DENGUE

• Dengue


  Mosquito-borne infection caused by a flavivirus, characterized by fever, severe headache, muscle and joint pain, nausea and vomiting, eye pain, and rash
• Dengue viruses


  • Spread to people through the bite of an infected Aedes species (Ae. aegypti or Ae. albopictus) mosquito
  • Caused by one of four related viruses: dengue virus 1, 2, 3, and 4
  • A person can be infected with dengue multiple times in their life
• Almost half of the world's population, about 4 billion people, live in areas with a risk of dengue
• Each year, up to 400 million people are infected by a dengue virus. Approximately 100 million people get sick from infection, and 40,000 die from severe dengue
• Clinical disease


  1. Begins 4–7 days (range, 3–14 days) after an infective mosquito bite

  2. Onset of fever may be sudden or there may be prodromal symptoms of malaise, chills, and headache

  3. Pains soon develop, especially in the back, joints, muscles, and eyeballs

  4. Fever lasts from 2 to 7 days, corresponding to peak viral load

  5. Temperature may subside on about the third day and rise again about 5–8 days after onset ("saddleback" form)

  6. Myalgia and deep bone pain (breakbone fever) are characteristic

  7. A rash may appear on the third or fourth day and last for 1–5 days

  8. Lymph nodes are frequently enlarged
• Dengue hemorrhagic fever or dengue shock syndrome


  Severe syndrome that may occur in individuals (usually children) with passively acquired (as maternal antibody) or preexisting nonneutralizing heterologous dengue antibody caused by a previous infection with a different serotype of virus
• Symptoms of severe dengue

  1. Belly pain, tenderness, vomiting, bleeding from the nose or gums, vomiting blood, or blood in the stool, feeling tired, restless, or irritable

  2. Can lead to life-threatening shock in some patients
• Severe dengue can result in shock, internal bleeding, and even death
• Transmission of dengue viruses

  1. Through infected mosquito bites

  2. From mother to child during pregnancy or around the time of birth

  3. Through infected blood, laboratory, or healthcare setting exposures
• Reverse transcriptase PCR (RT-PCR)-based methods

  Available for rapid identification and serotyping of dengue virus in acute-phase serum, roughly during the period of fever
• Serologic diagnosis


  • Complicated by cross-reactivity of IgG antibodies to heterologous flavivirus antigens
  • Most commonly used methods are envelope/membrane viral protein-specific capture IgM or IgG ELISA and the HI test
  • IgM antibodies develop within a few days of illness
  • Neutralizing and hemagglutination-inhibiting antibodies appear within a week after the onset of dengue fever
  • Analysis of paired acute and convalescent sera to show a significant rise in antibody titer is the most reliable evidence of an active dengue infection
• Four serotypes of the dengue virus

  • Infection confers lifelong protection against that serotype, but cross-protection between serotypes is of short duration
  • Reinfection with a virus of a different serotype after the primary attack is more apt to result in severe disease (dengue hemorrhagic fever)
• Pathogenesis of severe dengue syndrome

  • Involves preexisting dengue antibody
  • Virus–antibody complexes are formed within a few days of the second dengue infection and the nonneutralizing enhancing antibodies promote infection of higher numbers of mononuclear cells followed by the release of cytokines, vasoactive mediators, and procoagulants, leading to the disseminated intravascular coagulation seen in the hemorrhagic fever syndrome
  • Cross-reactive cellular immune responses to dengue virus may also be involved
• Dengue viruses are distributed worldwide in tropical regions
• In the past 20 years, epidemic dengue has emerged as a problem in the Americas
• The changing disease patterns are probably related to rapid urban population growth, overcrowding, and lax mosquito control efforts
• The risk of the hemorrhagic fever syndrome is about 0.2% during the first dengue infection but is at least 10-fold higher during infection with a second dengue virus serotype
• The fatality rate with dengue hemorrhagic fever can reach 15% but can be reduced to less than 1% with proper treatment
• The ratio of inapparent to apparent infections is variable but may be about 15 to one for primary infections; the ratio is lower in secondary infections
• Dengue epidemics in urban communities

  1. Explosive and involve appreciable portions of the population

  2. Often start during the rainy season, when the vector mosquito, A aegypti, is abundant

  3. The mosquito breeds in tropical or semitropical climates in water-holding receptacles or in plants close to human dwellings
• A aegypti


  • The primary vector mosquito for dengue in the Western Hemisphere
  • The female acquires the virus by feeding upon a viremic human
  • After a period of 8–14 days, mosquitoes are infective and probably remain so for life (1–3 months)
  • In the tropics, mosquito breeding throughout the year maintains the disease
• World War II was responsible for the spread of dengue from Southeast Asia throughout the Pacific region
• Only dengue type 2 was present in the Americas for years. Then, in 1977, a dengue type 1 virus was detected for the first time in the Western Hemisphere. In 1981, dengue type 4 was first recognized in the Western Hemisphere followed in 1994 by dengue type 3
• Endemic dengue in the Caribbean and Mexico is a constant threat to the United States, where A aegypti mosquitoes are prevalent in the summer months
• Aedes albopictus, a mosquito of Asian origin, was discovered in Texas in 1985; by 1989 it had spread throughout the southeastern United States, where A aegypti, the principal vector of dengue virus, is prevalent. In contrast to A aegypti, which cannot overwinter in northern states, A albopictus can overwinter farther north, increasing the risk of epidemic dengue in the United States
• Treatment of dengue


  • No antiviral drug therapy
  • Dengue hemorrhagic fever can be treated by fluid replacement therapy
  • Therapeutic antibodies able to neutralize multiple genotypes of dengue are also under development
• Prevention and control of dengue

  1. Avoid mosquito bites

  2. Eliminate mosquito breeding places and use insecticides

  3. Use screened windows and doors to reduce exposure to the vectors
• Dengue vaccine Dengvaxia


  • Recommended for U.S. territories of American Samoa, Puerto Rico, and the U.S. Virgin Islands, and freely associated states, including the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau
  • Approved for use in children aged 9–16 years with laboratory-confirmed previous dengue virus infection and living in areas where dengue is endemic
  • Not approved for use in U.S. travelers who are visiting but not living in an area where dengue is common
  • Sanofi-Pasteur will stop manufacturing Dengvaxia due to lack of demand in the global market
• There are two other dengue vaccines either approved or in late stages of development, but they are not currently available in the United States
• Key facts about dengue

  • About one in four people infected with dengue will get sick
  • For people who get sick with dengue, symptoms can be mild or severe
  • Severe dengue can be life-threatening within a few hours and often requires care at a hospital