Dengue and Dengue Hemorrhagic Fever

DuaneJ. Gubler

engue and dengue hemorrhagic fever (DHF) are caused

by infection with dengue viruses. There are four dengue
serotypes: 1, 2, 3, and 4. These viruses are related closely to each
other antigenically, and, as a result, serological tests reflect
extensive cross-reactivity. However, infection with any seroty-pe
does not provide cross-protective immunity against the others.
Persons living in an endemic area can be infected with each of
the four dengue serotypes during their lifetime.
Infection with dengue viruses is transmitted through the bite
of an infective AMes aegypti mosquito. Ae aegypti is a small, black
and white, highly domesticated mosquito that prefers to lay its
eggs in artificial containers commonly found in and around
homes in the tropics, for example, containers used for water
storage, flower vases, old automobile tires, and buckets that
collect rainwater. The adult mosquitoes prefer to rest indoors,
are unobtrusive, and prefer to feed on humans during daylight
hours. As a result, inhabitants rarely are aware of the presence
of this mosquito, making its control difficult.
After a person is bitten by an infective mosquito, the virus
undergoes an incubation period of 3 to 14 days (average, 4-6
days), after which the person may experience acute onset of
fever accompanied by a variety of nonspecific signs and symptoms. During this acute febrile period, which may be as short as
2 days and as long as 10 days, dengue viruses may circulate in
the infected person's peripheral blood. If other Ae aegypti
mosquitoes bite the ill person during this febrile viremic stage,
those mosquitoes may become infected and subsequently transmit the virus to other uninfected persons, after an extrinsic
incubation period of 8 to 12 days.
'Dengue viruses and Ae aegypti mosquitoes are distributed
throughout the tropical areas of the world (Fig 1); more than 2.5
billion people live in dengue-endemic areas. 1-3 Currently, dengue fever causes more illness and death than any other arboviral
disease acquired by humans. Each year, an estimated 50 to 100
million cases of dengue fever and several hundred thousand
cases of DHF occur, depending on epidemic activity. 4,5 The
severe and fatal form of the disease, DHF, is a leading cause of
hospitalization and death among children in many Southeast
Asia countriesfi Epidemics of DHF first occurred in Southeast
Asia in the 1950s, spread to the South Pacific Islands in the
1970s, and reached the Caribbean basin in the 1980s. 3,5-8
Current evidence suggests that the pattern of severe hemor-

From She Division of Vector-Borne l:@ctious Diseases, National Centerfor

Infectious Diseases, Centers"for Disease Control and Prevention, Public Health
Service, US Department ofHealth and Human Services,Fort Collins, CO.
Please address correspondenceto Duane J. Gubler, ScD, Director, Dibision of
Vector-BorneInfectiousDiseases,National Centerfor InfectiousDiseases, Centersfor
Disease Controland Prevention, Public Health Service, U.S. Department ofHealth
and Human Services,PO Box 2087, Fort Collins, CO 80522.
This is a US government work. There are no restrictionson its"use.
1045-1870/97/0801-000350. 00/0

rhagic disease is evolving in the American region in a manner

similar to the way it did in Southeast Asia in the 1960s. 9

Changing Disease Patterns

Dengue fever has been known in the medical literature for more
than 200 years but was characterized by relatively infrequent
epidemics until the 1950s. The disease pattern associated with
dengue changed with the ecological disruption in Southeast Asia
during and after World War II, which created ideal conditions
for increased transmission of mosquito-borne diseases in urban
areas. In this setting, a global pandemic of dengue began,
epidemic transmission increased, hyperendemicity (the cocirculation of multiple dengue virus serotypes) developed in Southeast Asian cities, and DHF, a newly described disease,
emerged. 3,5,J~ The first known epidemic of DHF occurred in
Manila, Philippines, in 1953 to 1954, but within 20 years it had
spread throughout Southeast Asia; by the mid- 1970s, DHF had
become a leading cause of hospitalization and death among
children in the region. 6 In the 1980s and 1990s, dengue transmission in Asia further intensified, with increased incidence and
geographical expansion of epidemic DHF west into India,
Pakistan, Sri Lanka, and the Maldive Islands and east into
China) ,5,I~At the same time, the geographical distribution of
epidemic DHF was expanding into new regions: the Pacific
Islands in the 1970s and i980s and the American tropics in the
1980s and 1990s. 2,3,5,7-11
Epidemiological changes in the Americas have been the
most dramatic. In the t960s and most of the 1970s, epidemic
dengue was rare in the American region because the principal
mosquito vector, Ae aegypti, had been eradicated from most of
Central and South America. 9,II The eradication program was
discontinued in the early 1970s, and this species then began to
reinvade those countries in which it had been eradicated. By the
1990s, Ae aegypti had regained the geographical distribution it
had before "eradication" (Fig 2). Epidemic dengue invariably
developed after reinfestation of a country by Ae aegypti. By the
1980s, the American region was experiencing major epidemics
of dengue in countries that had been free of the disease for 35 to
130 years. 3,9,u With increased epidemic actMty came the
development of hyperendemicity and the emergence of epidemic DHF, much as had occurred in Southeast Asia 25 years
earlier. 9 From 1981 to 1995, 16 American countries reported
laboratory-confirmed DHF (Fig 3). 3,5,11
Although Africa has not had a major epidemic of D t t F yet,
sporadic cases have occurred because epidemic dengue fever has
increased markedly in the past 15 years. Before the 1980s, little
was known of the distribution of dengue viruses in Africa. Since
then, however, major epidemics caused by all four serotypes
have occurred in both East and West Africa. Outbreaks have
been more common in East Africa in the 1990s, with major
epidemics in Djibouti in 1991 and inJeddah, Saudi Arabia, in

Seminars in _PediatricJ~nJkctiousDiseases, Vol 8, No l (Janua~.y), 1997.'pp 3-9