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Example-examBasicsofInfectiousDiseases(NEM-20806)2015/16: Question1:The‘diseasetriangle’isaconceptualmodelusedtobetter understandtheepidemiologicaldynamicsofinfectiousdiseases. A. Whatarethethreefactorsthatmakethecornersofthedisease triangle? [ANSWER(2points):environment,infectiousagent,andhost] B. Howcanthediseasetrianglehelptounderstandasuddenoutbreak ofaninfectiousdisease? [ANSWER(4points):theepidemiologicaloutcomeofaninfectiousdisease isdeterminedbyinteractionsbetweenenvironment,pathogen,andhost. Suddenoutbreaksofinfectiousdiseasesalwaysinvolveachangeeitherin theenvironment,inthepathogen,orinthehost.Changesinthe environmentmayforinstanceenablethetransmissionofpathogenfroma novelsource(e.g.reservoirhostinjungle).Specificgeneticchangesin pathogensmayincreasetheirvirulence(e.g.mutationsinvirussurface proteins).Changesinhostbehaviourmayenhancethetransmissionofthe causalagent.Forexample,thecurrentaggregationofthousandsofpeople inrefugeecampsindroughtstrickenEastAfricagreatlyenhancesthe likelihoodoftransmissionofinfectiousdiseases.] C. Applythediseasetriangletoexplainarecentpandemicofan infectiousdisease. [ANSWER(2points):theswinefluepidemicisthoughttohaveoccurred afterageneticrecombinationintheviralgenomeofaninfluenzavirus (pathogenfactor).People(hostfactor)lackedimmunitytothisnewhighly virulentvirus,whileinternationaltravelling(environmentalfactor)of carriersofthevirusallowedforarapidspreadofthediseasethroughout theglobalcommunity.] Question2: Mostpeoplegetmicrobialinfectionswhentheirimmunesystemsare weakened.Nevertheless,alsopeoplehavinganormalfunctioningimmune systemcangetinfectedbypathogenicbacteria. A. Explainhowbacteriacancausediseasedespitethepresenceofa functioningimmunesystem(2points) B. Giveexamplesofimmuneevasionmechanism(atleast3) (4points) C. Explainwhythedevelopmentofantibioticresistanceisaproblemin healthcare(4points) Thisquestionhasbeendiscussedinthelecture.Seeforanswerslectureslides. Question3: Despitetheoccurrenceofmanyfungalspecies,fungiarenotknownas majorhumanpathogens. A. Explainwhyfungigenerallydonotcauseseverediseasesonhumans andanimals.(4points) B. Oncesufferingfromasystemicmycosis,mortalityisgenerallyvery high.Explainwhyitisdifficulttodevelopantifungaldrugs.(3 points) C. Systemicmycosescanbedividedintotrueandopportunistic systemicmycoses.Howmanyfungalspeciescancausetruesystemic mycosesandhowmanyfungalspeciescancauseopportunistic systemicmycoses?(3points) Thisquestionhasbeendiscussedinthelecture.Seeforanswersthelecture slides. Question4: A. Whatisthedifferencebetweenadirectlytransmittedandan indirectlytransmittedpathogen?(Usediagramstoillustrateyour answer;4points) [ANSWERS:Adirectlytransmittedprotozoanpassesfromonehosttoanother withouttheneedforavector.Directtransmissionmaybethroughamedium suchassoilorwater. Anindirectlytransmittedprotozoanparasitehasatransmissioncyclewhich involvesavector.Theprotozoanistransmittedfromonehosttoanotherviaa vectorwhichmaybeaninsect.] B. Givetwoexamplesofdirectlytransmittedprotozoanpathogens (2 points) [ANSWERS:Directlytransmitted:Examplesinclude,Giardiasis(Giardia duodenalisandGiardialamblia),Toxoplasmosis(Toxoplasmagondii)] C. Givetwoexamplesofindirectlytransmittedprotozoanpathogens(2 points) [ANSWERS:Indirectlytransmitted(vectorborne):Examplesinclude,Chagas disease(Trypanosomacruzi),Africantrypanosomiasis(Trypanosomabruceispp), Leishmaniasis(Leishmaniaspp),Malaria(Plasmodiumspp).] D. Whataresomeofthechallengesinvolvedinthecontrolofprotozoan pathogens?2points [ANSWERS:Antigenicvariation,evasionofhostimmunesystem,natural reservoirsofinfection,vectorsbecomeresistanttoinsecticidesusedtocontrol them,parasitesbecomeresistanttothedrugsusedtotreatinfection.] Question5. A. List three ways in which arthropods may be of public health importancetohumansandgiveoneexampleforeach.(6points) [ANSWERS:Nuisancebiting(e.g.headlice,mosquitobites,midges);Allergiesto biteorsting(e.g.bee,wasp,ant,mosquito);Diseasecausingagent(e.g.Myiasis bythehumanbotfly,Dermatobiahominis);Diseasevector(e.g.mosquitoes transmittingmalaria,tickstransmittinglymedisease).] B. WhatisthecausativeagentofLymediseaseandhowisthisdisease transmitted?(2points) [ANSWERS:Causativeagent=Borreliabacteria.Transmittedfromonehostto anotherthroughbitesofinfectedticks(thesheeptickIxodesricinus).] C. HowcaninfectionwithLymediseasebeprevented? (2points) [ANSWERS:Tickchecks-removetickwithin24hoursofattachment;Useof DEET-containingrepellentstopreventtickbites.] Question6 Acysteineproteaseinhibitorfromthemurineparasitichelminth Heligmosomoidespolygyrus(Hp-CPI)isabletomodulatedendriticcell functionandsubsequentresponsesoftheadaptiveimmunesystem. A. Describestep-by-stephowforeigncompounds(e.g.PAMP’sor antigens)arebeingperceivedbydendriticcellsandultimatelylead toThelpercellactivation?[2points] [Answers:PerceptionbyPRR’s,endocytosis,fusionwithlysosomes,loadingonto MHC-IImolecules,antigenpresentationandTcellactivation.] Inthefigurebelowyoucanfindtheeffectofrecombinant(r)Hp-CPIon mousebonemarrow-deriveddendriticcells,whicharestimulatedwith ligandsforTLR4(LPS)andTLR9(CpG). CD40 CD80 CD86 MHC-II MFI:meanfluorescentintensity(ameasureforexpressionlevel) B. PolarisationofTcellsdependsonthreedistinctsignalsgivenby antigenpresentingcells.Whichofthesethreesignalsareaffectedby Hp-CPIasstatedinthefigure?[2points] [Answers:Signal1–antigenpresentation;Signal2–co-stimulation;Signal3– cytokines] C. KnowingtheeffectthatHp-CPIhasondendriticcells,whichtypeofT helpercellresponsewillyouexpect?Furthermore,whatdoyou expecttobetheeffectonthetypeofantibodiesthatwillbeproduced byB-cells?[3points] [Answers:ReductionofIL-12=>suppressionofTh1responses;ReductionofIL6=>suppressionofTh17responses,favoringTregs;Th2dominatedimmune responsesaretheresult;Th2typeimmunitywillfavortheproductionof IgE/IgG4byBcells] D. BesidestheimmunomodulatorypropertiesillustratedaboveforHpCPI,helminthsemploymultipleothermechanismstomodulatehost immuneresponses.Giveatleast3otherexamples.[3points] [Answers:Proteases,proteaseinhibitors,chemokineblockersandanti-oxidants toinhibiteosinophilrecruitmentandeffectorfunctions;antibodyclassswitching fromIgEtoIgG4tolimiteosinophildegranulation;alternativeactivationof macrophagestoblockTh1responsesandinducewoundhealing;promoting regulatoryTcelldevelopment;promotinglymphocytehyporesponsiveness (anergy),cytokinemimics(e.g.TGF-b1),etc….] Question7: Helminthparasiteshaveanumberofcharacteristicfeaturesthatmakes themdifferentfromothercausalagentsofinfectiousdiseases. A. Helminthparasitescannotoutpacetheimmunesystemofthehost. Explainwhy. [ANSWER(4points):Helminthsdonotreplicateinsideasinglehost individual.Theparasiteloadofanindividualresultsfrommultiple infectionswithparasites/eggs.Unlikevirusesandbacteria,replicationof helminthparasitesisnotfasterthannormalresponsetimeoftheimmune systemofthehost.] B. Givetwoothercharacteristicfeaturesofhelminthparasites. [ANSWER(onepointeach): Persistenceofindividualparasites(severalyears),andthelowmortality ratesassociatedwithparasiticdiseasesinthehost] C. Somehelminthparasitescangointoadevelopmentalarrest.Give tworeasonswhyadevelopmentalarrestcanbebeneficialfora parasite. [ANSWER(2pointsforeachgoodanswer): Developmentalarresthelpstheparasitestosurviveadverseconditionsin absenceofahost(i.e.eggsofAscarissurvive>10years),and developmentalarrestisusedasameansfordemographiccontrolto preventthatthebuildupofparasiteinfectionsinahostpopulation becomesohighthatitincreasesthemortality.Realizethathelminth parasitesareobligateparasitesthatwanttopersistforalongtimein livinghost.Earlydeathofahostisnotastablestrategyfortheparasite.] Question8: A. DrawtheProductionFunctionforlivestockproductionandshowthe impactofdiseaseonthisFunction(2points). B. Mentionatleast2differencesbetweenproductiondiseasesand HighlyContagiousLivestockDiseases(HCLD;2points). [ANSWERS:Cause:diseaseagent<>lossoffreestatus Impacts:decreasedproduction(efficiency)<>measurestocontrolthe disease Aim:mitigation<>regainfreestatusasap] C. Mentionthefourcategoriesofmonetarycoststhatcanbecausedby anoutbreakofaHighlyContagiousLivestockDisease(HCLD;2 points). [ANSWERS:DirectCosts(DC);DirectConsequentialCosts(DCC);Indirect ConsequentialCosts(ICC);AftermathCosts(AC)] D. BesidesthemonetaryimpactsdiscussedinLecture1,variousother factorscanaffecttheimpactofaHighlyContagiousLivestock Disease(HCLD);mentionatleastthreeofsuchfactors(2points). [ANSWERS:Zoonoticnatureofthedisease;Hobby/Non-commercial farmers;Productionstructure;Regionwherethediseaseoccurs;Control strategyapplied] E. IfyoucompareFoot-and-MouthDisease(FMD)andHighly PathogenicAvianInfluenza(HPAI),whatisthemostimportant differencewithregardtoimpactonsociety?(1point) [ANSWER:ZoonoticnatureofHPAI] F. Hastheaboveanswereddifferencethesameimportanceinall countriesallovertheworld?Providetogetherwithyouranswera shortexplanationoranillustration.(1point) [ANSWER:No;seeHPAIinSE-Asia:muchmorefearforhumanhealth, thereforeuseofvaccin;plus:infrastructureforcontrolisquitedifferent, thereforemeasuresatvillagelevel.] Question9: KuruwasadeadlypriondiseaseinPapuaNewGuinea. A. HowwasKurudiseasetransmittedbetweenmembersoftheForay tribe?(1point) [ANSWER:Viaritualisticcannibalism.] B. WhyweremorefemalesinfectedwithKuruthanmen?(1point) (ANSWER:Moreintensiveroleforwomenintherituals.] C. Name2changesintissuesofthebrainthatcharacterizeprion diseases.(2points) [ANSWER:1.vacuoles/spongiformtissues;2.amyloidplaques/protein deposits/prionfibrils] D. SpellouttheabbreviationsPrPc,PrPsc,PrPsen,PrPres.(2points) [ANSWER:Prionprotein-cellular,scrapie,sensitive,resistant] E. Dr.CharlesWeismannperformedcrucialanimalexperimentsto showspecificityintheinductionofpriondisease(scrapieinmice). Whichmousedevelopsseverediseasewhenchallenged(“infected”) withhamsterscrapie:transgenicmiceexpressing5-10timesmore prionsortransgenicmiceexpressinghamsterprions?Explainyour answer.(4points). [ANSWER:Transgenicmiceexpressinghamsterprions,onlythesemiceare susceptibletothedisease.Miceexpressingmouseprionsdonotdevelopdisease uponchallengewithhamsterscrapie.]