dengue fever

Dengue Fever

Dr .AAMIR HALEEM F.C.P.S. (MEDICINE)

Dengue fever

genus Flavivirus, family Flaviviridae also known as breakbone fever.

(bonecrusher disease) Aedes aegypti

http://en.wikipedia.org/wiki/Flavivirus

http://en.wikipedia.org/wiki/Flaviviridae

http://en.wikipedia.org/wiki/Aedes_aegypti

WHO says some 2.5 billion people, two fifths of the world's population, are now at risk from dengue and estimates that there may be 50 million cases of dengue infection worldwide every year.

epidemic in more than 100 countries

http://en.wikipedia.org/wiki/WHO

Dengue Fever

Dengue virus Most prevalent vector-

borne viral illness in the world

Main mosquito vector is Aedes aegypti

Year round transmission

Incidence

50-100 million dengue fever infections per year globally

500,000 cases of severe dengue, dengue hemorrhagic fever or dengue shock syndrome

100-200 cases annually in U.S. Average case fatality 5%

Distribution

Endemic in more than 100 tropical and subtropical countries

Pandemic began in Southeast Asia after WW II with subsequent global spread

Several epidemics since 1980s

Distribution is comparable to malaria

Dengue Viral Infection(10,000)

Asymptomatic(majority) (9000)

Symptomatic(1000)

Viral Syndrome(500

DF(400)

DHF(100)

Plasma leakage

DHF(98%)

DSS(1-2%)

04/12/2023 LAKKUMAR FERNANO 7

Unusual dengue-

expanded dengue

syndrome(<<1%)

With bleedin

g

No bleedin

g

Incubation period

3-14 days (commonly 4-7 days)

Clinical Presentation

Spectrum of illness • non-specific febrile illness• classic dengue• dengue hemorrhagic fever• dengue shock syndrome• other (CNS dysfunction, liver failure,

myocarditis)

Classic Dengue Acute febrile illness with headache, retro-orbital

pain, myalgias, arthralgias “Break-bone fever” High fever 5-7 days Second fever for 1-2 days in 5% patients Followed by marked fatigue days to weeks Classic dengue 15-60% of infections Nausea, vomiting, diarrhea (30%) Macular or maculopapular confluent rash (50%) Respiratory symptoms: cough, sore throat (30%)

Dengue Hemorrhagic Fever

WHO classification of DHF Thrombocytopenia (platelet count <100,000) Fever 2-7 days Hemorrhagic manifestations with a positive

tourniquet test, petechiae, ecchymoses or mucosal bleeding.

Hemoconcentration or evidence of plasma leakage (ascites, effusion, decreased albumin)

Dengue Hemorrhagic Fever

Usually occurs in secondary infections after actively or passively (maternal) acquired immunity to a different viral serotype

Only 2-4% of secondary infections result in severe disease

Mortality is 10-20% if untreated, but decreases to <1% if adequately treated

Plasma leakage may progress to dengue shock syndrome

Disease Factors

Dengue-2 serotype most virulent Increased severity with secondary infections Increased risk in children <15 years and elderly. Greatest risk of DHF in infants. More severe in females Increased mortality with comorbid conditions Less common in malnourished children

Clinical Case Definition forDengue Hemorrhagic Fever

Fever, or recent history of acute fever Hemorrhagic manifestations Low platelet count (100,000/mm3 or less) Objective evidence of “leaky capillaries:”

elevated hematocrit (20% or more over baseline)

low albumin pleural or other effusions

4 Necessary Criteria:

Four Grades of DHF

Grade 1 Fever and nonspecific constitutional symptoms Positive tourniquet test is only hemorrhagic

manifestation Grade 2

Grade 1 manifestations + spontaneous bleeding Grade 3

Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)

Grade 4 Profound shock (undetectable pulse and BP)

DF or DHF?

DF vs DHF Important to differentiate Two different clinical conditions from the

beginning of the illness; Though they look very similar on the first 2 days

However badly managed DF will never become DHF (DF does not progress to DHF)

16LAKKUMAR FERNANO04/12/2023

Difference between DF & DHF

Dengue Fever(DF) No plasma leakage Plt may be decreased to <100,000 in about

50% of patients Leucopenia (<5000) also present Headache, muscle/ joint/ bone pain,

haemorrhagic manifestations seen in both DF and DHF

MP rash seen more in DF than DHF


Hemorrhagic Manifestations of DF Skin hemorrhages:

petechiae, purpura, ecchymoses Gingival bleeding Nasal bleeding Gastrointestinal bleeding:

hematemesis, melena, hematochezia Hematuria

Haemorrhagic Manifestations not enough to call it DHF


Difference between DF & DHF

Dengue Fever(DF) No plasma leakage – but H’agic manifestations

can occur Platelets drop to <100,000 in about 50% (NOT

ALL) Occasionally even to as low as 5000!!! But when it is < 50,000 significant chance that it

is not just DF


Dengue Haemorrhagic Fever(DHF)

Key feature is PLASMA LEAK Haemorrhagic manifestations + (at least +ve

Hess’s) (tender hepatomegaly- more in DHF) Plt < 100,000 in ALL Plasma leakage:

• Rising Hct 20% or More OR even less but towards 20% if on IV fluids or on excess oral fluids,






• Se Cholesterol <100mg/dl• Se Albumin <3.5 g/dl






• Se Cholesterol <100mg/dl (or drop of 20mg/dl)• Se Albumin <3.5 g/dl (or drop of 0.5g/dl)


Natural Course of DHF


Febrile phase: High fever for 2 – 7 days

Critical phase:Plasma leakage Lasts 24- 48 hUsually on D5/ D6, but earliest on D3

Convalescent phase:2-5 daysLonger in adults

Natural Course of DF


Febrile phase: High fever for 2 – 7 days

Convalescent phase:2-5 daysLonger in adults

No critical phase in DF!!!

Patient is in critical phase and confirmed to be DHF if … Fever D 3 or beyond Platelet < 100,000 (WBC < 5,000) Evidence of plasma leak

Effusions : pleura/ peritoneum (CXR/ USS) Hct rise of 20% from baseline Low albumin/ low cholesterol

Hemorrhagic manifestations (not essential if objective evidence of plasma leak+)


Laboratory confirmation of dengue infection NOT essential

Detection of critical phase

Defervescence Drowsy Rapid pulse Narrow pulse pressure (≤20 mmHg) Hypotension Rising Haematocrit Low Albumin level Low Cholesterol level


Haematocrit

Rise of Hct by 20% over the baseline indicates leakage

Eg: if baseline PCV 35% 42% = 20% rise


Danger Signs inDengue Hemorrhagic Fever

Abdominal pain - intense and sustained

Persistent vomiting Abrupt change from fever to

hypothermia, with sweating and prostration

Restlessness or somnolence

Martínez Torres E. Salud Pública Mex 37 (supl):29-44, 1995.

Clinical Case Definition for Dengue Shock Syndrome

4 criteria for DHF Evidence of circulatory failure manifested

indirectly by all of the following: Rapid and weak pulse Narrow pulse pressure ( 20 mm Hg) OR

hypotension for age Cold, clammy skin and altered mental status

Frank shock is direct evidence of circulatory failure

Unusual Presentationsof Severe Dengue Fever

Encephalopathy Hepatic damage Cardiomyopathy Severe gastrointestinal

hemorrhage

Signs and Symptoms ofEncephalitis/Encephalopathy

Associated with Acute Dengue Infection

Decreased level of consciousness: lethargy, confusion, coma

Seizures Nuchal rigidity Paresis

Physical Exam

Nonspecific findings Conjunctival injection,

pharyngeal erythema, lymphadenopathy, hepatomegaly (20-50%)

Macular or maculopapular rash (50%)

tourniquet test The tourniquet test is performed by inflating a

blood pressure cuff to a point mid-way between the systolic and diastolic pressures for five minutes. A test is considered positive when 10 or more petechiae per 2.5 cm2 (1 inch)are observed. In DHF, the test usually gives a definite positive result (i.e. >20 petechiae). The test may be negative or mildly positive during the phase of profound shock.

Laboratory Findings

Leucopenia Thrombocytopenia (<100,000) Modest liver enzyme elevation (2-5x nml) Serology:• Anti-dengue IgM• Anti-dengue IgG• Dengue NS1 antigen• Dengue RNA by PCR• Dengue Virus culture

Virology

Flavivirus family Small enveloped

viruses containing single stranded positive RNA

Four distinct viral serotypes (Den-1, Den-2, Den-3, Den-4)

Dengue Viruses

Four closely related single-stranded RNA

Dengue viruses (DEN-1, DEN-2, DEN-3 and

DEN-4)

Each serotype provides specific lifetime

immunity, and short-term cross-immunity (A

person can be infected as many as four times,

once with each serotype)

All serotypes can cause severe and fatal

disease

Pathophysiology

Transmitted by the bite of Aedes mosquito (Aedes aegypti)

Incubation 3-14 days Acute illness and

viremia 3-7 days Recovery or

progression to leakage phase

Dengue Mosquito

Aedes aegypti is the most important dengue mosquito It breeds in collections of water close to dwellings Common breeding sites are;

- Domestic water storage containers - tanks, jars, drums, flower vases with water

- Roof gutters /sun shades

- Used tyres, discarded tins, cans, pots, yogurt cups, polythene bags, tree axils &

- Many more places where rain water collects

The most common epidemic vector of dengue in the world is the Aedes aegypti mosquito. It can be identified by the white bands or scale patterns on its legs and thorax.

Replication and Transmissionof Dengue Virus (Part 1)

1. Virus transmitted to human in mosquito saliva

2. Virus replicates in target organs

3. Virus infects white blood cells and lymphatic tissues

4. Virus released and circulates in blood

3

4

1

2

Replication and Transmissionof Dengue Virus (Part 2)

5. Second mosquito ingests virus with blood

6. Virus replicates in mosquito midgut and other organs, infects salivary glands

7. Virus replicates in salivary glands

6

7

5

Treatment

No specific therapy Supportive measures: adequate hydration acetaminophen (if no liver dysfunction) avoid ASA and NSAIDs DHF or DHF w/ shock: IV fluid resuscitation and hospitalization blood or platelet transfusion as needed

Fluid Management in Dengue..

Initially (During the 1st 2 days)

dengue shock is extremely rare within 1st 2 days

There is NO LEAKAGE Can give fluids freely How Much to Give?

GIVE THE NORMAL MAINTENANCE(M) or More as replacement if there is vomiting diarrhoea

Give electrolyte solutions not plain water


Fluid Management in Dengue

The critical phase is only 48 hrs (24- 50+) Some fluid restriction is essential

during the critical phase(24-48hrs) The final outcome/morbidity/mortality

will largely depend on the fluid management of the critical phase

LAKKUMAR FERNANO 4704/12/2023

Fluid Management in Dengue…

After 3rd Day May start leaking any time DONT ASK TO DRINK PLENTY OF FLUIDS SOME FLUID RESTRICTION IS USEFUL

LOOK FOR SIGNS OF LEAKING & platelets dropping <100,000


WITH THE NEW GUIDELINES ...AND WITH CORRECT FLUID THERAPY

IN DENGUE THERE SHOULD BE

NO WALKED IN , DEAD PATIENTS!!!

How can we achieve this?

How to time the onset of critical phase and predict end .... Have serial FBCs done during the illness

, ideally from the same reliable lab

Beyond Day 3...when WBC is dropping below(or close to) 5000 and platelets are <150,000 and dropping do more than once/day

DO FBC – Not PCV & Platelets!!!

How to time the onset of critical phase?

17th 8 am

18th

8 am18th 8 pm

19th

8 am19th

8 pm20th 8 am

20th 8 pm

21st

8 am21st

8 pm

WBC 3200 2800 1900 2900 3700 4500 6000 7000 7300

N % 53 41 31 26 25 31 33 43 58

L % 44 56 68 71 73 67 66 55 41

PCV %

39 36 39 42 43 39 44 43 38

Plt 252000

121000

110000

61000 22000 18000 12000 8000 19000

Onset End

How to confirm pt is in the critical phase..?

Look for evidence of LEAKING effusions pleural and/or peritoneal cavities

Oedema, facial puffiness, leg/arm swelling are not suggestive of leaking but only suggest fluid overload

Look for evidence of LEAKING effusions pleural and/or peritoneal cavities

Do not wait till these are clinically detectable Do USS chest/abdomen (rpt if needed) CXR R/lat decubitus (or PA for follow up and

when clinically detectable) Very occasionally a very small pl effusion

may be seen in pts with DF or when platelets are >100,000 but without other evidence of leaking; they will not progress (rpt CXR)

L/sided effusion absorbing fluid?

Once in the critical phase...Monitor properly Pulse; BP;

HCT.....accurate values are needed for correct

decision making on changes of fluid rates!

Use capillary HCT(PCV) - What we get from FBC counts are not always good

for comparison Venous HCT in a patient with IV fluids running can be

sometimes misleading Except while in prolonged and profound shock

Capillary HCT is the BEST-NOT VENOUS!!!

Pulse and BP

Not always easy manually Sp. If oedematous / fluid overloaded

Use a monitor (multi para monitor ) When the values on the monitor are

doubtful re-check with another monitor If TWO monitors give similar values

believe the monitor even if you cannot confirm manually

UOP (Urine Output)..

When to catheterize...??

Pros and cons of catheterization..

If platelets counts are dropping fast and coming low better to do it before it drops too much to avoid bleeding while catheterizing..

Measure UOP every hour > 0.5ml/kg/hr

Calculated for IBW and NOT for actual BW

Duration of critical phase...

Total maximum duration of leaking is only 48 hrs if it start slowly

Once the patient is in SHOCK the leaking will usually end in 24 hrs look to see whether fluids can be reduced a lot or stopped after 24 hrs...

Also patients who leak very rapidly with counts dropping sharply be prepared to anticipate relatively short period of leaking

In Infants too it may be short 24hrs

Duration of critical phase...

Your initial timing may proved to be sometimes wrong!!! Be prepared to change what you decided earlier / or shift the timing based on more information you receive while Mx

Fluid therapy...

Each patient can be managed in many different ways and with different rate and choice of IV fluids but try to master the ways of giving the ‘smoothest’ and the most ‘uneventful’ recovery for the pt

AIM: AVOID BOTH SHOCK & FLUID OVERLOAD

Fluid Management in Dengue…

Once patient is in the critical phase (24-48hrs)

TOTAL FLUIDS= MAINTENANCE+5% DEFICIT

OVER THE ENTIRE CRITICAL PHASE (USUALLY 48 HRS)


Fluid quota for critical phase...

Calculation M+5%Maintenance 1st 10 kg 100ml/kg 2nd 10 kg 50ml/kg Balance wt 20ml/kg

5% body wt = 50ml/kg

Eg: 22kg (100x10 + 50x10+ 20x2) + 50x 22

1540 + 1100 = 2640ml


Fluid Management during the critical phase (DON’T OVER LOAD LEAKING VESSELES)

Total amount of fluids = Maintainance + 5% deficit

This includes both IV and oral fluids This amount of fluids is given over 24-48

hours Ideal body weight or actual body weight is

used for calculation (whichever is smaller) BUT Maximum body weight for which fluid

is calculated is only 50kg in ALL children, adults, pregnancy..LAKKUMAR FERNANO 6304/12/2023

TOTAL FLUID VOLUME IN CRITICAL PHASE(usually 48HRS) Fluid volume equivalent to (FLUID

QUOTA) Maintenance(only one day’s calculated volume) +

5% of body weight(i.e 50ml/kg) calculated for ideal body weight (or actual body weight if it is lower than IBW; maximum BW only 50kg) is the total fluid volume that should be given during the entire critical phase(leaking phase) irrespective of its length! This is usually 24-48 hrs and most patients it is 48 hours. Occasionally it 50 hrs or little more. Still one should try not to exceed this volume. (*note that it is almost one day’s fluids that is given over 2 days and maximum weight for which fluid is calculated is 50kg even if the actual weight is well above 50kg) 64LAKKUMAR FERNANO04/12/2023

Fluid Management during the critical phase

In shock M+5% should be given over 24 h In non shock over 48 h If allocated fluid volume exceeds and

shock still remains can give, but keeping in mind about the amount exceeded

If UOP is 0.5-1 ml/ kg/h then the amount of fluid given is adequate

If UOP is more that it suggests too much fluid


Critical Phase Fluids in DHF The maximum recommended total critical

phase fluid volume for any given pt will not exceed 4600ml

Maximum BWt 50 kg M+5% - (maintenance – 100x10+ 50x10 + 20x 30 +

(50x 50) When pt is in hospital or seen from the

onset When Mx begins with the onset of leaking total fluids

should be given over 48 hrs. When Pt presents in SHOCK

The pt is already in the peak of leaking and has only 24 more hrs before the leaking stop. The total M+5% can here be given over 24 hrs 66LAKKUMAR FERNANO04/12/2023

IV fluids Normal Saline/ Hartmann <6/12 may use N/2 Dextran 40 (Dextran 40 in Saline) – Hyper-oncoticosmolarity of 310

mOsm/L. Oncotic pressure 1693 mmHg. Sodium Content — Dextran 40 10% in sodium chloride 0.9%

provides 77 mEq of--> High oncotic pressure volume expender Molecular wt 10,000- 100,000(average 40,000) when given as a

bolus all molecules tend to stay together 6% Hetastarch (voluvan)

- osmolality -308mosm/ mol wt 100,000 – leaking less ; volume expansion –less

*** about 60% of pts with dengue shock could be managed only with crystalloids


WHAT FLUIDS AND WHEN?

Initially when pt come in shock (with no fluid overload) give N saline(crystalloids). If BP pulse not recordable give as fast as possible –free flow or 20ml/kg but only till BP/pulse can be felt After this only 10ml/kg boluses After 2 saline boluses consider colloids


When to give colloids?

Crystalloids also leak through leaky capillaries during leaking phase and will not hold on volume and PCV for long(not more that 1-2 hrs)

Colloids will not leak easily and will hold on to volume and maintain PCV for longer period (4-5 hrs)

BEST COLLOID IS DEXTRAN 40! What about FFP will also readily leak !


Plasma (FFP) transfusion

FFP almost have no place in the treatment of DHF/DSS! Too large amount (40-50 ml/kg) to be given in

order to correct coagulopathy It is not effective in holding the intravascular

volume because it iso-oncotic (the osmolarity is about 280-300 milli-osmole readily leak!!!

**if FFP is given to provide clotting factors for pt with liver failure what is the point in allowing it to leak out of the vascular compartment by giving it during leaking phase?

If you are to keep FFP within the circulation better to give it AFTER the leaking stops!If you give Vit K from the time you notice significant rise of LFTs even such need could be avoided!04/12/2023 71LAKKUMAR FERNANO

Crystalloid100%

Colloid20-25%Blood

10-15%

Blood & blood component used in DHF/DSS patients


Platelet 0.4%

Courtesy of Prof Siripen- Thailand

Fluids that could be used as IV push for resuscitation N saline,(FFP,) Haemaccel,gelfundin,

hetastarch If pulse/BP un-recordable give 20ml/kg fast

(DHF IV) If not(some pulse+) give 10ml/kg,

In dengue leaking is generally <10ml/kg/hr

After resuscitated change to crystalloid **FOR INITIAL RESUSCITATIONDO NOT

USE DEXTRAN as its hyperosmoler nature may not open microcirculation


Use of colloids- Dextran40

One dose of dextran (10ml/kg/bolus) will bring down the haematocrit by 10 points during critical phase

If Hct is 52% it should drop to 42% (or 43%)

LAKKUMAR FERNANO04/12/2023

How much colloids to give? Needed only during critical phase Both Dextran and hetastarch should ONLY

be given as BOLUSES (NEVER as a continuous drip). 10ml/kg iv

Dextran 40 maximum 3 doses(total 30ml/kg/day) per 24 hr period (i.e 6 doses over 48hrs) Before Dextran take blood for cross matching

Hetastarch maximum 5 doses over 24 hrs(10 boluses over 48 hrs)


During critical 48 hrs...

While giving fluid to maintain pulse/BP/PCV If enough fluid left from total quota (M+5%)

give crystalloids If only little fluid is left from quota use more

colloids. (keeping in mind the maximum)

Keeping checking ..., “On a time scale are you heading for fluid overload?” if so, switch to a colloid


Furosemide*(frusemide)..

Colloids when there is fluid overload.. When there is evidence of fluid overload

use Furosemide with starch or dextran. (0.5-1mg/kg halfway during the bolus)

But when furosemide is given be prepared to wait with the pt for at least 60minutes after the injection (effects like BP drop will occur within 60min)

(* BNF’s spellings)


when platelets are low may need but only in very exceptional circumstances (Thailand only in <0.4% of pts with DHF) Each platelet pack is 50-150ml contribute to

fluid overload No prophylaxis plt. transfusion At the initial phase the platelet drop >.100,000

is due to BM suppression but later when it drops <100,000 the cause is increase platelet consumption and the BM become hypercellular with increase production


Platelet transfusion-

Fluids during end of leaking phase... even if PCV is high if pt is well and pulse BP

OK do not try to correct the PCV Reabsorption will start soon and PCV will

come down. WAIT


New fluid regimen...

A form of fluid restriction during leakage phase Help prevent FLUID OVERLOAD Also prevent shock – give what is needed to

maintain BP, Pulse and

produce enough UOP (0.5-1ml/kg/hr)

Prevention of shock avoid organ failure, avoid DIC, coagulopathy due to Liver failure


LAKKUMAR FERNANO 81

Pts with complications ....

Usually due toPROLONG SHOCKFLUID OVERLOAD

04/12/2023

Prolonged shock

10 hours untreated - Death!!!> 4 hours untreated

Liver failure- prognosis 50% Liver + Renal failure - prognosis10% 3 organs failure (+respiratory failure) –

Prognosis is a miracle!!!


Complicated DHF When a pt is deteriorating with no

response to fluid therapy….

A: AcidosisB: BleedingC: CalciumS: Sugar


Acidosis

Acidosis is common in profound shock Prolonged acidosis makes patients more

prone to DIC Correct acidosis if pH is <7.35 and if

HCO3- level <15 mmol/l One may use empirical NaHCO3 1ml/kgs

slow bolus (max 10ml) diluted in equal volume

(may repeat upto 50ml)84LAKKUMAR FERNANO04/12/2023

Hypocalcaemia

Every patient with complicated DHF has hypocalcaemia.

Dengue patients who develop convulsions are likely to have hypocalcaemia.(may give them empirical calcium)

Detection of hypocalcaemia: Measure serum Ca2+ level Corrected QT interval in ECG


When to give calcium?

If the patient is complicated , and deteriorating or not showing expected improvement to fluid Rx think of hypocalcaemia.

Give empirical calcium to such pts Dose 1ml/kg of 10% Ca Gluconate slow bolus

diluted in N saline over 10-15 min(look for

bradycaria while pushing slowly) Max: 10ml. Can even give every 6Hrs if pt is not improving


Bleeding... When to suspect...?(when overt bleeding

absent) 1. At presentation ...

After 20 ml fast NS bolus No pulse !! Get ready with blood in case it is needed ask for uncross matched O-ve blood and also sent for DT

Cant sustain BP even after colloid bolus and adequate fluid resus

PCV drop without pt improving PCV drop > 10 points after 10ml/kg dextran x

1hr

Also consider blood transfusion If blood loss visible eg H’,mesis etc is >

10% of blood volume Even with bleeding the PCV drop may

take time(4-5hrs). When the pt does not show improvement

important to do repeat PCVs frequently

How to manage bleeding

Use PRC or WB PRC as 5ml/kg at a time If there is fluid

overload(most frequently) WB-as 10ml/kg (if no fluid overload) Even if bleeding is likely and if PCV is

>45% do not give blood without bringing down the PCV first by giving a colloid.

Most of the time with blood give 0.5-1mg kg of frusemide at the middle


Mortality/Morbidity

Treated DHF/DSS is associated with a 3% mortality rate.

Untreated DHF/DSS is associated with a 50% mortality rate.

Vaccination

No current dengue vaccine Estimated availability in 5-10 years Vaccine development is problematic as the

vaccine must provide immunity to all 4 serotypes Lack of dengue animal model Live attenuated tetravalent vaccines under

phase 2 trials New approaches include infectious clone DNA

and naked DNA vaccines

Prevention

Biological: Target larval stage of Aedes in large water

storage containers Larvivorous fish (Gambusia), endotoxin

producing bacteria (Bacillus), copepod crustaceans (mesocyclops)

Chemical: Insecticide treatment of water containers Space spraying (thermal fogs)

Public Health

Major and escalating global public health problem

Global demographic changes: urbanization and population growth with substandard housing, water, and waster management systems

Deteriorating public health infrastructure with limited resources resulting in “crisis management” not prevention

Increased travel Lack of effective mosquito control

Mosquito control: Options available

“Mosquitoes take about 7 days to

complete life cycle.

The first three Stages: eggs,larva

and pupa are aquatic.

Therefore, the best way to

prevent mosquito breeding isto remove

stagnant clear water”

THANK YOUYou’re welcome!

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