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 Dengue – A Flavivirus- EM- Cell culture Transmitted by mosquito Aedes aegypti
Viral Illnesses - Propagation
Human Human
HumanZoonotic Accidental
Virus
Arthropod
Rodent
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
1. FM – Fever – Myalgia complex
2. AR – Arthritis – Rash complex
3. HF – Haemorrhagic Fever
4. 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
The Virus The Vector
Interaction
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
Dengue Transmission Cycle
Dengue Transmission
Dengue Illnesses - Propagation
Natural History of Dengue
Human Inf In apparent
DFM
Primary
DHF/DSS
30%
69%
01%
Re infection
Secondary
DHF/DSS
10%
Recovery100%
Death5%
95%
DHF Endemicity
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
Initial Immunogenecity
Immune Complexes
Attack on Host Immune Cells
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
Petechiae
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
DHF – Clinical Criteria
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 moremore over baseline or
Low albumin, pleural effusion
Criteria for DSS
The four criteria of DHF Evidence of circulatory failure
1. Rapid and weak pulse
2. Narrow pulse pressue (less than 20mm)
3. Hypotension for the age
4. Cold clammy skin
5. 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
Ecchymosis – Periorbital Edema
Large Subcutaneous Bleed
Capillary Damage
Tourniquet Test
Inflate blood pressure cuff to a pointmidway between systolic and diastolicpressure for 5 minutes
Positive test: 20 or more petechiaeper 1 inch² (6.25 cm²)
Tourniquet Test
PEI = A / B x 100
Pleural Effusion
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
Unusual Presentations of Dengue
Encephalopathy Hepatic damage Cardiomyopathy Severe GI bleeding
Differential Diagnosis
FM complex1. Anicteric leptospirosis
2. Rickettsial fevers
3. Influenza, Measles, Rubella DHF / DSS
1. Other hemorrhagic fevers
2. DIC due to septicemia
3. Complicated Malaria
4. Meningococcemia
Laboratory Diagnosis
Complete Blood Counts Hematocrit Platelet Count Serum GOT, GPT Serum Albumin Proteinuria, hematuria Immunological Tests Chest Skiagram
Laboratory Diagnosis
Leucopenia. Thrombocytopenia Increased SGOT, SGPT Rising Ab titre in paired sera Antigen detection ELISA IgM-capture ELISA within few hours Reverse transcription PCR confirmatory IgG ELISA significant of past infection
Immuno Detection Tests
ELISA Plate IgM-capture ELISA
Treatment of DF
Supportive measures - Vector barrier Avoid Aspirin and if possible NSAIDs Steroids should not be used Fluid replacement to avoid hemoconc. Children below 12 require careful watch
for DHF / DSS No antiviral agents are of proven value
DHF / DSS
Intensive Care
Oxygen
Rehydration
Barrier Nursing
Mosquito Screen
Common Misconceptions- DHF
Dengue + bleeding = DHF DHF is fatal only due to hemorrhage
No Majority of deaths are due to shock Poorly managed DF turns into DHF Positive tourniquet = DHF
it is not specific for DHF,
it indicates capillary fragility of any origin
More Common Misconceptions
DHF is only a pediatric illness –
No, All ages may be involved DHF is a problem of poor families –
No, in fact they may not have
immune complexes to required level Tourists will get DHF –
No, in fact they are at low risk
Management of DHF/DSS
Close monitoring of hypotension/shock Oxygen administration IV. Infusion of crystalloids/colloids Platelet transfusion Clotting factors replacement Case fatality is 5% in good centers
Fluid Balance
Continue monitoring after defervescence Serial hematocrits, BP, Urine output Fluid replacement is twice the requirement 1500 ml + 2 x (weight-20) – for 60 kg wt.
Eg. {1500 + 2 x (60-20)} x 2
= {1500 + (2x 40)} x 2 = (1500 + 800) x 2
= 2300 x 2 = 4600 ml = 10 pints
Immunization
Each serotype produces life long immunity There is not efficacious vaccine available Vaccine needs to be tetravalent Live attenuated vaccines possible Several candidate vaccines are on trials It may be harmful to vaccinate in view
of the pathogenesis of DHF/DSS
Vector Control
Biological1. Largely experimental
2. Use of fish to feed on larvae Environmental
1. Elimination of larval habitat
2. Most likely successful strategy Purpose of control
To reduce female vector density
Vector Control of Dengue
Mosquito control is expensive –impossible Destruction of breeding sites – viable Spraying insecticides for adult control- ? Individual measures to avoid vector contact
1. Mosquito screens, repellents (DEET)
2. Permithrin impregnated clothing Non degradable tires, long life plastics-avoid
Challenge
Achieve active community involvement Solicit input from the earliest program
planning stages Encourage community ownership True community participation is key
Bibliography
World Health Organization Reports Pan American Health Organization Center for Diseases Control, Atlanta National Institute of Communicable
Diseases, New Delhi Bangladesh Center for Dengue Harrison's Principles of Internal
Medicine, 15 ed.
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