“The 2009 WHO dengue case classification:
Evidence for its development and its application”
Dengue case classification by severity
Without
with
warning signs
Criteria for dengue ± warning signs
Probable dengue
Live 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 sign
Laboratory confirmed
dengue
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
(important when no sign of plasma
leakage)
* Requiring strict observation
and medical intervention
Severe dengue
1.Severe plasma leakage
2.Severe haemorrhage
3.Severe organ impairment
Criteria for severe dengue
1. Severe plasma leakage
leading to:
• Shock (DSS)
• Fluid accumulation with
respiratory distress
2. Severe bleeding
as evaluated by clinician
3. Severe organ involvement
• Liver: AST or ALT>=1000
• CNS: Impaired
consciousness
• Heart and other organs
WHO/TDR 2009
Dengue ± warning signs
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
16.03.2015
Seite 1
Firstly many thanks for the invitation:
but firstly greetings from Heidelberg,..
Dengue case classification by severity
Without
with
warning signs
Criteria for dengue ± warning signs
Probable dengue
Live 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 sign
Laboratory confirmed
dengue
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
(important when no sign of plasma
leakage)
* Requiring strict observation
and medical intervention
Severe dengue
1.Severe plasma leakage
2.Severe haemorrhage
3.Severe organ impairment
Criteria for severe dengue
1. Severe plasma leakage
leading to:
• Shock (DSS)
• Fluid accumulation with
respiratory distress
2. Severe bleeding
as evaluated by clinician
3. Severe organ involvement
• Liver: AST or ALT>=1000
• CNS: Impaired
consciousness
• Heart and other organs
WHO/TDR 2009
Dengue ± warning signs
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
Outlook
Further studies soon available on
warning signs and case definitions
Previous ICDs
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
Dengue case classification by severity
Dengue ± warning signs
Without
3. Conclusions
4. Questions/Discussion
with
warning signs
Criteria for dengue ± warning signs
Probable dengue
Live 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 sign
Laboratory confirmed
dengue
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
(important when no sign of plasma
leakage)
* Requiring strict observation
and medical intervention
Severe dengue
1.Severe plasma leakage
2.Severe haemorrhage
3.Severe organ impairment
Criteria for severe dengue
1. Severe plasma leakage
leading to:
• Shock (DSS)
• Fluid accumulation with
respiratory distress
2. Severe bleeding
as evaluated by clinician
3. Severe organ involvement
• Liver: AST or ALT>=1000
• CNS: Impaired
consciousness
• Heart and other organs
WHO/TDR 2009
2. Evidence of the application
The context:
From science to
practice and viceversa, with the best
available evidence
Standardised
dengue
course
material
Technical
handbook:
surveillance,
dengue
outbreak
prediction/
detection/
response
Dengue case classification by severity
Without
with
warning signs
Criteria for dengue ± warning signs
Probable dengue
Live 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 sign
Laboratory confirmed
dengue
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
(important when no sign of plasma
leakage)
* Requiring strict observation
and medical intervention
Severe dengue
1.Severe plasma leakage
2.Severe haemorrhage
3.Severe organ impairment
Criteria for severe dengue
1. Severe plasma leakage
leading to:
• Shock (DSS)
• Fluid accumulation with
respiratory distress
2. Severe bleeding
as evaluated by clinician
3. Severe organ involvement
• Liver: AST or ALT>=1000
• CNS: Impaired
consciousness
• Heart and other organs
WHO/TDR 2009
Dengue ± warning signs
Technical
handbook
for dengue
vector
control
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
Evidence for the development:
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:
Dengue case classification by severity
Without
with
warning signs
Criteria for dengue ± warning signs
Probable dengue
Live 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 sign
Laboratory confirmed
dengue
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
(important when no sign of plasma
leakage)
* Requiring strict observation
and medical intervention
Severe dengue
1.Severe plasma leakage
2.Severe haemorrhage
3.Severe organ impairment
Criteria for severe dengue
1. Severe plasma leakage
leading to:
• Shock (DSS)
• Fluid accumulation with
respiratory distress
2. Severe bleeding
as evaluated by clinician
3. Severe organ involvement
• Liver: AST or ALT>=1000
• CNS: Impaired
consciousness
• Heart and other organs
WHO/TDR 2009
Dengue ± warning signs
The full model and
practical applications:
A model dengue case
management
algorithm
(may need adaptation to
local settings)
Evidence for the development:
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
understandable for all health care staff
patient
management
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,
The expert consensus meeting in PAHO
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.
The expert consensus meeting in PAHO
Conclusion: The expert panel recommends to
1)
2)
3)
4)
update ICD10,
2) include D/SD in country epidemiological reports,
3) implement studies improving sensitivity/specificity of the
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
Outlook
Further studies soon available on
warning signs and case definitions
Previous ICDs
Many thanks for your questions
And many, many thanks for not
asking any!