2 Dengue is a tropical febrile disease Dengue Fever is a tropical febrile diseaseFebrile = Fever causingEndemic in Latin America, Africa and South and Southeast Asia and the PacificClassified by WHO as a neglected tropical disease
3 …and become a MAJOR pandemic in the last 50 years Endemic in more than 100 countries2.5 billion people at risk...and has become a MAJOR epidemicEstimated 50 to 100 million cases annually, with several 100,000 cases of the more severe form dengue hemorrhagic feverEndemic in more than 100 countriesLeading cause of death in children in some Asian countriesOver 2.5 billion people at risk for infection, 2/5 of the world’s populationCase-fatality rate for DHF averages 5 percent and 58,000 deaths have been attributed to dengue in the past 40 years
5 How is it spread? Aedes albopictus Aedes aegypti Aedes aegypti A. aegypti can acquire the virus only when the infected person has the virus circulating in their bloodstreamCan be transmitted through other members of the subgenus StegomyiaAdapted to urban manmade environmentsLikes to live in open water containers, tires, etc.Restricted to tropical areas and seasonalIncubation time in mosquito can vary with temperature, strain of virus, species of mosquito and amount of virus ingestedGoes over much of mosquito anatomy but transmitted because in salivary glandsOnce mosquito is infected, can transmit virus for the rest of its lifeVertical transmission in mosquitoes can occur but generally not at very high ratesAedes aegypti
6 How it get into our body?1.The virus is inoculated into humans with the mosquito saliva.2.The virus localizes and replicates in various target organs, for example, local lymph nodes and the liver.3.The virus is then released from these tissues and spreads through the blood to infect white blood cells and other lymphatic tissues.4.The virus is then released from these tissues and circulates in the blood.5.The mosquito ingests blood containing the virus.6.The virus replicates in the mosquito midgut, the ovaries, nerve tissue and fat body. It then escapes into the body cavity, and later infects the salivary glands.7.The virus replicates in the salivary glands and when the mosquito bites another human, the cycle continues.
7 Patients may also report other symptoms, such as itching and aberrations in the sense of taste, particularly a metallic taste. In addition, there have been reports of severe depression after the acute phase of the illness.
8 4 Dengue clinical syndromes Undifferentiated fever;Classic dengue fever;Dengue hemorrhagic fever (DHF)Dengue shock syndrome (DSS)Dengue shock syndrome is actually a severe form of DHF.
9 Four Stages of DHF Stage 1 Fever and nonspecific constitutional symptomsPositive tourniquet test is only hemorrhagic manifestationStage 2Stage 1 manifestations + spontaneous bleedingStage 3Signs of circulatory failure(rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)Stage 4Profound shock (undetectable pulse and BP)
10 Dengue Hemorrhagic Fever Danger Signs inDengue Hemorrhagic FeverDanger Signs in Dengue Hemorrhagic FeverAbdominal pain - intense and sustainedPersistent vomitingAbrupt change from fever to hypothermia, with sweating and prostrationRestlessness or somnolence*All of these are signs of impending shock and should alert clinicians that the patient needs close observation and fluids.
12 How did it become a major public health problem? Ineffective mosquito controlRapid population growthNon-biodegradable packagingRapid increase in air travelReasons for DHF and DF as a major public health problemEffective mosquito control is virtually non-existent in most dengue-endemic countries of the worldToo much emphasis on ultra-low volume sprays of insecticide for adult mosquito control that is not effective for controlling Ae. AegyptiDemographic changes of uncontrolled population growth and urbanizationIncrease in non-biodegradable packaging for goods and difficulty of disposing of tiresIncreased travel of humans by airplaneOver 50% of US departures are to tropical areasPublic health infrastructure to deal with vector-borne diseases has deteriorated in most countries of the worldCrisis mentality- emphasis on emergency control methods rather than developing methods to prevent transmissionBecause of lack of money and resources
13 The Dengue Virus Family Flaviviridae Same family as Yellow Fever 4 viral serotypesFamily FlaviviridaeSame family as Yellow FeverDengue virus molecular biology4 viral serotypesFamily Flaviviridae (same family as yellow fever)Spherical particles with a lipid envelope enclosing capsidRNA genome made of single strand messenger positive RNA approximately 11 kb in lengthGenome encodes single open reading frameLong polyprotein is processed by viral and host cell proteases to produce 10 viral proteins
14 Single strand positive RNA Genome Dengue is an RNA VirusCapsid (core)2. Membrane3. EnvelopeSingle strand positive RNA Genome50 nm
15 Secondary infections tend to produce DHF…. Antibodies enhance viral replication!Pathology of the dengue virusBinding is mediated by the envelope glycoprotein to the cell surfaceOriginal Antigenic sin- antibodies and t cells specific for one strain still recognize different strain because of similarities but aren’t as good at respondingThis is called antibody-dependent enhancement- increase in infection of monocytic cells by dengue virusescomplexes of dengue with bound antibody can interact via the free Fc region of immunoglobulin with fcgamma receptors on the cell surface of monocytic cellsIncreases the binding of the virus to the cell
16 There is no specific treatment for DHF ! Treatment of DFOnly supportive (treatment of symptoms)Assess for dehydration and ability to drink fluidsTherapy for pain (avoid aspirin because of exacerbating hemorrhagic tendencies)TreatmentFluid replacement through IVMedication to reduce feverBlood transfusion if neededCan only treat the symptoms
17 How can we stop it? Mosquito control: Improved water storage InsecticidesIntroduction of mosquito-eating fishand copepods
18 Even Better: A Vaccine Tetravalent live attenuated Intertypic chimaeric vaccineChimaeric vaccineEffective vaccine still in progressTypes of VaccinesTetravalent live attenuated vaccineAttenuated viruses of all four serotypes were developed at Mahidol university, ThailandSuccessfully completed phase 2 clinical trialsPhase 3 trials underwayContains an antigen from each serotypeIntertypic chimaeric vaccineStructural genes from the cDNA copy of an attenuated strain of dengue virus of a given serotype is replaced by the corresponding genes of a different dengue virus serotypeChimaeric vaccinesReplaces the E gene of the 17D yellow fever vaccine with the analogous gene of the vaccine targeted flavivirusPediatric Dengue Vaccine InitiativeEstablished in 2003 at the International Vaccine Institute in Seoul, South KoreaMission:Accelerate evaluation of candidate dengue vaccinesIntroduction of improved diagnosticsTo introduce affordable safe vaccines in dengue endemic countriesAlso serves as a forum for improved advocacy and coordination of global efforts on dengue vaccine developmentFunded by the Rockefeller foundation, bill and Melinda gates foundation, and the WHO
19 Reference"Dengue." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 16 Mar Web. 30 Mar <Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention, and Control. 2nd ed. Geneva: World Health Organization, Print."Dengue." World Health Organization. World Health Organization. Web. 30 Mar <Gubler, D. J., and Goro Kuno, eds. Dengue and Dengue Hemorrhagic Fever. Wallingford, Oxon, UK: CAB International, Print.Liu, J-W. ,Khor, B-S., Lee, C-H. et al. Dengue Haemorrhagic Fever in Taiwan Dengue Bulletin