Dengue and DHF

PPS Interim

GuidelinesGuidelines

Epidemiology

• DF and DHF is the most important arthropod-borne

viral disease among humans

• In the last 50 years, cases have multiplied 30-fold

– Increasing geographic expansion to new countries causing – Increasing geographic expansion to new countries causing

high mortalities in early phase of outbreaks

– Shifted from urban to rural settings

– Public health emergency of international concern with

implications for health security due to disruption and rapid

epidemic spread beyond national borders

World Health Assembly 2005; Resolution 58.5

EpidemiologyEpidemiology

• ~ 2.5 billion people live in dengue endemic

countries

– WHO SEA region and Western Pacific: 1.8 B (>70%)

at risk population bear ~75% of current global at risk population bear ~75% of current global

disease burden

• WestPac: Cambodia, Philippines, Malaysia and

Vietnam reported >1 M cases (2001-2008)

– CFR highest in Cambodia and the Philippines

2002 2005 2006

I 1.9 0 0II 29.6 4.1 0III 7.3 0 10.5

IV-A 13.3 3.9 37.8IV-B 0 0 0

V 10.6 6.8 0

DENGUE FEVER MORBIDITY

Source: Department of Health 2006

V 10.6 6.8 0VI 40 32.9 0VII 12.9 0.02 132.2VIII 23.6 0 0IX 20.5 0 0X 27.5 0 0XI 9.4 0 0XII 17.3 2.1 207.0

NCR 23.5 4.7 19.2CAR 7.1 22.2 152.3

CARAGA 9.3 0 0ARMM 0.8 0 0

Dengue Cases and Deaths by Sentinel Hospital

•NCR, Jan. 1 to Sept 29 (n=4,386)

Sentinel Hospitals in NCR Cases Deaths CFR (%)

SLH 1,640 1 0.06PCMC 500 3 0.6The Medical City 384 0 0

Quirino Memorial MC 286 2 0.7Rizal MC 165 5 3St. Lukes Medical Center 245 0 0NCH 158 2 1.3 Manila Doctors H 122 0 0Tondo Medical Center 92 0 0 San Juan de Dios Hospital 67 0 0Mandaluyong MC 82 0 0Mandaluyong MC 82 0 0Jose Reyes MMC 87 0 0UERMMMC 88 0 0AFPMC 53 0 0Ospital Ng Makati 49 1 2Chinese General Hospital 67 1 1.5San Juan MC 49 0 0RITM 74 0 0Manila Adventist Medical Cntr 28 0 0Taguig City MC 51 1 2Makati Medical Cntr 16 1 6Valenzuela General Hospital 32 3 9.4Las Pinas Gen H and Satellite Trauma Center 13 1 4.8Pasay City Gen Hospital 9 0 0Amang Rodriguez Medical Center 15 2 13Lourdes Hospital 1 0 0

Total 4,386 23 0.5

Dengue Cases by Year

•NCR, 1998 – 2007 (Jan. 1 to Sept. 29, 2007)

6000

8000

10000

12000

0

2000

4000

6000

Cases 5949 1741 2413 2413 2964 3757 4002 5787 11,42 4,386

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Dengue

• Caused by an arbovirus transmitted by Aedes mosquitoes.

• Highly seasonal in many countries in Asia and South AmericaSouth America

• Illness starts with acute onset of fever remaining continuously high for 2-7 days

• Most children recover but a small proportion develop severe disease

Increased

capillary

fragility

Thrombocytopenia

DHF: PATHOGENESIS

Thrombocytopenia

↓↓↓↓ blood coagulation factors:

fibrinogen, factors II,

V, VII, IX

Dengue Guidelines

2008 – PPS’ first evidence-based guidelines on Dengue Fever and Dengue Hemorrhagic Fever1

2009 - WHO “Dengue Guidelines for Diagnosis, 2009 - WHO “Dengue Guidelines for Diagnosis, Treatment, Prevention and Control- New edition 2009.”2

Dengue Guidelines

Two most important differences:

1. Dengue case classification

2. Clinical management

2010 INTERIM GUIDELINES ON FLUID MANAGEMENT OF DF/DHF

Objectives

1. To compare the Dengue Case Classification used in the 2008 PPS Dengue evidence-based guidelines and the proposed 2009 WHO Dengue Guidelines

2. To update the section on fluid management of the 2008 PPS Dengue evidence-based guidelines

3. To develop clinical algorithms on fluid resuscitation of patients with dengue based on presenting clinical features and based on the presence of compensated or uncompensated shock

2010 INTERIM GUIDELINES ON FLUID MANAGEMENT OF DF/DHF

Target Population

- pediatricians- family physicians- general practitioners- general practitioners- other healthcare professionals of various specialties

both in the private and government settings who are involved in the diagnosis and management of patients with dengue.

DENGUE CASE CLASSIFICATION

WHO Guidelines adopted by 2008 PPS guidelines:

DHF cases must fulfill all the following four criteria:1. fever or a history of acute fever lasting 2-7 days2. at least one of the ff hemorrhagic tendencies:

(+) TT, petechiae, purpura, ecchymoses;(+) TT, petechiae, purpura, ecchymoses;bleeding from mucosa, GIT, injection sites, orother location

3. thrombocytopenia with PC ≤ 100,000/µl4. hemoconcentration - ≥20% rise in hematocrit

relative to baseline or evidence of plasma leakage (i.e. pleural effusion, ascites, and/or hypoproteinemia)

SPECTRUM OF DENGUE INFECTION

DENGUE VIRUS INFECTION

Undifferentiated fever

ASYMPTOMATIC

Undifferentiated fever

Dengue Fever

Dengue Hemorrhagic Fever

w/o bleeding

w/ bleeding

No shock

DSS

WHO, Regional Guidelines on Dengue, prevention and

control, 2006

SYMPTOMATIC

This model for classifying dengue is currently being tested in 18 countries by comparing its performance in practical

settings to the existing WHO case classification. (Dengue Guidelines for Diagnosis, Treatment, Prevention and Control, WHO,

2009)

1 2 3 4 5 6 7 8 9 10Days ofIllness

Temp

Potential Shock Reabsorption

400C

Course of Dengue FeverCourse of Dengue Fever

PotentialClinicalissues

Laboratorychanges

SerologyandVirology

Febrile Critical Recovery phase

Dehydration

Hematocrit

Platelet

Viremia IgM/IgG

ShockBleeding

Organ Impairment

ReabsorptionFluid overload

Clinical Problems during the

Different phases of Dengue

Clinical Problems during the

Different phases of Dengue

1. FebrilePhase

Dehydration; high fever may cause neurological disturbances and febrile seizures in young children

2. Critical Shock from plasma leakage; severe 2. CriticalPhase

Shock from plasma leakage; severe hemorrhage; organ impairment

3. RecoveryPhase

Hypervolemia; (only if intravenous fluid therapy has been excessive and/or has extended into this period)

DENGUE CASE CLASSIFICATION

2009 WHO case classification

- results of the validation study through a prospective multicenter study is expected to be prospective multicenter study is expected to be available before the end of 2010

- therefore, there is no recommendation yet to adapt this proposed 2009 case classification of dengue

Comparison: Current WHO/PPS and the Proposed 2009 WHO Case Classification

CURRENT WHO/PPS classificationDengue Fever

Probable:

Acute febrile illness w/ ≥2 of the ff:

PROPOSED WHO Classification

Non-severe Dengue w/o Warning Signs

Probable dengue:

• live in /travel to dengue Acute febrile illness w/ ≥2 of the ff:

headache

retro-orbital pain

arthralgia

rash

hemorrhagic manifestations

leukopenia; and

supportive serology

• live in /travel to dengue endemic area

• fever and 2 of the ff criteria:

• nausea, vomiting

• rash

• aches and pains

• tourniquet test positive

• leukopenia

Comparison: Current WHO/PPS and the Proposed 2009 WHO Case Classification

CURRENT WHO/PPS classification

Dengue Fever

Confirmed:

PROPOSED WHO Classification

Non-severe Dengue w/o

Warning Signs

Laboratory-confirmed dengueConfirmed:

a case confirmed by

laboratory criteria

Laboratory-confirmed dengue

(important when no sign of

plasma leakage)

Comparison: Current WHO/PPS and the Proposed 2009 WHO Case Classification

CURRENT WHO/PPS classif

DHF Grade 1

fever with non-specific

constitutional signs

&symptoms :

PROPOSED WHO Classification

Non-severe Dengue w/ or w/o

Warning Signs

Fever and 2 of the ff :

&symptoms :

anorexia, vomiting,

abdominal pain

(+) TT &/or easy

bruisingas the only

hemorrhagic manife

Nausea, vomiting

Rash

Aches and pains

(+) TT

Leukopenia

• Any warning sign*

Comparison: Current WHO/PPS and the Proposed 2009 WHO Case Classification

CURRENT WHO/PPS classif

DHF Grade 2

Grade I manifestations

PROPOSED WHO ClassificationDengue withWarning signs*

Abdominal pain or tenderness

Persistent vomiting

Clinical fluid accumulation

Plus

spontaneous bleeding

usually skin or other

hemorrhages

( mucocutaneous), GIT

Clinical fluid accumulation

Mucosal bleed

Lethargy, restlessness

Liver enlargement >2 cm

Laboratory: increase in HCT concurrent with rapid decrease in platelet count

*requiring strict observation and medical intervention

Comparison: Current WHO/PPS and the Proposed 2009 WHO Case Classification

CURRENT WHO/PPS classifDHF Grade 3 (DSS)

Circulatory failure manifested by rapid,weak pulse and narrowing of pulse pressure or

PROPOSED WHO ClassificationSevere dengue

if the patient is from an area of

dengue risk presenting with:narrowing of pulse pressure or hypotension, with the presence of cold clammy skin and restlessness

DHF Grade 4 (DSS)

Profound shock with undetectable blood pressure or pulse

fever 2–7 days plus any of the ff:

Severe plasma leakage, leading to:

Shock

Fluid accumulation with respdistress

Severe bleeding, as evaluated by clinician

Comparison: Current WHO/PPS and the Proposed 2009 WHO Case Classification

CURRENT WHO/PPS classif PROPOSED WHO Classification

Severe dengue

Severe organ impairmentSevere organ impairment

Liver: AST or ALT ≥ 1000

CNS: impaired consciousness

Heart and other organs

Treatment

Proposed WHO Classification

• Most children managed at home provided parents

have reasonable access to hospital

– Counsel mother to bring child back for daily follow-up

but to return immediately if any of the ff. occurbut to return immediately if any of the ff. occur

• Severe abdominal pain

• Persistent vomiting

• Cold clammy extremities

• Lethargy or restlessness

• Bleeding e.g. black stools or coffee-ground vomit

Treatment

• Encourage oral fluid intake with clean H20 or ORS solution

• Paracetamol for high fever in an uncomfortable child. No aspirin or ibuprofenNo aspirin or ibuprofen

• Follow-up daily until temperature is normal. Check Hct daily where possible. Check for signs of severe disease

• Admit for signs of severe disease (mucosal or skin severe bleeding, shock, altered mental state, convulsions or jaundice) or with rapid or marked Hct rise

While new studies are being retrieved and evaluated, the updated CPG will have to await results of the validation studies being conducted by the WHO on their proposed dengue case classification and management guidelines. This will be crucial in order to come up with more comprehensive data on which to base comprehensive data on which to base recommendations for best practices on the management of dengue. The results of the validation studies are expected to be available before the end of

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