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Dengue Fever: Where Do We Go From Here?

By: Sherin Pathickal, PharmD Candidate c/o 2016

Dengue Fever, widely known as “break-bone fever,” is an illness that causes pain in the joints and muscles, and is often described by those infected as comparable to the feeling of breaking a bone.1 It is spread by mosquitoes and has a painful array of symptomology such as headaches, severe joint pain, fever, and bleeding.1 Although these symptoms are reminiscent of the flu, Dengue Fever causes a decrease in white-blood-cells, potentially leading to hemorrhagic fever, bleeding, shock, and death.2 The World Health Organization has reported that nearly 390 million people are currently afflicted with Dengue Fever, and that nearly 40% of all people live in areas that put them at risk for this disease.2 Furthermore, this disease has become an endemic in Nicaragua, has been seen for the first time in nearly 70 years in Western Australia, and has shown to be more deadly and severe now than in the last 20 years in Thailand.2

As the first occurrences of Dengue Fever were recently found on United States soil, this infection has become even more problematic. The first case in the U.S was seen in Houston, Texas. Since August 28th, nearly eight known cases were identified in Florida and were all found to be of local origin, indicating that the disease was not carried from abroad but is prevalent in the mosquito population of the United States.3 As of mid-November, cases have been seen throughout Texas and New York, signaling that these local infections are spreading more readily than previously believed.3 This disease has specifically been attributed to bites that were inflicted in the summer by the Aedes aegypti or Asian Tiger mosquito.1 With large amounts of rainfall leading to standing water, warmer climates, and highly densely populated areas, it is no wonder that Dengue Fever is on the rise.3

Although not contagious from person to person, Dengue Fever can be quickly spread by mosquitoes. In addition to the more common symptoms listed previously, other characteristics of this disease include a maculopapular rash along the extremities and chest, eye pain, skin hypersensitivity, and GI complications.4 The severity of disease varies greatly, as patients can present with an uncomplicated fever, a more serious hemorrhagic fever, or the most severe shock syndrome. There are no early warning signs that one may have the disease until the symptoms appear, which can typically take between 3 to 14 days following the initial infection. The disease itself usually lasts around 4 to 7 days.1 Unfortunately, there are currently no approved vaccines or treatments for Dengue Fever.2

Despite the fact that no approved vaccines or major treatments currently exist to combat this invasive disease, it is imperative that the illness be diagnosed as quickly as possible so as to prevent any further damage to the patient’s health. Once diagnosed, the CDC recommends hospitalization in order to adequately manage the illness.5 During a patient’s stay in the hospital, the patient is treated with fluid replacement therapy in order to prevent dehydration, is told to rest, and is given analgesics to help with the pain associated with Dengue Fever.5 Due to the nature of the disease, it is advised that all patients be put on pain relievers containing only acetaminophen as opposed to aspirin or aspirin-like medications. This is because Dengue Fever has the potential to cause thrombocytopenia which increases a patient’s propensity to bleed, a risk that would only be potentiated by anti-platelet drugs such as aspirin.5 Generally, with adequate rest, fluids, and pain management, the patient normally recovers.5

With very few treatment options available and with the threat of Dengue Fever on the rise, it is clear that the need to formulate and develop an approved vaccine is of utmost importance. The pharmaceutical manufacturing company, Sanofi, became one of the first to develop a potential vaccine in 2012. However, this vaccine proved to be only 30% effective during the first phase of the clinical trials.6 The question is then asked, why is this vaccine so hard to formulate? Dengue Fever has four major strains, and all four must be protected against in order for the vaccine to be truly effective.2 If one becomes infected with a single strain of the disease, they are more susceptible to the other strains as well. 7 The vaccine formulated by Sanofi has only shown to be protective against 3 of the 4 strains, indicating that further research is needed, and it is hoped that by 2015 a more suitable vaccine will be formulated.2

Despite these setbacks, other groups and organizations throughout the world are working on developing an effective vaccine. In Colorado, a vaccine formulated by a team lead by Dr. Claire Huang entered Phase II of the clinical trials in 2012. The vaccine has shown to be effective against all four strains by allowing those who receive the vaccine to develop antibodies to the different types of Dengue Fever.7 In Baltimore, Anna Durbin and her team led a similar study, and results indicated that one particular combination of the vaccine known as TV003 was most effective at producing the desired immune response after just a single dose during Phase I trials.8 As can be seen from all three studies, further research and development is still needed, but with the proper resources and education the desired responses can soon be obtained. However, what remains certain is that we are facing a race against time as this disease becomes more deadly.

As researchers hurry to develop treatment options and a preventative vaccine, an organization known as Eliminate Dengue has been working towards reproducing mosquitoes that carry Wolbachia bacteria in Vietnam.2 Although how the bacteria prevent mosquitoes from developing Dengue Fever is still unclear, this bacteria helps lower the risk of passing the disease on to humans.2 These mosquitoes have been found to outlive and thrive over mosquitoes that have been infected with Dengue Fever, giving further strength to its use as a measure against the spread of the disease.2

As future healthcare professionals, it is vital that we recognize the signs and symptoms associated with mosquito-borne diseases, as many patients may not realize that they have been bitten or exposed. Because many of the initial symptoms are so closely related to those of the flu and other air borne viruses, Dengue Fever is often misdiagnosed which can lead to further complications for the patient.1 As a result, it is imperative that the patient be treated as soon as possible. Furthermore, we should stress prevention methods during high-risk seasons by educating people to wear skin covering clothing and using mosquito repellent.1 In doing so, this disease can hopefully be eradicated within the United States before it becomes yet another endemic.

SOURCES:

  1. Bixler J. Florida confirms 24 cases of dengue fever in Key West. CNN Health. http://www.cnn.com/2010/HEALTH/08/03/dengue.virus.florida/index.html. August 3 2010.
  2. Campbell C. If you’re not worried about dengue fever, here’s why you should be. Time. November 2013.
  3. Sutton J, Shoichet C. 8 dengue cases detected in Florida. CNN Health. http://www.cnn.com/2013/08/27/health/florida-dengue/index.html. August 28, 2013. Accessed January 10, 2014.
  4. Peters, C. Infections Caused by Arthropod and Rodent-borne Viruses. Harrison’s Principles of Internal Medicine. By Dan L. Longo and Tinsley Randolph Harrison. 18th ed. New York: McGraw-Hill, Medical, 2012.
  5. Centers for Disease Control and Prevention. Symptoms and what to do if you think you have Dengue. http://www.cdc.gov/Dengue/symptoms/. Updated September 27, 2012. Accessed January 9, 2014.
  6. Pollack A. In a setback, Sanofi’s Dengue Fever vaccine falls short of its goal. The New York Times. http://www.nytimes.com/2012/09/11/health/a-dengue-vaccine-falls-short-of-expectations.html?_r=0. September 10, 2012.
  7. Centers for Disease Control and Prevention. Developing a vaccine. http://www.cdc.gov/24-7/protectingPeople/dengue/developing_vaccine.html. Updated January 6, 2012. Accessed January 10, 2014.
  8. National Institutes of Health. NIH-developed candidate Dengue vaccine shows promise in early-stage trial. http://www.nih.gov/news/health/jan2013/niaid-23.htm. Updated January 23, 2013. Accessed January 10, 2014.
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