Definition

By Mayo Clinic Staff

Dengue (DENG-gay) fever is a mosquito-borne disease tat occurs in tro!ical and subtro!ical
areas of te "orld# Mild dengue fever causes ig fever$ ras$ and muscle and %oint !ain# &
severe form of dengue fever$ also called dengue emorragic fever$ can cause severe bleeding$ a
sudden dro! in blood !ressure (soc') and deat#
Millions of cases of dengue infection occur "orld"ide eac year# Dengue fever is most common
in Souteast &sia and te "estern (acific islands$ but te disease as been increasing ra!idly in
)atin &merica and te Caribbean#
*esearcers are "or'ing on dengue fever vaccines$ but te best !revention for no" is to reduce
mosquito abitat in areas "ere dengue fever is common#
Symptoms
By Mayo Clinic Staf
Many !eo!le$ es!ecially cildren and teens$ may e+!erience no signs or sym!toms during a mild
case of dengue fever# ,en sym!toms do occur$ tey usually begin four to -. days after te
!erson is bitten by an infected mosquito# Signs and sym!toms of dengue fever most commonly
include/
Fever, up to 106 F (41 C)
Headaches
Muscle, one and !oint pain
"ain ehind your eyes
0ou migt also e+!erience/
#idespread rash
$ausea and vo%itin&
Minor leedin& 'ro% your &u%s or nose
Most !eo!le recover "itin a "ee' or so# 1n some cases$ o"ever$ sym!toms "orsen and can
become life-treatening# Blood vessels often become damaged and lea'y$ and te number of
clot-forming cells in your bloodstream falls# 2is can cause/
Bleedin& 'ro% the nose and %outh
Severe ado%inal pain
"ersistent vo%itin&
Bleedin& under the s(in, )hich %ay loo( li(e ruisin&
"role%s )ith your lun&s, liver and heart
When to see a doctor
1f you3ve recently visited a region in "ic dengue fever is 'no"n to occur and you suddenly
develo! a fever$ see your doctor#
Causes
By Mayo Clinic Staff
Dengue fever is caused by any one of four dengue viruses s!read by mosquitoes tat trive in
and near uman lodgings# ,en a mosquito bites a !erson infected "it a dengue virus$ te virus
enters te mosquito# ,en te infected mosquito ten bites anoter !erson$ te virus enters tat
!erson3s bloodstream#
&fter you3ve recovered from dengue fever$ you ave immunity to te virus tat infected you 4
but not to te oter tree dengue fever viruses# 2e ris' of develo!ing severe dengue fever$ also
'no"n as dengue emorragic fever$ actually increases if you3re infected a second$ tird or
fourt time#
Risk factors
By Mayo Clinic Staff
5actors tat !ut you at greater ris' of develo!ing dengue fever or a more severe form of te
disease include/
Living or traveling in tropical areas. Being in tro!ical and subtro!ical areas around te
"orld 4 es!ecially in ig-ris' areas$ suc as Souteast &sia$ )atin &merica and te
Caribbean 4 increases your ris' of e+!osure to te virus tat causes dengue fever#
Prior infection with a dengue fever virus. (revious infection "it a dengue fever virus
increases your ris' of aving severe sym!toms if you3re infected a second time# 2is is
es!ecially true for cildren#
Complications
By Mayo Clinic Staff
1f severe$ dengue fever can damage te lungs$ liver or eart# Blood !ressure can dro! to
dangerous levels$ causing soc' and$ in some cases$ deat#
Preparing for your appointment
By Mayo Clinic Staf
0ou3ll li'ely start by seeing your family doctor or !rimary care !rovider# But in some cases$
"en you call to set u! an a!!ointment$ you migt be referred instead to a doctor "o
s!eciali6es in infectious diseases#
Because a!!ointments can be brief$ and because tere3s often a lot of ground to cover$ it3s a good
idea to be "ell !re!ared for your a!!ointment# 7ere3s some information to el! you get ready$
and "at to e+!ect from your doctor#
What you can do
Write down any symptoms you're experiencing, includin& any that %ay
see% unrelated to the reason 'or )hich you scheduled the appoint%ent*
Write down key personal information. +ist your international travel
history, )ith dates and countries visited and %edications ta(en )hile
travelin&* Brin& a record o' your i%%uni,ations, includin& pre-travel
i%%uni,ations*
Make a list of all your medications. .nclude any vita%ins or supple%ents
you ta(e re&ularly*
Take a family member or friend along, i' possile* So%eti%es it can e
di/cult to soa( up all the in'or%ation conveyed durin& an appoint%ent*
So%eone )ho acco%panies you %ay re%e%er so%ethin& that you %issed
or 'or&ot*
Write down questions to ask your doctor. 0our ti%e )ith your doctor is
li%ited, so preparin& a list o' 1uestions )ill help you %a(e the %ost o' your
ti%e to&ether* +ist your 1uestions 'ro% %ost i%portant to least i%portant in
case ti%e runs out*
5or dengue fever$ some basic questions to as' your doctor include/
#hat is li(ely causin& %y sy%pto%s or condition2
#hat (inds o' tests do . need2
#hat3s the est course o' action2
Ho) lon& )ill it e e'ore .3% 'eelin& etter2
4re there any lon&-ter% efects o' this illness2
5o you have any rochures or other printed %aterial that . can ta(e ho%e
)ith %e2 #hat )esites do you reco%%end2
1n addition to te questions tat you3ve !re!ared to as' your doctor$ don3t esitate to as' for
furter e+!lanation if you3re confused#
What to expect from your doctor
Be !re!ared to ans"er questions from your doctor$ suc as/
#hen did your sy%pto%s e&in2
Have your sy%pto%s een continuous or occasional2
Ho) severe are your sy%pto%s2
5oes anythin& see% to %a(e your sy%pto%s etter or )orse2
#here have you traveled in the past %onth2
#ere you itten y %os1uitoes )hile travelin&2
Have you een in contact recently )ith anyone )ho )as ill2
Tests and diagnosis
By Mayo Clinic Staff
Diagnosing dengue fever can be difficult$ because its signs and sym!toms can be easily
confused "it tose of oter diseases 4 suc as malaria$ le!tos!irosis and ty!oid fever#
0our doctor "ill li'ely as' about your medical and travel istory# Be sure to describe
international tri!s in detail$ including te countries you visited and te dates$ as "ell as
any contact you may ave ad "it mosquitoes#
Certain laboratory tests can detect evidence of te dengue viruses$ but test results usually
come bac' too late to el! direct treatment decisions#
Treatments and drugs
By Mayo Clinic Staff
No s!ecific treatment for dengue fever e+ists# 0our doctor may recommend tat you drin' !lenty
of fluids to avoid deydration from vomiting and ig fever# &cetamino!en (2ylenol$ oters)
can alleviate !ain and reduce fever# &void !ain relievers tat can increase bleeding com!lications
4 suc as as!irin$ ibu!rofen (&dvil$ Motrin$ oters) and na!ro+en sodium (&leve$ oters)#
1f you ave severe dengue fever$ you may need/
Su!!ortive care in a os!ital
1ntravenous (18) fluid and electrolyte re!lacement
Blood !ressure monitoring
2ransfusion to re!lace blood loss
Prevention
By Mayo Clinic Staff
& dengue fever vaccine is in develo!ment$ but isn3t generally available# 1f you3re living or
traveling in an area "ere dengue fever is 'no"n to be$ te best "ay to avoid dengue fever is to
avoid being bitten by mosquitoes tat carry te disease#
1f you are living or traveling in tro!ical areas "ere dengue fever is common$ tese ti!s may el!
reduce your ris' of mosquito bites/
Stay in air-conditioned or well-screened housing. 1t3s !articularly im!ortant to 'ee!
mosquitoes out at nigt#
Reschedule outdoor activities. &void being outdoors at da"n$ dus' and early evening$
"en more mosquitoes are out#
ear protective clothing. ,en you go into mosquito-infested areas$ "ear a long-
sleeved sirt$ long !ants$ soc's and soes#
!se mos"uito repellent. (ermetrin can be a!!lied to your cloting$ soes$ cam!ing gear
and bed netting# 0ou can also buy cloting made "it !ermetrin already in it# 5or your
s'in$ use a re!ellent containing at least a -. !ercent concentration of DEE2#
Reduce mos"uito ha#itat. 2e mosquitoes tat carry te dengue virus ty!ically live in
and around ouses$ breeding in standing "ater tat can collect in suc tings as used
automobile tires# *educe te breeding abitat to lo"er mosquito !o!ulations#
66666666666666666666666666666666666666666666666666666666666666666666666666666
Dengue fever (9: ;d < e ; or 9S ;d < i ;)$ also 'no"n as #reak#one fever$ is a mosquito-
borne tro!ical disease caused by te dengue virus# Sym!toms include fever$ eadace$ muscle
and %oint !ains$ and a caracteristic s'in ras tat is similar to measles# 1n a small !ro!ortion of
cases te disease develo!s into te life-treatening dengue hemorrhagic fever$ resulting in
bleeding$ lo" levels of blood !latelets and blood !lasma lea'age$ or into dengue shock
syndrome$ "ere dangerously lo" blood !ressure occurs#
Dengue is transmitted by several s!ecies of mosquito "itin te genus Aedes$ !rinci!ally A.
aegypti# 2e virus as five different ty!es=
>-?
infection "it one ty!e usually gives lifelong
immunity to tat ty!e$ but only sort-term immunity to te oters# Subsequent infection "it a
different ty!e increases te ris' of severe com!lications# &s tere is no commercially available
vaccine$ !revention is sougt by reducing te abitat and te number of mosquitoes and limiting
e+!osure to bites#
2reatment of acute dengue is su!!ortive$ using eiter oral or intravenous reydration for mild or
moderate disease$ and intravenous fluids and blood transfusion for more severe cases# 2e
number of cases of dengue fever as increased dramatically since te -@A.s$ "it bet"een B.
and BCD million !eo!le infected yearly#
>C?>E?
Early descri!tions of te condition date from -FF@$
and its viral cause and te transmission "ere figured out in te early C.t century# Dengue as
become a global !roblem since te Second ,orld ,ar and is endemic in more tan
--. countries# &!art from eliminating te mosquitoes$ "or' is ongoing on a vaccine$ as "ell as
medication targeted directly at te virus#
Signs and symptoms
Sche%atic depiction o' the sy%pto%s o' den&ue 'ever
2y!ically$ !eo!le infected "it dengue virus are asym!tomatic (D.G) or only ave mild
sym!toms suc as an uncom!licated fever#
>C?>H?>B?
Iters ave more severe illness (BG)$ and in a
small !ro!ortion it is life-treatening#
>C?>B?
2e incubation !eriod (time bet"een e+!osure and
onset of sym!toms) ranges from EJ-H days$ but most often it is HJF days#
>A?
2erefore$ travelers
returning from endemic areas are unli'ely to ave dengue if fever or oter sym!toms start more
tan -H days after arriving ome#
>F?
Cildren often e+!erience sym!toms similar to tose of te
common cold and gastroenteritis (vomiting and diarrea)
>D?
and ave a greater ris' of severe
com!lications$
>F?>@?
toug initial sym!toms are generally mild but include ig fever#
>@?
Clinical course
Clinical course o' den&ue 'ever
7108
2e caracteristic sym!toms of dengue are sudden-onset fever$ eadace (ty!ically located
beind te eyes)$ muscle and %oint !ains$ and a ras# 2e alternative name for dengue$
Kbrea'bone feverK$ comes from te associated muscle and %oint !ains#
>C?>--?
2e course of infection
is divided into tree !ases/ febrile$ critical$ and recovery#
>-.?
2e febrile !ase involves ig fever$ !otentially over H. LC (-.H L5)$ and is associated "it
generali6ed !ain and a eadace= tis usually lasts t"o to seven days#
>-.?>--?
Nausea and vomiting
may also occur#
>@?
& ras occurs in B.JD.G of tose "it sym!toms
>--?>-C?
in te first or second
day of sym!toms as flused s'in$ or later in te course of illness (days HJF)$ as a measles-li'e
ras#
>-C?>-E?
& ras described as Kislands of "ite in a sea of redK as also been described#
>-H?
Some
!eteciae (small red s!ots tat do not disa!!ear "en te s'in is !ressed$ "ic are caused by
bro'en ca!illaries) can a!!ear at tis !oint$
>-.?
as may some mild bleeding from te mucous
membranes of te mout and nose#
>F?>--?
2e fever itself is classically bi!asic or saddlebac' in
nature$ brea'ing and ten returning for one or t"o days#
>-E?>-H?
1n some !eo!le$ te disease !roceeds to a critical !ase as fever resolves#
>@?
During tis !eriod
tere is lea'age of !lasma from te blood vessels "ic ty!ically lasts one to t"o days#
>-.?
2is
may result in fluid accumulation in te cest and abdominal cavity as "ell as de!letion of fluid
from te circulation and decreased blood su!!ly to vital organs#
>-.?
2ere may also be organ
dysfunction and severe bleeding$ ty!ically from te gastrointestinal tract#
>F?>-.?
Soc' (dengue
soc' syndrome) and emorrage (dengue emorragic fever) occur in less tan BG of all cases
of dengue$
>F?
o"ever tose "o ave !reviously been infected "it oter seroty!es of dengue
virus (Ksecondary infectionK) are at an increased ris'#
>F?>-B?
2is critical !ase$ "ile rare$ occurs
relatively more commonly in cildren and young adults#
>@?
2e recovery !ase occurs ne+t$ "it resor!tion of te lea'ed fluid into te bloodstream#
>-.?
2is
usually lasts t"o to tree days#
>F?
2e im!rovement is often stri'ing$ and can be accom!anied
"it severe itcing and a slo" eart rate#
>F?>-.?
&noter ras may occur "it eiter a
maculo!a!ular or a vasculitic a!!earance$ "ic is follo"ed by !eeling of te s'in#
>@?
During tis
stage$ a fluid overload state may occur= if it affects te brain$ it may cause a reduced level of
consciousness or sei6ures#
>F?
& feeling of fatigue may last for "ee's in adults#
>@?
ssociated problems
Dengue can occasionally affect several oter body systems$
>-.?
eiter in isolation or along "it
te classic dengue sym!toms#
>D?
& decreased level of consciousness occurs in .#BJAG of severe
cases$ "ic is attributable eiter to inflammation of te brain by te virus or indirectly as a
result of im!airment of vital organs$ for e+am!le$ te liver#
>D?>-H?
Iter neurological disorders ave been re!orted in te conte+t of dengue$ suc as transverse
myelitis and Guillain-BarrM syndrome#
>D?
1nfection of te eart and acute liver failure are among
te rarer com!lications#
>F?>-.?
Cause
!irology
Main article9 5en&ue virus
4 :;M %icro&raph sho)in& den&ue virus virions (the cluster o' dar( dots near the
center)
Dengue fever virus (DEN8) is an *N& virus of te family Flaviviridae= genus Flavivirus# Iter
members of te same genus include yello" fever virus$ ,est Nile virus$ St# )ouis ence!alitis
virus$ Na!anese ence!alitis virus$ tic'-borne ence!alitis virus$ :yasanur forest disease virus$
and Ims' emorragic fever virus#
>-H?
Most are transmitted by artro!ods (mosquitoes or tic's)$
and are terefore also referred to as arboviruses (artro!od-borne viruses)#
>-H?
2e dengue virus genome (genetic material) contains about --$... nucleotide bases$ "ic code
for te tree different ty!es of !rotein molecules (C$ !rM and E) tat form te virus !article and
seven oter ty!es of !rotein molecules (NS-$ NSCa$ NSCb$ NSE$ NSHa$ NSHb$ NSB) tat are only
found in infected ost cells and are required for re!lication of te virus#
>-B?>-A?
2ere are five
>-?

strains of te virus$ called seroty!es$ of "ic te first four are referred to as DEN8--$ DEN8-C$
DEN8-E and DEN8-H#
>H?
2e distinctions bet"een te seroty!es is based on te teir
antigenicity#
>-F?
Transmission
:he %os1uito Aedes aegypti 'eedin& on a hu%an host
Dengue virus is !rimarily transmitted by Aedes mosquitoes$ !articularly A. aegypti#
>H?
2ese
mosquitoes usually live bet"een te latitudes of EBL Nort and EBL Sout belo" an elevation of
-$... metres (E$E.. ft)#
>H?
2ey ty!ically bite during te day$ !articularly in te early morning
and in te evening$
>-D?>-@?
but tey are able to bite and tus s!read infection at any time of day all
during te year#
>C.?
Iter Aedes s!ecies tat transmit te disease include A. albopictus$ A.
polynesiensis and A. scutellaris#
>H?
7umans are te !rimary ost of te virus$
>H?>-H?
but it also
circulates in nonuman !rimates#
>C-?
&n infection can be acquired via a single bite#
>CC?
& female
mosquito tat ta'es a blood meal from a !erson infected "it dengue fever$ during te initial CJ
-. day febrile !eriod$ becomes itself infected "it te virus in te cells lining its gut#
>CE?
&bout DJ
-. days later$ te virus s!reads to oter tissues including te mosquito3s salivary glands and is
subsequently released into its saliva# 2e virus seems to ave no detrimental effect on te
mosquito$ "ic remains infected for life#
>A?
Aedes aegypti !refers to lay its eggs in artificial
"ater containers$ to live in close !ro+imity to umans$ and to feed on !eo!le rater tan oter
vertebrates#
>A?
Dengue can also be transmitted via infected blood !roducts and troug organ donation#
>CH?>CB?
1n
countries suc as Singa!ore$ "ere dengue is endemic$ te ris' is estimated to be bet"een -#A
and A !er -.$... transfusions#
>CA?
8ertical transmission (from moter to cild) during !regnancy
or at birt as been re!orted#
>CF?
Iter !erson-to-!erson modes of transmission ave also been
re!orted$ but are very unusual#
>--?
2e genetic variation in dengue viruses is region s!ecific$
suggestive tat establisment into ne" territories is relatively infrequent$ des!ite dengue
emerging in ne" regions in recent decades#
>@?
"redisposition
Severe disease is more common in babies and young cildren$ and in contrast to many oter
infections it is more common in cildren tat are relatively "ell nourised#
>F?
Iter ris' factors
for severe disease include female se+$ ig body mass inde+$
>@?
and viral load#
>CD?
,ile eac
seroty!e can cause te full s!ectrum of disease$
>-B?
virus strain is a ris' factor#
>@?
1nfection "it
one seroty!e is tougt to !roduce lifelong immunity to tat ty!e$ but only sort term !rotection
against te oter tree#
>H?>--?
2e ris' of severe disease from secondary infection increases if
someone !reviously e+!osed to seroty!e DEN8-- contracts seroty!e DEN8-C or DEN8-E$ or if
someone !reviously e+!osed to DEN8-E acquires DEN8-C#
>-A?
Dengue can be life-treatening in
!eo!le "it cronic diseases suc as diabetes and astma#
>-A?
(olymor!isms (normal variations) in !articular genes ave been lin'ed "it an increased ris' of
severe dengue com!lications# E+am!les include te genes coding for te !roteins 'no"n as
2N5O$ mannan-binding lectin$
>C?
C2)&H$ 2G5P$
>-B?
DC-S1GN$ ()CE-$ and !articular forms of
uman leu'ocyte antigen from gene variations of 7)&-B#
>@?>-A?
& common genetic abnormality in
&fricans$ 'no"n as glucose-A-!os!ate deydrogenase deficiency$ a!!ears to increase te ris'#
>CD?
(olymor!isms in te genes for te vitamin D rece!tor and 5cQ* seem to offer !rotection
against severe disease in secondary dengue infection#
>-A?
$echanism
,en a mosquito carrying dengue virus bites a !erson$ te virus enters te s'in togeter "it te
mosquito3s saliva# 1t binds to and enters "ite blood cells$ and re!roduces inside te cells "ile
tey move trougout te body# 2e "ite blood cells res!ond by !roducing a number of
signaling !roteins$ suc as cyto'ines and interferons$ "ic are res!onsible for many of te
sym!toms$ suc as te fever$ te flu-li'e sym!toms and te severe !ains# 1n severe infection$ te
virus !roduction inside te body is greatly increased$ and many more organs (suc as te liver
and te bone marro") can be affected# 5luid from te bloodstream lea's troug te "all of
small blood vessels into body cavities due to ca!illary !ermeability# &s a result$ less blood
circulates in te blood vessels$ and te blood !ressure becomes so lo" tat it cannot su!!ly
sufficient blood to vital organs# 5urtermore$ dysfunction of te bone marro" due to infection of
te stromal cells leads to reduced numbers of !latelets$ "ic are necessary for effective blood
clotting= tis increases te ris' of bleeding$ te oter ma%or com!lication of dengue fever#
>CD?
!iral replication
Ince inside te s'in$ dengue virus binds to )angerans cells (a !o!ulation of dendritic cells in
te s'in tat identifies !atogens)#
>CD?
2e virus enters te cells troug binding bet"een viral
!roteins and membrane !roteins on te )angerans cell$ s!ecifically te C-ty!e lectins called
DC-S1GN$ mannose rece!tor and C)ECB&#
>-B?
DC-S1GN$ a non-s!ecific rece!tor for foreign
material on dendritic cells$ seems to be te main !oint of entry#
>-A?
2e dendritic cell moves to te
nearest lym! node# Mean"ile$ te virus genome is translated in membrane-bound vesicles on
te cell3s endo!lasmic reticulum$ "ere te cell3s !rotein syntesis a!!aratus !roduces ne" viral
!roteins tat re!licate te viral *N& and begin to form viral !articles# 1mmature virus !articles
are trans!orted to te Golgi a!!aratus$ te !art of te cell "ere some of te !roteins receive
necessary sugar cains (glyco!roteins)# 2e no" mature ne" viruses bud on te surface of te
infected cell and are released by e+ocytosis# 2ey are ten able to enter oter "ite blood cells$
suc as monocytes and macro!ages#
>-B?
2e initial reaction of infected cells is to !roduce interferon$ a cyto'ine tat raises a number of
defenses against viral infection troug te innate immune system by augmenting te !roduction
of a large grou! of !roteins mediated by te N&:-S2&2 !at"ay# Some seroty!es of dengue
virus a!!ear to ave mecanisms to slo" do"n tis !rocess# 1nterferon also activates te
ada!tive immune system$ "ic leads to te generation of antibodies against te virus as "ell as
2 cells tat directly attac' any cell infected "it te virus#
>-B?
8arious antibodies are generated=
some bind closely to te viral !roteins and target tem for !agocytosis (ingestion by s!eciali6ed
cells and destruction)$ but some bind te virus less "ell and a!!ear instead to deliver te virus
into a !art of te !agocytes "ere it is not destroyed but is able to re!licate furter#
>-B?
#e$ere disease
1t is not entirely clear "y secondary infection "it a different strain of dengue virus !laces
!eo!le at ris' of dengue emorragic fever and dengue soc' syndrome# 2e most "idely
acce!ted y!otesis is tat of antibody-de!endent enancement (&DE)# 2e e+act mecanism
beind &DE is unclear# 1t may be caused by !oor binding of non-neutrali6ing antibodies and
delivery into te "rong com!artment of "ite blood cells tat ave ingested te virus for
destruction#
>-B?>-A?
2ere is a sus!icion tat &DE is not te only mecanism underlying severe
dengue-related com!lications$
>C?
and various lines of researc ave im!lied a role for 2 cells and
soluble factors suc as cyto'ines and te com!lement system#
>CD?
Severe disease is mar'ed by te !roblems of ca!illary !ermeability (an allo"ance of fluid and
!rotein normally contained "itin blood to !ass) and disordered blood clotting#
>D?>@?
2ese
canges a!!ear associated "it a disordered state of te endotelial glycocaly+$ "ic acts as a
molecular filter of blood com!onents#
>@?
)ea'y ca!illaries (and te critical !ase) are tougt to
be caused by an immune system res!onse#
>@?
Iter !rocesses of interest include infected cells tat
become necrotic4"ic affect bot coagulation and fibrinolysis (te o!!osing systems of blood
clotting and clot degradation)4and lo" !latelets in te blood$ also a factor in normal clotting#
>CD?
Diagnosis
Warning signs
7<87=<8
#orsenin& ado%inal pain
>n&oin& vo%itin&
+iver enlar&e%ent
Mucosal leedin&
Hi&h he%atocrit )ith lo)
platelets
+ethar&y or restlessness
Serosal efusions
2e diagnosis of dengue is ty!ically made clinically$ on te basis of re!orted sym!toms and
!ysical e+amination= tis a!!lies es!ecially in endemic areas#
>C?
7o"ever$ early disease can be
difficult to differentiate from oter viral infections#
>F?
& !robable diagnosis is based on te
findings of fever !lus t"o of te follo"ing/ nausea and vomiting$ ras$ generali6ed !ains$ lo"
"ite blood cell count$ !ositive tourniquet test$ or any "arning sign (see table) in someone "o
lives in an endemic area#
>C@?
,arning signs ty!ically occur before te onset of severe dengue#
>-.?

2e tourniquet test$ "ic is !articularly useful in settings "ere no laboratory investigations are
readily available$ involves te a!!lication of a blood !ressure cuff at bet"een te diastolic and
systolic !ressure for five minutes$ follo"ed by te counting of any !etecial emorrages= a
iger number ma'es a diagnosis of dengue more li'ely "it te cut off being more tan -. to
C. !er - inc
C
(A#CB cm
C
)#
>-.?>E.?
2e diagnosis sould be considered in anyone "o develo!s a fever "itin t"o "ee's of being
in te tro!ics or subtro!ics#
>@?
1t can be difficult to distinguis dengue fever and ci'ungunya$ a
similar viral infection tat sares many sym!toms and occurs in similar !arts of te "orld to
dengue#
>--?
Iften$ investigations are !erformed to e+clude oter conditions tat cause similar
sym!toms$ suc as malaria$ le!tos!irosis$ viral emorragic fever$ ty!oid fever$ meningococcal
disease$ measles$ and influen6a#
>F?>E-?
2e earliest cange detectable on laboratory investigations is a lo" "ite blood cell count$ "ic
may ten be follo"ed by lo" !latelets and metabolic acidosis#
>F?
& moderately elevated level of
aminotransferase (&S2 and &)2) from te liver is commonly associated "it lo" !latelets and
"ite blood cells#
>@?
1n severe disease$ !lasma lea'age results in emoconcentration (as indicated
by a rising ematocrit) and y!oalbuminemia#
>F?
(leural effusions or ascites can be detected by
!ysical e+amination "en large$
>F?
but te demonstration of fluid on ultrasound may assist in te
early identification of dengue soc' syndrome#
>C?>F?
2e use of ultrasound is limited by lac' of
availability in many settings#
>C?
Dengue soc' syndrome is !resent if !ulse !ressure dro!s to
R C. mm 7g along "it !eri!eral vascular colla!se#
>@?
(eri!eral vascular colla!se is
determined in cildren via delayed ca!illary refill$ ra!id eart rate$ or cold e+tremities#
>-.?
Classi%cation
2e ,orld 7ealt Irgani6ation3s C..@ classification divides dengue fever into t"o grou!s/
uncom!licated and severe#
>C?>C@?
2is re!laces te -@@F ,7I classification$ "ic needed to be
sim!lified as it ad been found to be too restrictive$ toug te older classification is still "idely
used
>C@?
including by te ,orld 7ealt Irgani6ation3s *egional Iffice for Sout-East &sia as of
C.--#
>EC?
Severe dengue is defined as tat associated "it severe bleeding$ severe organ
dysfunction$ or severe !lasma lea'age "ile all oter cases are uncom!licated#
>C@?
2e -@@F
classification divided dengue into undifferentiated fever$ dengue fever$ and dengue emorragic
fever#
>F?>EE?
Dengue emorragic fever "as subdivided furter into grades 1J18# Grade 1 is te
!resence only of easy bruising or a !ositive tourniquet test in someone "it fever$ grade 11 is te
!resence of s!ontaneous bleeding into te s'in and else"ere$ grade 111 is te clinical evidence
of soc'$ and grade 18 is soc' so severe tat blood !ressure and !ulse cannot be detected#
>EE?

Grades 111 and 18 are referred to as Kdengue soc' syndromeK#
>C@?>EE?
&aboratory tests
#hen laoratory tests 'or den&ue 'ever eco%e positive )here day ,ero is the start
o' sy%pto%s, 1st re'ers to in those )ith a pri%ary in'ection, and =nd re'ers to in
those )ith a secondary in'ection*
7<8
2e diagnosis of dengue fever may be confirmed by microbiological laboratory testing#
>C@?>EH?
2is
can be done by virus isolation in cell cultures$ nucleic acid detection by (C*$ viral antigen
detection (suc as for NS-) or s!ecific antibodies (serology)#
>-A?>E-?
8irus isolation and nucleic
acid detection are more accurate tan antigen detection$ but tese tests are not "idely available
due to teir greater cost#
>E-?
Detection of NS- during te febrile !ase of a !rimary infection may
be greater tan @.G o"ever is only A.JD.G in subsequent infections#
>@?
&ll tests may be
negative in te early stages of te disease#
>F?>-A?
(C* and viral antigen detection are more accurate
in te first seven days#
>@?
1n C.-C a (C* test "as introduced tat can run on equi!ment used to
diagnose influen6a= tis is li'ely to im!rove access to (C*-based diagnosis#
>EB?
2ese laboratory tests are only of diagnostic value during te acute !ase of te illness "it te
e+ce!tion of serology# 2ests for dengue virus-s!ecific antibodies$ ty!es 1gG and 1gM$ can be
useful in confirming a diagnosis in te later stages of te infection# Bot 1gG and 1gM are
!roduced after BJF days# 2e igest levels (titres) of 1gM are detected follo"ing a !rimary
infection$ but 1gM is also !roduced in reinfection# 1gM becomes undetectable E.J@. days after a
!rimary infection$ but earlier follo"ing re-infections# 1gG$ by contrast$ remains detectable for
over A. years and$ in te absence of sym!toms$ is a useful indicator of !ast infection# &fter a
!rimary infection 1gG reaces !ea' levels in te blood after -HJC- days# 1n subsequent re-
infections$ levels !ea' earlier and te titres are usually iger# Bot 1gG and 1gM !rovide
!rotective immunity to te infecting seroty!e of te virus#
>A?>--?>-A?
2e laboratory test for 1gG and
1gM antibodies can cross-react "it oter flaviviruses and may result in a false !ositive after
recent infections or vaccinations "it yello" fever virus or Na!anese ence!alitis#
>@?
2e
detection of 1gG alone is not considered diagnostic unless blood sam!les are collected -H days
a!art and a greater tan fourfold increase in levels of s!ecific 1gG is detected# 1n a !erson "it
sym!toms$ te detection of 1gM is considered diagnostic#
>A?
Prevention
4 1<=0s photo&raph o' eforts to disperse standin& )ater and thus decrease
%os1uito populations
2ere are no a!!roved vaccines for te dengue virus#
>C?
(revention tus de!ends on control of
and !rotection from te bites of te mosquito tat transmits it#
>-D?>EA?
2e ,orld 7ealt
Irgani6ation recommends an 1ntegrated 8ector Control !rogram consisting of five elements/
>-D?
1* 4dvocacy, social %oili,ation and le&islation to ensure that pulic health
odies and co%%unities are stren&thened?
=* Collaoration et)een the health and other sectors (pulic and private)?
@* 4n inte&rated approach to disease control to %aAi%i,e use o' resources?
4* ;vidence-ased decision %a(in& to ensure any interventions are tar&eted
appropriately? and
B* Capacity-uildin& to ensure an ade1uate response to the local situation*
2e !rimary metod of controlling A. aegypti is by eliminating its abitats#
>-D?
2is is done by
getting rid of o!en sources of "ater$ or if tis is not !ossible$ by adding insecticides or biological
control agents to tese areas#
>-D?
Generali6ed s!raying "it organo!os!ate or !yretroid
insecticides$ "ile sometimes done$ is not tougt to be effective#
>B?
*educing o!en collections of
"ater troug environmental modification is te !referred metod of control$ given te concerns
of negative ealt effects from insecticides and greater logistical difficulties "it control agents#
>-D?
(eo!le can !revent mosquito bites by "earing cloting tat fully covers te s'in$ using
mosquito netting "ile resting$ and;or te a!!lication of insect re!ellent (DEE2 being te most
effective)#
>CC?
7o"ever$ tese metods a!!ear not to be sufficiently effective$ as te frequency of
outbrea's a!!ears to be increasing in some areas$ !robably due to urbani6ation increasing te
abitat of A. aegypti# 2e range of te disease a!!ears to be e+!anding !ossibly due to climate
cange#
>-?
$anagement
2ere are no s!ecific antiviral drugs for dengue$ o"ever maintaining !ro!er fluid balance is
im!ortant#
>@?
2reatment de!ends on te sym!toms#
>EF?
2ose "o are able to drin'$ are !assing
urine$ ave no K"arning signsK and are oter"ise ealty can be managed at ome "it daily
follo" u! and oral reydration tera!y#
>EF?
2ose "o ave oter ealt !roblems$ ave K"arning
signsK or "o cannot manage regular follo" u! sould be cared for in os!ital#
>F?>EF?
1n tose "it
severe dengue care sould be !rovided in an area "ere tere is access to an intensive care unit#
>EF?
1ntravenous ydration$ if required$ is ty!ically only needed for one or t"o days#
>EF?
2e rate of
fluid administration is titrated to a urinary out!ut of .#BJ- m);'g;$ stable vital signs and
normali6ation of ematocrit#
>F?
2e smallest amount of fluid required to acieve tis is
recommended#
>EF?
1nvasive medical !rocedures suc as nasogastric intubation$ intramuscular
in%ections and arterial !unctures are avoided$ in vie" of te bleeding ris'#
>F?
(aracetamol
(acetamino!en) is used for fever and discomfort "ile NS&1Ds suc as ibu!rofen and as!irin
are avoided as tey migt aggravate te ris' of bleeding#
>EF?
Blood transfusion is initiated early in
!eo!le !resenting "it unstable vital signs in te face of a decreasing hematocrit$ rater tan
"aiting for te emoglobin concentration to decrease to some !redetermined Ktransfusion
triggerK level#
>ED?
(ac'ed red blood cells or "ole blood are recommended$ "ile !latelets and
fres fro6en !lasma are usually not#
>ED?
Corticosteroids do not a!!ear to affect outcomes and may
cause arm$ tus are not recommended#
>E@?
During te recovery !ase intravenous fluids are discontinued to !revent a state of fluid
overload#
>F?
1f fluid overload occurs and vital signs are stable$ sto!!ing furter fluid may be all
tat is needed#
>ED?
1f a !erson is outside of te critical !ase$ a loo! diuretic suc as furosemide
may be used to eliminate e+cess fluid from te circulation#
>ED?
%pidemiology
See also9 5en&ue 'ever outrea(s
;pide%ic den&ue and A. aegypti
A. aegypti, )ithout epide%ic den&ue
Most !eo!le "it dengue recover "itout any ongoing !roblems#
>C@?
2e mortality is -JBG
"itout treatment$
>F?
and less tan -G "it adequate treatment=
>C@?
o"ever severe disease carries
a mortality of CAG#
>F?
Dengue is endemic in more tan --. countries#
>F?
1t infects B. to
BCD million !eo!le "orld"ide a year$ leading to alf a million os!itali6ations$
>C?>E?
and
a!!ro+imately CB$... deats#
>D?
5or te decade of te C...s$ -C countries in Souteast &sia "ere
estimated to ave about E million infections and A$... deats annually#
>H.?
1t is re!orted in at least
CC countries in &frica= but is li'ely !resent in all of tem "it C.G of te !o!ulation at ris'#
>H-?
1nfections are most commonly acquired in te urban environment#
>A?
1n recent decades$ te
e+!ansion of villages$ to"ns and cities in endemic areas$ and te increased mobility of !eo!le
as increased te number of e!idemics and circulating viruses# Dengue fever$ "ic "as once
confined to Souteast &sia$ as no" s!read to Soutern Cina$ countries in te (acific Icean
and &merica$
>A?
and migt !ose a treat to Euro!e#
>B?
*ates of dengue increased E. fold bet"een -@A. and C.-.#
>HC?
2is increase is believed to be due
to a combination of urbani6ation$ !o!ulation gro"t$ increased international travel$ and global
"arming#
>C?
2e geogra!ical distribution is around te equator "it F.G of te total C#B billion
!eo!le living in endemic areas from &sia and te (acific#
>HC?
&n infection "it dengue is second
only to malaria as a diagnosed cause of fever among returning travelers#
>--?
1t is te most common
viral disease transmitted by artro!ods$
>-B?
and as a disease burden estimated at -$A.. disability-
ad%usted life years !er million !o!ulation#
>-A?
2e ,orld 7ealt Irgani6ation counts dengue as
one of seventeen neglected tro!ical diseases#
>HE?
)i'e most arboviruses$ dengue virus is maintained in nature in cycles tat involve !referred
blood-suc'ing vectors and vertebrate osts#
>A?
2e viruses are maintained in te forests of
Souteast &sia and &frica by transmission from female Aedes mosquitoes4of s!ecies oter tan
A. aegypti4to er offs!ring and to lo"er !rimates#
>A?
1n to"ns and cities$ te virus is !rimarily
transmitted by te igly domesticated A. aegypti# 1n rural settings te virus is transmitted to
umans by A. aegypti and oter s!ecies of Aedes suc as A. albopictus#
>A?
Bot tese s!ecies ave
ad e+!anding ranges in te second alf of te C.t century#
>@?
1n all settings te infected lo"er
!rimates or umans greatly increase te number of circulating dengue viruses$ in a !rocess called
am!lification#
>A?
&istory
2e first record of a case of !robable dengue fever is in a Cinese medical encyclo!edia from te
Nin Dynasty (CABJHC. &D) "ic referred to a K"ater !oisonK associated "it flying insects#
>HH?
>HB?
2e !rimary vector$ A. aegypti$ s!read out of &frica in te -Bt to -@t centuries due in !art to
increased globali6ation secondary to te slave trade#
>@?
2ere ave been descri!tions of e!idemics
in te -Ft century$ but te most !lausible early re!orts of dengue e!idemics are from -FF@ and
-FD.$ "en an e!idemic s"e!t across &sia$ &frica and Nort &merica#
>HB?
5rom tat time until
-@H.$ e!idemics "ere infrequent#
>HB?
1n -@.A$ transmission by te Aedes mosquitoes "as confirmed$ and in -@.F dengue "as te
second disease (after yello" fever) tat "as so"n to be caused by a virus#
>HA?
5urter
investigations by Non Burton Cleland and Nose! 5ran'lin Siler com!leted te basic
understanding of dengue transmission#
>HA?
2e mar'ed s!read of dengue during and after te Second ,orld ,ar as been attributed to
ecologic disru!tion# 2e same trends also led to te s!read of different seroty!es of te disease to
ne" areas$ and to te emergence of dengue emorragic fever# 2is severe form of te disease
"as first re!orted in te (ili!!ines in -@BE= by te -@F.s$ it ad become a ma%or cause of cild
mortality and ad emerged in te (acific and te &mericas#
>HB?
Dengue emorragic fever and
dengue soc' syndrome "ere first noted in Central and Sout &merica in -@D-$ as DEN8-C "as
contracted by !eo!le "o ad !reviously been infected "it DEN8-- several years earlier#
>-H?
'tymology
2e origins of te S!anis "ord dengue are not certain$ but it is !ossibly derived from dinga in
te S"aili !rase Ka-dinga pepo$ "ic describes te disease as being caused by an evil s!irit#
>HH?
Slaves in te ,est 1ndies aving contracted dengue "ere said to ave te !osture and gait of a
dandy$ and te disease "as 'no"n as Kdandy feverK#
>HF?>HD?
2e term Kbrea'bone feverK "as a!!lied by !ysician and 9nited States 5ounding 5ater
Ben%amin *us$ in a -FD@ re!ort of te -FD. e!idemic in (iladel!ia# 1n te re!ort title e uses
te more formal term Kbilious remitting feverK#
>H@?
2e term dengue fever came into general use
only after -DCD#
>HD?
Iter istorical terms include Kbrea'eart feverK and Kla dengueK#
>HD?
2erms
for severe disease include Kinfectious trombocyto!enic !ur!uraK and K(ili!!ineK$ K2aiK$ or
KSinga!ore emorragic feverK#
>HD?
"ulic health o/cers releasin& P. reticulata 'ry into an artiCcial la(e in the +a&o
$orte district o' BrasDlia, Bra,il, as part o' a vector control efort
*esearc efforts to !revent and treat dengue include various means of vector control$
>B.?
vaccine
develo!ment$ and antiviral drugs#
>EA?
,it regards to vector control$ a number of novel metods ave been used to reduce mosquito
numbers "it some success including te !lacement of te gu!!y (Poecilia reticulata) or
co!e!ods in standing "ater to eat te mosquito larvae#
>B.?
&ttem!ts are ongoing to infect te
mosquito !o!ulation "it bacteria of te Wolbachia genus$ "ic ma'es te mosquitoes !artially
resistant to dengue virus#
>@?>B-?
2ere are also trials "it genetically modified male A. aegypti tat
after release into te "ild mate "it females$ and render teir offs!ring unable to fly#
>BC?
2ere are ongoing !rograms "or'ing on a dengue vaccine to cover all four seroty!es#
>EA?
No"
tat tere is a fift seroty!e tis "ill need to be factored in#
>-?
Ine of te concerns is tat a
vaccine could increase te ris' of severe disease troug antibody-de!endent enancement
(&DE)#
>BE?
2e ideal vaccine is safe$ effective after one or t"o in%ections$ covers all seroty!es$
does not contribute to &DE$ is easily trans!orted and stored$ and is bot affordable and cost-
effective#
>BE?
&s of C.-C$ a number of vaccines "ere undergoing testing#
>-@?>BE?
2e most develo!ed
is based on a "ea'ened combination of te yello" fever virus and eac of te four dengue
seroty!es#
>-@?>BH?
1t is o!ed tat te first !roducts "ill be commercially available by C.-B#
>EA?
&!art from attem!ts to control te s!read of te Aedes mosquito and "or' to develo! a vaccine
against dengue$ tere are ongoing efforts to develo! antiviral drugs tat "ould be used to treat
attac's of dengue fever and !revent severe com!lications#
>BB?>BA?
Discovery of te structure of te
viral !roteins may aid te develo!ment of effective drugs#
>BA?
2ere are several !lausible targets#
2e first a!!roac is inibition of te viral *N&-de!endent *N& !olymerase (coded by NSB)$
"ic co!ies te viral genetic material$ "it nucleoside analogs# Secondly$ it may be !ossible to
develo! s!ecific inibitors of te viral !rotease (coded by NSE)$ "ic s!lices viral !roteins#
>BF?

5inally$ it may be !ossible to develo! entry inibitors$ "ic sto! te virus entering cells$ or
inibitors of te BS ca!!ing !rocess$ "ic is required for viral re!lication#
>BB?