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Leptospira

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A 33-year-old man comes to the clinic because of fever, chills, and muscle aches that began two days ago. He reports a non-productive cough with nausea and diarrhea. Two weeks ago, he returned from a kayaking trip to Hawaii. None of his travel companions have been ill. The patient appears lethargic. His temperature is 38.1°C (100.6°F), pulse is 80/min, respirations are 22/min, and blood pressure is 135/80 mm Hg. Physical examination shows scleral icterus with bilateral conjunctival suffusions. His spleen can be palpated. Which of the following is the most likely diagnosis?

Transcript

Content Reviewers:

With Leptospira, “lepto” means thin, and “spira” means coil.

So Leptospira is a genus of spiral bacteria known to cause leptospirosis, a zoonotic infection, meaning it can be transmitted from animals such as rodents, to humans; especially people who work in sewers and waters contaminated by these animals’ urine.

The Leptospira genus has over 20 species, and the most common species that causes leptospirosis in humans is Leptospira interrogans.

Now, Leptospira is a tiny spiral bacteria, that stains poorly with Gram staining, because it doesn’t retain the Gram dyes well, so it’s classically considered gram-negative.

It’s also too tiny to be seen with a light microscope, so to visualize it, a darkfield microscope with use of immunofluorescence is required.

Leptospira is also a motile bacteria because it has flagella that help it move around.

Finally, it doesn’t form spores and it’s aerobic, meaning it needs oxygen to grow.

Currently, little is known about the pathogenesis of this bacteria, but we do know that it possesses a number of virulence factors, which are like assault weaponry that help it attack and destroy the host cells.

These include toxins and some immunogenic molecules such as lipopolysaccharide, or LPS, that triggers an immune response, causing inflammation.

For example, Leptospira interrogans, the most common cause of leptospirosis, has adhesins, which are proteins that help this bacteria attach to the host’s cells - usually epithelium, monocytes, and macrophages.

It also releases Sphingomyelinase C toxin, which destroys red blood cells as well as the endothelium of the capillaries, causing hemorrhage.

Most commonly, Leptospira gets into the host system via abrasions or cuts on the skin.

Alternatively, it can get in through the conjunctive of the eyes, especially in people who go swimming in contaminated waters.

Rarely, infection can follow eating contaminated food.

Serious problems start when this bacteria gets into the bloodstream, from where it can move to infect other organs. This typically happens in two stages.

In the first stage, there’s an immune response to bacteremia, which clinically manifests as fever, but the bacteria are confined to the bloodstream and there are no signs of end-organ damage.

In the second stage, also known as Weil disease, the infection becomes more severe, as the bacteria spread to almost all internal organs.

Frequently affected organs include the liver, where the bacterial toxins damage liver sinusoids and hepatocytes, causing bilirubin to spill into the bloodstream - which clinically translates as jaundice.

When the lungs are affected, the toxins damage the alveolar-capillary membranes, which can result in bleeding within the alveoli.

If Leptospira gets to the kidneys, it may infect the interstitium, causing interstitial nephritis, or it may cause an inflammatory reaction that damages the renal tubules, resulting in acute tubular necrosis.

Finally, sometimes the bacteria can even migrate from the bloodstream, and use its toxins to break through the endothelial cells that make up the blood-brain barrier to get into the cerebrospinal fluids or CSF, causing meningitis.

Risk factors for leptospirosis include some professions, like people who work in rice-paddies, sugarcane plantations, or people who swim or wade in waters contaminated by animal urines.