PRIMEVIEW

DENGUE INFECTION
For the Primer, visit doi:10.1038/nrdp.2016.55
The bite of an infected
mosquito leads to DENV DIAGNOSIS
Dengue is a mosquito-borne disease infection of several
PATHOPHYSIOLOGY INFECTION
caused by infection with dengue virus cell types, including
(DENV). Clinically, the disease can range macrophages, dendritic The 2009 WHO guidelines are used to clinically
from a mild febrile illness (previously cells and Langerhans cells classify dengue and identify patients at risk of
called dengue fever) through to dengue High viral loads and fever
progressing from mild to severe illness. Diagnosis
with warning signs and severe dengue, follow 4–7 days later
of presumptive dengue with or without warning
which includes what were previously
signs is made if the patient lives in or has recently
called dengue haemorrhagic fever (DHF)
travelled to a dengue-endemic area and has
and dengue shock syndrome (DSS).
symptoms such as fever, vomiting or aches and
pains. Warning signs
ACUTE PHASE of severe disease
EPIDEMIOLOGY Confirmation
include abdominal
of a dengue
pain, mucosal diagnosis is made
DENVs are transmitted by Aedes aegypti bleeding and clinical by laboratory
mosquitoes and are widespread throughout the fluid accumulation, testing. This can
tropics. The global expansion of DENVs began whereas hallmarks involve assaying
with the South-East Asian dengue pandemic in of severe disease
Plasma leakage and abnormal for DENV RNA or
the 1950s and was facilitated by the effects of include severe plasma the NS1 protein
haemostasis underlie DHF and Second DENV
globalization, such as increased air travel. Over leakage leading to in blood, serum or
DSS. Although their causes are infections are often
half of the world’s population are at risk of DENV more severe than the first DSS, severe bleeding plasma, as well as
not well understood, antibody- CRITICAL PHASE
infection. Each year, an estimated 360 million because non-neutralizing and severe end- for anti-DENV IgM.
dependent enhancement and
DENV infections occur, resulting in 2 million cases anti-DENV antibodies can organ involvement.
the DENV protein NS1 are
of severe disease and 21,000 deaths. enhance infection
probably important contributors.

MANAGEMENT
PREVENTION
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As there is no antiviral therapy for dengue,
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Prevention focuses on mosquito control using me Shock management involves supportive care. The
strategies such as larval source reduction, majority of patients with dengue have mild
CONVALESCENCE
insecticide spraying and community febrile illness and treatment is commonly bed
outreach and education. Although some rest, oral fluids and analgesics. Treatment of
countries, such Singapore and Cuba, achieved dengue with warning signs and severe dengue
temporary dengue control using Recovery involves cessation involves the replacement of fluids lost owing
these approaches, their of plasma leakage and to capillary leakage with
inconsistent application OUTLOOK reabsorption of lost fluids intravenous fluid therapy.
and the introduction Haemorrhages most commonly
of DENVs from To succeed in preventing dengue, development of new control tools, and live attenuated vaccines. occur in the gastrointestinal
neighbouring mosquito control efforts will need the study of insecticide resistance Recently, a live recombinant system, where they can
countries to be sustained in the long term and improved surveillance. Several tetravalent vaccine received manifest as haematemesis
eventually led to and conducted at the regional level dengue vaccines are currently approval from the WHO and is now (vomiting of blood)
the re-emergence to prevent the spread of DENVs being tested in clinical trials, registered in several countries, and/or melaena (black,
of epidemic from adjacent endemic areas. including recombinant subunit providing a promising new tar-like faeces), and are treated
DENV transmission. This effort will be aided by the vaccines, an inactivated vaccine pathway towards dengue control. using blood transfusions.

Designed by Laura Marshall Article number: 16056; doi:10.1038/nrdp.2016.56; published online 18 Aug 2016
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