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USMLE® Step 1 questions

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A 46-year-old woman presents to the hospital with two weeks of fever, myalgia, and conjunctivitis. These symptoms started after a hurricane-affected her village. Bloodwork is pertinent for significantly elevated creatinine and total bilirubin. Lumbar puncture is performed, and examination of the cerebrospinal fluid under light microscopy does not reveal any organisms. Which of the following is the most likely pathogen responsible for this patient’s symptoms?  

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icterohemorrhagic leptospirosis p. 145

Leptospira spp.

animal transmission p. 147

spirochete p. 144

Leptospira interrogans p. , 145

Leptospirosis p. 145, 147

Jaundice p. 402

leptospirosis p. 145


Leptospira interrogans p. , 145


leptospirosis p. 145


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.


Leptospira is a genus of tiny spiral gram-negative bacteria that can be seen under a darkfield microscope. It's a motile and aerobic bacteria, and it doesn't form spores. Leptospira causes a zoonotic infection called leptospirosis, which has two phases. During the first phase, there are non-specific symptoms such as fever and headache. During the second phase, also called Weil disease, there may be signs of end-organ damage like jaundice, a cough, dyspnea and hemoptysis, reduced urine output, and fluid retention, depending on the affected organs. Diagnosis is done with ELISA which detects antibodies against leptospira antigens in one's serum; by visualizing the bacteria in biological samples using a darkfield microscope; or with PCR to detect bacterial DNA.


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