INITIATIVE FOR VECTOR AND INSECT SCIENCE AT BOSTON COLLEGE

 

DENGUE FEVER AND

DENGUE HEMORRAGHIC FEVER

By John P. Roche

WHAT ARE DENGUE FEVER AND DENGUE HEMORRAGHIC FEVER?
Dengue fever is caused by an RNA flavivirus that is spread by the bites of mosquitoes. The symptoms of dengue include fever, headache, rash, severe pains in the muscles and joints, and pain behind the eyes. The severe muscle pains have led some to call the disease "break bone fever". Whereas dengue fever is rarely fatal, dengue hemorraghic fever is a severe disease that leads to death in approximately 5% of cases. Individuals with dengue hemorraghic fever suffer an increase in vascular permeability, causing them to lose plasma; if untreated, this loss of plasma can lead to a dangerous drop in fluid volume (known as dengue shock syndrome) and death. Dengue hemorraghic fever is seen most often in children younger than 15 years old. It is also seen most often in individuals who were previously infected with simple dengue fever.

The dengue flavivirus occurs in four different serotypes, DEN-1, DEN-2, DEN-3, and DEN-4. Contracting one form of dengue fever provides lifelong immunity from that serotype, but not from the other serotypes. Cases of dengue fever occur primarily in urban areas in the tropics. Estimates of the worldwide rate of dengue infection range from 20 million to 100 million cases each year, with an estimated 24,000 cases leading to mortality annually. Dengue fever and dengue hemorraghic fever are both expanding health problems. Increases in urbanization, increases in international travel and trade, and decreases in public-health infrastructure in many countries have contributed to an alarming increase in the incidence of cases. The number of cases of dengue fever in the Americas increased by more than 100% between 1995 and 1998, and the number of cases of dengue hemorraghic fever worldwide increased by over 400% between 1970 and 1995. [As of 2016, the CDC estimates that dengue is endemic to 100 countries, and causes the loss of over 20,000 lives each year.]

HOW DO PEOPLE CONTRACT DENGUE FEVER AND DENGUE HEMORRAGHIC FEVER?
Humans contract dengue fever from bites of infected female mosquitoes of the genus Aedes.  Aedes aegypti is the primary vector in most regions. When a female Aedes mosquito bites a person infected with dengue, the virus incubates in the insect's body for 8–11 days, after which the mosquito can spread the disease to other humans for the remainder of the insect's life span (15–65 days). Once the virus enters a human, it circulates in the bloodstream for two to seven days, during which time the virus can be spread to other blood-feeding Aedes mosquitoes. Humans are the primary reservoir for the virus, although some scientists have hypothesized that monkeys can also serve as reservoirs.

Aedes aegypti originated in Africa, where it relied on temporary puddles of rain water in which to breed. The species subsequently expanded through much of the tropics, spread by ships, and then perhaps also by airplanes. Today there are two subspecies of Aedes aegypti, Ae. aegypti queenslandensis, the wild form in Africa, which is not a significant vector of dengue, and Ae. aegypti formosus, a primarily urban mosquito that transmits dengue to humans in many parts of the tropics. In the past, Aedes aegypti had to rely on temporary pools of rainwater in which to breed. Today, however, widespread urbanization has supplied Aedes aegypti with abundant man-made pools of water in which to breed.

Aedes albopictus was originally the primary vector of dengue fever, and remains a major vector in Asia. This species has recently spread to Central America and the U.S., where it is a secondary vector of the disease. Whereas Ae. aegypti formosus is primarily urban, Aedes albopictus is rural, thus increasing the ecological range of habitats in which people can become infected.

Some researchers hypothesize that dengue hemorraghic fever results when a person who has been sensitized by a previous infection by one dengue serotype is infected with a second dengue serotype. This explanation is supported by the observations that dengue hemorraghic fever is most common in individuals who previously had dengue fever, and that dengue hemorraghic fever is much more common in residents of endemic areas than in visitors to endemic areas. If exposure to multiple serotypes triggers dengue hemorraghic fever, then the spread of the different serotypes into new regions via international trade (e.g., shipments of used tires) and intercontinental travel could further increase the incidence of this dangerous disease.

WHAT ARE THE GEOGRAPHIC DISTRIBUTIONS OF DENGUE FEVER AND DENGUE HEMORRAGHIC FEVER?
Dengue fever and dengue hemorraghic fever occur in Central America, South America, sub-Saharan Africa, Southern Asia, and the Western Pacific. Dengue fever has appeared in Texas within the United States three times during the last several decades. Both Aedes aegypti and Aedes albopictus vectors live in the United States, and so dengue outbreaks in that country are always a possibility. Increased frequency of international travel has accelerated the spread of different dengue serotypes around the world. For example, DEN-2 was detected in the Americas in 1970, DEN-1 in 1977, and DEN-4 in 1981. The DEN-3 serotype, which had previously existed in the Americas and then disappeared, made a reappearance in 1994.

HOW CAN DENGUE FEVER AND DENGUE HEMORRAGHIC FEVER BE TREATED AND CONTROLLED?
Vaccines. Vaccines that are effective against all four serotypes of dengue fever are needed. Such tetravalent vaccines are not currently available for distribution, but one has been developed at Mahidol University in Thailand, in association with the World Health Organization. The vaccine, which appears to be safe, is currently undergoing clinical trials.

Treatment. Treatment of dengue fever and dengue hemorraghic fever involves treatment of symptoms. With dengue hemorraghic fever, intensive support therapy, especially replacement of lost fluid volume when plasma leaks from the circulatory system, is tremendously important. Support therapy involving fluid replacement can reduce dengue hemorraghic fever mortality rates from greater than 20% to less than 1%. Accurate detection of dengue is now possible with IgM-capture ELISA serological tests. Surveillance is important so that public-health and mosquito-control agencies can be alerted and mobilized prior to the outbreak of epidemics. Unfortunately, surveillance is currently inadequate in many countries, including the United States.

Vector Control. Control of Aedes vectors can contribute significantly to reductions in dengue infection rates. In the 1950s and 1960s, the Pan American Health Organization succeeded in eradicating Aedes aegypti from many areas of Central and South America, and epidemics of dengue were rare in those decades. However, when the eradication program was stopped, Aedes aegypti, and subsequently dengue, returned.

A primary method of controlling Aedes populations is by depriving female Aedes of pools of water in which to lay eggs. Covering cisterns, barrels, jars, and other water storage vessels, as well as discarding old tires and modernizing waste-water and solid-waste treatment systems, could reduce Aedes populations considerably. Additional

methods of control include oviciding bodies of water to kill mosquito eggs with compounds such as household bleach, larviciding pools of water to kill larval mosquitoes, and adulticiding with aerosol canisters. Surface spraying and/or aerial spraying are also sometimes used in severe outbreaks. Whereas female Aedes aegypti cannot transmit
dengue to their eggs (transovarial transmission), Aedes albopictus can; this may make oviciding and/or larviciding particularly important to control the spread of dengue via Aedes albopictus.

As with all insect-borne diseases, simple personal protection, such as wearing long sleeves, applying insect repellent, and avoiding locations with high vector densities, is also important. Because Aedes mosquitoes are active in the daytime, personal protection strategies differ somewhat from those for mosquitoes active in the night time, such as members of the genera Anopheles and Culex.

Public Education. Public education about dengue and its vectors has been highly effective in some regions, including Panama and Cuba. Public education is particularly important with this disease because of the widespread, urban nature of dengue's vectors, and because of the vital importance of intensive supportive therapy for those with dengue hemorraghic fever.

WHERE CAN YOU FIND OUT MORE ABOUT DENGUE FEVER AND DENGUE HEMORRAGHIC FEVER?
Isturiz, R. E., Gubler, D. J., and Brea del Castillo, J. 2000. Dengue and dengue hemorrhagic fever in Latin America and the Caribbean. Infectious Disease Clinics of North America 14: 121-140.

Shirtcliffe, P., Cameron, E., Nicholson, K. G., and Wiselka, M. J. 1998. Don't forget dengue! Clinical features of dengue fever in returning travelers. Journal of the Royal College of Physicians of London 32: 235-237.

Gubler, D. J. 1998. Dengue and dengue hemorrhagic fever. Clinical Microbiology Reviews 11: 480-496.

Guerrant, R. L., Walker, D. H., and Weller, P. F. (Eds.) 2001. Essentials of Tropical Infectious Diseases. W. B. Saunders, Philadelphia.

Beaty, B. J., and Marquardt, W. C. (Eds.) 1996. The Biology of Disease Vectors. Univ. of Colorado Press, Niwot, Colorado.

The World Health Organization: http://www.who.int/health-topics/dengue.htm

UNDP-World Bank-WHO-Special Programme for Research and Training in Tropical Diseases:

http://www.who.int/tdr/diseases/dengue/default.htm

The Centers for Disease Control: http://www.cdc.gov/ncidod/dvbid/dhfacts.htm

[Reprinted from the Initiative for Vector and Insect Science website.]