DENGUE FEVER Prof. Dr. Muhammad Ali Khan MBBS, DCH, MRCP (UK) Secretary DEAG Punjab Ex Head Department of Pediatrics SIMS/Services Hospital Lahore

Dengue Virus Family : Flaviviridae Genus : Flavivirus Serotypes : DV1, DV2, DV3, DV4 Enveloped virus 3 major proteins SS positive sense RNA Dr. S Guanasena

Viral Serotypes DV1 DV2 DV3 DV4 Subgroups and clades One or more virus types in circulation during an epidemic

Spectrum of Disease Asymptomatic Mild viral syndrome DF DHF 95% 5%

Clinical course of Dengue

Dengue Infection Clinically significant Dengue infection may be 1. Simple dengue fever (DF) 2. Dengue hemorrhagic fever (DHF) (plasma leak <5%) 3. Dengue Shock Syndrome (DSS) (plasma leak >5%)

Clinical Features – DF Fever > 2 and < 10 days (essential criterion) Headache Retro orbital pain Myalgia Arthralgia/ severe backache/ bone pains Rash Bleeding manifestations (epistaxis, hematemesis, bloody stools, menorrhagia, hemoptysis) Abdominal pain Decreased urinary output despite adequate fluid intake Irritability in infants

DHF or DLF

cellular dysfunction and SHOCK A complex clinical syndrome of decreased blood flow to body tissues resulting in cellular dysfunction and eventual organ failure

Plasma leaks - Pathophysiology Host response Subsequent infection Previous IgG Neutralizing (protective) non neutralizing (replication enhancing) Increased viremia increased TNF, interferon, interleukin-2 and hypocomplementemia endothelial injury and increased leakage Viral response

Pathophysiology of DHF Increased capillary permeability Protein rich fluid exudes into the interstitial space - Pleural effusion , Ascites etc. Circulatory volume collapses – SHOCK Sympathetic over activity Vasoconstriction, tachycardia Loss of volume Reduces pulse pressure Blood becomes thick due to loss of fluid Rising hematocrit and delayed capillary filling Compromised renal and hepatic perfusion – Reduced urine output and tender hepatomegaly

Patho-physiology of DHF Management of DHF during the critical stage is that of Shock But there is one important consideration: Fluid is not being lost out but it is going to 3rd space and will be resorbed back so Over-enthusiastic fluid replacement during the critical phase – when the fluid is oozing out - would result in fluid over load during the recovery phase

Patho-physiology of DHF People do not die of hemorrhage in DHF They die Either due to shock and 20 organ failure Or due to Pulmonary edema & fluid over load during the recovery phase

End organ failure in DHF Approximate outcomes Single organ failure - mortality = 40% Two organ Failure - mortality = 80% Three organ failure - mortality = >99%

Case review ( of 9 deaths at Services Hospital ) 8 died of profound shock and associated end organ failure Only one had suspected CVA as a cause of death

Clinical course of DHF Course of simple Dengue fever is generally uneventful and non-fatal Whereas DHF can be life-threatening Differentiating DF from DHF is critical

Clinical course of DHF Both the DF and DHF can have bleeding tendencies therefore: Bleeding is not the differentiating point between the two

Clinical course of DHF Clinical course can be divided into three stages Febrile Phase Critical Phase Recovery Phase

Clinical course of DHF Febrile Phase High fever Some petechial hemorrhages With generalized aches & pains and headache; this usually lasts two to seven days People generally don’t die during this stage

Clinical course of DHF Critical Phase Starts with the resolution of fever Occurs in a few people Lasts for just 24-48 hours or so Is associated with plasma leak – volume depletion & shock This is the phase where management is critical

Clinical course of DHF DHF is classically associated with Plasma leak into the 3rd compartment And circulatory compromise

Signs of plasma leak in DHF Patient is not feeling well with resolution of fever Warning signs Low pulse pressure <20 mm Low urine output Delayed capillary filling Tender hepatomegaly

Signs of impending DHF Warning signs (lab reports) Increasing hematocrit Edema of the gall bladder, ascites or pleural effusion Low albumin Low cholesterol Acute fall in platelet count

Highly Suggestive of DHF Confirmed DHF** Disproportionate tachycardia Narrowing of pulse pressure < 20 mm CRFT > 2 secs Tender hepatomegaly (DHF likely) Haemoconcentration HCT 20% rise from baseline or rise approaching 20% if patient already on IV fluids Biochemistry Serum albumin < 3.5 g/dl or 0.5 gm/dl fall during illness Non fasting serum cholesterol < 100 mg/dl or 20mg/dl fall during illness Oedematous gall bladder wall on U/S Ascites on U/S Pleural effusions (CXR Right lateral decubitus or chest U/S to detect minimal effusion) ** Definitive evidence of plasma leakage

Rate of Fluid loss and intake (Critical Phase)

Clinical course of DHF Recovery Phase Volume gets resorbed Volume over-load may occur This is the phase where people die because of the problems faced during the critical stage

Lab Diagnosis

IgM antibody to the secondary infecting DV serotype IgG antibody - specific to the initial infecting DV serotype + cross reacting antibody IgM antibody to the secondary infecting DV serotype Following primary infection – Specific antibody response + CMI (memory T cells) Cross reactive antibody response + CMI (memory T cells) Dr. S Guanasena

Investigations CBC and platelet count First 5 days >5 days NS 1 PCR IgM IgG

Update on vaccine Chimera vaccine Attenuated vaccine Yellow fever & dengue Launched 2016 Partial immunity Risk of secondary infection Attenuated vaccine 6-8 cycles in DKC (Dog kidney cells)

HAVE WE DONE ENOUGH? Asia pacific strategic plan for control of Dengue (2010-2015) Decrease prevalence by 10% per year Keep DHF mortality below 1% What are our Goals?????

Current situation in Punjab Lahore 2011 Rawalpindi 2015 DEN 2 Innumerable Few DHF DEAG TRINED MEDICS AND PARAMEDICS = 13000 DEN 1,2,3,4 2349 cases (uptill 27-10-2015) > 300 cases of DHF and DSS 10 deaths

Current situation in Punjab Lahore, 2016 Rawalpindi, 2016 DEN 1 109 Few DHF No death DEAG TRINED MEDICS AND PARAMEDICS = 3165 DEN 1,2,3 299 18 03 deaths

Take Home message We can prevent quite a few deaths ---- if we can Differentiate DF from DHF Diagnose the onset of critical phase (phase of leaking) Give appropriate fluids

Thank you