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

Transcription

1 The 2009 WHO dengue case classification: Evidence for its development and its application Dengue case classification by severity Dengue ± warning signs Severe dengue Without with warning signs 1.Severe plasma leakage 2.Severe haemorrhage 3.Severe organ impairment 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 (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 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 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 Olaf.Horstick@uni-heidelberg.de Seite 1

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

3 Dengue case classification by severity Dengue ± warning signs Severe dengue Without with warning signs 1.Severe plasma leakage 2.Severe haemorrhage 3.Severe organ impairment 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 (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 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

4 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 Usefulness Strength Towards severity of disease and early detection of severe cases Especially for clinical management, but also for improved surveillance Inclusion of all severe clinical pictures of dengue Helpful for clinical management without laboratory facilities No relation to severity (especially DHF) ICD ICD 11 Previous ICDs Outlook Further studies soon available on warning signs and case definitions

5 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 Dengue case classification by severity Dengue ± warning signs Severe dengue 3. Conclusions 4. Questions/Discussion Without 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 (important when no sign of plasma leakage) with warning signs Criteria for dengue ± warning signs 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 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

6 The context: From science to practice and viceversa, with the best available evidence Technical handbook: surveillance, dengue outbreak prediction/ detection/ response Standardised dengue course material Dengue case classification by severity Dengue ± warning signs Severe dengue with 1.Severe plasma leakage Without warning signs 2.Severe haemorrhage 3.Severe organ impairment Criteria for dengue ± warning signs Criteria for severe dengue Probable dengue Warning signs* 1. Severe plasma leakage Live in/travel to dengue Abdominal pain or leading to: endemic area. Fever and 2 tenderness Shock (DSS) of the following criteria: Persistent vomiting Fluid accumulation with Nausea, vomiting Clinical fluid accumulation respiratory distress Rash Mucosal bleed Aches and pains Lethargy; restlessness 2. Severe bleeding Tourniquet test positive Liver enlargement >2cm as evaluated by clinician Leucopenia Laboratory: Increase in HCT 3. Severe organ involvement Any warning sign concurrent with rapid Liver: AST or ALT>=1000 Laboratory confirmed decrease in platelet count CNS: Impaired dengue (important when no sign of plasma * Requiring strict observation consciousness leakage) and medical intervention Heart and other organs WHO/TDR 2009 Technical handbook for dengue vector control

7 Evidence for the development: The DenCo study

8 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

9 Evidence for the development: case numbers The DenCo study

10 The DenCo study Evidence for the development:

11 Evidence in the development: the DenCo study: Alexander et al.

12 Evidence used for the development of the WHO 2009 dengue case classifcation: An expert consensus four regional meetings, followed by one global meeting

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

14 The full model: Dengue case classification by severity Dengue ± warning signs Severe dengue Without with warning signs 1.Severe plasma leakage 2.Severe haemorrhage 3.Severe organ impairment 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 (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 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

15 The full model and practical applications: A model dengue case management algorithm (may need adaptation to local settings)

16 Evidence for the development:

17 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

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

19 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

20 Evidence found for or against the use of the WHO 2009 case classification in the systematic review

21 Descriptive analysis of the studies found:

22 Studies analysing sensitivity/specificity of dengue/severe dengue

23 Studies analysing warning signs

24 Studies analysing triage

25 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

26 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

27 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)

28 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,

29 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.

30 The expert consensus meeting in PAHO 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.

31 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 Usefulness Strength Towards severity of disease and early detection of severe cases Especially for clinical management, but also for improved surveillance Inclusion of all severe clinical pictures of dengue Helpful for clinical management without laboratory facilities No relation to severity (especially DHF) ICD ICD 11 Previous ICDs Outlook Further studies soon available on warning signs and case definitions

32 Many thanks for your questions And many, many thanks for not asking any!