Aedes aegypti Mosquito

DENGUE FEVER

World Distribution of Dengue 1999

Areas infested with Aedes aegyptiAreas with Aedes aegypti and recent epidemic dengue

GLOBAL STATUS

• New infections annually: 50 million• Deaths: 24,000 annually• People at risk: 2.5-3 billion• Hospitalized cases: 500 000/year(90% of those affected are children)• Disease burden: 465,000 DisabilityAdjusted Life Years (DALY)

0

20,000

40,000

60,000

80,000

100,000

Cases

2005 Dengue Outbreak

Cases Deaths

Cases 90,000 3,000 31,000 4,800

Deaths 15,000 0 58 50

India, (West Bengal)

Sri Lanka Thailand Pakistan

DENGUE OUT BREAK IN SOUTH DENGUE OUT BREAK IN SOUTH EAST ASIA IN 2005EAST ASIA IN 2005

0

500

1000

1500

2000

2500

3000

3500

Cases

Dengue Fever In 2006

Cases Deaths

Cases 3331 3230 1836 400

Deaths 49 50 30 4

India Pakistan Karachi Lahore

DENGUE OUT BREAK IN PAKISTAN DENGUE OUT BREAK IN PAKISTAN (2006)(2006)

Manifestation Of Dengue Virus Infections

ASYMPTOMATICASYMPTOMATIC

DSS

SYMPTOMATICSYMPTOMATIC

Without haemorrhage

With unusual haemorrhage

No shock

Undifferentiated Fever

Dengue Fever

DengueHaemorrhagicFever

A) Undifferentiated Fever

• May be the most common manifestation of dengue

• Prospective study found that 87% of students infected were either asymptomatic or only mildly symptomatic

• Other prospective studies including all age- groups also demonstrate silent transmission

DS Burke, et al. A prospective study of dengue infectionsin Bangkok. Am J Trop Med Hyg 1988; 38:172-80.

2A) Clinical Characteristicsof Dengue Fever

• Fever• Headache• Muscle and joint pain• Nausea/vomiting• Rash• Hemorrhagic manifestations

2B)Hemorrhagic Manifestationsof Dengue

• Skin hemorrhages: petechiae, purpura, ecchymoses

• Gingival bleeding• Nasal bleeding• Gastro-intestinal bleeding:

hematemesis, melena, hematochezia• Hematuria• Increased menstrual flow

C1) Clinical Case Definition forDengue Hemorrhagic Fever

1. Fever, or recent history of acute fever2. Hemorrhagic manifestations3. Low platelet count (100,000/mm3 or less)4. Objective evidence of “leaky capillaries:”

– elevated hematocrit (20% or more over baseline)

– low albumin– pleural or other effusions

4 Necessary Criteria:4 Necessary Criteria:

Four Grades of DHFFour 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)

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.

Warning Signs for Dengue Shock

When Patients Develop DSS:• 3 to 6 days after onset of symptoms

Initial Warning Signals:• Disappearance of fever• Drop in platelets• Increase in hematocrit

Alarm Signals:• Severe abdominal pain• Prolonged vomiting• Abrupt change from fever to hypothermia• Change in level of consciousness (irritability or somnolence)

Four Criteria for DHF:• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets

C2) 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

Risk Factors Reported for DHF

• Virus strain• Pre-existing anti-dengue antibody

– previous infection– maternal antibodies in infants

• Host genetics• Age

Risk Factors for DHF (continued)

• Higher risk in secondary infections• Higher risk in locations with two or more

serotypes circulating simultaneously at high levels (hyperendemic transmission)

Increased Probability of DHF

Hyperendemicity

Increased circulationof viruses

Increased probabilityof secondary infection

Increased probability ofoccurrence of virulent strains

Increased probability ofimmune enhancement

Increased probability of DHFGubler & Trent, 1994

Viral Risk Factorsfor DHF Pathogenesis

• Virus strain (genotype)– Epidemic potential: viremia level,

infectivity• Virus serotype

– DHF risk is greatest for DEN-2, followed by DEN-3, DEN-4 and DEN-1

Clinical Evaluation in Dengue Fever

• Blood pressure• Evidence of bleeding in skin or other

sites• Hydration status• Evidence of increased vascular

permeability-- pleural effusions, ascites• Tourniquet test

Petechiae

Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrilephase: viremia and antibody responses. J Infect Dis 1997; 176:322-30.

AB

PEI = A/B x 100

Pleural Effusion IndexPleural Effusion Index

Tourniquet Test

• Inflate blood pressure cuff to a point midway between systolic and diastolic pressure for 5 minutes

• Positive test: 20 or more petechiae per 1 inch2 (6.25 cm2)

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 12.

Positive Tourniquet Test

Laboratory Testsin Dengue Fever

• Clinical laboratory tests– CBC--WBC, platelets, hematocrit– Albumin– Liver function tests– Urine--check for microscopic hematuria

• Dengue-specific tests– Virus isolation– Serology

Laboratory Methods for Dengue Diagnosis

• Virus isolation to determine serotype of the infecting virus

• IgM ELISA test for serologic diagnosis

Temperature, Virus Positivity and Anti-Dengue IgM , by Fever Day

Dengue IgMMean Max. Temperature Virus

Adapted from Figure 1 in Vaughn et al.,J Infect Dis, 1997; 176:322-30.

Fever Day

0

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Perc

ent V

irus

Pos

itive

-4 -3 -2 -1 0 1 2 3 4 5 6

39.5

39.0

38.5

38.0

37.5

37.0

Tem

pera

ture

(deg

rees

Cel

sius

)

Den

gue

IgM

(EIA

uni

ts)300

150

0

75

225

Outpatient Triage

• No hemorrhagic manifestations and patient is well-hydrated: home treatment

• Hemorrhagic manifestations or hydration borderline: outpatient observation center or hospitalization

• Warning signs (even without profound shock) or DSS: hospitalize

Patient Follow-Up

• Patients treated at home– Instruction regarding danger signs– Consider repeat clinical evaluation

• Patients with bleeding manifestations– Serial hematocrits and platelets at least daily

until temperature normal for 1 to 2 days• All patients

– If blood sample taken in first 5 days after onset, need convalescent sample between days 6 - 30

– All hospitalized patients need samples on admission and at discharge or death

Treatment of Dengue Fever& DHF I & II

• Fluids• Rest• Antipyretics (avoid aspirin and non-

steroidal anti-inflammatory drugs)• Monitor blood pressure, hematocrit,

platelet count, level of consciousness

Treatment of DHF III & IV

All above treatment +– In case of severe bleeding, give fresh whole blood 20 ml/kg as a bolus– Give platelet rich plasma transfusion exceptionally when platelet counts are below 5,000–10,000/ mm3 .– After blood transfusion, continue fluid therapy at 10 ml/kg/h and reduce it stepwise to bring it down to 3 ml/kg/h and maintain it for 24-48 hrs

•1 unit of RD(Random Donor) Plt. (50ml) per 10 Kg body weight.---- expected to increas the Plt. Count 5000-10000/uL. (If No splenomegaly, Fever or DIC)•Alloimmunized (who have received multiple transfusions and thus sensitized) may have little or no increase in the count.•They can be best served by SDAP(Single Donor Apheresis Platelets) as 1 SDAP unit(150ml)=6 RD units

CCI= Post transfusion count – Pre transfusion count X BSANumber of Platelets transfused X 10 11

Evaluation of Refractoriness of RD units

Treatment of DHF III & IV

Appropriate if-CCI is 10X10 9 /ml in 1 hr post transfusion sample and/or-CCI is 7.5X10 9/ml in 18-24 hr post transfusion sample.

Treatment of Dengue Fever

Raw papaya leaves, 2 pcs just cleaned and pound and squeeze with filter cloth. You will only get one tablespoon per leaf. So two tablespoon per serving once a day.Do not boil or cook or rinse with hot water, it will loose its strength. Only the leafy part and no stem or sap.It is very bitter and you have to swallow it like Won Low Kat. But it works.

Papaya Juice vs. Dengue ?

Source: from Indonesia March 2005

Indications for Hospital Discharge

• Absence of fever for 24 hours (without anti-fever therapy) and return of appetite

• Visible improvement in clinical picture• Stable hematocrit• 3 days after recovery from shock• Platelets 50,000/mm3

• No respiratory distress from pleural effusions/ascites

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 69.

Common Misconceptions aboutDengue Hemorrhagic Fever

Dengue + bleeding = DHF Need 4 WHO criteria, capillary permeability

DHF kills only by hemorrhage Patient dies as a result of shock

Poor management turns dengue into DHF Poorly managed dengue can be more severe, but

DHF is a distinct condition, which even well-treated patients may develop

Positive tourniquet test = DHF Tourniquet test is a nonspecific indicator of capillary

fragility

More Common Misconceptions about Dengue Hemorrhagic Fever

DHF is a pediatric disease All age groups are involved in the Americas

DHF is a problem of low income families All socioeconomic groups are affected

Tourists will certainly get DHF with a second infection Tourists are at low risk to acquire DHF

Dengue Vaccine?

• No licensed vaccine at present• Effective vaccine must be tetravalent• Field testing of an attenuated tetravalent

vaccine currently underway• Effective, safe and affordable vaccine will not

be available in the immediate future

Prevention

•The main tactic used in fighting Dengue is eradicating the mosquito.•Public spraying for mosquitoes is the most important aspect of this approach.•Personal prevention involces the use of mosquito nets, repellents, cover exposed skin, use of DEET-impregnated bednets, and avoiding endemic areas.

CONTACT

alauddinsarwar@gmail.comdoctoralauddin@yahoo.co.in