Case

A 34-year old female visited the emergency department with flu-like symptoms. She had been suffering from headaches and muscle cramps the last seven days, and had a fever up to 39°C. For the past two days, the headaches had gotten worse. Last night she woke up in the middle of the night with nausea and vomited three times. This week, she had noted a dark discolouration of her urine and complained of thirst. When asked, she indicated mild abdominal pains in the right lower quadrant as well. Last summer she visited the South of France, in the last week of her holidays she participated in a mud run and obstacle race. Her medical history was unremarkable, and aside from the painkillers (acetaminophen) she had been taking for her current complaints she was not on any medication.

A full neurological examination was performed. The patient was alert and ill-looking, had a temperature of 38.1°C, and showed some degree of neck stiffness. There was a dislike to bright lights. Upon examination of the abdomen there was flank pain on the right side but no tenderness. Laboratory tests indicated reduced kidney function, with a glomerular filtration rate (GFR) of 17 (>90), and a creatinine level of 270 (88-128). General infection parameters were increased with a C-reactive protein (CRP) of 140 (<2). A lumbar puncture was performed that showed increased leukocytes of 513 (<5) and increased protein levels.

The patient was admitted to the hospital with an aseptic meningitis. Due to the combination of renal insufficiency and meningitis, patient was tested for leptospirosis. One day after hospital admittance IgM testing for leptospirosis turned positive. She was treated with penicillin intravenously, and switched to doxycycline orally upon dismissal. Kidney function restored quickly after treatment.  

Background

Leptospirosis is an infectious disease of humans and animals that is caused by pathogenic spirochetes of the genus Leptospira. It is considered the most common zoonosis in the world and is associated with rodents in settings of poor sanitation, agricultural occupations, and increasingly "adventure" sports or races involving fresh water, mud, or soil exposure.

Leptospirosis ranges in severity from a mild illness suggesting a viral infection to a multi-systemic syndrome with unique features. It is characterised by sudden onset of the following:

- Fever (38-40°C)

- Rigors

- Headache, retro-orbital pain, photophobia

- Conjunctival suffusion

- Dry cough

- Nausea and vomiting, diarrhoea

- Muscle pain localized to the calf and lumbar areas

More severe disease manifests as icteric leptospirosis, also known as Weil's disease, with the following features:

- Icterus or frank jaundice

- Renal failure with oliguria

- Hemorrhagic features

- Systemic inflammatory syndrome or shock

Leptospirosis is presumed to be the most widespread zoonosis in the world. The source of infection in humans is usually either direct or indirect contact with the urine of an infected animal. The incidence is significantly higher in warm-climate countries than in temperate regions; this is due mainly to longer survival of leptospires in the environment in warm, humid conditions.

The great majority of infections caused by leptospires are either subclinical or of very mild severity, and patients will probably not seek medical attention. A smaller proportion of infections, but the overwhelming majority of the recognised cases, present with a febrile illness of sudden onset.

Aseptic meningitis may be found in ≤25% of all leptospirosis cases . Icteric leptospirosis is a much more severe disease in which the clinical course is often very rapidly progressive. Severe cases often present late in the course of the disease, and this contributes to the high mortality rate, which ranges between 5 and 15%. Between 5 and 10% of all patients with leptospirosis have the icteric form of the disease and may account for a significant minority of all causes of aseptic meningitis. The jaundice occurring in leptospirosis is not associated with hepatocellular necrosis, and liver function returns to normal after recovery. The complications of severe leptospirosis emphasise the multi-systemic nature of the disease. Leptospirosis is a common cause of acute renal failure (ARF), which occurs in 16 to 40% of cases. Cardiac, pulmonary, and ocular involvement may occur as well. 

Antimicrobial therapy is indicated for the severe form of leptospirosis, but its use is controversial for the mild form of leptospirosis. Mild leptospirosis is treated with doxycycline, ampicillin, or amoxicillin. For severe leptospirosis, intravenous penicillin G has long been the drug of choice, although the third-generation cephalosporins cefotaxime and ceftriaxone have become widely used. Alternative regimens are ampicillin, amoxicillin, or erythromycin. Patients with severe disease should remain hospitalised until adequate resolution of organ failure and clinical infection.