Dengue Hemorrhage Fever 2

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DENGUE HEMORRHAGIC FEVER Dr. CHOEUNG Chea MD, MMed (Paediatrics) Diseases in Childhood Updated : April 2008 2

• Dengue virus

cMlgeTAmnusStamryHkarxaMe bs; infected Aedes aegypti. • Virus

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eFVIdMeNIrkñúgcrnþQaménmn usSEdlva)anxaM eFVIeLIgkñúgkMLúgeBl EdlGñkCMgWmanRKunekþA. Uninfected mosquitoes Gacqøg virus RbsinebIva)anxaMmnusSEdlkM

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THE VIRUS • Dengue virus sßitenAkñúg family Flaviridae. • Dengue virus man 4 serotypes (DEN-1, DEN2, DEN-3, DEN-4)

EdleKGacEbgEckva)anedaysar serological methods. • .kalNamnusSqøgvIrusén serotype

NamYy vanwgbegáIteGayman immunity mYyCIvitRbqaMgnwg reinfection edaysarvirusén serotype

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THE HOST • .kñúgcMeNam serotypes TaMg4

énvIrusénCMgWRKunQam vIrusén serotypes NamYyk¾edayGacbgáeGayma n DF and DHF )anEdr . • Dengue shock syndrome (DSS)

ekIteLIgenAelI – .buKþlEdlFøab;qøgCMgWRKu nQamBImunmk (Previous dengue infection)

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THE HOST • Incubation manryHeBl 3-14 éf¶ • Acute phase of infection: 5-7 éf¶ • Followed by an immune respond • Infection

elIkTImYybegáIteGayman immunity mYyCIvitRbqaMgnwg reinfection edaysarvirusén serotype RbePTenaH b:uEnþvabegáIteGayman immunity temporary and partial

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DF

DHF

DENGUE PATHOGENESIS

Ag-Ab-complement complex Serous

-Fever

effusion

-Flushed face

Hepatomegaly

-Headache

Hypoprotidemia

-Retro-orbital pain -Myalgia

↑ capillary

-Arthralgia

permeability

-Rash

Dead

(pleural, ascite)

Hypovolemia (haemoconcentration)

Thrombocytopenia*

Acidosis Shock

DIC

-Haemorrhagic

Intestinal

manifestation

haemorrhage

-Leucopenia

*Trombocytopenia is not constant in DF

Anoxia

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Primary Dengue infection

Chemical substances released: C3a, C5a, IL-1, IL-6, TNF-α, Histamine

↑ -Excessive used for platelet aggravation -Consumptive coagulopathy

↑

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• Dysregulation of host immune response against virus • Direct viral effect

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Manifestation of dengue virus infection Asymptomatic Undifferentiate fever Dengue fever (DF)

Classical DF DF with unusual haemorrhage

Symptomatic Dengue haemorrhagic fever (DHF)

No shock (DHF grade I and II) With shock (DHF grade III and IV) 11

Febrile phase

Afebrile phase

Acute and very high fever + m inm anaggravation énCM gW eT(xu sBI 2 or more of following signs: DHF), fÞ yeTAvij sPaBrbs;Gñ ú kCM gW •Flushed face and/or conjunctival m ankarRbesIreLIg injection •Headache •Retro-orbital pain •Cutaneous rash •Haemorrhagic manifestation (petechiae, Tourniquet test+) •Leucopenia •Ht: normal

•Ht: always normal •Platelet: normal or ↓ 12

Above DF signs + always very sensitive hepatomegaly (abdominal pain)

The child status deteriorates: •somnolence •important asthenia •abdominal pain •hemodynamic status ± compensated •No signs of shock

•Ht: still normal •Platelets: still normal

•Ht: ↑ ≥ 20% of normal value •Platelets: ↓ ≤ 100.000/mm3 13

Same symptoms as DF/DHF

Same symptoms as DHF + signs of circulatory failure with shock

•Ht: still normal •Platelets: still normal

•Ht: ↑ ≥ 20% of normal value (except digestive haemorrhage) •Platelets: ↓ ≤ 100.000/mm3

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Grading the severity of dengue infection

Type Grade

DF

I DHF II

Symptoms

Laboratory

Fever with 2 or more of the following signs: flushed face, headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic signs

-Leucopenia - +/- Thrombocytopenia -Normal Ht

Above signs plus: -Thrombocytopenia and/or bruising ≤ 100.000/mm3 (ecchymosis) -↑ Ht ≥ 20% of normal value Above signs plus -Thrombocytopenia or haemorrhage ≤ 100.000/mm3 -↑ Ht ≥ 20% of normal value 15

Grading the severity of dengue infection Type Grade

III

Symptoms

Laboratory

Above signs plus (weak and rapid pulse, narrow BP, hypotension, cold and clammy skin, restlessness

-Thrombocytopenia ≤ 100.000/mm3 -↑ Ht ≥ 20% of normal value (except digestive haemorrhage)

DSS IV

with undertectable pulse and/or BP

-Thrombocytopenia ≤ 100.000/mm3 -↑ Ht ≥ 20% of normal value (except digestive haemorrhage)

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• Raise the blood pressure to mid way between systolic and diastolic pressure for 5 minutes. • Release the pressure and wait for 1 minute before reading the result. • Positive test is considered when there is ≥10 petechia per square inches or 2.5 cm square cm

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• Age ≤ 2 years = 30-35% • Age > 2-10 years = 35-40% • Age > 10 years = 40-45%

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• Uncomplicated DHF case: Ht & Platelet count • Complicated DHF case: – – – – – – –

Blood sugar Blood electrolyte Liver function test Renal function test Blood gas Coagulogram (PTT, PT, TT) 19

• – 1. Viral isolation – 2. Polymerase Chain Reaction (PCR) – 3. Antigen detection infixed tissues

• – Serology test- : detectable around or after the time of defervescence (usually day 5-7 of illness) 20

Differential Diagnosis • .kRBa©il: RKunekþAxøaMg 3940oC with oculo-nasal and bronchitic catarrh. Rash, specific to the disease on the 4th-5th day and persistent fever during the rash.

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Differential Diagnosis • Rubella (German measles):

RKunekþAmFümkñúgkMLúgeBl 3-4 éf¶ rYcbnþeday rash, which characterized the disease. Retro-cervical and occipital lymphadenopahties are common.

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Differential Diagnosis • : fever progressively increasing up to 39-40oC and persistent after the 7th day, saburral tongue and rumbling of the right iliac fossa. • : fever with thrombocytopenia often associated. History of travel or live in a malaria endemic zone. The fever persists over 7 days. • : the shock with thrombocytopenia, caused by the meningococcemia before the appearance of a necrotic purpura, can simulate DSS.

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• Febrile phase (2-7 days): – .eGayGñkCMgWsMrakeGay)aneRc

In ,Oral rehydration – . RbsinebIkMedA >38oC RtUveGay Paracetamol 10mg/kg/dose, kMueGayelIsBI 4dgkñúgmYyéf¶ – .minRtUveGay ASPIRIN eT – .RtYtBinitü pla/Ht erógral;éf¶;cab;éf¶TI 3 eTA • Afebrile phase (2-3 days):

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• Convalescence phase (7-10 days): – .KµandMbUnµanGVIBiesseT (No special advice) – .kumarGacjaMcMNIGaharFmµ

ta

(Normal diet without any restriction)

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• The manifestations and management of DHF during the febrile phase are the same as DF.

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• - 5%D/NSS - 5%D/N/2* (only for < 1 year of age) - 5%DLR - 5%DAR • - 10% Dextran 40 - 10% Haes-Sterile = Dextrose, = Normal Saline Solution, = Acetate Ringer, = Lactate Ringer

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IV fluid therapy for DHF grade I & II

No improvement, stationary (2) Improvement (1) IV fluid 3 ml/kg/h another 3h

Continue with the same IV fluid for another 1 – 3h Reevaluation VS hourly

Reevaluation Ht, VS hourly Improvement Further Improvement ↓IV fluid to 1.5 ml/kg/h over 3h Still improvement IV fluid 1.5 ml/kg/h over 24 – 48h and stop

aggravation (3) ↑ IV fluid to 6 ml/kg/h 1 – 3h More aggravation (4) See DHF grade III or IV 31

1. Improvement: ↓ Ht, stable pulse & Blood Pressure, ↑ urine diuresis 2. No improvement, stationary: Pulse and BP not changed and still having oliguria 3. Aggravation: pulse faster and oliguria 4. More aggravation: weak and rapid pulse or not detectable, narrow pulse pressure, hypotension or not measurable blood pressure 32

• Convalescent phase: – .jaMcMNIGaharFmµta – .mintMrUveGayeRbIfñaMeLIy

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Type of solutions • Crystalloid solutions: - 5%D/NSS - 5%DLR* - 5%D/AR • Colloid solution: - Dextran 40 - Fresh whole blood (FWB) * Lactate Ringer solutions are contra-indicated in case of acidosis. NSS or Acetate Ringer should be used instead of LR in case of shock 35

IV fluid therapy for DHF grade III

Improvement ↓ IV to 6 ml/kg/h over 3h Further Improvement ↓IV to 3 ml/kg/h over 6h Always improvement ↓IV to 1.5 ml/kg/h over 24 – 48h and stop

No improvement Control Ht

Ht ↑ Dextran 40 10ml/kg/h and repeated if necessary (not exceed 30ml/kg/day) No improvement ASCB* see complications guideline

Ht ↓ FWB 10ml/kg/h

Improvement ↓ IV fluid of crystalloid from 10 → 6 → 3 → 1.5 ml/kg/h 36

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– Acidosis (Bicarbonate Na 8.4% 1ml/kg/dose)

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– Blood sugar (<60mg%) → D10% 5ml/kg/dose.

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– Calcemia ( Ca gluconate 10% 1ml/kg/dose Max: 1 ampoule

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- Bleeding → Blood Transfusion, Platelet Transfusion

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• If shock: (nasal prongs) - Infant < 1 year = 1L/min - Children > 1 year = 2L/min

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• Crystalloid solutions: - NSS - AR • Colloid solution: - Dextran 40 - Fresh Whole Blood

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IV fluid therapy for DHF grade IV NSS or AR 10ml/kg bolus Improvement

No improvement

5%NSS/DAR 10ml/kg 1 – 2h Improvement

NSS/AR 10ml/kg bolus

No improvement

Improvement

No improvement

Lab: Hct, blood gas, ionogram, Ca, LFT, BUN, creatinin, glucose

↓ IV 10 → 6 → 3 → 1.5 ml/kg/h discontinue IV after 24 – 48h

Hct ↑ Dextran 40 10ml/kg/h and repeated if necessary

Improvement

Hct ↓ FWB 10ml/kg/h

No improvement

Improvement

ASCB and see complications guideline

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• .tamdan: Vital sign (CIBcr-

sMBaFQamcgVak;degðIm- kMedA), capillary refill time nig SpO2 erógral; 15-30 min. • Urine hourly

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• The common causes: – Early IV fluid therapy in the early febrile phase – Use of hypotonic solution – Do not reduce the rate of IV fluid and do not discontinue IV fluid when entering convalescence period – Do not use colloidal solution when indicates – Do not give blood transfusion when there is concealed bleeding and continue giving crystaloid and colloidal solutions – Do not calculate the amount of IV fluid according to ideal body weight in obese/overweight patients 43

• Use ideal body weight (weight for age) to calculate the IV fluid in overweight/obese patients • Maximum weight for IV calculation is 50 kg (for adult and overweight patients)

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• .ehImRtbkEPñk • .CIBcrvayxøaMg • Dyspnea (cgVak;degðImjab;) • Crepitation enAelIsYtTaMgsgxag • .TMhMeføImeLIgFM (Hepatomegaly) • Turgescence of jugular veins • CXR follow the heart size: increase the heart size 45

• Change IV fluid to Dextran 40 • Insert urinary catheter with special precaution • Furosemide 1mg/kg/dose IV. Vital signs should be monitored every 15 min for at least 1 hour after furosemide and observe clinical signs of shock • : Colloidal solution: Dextran 40 10ml/kg/h IV over 10-15 minutes or until the patient has stable vital signs, usually not more than 30 min and then 46 switch to crystalloid solution.

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cgVak;degðIm nig cgVak;ebHdUg .Gayu cgVak;degðIm eTAtamGayu

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cgVak;ebHdUg (qñaM ) (kñúg 1 naTI) (kñúg 1 naTI)

• • • •

<1 2–5 5 – 12 > 12

30-40 20-30 15-20 12-15

110-160 95-140 80-120 60-100

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sMrab;eGayGñkCMgW • .KµanRKunekþAy:agtic 24 ecjeTApÞH •

em:agedayKµankareRbIfñaMbB a©úHkMedAeT . .GñkCMgWcab;epþImXøanGaha reLIgvij

• Visible clinical improvement • .GñkCMgWmanenameRcIn • Stable haematocrit • .qøgputy:agtic recovery from shock •

2 éf¶eRkayBI 48

THANK YOU

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