USMLE® Step 1 Question of the Day: Pathogen test

Prepare for your USMLE Step 1 exam with this question focused on identifying pathogens in immunocompromised patients. Understand the presentation and diagnostic features of Cryptococcus neoformans and other pathogens in similar settings.

A 45-year-old man is brought to the emergency department due to confusion and altered mental status. His friend, who brought him in, states the patient has been complaining of fevers accompanied by malaise for the past 2 weeks. The patient is currently living in a homeless shelter, but oftentimes he is seen sleeping on the streets by his friends. Medical history is unknown, but a month ago the patient was hospitalized for Pneumocystis jirovecii (formerly P. carinii) pneumonia. Temperature is 38.5°C (101.3°F), pulse is 80/min, and blood pressure is 135/85 mmHg. On physical examination, the patient is lethargic and mildly confused. Neck is supple, and there are no focal signs. The patient’s arms show multiple needle marks. The pathogen most likely responsible for this patient’s condition is most likely to show which of the following on further testing? 

A. Nonseptate hyphae branching at wide angles

B. Budding, encapsulated yeast  

C. Septate hyphae branching at acute angles  

D. Forms germ tubes at hot temperatures  

E. Gram-positive, lancet-shaped diplococci

Scroll down for the correct answer!

The correct answer to today's USMLE® Step 1 Question is...

B. Budding, encapsulated yeast

Before we get to the Main Explanation, let's look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

A. Nonseptate hyphae branching at wide angles

Incorrect:These features depict Mucor and Rhizopus spp. that can cause mucormycosis in diabetic ketoacidosis and/or neutropenic patients (e.g. leukemia). Mucormycosis typically presents as headache, facial pain, and a black necrotic eschar on the affected area because the fungi proliferate in blood vessel walls.  

C. Septate hyphae branching at acute angles 

Incorrect: These features depict Aspergillus fumigatus, which is a type of fungus that can be found throughout the environment. Healthy individuals are usually asymptomatic, but immunocompromised patients are at risk for developing invasive disease. It classically presents with fever, chest pain, shortness of breath, cough, and/or hemoptysis. 

D. Forms germ tubes at hot temperatures

Incorrect: These features depict Candida albicans, which is a dimorphic fungus that forms pseudohyphae and budding yeasts at 20°C and germ tubes at 37°C. Immunocompromised hosts are at risk for invasive disease. Invasive candidiasis can present anywhere from minimal fever to acute sepsis syndrome (similar to bacterial infection). However, it is not typically a cause of meningitis.  

E. Gram-positive, lancet-shaped diplococci

Incorrect: Gram-positive, lancet-shaped diplococci describes Streptococcus pneumoniae, which is the most common cause of bacterial meningitis in adults of all ages. However, pneumococcal meningitis typically causes severe, life-threatening manifestations within hours to days of inoculation, not weeks as in this patient.

Main Explanation

This patient is immunocompromised (recent Pneumocystis jirovecii infection, with evidence of risk factors such as needle marks and homelessness), likely due to undiagnosed HIV infection. The constellation of indolent course, headaches and immunosuppression, from the options above, favors the diagnosis of Cryptococcus neoformans meningitis (neck stiffness is absent in 2/3 of patients). The subacute and chronic nature of this condition is caused by capsular proteins produced by Cryptococcus which obstruct cerebrospinal fluid outflow, resulting in symptoms of elevated intracranial pressure (e.g., headache, vomiting, confusion, cranial nerve VI palsy).  

Cryptococcus neoformans is a budding, heavily encapsulated yeast (not dimorphic) that can be found in soil and pigeon droppings. It is acquired through inhalation of spores with hematogenous dissemination to the brain meninges. Confirmation of diagnosis requires identification of the encapsulated yeast in cerebrospinal fluid (e.g. India ink stain) or detection of the polysaccharide antigen.  

Major Takeaway

Cryptococcus neoformans is a budding, heavily encapsulated yeast that can cause meningoencephalitis almost exclusively in immunocompromised patients. It typically presents with an indolent course with headache fever and malaise due to elevated intracranial pressure. Stiff neck and photophobia are not always present.   

References

Zunt JR, Baldwin KJ. Chronic and subacute meningitis. Continuum (Minneap Minn). 2012 Dec;18(6 Infectious Disease):1290-318. doi: 10.1212/01.CON.0000423848.17276.21. PMID: 23221842. USMLE Step 1: 2019 a student-to-student guide. New York: McGraw-Hill Medical. 

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