“the 2009 who dengue case classification: evidence for its...

16.03.2015 Seite 1

“The 2009 WHO dengue case classification: Evidence for its development and its application”

Dr Olaf Horstick, FFPH(UK), PhD(D), MSc, MPH, DTM&P, MD(D)

Director of the Teaching Unit

University Hospital Heidelberg, Institute of Public Health, Germany

[email protected] www.klinikum.uni-heidelberg.de/who-we-are

Dengue case classification by severity

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warning signs1.Severe plasma leakage 2.Severe haemorrhage3.Severe organ impairment

Severe dengueDengue ± warning signs

Probable dengueLive in/travel to dengue endemic area. Fever and 2 of the following criteria:• Nausea, vomiting• Rash• Aches and pains• Tourniquet test positive• Leucopenia• Any warning signLaboratory confirmed dengue(important when no sign of plasma leakage)

Warning signs*• Abdominal pain or tenderness• Persistent vomiting• Clinical fluid accumulation• Mucosal bleed• Lethargy; restlessness• Liver enlargement >2cm• Laboratory: Increase in HCT concurrent with rapid decrease in platelet count

* Requiring strict observation and medical intervention

1. Severe plasma leakageleading to:• Shock (DSS)• Fluid accumulation with

respiratory distress

2. Severe bleedingas evaluated by clinician

3. Severe organ involvement• Liver: AST or ALT>=1000 • CNS: Impaired consciousness • Heart and other organs

Criteria for dengue ± warning signs Criteria for severe dengue

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Firstly many thanks for the invitation: but firstly greetings from Heidelberg,..


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WHO 2009 DCC WHO 1997 DCC

Development Series of studies, both quantitative and qualitative

Expert consensus

Validation Tested in many different countries No validation process

Focus Towards severity of disease and early detection of severe cases

No relation to severity (especially DHF)

Usefulness Especially for clinical management, but also for improved surveillance

Strength Inclusion of all severe clinical pictures of dengue Helpful for clinical management without laboratory facilities

ICD ICD 11 Previous ICDs

Outlook Further studies soon available on warning signs and case definitions

Content of this session 1. Evidence used for the development of the WHO 2009

dengue case classification – compared to the WHO 1997 dengue case classification

2. Evidence of the application

3. Conclusions

4. Questions/Discussion


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The context: From science to

practice and vice-versa, with the best available evidence

Standardised dengue course material

Technical handbook: surveillance, dengue outbreak prediction/ detection/ response

Technical handbook for dengue vector control


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Evidence for the development:

The DenCo study

Evidence for the development: Methods

The DenCo study

- Prospective hospital based multicentre study - Local centres of excellence - Broad spectrum of patients, recruited early and followed daily with a detailed case report form - Hct and platelets done at least daily - Other tests (e.g. liver & renal function) done at least twice during acute illness - X-ray and/or ultrasound on hospitalised patients within 24h of defervescence - WHO trained monitoring according to GCP

Evidence for the development: case numbers

The DenCo study


The DenCo study

Evidence in the development: the DenCo study:

Alexander et al.

Evidence used for the development of the WHO 2009 dengue case classifcation:

An expert consensus – four regional meetings, followed by one global meeting

Evidence used for the 2009 WHO dengue case classification: the global expert meeting

The full model:


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The full model and practical applications:

A model dengue case

management algorithm

(may need adaptation to local settings)

Evidence used for the development of the 2009 WHO dengue case classification:

The analysis has shown that the revised dengue case classification is better able to - standardise clinical management - raise awareness about unnecessary interventions - match patient categories with specific treatment instructions

- make the key messages of patient management understandable for all health care staff

The WHO 2009 dengue case classification: Evidence of its use in a systematic review

Methods: systematic review 1. A systematic search covering all relevant studies for a given research question 2. A systematic analysis, following a clearly defined analytical concept - Unlike meta-analysis capable of integrating quantitative and qualitative data - Never a single expert opinion, but a consensus between several experts - Resulting in practical recommendations, linking research and practice

Evidence found for or against the use of the WHO 2009 case classification

in the systematic review

Descriptive analysis of the studies found:

Studies analysing sensitivity/specificity of dengue/severe dengue

Studies analysing warning signs

Studies analysing triage

Conclusions of the 12 studies - D/SD defines clearly severity of disease, thus helping clinical

decision-making/contributing to reducing mortality - Local adaptation of hospitalisation criteria may be necessary to

not increase workloads - Diagnosis of dengue with clinical parameter only continues to be

difficult, it is recommended to await the evidence of the currently ongoing large clinical trials to modify the case definitions and the warning signs

- It is recommendable to study the performance of D/SD for triage, especially in outbreak situations

- For epidemiology and global data collection, a unified system would be the biggest advantage

- For other research, D/SD may open new opportunities with a fresh look at underlying pathology, now that the spectrum of disease is better described

The expert consensus meeting in PAHO A two-days side event at the bi-annual dengue course at

the Instituto Pedro Kuori in La Habana, Cuba

Methods: A two day expert consensus meeting in La Habana/Cuba aimed to 1) share experiences from PAHO member states applying D/SD, 2) present national/local data using D/SD, 3) agree - with a formal consensus group - on recommendations for or against using D/SD Using a formal expert consensus exercise (nominal group technique)

The expert consensus meeting in PAHO

Eight key questions were discussed, concluding: 1) D/SD is useful describing disease progression because it considers the dynamic nature of the disease 2) D/SD helps defining dengue cases correctly for clinical studies, because it defines more precisely disease severity and allows evaluating dynamically the progression of cases, 3) D/SD describes correctly all clinical forms of severe dengue. Further standards need to be developed regionally, especially related to severe organ involvement, 4) D/SD allows for pathophysiological research identifying - in a sequential manner - the clinical manifestations of dengue related to pathophysiological events, 5) the warning signs help identifying early cases at risk of shock (children and adults) pathophysiology of the warning signs deserves further studies, 6) D/SD helps treating individual dengue cases and also the re-organisation of health care services for outbreak management, 7) D/SD helps diagnosing dengue, in presumptive diagnosis and following-up of the disease, because of its high sensitivity and high negative predictive value,


Eight key questions were discussed, concluding: (continued) 8) There is currently no update of the International Disease Classification10 (ICD10) to include the new classification of dengue (D/SD), therefore there are not enough experiences of epidemiological reporting. Once D/SD has been implemented in epidemiological surveillance, D/SD allows to 1) identify severity of dengue cases in real time, for any decision-making on actions, 2) measure and compare morbidity and mortality in countries, but also globally and 3) trigger contingency plans early, not only based on the number of reported cases, but also on the reported severity of cases.


Conclusion: The expert panel recommends to 1) update ICD10, 2) 2) include D/SD in country epidemiological reports, 3) 3) implement studies improving sensitivity/specificity of the 4) dengue case definition.

WHO 2009 DCC WHO 1997 DCC

Development Series of studies, both quantitative and qualitative

Expert consensus

Validation Tested in many different countries No validation process

Focus Towards severity of disease and early detection of severe cases

No relation to severity (especially DHF)

Usefulness Especially for clinical management, but also for improved surveillance

Strength Inclusion of all severe clinical pictures of dengue Helpful for clinical management without laboratory facilities

ICD ICD 11 Previous ICDs

Outlook Further studies soon available on warning signs and case definitions

Many thanks for your questions

And many, many thanks for not asking any!

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