Dengue

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

Review article
Current Concepts

Dengue
Cameron P. Simmons, Ph.D., Jeremy J. Farrar, M.D., Ph.D.,
Nguyen van Vinh Chau, M.D., Ph.D., and Bridget Wills, M.D., D.M.

D

engue is a self-limited, systemic viral infection transmitted
between humans by mosquitoes. The rapidly expanding global footprint of
dengue is a publichealth challenge with an economic burden that is currently unmet by licensed vaccines, specific therapeutic agents, or efficient vectorcontrol strategies. This review highlights our current understanding of dengue,
including its clinical manifestations, pathogenesis, tests that are used to diagnose it,
and its management and prevention.

De ter mina n t s of the Cur r en t Dengue Pa ndemic
Theglobal burden of dengue is large; an estimated 50 million infections per year occur across approximately 100 countries, with potential for further spread (Fig. 1).1
Central to the emergence of dengue as a public health problem has been the dispersal
of efficient mosquito vectors across much of the tropical and subtropical world. The
primary vector, the urban-adapted Aedes aegypti mosquito, hasbecome widely distributed across tropical and subtropical latitudes. It emerged from Africa during the slave
trade in the 15th through 19th centuries, spread into Asia through commercial exchanges in the 18th and 19th centuries, and has spread globally with the advent of
increased travel and trade in the past 50 years.2 In addition, the geographic range of
a secondary vector, A. albopictus, hasdramatically expanded in recent years.3 Globalization of trade, in particular the trade of tires from used vehicles, is thought to explain the dispersal of eggs and immature forms of these arboviral vectors into new
territories.4 Endemicity has also been facilitated by rapid urbanization in Asia and
Latin America, resulting in increased population density with an abundance of vectorbreedingsites within crowded urban communities and the areas surrounding them.
Dengue infections in Africa remain largely unquantified, but recent outbreaks suggest that substantial parts of the continent may be at risk for increasing dengue
transmission. More surveillance is required to assess the true burden of disease (see the
Supplementary Appendix, available with the full text of this article atNEJM.org).
Vector control, through chemical or biologic targeting of mosquitoes and removal
of their breeding sites, is the mainstay of dengue prevention, but this approach has
failed to stop disease transmission in almost all countries where dengue is endemic.
Antigenic diversity of the dengue virus is important, since the lack of long-term
cross-immunity among the four virus types allows formultiple sequential infections.
Thus, the spread of dengue illustrates how global trade (and the transport of the
mosquito vectors), increasing travel within and between countries (and the movement of viremic people), urban crowding (which is conducive to multiple infections
from an infected mosquito), and ineffective vector-control strategies have supported
a pandemic in the modern era. With theincreasingly global spread of dengue,
practicing physicians in temperate North America, Europe, Australia, and Japan are

n engl j med 366;15

nejm.org

From the Oxford University Clinical Research Unit and Wellcome Trust Major
Overseas Programme (C.P.S., J.J.F., B.W.),
Hospital for Tropical Diseases (N.V.C.),
Ho Chi Minh City, Vietnam; and the
Centre for Tropical Medicine, Universityof Oxford, Churchill Hospital, Oxford,
United Kingdom (C.P.S., J.J.F., B.W.). Address reprint requests to Dr. Farrar at the
Hospital for Tropical Diseases, Oxford
University Clinical Research Unit, 190
Ben Ham Tu, Quan 5, Ho Chi Minh City,
Vietnam, or at jfarrar@oucru.org.
N Engl J Med 2012;366:1423-32.
Copyright © 2012 Massachusetts Medical Society.

april 12, 2012

The New England...