Dengue fever


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Dengue fever

  1. 1. DENGUE FEVER Dr. Anita Lamichhane Deptt. Of pediatrics Shaikh Zayed Hospital
  2. 2. Etiological Agent
  3. 3. Dengue virus <ul><li>Single stranded RNA virus,Arbovirus belonging to flaviviridae family </li></ul><ul><li>4 antigenically distinct serotypes-DEN 1, 2,3, 4. </li></ul><ul><li>DEN-1, DEN-2 were prevalent until 1980s </li></ul><ul><li>DEN-3 is predominant in recent outbreak </li></ul><ul><li>DEN-4 primarily detected in secondary dengue infections </li></ul><ul><li>Serotype provides specific life time immunity and short term cross immunity </li></ul>
  4. 4. Dengue virus transmission <ul><li>Two general patterns </li></ul><ul><li>Epidemic Dengue – dengue virus is introduced into a region as an isolated event that involves a single viral strain(Asia,Africa,America) </li></ul><ul><li>Hyperendemic Dengue -continuous circulation of multiple viral serotypes in an area where a large pool of susceptible hosts & a competent vector are constantly present,predominant pattern of global transmission. </li></ul>
  5. 6. The vector-Aedes aegypti <ul><li>Transmitted by the infected female Aedes aegypti </li></ul><ul><li>Can be identified by the white bands or scale patterns on its legs and thorax </li></ul><ul><li>Primarily a daytime feeder </li></ul><ul><li>Found in tropical & subtropical region </li></ul><ul><li>Lives around human habitation </li></ul><ul><li>Lays egg & produces larvae preferentially in artificial containers </li></ul>
  6. 7. Vector & its transmission <ul><li>0 5 8 12 16 20 24 28 </li></ul><ul><li>DAYS </li></ul><ul><li> Illness Illness </li></ul><ul><li>Human #1 Human #2 </li></ul>Mosquito feeds/acquires virus Mosquito refeeds/transmits virus Viremia Intrinsic incubation period Extrinsic incubation period Viremia
  7. 8. Replication & transmission of Dengue virus <ul><li>Virus inoculated into a human being with mosquito saliva </li></ul><ul><li>The virus localizes and replicates in various target organs-local lymph nodes & liver  released  spreads through the blood  infect the WBCs & reticuloendothelial system(dendritic cells,hepatocytes,endothelial cells) </li></ul><ul><li>The mosquito ingests blood containing the viruses (on biting an infective person) </li></ul>
  8. 9. <ul><li>Virus replicates in the midgut,ovaries,nerve tissue, fat body of the mosquito </li></ul><ul><li>It then escapes into the body cavity and later on infects the salivary glands </li></ul><ul><li>In the salivary glands, the virus replicates </li></ul><ul><li>When the mosquito bites another human ,the life cycle continues </li></ul><ul><li>Humans are the primary reservoir of infection </li></ul>
  9. 10. Vector <ul><li>Aedes aegypti/Aedes albopictus </li></ul><ul><li>The female mosquito feeds on blood ( they need the protein found in blood to produce eggs) </li></ul><ul><li>Male mosquitoes feed only on plant nectar. </li></ul><ul><li>The mosquito is attracted by the body odours, carbon dioxide and heat emitted from the animal or humans . </li></ul>
  10. 11. Aedes aegypti Mosquito life cycle <ul><li>Eggs are laid on the walls of water-filled containers in the house and patio. </li></ul><ul><li>The eggs can survive for months and hatch when submerged in water. </li></ul><ul><li>Female mosquitoes lay dozens of eggs up to 5 times during their life time. </li></ul><ul><li>The mosquito life cycle, takes 8 days and occurs in water. Adult mosquitoes live for one month. </li></ul>
  11. 12. <ul><li>Adult mosquitoes “usually” rest indoors in dark areas (closets, under beds, behind curtains); only female mosquitoes bite humans. </li></ul><ul><li>The dengue mosquito can fly several hundred yards looking for water-filled containers to lay their eggs. </li></ul><ul><li>The dengue mosquito does not lay eggs in ditches, drainages, canals, wetlands, rivers or lakes </li></ul>
  12. 13. Aedes aegypti
  13. 14. Aedes albopictus
  15. 16. <ul><li>Rapid activation of the complement system </li></ul><ul><li>Blood level of soluble TNF receptor, interferon-gamma,& IL-2 are </li></ul><ul><li>C1q,C3,C4,C5-8 & C3 proactivators are </li></ul><ul><li>These factors interact at the endothelial cell to produce vascular permeability through the nitric oxide final pathway </li></ul>
  16. 17. <ul><li>The blood clotting & fibrinolytic system are & levels of factor XII are </li></ul><ul><li>Capillary damage allows fluid, electrolytes & small proteins ,red cells to leak into extravascular spaces </li></ul><ul><li>This internal redistribution of fluid together with deficits caused by fasting, thirst,vomiting results in hemoconcentration,hypovolaemia, increase cardiac work, tissue hypoxia, metabolic acidosis & hyponatremia </li></ul>
  18. 19. Four dengue clinical syndrome <ul><li>Undifferentiated fever </li></ul><ul><li>Classic dengue fever </li></ul><ul><li>Dengue hemorrhagic fever(DHF) </li></ul><ul><li>Dengue Shock Syndrome (DSS)- a severe form of DHF </li></ul>
  19. 20. Undifferentiated fever <ul><li>Most common presentation </li></ul><ul><li>Silent transmission </li></ul><ul><li>Incubation period of 3-14 days(average 4-7 days) </li></ul><ul><li>Sudden onset of fever, biphasic </li></ul><ul><li>Severe headache(retro-orbital) </li></ul>
  20. 21. <ul><li>Myalgias & arthalgias that may be severe </li></ul><ul><li>Nausea & vomiting </li></ul><ul><li>Rash may be present at the different stages of illness- maculpapular, petechial, erythematous </li></ul><ul><li>Hemorrhagic manifestations </li></ul>
  22. 23. Dengue Hemorrhagic Fever <ul><li>Usually develops around 3 rd -7 th day of illness </li></ul><ul><li>There is rapid onset of plasma leakage, altered hemostasis, and damage to the liver, resulting in severe fluid losses and bleeding </li></ul><ul><li>Skin hemorrhage- petechiae, purpura, ecchymosis </li></ul><ul><li>Gingival & nasal bleeding,Hematuria </li></ul><ul><li>GI bleeding- haetamesis,melena,haematochezia </li></ul>
  23. 24. <ul><li>Plasma leakage is due to increased capillary permeability ;manifest as hemoconcentration, pleural effusion & ascites. </li></ul><ul><li>Bleeding due to capillary fragility & thrombocytopenia </li></ul><ul><li>Liver damage manifests as increases in levels liver enzymes, low albumin levels, and deranged coagulation parameters(PT,PTT) </li></ul>
  24. 25. 3 phases of DHF <ul><li>Febrile phase : 2-7 days </li></ul><ul><ul><li>Sudden onset fever </li></ul></ul><ul><ul><li>Severe headache </li></ul></ul><ul><ul><li>Epigastric discomfort,anorexia, vomiting </li></ul></ul><ul><ul><li>Arthralgia, myalgia </li></ul></ul><ul><ul><li>Flushing </li></ul></ul><ul><ul><li>Tender hepatomegaly, splenomegaly </li></ul></ul><ul><ul><li>Maculopapular rash </li></ul></ul>
  25. 26. Leakage phase <ul><ul><li>1 ST 24-48 HOURS </li></ul></ul><ul><ul><li>Pleural effusion </li></ul></ul><ul><ul><li>Ascities </li></ul></ul><ul><ul><li>Pericardial effusion </li></ul></ul><ul><ul><li>Haemorrhagic menifestation </li></ul></ul><ul><ul><li>Haematemesis,malena ,epistaxis & menorrhagia </li></ul></ul>
  26. 27. Convalescent phase <ul><ul><li>Short & uneventful </li></ul></ul><ul><ul><li>Short & uneventful </li></ul></ul><ul><ul><li>Return of appetite </li></ul></ul><ul><ul><li>Bradycardia </li></ul></ul><ul><ul><li>Recovery rash </li></ul></ul><ul><ul><li>Severe itching on palms & soles </li></ul></ul><ul><ul><li>of appetite </li></ul></ul><ul><ul><li>Bradycardia </li></ul></ul><ul><ul><li>Recovery z </li></ul></ul>
  27. 28. Criteria to label Dengue Hemorrhagic Fever
  28. 29. WHO case definition of DHF <ul><li>Fever-sudden onset 2-7 days </li></ul><ul><li>Hemorrhagic manifestations with positive tourniquet test </li></ul><ul><li>Low platelet count(1,00,000/mm 3 or less) </li></ul><ul><li>Objective evidence of plasma leak syndrome </li></ul><ul><ul><li>Hematocrit ≥ 20% above baseline </li></ul></ul><ul><ul><li>Low albumin </li></ul></ul><ul><ul><li>Pleural/pericardial effusions </li></ul></ul>
  29. 30. Four grades of DHF <ul><li>Grade I - Fever & non-specific constitutional symptoms </li></ul><ul><li>Positive tourniquet test is only hemorrhagic manifestations </li></ul><ul><li>Grade II- Grade I manifestations + spontaneous bleeding </li></ul><ul><li>Grade III -signs of circulatory failure </li></ul><ul><li>Grade IV- profound shock (undetectable pulse & BP) </li></ul>
  30. 31. Danger signs in Dengue Hemorrhagic Fever <ul><li>Abdominal pain-intense & sustained </li></ul><ul><li>Persistent vomiting </li></ul><ul><li>Abrupt change from fever to hypothermia, with sweating </li></ul><ul><li>Change in mental status of the patient </li></ul>
  31. 32. Unusual presentation of Severe Dengue Fever <ul><li>Encephalopathy </li></ul><ul><li>Liver failure or fulminant hepatitis </li></ul><ul><li>Demonstrated by Increase aminotransferas, increase bilirubin, incresae PT,APTT </li></ul><ul><li>Cardiomyopathy-conduction defects, myocarditis </li></ul><ul><li>Severe GI hemorrhage </li></ul>
  32. 33. Risk Factors <ul><li>Age: all groups are affected </li></ul><ul><li>Pre-existing anti –dengue antibody,either caused by previous infection or to maternal antibodies passed to infants </li></ul><ul><li>Higher risk in secondary infections </li></ul><ul><li>Higher risk inlocations with two or more seroypes circulating simultaneously at high levels </li></ul>
  34. 35. <ul><li>Inflate BP cuff to a point midway between SBP & DBP for 5 minute </li></ul><ul><li>After deflating the cuff, wait for the skin to return to its normal colour ,then count the number of petechiae visible in one inch-square area on the ventral surface of the forearm </li></ul><ul><li>Positive test: 20 0r more petechiae per one inch 2 </li></ul>
  35. 36. Positive Tourniquet Test <ul><li>A typical positive result from a tourniquet test may look like. This patient </li></ul><ul><li>has more than 20 petechiae per square inches. </li></ul>
  36. 37. Dengue Shock Syndrome
  37. 38. Four criteria <ul><li>Evidence of circulatory failure, manifested indirectly by all of the following </li></ul><ul><ul><li>Rapid & weak pulse </li></ul></ul><ul><ul><li>Narrow pulse pressure (≤ 20 mm Hg or hypotension for age) </li></ul></ul><ul><ul><li>Cold, clammy skin & altered mental status </li></ul></ul><ul><ul><li>Frank shock </li></ul></ul>
  38. 39. Laboratory tests in Dengue Fever <ul><li>Complete blood count: </li></ul><ul><ul><li>WBC-leucopenia,lymphocytosis </li></ul></ul><ul><ul><li>Platelets-thrombocytopenia </li></ul></ul><ul><ul><li>Hematocrit:≥20% of the baseline </li></ul></ul><ul><li>Liver function tests: </li></ul><ul><ul><li>serum aminotransferases:deranged </li></ul></ul><ul><ul><li>Serum bilirubin:increased </li></ul></ul><ul><ul><li>serum albumin:low </li></ul></ul>
  39. 40. <ul><li>Coagulation studies –PT,APTT:prolongrd </li></ul><ul><li>Serum electrolytes:deranged </li></ul><ul><li>Blood gases:metabolic acidosis </li></ul><ul><li>Tourniquet test:positive </li></ul><ul><li>Complement levels:low </li></ul><ul><li>Blood urea:raised </li></ul><ul><li>Chest X-ray- for effusions </li></ul><ul><li>ECG- sinus bradycardia, prolonged PR interval </li></ul>
  40. 41. <ul><li>Serological diagnosis </li></ul><ul><ul><li>ELISA </li></ul></ul><ul><ul><li>Anti dengue IgM & IgG Ab </li></ul></ul><ul><ul><li>Sensitivity 84-98% </li></ul></ul><ul><ul><li>Specificity 100% </li></ul></ul><ul><ul><li>Haemagglutination inhibition test </li></ul></ul><ul><ul><li>Complement fixation test </li></ul></ul><ul><li>Virus isolation </li></ul><ul><li>Molecular detection - PCR </li></ul>
  41. 42. Treatment <ul><li>Mainly Supportive </li></ul><ul><li>No hemorrhagic manifestations & well hydrated: patient sent home with instructions for “follow up” </li></ul><ul><li>If hemorrhagic manifestations/hydration status borderline-patient observed in hospitals </li></ul><ul><li>If warning signs are present even without evidence of shock or if DSS present-hospitalized </li></ul>
  42. 43. <ul><li>Intravenous fluids with Electrolyte balance </li></ul><ul><li>Antipyretics-acetaminophen(aspirin and NSAIDS should be avoided as they interfere with platelet function) </li></ul><ul><li>H2 blockers,antiemetics(Domperidone) </li></ul><ul><li>Platelet and FFP transfusion when needed </li></ul><ul><li>Monitoring of BP, urine output, platelet count and hematocrit </li></ul><ul><li>Soft,balanced nutritious diet </li></ul>
  43. 44. Mosquito barrier <ul><li>Needed until fever subsides(to prevent Aedes aegypti mosquito from biting patients & acquiring virus) </li></ul><ul><li>Patients should be kept ideally in screened room or under mosquito net </li></ul>
  44. 45. Treatment of DHF & DSS <ul><li>A medical emergency </li></ul><ul><li>Admit in ICU </li></ul><ul><li>Keep the patient in supine position </li></ul><ul><li>Immediate evaluation of vital signs & degrees of hemoconcentration, dehydration & electrolyte imbalance </li></ul><ul><li>Rapid I/v replacement with wide bore cannula –N/S ideal fluid of choice </li></ul>
  45. 46. <ul><li>Monitor CBC, LFTs, S/E, PT/APTT </li></ul><ul><li>When pulse pressure is ≤ 10 mmHg or when elevation of Hct persists after replacement of fluids; plasma or colloids are indicated </li></ul><ul><li>FFP & platelets for bleeding </li></ul><ul><li>No role of corticosteroids </li></ul><ul><li>Look for evidence of complications </li></ul><ul><li>Avoid hypervolaemia </li></ul>
  46. 47. Complications <ul><li>Fluid & electrolyte losses </li></ul><ul><li>Myocarditis </li></ul><ul><li>Hepatic dysfunction </li></ul><ul><li>Febrile convulsions </li></ul><ul><li>Residual brain damage </li></ul><ul><li>Encephalopathy </li></ul><ul><li>Disseminated Intravascular coagulation </li></ul><ul><li>Dengue shock syndrome </li></ul>
  47. 48. Indications for hospital discharge <ul><li>Absence of fever for 24 hours(without anti-fever therapy) & return of appetite </li></ul><ul><li>Visible improvement in clnical picture </li></ul><ul><li>Stable haematocrit </li></ul><ul><li>3 das after recovery from shock </li></ul><ul><li>platelets ≥ 50,000/mm 3 </li></ul><ul><li>No respiratory distress from pleural effusion/ascites </li></ul>
  48. 49. Return IMMEDIATELY to clinic or emergency department if <ul><li>any of the following warning signs appear : </li></ul><ul><li> Severe abdominal pain or persistent vomiting </li></ul><ul><li> Red spots or patches on the skin </li></ul><ul><li> Bleeding from nose or gums , Vomiting blood </li></ul><ul><li> Black, tarry stools </li></ul><ul><li> Drowsiness or irritability </li></ul><ul><li> Pale, cold, or clammy skin </li></ul><ul><li> Difficulty breathing </li></ul>
  49. 50. Dengue Vaccine <ul><li>No licensed vaccine at present </li></ul><ul><li>Effective vaccine must be tetravalent </li></ul><ul><li>Field testing of an attenuated tetravalent vaccine currently underway </li></ul>
  50. 51. PREVENTION
  51. 52. Vector control <ul><li>Chemical control- </li></ul><ul><ul><li>Larvicides may be used to kill the immature aquatic stages </li></ul></ul><ul><ul><li>Ultra-low volume fumigation is effective against adult mosquitoes </li></ul></ul><ul><ul><li>Mosquitoes may have resistance to commercial aerosols spray </li></ul></ul>
  52. 53. <ul><li>Biological control </li></ul><ul><li>- largely experimental </li></ul><ul><li>-Placing fish in containers to eat the larvae </li></ul><ul><li>Environmental control </li></ul><ul><ul><li>Elimination of larval habitats </li></ul></ul><ul><ul><li>Most likely method to be effective in the long term </li></ul></ul>
  53. 54. Prophylaxis <ul><li>Avoiding mosquito bites </li></ul><ul><ul><li>Use of insecticides </li></ul></ul><ul><ul><li>Repellents </li></ul></ul><ul><ul><li>Body covering with clothing </li></ul></ul><ul><ul><li>Screening of house </li></ul></ul><ul><ul><li>Destruction of the vector breeding sites </li></ul></ul><ul><ul><li>Using mosquito nets </li></ul></ul>
  54. 55. <ul><li>If storage is mandatory, a tight fitting lid or a thin layer of oil may prevent egg laying or hatching </li></ul><ul><li>A larvicide (Abate) available as a 1% sand –granule formations may be added safely to drinking water </li></ul>
  55. 56. Why to control??/Purpose of control <ul><li>Reduce female vector density to a level below which epidemic vector transmission will not occur </li></ul><ul><li>The minimum vector density to prevent epidemic transmission is unknown </li></ul>
  56. 57. Program to minimize the impact of epidemic <ul><li>Teaching the medical community how to diagnose and mange DHF </li></ul><ul><li>Educating the general public to encourage & enable them to carry out vector control in their home and neighborhood </li></ul>
  57. 58. Common containers in which eggs develop into adult dengue mosquitoes:
  58. 59. Recent advances <ul><li>Gene-modified mosquitos could stop dengue fever : genetically modified mosquitoes wee released last year at sites in Malaysia and the Cayman Islands. </li></ul>
  59. 60. Key Message <ul><li>Dengue infection is preventable disease </li></ul><ul><li>No direct person to person transmission </li></ul><ul><li>Prevent Man – Mosquito contact to prevent the disease </li></ul>