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Commentary
Persistent Emergence of Dengue
Charles H. Calisher*
*Colorado State University, Fort Collins, Colorado, USA
Suggested
citation for this article
The disease dengue fever (DF; also known as breakbone fever, dandy fever,
and by other names) can be caused by any of 4 viruses within the virus
family Flaviviridae, genus Flavivirus, i.e., dengue virus
types 1–4 (DENV-1–4). Dengue fever is a short-duration, nonfatal illness
characterized by sudden onset of headache, retroorbital pain, high fever,
joint pain, and rash. Whereas uncomplicated DF usually is the case, the
picture can be much darker than that. Through a mechanism known as immune
enhancement, sequential infections with certain dengue viruses set the
stage for a far more serious complication, dengue hemorrhagic fever (DHF)
and dengue shock syndrome, so that having uncomplicated DF can presage
having DHF (1).
DHF is characterized by high fever, vascular permeability, bleeding,
enlargement of the liver, and circulatory failure (dengue shock syndrome).
In mild or moderate cases, signs and symptoms subside after the fever
subsides, but in severe cases the patient's condition suddenly deteriorates,
body temperature decreases, and the circulatory system begins to fail.
The patient then may quickly go into shock and die within a day, or quickly
recover, if volume therapy is instituted (2).
Dengue viruses are transmitted from person to person or from monkey to
monkey through infected female mosquitoes of the genus Aedes. The
mosquito acquires the virus by taking a blood meal from an infected human,
the principal amplifying host for these viruses, or from an infected monkey.
Humans circulate these viruses in their blood (viremia) for 7 to 10 days
after infection, allowing ample time for mosquitoes, often many mosquitoes,
to feed and become infected. After an intrinsic incubation period of 1
week to 10 days, the mosquito is capable of transmitting the virus to
a new host while blood feeding.
During epidemics of dengue, attack rates may be 80%–90% in susceptible
persons. Although, it is not usually recognized, more than half the people
who are infected with a dengue virus may be asymptomatic, which would
indicate a substantial underreporting of infections. These comprise a
substantial number of people who may have been primed for more serious
illness at a later date and are unaware of their situation.
The global prevalence of dengue has increased substantially recently.
Dengue is endemic in ≈100 countries in Southeast Asia, Africa, the
Western Pacific, the Americas, Africa, and the eastern Mediterranean area
(available from http://www.who.int/mediacentre/factsheets/fs117/en/),
with imported cases essentially everywhere tourists, business people,
and military personnel travel, whether dengue is recognized there or not.
More than 2 billion of the approximately 6.5 billion inhabitants of this
planet are at risk of acquiring dengue, and the World Health Organization
has estimated that "there may be 50 million cases of dengue infection
worldwide every year" (available from http://www.who.int/mediacentre/factsheets/fs117/en/).
However, this is a misstatement. Either there are 50 million dengue infections
(some with illness, some not) or there are 50 million people sick with
dengue each year. Infections are not the same as illnesses.
The mild form of dengue is a serious annoyance and often is painful for
those with it. However, DHF is the major international public health concern.
Before 1970, a total of 9 countries had reported DHF epidemics; by 1995,
>4 times that number reported such outbreaks. Most of these countries
are in Southeast Asia and the Western Pacific, but with the worldwide
spread of all dengue types, this disease threatens residents in tropical
and subtropical regions, predominantly in urban and semiurban areas. In
2001, ≈600,000 cases of dengue were reported in the Americas, of
which 15,000 were cases of DHF, more than twice the number of DHF cases
in the Americas in 1995 (available from http://www.who.int/mediacentre/factsheets/fs117/en/).
In 2001 alone, Brazil reported nearly 400,000 cases, including 670 cases
of DHF. Not only is the geographic distribution of dengue spreading, but
the seriousness of its complications is being recognized (available from
http://www.cdc.gov/search.do?action=search&queryText=dengue).
An estimated 500,000 persons with DHF require hospitalization each year,
a substantial proportion of whom are children. Tragically, DHF is a leading
cause of hospitalization and death of children in several Asian countries.
Case-fatality rates can exceed 20%, are usually 2.5%, but can be reduced
to <1% with rapid recognition and proper treatment.
In countries that are prepared for dengue and its complications, diagnostic
services are available. We are able to sequence these viruses and determine
their origins and evolutionary determinants. We can, to some degree, control
the vector mosquitoes (Aedes aegypti and Ae. albopictus).
Our knowledge of the pathophysiology of DHF is quite sophisticated (2,3).
A vast literature is available about these viruses and the diseases they
cause. Why, then, does dengue continue to spread? If we cannot eradicate
dengue (and its vector Ae. aegypti) from populations on islands,
from where can we eradicate it? Politics or misdirected funding, as always,
has something to do with this, but the situation is much more complicated
than that. Unless transovarial transmission (passage of virus from female
to offspring through the egg) is much more important than it appears to
be, other mechanisms are at play. Univalent vaccines for these viruses
have been prepared but, for the most part, health authorities are (justifiably)
unwilling to use such vaccines because they have the potential to stimulate
the production of antibodies, which would prime vaccinees for DHF by immune
enhancement. Fortunately, novel approaches (development of incompetent
mosquitoes), development of modern tetravalent vaccines, and development
of chimeric vaccine viruses (4), using classic as well
as molecular approaches will soon be available and hold out promise of
tools we need to eliminate or eradicate this scourge.
This issue of Emerging Infectious Diseases includes some very interesting
reports on dengue and its clinical complications, dengue diagnosis, and
dengue epidemiology. These add considerably to the scientific record.
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Charles H.
Calisher
Dr. Calisher
is professor of microbiology in the Arthropod-borne and Infectious
Diseases Laboratory, Department of Microbiology, Immunology, and
Pathology, Colorado State University. His interests include arboviruses
and the diseases they cause, the biology of arthropod vectors of
viruses, rodent-borne viruses and the diseases they cause, and the
epidemiology of viruses.
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References
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viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing
antibody. J Exp Med. 1977;146:201–17.
- Halstead SB. Pathogenesis
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- Mongkolsapaya J, Dejnirattisai W, Xu X, Vasanawathana S, Tangthawornchaikul
N, Chairunsri A, et al. Original
antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic
fever. Nat Med. 2003;9:921–7.
- Guirakhoo F, Pugachev K, Zhang Z, Myers G, Levenbook I, Draper K,
et al. Safety
and efficacy of chimeric yellow fever-dengue virus tetravalent vaccine
formulations in nonhuman primates. J Virol. 2004;78:4761–75.
Suggested citation
for this article:
Calisher CH. Persistent
emergence of dengue. Emerg Infect Dis [serial on the Internet]. 2005 May
[date cited]. Available from http://www.cdc.gov/ncidod/EID/vol11no05/05-0195.htm
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