dengue; bone break fever; dandy fever; Duengero fever; 7 day fever

Introduction

Mosquito-transmitted arbovirus infection.

Epidemiology

• transmitted by mosquito Aedes aegypti
  • not sexually transmitted
• hemorrhagic fever & shock uncommon in patients > 12 years of age
• females affected > males
• white affected > blacks
• diagnosed in the U.S. almost exclusively among travelers returning from tropical areas
• cases have emerged in Florida, New Mexico
• 390 million cases worldwide each year
• most prevalent mosquito-borne infection in the world
• endemic areas include Southeast Asia, South Pacific, Central America, South America, & the Carribbean
• Phillipines declares National dengue epidemic Aug 2019
• U.S. travelers most often acquire Dengue in the Caribbean, Southeast Asia, & Oceania
• reported cases up 8-fold since 2000 with 4.2 million cases reported in 2022
• countries in the Americas have reported more than 9.7 million dengue cases in 2024, twice as many as in all of 2023; none reported in the United States
• 3036 cases reported in the US & its territories in 2023
  • 2 cases of locally acquired dengue in Southern Calfornio October 2023
  • 1498 cases reported in Puerto Rico in 1st half of 2024
  • 2 locally acquired cases reported in Florida Keys 7/2/24
• climate change made 2024 the deadliest year of dengue

Pathology

• incubation period 3-15 days (4-7 days) (4-10 days)
• 4 antigenically similar serotypes
  • immunity to 1 serotype may not confer immunity to another
  • sequential infection with different serotypes may increase risk of hemorrhagic fever & shock
  • serotype 2 is most pathogenic
  • sequence of infection:
    • serotype 1 followed by serotype 2 has a higher morbidity than serotype 4 followed by serotype 2
• macrophage/monocyte infection
• malnutrition is protective

Clinical manifestations

• incubation period of 4-7 days
• may be asymptomatic
  • 1st time infection tends to be mild
  • 2nd infection can be more serious symptoms with hemorrhagic fever
• abrupt onset of symptoms
  • remitting after 3-4 days
  • relapsing fever 1-3 days later in some patients
• fever/chills (high fever)
• pain
  • frontal headache
  • retro-orbital pain
  • arthralgias
  • severe mylagias
  • bone pain
    • especially severe in the lumbar spine, thus "bone-break fever" (low back pain)
• gastrointestinal or respiratory symptoms may predominate
• erythematous morbilliform, punctate or petechial rash
  • begins on dorsal surface of hands & feet
  • spreads centrally to trunk
  • spares the palms & the soles
  • rash often develops 3-4 days after onset, corresponding to initial remission of fever
  • muscosal ulcerations
• minor spontaneous hemorrhage variable
  • bleeding common 56-75%, plasma leakage 14-30%
• petechial rash following inflation of blood pressure cuff (positive tourniquet test) distal arm a sign of microvascular fragility
• hemorrhagic fever & shock may occur with sequential infection with different serotypes
• liver disease 46-79%
• manifestations similar to chikungunya & Zika

Laboratory

• complete blood count:
  • leukopenia, neutropenia
  • thrombocytopenia
• alanine aminotransferase in serum (serum ALT) is elevated
• isolation of virus from blood early
  • Dengue virus RNA*
  • dengue + chikungunya + zika virus RNA
• dengue virus antigen
  • NS1 tests detect the non-structural protein 1 (NS1) of dengue virus
    • NS1 is secreted into the blood during a dengue infection
    • presence of NS1 in blood is consistent with acute phase dengue infection
• positive complement-fixation & neutralizing antibodies after 1st week
• dengue virus IgM in serum (positive 3-5 days after onset of fever)
• blood cultures are negative
• negative peripheral blood smears
• see ARUP consult

* also loincs for dengue virus DNA

CDC recommendations in areas where both Zika & dengue are endemic

• nucleic acid amplification testing (NAAT) for dengue & Zika on serum samples collected <= 7 days after symptoms begin.
• when NAAT results are negative, or serum samples are collected > 7 days after symptom onset, IgM antibody testing should be performed
• if IgM antibody results are positive & NAAT results are negative, neutralizing antibody testing as indicated
• for pregnant women:
  • serum & urine samples should be collected as soon as possible within 12 weeks of symptom onset for simultaneous NAAT & IgM serology for dengue & Zika
  • if IgM antibody results are positive & NAAT results are negative, neutralizing antibody testing as indicated

Diagnostic procedures

• positive tourniquet test
• ophthalmoscopy: abnormalities seen in 23% of primary infections

Complications

• hemorrhagic encephalitis
• dengue shock syndrome
  • vasculopathy
  • thrombocytopenia
  • coagulopathy
• hemophagocytic lymphohistiocytosis

Differential diagnosis

• Chikungunya incubation is 48-72 hours, 3-7 days
  • arthritis is more severe & synovitis is more likely with chikungunya
  • arthralgia is a predominant feature of chikungunya
    • usually bilateral & symmetric, more often involving distal joints (wrist, ankles) than the proximal joints (knees, hips, lumbar spine)
• Zika incubation is 3-14 days
  • rash not as prominent as Chikungunya or Zika
  • myalgia more prominent than Chikungunya or Zika
  • arthralgia less prominent than Chikungunya or Zika
  • bleeding not a feature of Chikungunya or Zika
  • shock not a feature of Chikungunya or Zika
  • conjunctivitis not a feature of dengue or Chikungunya
• typhoid fever
  • negative blood cultures & absence of GI symptoms distinguishing features from typhoid fever
• malaria
  • thrombocytopenia, abnormal liver function tests & negative peripheral blood smears render malaria unlikely

Management

• treatment is supportive
• prednisone not effective
• prevention:
  • mosquito avoidance, insect repellant
  • Dengue virus vaccine for secondary prevention in children & adolescents with laboratory-confirmed prior dengue infection

More general terms

• viral infection

Additional terms

• Aedes aegypti (Asian tiger mosquito)
• dengue virus
• dengue virus vaccine (Dengvaxia)

Patient information

dengue patient information