Dengue: The New Classification

Developed by clinicians and scientists of the DENCO study,

World Health Organization, Geneva

2

2005 to 2007

Objectives:

• Describe clinical disease in all age groups

and across a wide geographical range

• To develop a new candidate classification

3

Venezuela

Antwerp,Belgium

Philippines

Heidelberg,Germany

Vietnam

Malaysia

Thailand

TDR/WHO,Geneva

Europe

Latin America

Asia

Cuba

Liverpool,UK

Nicaragua

Brazil

DENCO Partners

4

Method

• Prospective hospital based multicentre study –local centres of excellence

• Children & adults, clinically suspected dengue

• Recruited < 7 days of illness and

• Daily follow-up with a detailed CRF

– Hct and platelets done at least daily

– Other tests (liver & renal function) at least twice during acute illness

– Radiological evidence of plasma leakage within 24h of defervescence

– WHO trained monitors

Flow chart of DENCO Study

A total of 2259 patients were recruited. 1734 were confirmed dengue or highly

suggestive and fulfilled minimum dataset required for the main analysis. About 90% of

patients were in-patients. Out-patients – Asian countries – 14% of patients, while in LA –

range bet 20 -50%.

Study population

N cases (%)

Continent

SE Asia

L America

1501 (86.6)

233 (13.4)

Age group

<15 years

≥ 15 years

1062 (61.2)

672 (38.8)

Day of illness at enrollment

≤2

3

4

5

6

77 (4.4)

294 (17.0)

598 (34.5)

562 (32.4)

203 (11.7)

7

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

DSS

DHF

DF

not classifiable

DF/DHF/DSS classification applied to DENCO patients (N=1734)

More than 40% of the patients could not be classified without using population haematocritdata

DHF

DSS

DF

Unclassifiable

8

DF/DHF/DSS classification including

population reference data for Hct (N=1734)

770

306

193

555

611 710

160 163

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

internal Hct baseline only plus external Hct baseline

DSS

DHF

DF

not classified

After including population reference data 18% still remain un-classifiable

9

Intermediate Tool: grading severity by

interventions

• Fluid Therapy

• Blood products

• Nursing care level

• Other interventions

Category 1 Standard

Category 2 Intermediate

Category 3 Major

Intermediate Tool: grading severity by

interventions

*Nursing care levels, individualised according to local practice:-

1 - in- or out-patient, free to walk around, standard observation protocol – e.g. 6 hourly

2 - hospitalised, more stringent observation protocol – e.g. 2-4 hourly

3 - bed rest, ICU level observation protocol – e.g. hourly

** At some sites certain blood products were given in response to abnormal laboratory findings rather than for clinical

reasons.Such interventions were classified in the moderate category.

Category 1

Standard Protocol

Category 2

Intermediate Protocol

Category 3

Major intervention

Nursing

care*Level 1 and no

intervention

Level 2 or 3 and no

intervention

Fluid

therapy

None IV fluids for maintenance

or rehydration

Shock resuscitation, or IV fluids (any)

for rehydration with nursing care level 3

Blood

products

None Platelets, fresh frozen

plasma or

cryoprecipitate** with n.

care level 1 or 2

Platelets, fresh frozen plasma or

cryoprecipitate with nursing care level 3

Whole blood, packed red cells, or any

combination of blood products

Other

interventio

ns

None Oxygen therapy

Diuretics without other

specific intervention

Oxygen therapy with n. care level 3

Respiratory support

Inotropic support

Specific treatment for liver, renal or

other organ failure

11

Classification by DF/DHF/DSS system

& by intervention category (N=1734)

306

555

691

710813

163 230

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

WHO classification DENCO by interventions

DSS / major

DHF / intermediate

DF / standard

not classified

DF/DHF/

DSS

classification

Classification by

intervention category

Cat. 1 (Standard)

Cat. 2 (Intermediate)

Cat. 3 (Major)

Total

DF 278 247 30 555

DHF (without DSS)

277 420 13 710

DSS 0 1 162 163

Un-classifiable 136 145 25 306

Total 691 813 230 1734

13

Classification by current WHO system

& by intervention category (N=1734)

414392

55

277

420

13

0

1

162

0

50

100

150

200

250

300

350

400

450

DF (N=861) DHF (N=710) DSS (N=163)

Category 1 (Standard) Category 2 (Intermediate) Category 3 (Major)

(6%)

(46%)

(39%)

14

All patients with clinical shock

DF 27

DHF

DSS 163

Not

classified20

27 + 20 = 47

Total 21047 / 210 = 22.4%

Uncomplicated0

Moderate 1

Severe 209

Total 210

Current WHO classification Classification by intervention

15

What about the 277 (39%) DHF patients classified as mild (standard) by intervention?

• In addition to thrombocytopenia and skin bleeding (or nose bleeding),

• most of these patients had radiological evidence of fluid accumulation*,

• some also clinical evidence and/or Hct > 20% compared to baseline

• BUT no intravenous fluid, on a standard observation protocol.

* 151 of the 277 (~55%) only had radiological evidence of fluid accumulation

16

306

555

691

710813

163 230

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

WHO classification DENCO by interventions

DSS / major

DHF / intermediate

DF / standard

not classified

Exploring a practical system: classify

Dengue into 3 levels of severity

1st step: identify criteria for severe disease to differentiate severe cases from moderate or uncomplicated cases (defined by intervention category)

2nd step: identify criteria for moderate disease in order to distinguish between moderate and uncomplicated cases

(13%)

17

Suggested indicators for severe dengue- one or more of the following

• Severe plasma leakage

– Clinical shock

– Any evidence of fluid accumulation with respiratory

distress

• Severe bleeding as evaluated by clinician

• Severe organ involvement

– Severe liver involvement with AST or ALT >= 1000

– Impaired consciousness with GCS < 15 or BCS < 5

• (Death caused by dengue)

Sensitivity = 96%

Specificity = 97% (n=210)

(n=6)

(n=7)

(n=1)

18

Classification into uncomplicated and

moderate disease – an example

• 3 or more present

– Clinical

• Clinical evidence of fluid accumulation

• Evidence of mucosal bleeding

• Liver enlarged

• Skin flush or rash

• Abdominal pain or tenderness

• Tourniquet test positive

– Laboratory

• WBC <= 2.0

• Percentage haematocrit increase >= 20

• Platelet count <= 50

Sensitivity = 77%

Specificity = 57%

19

SEVERE DENGUE

Watch for

Warning Signs

DENGUE

Binary classification

• Severe plasma

leakage

• Severe

bleeding

• Severe organ

impairment

Case Definition for Dengue

20

Objective: to compare the two

classification systems

1. Applicability in the clinical practice and in

surveillance,

2. Usefulness for triage and clinical management

and

3. User-friendliness and acceptance by health

staff.

21

S. Arabia

India

Indonesia

Malaysia

Philippines

Bolivia

Colombia

Cuba

Ecuador

El Salvador

Mexico

Nicaragua

Paraguay

Peru

Puerto Rico

Venezuela

Timeline of training and completion of the different data

collection instruments in 2009

■ training*

○ chart review* #

● staff

Questionnaires

◙ FGD

Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec.

■ ◙ ○●

■ ● ◙

■ ○ ●◙

■ ◙○●

■ ● ◙ ○

■ ○ ● ◙

■ ○●

■ ●◙

■ ○●◙

■ ○◙ ●

■ ○●

○■ ○ ●

■ ○ ●

■ ○ ●

Timeframe of project activities in 2009

month

■ ○ ◙●

■ ●

16 P

art

icip

ating c

ountr

ies

22

23

Comparison between Current WHO

classification and Revised classifiction

(by reviewer)

Match and mis-match of the DF/DHF/DSS and the revised

classifications in 1962 prospective chart reviews (130 missing

information excluded)

DF/DHF/DSS

classification

by expert

reviewer

Revised classification by expert reviewer Total

Not

classifiableD - WS D + WS Severe

Dengue

Not classifiable 23

(8.6%)

57

(21.3%)

159

(59.3%)

29

(10.8%)

286

(13.7%)

DF 7

(0.5%)

551

(41.8%)

684

(51.9)

75

(5.7%)

1317

(67.1%)

DHF 2

(0.7%)

8

(2.8%)

240

(83.0%)

39

(13.5%)

289

(14.7%)

DSS 0 0 12

(13.6%)

76

(86.4%)

88 (4.5%)

Total 32

(1.6%)

616

(31.4%)

1095

(55.8%)

219

(11.2%)

1962

25

Match and mis-match of the DF/DHF/DSS and the

revised classification systems

• Mismatches

• Independent of laboratory confirmation

• No significant differences in Asia with Latin

America

• Similar at all levels of the health care

system.

• More mismatches at tertiary level.

Asia (N= 1155) Latin America (N= 937)

Clinical

Symptom

n Platelet count

< 100,000

n Platelet count

< 100,000

Petechial

rash

215 193 (89.8%) 322 122 (37.9%)

Mucosal

bleed

238 215 (90.3%) 218 123 (56.4%)

Severe

bleed

17 17 (100%) 12 7 (58.3%)

Shock 64 59 (92.2%) 98 56 (57.1%)

Bleeding and Shock vs Thrombocytopenia

in 2092 prospective dengue patients

27

Conclusions

• Current classification is applied “loosely”.

A strict application leads to a substantial number

being reclassified.

• Application of the revised classification:

identified previously undetected severe cases.

• Both systems of classification: performance was

dependant on the training level of the person

classifying the case.

• A severity-based revised dengue classification

was positively validated in a large number of

countries.

28

Revised ICD – 11 Codes for Revised Dengue Classification (2009)

Dengue Control in Singapore

Dengue Control

Epidemiological

Surveillance of

Human Cases

Vector (Mosquito)

Surveillance &

Control

Regional Meeting-Chiang Rai

Dengue awareness – an innovative effort…

Regional Meeting-Chiang Rai

Programme Interventions

Clinical Management

National Guidelines on clinical management developed;

Diagnostic capacity enhanced and proper clinical management ensured through training of doctors and nurses;

Vector Control

Spot checking for vector density

Role of City Corporations—larvacides/fogging

Community education

Public awareness raising and campaign for reduction of breeding sources

Regional Meeting-Chiang Rai

National Guidelines for Clinical Management

of Dengue/DHF

Features of National Guidelines– Through consensus

– Uniform approach

– Simple and user friendly

– Usable in any setup of resource limitation

• Provide uniform understanding of :

– Case definition

– Structured management outline

– Communication guide

– Reporting

National Guidelines was adopted in 2000 by customizing SEARO Guidelines;

2nd edition in 2009 published

Regional Meeting-Chiang Rai

National control programmeORGANOGRAM

MOHFW

DGHS

Director, Disease Control

Programme Manager Dengue/ DHF

Deputy Programme Manager

City Corporation

(Dhaka, Chittagong, Rajshahi, Khulna, Sylhet, Barisal)

Municipalities ( Districts )

NGOs, Private Hospitals, Clinics

Reporting System

DGHS Control Room

District

Government Hospitals

Private Hospitals & Clinics

City Corporation

Private Practitioners

Others

Regional Meeting-Chiang Rai

Dengue Training for Scouts

Regional Meeting-Chiang Rai

Scouts are visiting houses …

Dengue Control

Activities in Sri Lanka

National Program Objective

Prevention and control of DF/DHF

Specific objectives

Enhance disease surveillance

Proper case management

Integrated vector management

Intersectoral coordination & social mobilization

Outbreak response

Research

1. Enhance disease surveillance

Strengthen early notification at OPD/ wards

Train doctors on standard case definition

Planning to establish 3 peripheral labs to

strengthen laboratory surveillance

Periodic district reviews (in identified high risk

areas)

Data on DF patients

Hospital

MOH District levelRE/ RMO

Coordination

National levelWRCD

Control activities

Control activities

Provision of e mail and internet facilities to

65 high risk MOOH areas to coordinate

control activities promptly

2. Implement integrated vector

management Entomological surveillance by AMC/ AFC/ MRI

Identification of breeding sites

Elimination of mosquito larvae through cleaning

Destroy adult mosquito by space spraying

Leagal enforcement for mosquito control

3. Proper case management

Guidelines and training manuals for training clinicians have been developed by Epidemiology Unit

Training of trainers

Regular training conducted in high risk areas

Conduction of death reviews in order to identify and rectify deficiencies

4. Intersectoral coordination &

social mobilization

Presidential Task Force 25.05.2010 -Members: Ministry of Health, Environment & Central Environment Authority, Local Government & Provincial Councils, Education, Defense, Media and Information, Disaster Management

COMBI training for high risk district teams

Development of district COMBI plans

Development of key messages for key target groups

Monitoring of implementation of COMBI activities

Advocacy - Highest Level

Ministries

• Health

• Local Govt.

• Environment

• Education

• Media

Mobilization of Civil Security Committees

Production of IEC materials

Specific behavioural messages are:

Inspect your premises once a week

Store tyres under cover

Scrub and clean water storage containers once a

week/ keep covered with mosquito proof

coverings

•

Mobilization of community volunteers

Mobilization of school children

5: Outbreak Response

Close monitoring of cases in geographical

regions

Early detection of outbreaks (based on

entomological data and case reporting)

Risk communication

Training of staff, building capacities of hospitals

Declaration of dengue weeks and media seminars

6: Research

Identify research priority areas( Epidemiology

Unit, Universities, RMO, PG trainees) and

mobilization of funds

Vector

Virus

Knowledge and behavior of the community

GENERAL OBJECTIVE OF DENGUE

CONTROL PROGRAM

1. Decreased of morbidity of DHF/Chikungunya cases.

2. Decreased of mortality (CFR) of DHF.

3. Prevention & control of DHF/Chikungunya outbreak.

1. Early diagnosis and prompt treatment

2. Improving epidemiological surveillance and

outbreak response

3. Integrated vector control (Risk factors prevention

and control)

4. Partnerships, capacity building, training and

survey/research

Policies and Programme

Larva checking by school

children

HOUSE VISITING

BY JUMANTIK (LARVA INSPECTOR)

LARVAE INSPECTION BY JUMANTIK

Checking of all

potential breeding

places such as

plastic barrels,

flower vase,

drinking container

for pet.

LARVAL INSPECTOR CADRES SHOWING SOURCE REDUCTION

KIT - 30 MINUTES EVERY FRIDAY AT 9.00 - 9.30AM IN

JAKARTA.

plus

3MLarviciding

Predator fish Mosquito insecticides

and repellants

Lighting and

ventilation

screen

POLITICAL SUPPORT FROM

HIGHEST LEVEL EXECUTIVE,

PRESIDENT OF INDONESIA

MINISTRY REGULATION:

• Decree from Health Minister about source reduction coordinated through working groups is effective way to prevent DF.

• Decree letter from Internal Affairs Minister about DF Control in Region through Source reduction activities.

”TOGETHER WE CAN”

1. Case fatality is still high in several districts

2. Increasing trends of dengue and CHK cases

3. Inadequate of surveillance

4. Low community and inter-sectoral participation

5. Increasing risk factors

6. Inadequate funds

Problem of DHF/Chikungunya

Control Programme

Future Plan (1)

1. Legislation

Review and develop existing legislation on DHF

control.

2. Strengthening collaboration/partnerships

3. Strengthening surveillance

• Update surveillance and response guidelines

• Training for surveillance staff in PHC and

District/Prov Health services

Future Plan (2)

4. Response

• Establish and training rapid response team in

sub dustrict/district level.

• Develop the cadre to check vector breeding

places.

5. Case management

• Revise case management guidelines and its

implementation

Future Plan (3)

• Implementation of new criteria of DHF cases trial in

hospitals.

• Develop early detection with RDT for DHF.

• Training of case management of DHF for MD in

PHC.

6. Laboratory

• Develop the capacity of lab diagnostic in provinces

• Develop surveillance based lab on Chik/DHF

Future Plan (4)

7. Communication using COMBI approach