Mosquitoes)and)the)diseases)they)transmit:)Dengue)Fever)Virus)Aedes aegypti 1"“We$can$look$forward$with$confidence$to$a$considerable$degree$of$freedom$from$infec7ous$diseases$at$a$7me$not$too$far$in$the$future.$Indeed$.$.$.$it$seems$reasonable$to$an7cipate$that$within$some$measurable$7me$.$.$.$all$the$major$infec7ons$will$have$disappeared” $$$$$$T.$Adian$Cockburn$1963)“We)can)close)the)book)on)infecAous)disease”)))U.S.)Surgeon)General)William)Steward)1969)In)the)mid)20th)century)there)was)considerable)opAmism)on)our)ability)to)combat)and)defeat)infecAons)diseases.)))))Some)of)the)reasons)for)this)are:) )1])vaccines)(yellow)fever,)))))))))))))small)pox,)polio)))))))2])cloroquine))))))3])DDT))))))Some)quotes)that)exemplify)this)aQtude:))2"Emerging)and)ReTemerging)infecAous)disease))• )An)emerging)disease)is)one)that)has)appeared)in)a))))populaAon)for)the)first)Ame,)or)that)may)have))))existed)previously)but)is)rapidly)increasing)in))))incidence)or)geographic)range)))• )ReTemerging,)or)resurging,)diseases)are)those)that))))have)been)around)for)decades)or)centuries,)but))))have)come)back)in)a)different)form,)different)) )))))))))))intensity,)or)a)different)locaAon)For)a)variety)of)reasons,)this)opAmism)was)misplaced)and)we)have)seen)the))emer gence)or)reTemergence)of)many)new)infecAous)diseases)since)then. ))These)new)diseases)are)classified)as)“Emerging)and)ReTemerging)infecAous)diseases”)3"The"NIAID"list"of"such"diseases"includes"more""Than"100"pathogens,"including:"(NIAID"=naAonal"insAtute"for"allergies"and"infecAous"disease)"Emerging)and)ReTemerging)infecAous)diseases)""Dengue)virus)Lyme"disease"Erhlichiosis"Yellow"fever"Tick"born"fevers"West"Nile"virus"Various"EncephaliAc"viruses"The"Plague"These"diseases"even"have"their"own"scienAfic"journal."4"The)Dengue)Virus)))• )Dengue)is)a)Flavivirus)(genus))• )belongs)to)the)Flaviviridae)family))• )This)family)includes)more)than)70)viruses:))40)are)mosquito)borne)viruses))16)are)Ackborne)viruses))18)have)no)known)vector)• )Other)well)known)flavivirusses:))West)Nile))Japanese)EncephaliAs))Yellow)fever"5"Four"Serotypes"of"Dengue":"I,"II,"III"and"IV")• )All)four)serotypes)produce)same)disease)• )InfecAon)with)one)serotype)produces)immunity)for))))remainder)of)life)against)that)serotype)))• )Very)limited)crossTimmunity)T>)two)months)–)1)year))A)serotype)is)a)variant)of)the)virus)that)is)recognized)by)different))AnAbodies.)You)can)think)of)these)as)different)“species”)of)virus.)6"7""Mosquito)bite)Aedes$aegyp7$IncubaAon)3T14)days)Febrile)Period)5T7)days)Convalesence)3)weeks))Symptoms)of)Dengue)infecAon:))5)possibiliAes:)))1])50%)asymptomaAc))))))2])undifferenAated)fever)(most)))))common)manifestaAon))))3])classic)dengue)fever)(fever)))))headache,)muscle)and)joint)pain)))))pain,)nausea/vomiAng,)))))rash))))• )dengue)hemorrhagicfever)(DHF))))(see)next)slide)))• )dengue)shock)syndrome)(DSS))If"classic"dengue"fever"develops:"8"WHO"definiAon"of"dengue"haemorrhagic"fever"has"been"in"use"since"1975;"all"four"criteria"must"be"fulfilled"to"be"classified"as"DHF:""a)"Fever,"bladder"problem,"constant"headaches,""""""severe"dizziness"and"loss"of"appeAte""b)"Haemorrhagic"tendency"(posiAve"tourniquet"test,"""""spontaneous"bruising,"bleeding"from"mucosa,"""""gingiva,"injecAon"sites,"etc.;"vomiAng"blood,"or"""""bloody"diarrhea)"c)"Low"platelet"count"(<100,000"platelets"per"""""mm³or"esAmated"as"less"than"3"platelets"per"""""""high"power"field)"d)"Evidence"of"plasma"leakage"(haematocrit"more"""""than"20%"higher"than"expected,"or"drop"in"""""haematocrit"of"20%"or"more"from"baseline"""""following"IV"fluid,"pleural"effusion,"ascites,""""""hypoproteinemia)"4])Dengue)haemorrhagic)fever)(DHF))9"Dengue"fever"Dengue""haemorrhagic""fever"10"5])Dengue$shock$syndrome$$=>$defined$as$dengue$hemorrhagic$fever$plus:$Treatment)is)aimed)at)prevenAng)Dengue)Shock)Syndrome)and)there)are)no)effecAve)drugs.)))))treatment)consists)mostly)of)administering)))intravenous)fluids)Fatality)rate)untreated)DHF)>)20%))With)treatment: ) )<)1%))• )Weak$rapid$pulse,$• $Narrow$pulse$pressure$(less$than$20$mm$Hg)$• $Cold,$clammy$skin$and$restlessness.)11")• )Classic)Dengue)fever)was)first)recognized)in)17th)century)and))))has)been)wellTknown)over)the)last)several)hundred)years)• )DHF)was)first)recognized)in)1950s)in)Philippines)))))and)Thailand)• )By)the)1970’s)nine)countries)experienced)DHF))• )Today)emerging)DHF)cases)are)caused)by)increased))))dengue)epidemics)in)the)Americas,)and)in)Asia,)DHF)))))has)become)a)leading)cause)of)))hospitalizaAon)and))death)among))))children)in)several)countries)Dengue)history)12"Dengue)impact))• )2.5)billion)people)at)risk)• )50T100)million)infecAons)yearly)• )500,000)Dengue)Haemorrhagic)Fever)cases)• )22,000)deaths,)mostly)children)13"Why)do)some)people)develop)DHF?)Several"ideas"were"proposed"to"explain"DHF:""• Various"forms"of"the"four"serotypes"cause"different"disease?"e>"No!"• Prior"exposure"to"other"serotypes"makes"disease"worse?e>""This"is"called"the"Immune"Enhancement"Hypothesis"• PopulaAon"increase"e>"more"people"so"higher"probibility"of"DHF?"Maybe.""• Human"GeneAcs"e>"Some"people"are"more"suscepAble"than"others?"14"Dengue)Hemorrhagic)Fever)1])Risk)for)DHF)increased)~100x)with)2nd)infecAon)(different)serotype)))2])Thailand,)2)cohort)studies)– DHF)rate)0)in)primary)infecAon)– DHF)occurs)at)1.8%)and)12.5%)with)2nd)infecAon.)))But)it)may)sAll)be)that)Virulence)may)also)vary)by)genotype)(within)serotypes))Am)J)Epidemiol)1984;120:653))AJTMH)1988;38:172)Two)studies)provided)data)for)the))immune)enhanced)hypothesis:)15"Why)do)some)people)develop)DHF?)Several"ideas"were"proposed"to"explain"DHF:""• Various"forms"of"the"four"serotypes"cause"different"disease?"• Prior"exposure"to"other"serotypes"makes"disease"worse?e>""This"is"called"the"Immune"Enhancement"Hypothesis"• PopulaAon"increase"e>"more"people"so"higher"probibility"of"DHF""• Human"GeneAcs"e>"Some"people"are"more"suscepAble"than"others?"This)is)now)widely)excepted))16"The)Dengue)Transmission)Cycle)Dengue"virus"originally"came"from"monkeys"in"a"sylvaAc"(forest)"cycle"but"is"currently"maintained"in"human"populaAons!""There"is"some"evidence"that"a"forest"cycle"sAll"exists","but"this"plays"no"role"in"causing"epidemics."SylvaAc)cycle)origin)17"EvoluAonary)relaAonships)between)Dengue ))vir
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