Diagnosis → Infectious Disease

Dengue fever

Etiology

Cause [qfu]

• Dengue virus is a single-stranded RNA Flavivirus within the family Flaviviridae

• Transmitted via mosquito bite of infected female Aedes aegypti and Aedes albopictus

• Very rare incidence of perinatal transmission, blood transfusion, organ transplantation, and sexual transmission

• Incubation period: 4-10 days

Pathophysiology [qfu]

1. Following a mosquito bite --> inoculation into the skin

2. Infects local immune cells (dendritic cells, macrophages, mast cells)

3. Lymphatic system --> regional lymph nodes --> bloodstream --> systemic viremia

4. Immune response:

   • Innate: interferon and natural killer cell activation

   • Adaptive: Dengue-specific B and T lymphocytes + neutralizing antibodies

5. Clinical presentation:

   • Asymtomatic

   • Mild flu-like symptoms: fever, headache, myalgia, arthralgia, rash

   • Severe disease characterized by:

     • Profound capillary permeability due to cytokine release

     • Hemorrhagic shock

     • Organ failure:

       • Bone marrow suppression: leukopenia and thrombocytopenia

       • Liver injury: Hepatitis, liver failure

       • Cardiac injury: myocarditis, pericarditis, pericardial effusion, arrhythmia

       • Neurologic involvement: encephalopathy, encephalitis, meningitis, cerebral hemorrhage, infarction, or ischemic stroke

       • Respiratory distress

       • Kidney failure

6. Recovery phase

   • Reabsorption of extravasated fluid and clinical improvement

Complications [qfu]

• Severe plasma leakage --> hypovolemic shock

• Coagulopathy --> bleeding: gastrointestinal, mucosal, or vaginal hemorrhage

• Organ failure: liver failure, myocarditis, encephalitis, kidney injury, respiratory failure, bone marrow suppression

• Neurologic complications: encephalitis, meningitis, Guillain-Barré syndrome and acute disseminated encephalomyelitis

• Sight-threatening ophthalmic inflammation

• Perinatal complications: maternal complications, fetal loss, and neonatal death

Risk factors [qfu]

• Environmental factors: Humidity, temperatures between 25°C and 30°C

• Prior dengue infection

• Extremes of age (children and older adults)

• Pregnancy

• Comorbidities (diabetes, hypertension, renal or cardiovascular disease)

Epidemiology

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Default, Northern America, Central Asia, Eastern Europe, Northern Europe, Southern Europe, Western Europe

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

South America

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Central America

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Caribbean

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Western Africa

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Middle Africa

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Eastern Africa

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Southern Africa

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Northern Africa

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Eastern Asia

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Southern Asia

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

South-eastern Asia

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Western Asia

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Australia and New Zealand

Incidence per 100.000 [qfu][q12][uc3][eyu][bwi][z9o][pbq]

Melanesia, Micronesia, Polynesia

Approach

• Laboratory tests: complete blood count, platelet count, hematocrit, liver enzymes, aPTT, PT-INR [qfu]

• PCR (typically positive during the first 5 days

• Serology:

  • Antigen testing (typically positive during the first 4 to 7 days)

  • Dengue IgM from day 4 after symptoms

• The tourniquet test reflects capillary fragility:

  >  10 petechiae per 2.5 cm (1 inch) square after maintaining cuff pressure midway between systolic and diastolic pressures for 5 minutes

• Imaging if complications:

  • Ultrasonography of the chest and abdomen

  • Chest x-ray

  • CT caput

Treatment

1. Profylaxis: Minimize exposure to infected Aedes mosquitoes [qfu]

   • Avoiding travel to endemic areas

   • Insect repellents

   • Clothing: wearing long-sleeved clothing and long pants

   • Bed nets

   • Mosquito-repellent coils

   • Remove standing water from containers (reservoirs)

   • Chemical control: insecticide

   • Vaccine: Dengvaxia

2. Treatment depends on severity: [qfu]

   • Dengue without warning signs (outpatient management)

   • Dengue with warning signs or comorbidity:

     Abdominal pain, persistent vomiting, mucosal bleeding, lethargy, restlessness, fluid accumulation, hepatomegaly, rising hematocrit, thrombocytopenia

   • Severe dengue

3. The triphasic clinical course:

   • Febrile

   • Critical/plasma-leakage

   • Recovery phase

4. No antiviral therapy is currently available

5. Supportive treatment:

   • Oral or IV hydration is the cornerstone of dengue management

   • Antipyresis

   • Acetaminophen

   • Monitoring vital status and urine output

   • Blood transfusion if hemorrhagic bleeding:

     • Gastrointestinal bleeding

     • Severe epistaxis

     • Heavy menstrual bleeding

   • Organ failure:

     • Coagulopathy --> vitamin K

     • Heart failure --> vasopressors

     • Respiratory failure --> ventilatory support

     • Kidney failure --> renal replacement therapy

Differential diagnoses

Adenovirus, Chikungunya, COVID-19, Crimean-Congo hemorrhagic fever, Ebola virus, Hantavirus, Herpes simplex, HIV, Influenza, Japanese encephalitis, Lassa fever, Leptospirosis, Malaria, Marburg virus disease, Measles, Mononucleosis, Rickettsia, Rubella, Sepsis, Tuberculosis, Typhoid fever, Viral hepatitis, West Nile virus, Yellow fever, Zika