Dengue Hemorrhagic Fever Management

Recognition of DengueFever/Dengue Haemorrhagic Fever (DF/DHF) Dengue Fever - an acute febrile illness of 2-7 days duration (sometimes with two peaks) with two or more of the following manifestations: headache Retro-orbital pain myalgia / arthralgia rash leukopenia Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999

Dengue Hemorrhagic Fever (DHF) - a severe case of dengue with hemorrhagic tendency evidenced by: Positive tourniquet test Petechiae, ecchymosis or purpura Bleeding from mucosa (epistaxis or bleeding from gums), injection sites or other sites Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999

Tourniquet Test AKA: Rumpel-Leede Capillary-Fragility Test determines capillary fragility. bp cuff is inflated to a point between the systolic and diastolic bp for 5min. (+): 10 or more petechiae per square inch. In DHF the test usually gives a definite positive result with 20 petechiae or more

Hematemesis or melena Thrombocytopenia ( ≤ 100,000/cu.mm ) Evidence of plasma leakage manifested by: – A >20% rise in hematocrit for age and sex – A >20% drop in hematocrit following treatment with fluids as compared to baseline – Signs of plasma leakage (pleural effusion, ascites or hypoproteinemia ) Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999

Dengue Shock Syndrome (DSS) - All the above criteria of DHF plus signs of circulatory failure manifested by the ff: rapid and weak pulse narrow pulse pressure (</= to 20mm Hg) hypotension for age cold and clammy skin Restlessness  or absent urine Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999

Grading the Severity of Dengue Infection Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999 DF / DHF Grade Symptoms Labs DF Fever with two or more of the ff: headache, retro-orbital pain, myalgia, arthralgia Leukopenia Thrombocytopenia < 100,000 No evidence of plasma loss DHF I Above signs plus positive tourniquet test Thrombocytopenia <100,000 Hct rise >20% DHF II Above signs plus spontaneous bleeding Thrombocytopenia <100,000 Hct rise >20% DHF III Above signs plus circulatory failure (weak pulse, hypotension restlessness) Thrombocytopenia <100,000 Hct rise >20% DHF IV Profound shock with undetectable blood pressure and pulse Thrombocytopenia <100,000 Hct rise >20%

Criteria For Hospitalization General Condition Continuous fever ≥ 3 days Lethargy Restlessness Generalized Flushing Excessive tiredness Poor appetite Dehydration Unable to tolerate orally / vomiting Diarrhea / frequent loose stools Abdominal Discomfort Right hypochondrium/epigastric pain Tender hepatomegaly Plasma leakage manifested by: Rapid rising hematocrit Hematocrit =/ ≥ 20% of baseline Pleural Effusion, ascites

Criteria For Hospitalization Hemorrhagic manifestations (+) tourniquet test Petechiae, ecchymoses, purpura Spontaneous mucosal bleeding Hematemesis, melena, hematochezia, thrombocytopenia Patients w/ bleeding regardless of platelet count W/out bleeding but platelet count is on rapid down trend Platelet count < 100,000/mm 3 Evidence of circulatory failure/shock as manifested by: Rapid & weak pulse Diminished peripheral pulses Narrowing of pulse pressure Hypotension for age Cool, mottled or pale skin Oliguria Tachypnea ( due to metabolic acidosis Changes in mental status, lethargy, restlessness

GENERAL MANAGEMENT OF DENGUE 1.) Rest 2.) Antipyretic Do not give Aspirin or Ibuprofen 3.) Oral rehydration therapy 4.) Food according to appetite Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999

Treatment Of Dengue with hemorrhage & shock 1.) Supportive measures 2.) Fluid Resuscitation Crystalloids vs Colloids 3.) Blood Component Therapy Packed Red Blood Cells Fresh Frozen Plasma / Cryoprecipitate Platelet concentrate 4.) Oxygen therapy 5.) Others Inotropes - Dopamine,Dobutamine, Epinephrine, Norepinephrine,Milrinone

CRYSTALLOIDS vs. COLLOIDS FLUID RESUSCITATION

Fluids Required for Intravenous Therapy Crystalloids Plain/ 5% dextrose in isotonic normal saline solution (NSS) Plain/5%dextrose in half-strength normal saline solution (O.45 %NaCl) Plain/5% dextrose in lactated Ringer’s solution (LRS) Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999

Fluids Required for Intravenous Therapy Colloids Dextran Hydroxyethyl starch Gelatin solutions Plasma Albumin

Theoretically, colloid solutions offer advantages over crystalloid solutions for emergency resuscitation: 1.) Immediate distribution of colloids within the intra vascular compartment 2.) Colloid molecules increase plasma oncotic pressure thereby altering the balance of fluid flux across the endothelium and drawing fluid back into the intra vascular compartment

DRAWBACK IN THE USE OF COLLOIDS: Colloids may leak into the interstitium and exert a reverse osmotic effect, drawing out intravascular fluid & worsening the shock Risk in developing acute renal failure Potential for allergic reactions Adverse effects on blood coagulation Expensive & not readily available

Advantages of Crystalloids: Cheap & Readily available Generally safe Reaction free

Studies on the Different Fluid Regimen in the Initial Resuscitation of DSS 1.) Fluid Replacement in DSS: A Randomized, Double Blind Comparison of the Four Intravenous Fluid Regimen by: Dung NM, Day NPJ, et al Clinical Infectious Disease, 1999: 29: 787 – 795 2.) Acute Management of DSS: A Randomized, Double Blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213 3.) Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B et al New England Journal Of Medicine, Sept 2005: 353, No 9: 877-889

The study aims to compare the efficacy of 4 fluid regimens in the initial resuscitation of DSS in children: Dextran Gelatin solution Lactated Ringers Normal Saline Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213

Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213 230 Vietnamese children with DSS admitted at the ICU of Dong Nai Pediatric Hospital, Bien Hoa, Dong Nai Province, Southern Vietnam Sept 1996 – Sept 1997 were included in the study

Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213 Results Ringers Lactate performed the least well due to the following reasons : Recovery times were longer Initial therapy was considered a failure Dextran was more likely to be required for treatment of the initial episode of shock Has greater # of children w/ profound shock

O.9% saline may be the crystalloid fluid of choice for resuscitation of the majority of patients with DSS Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213

The plasma volume – expanding capacity of the 2 crystalloid solutions is related to its sodium concentration: Normal Saline – 154 m M Lactated Ringers – 130 m M Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213

Conclusion The study is unable to demonstrate a clear benefit of any 1 of the 4 fluids in the treatment of children with DHF 111 For the majority of patients w/ less severe disease, the type of fluid used for resuscitation may not matter In more severely-ill patients , early treatment with colloids improve outcome Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213

383 Vietnamese children with moderately severe shock were randomly assigned to receive Ringer's lactate, 6 % dextran 70 (a colloid), or 6 % hydroxyethyl starch (a colloid) 129 Vietnamese children with severe shock were randomly assigned to receive one of the colloids 6 % dextran 70 or 6 % hydroxyethyl starch Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353, No 9:877-889

Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889 Results No significant difference among the fluids in terms of overall proportion of children requiring rescue colloid in either severity group Children in group 1 who received Ringer's lactate for primary resuscitation took longer to achieve initial cardiovascular stability than patients receiving either of the colloids

Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353, No 9:877-889 Results The time to final cardiovascular stability was not different among the fluid-treatment group No difference in either severity group in the requirement for colloid subsequent to the initial episode of shock, in the volume of rescue colloid or total parenteral fluid administered, in the final recovery times or in the number of days in the hospital

Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889 Results No significant differences in any adverse effects of the various fluid treatments except in the incidence of allergic type reactions No difference among the fluid treatment groups in the development of new bleeding manifestations, clinical fluid overload, objective measures of the over-all severity of vascular leakage or the use of furosemide

Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889 Conclusion: Most children with dengue shock syndrome respond well to judicious treatment with isotonic crystalloid solutions The cheapest and safest choice, Ringer's lactate , is as effective as either of the colloids for initial resuscitation of children with moderately severe shock Early intervention with colloid solutions is not indicated

Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889 Conclusion: The fluid regimen of Ringer's lactate at 25 ml / kg over a period of two hours is now supported by strong prospective evidence and should be recommended for children with moderately severe shock

Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353, No 9: 877-889 Conclusion: For those with severe shock , the situation is less clear-cut, and clinicians must continue to rely on personal experience, familiarity with particular products, local availability, and cost.

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 Compared the following outcomes of children w/ DSS using the standard WHO therapy vs instituted protocol for aggressive management: duration of ventilation ICU stay incidence of ARDS ICU & hospital mortality

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 114 patients admitted at the Kanchi Kamakoti Childs Trust Hospital in South India between July 1997 and December 1999 received WHO standard therapy 96 patients admitted at the Kanchi Kamakoti Childs Trust Hospital in South India between January 2000 and December 2001 received the instituted protocol for aggressive management

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 The 1st group ( W Group ): Included patients who received standard WHO-prescribed therapy Received volume resuscitation w/ isotonic fluids such as LR or Normal saline followed by colloids

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 The 2nd group or Treatment Protocol (P Group): Included patients who received other therapies in addition to the standard WHO-prescribed therapy Additional intervention employed in the P group: Use of Controlled Fluid Removal Therapy in patients w/ deterioration in respiratory function using : 1.) low dose Furosemide infusion ( FI ) 2.) Peritoneal dialysis ( PD )

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 Controlled fluid removal therapy employed in the P group was used in selected patients who developed substantial deterioration in respiratory function: Tachypnea Grunting Increased oxygen requirement Need for assisted ventilation Generalized pulmonary edema Serum albumin of <3.0 g% after restoration of normovolemia

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 1.) Low dose Furosemide infusion ( FI ) Preferred treatment in hemodynamically stable patients Used at 0.05-0.4 mg/kg/hr and titrated to maintain a urine output of 2-5 mL/kg/hr In the event of systemic hypoperfusion, the rate of fluid resuscitation was increased and FI was temporarily withheld

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 FAILURE OF FUROSEMIDE INFUSION: IF URINE OUTPUT DID NOT INCREASE TO 2 ML/KG/ HR DESPITE A MAXIMUM DOSE 0.4MG/KG/HR IF THE PATIENT EXPERIENCED FREQUENT EPISODES OF HEMODYNAMIC INSTABILITY ACUTE INTERMITTENT PERITONEAL DIALYSIS

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 Results: The duration of ventilation & mean length of ICU stay were significantly longer in the P group The need for ventilation and incidence of ARDS were not significantly different in the 2 groups

Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 W group P group Mean time of death (days) 1.4 4.5 Mortality Rate 22% 7% # of patients dying within 24 hours of admission to the ICU 13 out of 19 2 out 6 Causes of death 7 - Refractory shock 10 - MODS (ARDS and DIC) 2 - Fulminant hepatic failure 5 – Refractory shock 1 - Fulminant hepatic failure

Indications For Blood Products in Dengue Infection 1. ) PRBC - for volume depletion from massive bleeding 2.) Platelet concentrate – generally avoided unless: significant / massive bleeding regardless of PC PC < 10,000/mm 3 with impending /established CNS bleed or continuous bleeding from a pre – existing peptic ulcer 3.) FFP -for patients where coagulopathy causes massive bleeding

Protrombin & Partial Thromboplastin Time as a Predictor of Bleeding in Patients w/ patients with DHF Chua MN, Molanida R, et al South East Asian Journal Tropical Medicine & Public Health,1993; 24(1): 141-143

Protrombin & Partial Thromboplastin Time as a Predictor of Bleeding in Patients w/ patients with DHF Chua MN, Molanida R, et al South East Asian Journal Tropical Medicine & Public Health,1993; 24(1): 141-143 Conclusion: PTT can be an index in predicting bleeding in DHF. The tendency to bleed is greater with prolongation of > 30 seconds Platelet count can be a predictor of mortality, with death six times greater among those platelet count < 50,000/microliters than those whose platelet count was > 50,000/microliters PT can also predict bleeding in patients with DHF

Preventive transfusion in Dengue shock syndrome- is it necessary? Lum LC, Abdel-Latif Mel A, Goh AY. Chan PW, Lam SK (2003). J Pediatr, 143(5), Sep, pp 682-4 Preventive transfusion with platelet concentrates and FFP a in non-bleeding or fluid responsive DHF/DSS has not been shown to sustain the increase in platelet counts, prothrombin time or partial prothrombin time (PT/PPT) This practice has been shown to increase the incidence of fluid overload and pulmonary edema, and puts the patient at risk of blood-borne infections from multiple donors

Preventive transfusion in Dengue shock syndrome- is it necessary? Lum LC, Abdel-Latif Mel A, Goh AY. Chan PW, Lam SK (2003). J Pediatr, 143(5), Sep, pp 682-4 The liberal use of blood products in the treatment of DHF / DSS creates a real danger to the patient in addition to the unnecessary cost & an incorrect focus in the treatment The practice was stopped in 1997

Role of platelet transfusion in dengue hemorrhagic fever Kabra SK, Jain Y,Madhulika et al Indian Pediatr 1998; 35 : 452-454. Preventive transfusion with platelets & FFP are not necessary for treating DHF/DSS

Thrombocytopenia & Platelet transfusion in DHF & DSS Alex Chairulfatah, Setiabudi D, et al Institute of Tropical Medicine, Belgium, 1995; 75 (4) : 291-295 To evaluate the effect of platelet transfusions to prevent bleeding in DHF / DSS patients All patients admitted with DHF / DSS between August 1995 – March 1996 in 4 major hospitals in Bandung Indonesia were included in the study

Thrombocytopenia & Platelet transfusion in DHF & DSS Alex Chairulfatah, Setiabudi D, et al Institute of Tropical Medicine, Belgium, 1995; 75 (4) : 291-295 Conclusion In most DHF / DSS cases, platelet transfusions do not influence the incidence of severe bleeding

There are no prospective studies and consensus on platelet transfusion based on low platelet count w/ or w/out bleeding in dengue infection There are no randomised prospective studies to show that administration of FFP or platelet concentrates have improved the outcome of DHF / DSS in adults Clinical Practice Guidelines, Dengue Infection in Adults Dengue Consensus 2003, Academy of Medicine Malaysia Ministry of Health

RECOMBINANT ACTIVATED FACTOR ( rFV11a )

Recombinant Activated Factor VII ( rFVIIa ) Provide effective hemostasis in severe uncontrolled bleeding in patients without preexisting coagulopathy undergoing various major surgeries or in patients receiving warfarin for thromboprophylaxis Used in controlling life-threatening bleeding in Dengue Shock Syndrome

Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555 Objective: To evaluate the efficacy and safety of Recombinant Activated Factor VII (rFVIIa) in children aged < 18 years old with grade II or grade III Dengue hemorrhagic fever (DHF) who required blood component therapy for controlling bleeding episodes

Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555 Patients who had been admitted or referred to the following hospitals from July 2001 to December 2002 were included: Ramathibodi Hospital (Bangkok, Thailand) Buddhachinaraj Hospital (Phitsanuloke, Thailand) Supprasithprasong Hospital (Ubonrajchathani, Thailand) University of Santo Tomas (Manila, Philippines) Research Institute for Tropical Medicine (Muntinlupa City, Philippines)

Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555 The 1st dose of rFVIIa ( NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) or placebo at 100 ug/kg body weight was given by intravenous injection When the bleeding was not effectively controlled, a 2nd dose (100 ug/kg) was given 30 min after the first dose

Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555 Conclusion: rFVIIa appears to be useful as an adjunctive treatment to blood component replacement in controlling active bleeding episodes in children with grade II or grade III DHF when platelet concentrates are not available

Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555 The study could not show the effect of rFVIIa on the reduction of RBC transfusion requirement, possibly due to the small number of patients and non-optimized dose regimen of rFVIIa

Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555 Concerning safety, rFVIIa does not appear to aggravate clinical condition of patients with DHF grade II / III to full-blown DIC

The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome Ampaiwan Chuansumrita, Kanchana Tangnararatchakita, et al Blood Coagulation and Fibrinolysis 2004, 15:335–342 To report the use of recombinant activated factor VII (rFVIIa) in controlling life-threatening bleeding episodes in patients with grades III and IV DHF

The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome Ampaiwan Chuansumrita, Kanchana Tangnararatchakita, et al Blood Coagulation and Fibrinolysis 2004, 15:335–342 The rFVIIa (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) of 100 g/kg was given as a single dose or repeated doses at intervals of 4 h according to the bleeding symptoms

The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome Ampaiwan Chuansumrita, Kanchana Tangnararatchakita, et al Blood Coagulation and Fibrinolysis 2004, 15:335–342 Conclusion The use of rFVIIa, given as bolus injection of 100 g/kg as a single dose or repeated doses at intervals of 4 h for one to three doses seems to be effective in restoring hemostasis to control life-threatening bleeding in a limited series of patients with DSS

Role of the following in DHF: 1.) Immunoglobulin 2.) Steroids 3.) Dengue Vaccine

The use of intravenous gammaglobulin in dengue fever, a case report. Ascher DP , Laws HF , Hayes CG . Department of Pediatrics, 13th Air Force Medical Center, Manila, Phil Southeast Asian J Trop Med Public Health. 1989 Dec;20(4):549-54. The documented case of dengue fever with thrombocytopenia was managed with IV IgG. Clinically, and by laboratory parameters, the case dramatically improved after IV IgG administration The use of IV IgG in cases of thrombocytopenia associated with dengue has both theoretical advantages and disadvantages IV IgG may have a role in the management of DHF/DSS

Studies on the Role of Steroids in Dengue Shock Syndrome 1.) Failure of High – Dose Methylprednisolone in established DSS: A Placebo-Controlled, Double-Blind Study S Tassniyom, S Vasanawathana, et al Pediatrics, 1993 July; 92 (1): 111-5 2.) Failure of Hydrocortisone to Affect Outcome in DSS Sumarmo, Talogo W., et al Pediatrics 1982, January; 69 (1) 45-9 3.) Hydrocortisone in the Management of DSS Min M, U T, Aye M, et al Southeast Asian Journal of Tropical Public Health. Dec 1975; (4):573-9

Recommendations of the Scientific Working Group on Dengue (2000) Development live-attenuated tetravalent vaccines Guidelines for the safety of dengue vaccines Dengue vaccination may sensitize a recipient so that ensuing dengue infection could result in hemorrhagic fever (Halstead)

Is dengue vaccine possible? In principle, an effective vaccine against DV is highly feasible because: it causes only acute infection the virus replication is effectively controlled after a short period of 3 to 7 days of viremia. the individuals who have recovered from DV infection, are immune to rechallenge with the same type but not to other types of DV

Developing a vaccine for dengue is a very challenging task because: Dengue infections can be more severe in individuals who have dengue antibodies acquired passively or actively A suitable animal model to evaluate candidate dengue vaccines is not available

Dengue Vaccines Conventional vaccines Flavivirus-based recombinant vaccines Intertypic chimeric vaccines ChimeriVax vaccines Recombinant dengue vaccines based on non-flavivirus vectors

Dengue Vaccines Conventional vaccines: empirically attenuated strains of all four dengue serotypes have been created by repeated serial passage in non- permissive cell lines Mahidol vaccine (licensed to Aventis Pasteur): after reducing the concentrations of serotype 3 strain: about 71% seroconversion against all four types Walter Reed Army Institute for Research (licensed to Glaxo-SmithKline): 80-90% seroconversion against all four serotypes

THE KEY TO THE SUCCESS IN THE MANAGEMENT OF DENGUE IS… GOOD CLINICAL EVALUATION PROMPT & PRECISE INTERVENTION

Dengue Hemorrhagic Fever Management

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