Dengue fever

Dengue fever manifestations and management in children

1. Dengue in children - C.S.N.Vittal

2. Virus Is an arbovirus composed of single-stranded RNA Has 4 serotypes (DEN-1, 2, 3, 4)

3. Vector Is an arbovirus composed of single-stranded RNA Has 5 serotypes (DEN-1, 2, 3, 4 and 5) Transmitted by mosquitoes of the Stegomyia family, Aedes aegypti, a daytime biting mosquito,

4. Aedes aegypti Dengue transmitted by infected female mosquito Primarily a daytime feeder Lives around human habitation Lays eggs and produces larvae preferentially in artificial containers

5. Replication and Transmission of Dengue Virus Virus transmitted to human in mosquito saliva 2. Virus replicates target organs 3. Virus infects white blood cells and lymphatic tissues 4. Virus released and circulates in blood 3 4 1 2 Infectivity Period (about 7 days) Extrinsic Incubation Period (8–12 days) Intrinsic Incubation Period (3–14 days)

6. Replication and Transmission of Dengue Virus (Part 2) 5. Second mosquito ingests virus with blood 6. Virus replicates in mosquito midgut and other organs, infects salivary glands 7. Virus replicates in salivary glands 6 7 5

7. Modes of Transmission Mosquito bite Perinatal transmission Blood transfusion Organ transplantation Needle stick injury or laboratory accident

8. Vertical transmission & Neonatal dengue infection Incidence 1.6 - 64% peripartum maternal infection may increase the likelihood of symptomatic disease in the newborn Antibodies to the dengue virus in the dengue infected mother can cross the placenta and can cause severe dengue in newborn infants Clinical: Mild illness such as fever with petechial rash, thrombocytopenia and hepatomegaly, to severe illness with pleural effusion, gastric bleeding, circulatory failure, massive intracerebral haemorrhage

9. Case Definition Dengue Fever: An acute febrile illness of 2-7 days duration with two or more of the following manifestations: Headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations.

10. Case Definition Probable DF/ DHF : A case compatible with clinical description of dengue Fever during outbreak: OR Non-ELISA based NS1 antigen/ IgM positive. (A positive test by RDT will be considered as probable due to poor sensitivity and Specificity of currently available RDTs.)

11. Case Definition Confirmed dengue Fever: A case compatible with the clinical description of dengue fever with at least one of the following Isolation of the dengue virus (Virus culture + VE ) from serum, plasma, leucocytes. Demonstration of IgM antibody titre by ELISA positive in single serum sample. Demonstration of dengue virus antigen in serum sample by NS1-ELISA. IgG seroconversion in paired sera after 2 weeks with Four fold increase of IgG titre. Detection of viral nucleic acid by polymerase chain reaction (PCR).

12. Grading of DF/DHF (old) DF: Fever of 2-7 days with two or more of following- Headache, Retro orbital pain, Myalgia, Arthralgia with or without leukopenia, thrombocytopenia and no evidence of plasma leakage. DHF II Above plus some evidence of spontaneous bleeding in skin or other organs (black tarry stool, epistaxis, gum bleeds) and abdominal pain. Thrombocytopenia with platelet count less than 100000/ cu.mm and Hct rise more than 20% over baseline. DHF III (DSS): Above plus circulatory failure (weak rapid pulse, narrow pulse pressure < 20 mm Hg, Hypotension, cold clammy skin, restlessness). Thrombocytopenia with platelet count less than 100000/ cu.mm and Hct rise more than 20% over baseline. DHF IV (DSS): Profound shock with undetectable blood pressure or pulse. Thrombocytopenia with platelet count less than 100000/ cu.mm and Hct rise more than 20% over baseline

13. Dengue Epidemiology - WHO Dengue is now endemic in over 100 countries. As many as 3.6 billion people 40% of the world's population, reside in dengue-endemic areas. Each year, 400 million people are infected with dengue virus, 100 million become ill with dengue 21,000 deaths attributed to dengue are detected. Early identification of cases and timely initiation of correct clinical management can reduce the case fatality rate from 10% to 1%.

14. Pathogenesis • Circulation of infection‐enhancing antibodies at the time of infection e strongest risk factor for development of severe disease. • Rapid activation of the complement system. • Capillary damage ‐ internal redistribution of fluid, resulting in hemoconcentration, hypovolemia, increased cardiac work, tissue hypoxia, metabolic acidosis, and hyponatremia.

15. Pathogenesis of Severe Dengue Antibody-dependent enhancement (ADE) Occurs when nonneutralising antiviral antibodies enhance viral entry into host cells. Once inside the white blood cell, the virus replicates undetected, eventually generating very high virus titers leading to more severe disease . In Dengue - nonneutralizing heterotypic IgG anti-DENV antibodies produced during a person's first DENV infection (or sub-neutralizing level of antibodies in the case of infants who acquired IgG passively in utero) can form antibody-DENV complexes in the second infection that can allow uptake of DENV by macrophages. DENV then replicates in these macrophages thereby increasing viral production.

16. Clinical Manifestations of Dengue and Dengue Hemorrhagic Fever

17. Dengue Viral Infection Asymptomatic Symptomatic Dengue Fever Syndrome Without Hemorrhage DHF No Shock With Hemorrhage DSS Dengue Hemorrhagic Fever Undifferentiated Viral Syndrome DF DHF OLD

18. Dengue Clinical Syndromes New 1 2 3 4

19. Dengue viral infection Symptomatic As ymptomatic Mild Moderate Severe Undifferentiated DF Fever without complication like bleeding, hypotension and organ involvement Without evidence of capillary leakage Home Management DF with high risk and comorbid conditions DF with warning signs and symptoms Infants Old age Diabetes Hypertension Pregnancy CAD Hemoglobinopathies Immunocompromized patient Patient on steroids, anticoagulants or immunosuppressants DF warning signs and symptoms Recurrent vomition Abdominal pain/tenderness Generalized weakness / letharginess / restless Mild pleural effusion / ascites Hepatomegaly Increased Hct > 20% DHF I & II with minor bleeds DF/ DHF with significant hemorrhage DHF with shock ( DHF III & IV – DSS) Severe organ involvement (Expanded dengue syndrome) Severe metabolic disorder Choose Monitoring and possibly Hospitalization Tertiary level care 2009 Dengue Case Definitions

20. Suggested dengue case classification and levels of severity

21. Expanded Dengue Syndrome System Unusual or atypical manifestations CNS involvement Encephalopathy, encephalitis, febrile seizures, I/C bleed G.I. involvement Acute hepatitis / fulminant hepatic failure, cholecystitis, cholangitis, acute pancreatitis Renal involvement Acute renal failure, HUS, ATN Cardiac involvement Cardiac arrhythmia, cardiomyopathy, myocarditis, pericardial effusion Respiratory involvement Pulmonary edema, ARDS , pulmonary hemorrhage, pleural effusion Eye Conjunctival bleed, macular hemorrhage, visual impairment, optic neuritis Hematology DIC , Secondary HLH

22. CRITERIA FOR DENGUE ± WARNING SIGNS Probable dengue Live in /travel to dengue endemic area. Fever and 2 of the following criteria • Nausea, vomiting • Rash • Aches and pains • Tourniquet test positive • Leukopenia Any warning sign • Abdominal pain or tenderness • Persistent vomiting • Clinical fluid accumulation • Mucosal bleed • Lethargy, restlessness • Liver enlargement > 2 cm • Laboratory: Increase in HCT concurrent with rapid decrease platelet count *(requiring strict observation and medical intervention) Warning signs*

23. CRITERIA FOR SEVERE DENGUE

24. Risk Factors for Severe Dengue

25. The course of dengue illness Febrile Phase Critical Phase Recovery Phase

26. The course of dengue illness Probable adverse events

27. Febrile Phase of Dengue Typical duration of 0–7 days Biphasic fever possible Monitoring for  defervescence  and warning signs crucial to identify progression into the critical phase. Defervescence occurs between day 3 and day 8 of the illness.

28. Febrile Phase of Dengue Abrupt onset of high temperature + any of the following: Severe headache Retro orbital pain Myalgia Arthralgia Transient  macular  or  maculopapular  rash Minor hemorrhagic manifestations, for example  petechiae ,  ecchymosis , purpura,  epistaxis , bleeding gums,  hematuria , or a positive tourniquet test Facial flushing or erythema Injected oropharynx Anorexia                                         Some persons with dengue may only have fever Laboratory findings   Leukopenia Mild to moderate  thrombocytopenia h aspartate aminotransferase (AST) h alanine aminotransferase (ALT) Hyponatremia

29. Febrile Phase – Medical Complications Dehydration Hyponatremia Febrile seizures in young children Neurologic disease manifestations, including  encephalitis  and aseptic meningitis

30. Critical Phase – Clinical Manifestations Rapid decline in platelet count with a rise in hematocrit (HCT) Leukopenia up to 24 hours before platelet drop is recognized Presence of warning signs for severe disease Warning signs Clinical fluid accumulation, such as  ascites ,  pleural effusion Liver enlargement > 2 cm Severe abdominal pain\Persistent vomiting (at least 3 vomiting episodes within 24 hours) Mucosal bleed Lethargy or restlessness

31. Bleeding Manifestations in Patients with Dengue Mild hemorrhagic manifestations (in 1/3 cases) petechiae, purpura, epistaxis, and gingival bleeding Might be due to increased capillary fragility as a result of thrombocytopenia or platelet dysfunction. Major mucosal bleeding gastrointestinal or vaginal - in dengue patients can be occult and is often associated with prolonged shock and metabolic acidosis.

32. Causes of Bleeding in DF/ DHF Abnormal coagulogram Thrombocytopenia Platelet dysfunction • Prothombin complex deficiency secondary to Liver involvement Endothelial injury DIC and Prolong aPTT Decrease fibrinogen level Increase level of fibrinogen degradation product (FDP) Increase level of D-Dimer Consumptive coagulopathy (activation of mononuclear phagocytes) Sequestration of platelets

33. Coagulopathy Due to loss of essential coagulation proteins due to plasma leakage. Interactions between dengue virus nonstructural protein 1 (NS1) and the endothelial glycocalyx layer may cause a change in filtration characteristics, resulting in leakage of plasma proteins and release of heparan sulfate into the circulation. Heparan sulfate , which can function as an anticoagulant, might contribute to the coagulopathy

34. Thrombocytopenia Thrombocytopenia is defined by the World Health Organization (WHO) as a platelet count of less than or equal to 100,000/ μ L . Causes Early pancytopenic suppression of the bone marrow either by direct infection of progenitor cells or by macrophages that activate T-cells that release cytokines that suppress hematopoeisis . Peripheral immune mediated platelet destruction via dengue virus binding to platelet in presence of NS1 antibody, so that the half-life of platelets are decreased in dengue patients. DIC Peripheral sequestration of platelets

35. Dengue virus infection Production of antibodies/presence of enhancing antibodies Antigen antibody reaction with complement activation Deposition on vessels, various tissues and platelets Clinical manifestations of coagulopathy (bleeding) Activation of T- cells Production of various chemical mediators Increased vascular permeability Clinical manifestations of vasculopathy (capillary leakage) Hypotension/shock Pleural effusion Ascites Bleeding Organ involvement Patho-physiology of DF/ DHF

36. Clinical Features of of DF/ DHF Undifferentiated dengue Fever ( UDF ) Severe dengue Fever Dengue Fever with warning signs and symptoms: Expanded dengue Syndrome (EDS)

37. Critical Phase – Lab Findings and Medical Complications Laboratory findings Increase in HCT or hemoconcentration Moderate to severe thrombocytopenia Leukopenia Transient increase in activated partial- throboplastin time ( aPTT ) with decrease in  fibrinogen Medical complications during the critical phase include the following: Hypovolemic shock from plasma leakage End organ impairment due to prolonged shock Severe hemorrhage Encephalopathy

38. Recovery Phase of Dengue Patient improvement Gradual reabsorption of  extravasated  fluid (such as from plasma leakage) over 48–72 hours Increased diuresis (patient might wet bed)  Hemodynamic status stabilizes Patient can temporarily become bradycardic (but hemodynamically stable)

39. Recovery Phase - Clinical Manifestations A second rash that might be macular or erythematous with small circular islands of normal, unaffected skin. This convalescent rash can be very pruritic and desquamate. Severe fatigue Laboratory findings   HCT stabilizes or is slightly lower due to a dilutional effect of reabsorbed plasma (hemodilution) White blood count (WBC) begins rising soon after defervescence Platelet count increases following WBC recovery

40. Recovery Phase - Medical Complications Hypervolemia and acute pulmonary edema   can occur if intravenous fluid (IVF) therapy has been excessive or extended too long. Organ impairment   can result in the event of prolonged or  refractory  shock. This might include ischemic hepatitis and hepatic encephalopathy. Nosocomial   or   hospital-acquired infections ,  can occur, especially in infants and elderly patients.

41. Causes of Death Unrecognized dengue without appropriate medical management Unrecognized or prolonged shock Unrecognized occult hemorrhage Fluid overload Nosocomial infections Liver failure

42. Diagnosis

43. Tourniquet Test 1. Take the patient's blood pressure and record it, for example, 100/70. 2. Inflate the cuff to a point midway between SBP and DBP and maintain for 5 minutes. 3. Reduce and wait 2 minutes. 4. Count petechiae below antecubital fossa. A positive test is 10 or more petechiae per 1 square inch . More likely to be positive near time of defervescence Less likely to be positive in patients with shock Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 12.

44. Lab tests Antigen NS1 test ELISA- IgG , IgM antibodies Blood cultures- isolate the virus Full blood count Hct Liver function test PCR- Nucleic acid detection

45. Dengue diagnostic and sample characteristics Clinical sample Diagnostic method Methodology Time to results Virus detection and its components Acute serum (1-5 days of fever) and necropsy tissue Viral isolation Mosquito or mosquito cell culture inoculation One week or more Nucleic acid detection RT-PCR and real time RT-PCR 1 to 2 days Antigen detection NS1 Ag rapid tests Minutes NS1 Ag ELISA 1 day Immuno-histochemistry 2-5 days Serological response Paired sera (acute serum 1-5 days and 2 nd serum 15-21 days after) IgM or IgG seroconversion ELISA HIA 1-2 days Neutralization test Min 7 days Serum after day 5 of fever IgM detection (recent infection) ELISA 1 or 2 days Rapid tests Minutes IgG detection IgG ELISA HIA 1 or 2 days

46. Interpretation of dengue diagnostic tests [adapted from Dengue and Control (DENCO) study] Highly suggestive Confirmed One of the following: IgM + ve in a single serum sample IgG + ve in a single serum sample with a HI titre of 1280 or greater One of the following: PCR + Virus culture + IgM seroconversion in paired sera Four fold IgG titer increase in paired sera

47. Differential Diagnosis of Dengue Influenza Measles Rubella Malaria Typhoid fever Leptospirosis Meningococcemia Rickettsial infections Bacterial sepsis Other viral hemorrhagic fevers

48. A stepwise approach to the management of dengue

49. Step I History, including information on symptoms, past medical & family history Physical examination, including full physical and mental assessment Investigation, including routine laboratory and dengue-specific laboratory Step II Diagnosis, assessment of disease phase and severity Step III Disease notification Management decisions. Depending on the clinical manifestations and other circumstances, patients may: –  be sent home (Group A) ; –  be referred for in-hospital management (Group B) ; –  require emergency treatment and urgent referral (Group C). A stepwise approach to the management of dengue

50. Patient Assessment Steps

51. Patient Assessment Steps

52. Patient Assessment Steps

53. Patient Assessment Steps Step 2: Clinical Assessment General Assessment: Mental state Hydration state Hemodynamic state Clinical e/o. warning signs Bleeding manifestations: mucosal bleeding Abdominal tenderness Liver enlargement Fluid accumulation,: pl effusion, ascites Other imp signs: Rash Tachypnoea/acidotic breathing: indicates shock Torniquet test: repeat if – ve

54. Hemodynamic Assessment Clinical Parameters

55. Parameters Conscious level Capillary refill time Extremities (color, temp) Peripheral Pulse volume Heart rate (HR) Pulse pressure (PP) Blood pressure (BP) Respiratory rate (RR) Urine output } } Organ perfusion (brain) Cardiac output Organ perfusion (kidney) Peripheral perfusion Respiratory compensation for tissue hypoxia

56. Parameters Stable condition Compensated shock Conscious level Clear and lucid Clear and lucid Capillary refill time Brisk(less than 2 sec) Prolonged (>2 sec) Extremities (color, temp) Warm and pink Cold peripheries Peripheral Pulse volume Good volume Weak & thready Heart rate (HR) Normal HR for age Tachycardia for age Pulse pressure (PP) Normal PP for age Normal systolic pressure Rising diastolic pressure Blood pressure (BP) Normal BP for age Narrowing of PP Postural hypotension Respiratory rate (RR) Normal RR for age ‘Quiet tachypnea’ Urine output Normal Reducing trend Normal brain function Reduced kidney perfusion Tissue acidosis Reduced Peripheral perfusion Reduced cardiac output } }

57. Parameters Stable condition Compensated shock Hypotensive shock Conscious level Clear and lucid Clear and lucid Restless, combative Capillary refill time Brisk(less than 2 sec) Prolonged (>2 sec) Very prolonged, mottled skin Extremities (color, temp) Warm and pink Cold peripheries Cold and clammy Peripheral Pulse volume Good volume Weak & thready Feeble or absent Heart rate (HR) Normal HR for age Tachycardia for age Severe tachycardia or bradycardia in late shock Pulse pressure (PP) Normal PP for age Normal systolic pressure Rising diastolic pressure Hypotension Unrecordable BP Blood pressure (BP) Normal BP for age Narrowing of PP Postural hypotension Narrowed pulse pressure ( < 20 mm Hg) Respiratory rate (RR) Normal RR for age ‘Quiet tachypnea’ Kussamal breathing Urine output Normal Reducing trend Oliguria or anuria } } Reduced brain function Reduced Peripheral perfusion No kidney perfusion Severe t issue acidosis Reduced cardiac output

58. Definition of hypotension Adults : Systolic blood pressure of < 90 mm Hg or Meal arterial pressure < 70 mm Hg or Systolic blood pressure decrease of > 40 mm Hg or < 2 SD below normal for age (Hypertensive patients) Children upto 10 year of age : The 5 th centile for systolic pressure 70 + (age in years X 2) mm HG

59. Pearls in clnical examination of dentue patients The “5-in-1 maneuver” magic touch – CCTV-R Hold patient’s hand to evaluate peripheral perfusion Save life in 30 seconds by recognizing shock

60. Algorithm for management of Dengue Warning Signs

61. Group A Outpatient Management During the febrile phase (may last 2–7 days) and subsequent critical phase (1–2 days), your clinic should Follow CBCs Watch for dehydration
Watch for warning signs, including decreasing platelet count and increasing hematocrit Watch for defervescence (beginning of critical phase)

62. Group A Advise patient or their family to do the following Control the fever Prevent dehydration Prevent spread of dengue within your house Watch for warning signs as temperature declines 3 to 8 days after symptoms began. Severe abdominal pain or persistent vomiting Red spots/patches on skin Bleeding from nose or gums Vomiting blood, Black, tarry stools Drowsiness or irritability Pale, cold, or clammy skin Difficulty breathing

63. Group B - Pts with Waning Signs Admit Obtain baseline CBC Monitor fluid I/O Encourge oral fluids Monitor vital sings q4h Adequate? Check Hct IV fluids (NS.RL) 5-7 ml/kg/ hr for 1-2 hrs 3-5 ml/kg/ hr for 2-4 hrs Keep monitoring Check Hct Observe for shock, warning signs of severe dengue Group C management If NO improvement or Compensated or Hyootensive shock If improvement - YES Reduce isotonic crystalloids in stepwise manner 5–10 ml/kg/hour for 1–2 hours 3–5 ml/kg/hour for 2–4 hours 2–3 ml/kg/hour for 2–4 hours

64. Group B - Pts with Waning Signs Some patients in Group B have warning signs and are hemoconcentrated  but are not in shock. If they are in shock, they are in group C. Before giving them IVFs, obtain a reference or baseline HCT. Follow the algorithm below.   Give isotonic IVFs at 5–7 mL/kg/hr. Reduce after 1–2 hours to 3–5 mL/kg/ hr for 2–4 hours if clinical status allows and reassess the patient’s condition (vital signs, capillary refill, urine output). Repeat the HCT. If the HCT remains the same or rises minimally, reduce rate to 2–3 mL/kg/ hr for 2–4 hours, then reassess HCT. If vital signs worsen and HCT rapidly rises, increase rate to 5–10 mL/kg/ hr for 1–2 hours. Reassess the clinical status; repeat HCT and revise IVF rates accordingly.

65. Initiate Intravenous therapy @ 10ml/kg over 1 hour Reassess Clinical Status Reduce IV fluids stepwise 6ml/kg/ hr for 2-4 hours 3 ml/kg/ hr for 2-4 hours 3-1.5 ml/kg/ hr for 2-4 hrs Further improvement If worsening 10-20 ml/kg for 1 hour If improvement after 2 nd bolus, reduce to 7-10 ml/kg for 1-2 hours If no improvement & if HCT decreases > blood transfusion Group C - Pts with Compensated Shock HDHF Grades I & II Hemodynamic status improved Discontinue IV after 24-48 hr Hemorrhagic tendencies, thrombocytopenia, Hct rise > 20%

66. Check Hematocrite Improvement Crystalloid/Colloid 10 ml/kg for 1 hr , then reduce to 5-7 ml/kg 1-2 hrs 3-5 ml/kg/ hr for 2-4 hrs 2-3 ml/kg/ hr for 2-4 hrs If Hct increases or is high adm 3 rd bolus fluid (colloid) 10-20 ml/kg over 2 hrs HCT decreasing Consider significant occult /overt bleed Initiate blood transfusion HCT increasing or high Adm 2nd bolus fluid (colloid) 10-20 ml/kg over ½ to 1 hr No improvement Yes No Stop After 48 hrs Group C - Pts with Hypotensive Shock Fluid resuscitation with 20 ml/kg over 15 minutes isotonic crystalloid or colloid

67. Targets of fluid resuscitation Improving central and peripheral circulation Decreasing tachycardia Improving BP and pulse volume Warm and pink extremities with a capillary refill time < 3 seconds Improving end-organ perfusion Achieving a stable conscious level (more alert or less restless) Urine output ≥ 0.5 ml/kg/hour Decreasing metabolic acidosis.

68. Points to remember in fluid resuscitation No hypotonic fluids. Cautious with glucose containing fluids like DNS. Targeting a minimally acceptable hourly urine output (0.5–1 mL/kg/hr) is an effective and inexpensive monitoring modality. A urine output of more than 1.5–2 mL/kg/hr should prompt reduction in fluid infusion rates, provided hyperglycemia has been ruled out. In case of persistent shock, after fluid resuscitation, if the hematocrit continues to decline, internal bleeding should be suspected. Blood transfusion is life-saving and should be given as soon as severe bleeding is suspected or recognized. Do not wait for the haematocrit to drop too low before deciding on blood transfusion. Prefer fresh blood. Use Ideal Body Weight to calculate IV fluid rates in Obese children.

69. WHEN TO STOP INTRAVENOUS FLUIDS Features of intra vascular compartment overload • Hypertension with good volume pulse. Breathing difficulties, pulmonary edema. 48 hours after defervescence.

70. Management of Dengue Patient - Summary GROUP-A GROUP-B GROUP-C Give anticipatory guidance prior to sending patient home (Refer to patient handout) Admit patient to hospital In addition to Group B management, do the following: Follow-up daily Monitor hemodynamic status frequently Use colloids for refractory shock Do serial CBCs Use HCT to determine interventions Monitor for occult bleeding Identify warning signs early Use isotonic IVFs judiciously Correct metabolic acidosis and electrolyte abnormalities as needed *Do not use prophylactic platelet transfusions.

71. Discharge criteria (all of the following conditions must be present) Clinical No fever for 48 hours. Improvement in clinical status general well-being, appetite, haemodynamic status, urine output, no respiratory distress Laboratory Increasing trend of platelet count. Stable haematocrite without intravenous fluids.

72. Dengue Vaccine? No licensed vaccine at present Effective vaccine must be tetravalent Field testing of an attenuated tetravalent vaccine currently underway Effective, safe and affordable vaccine will not be available in the immediate future

73. Avoid mosquito bites when traveling in tropical areas: Use mosquito repellents on skin and clothing. Wear long-sleeved shirts and long pants tucked into socks. Avoid heavily populated residential areas. When indoors, stay in air-conditioned or screened areas. Use bednets if sleeping areas are not screened or air-conditioned. If you have symptoms of dengue, report your travel history Eliminate mosquito breeding sites in areas where dengue might occur: Eliminate mosquito breeding sites around homes. Discard items that can collect rain or run-off water, esp. old tires. Regularly change the water in outdoor bird baths and pet and animal water containers.  Prevention

74. Thank You - Dr. C.S.N.Vittal