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 circulatingdengue 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.
PATHOPHYSIOLOGY OF INFECTION & ITSCONSEQUENCES. 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 DENGUE Non-severe dengue Non-severe dengue with Severe dengue without warning signs warning signsProbable dengue •Abdominal pain/ •Severe plasma leakage•Live in/travel to endemic tenderness leading toarea •Persistent vomiting •Circulatory compromise/•Fever & 2 of the following •Clinical fluid accumulation shock /DSScriteria: •Mucosal bleed (tachy,cold&clammy •Nausea&vomiting •Lethargy & restlessness extremities, cap refill •Rash •Liver enlargement >2cm time >3sec, undetectable •Aches&pains •Lab: incrase haematocrit pulse, late phase: •Tourniquet test concurrent with rapid unrecordable BP) positive decrease in platelet count. •Fluid accumulation with/ •Leucopenia without respiratory •No warning sign distress.Laboratory-confirmed •Severe bleedingdengue. •Severe organ involvement. •Liver: AST/ALT >/= 1000 •CNS: impaired consciousness •Heart & other organs.
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
Virusisolation 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.
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 BETREATED AT HOME.
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/Denguepub lication/en/index.html Dengue- Guidelines for Diagnosis, Treatment, Prevention & Control. New Edition 2009. world Health Organization: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.p df 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