Dengue fever

DENGUE FEVER PRESENTED BY: SITI NUR HAMIZAH HAMIDON

INTRODUCTION

Ac. Febrile illness Viruses belonging to Flaviviridae family Characterized by:

Biphasic fever Myalgia Arthralgia Rash

EPIDEMIOLOGY

Endemic in Africa, America, Eastern Mediterranean, SEAR, & Western Pacific.

During epidemics- attack rates may reach 80-90%.

Est 500000 cases of DHF requires hospitalization each year.

With modern intensive support therapy DHF case fatality rate are reduced to <1%.

SCENARIO IN MALAYSIA

Increasing trend of DF&DHF. Incidence rate in 1999 = 44.3 cases/100000 population Incidence rate in 2007 = 181 cases/100000 population. National target = <50cases/100000 population Incidence rate is higher in age group >15 yrs. Highest

among working & school going age group. Case fatality rate both DF&DHF remain well below

0.3% since 2002. 70-80% cases were reported from urban areas prob

due to high density of population and rapid development activities which favour transmission.

VIRUS

4 serotypes of dengue viruses DENV-1 DENV-2 DENV-3 DENV-4

Arbovirus-from family Flaviviridae. Single stranded RNA virus. Spherical,

50nm diameter, envelop protein bears epitopes that are unique to serotype.

All four serotypes can be isolated at any one time but the predominant circulating dengue virus will show sinusoidal pattern.

TRANSMISSION

Transmitted to humans through bites of infective female Aedes mosquitoes. Aedes aegypti Aedes albopictus

Humans are the main amplifying host. Incubation period 5-8 days. The virus circulates in the blood of infected

humans for 2-7 days, at approximately the same time they have fever.

Aedes aegypti

Aedes albopictus

PATHOPHYSIOLOGY OF INFECTION & ITS CONSEQUENCES.

Dengue viral infection asso with thrombocytopenia, the cause is molecular mimicry b/w dengue virus proteins & endogenous self-proteins.

Generation of antibodies against dengue virus proteins which cross-react with platelet surface proteins and thus cause thrombocytopenia.

There is activation of blood clotting and fibrinolytic pathways.

Mild DIC, liver injury & thrombocytopenia together contribute to hemorrhagic tendency.

DHF Sequential infection with any 2 of the 4

serotpes og dengue virus result in DHF/DSS in endemic area.

How 2nd dengue infection causes severe disease and why only some patients get severe disease remains unclear.

Suggested that residual Ab produced during 1st infection are able to neutralize a second viral infection with the same serotype.

When no neutralizing Ab are present (i.e: infection due to other serotype), the second infection is under the influence of enhancing Ab & the resulting infection and disease are severe.

Serotype cross reactive antibodies generated from previous primary infection with particular dengue viral serotype are not highly specific for the other serotypes involve in secondary infections.

Hence, the bind to virion but do not neutralize them, and instead increase their uptake by cells like tissue dendritic cells, monocytes and macrophages leading to more rapid activation and proliferation of memory T-cells

Cytokines produces by activated T-cells lead to pathogenesis of DHF/DSS.

Cytokines causes vascular compromise and hemorrhage. The endothelial cell dysfunction is manifested by diffuse increase in capillary permeability microvascular leakage,hemoconcentration, and circulatory insufficientcy.

CLINICAL COURSE OF DENGUE INFECTION After the incubation period, the illness

begins abruptly and will be followed by 3 phases. Febrile phase Critical phase Recovery phase.

NEW CLASSIFICATION OF DENGUENon-severe dengue

without warning signs

Non-severe dengue with warning signs

Severe dengue

Probable dengue•Live in/travel to endemic area•Fever & 2 of the following criteria:• Nausea&vomiting• Rash• Aches&pains• Tourniquet test

positive• Leucopenia• No warning sign

Laboratory-confirmed dengue.

•Abdominal pain/ tenderness•Persistent vomiting•Clinical fluid accumulation•Mucosal bleed•Lethargy & restlessness•Liver enlargement >2cm•Lab: incrase haematocrit concurrent with rapid decrease in platelet count.

•Severe plasma leakage leading to

•Circulatory compromise/ shock /DSS (tachy,cold&clammy extremities, cap refill time >3sec, undetectable pulse, late phase: unrecordable BP)•Fluid accumulation with/ without respiratory distress.

•Severe bleeding•Severe organ involvement.

•Liver: AST/ALT >/= 1000•CNS: impaired consciousness•Heart & other organs.

TOURNIQUET TEST

LABORATORY INVESTIGATIONS Disease monitoring lab test:

White cell count Early febrile phase usually normal but decrease rapidly as disease

progresses. Haematocrit

Rising HCT is a marker of plasma leakage and helps to differentiate b/t DF & DHF.

May be masked in patients with concurrent significant bleeding & those who received fluid therapy.

Setting pt’s baselineHCT in early febrile phase will be useful in recognition of a rising HCT.

Thrombocytopenia Early febrile phase- platelet count usually w/in normal range. Decrease repidly as disease progresses to late febrile phase. May remain low for first few days of recovery.

LFT Greater elevation of AST as compared to ALT. Degree of elevation higher in DHF compared to DF.

Diagnostic test: Antibody detection (serology)

Haemagglutination Inhibition Test Dengue IgM test Indirect IgG ELISA test

Virus isolation Detection of virus genetic materials (PCR) Detection of dengue virus protein (NS1

Antigen)

False positive dengue serology : Cross reaction with:

other flaviviris – Japanese Encephalitis non-flavivirus – malaria, leptospirosis, toxoplasmosis,

syphilis Connective issue disease – rheumatoid arthritis.

STEPWISE APPROACH

CRITERIA FOR ADMISSION

TREATMENT

Symptomatic treatment + aggressive, supportive fluid therapy

Fever (antipyretic; Paracetamol): Max dose: 60mg/kg daily in divided doses

oral or IV (15mg/kg every 6h) Rectal: 20mg/kg every 8h Avoid salicylates & NSAIDs (bleeds) Monitoring. DIC: can give FFP, platelet concentrates

CLINICAL & LAB CRITERIA FOR PT WHO CAN BE TREATED AT HOME.

DIFFERENTIAL DIAGNOSIS OF DENGUE FEVER

PROGNOSIS

Left untreated: mortality rate can be upto 40-50%

Early recognition & appropriate fluid therapy 1-5%

Early detection of shock → excellent prognosis

Prolonged shock + cold extremities, unrecordable BP → difficult

PREVENTION No approved vaccines approach yet Integrated Vector Control programmea. Advocacy, social mobilization, legislation to ensure

public health bodies & communities are strengthenedb. Collaboration of health & other sectorsc. Integrated approach to disease control with maximum

use of resourcesd. Evidence-based decision makinge. Capacity building to ensure adequate response Eliminate its habitats (empty water container/ +

insecticides) Reducing open collection of water Environmental modification Mosquito netting & insect repellent

REFERENCE Ghai Essential Pediatrics, 7th Edition, CBS publication, page 196-

200. Medicine Prep Manual for Undergraduates, 4th Edition, Elsevier

Publication, page 751-755. Dengue haemorrhagic fever: diagnosis, treatment,

prevention and control. 2nd edition. Geneva : World Health Organization. : http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/index.html

Dengue- Guidelines for Diagnosis, Treatment, Prevention & Control. New Edition 2009. world Health Organization: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

http://www.who.int/csr/disease/dengue/en/ Clinical Practice Guidelines- Management of Dengue Infection in

Adults. Revised 2nd Edition. Ministry of Health Malaysia.: http: www.moh.gov.my

Thank you