BONUS WEEKEND QUESTION

TOPIC: Infectious Disease

Nov 09, 2024

Today’s bonus weekend question will test your understanding of a high-yield, commonly tested infectious disease concept.

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A 45-year-old male with a history of HIV presents with headache, confusion, and mild fever. Physical examination reveals nuchal rigidity. Lumbar puncture yields the following cerebrospinal fluid findings:

•Opening pressure: 250 mmH₂O
•WBC: 100 cells/mm³ (predominantly lymphocytes)
•Glucose: 40 mg/dL
•Protein: 120 mg/dL

Which of the following diagnostic tests is most appropriate for identifying the causative agent in this case?

A) India ink preparation
B) Gram stain
C) Polymerase chain reaction
D) Acid-fast stain
E) Latex agglutination for Neisseria meningitidis

Detailed Breakdown of Answers + Correct Answer Below ⏬

ANSWER + QUESTION BREAKDOWN

It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:

Step 1. Read the last line to get to the heart of the question: “Which of the following diagnostic tests is most appropriate for identifying the causative agent in this case?”

Step 2: Is this a first-, second-, or third-order question?
Answer: 3rd order. 1st: Diagnose the condition; 2nd: Identify the most likely organism based on presentation; 3rd: Identify the most appropriate way to confirm your diagnosis.

Step 3: Read the vignette carefully and ask yourself: “Based on my diagnosis and the causative organism, which diagnostic test can I use to confirm it?”

Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.

GENERAL ANALYSIS

This vignette describes a 45-year-old male with HIV who presents with headache, confusion, mild fever, and nuchal rigidity, suggesting meningitis. The CSF findings are consistent with a particular cause, and his immune status should point us toward the most likely pathogen.

ANSWER CHOICES:

CHOICE A: India ink preparation

Explanation: India ink preparation is a diagnostic test used to visualize Cryptococcus neoformans, a yeast that causes meningitis, particularly in immunocompromised patients such as those with HIV. The test highlights the organism's thick polysaccharide capsule, which appears as a clear halo against a dark background.

CHOICE B: Gram stain

Explanation: Gram stain is typically used to identify bacterial pathogens in cases of bacterial meningitis. While Gram stain is useful for detecting bacteria, this patient’s CSF findings (lymphocytic pleocytosis, low glucose, high protein) are more consistent with fungal or viral meningitis rather than bacterial meningitis.

CHOICE C: Polymerase chain reaction

Explanation: PCR would be appropriate to confirm enteroviral infections, which can cause viral (aseptic) meningitis. Enteroviral meningitis typically presents with normal glucose levels in the CSF and less pronounced elevations in protein compared to this case. Additionally, enteroviral infections are less common in immunocompromised patients compared to fungal infections like cryptococcal meningitis.

CHOICE D: Acid-fast stain

Explanation: Acid-fast staining is used to detect Mycobacterium tuberculosis, which can cause tuberculous meningitis. While tuberculous meningitis can present similarly to cryptococcal meningitis (with lymphocytic pleocytosis and low glucose), cryptococcal meningitis is far more common in patients with advanced HIV/AIDS. Additionally, acid-fast staining has low sensitivity for detecting tuberculosis in CSF.

CHOICE E: Latex agglutination for Neisseria meningitidis

Explanation: Latex agglutination can be used to detect antigens from bacteria such as Neisseria meningitidis, which causes bacterial meningitis. Bacterial meningitis typically presents with neutrophilic pleocytosis (not lymphocytic), very low glucose levels, and much higher protein concentrations than seen here. This patient’s presentation and CSF findings are more consistent with fungal (cryptococcal) or viral causes rather than bacterial.

FINAL VERDICT…

The patient’s presentation—headache, confusion, fever, nuchal rigidity—and CSF findings (elevated opening pressure, lymphocytic pleocytosis, low glucose, high protein) are highly suggestive of cryptococcal meningitis. This condition is particularly common in patients with advanced HIV/AIDS due to their immunocompromised state.

An India ink preparation is the most appropriate diagnostic test to confirm this suspicion, which allows visualization of Cryptococcus neoformans by highlighting its characteristic polysaccharide capsule. While other tests, such as cryptococcal antigen testing or culture, can also be used for diagnosis, India ink preparation provides a rapid preliminary diagnosis.

Thus, India ink preparation is the most appropriate diagnostic test for identifying Cryptococcus neoformans in this patient’s CSF.

CORRECT ANSWER: A) India ink preparation