effects; tetracyclines can decrease effects |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
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| Precautions | Adverse effects include hypersensitivity reactions (eg, rash, exfoliative dermatitis), serum sickness (eg, fever, chills, edema, arthralgia, prostration), anaphylactic reactions, interstitial nephritis, drug fever, rare hemolytic anemia, reduced WBC and platelet counts, neuropathy, and neurotoxicity; caution in impaired renal function |
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Drug Name
| Erythromycin (EES, E-Mycin, Ery-Tab) -- Inhibits RNA-dependent protein synthesis, possibly by stimulating dissociation of peptidyl t-RNA from ribosomes. This inhibits bacterial growth. Excreted into bile via liver. |
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| Adult Dose | 500 mg IV qid |
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| Pediatric Dose | 30-50 mg/kg/d IV divided tid/qid |
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| Contraindications | Documented hypersensitivity; hepatic impairment |
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| Interactions | May increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; lovastatin and simvastatin increase risk of rhabdomyolysis |
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| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
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| Precautions | Adverse effects include GI symptoms (eg, abdominal discomfort and cramping, nausea and vomiting, diarrhea), elevated LFTs, mild allergic reactions, and transient hearing loss with high doses; caution in liver disease; estolate formulation may cause cholestatic jaundice; GI side effects common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur |
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| | FOLLOW-UP | Section 8 of 10    | | Deterrence/Prevention:
- Prevention is difficult because the organism has not been eradicated from wild animals, which constantly infect domestic animals.
- Vaccines are offered to high-risk workers in some European and Asian countries (eg, rice workers in Italy). Vaccines are not used in the US.
- Doxycycline, in the dose of 200 mg every week, has demonstrated efficacy of 95% against leptospirosis and may be given to help prevent the disease in those exposed. This regimen is recommended for those with short-term exposure and is not for repeated exposure over protracted periods of time.
Prognosis:
- Most patients with leptospirosis recover.
- The highest mortality rates are in elderly patients and in those with Weil syndrome.
- Pregnant women also face a high rate of fetal mortality, as infected women have a higher-than-normal incidence of spontaneous abortion if the infection is acquired in the early months of pregnancy.
- Patients with hepatic dysfunction and renal failure have a good chance of recovering renal and hepatic dysfunction in the long term.
Medical/Legal Pitfalls:
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