Dengue and severe dengue

15 April 2019

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Key facts
 Dengue is a mosquito-borne viral infection.
 The infection causes flu-like illness, and occasionally develops
into a potentially lethal complication called severe dengue.
 The global incidence of dengue has grown dramatically in recent
decades. About half of the world's population is now at risk.
 Dengue is found in tropical and sub-tropical climates worldwide,
mostly in urban and semi-urban areas.
 Severe dengue is a leading cause of serious illness and death
among children in some Asian and Latin American countries.
 There is no specific treatment for dengue/ severe dengue, but early
detection and access to proper medical care lowers fatality rates
below 1%.
 Dengue prevention and control depends on effective vector control
measures.

Dengue is a mosquito-borne viral disease that has rapidly spread in all

regions of WHO in recent years. Dengue virus is transmitted by female
mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae.
albopictus. This mosquito also transmits chikungunya, yellow fever and Zika
infection. Dengue is widespread throughout the tropics, with local variations in
risk influenced by rainfall, temperature and unplanned rapid urbanization.

Severe dengue was first recognized in the 1950s during dengue epidemics in
the Philippines and Thailand. Today, severe dengue affects most Asian and
Latin American countries and has become a leading cause of hospitalization
and death among children and adults in these regions.
1
Dengue is caused by a virus of the Flaviviridae family and there are 4 distinct,
but closely related, serotypes of the virus that cause dengue (DEN-1, DEN-2,
DEN-3 and DEN-4). Recovery from infection by one provides lifelong
immunity against that particular serotype. However, cross-immunity to the
other serotypes after recovery is only partial and temporary. Subsequent
infections (secondary infection) by other serotypes increase the risk of
developing severe dengue.

Global burden of dengue

The incidence of dengue has grown dramatically around the world in recent
decades. A vast majority of cases are asymptomatic and hence the actual
numbers of dengue cases are underreported and many cases are
misclassified. One estimate indicates 390 million dengue infections per year
(95% credible interval 284–528 million), of which 96 million (67–136 million)
manifest clinically (with any severity of disease).1 Another study, of the
prevalence of dengue, estimates that 3.9 billion people, in 128 countries, are
at risk of infection with dengue viruses.2

Member States in three WHO regions regularly report the annual number of
cases. The number of cases reported increased from 2.2 million in 2010 to
over 3.34 million in 2016. Although the full global burden of the disease is
uncertain, the initiation of activities to record all dengue cases partly explains
the sharp increase in the number of cases reported in recent years.

Other features of the disease include its epidemiological patterns, including

hyper-endemicity of multiple dengue virus serotypes in many countries and
the alarming impact on both human health and the global and national
economies. Dengue virus is transported from one place to another by infected
travelers.

Distribution trends

Before 1970, only 9 countries had experienced severe dengue epidemics. The
disease is now endemic in more than 100 countries in the WHO regions of
Africa, the Americas, the Eastern Mediterranean, South-East Asia and the
Western Pacific. The America, South-East Asia and Western Pacific regions
are the most seriously affected.

Cases across the Americas, South-East Asia and Western Pacific exceeded
1.2 million in 2008 and over 3.342million in 2016 (based on official data
submitted by Member States). Recently the number of reported cases has
continued to increase. In 2015, 2.35 million cases of dengue were reported in
the Americas alone, of which 10 200 cases were diagnosed as severe dengue
causing 1181 deaths.

Not only is the number of cases increasing as the disease spreads to new
areas, but explosive outbreaks are occurring. The threat of a possible
outbreak of dengue fever now exists in Europe as local transmission was
reported for the first time in France and Croatia in 2010 and imported cases
were detected in 3 other European countries. In 2012, an outbreak of dengue
on the Madeira islands of Portugal resulted in over 2 000 cases and imported
cases were detected in mainland Portugal and 10 other countries in Europe.
Among travellers returning from low- and middle-income countries, dengue is
the second most diagnosed cause of fever after malaria.

In 2015, Delhi, India, recorded its worst outbreak since 2006 with over 15 000
cases. The Island of Hawaii, United States of America, was affected by an
outbreak with 181 cases reported in 2015 and ongoing transmission in 2016.
The Pacific island countries of Fiji, Tonga and French Polynesia have
continued to record cases.

The year 2016 was characterized by large dengue outbreaks worldwide. The
Region of the Americas region reported more than 2.38 million cases in 2016,
where Brazil alone contributed slightly less than 1.5 million cases,
approximately 3 times higher than in 2014. 1032 dengue deaths were also
reported in the region. The Western Pacific Region reported more than 375
000 suspected cases of dengue in 2016, of which the Philippines reported 176
411 and Malaysia 100 028 cases, representing a similar burden to the
previous year for both countries. The Solomon Islands declared an outbreak
with more than 7000 suspected. In the African Region, Burkina Faso reported
a localized outbreak of dengue with 1061 probable cases.

In 2017, a significant reduction was reported in the number of dengue cases

in the Americas - from 2 177 171 cases in 2016 to 584 263 cases in 2017.
This represents a reduction of 73%. Panama, Peru and Aruba were the only
countries that registered an increase in cases during 2017. Similarly, a 53%
reduction in severe dengue cases was also recorded during 2017. The post
Zika outbreak period (after 2016) has seen a decline of cases of dengue and
the exact factors leading to this fall decrease is still unknown. WHO’s
Western Pacific Region has reported dengue outbreaks in several countries in
the Pacific, as well as the circulation
3 of DENV-1 and DENV-2 serotypes.
After a drop in the number of cases in 2017-18, sharp increase in cases is
being observed in 2019. In the Western Pacific region, increase in cases have
been observed in Australia, Cambodia, China, Lao PDR, Malaysia,
Philippines, Singapore, Vietnam while Den- 2 was reported in New Caledonia
and Den-1 in French Polynesia. Dengue outbreaks have also been reported in
Congo, Côte d’Ivoire, Tanzania in the African region; Several countries of the
American region has also observed an increase in the number of cases.An
estimated 500 000 people with severe dengue require hospitalization each
year, and with an estimated 2.5% case fatality, annually. However, many
countries have reduced the case fatality rate to less than 1% and
globally, 28% decline in case fatality have been recorded between 2010 and
2016 with significant improvement in case management through capacity
building at country level.

Transmission
The Aedes aegypti mosquito is the primary vector of dengue. The virus is
transmitted to humans through the bites of infected female mosquitoes. After
virus incubation for 4–10 days, an infected mosquito is capable of transmitting
the virus for the rest of its life.

Infected symptomatic or asymptomatic humans are the main carriers and

multipliers of the virus, serving as a source of the virus for uninfected
mosquitoes. Patients who are already infected with the dengue virus can
transmit the infection (for 4–5 days; maximum 12) via Aedesmosquitoes after
their first symptoms appear.

The Aedes aegypti mosquito lives in urban habitats and breeds mostly in
man-made containers. Unlike other mosquitoes Ae. aegypti is a day-time
feeder; its peak biting periods are early in the morning and in the evening
before dusk. Female Ae. aegypti bites multiple people during each feeding
period. Aedes eggs can remain dry for over a year in their breeding habitat
and hatch when in contact with water.

Aedes albopictus, a secondary dengue vector in Asia, has spread to North

America and more than 25 countries in the European Region, largely due to
the international trade in used tyres (a breeding habitat) and other goods (e.g.
lucky bamboo). Ae. albopictus is highly adaptive and, therefore, can survive in
cooler temperate regions of Europe. Its spread is due to its tolerance to
temperatures below freezing, hibernation, and ability to shelter in
microhabitats. 4
 Characteristics
Dengue fever is a severe, flu-like illness that affects infants, young children
and adults, but seldom causes death.

Dengue should be suspected when a high fever (40°C/104°F) is accompanied

by 2 of the following symptoms: severe headache, pain behind the eyes,
muscle and joint pains, nausea, vomiting, swollen glands or rash. Symptoms
usually last for 2–7 days, after an incubation period of 4–10 days after the bite
from an infected mosquito.

Severe dengue is a potentially deadly complication due to plasma leaking,

fluid accumulation, respiratory distress, severe bleeding, or organ impairment.
Warning signs occur 3–7 days after the first symptoms in conjunction with a
decrease in temperature (below 38°C/100°F) and include: severe abdominal
pain, persistent vomiting, rapid breathing, bleeding gums, fatigue,
restlessness and blood in vomit. The next 24–48 hours of the critical stage
can be lethal; proper medical care is needed to avoid complications and risk
of death.

Treatment
There is no specific treatment for dengue fever.

For severe dengue, medical care by physicians and nurses experienced with
the effects and progression of the disease can save lives – decreasing
mortality rates from more than 20% to less than 1%. Maintenance of the
patient's body fluid volume is critical to severe dengue care.

Immunization

The first dengue vaccine, Dengvaxia® (CYD-TDV) developed by Sanofi

Pasteur was licensed in December 2015 and has now been approved by
regulatory authorities in 20 countries for use in endemic areas in persons
ranging from 9-45 years of age. In April 2016, WHO issued a conditional
recommendation on the use of the vaccine for areas in which dengue is highly
endemic as defined by seroprevalence of 70% or higher. In November 2017,
the results of an additional analysis to retrospectively determine serostatus at
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the time of vaccination were released. The analysis showed that the subset of
trial participants who were inferred to be seronegative at time of first
vaccination had a higher risk of more severe dengue and hospitalizations from
dengue compared to unvaccinated participants.

WHO position

The live attenuated dengue vaccine CYD-TDV has been shown in clinical trials to be
efficacious and safe in persons who have had a previous dengue virus infection
(seropositive individuals), but carries an increased risk of severe dengue in those who
experience their first natural dengue infection after vaccination (seronegative
individuals).

For countries considering vaccination as part of their dengue control

programme, pre-vaccination screening is the recommended strategy. With this
strategy, only persons with evidence of a past dengue infection would be
vaccinated (based on an antibody test, or on a documented laboratory
confirmed dengue infection in the past).

Decisions about implementing a pre-vaccination screening strategy will require careful

assessment at the country level, including consideration of the sensitivity and specificity
of available tests and of local priorities, dengue epidemiology, country-specific dengue
hospitalization rates, and affordability of both CYD-TDV and screening tests.

Vaccination should be considered as part of an integrated dengue prevention and

control strategy. There is an ongoing need to adhere to other disease preventive
measures such as well-executed and sustained vector control. Individuals, whether
vaccinated or not, should seek prompt medical care if dengue-like symptoms occur.

Prevention and control

At present, the main method to control or prevent the transmission of dengue
virus is to combat vector mosquitoes through:

 preventing mosquitoes from accessing egg-laying habitats by

environmental management and modification;
 disposing of solid waste properly and removing artificial man-made
habitats;
 covering, emptying and cleaning of domestic water storage containers
on a weekly basis;
 applying appropriate insecticides to water storage outdoor containers;
 using of personal household protection measures, such as window
screens, long-sleeved clothes, repellents, insecticide treated materials,
coils and vaporizers (These6 measures have to be observed during the
 day both at home and place of work since the mosquito bites during the
day);
 improving community participation and mobilization for sustained vector
control;
 applying insecticides as space spraying during outbreaks as one of the
emergency vector-control measures;
 active monitoring and surveillance of vectors should be carried out to
determine effectiveness of control interventions.

Careful clinical detection and management of dengue patients can

significantly reduce mortality rates from severe dengue.

 Global Strategy for dengue prevention and control, 2012–2020, Chapter

2

WHO response
WHO responds to dengue in the following ways:

 supports countries in the confirmation of outbreaks through its

collaborating network of laboratories;
 provides technical support and guidance to countries for the effective
management of dengue outbreaks;
 supports countries to improve their reporting systems and capture the
true burden of the disease;
 provides training on clinical management, diagnosis and vector control
at the regional level with some of its collaborating centres;
 formulates evidence-based strategies and policies;
 develops new tools, including insecticide products and application
technologies;
 gathers official records of dengue and severe dengue from over 100
Member States; and
 publishes guidelines and handbooks for surveillance, case
management, diagnosis, dengue prevention and control for Member
States.

(1) Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL et.al.
The global distribution and burden of dengue. Nature;496:504-507.
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(2) Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG et
al. Refining the global spatial limits of dengue virus transmission by evidence-
based consensus. PLoS Negl Trop Dis. 2012;6:e1760.
doi:10.1371/journal.pntd.0001760.