DENGUE AND ITS MANAGEMENT

COUNTRIES / AREAS AT RISK OF DENGUE TRANSMISSION

DENGUE : EPIDEMIOLOGY Average Annual No. Of Dengue Fever Cases Reported To WHO And Average Annual Number Of Countries Reporting Dengue

DENGUE FEVER : INTRODUCTION ‘Break-bone fever’ (Haddi tod bukhar) Four dengue virus serotypes, i.e. Dengue 1-4. Infection with one serotype provides life-long immunity against reinfection by that same serotype, but not against the other serotypes.

DENGUE FEVER : INTRODUCTION Principal mosquito vector is Aedes aegypti . Adult mosquitoes shelter indoors and bite during the daytime. Other vectors of less importance: Ae albopictus, Ae polynesiensis Ae scutellaris

LIFE CYCLE OF AEDES MOSQUITO

DENGUE FEVER : INCUBATION PERIOD Incubation Period : Commonly, it is 5-6 days ( 3-10 days )

DENGUE FEVER : PATHOPHYSIOLOGY Risk of severe disease is increased at least 15-fold during repeat (secondary) compared to primary dengue infections . Various mechanisms suggested : Antibody-dependent enhancement or ADE , Complement activation by virus-antibody complexes T-cell mediated immunopathology

DENGUE FEVER : PATHOPHYSIOLOGY DOMINANT HYPOTHESIS ADE : SECONDARY INFECTION PRE-EXISTING NON-NEUTRALISING ANTIBODIES OPSONISE THE VIRUS ENHANCES VIRAL UPTAKE AND REPLICATION IN MACROPHAGES. LEAD TO HIGHER VIRAL LOADS

DENGUE FEVER : PATHOPHYSIOLOGY DOMINANT HYPOTHESIS ADE : LEAD TO HIGHER VIRAL LOADS INFECTED MONOCYTES TO RELEASE VASOACTIVE MEDIATORS THROMBOCYTOPENIA, VASCULOPATHY, COAGULOPATHY ENDOTHELIAL DAMAGE LEADS TO CAPILLARY LEAK OR FRANK BLEED MANIFESTATIONS OF SEVERE DENGUE

DENGUE FEVER : PRESENTATION Symptomatic Dengue Infection Undifferentiated fever Dengue Hemorrhagic Fever Dengue Fever Without Hemorrhage With Unusual hemorrhage Dengue Shock Syndrome No Shock

DENGUE FEVER : WHO CASE DEFINTION 􀂄 Fever or history of acute fever, lasting 2-7 days, occasionally biphasic. 􀂄 Bleeding (Haemorrhagic tendencies) – A Positive Tourniquet Test (TT) – Petechiae, Ecchymosis, Or Purpura – Bleeding From The Mucosa, Gastrointestinal Tract, Injection Sites Or Other Locations – Haematemesis Or Melena

DENGUE FEVER : WHO CASE DEFINTION 􀂄 Thrombocytopaenia (100,000 cells / mm3 or less) 􀂄 Evidence of plasma leakage due to increased vascular permeability: – Rise in haematocrit > 20% – Drop in haematocrit following volume-replacement treatment > 20% – Pleural effusion, Ascites, and Hypoproteinaemia.

WHEN TO SUSPECT DENGUE FEVER In background of epidemic: Unusual rise in fever cases Associated with bleeding manifestation Fever not associated with URI symptoms

DENGUE FEVER Acute febrile illness of 2-7 days duration (BIPHASIC) with two or more of the following manifestations: Ø Headache Ø Retro -Orbital Pain Ø Myalgia / Arthralgia Ø Rash Ø Thrombocytopenia May Be Present. Ø Leukopenia ocassinally. There is no evidence of plasma loss. In children: Fever, nausea , vomiting, Hepatomegaly, thrombocytopenia more common

DENGUE DISEASE COURSE 0 2 4 6 8 10 12 14 16 18 IgG MOSQUITO BITE IgM 0 2 4 6 8 10 12 14 16 18 AFEBRILE CRITICAL HEMORRHAGE SHOCK Thrombocyto--penia IgG MOSQUITO BITE IgM FEVER VIREMIA RECOVERY

The dengue NS1 antigen-capture ELISA gave an overall sensitivity of 70-93.4% and a specificity of 100%. The sensitivity was significantly higher in acute primary dengue (97.3%) than in acute secondary dengue (70.0%). The positive predictive value of the dengue NS1 antigen-capture ELISA was 100% and negative predictive value was 97%.

TREATMENT : DENGUE FEVER & DHF

SOME TREATMENT PRINCIPLES MONITOR B L O O D P R E S S U R E HEMATOCRIT PLATELET COUNTS

SOME TREATMENT PRINCIPLES BLOOD PRESSURE Narrow pulse pressure (<20 mm Hg) Hypotension for age (this is defined as systolic pressure < 80 mmHg for those less than five years of age, or < 90 mmHg for those five years of age and older. HEMATOCRIT Haematocrit every two hours during the first six hours and later every four hours until stable. PLATELET COUNTS Should be done every 24 hrs

SOME TREATMENT PRINCIPLES HEMATOCRIT RISES + BP FALLING + ↓ URINE OUTPUT SIGN OF EXTRAVASATION OF FLUID FROM VASCULAR COMPARTMENT CONSIDER FOR I/V FLUIDS.

SOME TREATMENT PRINCIPLES HEMATOCRIT FALLS + BP FALLING + ↓ URINE OUTPUT SIGN OF INTERNAL BLEEDING CONSIDER FOR BLOOD TRANSFUSION.

SOME TREATMENT PRINCIPLES HEMATOCRIT FALLS + BP IMPROVING + ↑ URINE OUTPUT BACK SHIFT OF FLUID TO VASCULAR COMPARTMENT WATCH FOR FLUID OVERLOAD

SOME TREATMENT PRINCIPLES 20 10 7 5 3

TRIAGE OF DENGUE PATIENTS SEND BACK HOME: NO DHF/ DSS PLATELET COUNT > 1 LACKS BP NORMAL OBSERVATION : ANY SIGNS OF DHF ↓ PLATELETS ↓ TLC HCT ↑ > 10 % MILD SIGNS OF PLASMA LEAKAGE

Indications for admission are – rise in haematrocrit of 20% or more, a single haematocrit value of ›40%, platelets count of ≤ 50,000/cmm, spontaneous haemorrhage, signs and symptoms of shock, oliguria and circum-oral cyanosis.

TRIAGE OF DENGUE PATIENTS WARD : RESTLESSNESS PLATELET < 50 THOUSAND RESTLESSNESS/ DROWSY PULSE LOW , BP↓ ICU : COMPLICATIONS SIGNS OF MASSIVE BLEEDING DSS

TREATMENT : DENGUE FEVER & DHF Febrile Phase In the early febrile phase, it is not possible to distinguish DF from DHF. Their treatments are the same, i.e. symptomatic and supportive: Ø Rest. Ø Paracetamol Ø Do not give antibiotics as these do not help. Ø Oral rehydration therapy Ø Food should be given according to appetite.

TREATMENT : DENGUE FEVER & DHF Points To Remember: Ø Paracetamol : not more than 4 times in 24 hours Do not give Aspirin or Brufen / NSAIDS. Fear of : gastritis / bleeding. Reye’s syndrome (encephalopathy) , In children,

TREATMENT : DENGUE FEVER & DHF Points To Remember: Ø Oral rehydration therapy In Children oral rehydration solution or fresh juices are preferable (50ml/kg bodyweight - during the first 4-6 hrs. + maintenance fluids. ) Breastfeeding should be continued In adults Oral fluid intake of 2.5-4.0 litres should be given per day.)

DENGUE FEVER : DANGER SIGNS Severe Abdominal Pain, Passage Of Black Stools, Bleeding Into The Skin Or From The Nose Or Gums, Sweating Cold Skin All dengue patients must be carefully observed for complications for at least 2 days after recovery from fever. Patient who has no complication and who is afebrile for last 2-3 days does not need further observation.

TREATMENT OF AFEBRILE/ CRITICAL STAGE Afebrile Phase : 2-3 days after febrile illness Dengue Fever: Most patients will recover without complication. Bed rest Check platelets/haematocrit Oral fluids and electrolyte Therapy Convalescence Phase Further improvement in the condition. Duration – 7-10 days after critical Stage

TREATMENT OF AFEBRILE/ CRITICAL STAGE Dengue Haemorrhagic Fever Grades I Do not usually require intravenous fluid therapy ORT is sufficient. Intravenous fluid therapy may needed: Vomiting persistently or severely, Refusing to accept oral fluids. Patients with DHF grade I who live far away from the hospital or those who are not likely to be able to follow the medical advice should be kept in the hospital for observation. Intravenous fluid therapy before leakage is not recommended.

CHOICE OF FLUID FOR INTRAVENOUS THERAPY Crystalloid: 5% dextrose in isotonic normal saline solution (5% D/NSS) (b) 5% dextrose in half-strength normal saline solution (5% D/1/2/NSS) (c) 5% dextrose in lactated Ringer’s solution (5% D/RL) (d) 5% dextrose in acetated Ringer’s solution (5% D/RA) Colloid : a) Dextran 40 b) Plasma

DENGUE : FLUID REPLACEMENT The volume of fluid replacement should be just sufficient to maintain effective circulation during the period of plasma leakage. Excessive fluid replacement and continuation for a longer period after cessation of leakage will cause respiratory distress from massive pleural effusion, ascites, and pulmonary congestion / oedema.

3ml/kg/hr; 6ml/kg/hr; 10ml/kg/hr, and 20ml/kg/hr. DENGUE : FLUID REPLACEMENT For intravenous fluid therapy of patients with DHF, four regimens of flow of fluid are suggested.: 3ml/kg/hr; 6ml/kg/hr; 10ml/kg/hr, and 20ml/kg/hr.

DENGUE : FLUID REPLACEMENT In general, the volume required is maintenance plus 5-8% deficit.

DENGUE : PLATELET THERAPY Bleeding during DHF may occur due to number of factors such as thrombocytopenia, coagulopathy, vasculopathy. The main risk factor for severe bleeding in DSS was longer duration of shock. Thrombocytopenia and coagulopathy were not predictive of bleeding. The prevention of hemorrhage in DHF/ DSS should be directed at early recognition of shock and its prompt correction rather than transfusions of PC and FFP.

DENGUE : PLATELET THERAPY Platelet should be considered : <20,000/ cumm 20,000 – 40,000 with bleeding (Asian journal of transfusion science january 2007) No difference in the frequency of bleeding was observed comparing patients who received or those who did not receive a platelet transfusion (even in those with a platelet count < 25,000/ml). (Dengue bulletin volume 27, 2003)

DENGUE : PLATELET THERAPY One retrospective paediatric intensive care study showed no benefit in prophylactic platelet transfusion for thrombocytopenia <30,000/uL. (European society of Clinical Microbiology and Infectious Diseases Barcelona, Spain, April 2008)

ALWAYS REMEMBER: Cases of DHF should be observed every hour. Serial platelet and haematocrit determinations, are essential for early diagnosis of DHF. Timely intravenous therapy – can prevent shock and/or lessen its severity. If the patient’s condition becomes worse despite giving 20ml/kg/hr for one hour, replace crystalloid solution with colloid solution such as Dextran or plasma. As soon as improvement occurs replace with crystalloid.

ALWAYS REMEMBER: If improvement occurs, reduce the speed from 20 ml to 10 ml, then to 7 ml, and finally to 3 ml/kg. If haematocrit falls, give blood transfusion 10 ml/kg and then give crystalloid IV fluids at the rate of 10ml/kg/hr. In case of severe bleeding, give fresh blood transfusion about 20 ml/kg for two hours. Then give crystalloid at 10 ml/kg/hr for a short time (30-60 minutes) and later reduce the speed. In case of shock, give oxygen. For correction of acidosis (sign: deep breathing), use sodium bicarbonate

DONT’S Do not give Aspirin or Brufen/ NSAIDS. Do not give blood transfusion unless indicated, reduction in haematocrit or severe bleeding along with deterioration of vitals. Do not use steroid

DONT’S Antibiotics are of no use Do not change the speed of fluid rapidly, i.e. avoid rapidly increasing or rapidly slowing the speed of fluids. Insertion of nasogastric tube to determine concealed bleeding or to stop bleeding (by cold lavage) is not recommended since it is hazardous.

DENGUE : SIGNS OF RECOVERY Stable pulse, blood pressure and breathing rate Normal temperature No evidence of external or internal bleeding Return of appetite

DENGUE : SIGNS OF RECOVERY No vomiting Good urinary output Stable haematocrit Convalescent confluent petechiae rash

CRITERIA FOR DISCHARGING PATIENTS Absence of fever for at least 24 hours without the use of anti-fever therapy Return of appetite Visible clinical improvement Good urine output Minimum of three days after recovery from shock No respiratory distress from pleural effusion and no ascites Platelet count of more than 50,000/mm3

PREVENTION • Preventing breeding of Aedes mosquitoes • Protection from Aedes mosquitoes’ bites.

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