1. W HAT ` S N EW IN DHF: C LINICAL ASPECT Professor Siripen Kalayanarooj, Director, WHO Collaborating Centre for Case Management of Dengue/DHF/DSS, Queen Sirikit National Institute of Child Health.

2. 1. A DULTS IS MORE AFFECTED THAN C HILDREN

3. 2. Expanded Dengue Syndrome or Unusual Manifestations of Dengue Infant < 1 year old Commonly found in adults In newly outbreak countries In endemic countries where there are limited laboratory facilities

4. E XPANDED D ENGUE S YNDROME (EDS) Encephalopathy: confusion, seizure, coma Liver failure Renal failure Cardiac involvement: myocarditis Other organs involvement

5. C AUSES OF EDS Prolonged shock: Liver, renal, respiratory and other organs (unrecognized at the very beginning) Dengue infections in patients with underlying diseases: DM, HT, Heart diseases, Thalassemia, Liver and renal diseases, etc… Co-infections with other microbial agents: Dengue virus virulence: encephalitis, liver failure

6. C LINICAL MANIFESTATIONS OF EDS Mostly manifestations of DHF + Complications Underlying diseases Co-infections

7. C LUES TO DIAGNOSE EDS Detection of plasma leakage (early when the patients present to the healthcare facilities): Rising Hct ≥ 20% Pleural effusion: clinical, CXR – right lateral decubitus, ultrasound Ascites: clinical, ultrasound Hypoalbuminemia: serum albumin ≤ 3.5 gm% in normal nutritional status Other evidence of DHF: Thrombocytopenia especially when platelet count < 50,000 cells/cumm. Clinical bleeding

8. CXR – COMPARE BETWEEN 2 POSITIONS

9. E ARLY CLINICAL DIAGNOSIS & M ANAGEMENT Suspected EDS in patients with thrombocytopenia (platelet count ≤ 100,000 cells/cumm.) or clinical bleeding or shock with high fever (probably with encephalopathy) Look for evidence of plasma leakage, if positive more likely to have DHF with complication: 1. DHF with superimposed bacterial infections 2. DHF with liver injury: hepatitis, liver dysfunction/ failure 3. DHF with concealed internal bleeding (mostly GI bleed)

10. 3. D ENGUE C LASSIFICATIONS 1975, 1986, 1997, 20112009

11. D ENGUE C LASSIFICATION WHO 1975, 1986,1997, 2011 Undifferentiated febrile illness Dengue Fever (DF) Dengue hemorrhagic fever (DHF) Dengue Shock Syndrome (DSS) Expanded Dengue Syndrome (EDS) WHO TDR 2009 Dengue (D) Dengue ± Warning signs (D ± WS) Severe Dengue (SD) Original WHO Newly suggested

12. Asymptomatic Symptomatic Viral syndrome Dengue fever DHF Dengue virus infection Plasma leakage 100 400500 1,000 9,000 1-2 10,000 Expanded dengue syndrome 1.Prolonged shock: liver failure, renal failure,…Encephalopathy… 2.Co-morbidities 3. Co-infections 4. True dengue infection - encephalitis DHF DSS

14. S USPECTED DENGUE INFECTIONS : F EVER WITH ANY 2 OF THE FOLLOWINGS IN DENGUE ENDEMIC AREA Headache Retro-orbital pain Myalgia Arthralgia/ bone pain Rash Bleeding manifestations (Tourniquet positive) Leukopenia Rising Hct 10-15% Platelet ≤ 150,000 cels/cumm Nausea/ vomiting Rash Aches and pain Tourniquet positive Leukopenia Any warning signs Original WHOSuggested New Tourniquet positive + Leukopenia

15. AT QSNICH OPD: S USPECTED DENGUE CASES THAT NEED CLOSE OBSERVATION Tourniquet positive + Leukopenia 1,500 cases Warning signs: nausea/vomiting and abdominal pain 30,000+ cases (20 times more workload) Original Newly suggested

16. QSNICH: IPD (J UNE – A UGUST 2009) Confirmed dengue DFDHF + DSSDengueD with WS + SD 18072 + 2285160 + 29 180 94 85 189 Non- Dengue DFDHF + DSSDengueD with WS + SD 195 + 01013 + 1 19 5 10 14 Total clinical suspected dengue cases DFDHF + DSSDengueD with WS + SD 199 99 95 203 Confirmed = 274/298 = 91.9% Kalayanarooj S. J Med Assoc Thai 2011; 94(3); s74-83.

17. D IFFERENT BETWEEN THE TWO CLASSIFICATIONS Emphasize on plasma leakage* and abnormal hemostasis (platelet count ≤ 100,000 cells/cumm) : Rising Hct ≥ 20% Pleural effusion: PE, CXR (right lateral decubitus, ultrasound) Ascites: PE, ultrasound Hypoalbuminemia (Alb ≤ 3.5 gm%) Emphasize on warning signs* : Abdominal pain or tenderness Persistent vomiting Clinical fluid accumulation Mucosal bleed Lethargy, restlessness Liver > 2 cm Lab.: increase in Hct concurrent with rapid decrease in Platelet count Original WHOSuggested New *Need close monitoring

18. Day 1 2 3 4 5 6 7 8 9 Fever WBCWBC WBC 6,000-9,000 ≤5,000 Platelet count 200,000 ≤100,000 <50,000 Hct 35 38 45 (rising 20%) Albumin ≤3.5 gm% Cholesterol ≤100 mg% Hematocrit Plasma leakageStop leakage Pleural effusion, Ascites Reabsorption Shock IV fluid: NSS, DAR, DLR Colloid: 10%Dextran, 10%Haes-steril M+5% Deficit (= 4,600 ml in adult) Natural course of DHF Professor Siripen Kalayanarooj

19. E ARLY DIAGNOSIS BY CBC: G UIDE FOR MANAGEMENT DateHCTWBCPLT Day 2416,500160,000 Day 3434,200143,000 Day 4472,30090,000 Day 53970,000 A 20-year-old woman Good consciousness AST/AL:T = 62/59 BP = 90/70 mmHg, P 118/min

20. C OMPARE BETWEEN 2 CLASSIFICATIONS Follow up platelet and frequent Hct (at least q 6 hours) at critical period Can prevent shock and severe cases with complications of organs failure Follow warning signs which are non-specific Shock cannot be prevented. Organs failure as a consequence of prolonged shock are detected late with overt manifestations and poor prognosis Plasma leakage Warning signs

21. L AHORE E XPERIENCED (S EP.-N OV. 11) Total suspected cases : 600,000+ cases Confirmed 20,000 cases (< 4%) At the peak: 4,000-6,000 patients/day Admission 500-600 cases/day Death 10-15 cases per day

22. M ULTI - COUNTRY STUDY : 18 COUNTRIES V ALIDATION STUDY OF THE NEWLY SUGGESTED CLASSIFICATION Revised not classified Dengue without Warning Signs Dengue With Warning Signs Severe dengue Total Not classify 235715929268 DF7551684751,317 DHF2824039289 DSS00127688 Total326161,0952191,962 Barniol J et al: BMC Infectious Disease 2011,11: 106

23. O RIGINAL AND N EWLY SUGGESTED WHO C LASSIFICATION FOR D ENGUE S EVERITY : 2005-2010 ( TOTAL 494 PATIENTS ) Narvaez F et al: PlosNTD 2011, 5: e1397. DHF+DSS = 152 patients DW+SD = 467 patients

24. A DVANTAGES Proven in reducing CFR Can prevent shock so less severe cases and less complications No need for confirmed dengue laboratories (PCR, NS1Ag, IgM/IgG tests): diagnosis DHF/DSS by clinical criteria correct > 90% Easy and friendly use Use only clinical especially warning signs. No need for any laboratory tests to follow up: CBC Increase number of cases report so may be more effective control? Original WHO Suggested new

25. D ISADVANTAGES Need follow up of laboratory test especially CBC and frequent Hct monitoring Need close monitoring especially during 24- 48 hours of critical period of plasma leakage More workload to healthcare personnel, at least 20 times at OPD and 2 times for IPD More complication of fluid overload (admit and observe early with IV fluid infusion) More severe cases with EDS Need dengue confirm labs. except those with shock, with complication of fluid overload Increase in CFR Original WHO Suggested new

26. 4. IV FLUID MANAGEMENT IN SHOCK CASES 10 ml/kg/hr in children or 300-500 ml/hr in adult 20 ml/kg in 20 mins. and can repeat another 2 times Original WHO Newly suggested

27. 4. IV FLUID MANAGEMENT IN NON - SHOCK ( COMPENSATED SHOCK ) CASES 1.5 ml/kg/hr in children or M/2 in early and adjust rate accordingly to clinical, vital signs, Hct and urine output 5-7 ml/kg/hr Original WHO Newly suggested

28. 4. O THERS MANAGEMENT Colloidal solution: only plasma expander (hyper-oncotic) - 10% Dextran-40 in NSS No platelet prophylaxis except in adults with underlying HT and Plt < 10,000 cells/cumm. Any colloidal solution including FFP Platelet prophylaxis Original WHO Newly suggested

29. H OTLINE DHF: 089-2045522 – M.D. 089-2042255 – GN. SIRIPENK @ GMAIL. COM

30. Thank you !!!