Who Is Afraid Of Dengue Fever

PUBLIC ENEMY NO. 1

Dengue Haemorrhagic Fever Dr. SOMESH MEHROTRA Critical care Specialist Siddhi Vinayak Hospital Bareilly , UP, india 9837000048

To fight- you should know the enemy inside out

Four lives of Dengue virus • Family flaviviridae . • has four serovars.den1-den2,den3and den4 • Infection with one serotype confers long term immunity to that serotpt only

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Efficient vector susceptible to Dengue virus. Bites many human for a single meal in day time. Urban dweller

Global problem • Recognized in the Philippines in 1953.

Transmission of Dengue Viruses • Viruses are transmitted from humans to mosquitoes to humans • Next generation of mosquitoes • Human are the main amplifying hosts • Monkeys can also be reservoirs • The virus circulates in the blood approx. at the time of fever

OUT BREAK-PART I (Two important epidemiological patterns) DHF/DSS in where multiple dengue serotypes are endemic. Sporadic cases or small outbreaks in urban areas that steadily.increase in size Pattern of epidemic activity every 2-5 years.

OUT BREAK PART - II A second pattern Low endemicity Multiple Dengue serotypes Relatively low rates of infections

Pathology ……At autopsy Frequency of Hemorrhage • Skin and subcutaneous tissue<Mucosa of the GIT< Heart < Liver.<Subarachnoid or cerebral hemorrhage is rarely seen. • Serous effusion with a high protein content is seen in pleural and abdominal cavities but not in pericardial. • Light microscopy of blood vessels shows no significant changes in vascular walls. • Lymphocyte tissue shows an increased activity of B-lymphocyte system with Plasma cells and lymphoblastoid cells

Liver • There is focal necrosis of hepatic cells, swelling.

Kidney • Immune-complex type of glomerulonephritis which resolves completely in 3 weeks • Perivascular Oedema • Sderum complement, immunoglobulin and fibrinogen.

Bone marrow • Depression of all haematopoietic cells was observed, which would rapidly improve as fever subsided.

Pathogenesis of DHF/DSS • Vascular permeability. (Haemoconcentration, low pulse pressure. Sign of shock.)

• of the complement system

Disorder in haemostasis ( Vascular changes, Thrombocytopenia and coagulopathy.)

of C3 and C5 levels.

• Platelet defects both qualitative and quantitative.

Secondary Infections • Enhancement of virus replication in macrophages by heterotypic antibodies. • Cross-reactive but not neutralizing antibodies. • Cross-reactive CD4+ and CD8 + cytotoxic lymphocytes. • Cross Reaction

Classic Features Breakbone fever, sudden onset ,severe headache, retroorbital pain, and fatigue, severe myalgia and arthralgia . lasts five to seven days. • Rash, typically macular or maculopapular and confluent with the sparing of small islands of normal skin , near the time of defervescence, lasts for two to four days, and may have scaling and pruritus. • Flushed facies ( the first 24 to 48 hours), lymphadenopathy, injected conjunctivae, an inflamed pharynx, and mild respiratory and gastrointestinal symptoms.

Case Definitions •

Probable Dengue Fever

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An acute febrile illness with two or more of the following : — headache — retro-orbital pain —myalgia —rash —heamorrhagic manifestations —leukopenia and supportive serology : antibody titre >1280, a comparable IgG ELISA titre, or a positive IgM antibody test Or —occurrence at the same location and time as other confirmed cases of dengue fever.

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Case Difination Confirmed dengue fever •

Isolation of the dengue virus from serum or autopsy; or

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A fourfold or greater change in rciprocal IgG or IgM antibody titres to one or more dengue virus antigens in paried serum samples; or

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Dengue virus antigen in autopsy tissue, serum or C.S.F. samples by immunohistochemistry, immunofluorescence or ELISA; or

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Dengue virus genomic sequences in autopsy tissue serum or C.S.F. samples by PCR.

Case definition

Dengue haemorrhagic fever • •

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All of the following must be present Fever, or history of acute fever, lasting 2-7 days occasionally biphasic. Haemorrhagic tendencies(at least one of--) Tourniquest test 1. Petechiae, ecchymoses,purpura 2. Bleeding-mucosa,git,injection site 3. Haemetemesis, malena Thrombocytopenia (100000 cells per mm3 or less). Evidence of plasma leakage due to increased vascular permeability, manifested by at least one of the following. 1. A rise in PCV equal to or greater then. 2. A drop in the haematocrit following volume-replacement treatment equal to or greater than 20% of baseline; 3. Signs of plasma leakage such as pleural effusion, ascities and hypoproteinaemia.

Case Definition for Dengue Shock Syndrome • •

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All four points of DHF and ; Rapid and weak pulse. Narrow pulse pressure(< 20mm (2.7KPa)) or manifested by : Hypotension for age. Cold, clammy skin and restlessness.

Hg

Drugs for dengue

Tourniquet test

Blood pressure cuff on the upper arm to a point between the systolic and diastolic pressure for 5 minutes. Positive when 20 or more petechiae per 2.5cm. (1 inch) square are observed.

Grading severity of DHF Grade I : Fever + non-specific cc + tourniquet test and/or easy bruising. Grade II : Spontaneous bleeding. ………………..DSS……………….. Grade III : Circulatory failure i.e. a rapid, week pulse and narrowing of pulse pressure or hypotension, + cold, clammy skin and restlessness. Grade IV : Profound shock with undetectable blood pressure or pulse.

Indications for hospitalization for bolus intravenous fluid therapy may be necessary where significant dehydration (>10% of normal body weight) has occurred and rapid volume expansion is needed. Signs of significant dehydration include :

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Tachychardia Ivreased capillary refill time (>2s) Cool, mottled or pale skin Diminished peripheral pulses Changes in metal status Oliguria Sudden rise in haematocrit or continuously elevated haematocrit despite administration of fluids • Narrowing of pulse pressure (<20mmHg (2.7KPa)) • Hypotension (a late finding representing uncorrected shock).

DHF-treatment # ORS • Hyperpyrexia • Day of judgment;is the day of defervescence

DSS-treatment rapid replacement of fluid • RL ,ringer acetate, DNS, in< 20 minutes ,10-20ml/kg • Another bolus to total 20-30ml/kg ….Still shock• PCV rising—plasma, plasma substitute or albumin • If PCV falling—fresh blood

DSS- continued replacement • Plasma loss may continue for 24-48 hrs • CVP measurement • Reabsorption of extravasated plasma=pcv falls • Blood transfusion

Essential lab tests Hb%, Haematocrit, GBP • Serum electrolytes and blood gas studies • Platelet count, prothrombin time, partial thromboplastin time and thrombin time. • LFT,SGPT,SGOT, and serum protrins. • CXR

Unusual manifestations of dengue haemorrhagic fever • Acute hepatic failure • Maintainance of consciousness even in presence of severe shock

Criteria for discharging inpatients • • • • • •

Absence of fever for at least 24 hours. Return of appetite. Visible clinical improvement. Good urine out put. Stable haematocrit. Passing of at least 2 days after recovery from shock. • No respiratory distress from pleural effusion or ascites. • Platelet count of more then 1 lakh per mm3.

Chikungunya; that

which bends up

• Is the little sister clinically • Joint pains are the major feature of both acute and chronic phase • Ankle & wrist • Intense pain caused by the pressure on wrist is diagnostic • Lymphopenia, thrombocytopenia,hepatitis • High viremia causes direct man to man transmission • World wide 2 million cases

Perils of Platelet transfusion platelet concentrate -has contaminating wbcs ,plasma-from centrifuging fresh blood-Has 7x1010 Apherisis ;taken from a single donor 5x10 11 Storage;at rom temperature under agitation Room temperatue causes bacterial growth

Perils of platelet transfusion • Compatibility; destroyed by HLA1 protein on membranes –less commonly by ABO or specific antibodis • Indication for transfusion -prophylactic role to forestall bleeding is controversial • Threshold -by gados et all-remains at 20,000.per cc

Refractoriness . • • •

Perils of platelet transfusion

Nu. & condition of pl.extract. Fever, spelnomeghaly,drugs,DIC, Alloimmunization-from wbc,rbcs in pl.extract—irradation by ultraviolet B helps • TRAP study-apherisis ??? #

Future possibilities • • • •

Thrombopoietin#lyophilization #cold storage# infusible platelet membranes or other platelet substitutes

Drugs for Dengue • Corticosteroids’ • Carbazochrome –decreases capilary permeability • Ribavirin,-also for lassa fever • Interferon alpha • 6-azauridine • Last three drugs have some invitro antiviral activity

steroids 1: Southeast Asian J Trop Med Public Health. 1975 Dec;6(4):573-9. Links

Hydrocortisone in the management of dengue shock syndrome. Min M, U T, Aye M, Shwe TN, Swe T. A total of 98 patients with dengue shock syndrome admitted into Children's Hospital from February 1973 to February 1974 were randomly selected into 2 groups. A double blind controlled trial of the efficacy of pharmacologic doses of hydrocortisone hemisucinate was carried out. The 2 groups were confirmed to be completely matched by age, sex and severity of the disease. Nine deaths occurred out of 48 cases in the steroid group (Case Fatality Rate 18.75%) and 22 deaths out of 50 cases in the non-steroid group (Case Fatality Rate 44%), the difference being statistically significant. No significant difference was detected in fluid requirements and other morbidity pattern.

1: Pediatrics. 1993 Jul;92(1):111-5. Links Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Tassniyom S, Vasanawathana S, Chirawatkul A, Rojanasuphot S. Department of Pediatrics, Faculty of Medicine

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