Updated: 7/17/2018

Yellow Fever Virus

Review Topic
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  • A 40-year-old man presents to a hospital after flying from sub-Saharan Africa. He had been on a safari and had sustained multiple mosquito bites. He had not gotten his necessary vaccines, as the trip was planned last-minute. For the past 2 days, he has had fevers, chills, myalgias, and some vomiting. After landing, he had an episode of bloody vomiting. On physical exam, he has a high fever. He also has gingival bleeding, jaundice, and scleral icterus. On abdominal exam, he has hepatosplenomegaly. He is admitted for supportive care and close monitoring.
  • Classification
    • yellow fever virus
      • a positive-stranded, linear RNA virus
      • a flavivirus and arbovirus with icosahedral capsid
      • transmitted by Aedes mosquito
      • reservoir is human or monkey
  • Epidemiology
    • incidence
      • endemic in South America and Africa
    • risk factors
      • exposure to endemic areas
      • mosquito bites
  • Pathogenesis
    • the virus spreads via blood
    • it infects the liver
      • liver cells die via apoptosis
      • coagulopathy occurs due to loss of hepatic synthesis of clotting factors
  • Associated conditions
    • hemorrhagic fever
  • Prevention
    • live-attenuated virus vaccine
      • given at age 9-12 months in endemic areas
      • given 10 days prior to travel to endemic areas
  • Prognosis
    • most patients recover without complications
    • however, in severe cases, mortality rate is up to 60%    
  • Symptoms
    • most patients are asymptomatic
    • if symptomatic
      • flu-like prodrome
      • headache
      • myalgias
      • nausea
      • black vomitus
  • Physical exam
    • high fever
    • jaundice
    • scleral icterus
    • hepatomegaly
    • minor hemorrhage
      • epistaxis
      • mucosal bleeding
      • melena
  • Labs
    • diagnostic
      • reverse transcriptase-polymerase chain reaction
      • serology with enzyme-linked immunosorbent assay
    • transaminitis (AST > ALT)
    • elevated prothrombin and partial thromboplastin times
    • hyperbilirubinemia
  • Guaiac stool testing
    • occult blood
  • Liver biopsy
    • Councilman bodies
      • eosinophilic apoptotic globules
    • typically found on autopsy
  • Making the diagnosis
    • most cases are clinically diagnosed, especially in those who have recently traveled to an endemic area
  • Dengue fever
    • distinguishing factor
      • may also be hemorrhagic but does not affect the liver
      • will not present with jaundice, scleral icterus, and hepatomegaly
  • Chikungunya 
    • distinguishing factor
      • typically does not present with hemorrhage
  • Conservative
    • supportive care
      • indication
        • all patients
      • modalities
        • rehydration
        • close monitoring
        • pain control
  • Shock
  • Death
  • Prolonged weakness and fatigue

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2

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(M1.MC.4754) A 45-year-old male presents to the emergency room complaining of severe nausea and vomiting. He returned from a business trip to Nigeria five days ago. Since then, he has developed progressively worsening fevers, headache, nausea, and vomiting. He has lost his appetite and cannot hold down food or water. He did not receive any vaccinations before traveling. His medical history is notable for alcohol abuse and peptic ulcer disease for which he takes omeprazole regularly. His temperature is 103.0°F (39.4°C), blood pressure is 100/70 mmHg, pulse is 128/min, and respirations are 22/min. Physical examination reveals scleral icterus, hepatomegaly, and tenderness to palpation in the right and left upper quadrants. While in the examination room, he vomits up dark vomitus. The patient is admitted and started on multiple anti-protozoal and anti-bacterial medications. Serology studies are pending; however, the patient dies soon after admission. The virus that likely gave rise to this patient’s condition is part of which of the following families? Review Topic | Tested Concept

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