Updated November 19, 2014.

Every year an estimated 100 million people are infected with dengue or breakbone fever, and 500,000 people (mostly children) go on to develop its most serious and deadly iteration, dengue hemorrhagic fever.  Dengue is a scourge of developing nations, a mosquito-borne viral infection that thrives in tropical and subtropical climates which house about half the world's population.  Until recently, our only defense against the disease was symptomatic treatment like fluid resuscitation and pain relievers, and, of course, hope.

  But after more than 20 years of hard work, researchers are on the cusp of a real clinical breakthrough: an FDA-approved vaccination for the sometimes-deadly dengue virus.

 

What is dengue?

 

Dengue is a virus borne from the (figurative) bowels of mosquitos--specifically, Aedes aegypti.   This day-biting (bizarro vampire?) bug spreads sickness in the Americas, Southeast Asia, Africa and Indian subcontinent.  Occasionally, the disease can creep stateside and has been found in Florida and along the United States-Mexico border.

In Central and South America, the Caribbean, Africa and India, people infected with the virus usually develop classical dengue.  Four to 7 days after being bit, a person will develop symptoms like:

• high fever
• headache
• nausea
• vomiting
• myalgia  (muscle pain)
• joint ("breakbone") pain
• rash
• retro-orbital pain (pain around the eyes)
• facial flushing

After several days, the fever breaks, and a fine morbilliform (measles-like) rash spreads from the trunk to the face and arms and legs.  Of note, in small children, classical dengue can present only as a mild upper respiratory infection, which is reminiscent of the flu.

Dengue hemorrhagic fever is much more severe and usually hits urban environments in Southeast Asia.  This iteration of dengue kills more than 10% of those affected.  At first, dengue hemorrhagic fever follows a clinical course indistinguishable from classical dengue, but after the initial fever starts to wane, fatigue and shock take over.  Oh, and then there's thrombocytopenia (low platelet count) coupled with bleeding; bleeding from the nose and under the skin which is, in part, caused by increased vascular permeability.  Such increased vascular permeability can also flood the lungs with fluid causing pulmonary effusions.  If untreated, the shock becomes septic and results in stomach pain, vomiting, confusion, irritability and fever that alternates with hypothermia.

Dengue is usually diagnosed by clinical history, but blood tests (ELISA for immunoglobulin M) can confirm its presence.  Treatment is supportive and includes analgesics for pain relief and rehydration with both intravenous fluids and water.  Of note, acetaminophen (Tylenol) is used for pain relief because NSAIDs like aspirin have anticoagulation properties that could exacerbate the bleeding that already occurs during dengue.  To boot, acetaminophen has antipyretic or fever-reducing properties.

 

Enter the dengue vaccine

 

The WHO has ambitiously called for a 50 percent decrease in the number of deaths caused by dengue by 2020.  Heeding this call, drug maker Sanofi has been hard at work on a vaccine and results from a two-armed Phase 3 clinical trial conducted in both Asia and Latin America are promising.  For example, in the Latin American trial 20,869 children received either 3 doses of the vaccine or placebo (2 vaccinated participants:1 placebo-receiving participant) and were followed for 25 months with the following results:

• 60.8% efficacy against symptomatic dengue in participants aged 9 to 16 (176 cases developed in the larger vaccinated group versus 221 cases in the control group who received placebo treatment);
• 80.3% efficacy against hospitalization;
• 95.5% efficacy against severe dengue (think dengue hemorrhagic fever);
• serotype-specific efficacy for all 4 serotypes (the vaccine confers resistance against 4 flavors of dengue that are contained in the vaccine);
• no significant adverse effects (the vaccine was safe).

Encouragingly, the results of the Latin-American trial approximated those of the Asian trial.

 

What does the dengue vaccine mean to you?

 

Granted, if you live in the United States, you're probably at limited risk for infection with dengue.  But lest we forget, the world is bigger than our fifty states and territories.  For people around the world, the dengue vaccine will not only save lives but improve quality of life.  Furthermore, for many Westerners who travel overseas, the vaccine will probably deter the receipt of an unwanted souvenir: the dengue virus.

On a final note, we're living in what is amounting to a Golden Age of vaccine discovery.  Ever since the year 2000, we've witnessed the emergence of pneumococcal, meningococcal, rotavirus and HPV (shingles) vaccines.

 

Selected Sources

 

Peters CJ. Chapter 196. Infections Caused by Arthropod- and Rodent-Borne Viruses. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. . Accessed November 07, 2014.

VanRooyen MJ, Venugopal R. Chapter 156. World Travelers. In: Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T. eds. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e. New York, NY: McGraw-Hill; 2011.  Accessed November 07, 2014

“Efficacy of a Tetravalent Dengue Vaccine in Children in Latin America” by L Villar and colleagues published in NEJM on 11/3/2014.  Accessed from PubMed on 11/7/2014.