What is Dengue fever?

Dengue fever (pronounced DENG-gay), an illness caused by the Dengue virus, is a global public health concern that affects 50-100 million people annually [1]. Over the last 50 years, global Dengue infections have increased 30-fold. The virus has also spread geographically in many tropical and subtropical regions, including Central and South America, Africa, and South East Asia. In 2010, Dengue was reported in the southern US for the first time in more than half a century.

The Dengue virus is spread by bites from the Aedes aegypti mosquitoes, the same mosquitoes that carry the yellow fever virus and West Nile virus. Only female mosquitoes are a concern, however, as they are the ones that bite for blood while males drink nectar [2]. Interestingly, the virus does not make the mosquito sick, but the mosquito remains infected for its life — about 2 weeks, for most female mosquitoes. Some studies suggest that climate change may put even more communities at risk of Dengue, as changes in temperature and rainfall may affect the distribution of the mosquitoes [3].

In humans, the virus infects blood and immune cells, and causes mild to severe flu-like symptoms including fever, rash, headache, nausea, body pains, and vomiting. Children are at increased risk, and in several Asian countries, Dengue infection is a leading cause of death in children. The virus is particularly dangerous because there are four varieties, termed “serotypes”, and repeated infections by different serotypes can give rise to serious forms of the disease known as Dengue Hemorrhagic Fever or Dengue Shock Syndrome.

Bleeding from where?!

When our body is infected by a pathogen, one way that our immune system helps defeat the illness is by producing antibodies, which also protect us from future infections by the same pathogen. Sure enough, the first time a person is infected with one of the four serotypes of the Dengue virus, antibodies are produced and help the person recover from the flu-like symptoms in about a week.

The problem with Dengue becomes apparent when a person gets infected by a second or third serotype of the virus. Sometimes the antibodies produced from the first infection will protect you from all four serotypes. Other times, however, the antibodies not only fail to protect you, but instead end up enhancing the infection. Antibodies against one serotype can recognize but cannot mount a defense against the new invader, because the different serotypes have slightly different outer shell or “envelope”. As these antibodies coat the new virus, they inadvertently allow the new virus to easily enter and infect a broad range of immune cells, leading to serious tissue damage. This series of events is known as Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS). In the worst cases, DHF/DSS can cause bleeding from the nose, gums and skin, major fluid loss, and even death.

Unfortunately, there are currently no drugs that can kill the virus or even treat the symptoms of DHF/DSS — even aspirin and ibuprofen are not recommended, as they block the body’s ability to patch leaking blood vessels damaged by the virus. Patients typically receive bed rest, an anti-fever drug, and fluid replacement treatment [1].

How do we stop Dengue?

Many research groups worldwide are working to develop a vaccine to protect against Dengue, but it remains a huge challenge because of the four serotypes. Just think: if a vaccine stimulates your body to produce antibodies against any one serotype of the virus, it protects you against that one type, but the antibodies might put you at risk for DHF/DSS if you were to get infected with any of the other three forms in the future! Scientists are therefore developing a new strategy: “tetravalent” vaccines, which contain representative parts of all four types of the virus. Researchers are hopeful that this strategy will successfully protect against infections by any serotype [4].

Currently, the best way to make a big impact on this human illness is to think small — by fighting the mosquito that carries the virus, or “vector control”. Less contact with the mosquitoes means fewer chances to be bitten and get sick. International travelers to regions where Dengue is widespread are encouraged to wear long sleeves and use bug spray to ward off unwanted mosquito pests. In tropical and subtropical communities, installing screens in doors and windows physically keeps the mosquitoes out, reducing bug bites that occur in homes, schools and businesses. On the other hand, while bed nets are effective for preventing against malaria (another mosquito-carried disease), they are not helpful against Dengue, because the species of mosquito that carries the Dengue virus bites during the day.

Many governments are also working to improve sanitation systems and to clean trash out from streets to eliminate standing water, which serves as egg-laying grounds for the mosquitoes [1]. Some governments are combating outbreaks with chemical insecticides, employing teams of workers with hand-held spray systems, spray trucks that drive down community streets, or low flying planes. However, these efforts require a substantial amount of money, and are not an affordable option for many developing countries. In addition, the mosquitoes can evolve resistance to the insecticides over time [5], and these chemicals can furthermore be toxic to humans and ecosystems. The World Health Organization has thus set out very detailed guidelines for when and how these insecticides should be used [1].

Dengue is one tough virus, and the mosquitoes that carry it make the spread of the disease all the more difficult to contain. But with coordinated public health efforts to protect communities, and with researchers urgently developing vaccines and treatments, there is hope that the rise of this tropical infectious disease can be curbed.

Ann Fiegen Harvard GSAS – Division of Medical Sciences

References:

1. World Health Organization: 2009 Report on Dengue http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

2. Illinois Dept of Public Health: Mosquitoes and Disease http://www.idph.state.il.us/envhealth/pcmosquitoes.htm

3. Climate Change and Dengue Risk in the Caribbean http://www.aiaccproject.org/meetings/SanJose_03/Session6/Session6_AAmarakoon.ppt

4. Science Business: Dengue Vaccine in Phase 3 Clinical Trial http://sciencebusiness.technewslit.com/?p=1928

5. Lima, JBP et al. (2003) Resistance of Aedes aegypti to organophosphates in several municipalities in the state of Rio de Janeiro and Espírito Santo, Brazil. Am. J. Trop. Med. Hyg., 68: 329–333. http://www.ajtmh.org/cgi/reprint/68/3/329.pdf