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Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

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  1. 1. Dr. Sachin Verma MD, FICM, FCCS, ICFC Fellowship in Intensive Care Medicine Infection Control Fellows Course Consultant Internal Medicine and Critical Care Web:- Mob:- +91-7508677495References;1. Harrison´s principle of internal medicine -16th ed2. Park´s textbook of preventive and social medicine -17th ed3.
  2. 2. DENGUE
  3. 3. Virus vector and transmission Dengue VirusCauses dengue and dengue hemorrhagic feverIs an arbovirusTransmitted by mosquitoesComposed of single-stranded RNAHas 4 serotypes (DEN-1, 2, 3, 4)
  4. 4. Dengue VirusesEach serotype provides specific lifetimeimmunity, and short-term cross-immunityAll serotypes can cause severe and fataldiseaseGenetic variation within serotypesSome genetic variants within each serotypeappear to be more virulent or have greaterepidemic potential
  5. 5. Aedes aegyptiDengue transmitted byinfected female mosquitoPrimarily a daytime feederLives around humanhabitationLays eggs and produceslarvae preferentially inartificial containers.Diseases- yellow fever, filariadengue, chikungunya fever,rift valley fever.
  6. 6. Aedes aegypti: Distributionthroughout the world
  7. 7. Model of baseline transmissionpotential (1961-1990 climate)
  8. 8. Model of future transmission potential (2080s climate)
  9. 9. Population at % of total risk (billions) populationPopulation increase only2050s 3.2 342080s 3.5 35Population increase plusclimate change (HADCM2)2050s 4.1 442080s 5.2 52
  10. 10. Replication and Transmission of Dengue Virus1. Virus transmitted 1 to human in mosquito saliva 22. Virus replicates 4 in target organs3. Virus infects white 3 blood cells and lymphatic tissues4. Virus released and circulates in blood
  11. 11. Replication and Transmission of Dengue Virus5. Second mosquito 6 ingests virus with blood6. Virus replicates in mosquito midgut 7 and other organs, infects salivary glands 57. Virus replicates in salivary glands
  12. 12. Transmission of Dengue Virus by Aedes aegypti Mosquito feeds / Mosquito refeeds / acquires virus transmits virus Extrinsic Intrinsic incubation incubation period period Viremia Viremia0 5 8 12 16 20 24 28 DAYS Illness Illness Human #1 Human #2
  13. 13. Clinical Manifestations of Dengue and Dengue Hemorrhagic Fever Undifferentiated fever Classic dengue fever Dengue hemorrhagic fever Dengue shock syndrome
  14. 14. Undifferentiated FeverMay be the most common manifestation ofdengueProspective study found that 87% of patientsinfected were either asymptomatic or only mildlysymptomaticOther prospective studies including all age-groups also demonstrate silent transmission.
  15. 15. Clinical Characteristics of Dengue FeverFeverHeadacheMuscle and joint painNausea/vomitingRashHemorrhagic manifestations
  16. 16. Hemorrhagic Manifestations of DengueSkin hemorrhages: petechiae, purpura,ecchymosesGingival bleedingNasal bleedingGastro-intestinal bleeding:hematemesis, melena, hematocheziaHematuriaIncreased menstrual flow
  17. 17. Signs and Symptoms of Encephalitis/EncephalopathyAssociated with Acute Dengue InfectionDecreased level of consciousness:lethargy, confusion, comaSeizuresNuchal rigidityParesis
  18. 18. Clinical Case Definition forDengue Hemorrhagic Fever 4 Necessary Criteria:Fever, or recent history of acute feverHemorrhagic manifestationsLow platelet count (100,000/mm 3 or less)Objective evidence of “leaky capillaries:”– elevated hematocrit (20% or more over baseline)– low albumin– pleural or other effusions
  19. 19. Four Grades of DHFGrade 1– Fever and nonspecific constitutional symptoms– Positive tourniquet test is only hemorrhagic manifestationGrade 2– Grade 1 manifestations + spontaneous bleedingGrade 3– Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)Grade 4– Profound shock (undetectable pulse and BP)
  20. 20. Danger Signs inDengue Hemorrhagic FeverAbdominal pain - intense and sustainedPersistent vomitingAbrupt change from fever tohypothermia, with sweating andprostrationRestlessness or somnolence
  21. 21. Clinical Case Definition for Dengue Shock Syndrome 4 criteria for DHF Evidence of circulatory failure manifested indirectly by all of the following: – Rapid and weak pulse – Narrow pulse pressure (≤ 20 mm Hg) OR ( hypotension for age – Cold, clammy skin and altered mental status Frank shock is direct evidence of circulatory failure
  22. 22. Risk Factors Reported for DHFVirus strain :DHF risk is greatest for DEN-2, followedby DEN-3, DEN-4 and DEN-1Pre-existing anti-dengue antibody– previous infection– maternal antibodies in infantsHost genetics-females more affected,malnutrition protective.Age(<12)
  23. 23. Unusual Presentations of Severe Dengue FeverEncephalopathyHepatic damageCardiomyopathySevere gastrointestinal hemorrhage
  24. 24. Increased Probability of DHF Hyperendemicity Increased circulation Increased probability of viruses of secondary infection Increased probability of Increased probability ofoccurrence of virulent strains immune enhancement Increased probability of DHF
  25. 25. Pathogenesis of DHFSTEP 1- Homologous Antibodies Form Non- infectious Complexes 1 1 1 1 Dengue 1 virus Neutralizing antibody to Dengue 1 virus Non-neutralizing antibody 1 Complex formed by neutralizing antibody and virus
  26. 26. STEP2- Heterologous Antibodies of firstserotype infection form Infectious Complexes with second serotype 2 2 2 2 2 Dengue 2 virus Non-neutralizing antibody to Dengue 1 virus 2 Complex formed by non-neutralizing antibody and virus
  27. 27. STEP3 - Heterologous Complexes Enter More Monocytes, Where Virus Replicates 2 2 2 2 2 2 2 2 22 2 Dengue 2 virus Non-neutralizing antibody 2 Complex formed by non-neutralizing antibody and Dengue 2 virus
  28. 28. STEP4 –DHF pathogenesis Infected monocytes release vasoactive mediators, resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS
  29. 29. Clinical Evaluation in Dengue Fever Blood pressure Evidence of bleeding in skin or other sites Hydration status Evidence of increased vascular permeability-- pleural effusions, ascites Tourniquet test
  30. 30. Petechiae
  31. 31. Tourniquet TestInflate blood pressurecuff to a point midwaybetween systolic anddiastolic pressure for 5minutesPositive test: 20 or morepetechiae per 1 inch2(6.25 cm2)
  32. 32. Laboratory Tests in Dengue FeverClinical laboratory tests– CBC--WBC, platelets, hematocrit– Albumin– Liver function tests– Urine--check for microscopic hematuriaDengue-specific tests– Virus isolation– Serology
  33. 33. Laboratory Methods for Dengue Diagnosis- Virus isolation to determine serotype of the infecting virus IgM ELISA test for serologic diagnosis
  34. 34. Virus isolation: cell culture, mosquito inoculation& fluroscent antibody test
  35. 35. ELISA Plate
  36. 36. Collection and Processing of Samples for Laboratory Diagnosis Type of Time of Type of Specimen Collection Analysis Acute-phase When patient presents; Virus isolation blood collect second sample and/or serology(0-5 days after onset) during convalescence Convalescent-phase Between days 6 and 21 Serology blood after onset(≥ 6 days after onset)
  37. 37. Temperature, Virus Positivity and Anti-Dengue IgM , by Fever DayTemperature (degrees Celsius) 100 Dengue IgM (EIA units) 300 39.5 Percent Virus Positive 80 39.0 225 38.5 60 150 38.0 40 37.5 20 75 37.0 0 0 -4 -3 -2 -1 0 1 2 3 4 5 6 Fever Day Mean Max. Temperature Virus Dengue IgM
  38. 38. Management of dengue fever Outpatient TriageNo hemorrhagic manifestations and patient iswell-hydrated: home treatmentHemorrhagic manifestations or hydrationborderline: outpatient observation center orhospitalizationWarning signs (even without profound shock) orDSS: hospitalize
  39. 39. Warning Signs for Dengue Shock Alarm Signals: Alarm Signals: •• Severe abdominal pain Severe abdominal pain •• Prolonged vomiting Prolonged vomitingFour Criteria for DHF: Four Criteria for DHF: •• Abrupt change from fever Abrupt change from fever•• Fever Fever•• Hemorrhagic manifestations Hemorrhagic manifestations•• Excessive capillary permeability Excessive capillary permeability••≤ 100,000/mm33platelets ≤ 100,000/mm platelets to to hypothermia hypothermia Initial Warning Signals: Initial Warning Signals: • Change in level of Change in level of •• Disappearance of fever •WhenPatients Develop DSS: When Patients Develop DSS: Disappearance of fever consciousness (irritability consciousness (irritability •• Drop in platelets Drop in platelets •• 3 to 6 days after onset of 3 to 6 days after onset of •• Increase in hematocrit Increase in hematocrit or or symptoms symptoms somnolence)
  40. 40. Treatment of Dengue FeverFluidsRestAntipyretics (avoid aspirin and non-steroidal anti-inflammatory drugs)Monitor blood pressure, hematocrit,platelet count, level of consciousness
  41. 41. Treatment of Dengue FeverContinue monitoring after defervescenceIf any doubt, provide intravenous fluids, guidedby serial hematocrits, blood pressure, and urineoutputThe volume of fluid needed is similar to thetreatment of diarrhea with mild to moderateisotonic dehydration (5%-8% deficit)
  42. 42. Rehydrating Patients Over 40 kg Volume required for rehydration is twice the recommended maintenance requirement Formula for calculating maintenance volume: 1500 + 20 x (weight in kg - 20) For example, maintenance volume for 55 kg patient is: 1500 + 20 x (55-20) = 2200 ml For this patient, the rehydration volume would be 2 x 2200, or 4400 ml.
  43. 43. Treatment of Dengue FeverAvoid invasive procedures whenpossibleUnknown if the use of steroids,intravenous immune globulin, or platelettransfusions to shorten the duration ordecrease the severity ofthrombocytopenia is effectivePatients in shock may require treatmentin an intensive care unit
  44. 44. Indications for Hospital DischargeAbsence of fever for 24 hours (withoutanti-fever therapy) and return of appetiteVisible improvement in clinical pictureStable hematocrit3 days after recovery from shockPlatelets ≥ 50,000/mm3No respiratory distress from pleuraleffusions/ascites
  45. 45. Common Misconceptions about Dengue Hemorrhagic FeverDengue + bleeding = DHF Need 4 WHO criteria, capillary permeabilityDHF kills only by hemorrhage Patient dies as a result of shockPoor management turns dengue into DHF Poorly managed dengue can be more severe, but DHF is a distinct condition, which even well-treated patients may developPositive tourniquet test = DHF Tourniquet test is a nonspecific indicator of capillary fragility
  46. 46. DHF is a pediatric disease All age groups are involved in the AmericasDHF is a problem of low incomefamilies All socioeconomic groups are affectedTourists will certainly get DHF with asecond infection Tourists are at low risk to acquire DHF
  47. 47. Vector Control Methods: Chemical ControlLarvicides (organophosphorus compounds –fenthion ,abate) may be used to kill immatureaquatic stagesUltra-low volume fumigation ineffective againstadult mosquitoesMosquitoes may have resistance to commercialaerosol sprays
  48. 48. Vector Control Methods:Biological and Environmental ControlBiological control – Largely experimental – Option: place fish in containers to eat larvaeEnvironmental control – Elimination of larval habitats – Most likely method to be effective in the long term
  49. 49. Purpose of ControlReduce female vector density to a levelbelow which epidemic vectortransmission will not occurBased on the assumption thateliminating or reducing the number oflarval habitats in the domesticenvironment will control the vectorThe minimum vector density to preventepidemic transmission is unknown