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 29-year-old man presents to the clinic complaining of fatigue and loss of sensation in his lower legs. The patient notes no history of trauma or chronic disease but states that he spends a lot of time outside and often encounters wild animals. On examination, the patient has multiple dark lesions over the skin of his face and back, as well as a decreased sensation of fine touch and vibration bilaterally in the lower extremities. What is the morphology of the etiologic agent causing this patient’s symptoms?

An acid-fast, intracellular bacillus

Reactivation of latent viral infection

Maltose-fermenting gram-negative diplococci

A spirochete transmitted via tick

Gram-positive, branching anaerobe

A 57-year-old man presents to the emergency department for feeling weak for the past week. He states that he has felt much more tired than usual and has had a subjective fever during this time. The patient has a past medical history of IV drug use, hepatitis C, atrial fibrillation, cirrhosis, alcohol dependence, obesity, and depression. His temperature is 102°F (38.9°C), blood pressure is 157/98 mmHg, pulse is 110/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, you note a fatigued man with diffuse yellowing of his skin. Cardiopulmonary exam is notable for bibasilar crackles on auscultation. Abdominal exam is notable for abdominal distension, dullness to percussion, and a fluid wave. The patient complains of generalized tenderness on palpation of his abdomen. The patient is started on piperacillin-tazobactam and is admitted to the medical floor. On day 4 of his stay in the hospital the patient is afebrile and his pulse is 92/min. His abdominal tenderness is reduced but is still present. Diffuse yellowing of the patient's skin and sclera is still notable. The nurses notice bleeding from the patient's 2 peripheral IV sites that she has to control with pressure. A few new bruises are seen on the patient's arms and legs. Which of the following is the best explanation for this patient's condition?

Diffuse activation of the coagulation cascade

Decreased metabolism of an anticoagulant

Decreased renal excretion of an anticoagulant

A previously healthy 24-year-old woman comes to the physician because of a 1-day history of nausea and weakness. She is sexually active with 2 male partners and uses an oral contraceptive; she uses condoms inconsistently. Her last menstrual period was 4 days ago. Her temperature is 38.4°C (101°F). Physical examination shows right costovertebral angle tenderness. Pelvic examination is normal. Which of the following is the most likely cause of this patient's condition?

Ascending bacteria from the bladder

Noninfectious inflammation of the bladder

Ascending bacteria from the endocervix

Decreased renal calcium reabsorption

Viral hemorrhagic fevers — USMLE Lesson

VHFs - The Bleeding Fevers

Pathophysiology: Systemic infection causing endothelial damage → ↑ vascular permeability, hemorrhage, shock.
Transmission: Primarily zoonotic (rodents, bats) or arthropod-borne (mosquitoes, ticks).
Causative Agents:
- Filoviridae: Ebola, Marburg (highest mortality).
- Arenaviridae: Lassa fever (often with deafness).
- Bunyaviridae: Hantavirus (pulmonary syndrome), Rift Valley fever.
- Flaviviridae: Dengue, Yellow fever.

⭐ Dengue Fever classically presents with biphasic fever, severe myalgia ("breakbone fever"), rash, and potential for hemorrhagic complications or shock syndrome, especially on second infection with a different serotype.

Filoviridae - Thread of Terror

Viruses: Ebola, Marburg.
Structure: Filamentous, helical, enveloped, negative-sense ssRNA viruses.
Transmission: Direct contact with infected bodily fluids (blood, secretions). Reservoir: fruit bats.
Pathogenesis: Causes severe endothelial cell damage, leading to ↑ vascular permeability, massive hemorrhage, and shock. Often results in Disseminated Intravascular Coagulation (DIC).
Diagnosis: RT-PCR during acute illness.
Treatment: Primarily supportive care; monoclonal antibodies for Ebola.

⭐ On electron microscopy, filoviruses exhibit a characteristic filamentous, shepherd's crook morphology.

Ebola virus electron micrographs

Flaviviridae - Yellow Flags

Vector: Aedes mosquitoes.
Classic Triad: Jaundice, black vomit (hematemesis), and fever.
- Faget's Sign: Pulse-temperature dissociation (fever with relative bradycardia).
Pathology: Councilman bodies (apoptotic hepatocytes) on liver biopsy with mid-zonal necrosis.
Prevention: Live-attenuated vaccine available (contraindicated in immunosuppressed).

⭐ High-Yield: The name "yellow fever" comes from the characteristic jaundice seen in severe cases, caused by liver damage.

Yellow Fever: Liver Histology and Viral Particles

Arenaviridae - Sandy Killers

Virion: Enveloped, helical, ss(-)RNA (2 segments). Ribosomes give a "sandy" (Latin: arenosus) look on EM.
Transmission: Zoonotic, via aerosolized rodent excreta (urine, feces).
Key Pathogens:
- Lassa Fever Virus: West Africa. Causes hemorrhagic fever.
- LCMV (Lymphocytic Choriomeningitis Virus): Aseptic meningitis.
- South American HF: Junin (Argentine), Machupo (Bolivian).
Treatment: Supportive care; consider Ribavirin.

⭐ Lassa fever is notorious for causing sensorineural deafness as a sequela.

Arenavirus virion structure and genome organization

Bunyaviridae - Triple Threat

Structure: Enveloped, segmented (3), circular, ss(-)RNA virus.
Transmission: Zoonotic via arthropods (ticks, mosquitoes) or rodents.
Key Syndromes:
- Hantavirus: Transmitted by aerosolized rodent excreta.
  - Americas: Hantavirus Pulmonary Syndrome (HPS) - severe, rapid pulmonary edema.
  - Eurasia: Hemorrhagic Fever with Renal Syndrome (HFRS).
- Crimean-Congo Hemorrhagic Fever (CCHF): Transmitted by Hyalomma ticks.
- Rift Valley Fever (RVF): Transmitted by Aedes mosquitoes.

⭐ Hantavirus Pulmonary Syndrome is notorious for its rapid progression from flu-like symptoms to severe, non-cardiogenic pulmonary edema and shock.

High‑Yield Points - ⚡ Biggest Takeaways

All are enveloped RNA viruses with zoonotic reservoirs, primarily rodents or arthropods.

The unifying feature is endothelial cell damage, leading to capillary leak, hemorrhage, and shock.

Key virus families include Filoviridae (Ebola), Arenaviridae (Lassa), and Flaviviridae (Dengue, Yellow Fever).

Look for thrombocytopenia, petechiae, ecchymoses, and signs of multi-organ failure.

Human-to-human transmission via bodily fluids is a major concern for Ebola and Lassa fever.

Management is primarily supportive care; Ribavirin is an option for Lassa fever and CCHF.

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