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2@<A52@ mi''ion9+ of which B mi''ion 8B7A1>B mi''ion9 manifest c'inica''y

8with any se&erity of disease9.1 ,nother st"dy+ of the pre&a'ence of

den!"e+ estimates that >00 mi''ion peop'e+ in 12@ co"ntries+ are at

ris* of infection with den!"e &ir"ses.2

Mem%er tates in > 34 re!ions re!"'ar'y report the ann"a' n"m%er of 

cases. Cn 2010+ near'y 2.< mi''ion cases were reported. ,'tho"!h the f"''

!'o%a' %"rden of the disease is "ncertain+ the initiation of acti&ities to

record a'' den!"e cases part'y e6p'ains the sharp increase in the

n"m%er of cases reported in recent years.

ther feat"res of the disease inc'"de its epidemio'o!ica' patterns+

inc'"din! hyper$endemicity of m"'tip'e den!"e &ir"s serotypes in many

co"ntries and the a'armin! impact on %oth h"man hea'th and the

!'o%a' and nationa' economies.

Defore 170+ on'y co"ntries had e6perienced se&ere den!"e

epidemics. (he disease is now endemic in more than 100 co"ntries inthe 34 re!ions of ,frica+ the ,mericas+ the =astern Mediterranean+

o"th$=ast ,sia and the 3estern ;acic. (he ,merica+ o"th$=ast ,sia

and 3estern ;acic re!ions are the most serio"s'y aected.

Eases across the ,mericas+ o"th$=ast ,sia and 3estern ;acic

e6ceeded 1.2 mi''ion in 200@ and o&er > mi''ion in 201> 8%ased on

ocia' data s"%mitted %y Mem%er tates9. ?ecent'y the n"m%er of

reported cases has contin"ed to increase. Cn 201>+ 2.>5 mi''ion cases of 

den!"e were reported in the ,mericas a'one+ of which >7 B@7 cases

were of se&ere den!"e.

Not on'y is the n"m%er of cases increasin! as the disease spreads tonew areas+ %"t e6p'osi&e o"t%rea*s are occ"rrin!. (he threat of a

possi%'e o"t%rea* of den!"e fe&er now e6ists in ="rope and 'oca'

transmission of den!"e was reported for the rst time in France and

Eroatia in 2010 and imported cases were detected in > other ="ropean

co"ntries. Cn 2012+ an o"t%rea* of den!"e on the Madeira is'ands of

;ort"!a' res"'ted in o&er 2000 cases and imported cases were detected

in main'and ;ort"!a' and 10 other co"ntries in ="rope.

Cn 201>+ cases ha&e occ"rred in F'orida 8United tates of ,merica9 and

 G"nnan pro&ince of Ehina. en!"e a'so contin"es to aect se&era'

o"th ,merican co"ntries+ nota%'y Eosta ?ica+ 4ond"ras and Me6ico. Cn

,sia+ in!apore has reported an increase in cases after a 'apse of

se&era' years and o"t%rea*s ha&e a'so %een reported in aos. Cn 201<+

trends indicate increases in the n"m%er of cases in the ;eop'e-s

?ep"%'ic of Ehina+ the Eoo* Cs'ands+ FiHi+ Ma'aysia and Ian"at"+ with

en!"e (ype > 8=N >9 aectin! the ;acic Cs'and co"ntries after a

'apse of o&er 10 years. en!"e was a'so reported in Japan after a 'apse

of o&er 70 years. Cn 2015 an increase in the n"m%er of cases was

reported in Drai' and se&era' nei!h%o"rin! co"ntries. (he ;acic is'and

co"ntries of FiHi+ (on!a and French ;o'ynesia ha&e contin"ed to record

cases.

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,n estimated 500 000 peop'e with se&ere den!"e re"ire

hospita'iation each year+ a 'ar!e proportion of whom are chi'dren.

,%o"t 2.5 of those aected die.

Transmission

34/(?/tammers

 (he Aedes aegypti mos"ito is the primary &ector of den!"e. (he &ir"s

is transmitted to h"mans thro"!h the %ites of infected fema'e

mos"itoes. ,fter &ir"s inc"%ation for <A10 days+ an infected mos"ito

is capa%'e of transmittin! the &ir"s for the rest of its 'ife.

Cnfected h"mans are the main carriers and m"'tip'iers of the &ir"s+

ser&in! as a so"rce of the &ir"s for "ninfected mos"itoes. ;atients who

are a'ready infected with the den!"e &ir"s can transmit the infection

8for <A5 daysK ma6im"m 129 &ia Aedesmos"itoes after their rst

symptoms appear.

 (he Aedes aegypti mos"ito 'i&es in "r%an ha%itats and %reeds most'y

in man$made containers. Un'i*e other mos"itoes Ae. aegypti is a day$

time feederK its pea* %itin! periods are ear'y in the mornin! and in the

e&enin! %efore d"s*. Fema'e Ae. aegypti%ites m"'tip'e peop'e d"rin!each feedin! period.

 Aedes albopictus+ a secondary den!"e &ector in ,sia+ has spread to

North ,merica and ="rope 'ar!e'y d"e to the internationa' trade in "sed

tyres 8a %reedin! ha%itat9 and other !oods 8e.!. '"c*y %am%oo9. Ae.

albopictus is hi!h'y adapti&e and+ therefore+ can s"r&i&e in coo'er

temperate re!ions of ="rope. Cts spread is d"e to its to'erance to

temperat"res %e'ow freein!+ hi%ernation+ and a%i'ity to she'ter in

microha%itats.

Characteristics

en!"e fe&er is a se&ere+ )"$'i*e i''ness that aects infants+ yo"n!

chi'dren and ad"'ts+ %"t se'dom ca"ses death.

en!"e sho"'d %e s"spected when a hi!h fe&er 8<0°E/10<°F9 is

accompanied %y 2 of the fo''owin! symptoms: se&ere headache+ pain

%ehind the eyes+ m"sc'e and Hoint pains+ na"sea+ &omitin!+ swo''en

!'ands or rash. ymptoms "s"a''y 'ast for 2A7 days+ after an inc"%ation

period of <A10 days after the %ite from an infected mos"ito.

e&ere den!"e is a potentia''y dead'y comp'ication d"e to p'asma

'ea*in!+ )"id acc"m"'ation+ respiratory distress+ se&ere %'eedin!+ or

or!an impairment. 3arnin! si!ns occ"r >A7 days after the rst

symptoms in conH"nction with a decrease in temperat"re 8%e'ow

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>@°E/100°F9 and inc'"de: se&ere a%domina' pain+ persistent &omitin!+

rapid %reathin!+ %'eedin! !"ms+ fati!"e+ rest'essness and %'ood in

&omit. (he ne6t 2<A<@ ho"rs of the critica' sta!e can %e 'etha'K proper

medica' care is needed to a&oid comp'ications and ris* of death.

Treatment

 (here is no specic treatment for den!"e fe&er.

For se&ere den!"e+ medica' care %y physicians and n"rses e6perienced

with the eects and pro!ression of the disease can sa&e 'i&es A

decreasin! morta'ity rates from more than 20 to 'ess than 1.

Maintenance of the patient-s %ody )"id &o'"me is critica' to se&ere

den!"e care.

Immunization

 (here is no &accine to protect a!ainst den!"e. 4owe&er+ maHor pro!ress

has %een made in de&e'opin! a &accine a!ainst den!"e/se&ere den!"e. (hree tetra&a'ent 'i&e$atten"ated &accines are "nder de&e'opment in

phase CC and phase CCC c'inica' tria's+ and > other &accine candidates

8%ased on s"%"nit+ N, and p"ried inacti&ated &ir"s p'atforms9 are at

ear'ier sta!es of c'inica' de&e'opment. 34 pro&ides technica' ad&ice

and !"idance to co"ntries and pri&ate partners to s"pport &accine

research and e&a'"ation.

Prevention and control

34/(?/Er"mp

,t present+ the on'y method to contro' or pre&ent the transmission of

den!"e &ir"s is to com%at &ector mos"itoes thro"!h:

• pre&entin! mos"itoes from accessin! e!!$'ayin! ha%itats %y

en&ironmenta' mana!ement and modicationK

• disposin! of so'id waste proper'y and remo&in! articia' man$

made ha%itatsK• co&erin!+ emptyin! and c'eanin! of domestic water stora!e

containers on a wee*'y %asisK

• app'yin! appropriate insecticides to water stora!e o"tdoorcontainersK

• "sin! of persona' ho"seho'd protection s"ch as window screens+'on!$s'ee&ed c'othes+ insecticide treated materia's+ coi's and &aporiersK

• impro&in! comm"nity participation and mo%i'iation fors"stained &ector contro'K

• app'yin! insecticides as space sprayin! d"rin! o"t%rea*s as one

of the emer!ency &ector$contro' meas"resK

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• acti&e monitorin! and s"r&ei''ance of &ectors sho"'d %e carriedo"t to determine eecti&eness of contro' inter&entions.

WHO response

34 responds to den!"e in the fo''owin! ways:

• s"pports co"ntries in the conrmation of o"t%rea*s thro"!h itsco''a%oratin! networ* of 'a%oratoriesK

• pro&ides technica' s"pport and !"idance to co"ntries for theeecti&e mana!ement of den!"e o"t%rea*sK

• s"pports co"ntries to impro&e their reportin! systems andcapt"re the tr"e %"rden of the diseaseK

• pro&ides trainin! on c'inica' mana!ement+ dia!nosis and &ector

contro' at the re!iona' 'e&e' with some of its co''a%oratin! centresK

• form"'ates e&idence$%ased strate!ies and po'iciesK

• de&e'ops new too's+ inc'"din! insecticide prod"cts andapp'ication techno'o!iesK

• !athers ocia' records of den!"e and se&ere den!"e from o&er100 Mem%er tatesK and

• p"%'ishes !"ide'ines and hand%oo*s for case mana!ement+den!"e pre&ention and contro' for Mem%er tates.

1 Dhatt + Lethin! ;3+ Drady J+ Messina J;+ Far'ow ,3+ Moyes E et.a'.

 (he !'o%a' distri%"tion and %"rden of den!"e. Nat"reK<B:50<$507.2 Drady J+ Lethin! ;3+ Dhatt + Messina J;+ Drownstein J+ 4oen ,L et

a'. ?enin! the !'o%a' spatia' 'imits of den!"e &ir"s transmission %y

e&idence$%ased consens"s. ;o Ne!' (rop is. 2012KB:e17B0.

doi:10.1>71/Ho"rna'.pntd.00017B0