Dengue fever is caused by the dengue virus, which is transmitted by the Aedes aegypti mosquito. It has four distinct serotypes. The virus replicates in the mosquito and humans, who serve as the primary reservoir of infection. Symptoms range from a mild fever to the potentially lethal dengue hemorrhagic fever. There is no vaccine, so prevention depends on controlling the mosquito population and avoiding bites.

1. DENGUE FEVER Dr. Anita Lamichhane Deptt. Of pediatrics Shaikh Zayed Hospital

2. Etiological Agent

3. Dengue virus Single stranded RNA virus,Arbovirus belonging to flaviviridae family 4 antigenically distinct serotypes-DEN 1, 2,3, 4. DEN-1, DEN-2 were prevalent until 1980s DEN-3 is predominant in recent outbreak DEN-4 primarily detected in secondary dengue infections Serotype provides specific life time immunity and short term cross immunity

4. Dengue virus transmission Two general patterns Epidemic Dengue – dengue virus is introduced into a region as an isolated event that involves a single viral strain(Asia,Africa,America) 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.

6. The vector-Aedes aegypti Transmitted by the infected female Aedes aegypti Can be identified by the white bands or scale patterns on its legs and thorax Primarily a daytime feeder Found in tropical & subtropical region Lives around human habitation Lays egg & produces larvae preferentially in artificial containers

7. Vector & its transmission 0 5 8 12 16 20 24 28 DAYS Illness Illness Human #1 Human #2 Mosquito feeds/acquires virus Mosquito refeeds/transmits virus Viremia Intrinsic incubation period Extrinsic incubation period Viremia

8. Replication & transmission of Dengue virus Virus inoculated into a human being with mosquito saliva 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) The mosquito ingests blood containing the viruses (on biting an infective person)

9. Virus replicates in the midgut,ovaries,nerve tissue, fat body of the mosquito It then escapes into the body cavity and later on infects the salivary glands In the salivary glands, the virus replicates When the mosquito bites another human ,the life cycle continues Humans are the primary reservoir of infection

10. Vector Aedes aegypti/Aedes albopictus The female mosquito feeds on blood ( they need the protein found in blood to produce eggs) Male mosquitoes feed only on plant nectar. The mosquito is attracted by the body odours, carbon dioxide and heat emitted from the animal or humans .

11. Aedes aegypti Mosquito life cycle Eggs are laid on the walls of water-filled containers in the house and patio. The eggs can survive for months and hatch when submerged in water. Female mosquitoes lay dozens of eggs up to 5 times during their life time. The mosquito life cycle, takes 8 days and occurs in water. Adult mosquitoes live for one month.

12. Adult mosquitoes “usually” rest indoors in dark areas (closets, under beds, behind curtains); only female mosquitoes bite humans. The dengue mosquito can fly several hundred yards looking for water-filled containers to lay their eggs. The dengue mosquito does not lay eggs in ditches, drainages, canals, wetlands, rivers or lakes

13. Aedes aegypti

14. Aedes albopictus

15. PATHOPHYSIOLOGY

16. Rapid activation of the complement system Blood level of soluble TNF receptor, interferon-gamma,& IL-2 are C1q,C3,C4,C5-8 & C3 proactivators are These factors interact at the endothelial cell to produce vascular permeability through the nitric oxide final pathway

17. The blood clotting & fibrinolytic system are & levels of factor XII are Capillary damage allows fluid, electrolytes & small proteins ,red cells to leak into extravascular spaces 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

18. CLINICAL MANIFESTATIONS

19. Four dengue clinical syndrome Undifferentiated fever Classic dengue fever Dengue hemorrhagic fever(DHF) Dengue Shock Syndrome (DSS)- a severe form of DHF

20. Undifferentiated fever Most common presentation Silent transmission Incubation period of 3-14 days(average 4-7 days) Sudden onset of fever, biphasic Severe headache(retro-orbital)

21. Myalgias & arthalgias that may be severe Nausea & vomiting Rash may be present at the different stages of illness- maculpapular, petechial, erythematous Hemorrhagic manifestations

22. DENGUE HEMORRHAGIC FEVER

23. Dengue Hemorrhagic Fever Usually develops around 3 rd -7 th day of illness There is rapid onset of plasma leakage, altered hemostasis, and damage to the liver, resulting in severe fluid losses and bleeding Skin hemorrhage- petechiae, purpura, ecchymosis Gingival & nasal bleeding,Hematuria GI bleeding- haetamesis,melena,haematochezia

24. Plasma leakage is due to increased capillary permeability ;manifest as hemoconcentration, pleural effusion & ascites. Bleeding due to capillary fragility & thrombocytopenia Liver damage manifests as increases in levels liver enzymes, low albumin levels, and deranged coagulation parameters(PT,PTT)

25. 3 phases of DHF Febrile phase : 2-7 days Sudden onset fever Severe headache Epigastric discomfort,anorexia, vomiting Arthralgia, myalgia Flushing Tender hepatomegaly, splenomegaly Maculopapular rash

26. Leakage phase 1 ST 24-48 HOURS Pleural effusion Ascities Pericardial effusion Haemorrhagic menifestation Haematemesis,malena ,epistaxis & menorrhagia

27. Convalescent phase Short & uneventful Short & uneventful Return of appetite Bradycardia Recovery rash Severe itching on palms & soles of appetite Bradycardia Recovery z

28. Criteria to label Dengue Hemorrhagic Fever

29. WHO case definition of DHF Fever-sudden onset 2-7 days Hemorrhagic manifestations with positive tourniquet test Low platelet count(1,00,000/mm 3 or less) Objective evidence of plasma leak syndrome Hematocrit ≥ 20% above baseline Low albumin Pleural/pericardial effusions

30. Four grades of DHF Grade I - Fever & non-specific constitutional symptoms Positive tourniquet test is only hemorrhagic manifestations Grade II- Grade I manifestations + spontaneous bleeding Grade III -signs of circulatory failure Grade IV- profound shock (undetectable pulse & BP)

31. Danger signs in Dengue Hemorrhagic Fever Abdominal pain-intense & sustained Persistent vomiting Abrupt change from fever to hypothermia, with sweating Change in mental status of the patient

32. Unusual presentation of Severe Dengue Fever Encephalopathy Liver failure or fulminant hepatitis Demonstrated by Increase aminotransferas, increase bilirubin, incresae PT,APTT Cardiomyopathy-conduction defects, myocarditis Severe GI hemorrhage

33. Risk Factors Age: all groups are affected Pre-existing anti –dengue antibody,either caused by previous infection or to maternal antibodies passed to infants Higher risk in secondary infections Higher risk inlocations with two or more seroypes circulating simultaneously at high levels

34. TOURNIQUET TEST

35. Inflate BP cuff to a point midway between SBP & DBP for 5 minute 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 Positive test: 20 0r more petechiae per one inch 2

36. Positive Tourniquet Test A typical positive result from a tourniquet test may look like. This patient has more than 20 petechiae per square inches.

37. Dengue Shock Syndrome

38. Four criteria Evidence of circulatory failure, manifested indirectly by all of the following Rapid & weak pulse Narrow pulse pressure (≤ 20 mm Hg or hypotension for age) Cold, clammy skin & altered mental status Frank shock

39. Laboratory tests in Dengue Fever Complete blood count: WBC-leucopenia,lymphocytosis Platelets-thrombocytopenia Hematocrit:≥20% of the baseline Liver function tests: serum aminotransferases:deranged Serum bilirubin:increased serum albumin:low

40. Coagulation studies –PT,APTT:prolongrd Serum electrolytes:deranged Blood gases:metabolic acidosis Tourniquet test:positive Complement levels:low Blood urea:raised Chest X-ray- for effusions ECG- sinus bradycardia, prolonged PR interval

41. Serological diagnosis ELISA Anti dengue IgM & IgG Ab Sensitivity 84-98% Specificity 100% Haemagglutination inhibition test Complement fixation test Virus isolation Molecular detection - PCR

42. Treatment Mainly Supportive No hemorrhagic manifestations & well hydrated: patient sent home with instructions for “follow up” If hemorrhagic manifestations/hydration status borderline-patient observed in hospitals If warning signs are present even without evidence of shock or if DSS present-hospitalized

43. Intravenous fluids with Electrolyte balance Antipyretics-acetaminophen(aspirin and NSAIDS should be avoided as they interfere with platelet function) H2 blockers,antiemetics(Domperidone) Platelet and FFP transfusion when needed Monitoring of BP, urine output, platelet count and hematocrit Soft,balanced nutritious diet

44. Mosquito barrier Needed until fever subsides(to prevent Aedes aegypti mosquito from biting patients & acquiring virus) Patients should be kept ideally in screened room or under mosquito net

45. Treatment of DHF & DSS A medical emergency Admit in ICU Keep the patient in supine position Immediate evaluation of vital signs & degrees of hemoconcentration, dehydration & electrolyte imbalance Rapid I/v replacement with wide bore cannula –N/S ideal fluid of choice

46. Monitor CBC, LFTs, S/E, PT/APTT When pulse pressure is ≤ 10 mmHg or when elevation of Hct persists after replacement of fluids; plasma or colloids are indicated FFP & platelets for bleeding No role of corticosteroids Look for evidence of complications Avoid hypervolaemia

47. Complications Fluid & electrolyte losses Myocarditis Hepatic dysfunction Febrile convulsions Residual brain damage Encephalopathy Disseminated Intravascular coagulation Dengue shock syndrome

48. Indications for hospital discharge Absence of fever for 24 hours(without anti-fever therapy) & return of appetite Visible improvement in clnical picture Stable haematocrit 3 das after recovery from shock platelets ≥ 50,000/mm 3 No respiratory distress from pleural effusion/ascites

49. Return IMMEDIATELY to clinic or emergency department if any of the following warning signs appear :  Severe abdominal pain or persistent vomiting  Red spots or patches on the skin  Bleeding from nose or gums , Vomiting blood  Black, tarry stools  Drowsiness or irritability  Pale, cold, or clammy skin  Difficulty breathing

50. Dengue Vaccine No licensed vaccine at present Effective vaccine must be tetravalent Field testing of an attenuated tetravalent vaccine currently underway

51. PREVENTION

52. Vector control Chemical control- Larvicides may be used to kill the immature aquatic stages Ultra-low volume fumigation is effective against adult mosquitoes Mosquitoes may have resistance to commercial aerosols spray

53. Biological control - largely experimental -Placing fish in containers to eat the larvae Environmental control Elimination of larval habitats Most likely method to be effective in the long term

54. Prophylaxis Avoiding mosquito bites Use of insecticides Repellents Body covering with clothing Screening of house Destruction of the vector breeding sites Using mosquito nets

55. If storage is mandatory, a tight fitting lid or a thin layer of oil may prevent egg laying or hatching A larvicide (Abate) available as a 1% sand –granule formations may be added safely to drinking water

56. Why to control??/Purpose of control Reduce female vector density to a level below which epidemic vector transmission will not occur The minimum vector density to prevent epidemic transmission is unknown

57. Program to minimize the impact of epidemic Teaching the medical community how to diagnose and mange DHF Educating the general public to encourage & enable them to carry out vector control in their home and neighborhood

58. Common containers in which eggs develop into adult dengue mosquitoes:

59. Recent advances Gene-modified mosquitos could stop dengue fever : genetically modified mosquitoes wee released last year at sites in Malaysia and the Cayman Islands.

60. Key Message Dengue infection is preventable disease No direct person to person transmission Prevent Man – Mosquito contact to prevent the disease