Medical Lecture Note: Lecture Notes: Leptospirosis

Introduction

Leptospirosis is an emerging infectious disease of global importance.
The disease is caused by pathogenic leptospires.
It is characterized by a broad spectrum of clinical manifestations, varying from inapparent infection to fulminant.
In its mild form, leptospirosis may present as an influenza-like illness.
Severe leptospirosis is referred to as Weil's syndrome, characterized by jaundice, renal dysfunction, and hemorrhagic diathesis.

Etiologic Agents of Leptospirosis

Leptospires are spirochetes belonging to the order Spirochaetales and the family Leptospiraceae.
These organisms are coiled, thin, highly motile organisms with hooked ends and two periplasmic flagella; 6–20 μm long and ~0.1 μm wide.
They can be seen microscopically by dark-field examination and silver impregnation staining.
They require special media and conditions for growth and may take weeks for cultures to become positive.

Epidemiology of Leptospirosis

Leptospirosis is an important zoonosis with a worldwide distribution.
Rodents, especially rats, are the most important reservoir.
This infection occurs most commonly in the tropics.
Most cases occur in men, with a peak incidence during the summer and fall in Western countries and during the rainy season in the tropics.
Transmission of leptospires to humans may follow direct contact with urine, blood, or tissue from an infected animal or exposure to a contaminated environment.

Pathogenesis of Leptospirosis

The pathogenesis of leptospirosis is incompletely understood.
Leptospires enter the host through abrasions in the skin or through intact mucous membranes, especially the conjunctiva and the lining of the oro- and nasopharynx.
After entry of the organisms, leptospiremia develops, with subsequent spread to all organs.
Multiplication takes place in blood and in tissues, and leptospires can be isolated from blood and cerebrospinal fluid (CSF) during the first 4–10 days of illness.
All forms of leptospires can damage the wall of small blood vessels; this damage leads to vasculitis with leakage and extravasation of cells, including hemorrhages.
The most important known pathogenic properties of leptospires are adhesion to cell surfaces and cellular toxicity.
Although leptospires mainly infect the kidneys and liver, any organ may be affected.

In the kidney, leptospires migrate to the interstitium, renal tubules, and tubular lumen, causing interstitial nephritis and tubular necrosis. Hypovolemia due to dehydration or altered capillary permeability may contribute to the development of renal failure.
In the liver, centrilobular necrosis with proliferation of Kupffer cells may be found.
Pulmonary involvement is the result of hemorrhage and not of inflammation.
Invasion of skeletal muscle by leptospires results in swelling, vacuolation of the myofibrils, and focal necrosis.
In severe leptospirosis, vasculitis may ultimately impair the microcirculation and increase capillary permeability, resulting in fluid leakage and hypovolemia.

When antibodies are formed, leptospires are eliminated from all sites in the host except the eye, the proximal renal tubules, and perhaps the brain, where they may persist for weeks or months.

Clinical Manifestations of Leptospirosis

Many Leptospira-infected persons remain asymptomatic.
In symptomatic cases of leptospirosis, clinical manifestations vary from mild to serious or even fatal.
More than 90% of symptomatic persons have the relatively mild and usually anicteric form of leptospirosis, with or without meningitis.
Severe leptospirosis with profound jaundice (Weil's syndrome) develops in 5–10% of infected individuals.
The incubation period is usually 1–2 weeks but ranges from 2 to 20 days.
Typically, an acute leptospiremic phase is followed by an immune leptospiruric phase. The distinction between the first and second phases is not always clear, and milder cases do not always include the second phase.

Laboratory and Radiologic Findings of Leptospirosis

The kidneys are invariably involved in leptospirosis; mild proteinuria in anicteric leptospirosis to renal failure and azotemia in severe disease.
The erythrocyte sedimentation rate is usually elevated.
In anicteric leptospirosis, peripheral leukocyte counts range from 3000 to 26,000/L, with a left shift.
In Weil's syndrome, leukocytosis is often marked.
Those with leptospirosis typically have elevated serum levels of bilirubin and alkaline phosphatase as well as mild increases (up to 200 U/L) in serum levels of aminotransferases.
In Weil's syndrome, the prothrombin time may be prolonged but can be corrected with vitamin K.
Levels of creatine phosphokinase, which are elevated in up to 50% of patients with leptospirosis during the first week of illness, may help to differentiate this infection from viral hepatitis.
When a meningeal reaction develops, polymorphonuclear leukocytes predominate initially and the number of mononuclear cells increases later.
The protein concentration in the CSF may be elevated; CSF glucose levels are normal.
The most common radiographic finding is a patchy alveolar pattern that corresponds to scattered alveolar hemorrhage; and most often affect the lower lobes in the periphery of the lung fields.

Diagnosis of Leptospirosis

A definite diagnosis of leptospirosis is based either on isolation of the organism from the patient or on seroconversion or a rise in antibody titer in the microscopic agglutination test (MAT).
Leptospires can be isolated from blood and/or CSF during the first 10 days of illness and from urine for several weeks beginning at about 1 week.
Cultures most often become positive after 2–4 weeks, with a range of 1 week to 6 months.

Differential Diagnosis of Leptospirosis

Leptospirosis should be differentiated from other febrile illnesses associated with headache and muscle pain, such as:

Treatment of Leptospirosis

The most commonly used antibiotics is penicillin and doxycycline.
In milder cases, oral treatment with tetracycline, doxycycline, ampicillin, or amoxicillin should be considered.
For severe cases of leptospirosis, intravenous administration of penicillin G, amoxicillin, ampicillin, or erythromycin is recommended.
Patients with severe leptospirosis and renal failure may require dialysis.
Those with Weil's syndrome may need transfusions of whole blood and/or platelets. Intensive care may be necessary.

Prognosis of Leptospirosis

Most patients with leptospirosis recover.
Mortality rates are highest among patients who are elderly and those who have Weil's syndrome.
Leptospirosis during pregnancy is associated with high rates of fetal mortality.
Long-term follow-up of patients with renal failure and hepatic dysfunction has documented good recovery of renal and hepatic function.

Prevention of Leptospirosis

Individuals who may be exposed to leptospires through their occupations or their involvement in recreational water activities should be informed about the risks.
Measures for controlling leptospirosis include avoidance of exposure to urine and tissues from infected animals, vaccination of animals, and rodent control.

Medical Lecture Note