A 23-year-old woman presents with progressively worsening headache, photophobia, and intermittent fever that have lasted for 6 days. She says her headache is mostly frontal and radiates down her neck. She denies any recent history of blood transfusions, recent travel, or contact with animals. Her past medical history is unremarkable. She is sexually active with a single partner for the past 3 years. Her temperature is 38.5°C (101.3°F). On physical examination, she appears pale and diaphoretic. A fine erythematous rash is noted on the neck and forearms. A lumbar puncture is performed and CSF analysis reveals: Opening pressure: 300 mm H2O Erythrocytes: None Leukocytes: 72/mm3 Neutrophils: 10% Lymphocytes: 75% Mononuclear: 15% Protein: 100 mg/dL Glucose: 70 mg/dL Which of the following is the most likely diagnosis in this patient?

Lymphocytic choriomeningitis virus

A previously healthy 32-year-old man comes to the physician because of a 1-week history of upper back pain, dyspnea, and a sensation of pressure in his chest. He has had no shortness of breath, palpitations, fevers, or chills. He emigrated from Ecuador when he was 5 years old. He does not smoke or drink alcohol. He takes no medications. He is 194 cm (6 ft 4 in) tall and weighs 70.3 kg (155 lb); BMI is 19 kg/m2. His temperature is 37.2°C (99.0°F), pulse is 73/min, respirations are 15/min, and blood pressure is 152/86 mm Hg in the right arm and 130/72 mm Hg in the left arm. Pulmonary examination shows faint inspiratory wheezing bilaterally. A CT scan of the chest with contrast is shown. Which of the following is the most likely underlying cause of this patient's condition?

Atherosclerotic plaque formation

Congenital narrowing of the aortic arch

Infection with Trypanosoma cruzi

A 30-year-old forest landscape specialist is brought to the emergency department with hematemesis and confusion. One week ago she was diagnosed with influenza when she had fevers, severe headaches, myalgias, hip and shoulder pain, and a maculopapular rash. After a day of relative remission, she developed abdominal pain, vomiting, and diarrhea. A single episode of hematemesis occurred prior to admission. Two weeks ago she visited rainforests and caves in western Africa where she had direct contact with animals, including apes. She has no history of serious illnesses or use of medications. She is restless. Her temperature is 38.0℃ (100.4℉); the pulse is 95/min, the respiratory rate is 20/min; and supine and upright blood pressure is 130/70 mm Hg and 100/65 mm Hg, respectively. Conjunctival suffusion is noted. Ecchymoses are observed on the lower extremities. She is bleeding from one of her intravenous lines. The peripheral blood smear is negative for organisms. Filovirus genomes were detected during a reverse transcription-polymerase chain reaction. The laboratory studies show the following: Laboratory test Hemoglobin 10 g/dL Leukocyte count 1,000/mm3 Segmented neutrophils 65% Lymphocytes 20% Platelet count 50,000/mm3 Partial thromboplastin time (activated) 60 seconds Prothrombin time 25 seconds Fibrin split products positive Serum Alanine aminotransferase (ALT) 85 U/L Aspartate aminotransferase (AST) 120 U/L γ-Glutamyltransferase (GGT) 83 U/L Creatinine 2 mg/dL Which of the following is the most appropriate immediate step in management?

Intravenous fluids and electrolytes

Postexposure vaccination of close contacts

Parenteral artesunate plus sulfadoxine/pyrimethamine

A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?

"Can you tell me more about the symptoms you have been experiencing?"

"Does the diarrhea typically precede the constipation, or vice-versa?"

"Is the diarrhea foul-smelling?"

"Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"

"Are the symptoms worse in the morning or at night?"

A 24-year-old man presents with a painless genital ulcer for the past 2 weeks. He reports that he recently has been having unprotected sex with multiple partners. Past medical history is unremarkable. On physical examination, a single ulcer is present on the dorsal shaft of the penis which is circumscribed, indurated, and partially healed. There is moderate inguinal lymphadenopathy but no buboes. Which of the following tests would confirm the most likely diagnosis in this patient?

Perform a darkfield microscopic examination of a swab from the chancre

Swab the chancre and perform a saline wet mount

Fluorescent treponemal antibody absorption (FTA-ABS) test

Venereal Disease Research Laboratory (VDRL) test

Trypanosomes for USMLE Step 3: High-Yield Microbiology Lessons

Trypanosomes - The Basics

Organism: Single-celled, flagellated protozoan parasites.
Transmission: Vector-borne zoonoses.
Key Species & Vectors:
- Trypanosoma brucei (African Sleeping Sickness): Tsetse fly.
- Trypanosoma cruzi (Chagas Disease): Reduviid bug (📌 "Kissing bug" - bites around the mouth).
Morphology:
- Trypomastigote: Motile, C-shaped form with a flagellum found in blood smears.
- Amastigote: Non-motile, intracellular form (especially in T. cruzi).

Trypanosoma brucei in blood smear

⭐ T. brucei exhibits remarkable antigenic variation by changing its variable surface glycoproteins (VSGs), leading to recurrent waves of fever and parasitemia.

T. cruzi - Chagas' Kiss

Vector: Triatomine bug ("Kissing Bug"), a reduviid bug.
Transmission: Bites, then defecates; scratching inoculates feces with trypomastigotes.
Pathogenesis: Intracellular amastigotes replicate in host cells, especially cardiac and GI muscle.
Acute Phase (weeks):
- Often asymptomatic; may have fever, malaise.
- Chagoma: Local inflammatory nodule at bite site.
- Romana's sign: Unilateral periorbital swelling (classic finding).
Chronic Phase (decades later):
- Cardiomyopathy: Apical aneurysm, mural thrombus, arrhythmia, heart failure.
- Mega-syndromes: Megaesophagus (dysphagia), megacolon (constipation).

⭐ A key finding in Chagasic cardiomyopathy is an apical aneurysm of the left ventricle.

Trypanosoma cruzi trypomastigotes in blood smear

T. brucei - Sleeping Sickness

Vector: Tsetse fly (Glossina species).
Subspecies & Region:
- T. b. gambiense: West/Central Africa (chronic course).
- T. b. rhodesiense: East Africa (acute, more virulent course).
Clinical Progression:
- Early (Hemolymphatic): Painful chancre at bite site, intermittent fever, generalized lymphadenopathy.
  - Winterbottom's sign: Posterior cervical lymphadenopathy is characteristic.
- Late (Meningoencephalitic): Invasion of the CNS leads to headaches, personality changes, daytime somnolence, nighttime insomnia, and eventually coma/death.

⭐ Antigenic Variation: Trypanosoma brucei evades the host immune system by periodically switching its dense coat of Variable Surface Glycoproteins (VSGs), leading to waves of parasitemia and fever.

Life Cycle of Trypanosoma brucei

Diagnosis: Motile trypomastigotes on blood smear, lymph node aspirate, or in CSF.
Treatment: Varies by subspecies and disease stage (e.g., Pentamidine/Suramin for hemolymphatic; Melarsoprol for late-stage CNS).

Diagnosis & Rx - Find & Fight

Diagnosis:
- African (T. brucei): Find motile trypomastigotes on blood smear, lymph node aspirate, or in CSF for staging.
- American (T. cruzi): Giemsa-stained blood smear for acute phase; serology (ELISA, IFA) is crucial for diagnosing chronic disease.
Treatment:
- T. brucei: Suramin (rhodesiense) or Pentamidine (gambiense) for blood-stage. Melarsoprol or Eflornithine for CNS-stage.
- T. cruzi: Benznidazole or Nifurtimox for acute infection; chronic phase management is largely symptomatic.

⭐ Melarsoprol, an arsenic derivative for late-stage African trypanosomiasis, can cause a fatal reactive encephalopathy in 5-10% of patients.

High‑Yield Points - ⚡ Biggest Takeaways

Trypanosoma cruzi causes Chagas disease, transmitted by reduviid bugs, leading to cardiomyopathy and mega-syndromes.

Trypanosoma brucei causes African Sleeping Sickness, transmitted by tsetse flies, marked by a chancre and Winterbottom's sign.

Diagnosis for both involves identifying trypomastigotes on a blood smear.

Romana's sign (unilateral periorbital swelling) is a classic acute sign of Chagas disease.

Treat Chagas with benznidazole or nifurtimox.

Treat African sleeping sickness with suramin (blood-stage) or melarsoprol (CNS penetration).

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Trypanosomes