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Dengue Hemorrhagic fever

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  • Most common arboviral/arthropod born d/s transmitted worldwide,tropical/subtropical.One of the leading cause of hospital admission; and death of children in SEA. ----- Meeting Notes (3/27/12 14:40) -----
  • Aedes Index=NO: of house with Aedes larvae x 100 NO: of house inspected
  • *Virus replication takes place in RE cells-dendritic cells,Hepatocytes,Endothelial cells
  • Virulence,viral load,autoantibodies,T-cell activation,host genetic background
  • Secondary infection is a major risk factor for DHF.
  • Pprotein,albumin,RBCs—leak into extravascular spaces, Hypovolaemiashock
  • 2.5cm= 1 inch,may be helpful in febrile phase,additional tool for DF from other viral,–ve during shock
  • Normal value of PLT
  • s/s of circulatory failure,hypovolaemia,**liver congestion
  • Recovery rash- maculopapular mobiliform rash with islands of skin sparings/normal coin-sized skin b/t rash(isles of white in sea of red)
  • 93% +ve predictive value
  • H/o-Intake/UOP/Blood loss/Dehydration/BP/peripheral circulation
  • O/E-LOC,effusion/ascities/abdo;pain
  • FBC and serial pltmonitor disease progress
  • IgM may be –ve b4 D3.
  • Hourly monitor/pcv+Plt- QID
  • Maintainance-1-2days after that-overload?
  • DIC---Cryo or FFP
  • Don’t do-N/G tube,chest tube,central line,steroid,Ig
  • Transcript

    • 1. Dengue Haemorrhagic Fever Dr San Thitsa Aung08/12/12
    • 2. Introduction Agent ▪ Flavi virus , DHF virus serotype 1,2,3 and 4 Vector - Aedes aegypti* ▪ bite during daytime ▪ grow in clear water. - Aedes albopictus Host ▪ Common among age less than 15 year Environment ▪ Epidemic in rainy season Incubation period ▪ 1-7 days08/12/12
    • 3.  Endemic in Malaysia  4 serotypes circulating  Trends - cyclical pattern  1st reported in Penang  DHF 1962 (1st DHF outbreak)  Affects all age group  Most common among urban-semiurban population Highest incidence in working and school-going age group  Correlate with high Aedes Index in construction sites, factories and schools08/12/12
    • 4. Vector Borne Diseases Incidence Rate and Mortality Rate(per 100,000population)(Health Facts-2009)  Dengue  DHF  Malaria  Typhus  Plague  Yellow Fever08/12/12
    • 5. Number of Dengue Cases by States, Malaysia Epid Week 1 - 35; Year 2008 IR No. of No. ofNo. STATE (per 100,000 No. STATE IR Cases Cases pop)1. SELANGOR 13,139 259.1 9. MELAKA 597 79.22. WPKL 3,514 215.7 10. PAHANG 814 53.83. TERENGGANU 1206 110.2 11. LABUAN 56 63.94. PERAK 2,510 106.7 12. KEDAH 914 46.75. N. SEMBILAN 931 93.5 13. PERLIS 108 45.76. PENANG 1,251 80.9 14. SARAWAK 872 35.67. KELANTAN 1,689 105.9 15. SABAH 751 24.08. JOHOR 2,501 75.5 Until Wk 36 30,853 cases (62 deaths) 08/12/12
    • 6. Total No of admission = 4243 (Health Facts 2010)08/12/12
    • 7. PATHOGENESIS  Incompletely understood08/12/12
    • 8. Immune Enhancement Theory HalsteadAntibody-dependent enhancement Individuals who have had prior infection with one or more dengue virus serotype may develop low level of neutralizing Ab Infection-enhancing Ab Virus actually enhance the entry of different serotypes into mononuclear phagocytes↑replicate*resulting in the increased activation of complement and cytokines the release of mediators of vascular permeability. 08/12/12
    • 9.  1st infection: benign illness which sensitizes the patient  2nd infection (within 6/12): devastating immune reaction and circulation of infection-enhancing antibodies at the time of infection is risk factor for development of severe disease  Viraemia - directly predict severity08/12/12
    • 10. Pathophysiology In early stage of secondary dengue infections: ØRapid activation of complement system which interacts at the endothelial cell to produce increased vascular permeability Increased vascular permeability causes- plasma leakage,haemoconcentration,hypovolaemia,tissue hypoxia ,acidosis. ØActivation of coagulating cascade & fibrinolytic system08/12/12
    • 11. Increased systemic vascular permeability-cont:• Intravascular volume depletion  Hemoconcentration Starts at the end of the febrile stage and continues up to  24-48 hours after defervescence -- hypoproteinemia/hypoalbuminemia  pleural effusion, ascites  threatened shock and profound shock 08/12/12
    • 12. Bleeding Tendency1. Vasculopathy2. Thrombocytopenia3. Platelet dysfunction*4. Coagulopathy5. Liver damage 08/12/12
    • 13. Tornique test-Hess test  BP cuff pressure maintained between systolic and diastolic BP for 5 mins—  Positive-if >20 petechiae/ 2.5 cm 2 area  Increase capillary fragility08/12/12
    • 14. Thrombocytopenia < 100x109/L Begins to fall in the febrile stage Lowest in the shock stage Can reach a nadir of less than 10 x 10 9 /L Starts to rise by the second afebrile day and normalizes by 7 days 08/12/12
    • 15. Thrombocytopenia Mechanism of thrombocytopaenia Ø Decreased production and increased peripheral destruction § Immune complexes on platelets § Shortened survival of transfused platelets § Cross reactive platelet antibodies08/12/12
    • 16. Platelet dysfunction Impaired  ADP-induced platelet aggregation  ADP-releasing ability 08/12/12
    • 17. Coagulopathy Procoagulant markers increased in severe shock variable degree of reduction in coagulation factors II, V, VII, VIII, IX and X and low fibrinogen. Prolongation of APTT and PT There may be mild consumption coagulopathy to overt DIC. 08/12/12
    • 18. Classification Dengue virus infectionAsymptomatic Symptomatic Dengue Simple fever Dengue fever haemorrhagic (DF) fever (DHF) Without With unusual No shock Dengue shock haemorrhage haemorrhage syndrome (DSS)08/12/12
    • 19. Classical Dengue Feveru Infants &Young children Disease may be undifferentiated Characterised by fever 1-5 days,pharyngeal inflammation, rhinitis & mild cough Frequently passed undiagnosedu Older children and adult high grade fever with chills  occasionally severe back pain precedes the fever  severe headache, retro-orbital pain08/12/12
    • 20.  Transient macular gererlised rash that blanches under pressure(24-48 hr after fever)appear on the limbs and spread to involve trunk  Generalised lymphadenopathy  Anorexia,Nausea,Vomiting  Cutaneous hyperasthesia or hyperalgesia  1-2 days after defervescence-generalised morbiliform, maculopapular rash appears that spares the palms& soles,disappears in 1-5 days08/12/12
    • 21.  desqumation may occur  body temperature slightly elevated  biphasic temperature pattern08/12/12
    • 22. Dengue Haemorrhage Fever 1st phase • fever  malaise  vomiting  headache  anorexia  cough,pharyngeal injection  injection injection Conjuntival  Conjuntival injection08/12/12
    • 23. 2nd phase  Rapid clinical deteroration & collapse (1-5 days)  Cold &clammy extremities*  Weak rapid thready pulse  Warm trunk,flushed face  Restlessness* ,irritability  Midepigastric pain**  Rapid laboured respiration  Faint heart sounds08/12/12
    • 24.  Patichiae on forehead and extremities  Spontaneous ecchymosis may appear  Easy bruising and bleeding at venepuncture sites08/12/12
    • 25. Recovery • plasma leakage stop,reabsorption of ECF • general well being,haemodynamically stable • GIT symptoms subside • Classical rash-macular/maculopapular rash may appear* • HR↓ • PLT recover • WBCs return to N08/12/12
    • 26. Dengue recovery rash08/12/12
    • 27. Days after onset of fever Viraemia HI Ab IgG Fever ̊C Symptoms Haemorrhage Shock Platelet 109/L Hct %08/12/12
    • 28. Clinical Pointers to diagnosis  High fever of 3 or more then duration § Petechial haemorrhage, positive tourniquet test or other bleeding tendencies § Hepatomegaly § Pleural effusion or ascites  Shock  Fall in platelet count that precedes or occurs with a rise in haematocrit § Normal or low WBC with relative lymphocytosis  Maculopapular rash or generalised flushing Note: all criteria need not be present at the same time08/12/12
    • 29. Severe plasma leakage DSSPlueral AscitesEffusion 08/12/12
    • 30. WHO case definition of DHF ALL of the following criteria must be present: • Fever of high grade and continuous for 2-7 days duration. • Haemorrhagic diathesis or positive tourniquet test* except in shock. • Thrombocytopenia (less than 100,000/mm³) • Haemoconcentration (Hct ≥ 20% relative to baseline) or evidence of plasma leakage08/12/12
    • 31. Other clinical manifestations-  hepatomegaly  circulatory disturbances (cool extremities, capillary refil >2 sec, tachycardia)  a fall in haematocrit following volume replacement08/12/12
    • 32. WHO grading of DHF /DSS Grade 1  Fever with constitutional symptoms.  A positive Hess test. Grade 2  Spontaneous bleeding (skin ± other bleeds)  in addition to manifestations of grade 1 Grade 3  Circulatory failure (rapid weak pulse, pulse pressure < 20mmHg)  but systolic BP still normal Grade 4  Profound shock (hypotension,undetectable blood pressure and heart rate)08/12/12
    • 33. NOTE; • Grade 3 and 4 = Dengue Shock Syndrome • Thrombocytopenia and haemoconcentration (rise in PCV by 5 g%) differentiates Grade 1 and 2 DHF from DF • Clinical differentiation of grade 1 and 2 DHF from DF is not always clear cut due to variation in baseline haematocrit • All patients ill enough to need IV drip* should be notified as DHF if baseline haematocrit unknown08/12/12
    • 34. Inclinical practice  Dengue Fever08/12/12
    • 35. In clinical practice Dengue+/- warning /s Severe Probable -abdo;pain S plasma leakage -tender enlarged L S bleeding -persistent V+ S organ impair; -Mucosal bleed -fluid accumu: - ↑PCV - ↓Plt08/12/12
    • 36. DHF can be further graded as follows: • DHF with no shock • DHF with shock (DSS) which can be further graded into: - DHF with compensated shock • signs of shock – tachycardia out of proportion to temperature, decreased tissue perfusion as (cool extremities, late capillary refill time, narrow pulse pressure, weak pulses, oliguria, encephalopathy) • systolic pressure within the normal range08/12/12
    • 37. DHF with decompensated shock • signs of shock – tachycardia, cool extremities, late capillary refill time, weak or absent pulses, oliguria and altered conscious level • systolic hypotension08/12/12
    • 38. Assessment of circulation • fluid intake for previous 1-2 days, vomiting • urine output for past 24 hours and time of last micturation • bleeding* and amount • degree of dehydration • peripheral circulation - temperature and colour of extremities, capillary refill - distal pulses, pulse volume08/12/12
    • 39. • Mental status: headache, irritability, combativeness, drowsiness, coma, seizures (may indicate reduce cerebral perfusion, cerebral oedema or intracranial bleed) • Pleural effusion and ascites (third space loss*) • Abdominal pain (may indicate GI bleed, acute liver enlargement, hypovolaemia with intestinal ischaemia (shock) • Hypotension is a late sign.08/12/12
    • 40. Atypical presentationS  Acute abdominal pain, diarrhoea  severe gastrointestinal haemorrhage  Severe headache,convulsion, altered conscious level (encephalitis)  Hepatic failure,Obstructive jaundice,inceresed liver enzymes,Reye’s syndrome*  Acute renal failure  Haemolytic Uremic Syndrome  Disseminated intravascular coagulation08/12/12
    • 41. Laboratory investigations  FBC- WBC-normal/leucopenia  Platelet count  PCV  BUSE,Creatinine  PT/PTT  GxM  Blood culture  Dengue Blot Test08/12/12
    • 42. Laboratory Diagnosis Serology • Dengue IgM Dot Enzyme Immunoassay - interpret results in a clinical context. Serology may be negative in early. A repeat study in 10 days will help confirm the diagnosis. Virus isolation -the most definitive diagnostic test. Availability limited. • if patient dies soon after admission, a liver biopsy specimen sent in viral transport media may be useful in confirming the diagnosis. Dengue RNA PCR  • may be indicated to confirm diagnosis08/12/12
    • 43.  Dengue IgM08/12/12
    • 44. Management of Grade 1 & 2 DHF  Admission,place IV cannulae  Encourage oral fluids,IV ½ NS+D5% if unable to take orally/evidence of plasma leakage  Paracetamol for fever  Avoid NSAIDS  Monitor –clinical;PR,T o,HR,RR, BP, I/O,Urine specific gravity  PCV,PLT, Hb -8 to 12 hrly08/12/12
    • 45. Cont;  monitor- until T o returns to normal,in 1-2 days, throughout the critical period during the transition from febrile to afebrile phase(after 3rd day)  haemoconcentration usually precedes changes in pulse pressure and rate.08/12/12
    • 46. Management of DSS • Admit to ICU. • Obtain IV access. • Resuscitation: * • Monitor: - vital signs, peripheral perfusion - blood pressure hourly till stable - PCV or haematocrit & platelet count 6 hrly - urea & ectrolytes, serum creatinine - urine output - ABG08/12/12
    • 47. 08/12/12
    • 48. 08/12/12
    • 49. § Fluid maintenance:  - following fluid resuscitation, continue with 0.45%saline 5% dextrose at 1-2 times maintenance, guided by haematocrit, urine output and vital signs.  - in general, the duration of vascular permeability lasts 1-2 days following onset of shock  - after which further infusion of large volume of fluids may result in pulmonary oedema and pleural effusion.08/12/12
    • 50.  Electrolyte and metabolic disturbances: - hyponatremia and metabolic acidosis occur in DSS. Isotonic fluids and restoration of tissue perfusion correct both problems. - correct hypoglycaemia that may occur in liver failure08/12/12
    • 51. § Transfusion of blood and blood products. • Blood transfusion. Indications: - significant haemorrhage - persistent shock despite crystalloids and low or declining haematocrit Fresh whole blood is preferable. • Platelet concentrate :Indications; - platelet count < 50,000/mm³ with bleeding - platelet count < 10,000 - 20,000/mm³ Dose -- 10-20 ml/kg or 4 units/m² BSA over 1 hour.08/12/12
    • 52.  In the presence of Disseminated Intravascular coagulaton (DIC) Tx- cryoprecipitate (1 unit per 5 kg body weight ) followed by platelet concentrate (10-20 ml/kg or 4units/m² BSA over 1 hour) - fresh frozen plasma (10-20 ml/kg) • monitor coagulation profile regularly. i.e. PT, PTT, fibrinogen, D- dimer, or FPD and platelet counts.08/12/12
    • 53. • oxygen supplement via nasal cannula or mask • consider mechanical ventilation in - respiratory distress from massive pleural effusion, ascites or pulmonary oedema - severe shock with multi-organ failure - encephalopathy for cerebral resuscitation • H₂ antagonists and Vitamin K08/12/12
    • 54. Complications of DSS • Shock either persistent or recurrent • Pleural effusion and ascites • Bleeding - usually gastrointestinal • Hepatic dysfunction may result from dengue viral hepatitis or shock • Encephalopathy, usually occurs early before onset of plasma leakage • Beware of fluid overload and cardiac failure during the reabsorption phase08/12/12
    • 55. Special Notes § Insertion of nasogastric tube carries risk of trauma and bleeding. If required, use an oral route. § Blood product transfusion carry risk of disease transmission. Avoid if vital signs stable § Insertion of chest tubes carries risk of haemorrhage. Careful titration of iv fluids with doses of frusemide 0.25-0.5 mg/kg for 1-2 doses should make it possible to avoid chest tube insertion. § Central line insertion carries risk of bleeding. Intraosseous route is acceptable. § Use of steroids and immunoglobulin in DSS has no beneficial effect08/12/12
    • 56. Preventive measures  Vaccine underdevelopment  Avoiding mosquito bites by use of insecticides,repellents,body covering with clothing ,  Destruction of mosquito breeding sites  Larvicide- Abate added safely to drinking water08/12/12
    • 57.  References  Nelson Text Book of Paed (19th edition)  Illustrated Text Book  Paed: Protocol  CPG ,Ministry of Health Malaysia08/12/12

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