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Dengue Fever. Alternative Names. Onyong- Nyang Fever West Nile Fever Break Bone Fever Dengue like Disease. Background. Propagation of viral illnesses Transmission of viral illnesses Various families of Arbor viruses Manifestations of Arborviral illnesses
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Alternative Names • Onyong- Nyang Fever • West Nile Fever • Break Bone Fever • Dengue like Disease
Background • Propagation of viral illnesses • Transmission of viral illnesses • Various families of Arbor viruses • Manifestations of Arborviral illnesses • Dengue – A Flavivirus- EM- Cell culture • Transmitted by mosquito • Aedes aegypti
Viral Illnesses - Propagation Human Human Accidental Human Zoonotic Arthropod Rodent Virus
Transmission of Viral Illnesses • Droplet infection as in case of Measles, Influenza, Coryza etc. • Blood to blood transmission- HIV, HBV • Feco-oral – Rota, Polio • Direct contact – Herpes simplex etc • Arthropod borne –Dengue, JE, YF • Tick borne – CEE, Colorado TF
Arthropod borne Viral Diseases • Flavivirus – Mosquito borne – YF, DF,JE • Flavivirus – Tick Borne –CEE, RSSE, KFD • Buniyavirus – Mosquito- CE • Plebovirus – Sandfly Fever • Arinavirus – LCM virus • Colivirus – Colorado Tick fever • Vesiculovirus – Vesicular stomatitis • Alphavirus – E/W/V equine encephalitides
Manifestations of Arborviral Illnesses • Most Arboviral diseases are rural • Arboviral illnesses cause typical manifestations – Often overlap • The following clinical syndromes occur • FM – Fever – Myalgia complex • AR – Arthritis – Rash complex • HF – Haemorrhagic Fever • E – Encephalitis
Epidemiology of Dengue • The Dengue Virus • The Vector • Global distribution of Dengue • Transmission cycle – host – vector • Propagation of virus – I.P • Natural History of Dengue • Dengue Hemorrhagic fever – Endemicity pattern
Epidemiological Triangle The Host Interaction The Virus The Vector
The Agent Dengue Virus
The Dengue Virus • Flavivirus • Positive sense • Single stranded RNA virus • 40 to 50 nanometers • Four sero-sub types • Type 1 to 4 • Arthropod borne
Dengue Virus Electron Micrograms
Dengue Virus Cell Culture Of Dengue Virus
The Vector Aedes aegypti (Infected Female Mosquito) (rarely Aedes albapticus)
Peculiarities of A.aegypti • It is a day biting mosquito when normally coils, repellents, nets etc are not used • It breads in fresh water around homes • Lays eggs preferentially in water jars, discar- ded containers, coconut shells, old tires etc. • Can transmit trans-ovarially the infection • Year round breeding 250 N to 250 S • Tropics and sub-tropics are its favorite zones. It is an urban vector
Aedes aegypti Dengue, YF, CGF
Aedes aegypti Dengue Yellow Fever Chichungunya Fever
Dengue on the Globe Highly endemic Recently acquired
Dengue Fever • Caused by an arthropod borne virus • It is a zoonotic virus • Man is accidentally infected • Other vertebrates are the reservoirs • Dengue virus has 4 subtypes 1 to 4 • Positive sense, single str RNA- 40nm • Vector mosquito is Aedes aegypti
Mechanism of Transmission • Vector is infected after ingestion of blood meal from a viremic vertebrate • Virus multiplies in the system of vector for 2-3 weeks – extrinsic incubation pd. • Natural vertebrate partner has only transient viremia and doesn’t suffer • Virus is injected by the A.aegypti into man • After 2-7 days of IP, man develops FM,HF
Natural History of Dengue In apparent HumanInf 30% 100% Recovery DFM Re infection 69% 95% 10% Death Primary DHF/DSS Secondary DHF/DSS 5% 01%
Pathogenesis of DHF Immuno-pathogenic Cascade
Hypotheses on DHF - DSS • Neutralizing Ab are type specific nutralize the homologous sub type • Subsequent infection with heterologous sub type causes immune complexes • These Immune Complexes target the mononuclear lineage foe enhanced viral replication • Infected monocytes release vasoactive mediators causing vascular damage
Immunopathogenic Cascade of DHF/DSS • Macrophage – monocyte infection • Previous infection with heterologous Dengue serotype results in production of non protective antiviral antibodies • These Ab bind to the virion’s surface Fc receptor and focus the Dengue virus on to the target cells – macro/monocytes • T cell - cytokines, interferon, TNF alpha
The Disease Clinical Features
Dengue Presentations • Undifferentiated fever • Dengue Fever (DF) with the Fever- Myalgia (FM) presentation (classical) • Dengue Hemorrhagic Fever (DHF) • Dengue Shock Syndrome (DSS)
Hemorrhagic Manifestations • Skin hemorrhages:petechiae, purpura, ecchymoses • Gingival bleeding • Nasal bleeding • Gastro-intestinal bleeding: hematemesis, melena, hematochezia • Haematuria • Increased menstrual flow
Clinical Manifestations- DF • IP of 2 – 7 days - typical patient develops • Sudden onset of fever, chills, headache • Back pain with severe myalgia, arthralgia • Retro-orbital pain – break bone fever • Macular rash – in axillary area • Adenopathy, palatal vesicles, scleral inj. • Maculo-papular rash on trunk – extremities • Epistaxis and scattered petechiae
Other manifestations- DF • Anorexia. Nausea, vomiting • In apparent illness-to acute incapacitation • Illness is about 2–5 days, biphasic course • Pain on eye movements • Pain on palpating abdominal muscles • Primarily not a respiratory illness • Rare - aseptic meningitis • Complete recovery is the rule - asthenia
Dengue Haemorrhagic Fever (DHF) • Vascular instability • Decreased vascular integrity • Assault on macro vasculature • Decreased platelet function • Increased vascular permeability • Vascular disruption and local bleeds • Hypotension, hemoconcentration- shock
Criteria for DHF • Fever, or recent history of acute fever • Hemorrhagic manifestations • Low platelet count (100,000/mm 3 or less) • Objective evidence of “leaky capillaries:” Elevated hematocrit -20% or more more over baseline or 50% Low albumin, pleural effusion
Criteria for DSS • The four criteria of DHF • Evidence of circulatory failure • Rapid and weak pulse • Narrow pulse pressue (less than 20mm) • Hypotension for the age • Cold clammy skin • Altered mental status
Four Grades of DHF/DSS • Grade 1 Fever, Const. Symptoms, +ve tourniquet test • Grade 2 Grade 1 + Spontaneous bleeding • Grade 3 Signs of circulatory failure • Grade 4 Profound shock - B.P. Pulse not recordable
Tourniquet Test Inflate blood pressure cuff to a point midway between systolic and diastolic pressure for 5 minutes Positive test: 20 or more petechiae per 1 inch² (6.25 cm²)
Pleural Effusion PEI = A / B x 100
Clinical tests for DHF • Petechiae after tourniquet test • Overt bleed from previous GI lesions • Platelet count less than 100,000/ul • Low pulse pressure, cyanosis, effusions • Hypotension, Shock
DHF- Poor Prognostic Signs • Girl children under 12 with DHF/DSS • Severe hypotension and shock • Multifocal bleeding – abdominal pain • CNS encepahlopathy, fits, coma • Watch for preorbital edema, proteinuria postural or otherwise hypotension • Serotype 2 infection after type 4 • Malnutrition is protective