GREATAMERICAN DISEASES
TheirEffectsonthecourseofNorth AmericanHistory
IANR.TIZARD
JEFFREYM.B.MUSSER
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Introduction:HowinfectiousdiseaseshaveshapedAmericanHistoryxiii
1.Infectiousdiseasesandtheircauses1 Aworldofmicrobes4 Bacteria4 Viruses10 Protozoanparasites14 Zoonoses15 Pandemicsandepidemics17 References17
2.Immunityandrecoveryfrominfectiousdiseases19 Immunedefenses20 Innateimmunity21 Adaptiveimmunity24 Populationimmunity27 Vaccination27 Herdimmunity28 Immunization31 References36
3.Diseasesamongthefirstinhabitants37 NativeAmericandiseases38 TheMayacollapse42 References44
4.Tuberculosis Anotherancientdisease45 Theorganism46 Thedisease48 History49 Thetuberculosisepidemic51 References67
5.SyphilisandtheColumbianexchange69 Theorganism69 Thediseases70 History71 TheTuskegeeSyphilisStudy78 References83
6.Malariaandtheague 149285 Malarialparasites86 Thedisease88 History89 Newdiscoveries97 References105
7.Smallpox 1519:Thefirstvaccines107 Smallpox:Thedisease108 History109 Variolation117 Vaccination124 Eradication!132 References134
8.Measles 1531:Almostgone!137
9.Typhoidandtyphus 1607:Smellydifferences153 Typhoidfever154 Thedisease155 History157 Waterquality161 Currentstatus165
10.Yellowfever—1647:Mosquito-borneinvader173 Yellowfever174 History175 TheUnitedStates178 TheSpanish-Americanwar187 Yellowfevervaccine194 References196
11.Cholera 1832:Aworldwidepandemic197 Thebacterium198 Thedisease198 History199 References213
12.Poliomyelitis 1841:Thetriumphofvaccination215 Thedisease216 History217 JonasSalk224 AlbertSabin227 Globaleradication232 References234
13.InfectiousdiseasesandtheCivilWar235 Entericdiseases237 Measles240 Fevers242 Parasites248 Militaryhospitals249 Lessonslearned253 References254
Acknowledgments
TheauthorsthanktheassistanceprovidedbyDr.SuzanneBurnhamand RobertTizardinreviewingandcorrectingthetext.Asalways,thisbook wouldnothavebeenpossiblewithoutthesupportofourwives,Claire andKaren.
Introduction:Howinfectiousdiseaseshave shapedAmericanHistory
IanR.TizardandJeffreyM.B.Musser
DepartmentofVeterinaryPathobiology,CollegeofVeterinaryMedicine,TexasA&MUniversity, CollegeStation,TX,UnitedStates
Itisnowmorethan100yearssincethegreatinfluenzapandemicof1918 killedmorethan600,000Americans.Ithasbeenmorethan50yearssince JonasSalk’spoliovaccinebegantoeliminatethatscourgefromthecontinent.Diseasesthathadkilledthousandsandcausedwidespreaddespair anddeathhavebeenlargelyeliminatedorcontrolled.Therefore,theemergenceofthecoronavirusthatcausesCOVID-19cameasanuglyreminder thatinfectiousdiseaseshavenotbeeneliminated.Theyhavesimplybeen controlledtemporarily.Infectiousdiseaseswillcontinuetoreturnandkill becausetheyareanintegralpartoflifeonearth.Inthismicrobialworld, humansandotheranimalsaremerelyaresourcetobeexploitedbymicrobes.
ThehistoryoftheAmericashasbeendefinedbyinfectiousdiseases:from thedepopulationofNativeAmericansbyEuropeansmallpox,todiseases thatdeterminedthecourseoftheWarofIndependence,andtothemajor engineeringprojectsdesignedtoprovidecitizenswithcleanwaterandsewagetreatment.Diseasehasdefinedandinalargepartcontrolledourhistory. TheAmericasarenotuniqueinthisrespect.Othercountriesandcontinents havealsobeenprofoundlyaffectedbyinfectiousdiseaseoutbreaks.
Thatsaid,therehasbeenaperceptionthatthosediseaseswerebehindus. Infectiousdiseaseswerenolongerconsideredathreat.Manybelievedthatif morearrived,theycouldbehandled.Certainly,thehistoryofthe20thcenturysuggestsaprogressiveandinexorableimprovementinourhealth.On thefaceofit,weappearedtohavewon;webeatthemicrobes.
Thisofcoursewasanillusion.First,wemustnotextrapolatethesituation inthedevelopedworldtothelessdevelopedareasoftheworld.Second,we arebeginningtoseecracksappearinginourownmedicaldefenses,ranging fromantibioticresistanceinbacteriatovaccinerefusalbylargesegmentsof thepopulation.Mostimportantly,theresultsofoverpopulation,encroachmentonwildernessareas,andclimatechangehaveincreaseddiseaseinstabilityandtransmissibilityandprovidedbacteriaandviruseswithhitherto unexpectedopportunitiestospread.
InrichcountriessuchastheUnitedStates,lifeexpectancy,whichhad hoveredaround30–40yearsforhundredsofyears,begantoincrease;by 1900,ithadreached50,andby2010,ithadreached80.Welongoutlive thelifespanofourgrandparent’sgeneration.Thisincreaseispredominantly duetothecontrolofinfectiousdiseases.Antibiotics,waterchlorination,pasteurization,adequatesewagetreatment,andaboveall,vaccinationhaveprofoundlychangedthehumancondition.Thishasoccurrednotonlyinthe UnitedStatesbutalsoworldwide.Thegreatdiseasesdescribedinthisbook arelargelyfeaturesofadistantpast.
Priortothedevelopmentofmicrobiology,mostdiseasetreatmentswere uselessorworse.Theintroductionofvariolationatthebeginningofthe 18thcenturywasthefirstoccasionwhereamedicaltreatmentwasshown tobeeffective.EvenuptoWWIIandthediscoveryofantibiotics,doctors hadfeweffectivecuresforinfections.
Notwithstandingthemassiveincreaseinlifeexpectancyandaneffective doublingofourlifespan,whatwehaveseenoverthepast75yearshasbeen nomorethanatemporarylullinhostilities,apausewherewehopefully shoredupourdefensesandwaitedforthewartorecommence.Victory hasnotbeentotal.Aswithrealhumanwars,weappeartobeenteringa periodofasymmetricwarfarewhereourmajorweaponsmaybecircumventedbymoresubtleformsofmicrobialinvasion.
Anotherfeatureofourcurrentexpectationsofprolongedgoodhealthis anintoleranceofmassivecasualties.RecentdiseaseoutbreakssuchasSARS orZikavirushavekilledonlyafewthousands,afarcryfromthemassive pandemicsofthepast.Nevertheless,theyresultedinapanicthatsubsided oncethethreatwasremoved.This“panic-and-forget”patternwasafeature ofAmericanresponsestoinfectiousdiseasesformanyyearsuntilCOVID arrived.Therefore,itisappropriatetoremindourselvesofthatoverused adagethat“thosewhodonotrememberhistoryaredoomedtorepeat it.”Ifwearetomaintainourimprovedstatuswithrespecttoinfectiousdiseases,weneedtorememberanothercliche:Thepriceoffreedom(fromdisease)isalsoeternalvigilance.
Thediseasesthatwehavechosentoexploreinthistextarethoseweconsiderthemosthistoricallysignificant.Afterall,manyoftheoutbreakswedescribehavebeencoveredpreviouslywithentiretextsdedicatedtoindividual diseasesorepidemics.Nevertheless,webelievethataholisticapproachserves toplacetheNorthAmericaninfectiousdiseasehistoryinperspective.
Thisbookfollows,inpart,thecurriculumofourintroductorymicrobiologycourseatTexasA&MUniversitytitled“GreatDiseasesoftheWorld.” Thatcoursewasconceivedasanintroductorycourseinmicrobiology.Ratherthanteachtheratherdrytopicsofbiochemicalreactionsandmicrobial
diseases,wechosetofocusonthe“coolbits”ofmicrobiologyandthelurid historyofmanyinfectiousdiseases.Therefore,thisbookisnotdesignedtobea comprehensivelistofallthemajorinfectiousandparasiticdiseasesthathave affectedAmericansovertheyears.Rather,itisalookatthemostimportant and,inouropinion,themostinteresting.Wehopethatyouwillagree.
Thisbookdoesnotneedto,norisitintendedtobereadinalinearmannerfromthefirsttothelastpage.Thereaderorinstructorisfreetopickand choosethediseaseofinterestandtopicswithineachchapter.Mostaspectsof biologyandhistoryarenotlinearbutconvolutedandoftentimescircular. However,theorderofthediseasechaptersinthisbookischronological basedonwhentheywerefirstidentifiedandbegantocauseproblemsin NorthandCentralAmerica.
Oneconsistentfeatureofthehistoryofmedicineisanongoingdebate regardingspecificdiagnosespriortothemodernera.Untilabout150years ago,diagnosiswasasubjectiveart.Diseasediagnosiswasamatterofphysician opinionratherthanscience.Forthisreason,itisappropriatetoretainsome skepticismregardingthespecificcausesofmanyhistoricepidemics:wasit smallpoxorreallymeasles;wasittyphusortyphoid;wasitinfluenzaorcoronavirus?Thisintrinsicuncertaintyhasgivenrisetoaminoracademicindustry ofthoseseekingto“secondguess”widelyaccepteddiseaseattributions.Some oftheseclaimsarewildlyspeculative.Manyhavebeendismissedbyrecent discoveriesas,forexample,theunequivocalidentificationof Yersiniapestis asthecauseoftheearlyplaguepandemics.Ontheotherhand,someearly pandemicsattributedtoinfluenzamayreallyhavebeenduetocoronaviruses! Thecauseofsomehistoricoutbreakswilllikelyneverbeestablishedunless molecularevidencecanbeadducedbynewstudies.Itisalsoabundantlyclear thatmanyepidemicswerelikelyaresultofmultiplediseasesoccurringatthe sametime.However,experiencehasshownthatinmostcasestheoriginal diagnoseswerecorrect.Therefore,wehavetriedtoresistthetemptationto ascribenewcausestooldepidemics.Thatsaid,scienceandhistoryadvance handinhandandnodoubtsomesurprisesstillremaininstore.
InJanuary2020,newsemergedofyetanothercoronavirusoutbreakin Wuhan,China.Withinaremarkablyshorttime,itbecameapparentthat theworldwasinforapandemic,thelikesofwhichhadnotbeenseensince thegreatinfluenzapandemicinthefallof1918.Thediseasecausedbythis coronavirus,COVID-19,islikelytobewithusforalongtimeandthestory hasscarcelybegun.WehavesoughttoplaceCOVID-19initshistoricalcontext.Thepandemichasmanyfeaturesincommonwithepidemicsofthepast. Technologymaychangebuthumanbehaviordoesnot.Likewise,neitherhistorynorsciencestopwhenwesendourmanuscripttothepublisher.Ifitwas notCOVID,itwouldhavebeensomeotherdisease.Butthatisanotherstory.
InmemoryofDr.MohamedTawfikOmran—scholar,teacher, colleague,andfriend.
Infectiousdiseasesandtheir
causes Abstract
Weliveinaworlddominatedbymicrobes,bacteria,viruses,molds,andprotozoanparasites.Onlyafewarepathogensthatcauseinfectiousdiseases.Themostimportantare bacteriaandviruses.Bacteriaaresingle-celledorganisms.Therearemanyspeciesthat differinsize,shape,andmetabolism.Manyarenormalinhabitantsofbodysurfaces. Somecaninvadethebodyandcausetissuedestruction.Virusesaresmallmolecular constructsconsistingofnucleicacids,packagedinaproteinshell.Virusescanonlyreplicatewithinlivingcells.Someimportanthumandiseasessuchasmalariaarecausedby protozoanparasites.Infectiousdiseasesmaybeacquiredfromotherhumansordomestic/wildanimals so-calledzoonoses.Someoftheseorganismscancausediseasein healthyindividualswhileothersmayonlyattackindividualswhoseimmunedefenses areweakened.Wheninfectiousdiseaseoutbreaksdooccur,theymaybelocalizedor developintoepidemicsandpandemics.
Keywords: Bacteria,Viruses,Protozoa,Epidemic,Pandemic,Immunity,Pathogen, Virulence,Opportunistic,Zoonoses
Infectiousdiseaseshavehad,andcontinuetohave,profoundeffectsonthe courseofAmericanhistory.Historicallytheykilledmillions,causeduntold suffering,andplayedakeyroleinthecolonizationanddevelopmentof boththeUnitedStatesandCanada.Andtheyhavenotceased.In2020 theSARS-2coronavirus,thecauseofCOVID-19,escapedfromChina andspreadaroundtheworld.Itkilledmillionsofpeopleandcausedenormoussocialdisruption.
Inadditiontosocialfactors,theimpactofinfectiousdiseaseoutbreaks, epidemics,andpandemicsisdeterminedlargelybytwokeyfactors.One istheabilityofanorganismtocauseseriousdisease—itsvirulence.Theother istheabilityofhumanstocombattheseinfections,inotherwords,their immunity.Theoutcomeofsuchdiseasesisdeterminedbythebalance betweenvirulenceandimmunity.Thedeclineintheapparentimportance ofinfectiousdiseasesoverthepast100yearshasbeenadirectresultof improvedsanitationpracticesaswellasourgrowingabilitytoprevent
andtreattheseinfectionsthroughtheuseofvaccinesanddrugssuchasantibiotics.Intheabsenceofvaccinesanddrugs,organismsmayspread unchecked,especiallyinlarge,densepopulations [1].Thatisthecasein ourpresentoutbreakofCOVID-19.Itwascertainlythecaseinthepast beforemodernmedicineachieveditssuccessesanditwillremainthecase inthefuture.
Whiletheideathatsomediseaseswerecausedbyinvisiblemicroorganismswasfloatedfromtimetotime,thiswasmerespeculationuntilAntonie vanLeuwenhoekintheNetherlandslearnedhowtomakelensescapableof magnifyingupto275timesorgreater.Heusedtheseinsingle-lensmicroscopestoexamineadiversemixtureofbiologicalspecimens.Asaresult,he wasthefirsttoobservebacteriaandprotozoa [2].Whenheexaminedthe gunkfrombetweenhisteeth,hesawallsortsofsmallorganismsthathe called kleinediertjens—Dutchfor“smallanimals.”Thiswordwastranslated intoEnglishas“animalcules.”Thesecreatureswereswimmingaroundand hedrewanddescribedtheirshapes.Healsoexaminedhisownfecesand foundaparasiticprotozoanthatwenowcall Giardia.VanLeuwenhoek reportedthisfindingoforalbacteriainalettertotheRoyalSocietyinLondoninSeptember1683.
ThesignificanceofthesemicroscopicanimalculeswasnotreadilyapparentatthetimeandwhileotherthoughtfulindividualssuchasCotton MatherinBoston,madestatementsspeculatingthatinvisibleorganisms werethecauseofdisease,itwasnotuntilthescienceofmicrobiologydevelopedinthemid-19thcenturythatspecificorganismswererecognizedas causesofspecificdiseases.In1838,GottfriedEhrenberginGermanycalled theseanimalculesbacteria,fromtheGreek bakteria,meaning“alittlestick” sincetheywererod-shaped.
RobertKochinGermanywasthefirsttolinkaspecificbacteriumwitha diseasewhenheidentifiedtheanthraxbacillus [3].Kochwasaphysician workinginpracticeinWollstein,ineasternGermany.Asthedistrictmedical officer,hewasconfrontedbyanongoingoutbreakofanthrax.Adiseasethat hadkilledhundredsofpeopleandthousandsofcattle.Onexaminingthe bloodofdeadanimalsunderaveryprimitivemicroscope,Kochobserved rod-shapedstructures.Healsoshowedthatbloodfromasheepthathadjust diedofanthrax,wheninjectedintoamouse,wouldkillthemousewithin 24h.Thenhefoundtherod-shapedstructuresinthebloodandtissuesofthe mouse!Spleentissuefromthedeadmouse,wheninjectedintoanother mousewouldgivethesameresult—rapiddeath.Kochdeterminedthat therod-shapedstructureswerebacteria.Heeventuallydevelopedamethod
ofgrowingthebacteriaincultureandwasthusthefirsttolinkaspecific bacteriumtoaspecificdisease.Hispaperdemonstratingthatanthraxwas causedbythebacterium, Bacillusanthracis waspublishedin1876.
Asaresultofhisgrowingreputation,KochmovedtoBerlinandjoined theImperialHealthCollege.Herehemademoresignificantadvances.He foundthathecould“fix”bacteriatoaglassmicroscopeslidebydryingthem fromaliquidsolution;hecouldstainthemwithanilinedyes;heworkedon improvingmicroscopes;andwasthefirsttopublishphotographsofbacteria. Othersinhislaboratoryalsomadesignificantadvances.Forexample,the platetechniqueofgrowingbacteriainpureculturewasdevelopedinhislaboratory.Twoofhisassistants,WalterandFannieHessdiscoveredthatagar,a gelobtainedfromseaweed,couldbeusedtomakeanutrientmediumon whichbacteriacouldbecultured.Anotherofhisassistants,JuliusPetri designedashallowdish(nowcalledaPetridish)toholdtheagar-based mediumandpermitbacteriatogrowwithoutcontamination.Subsequently, RobertKochwentontodescribeotherdisease-causingbacteriasuchas Mycobacteriumtuberculosis in1882and Vibriocholerae in1883.Koch,asthe founderofthescienceofbacteriology,receivedtheNobelPrizeforMedicinein1905.
Fromthepointofviewofhistory,itisimportanttoemphasizethedates ofKoch’sdiscoveries.Anydiseasediagnosispriortothe1870smustbeconsideredspeculative.Physicianscoulddiagnosesomeveryobviousdiseases suchassmallpoxoryellowfeverbutinmanyotherdiseaseoutbreaks reportedpriortothe1870s,theircausesmustremainspeculative.Thisis especiallytrueofdiseaseswithnonspecificclinicalsignssuchasfeveror diarrhea.
AsaresultofKoch’sdiscoveries,bacteriologyrapidlydevelopedasadiscipline,andcompetingscientistssoughttobethefirsttoidentifythecauseof specificdiseases.Itwasnotuntiltheendofthe19thcenturythatprotozoan parasites,alsovisibleunderthemicroscopewithsuitablestains,were detectedandassociatedwithspecificdiseasessuchasmalariaandTexas Fever.Fungiwerealsoidentifiedasacauseofsomediseasesaroundthe sametime.
Bacteriaarenottheonlyorganismsthatcancausedisease.Virusescan invadeanddestroycellsandcausemanyseriousinfections.Virusesaresmall molecularcomplexesthatcannotbeseenunderalightmicroscope.Itwas notuntil1938whenthefirstviruswasobservedbyelectronmicroscopy. Priortothattimehowevertheirexistencehadbeeninferredbyfiltering bodyfluidstoremovebacteriaanddemonstratingthatthefilteredmaterial
wasstillinfectious.Thus,thefirstreportofa“filterablevirus”wasin1892 whenitwasfoundtobethecauseofadiseaseoftobaccoplants.
Aworldofmicrobes
Whilewearelargelyunawareofit,weliveinaworlddominatedby microbes,especiallybacteria.HalftheEarth’sbiomassconsistsofmicroorganisms.(Plantsaccountfor35%ofthebiomassandanimalsonlyabout 15%.)Microbesliveeverywhere,includinginsideandonourbodies.All ourbodysurfacescarryadensemicrobialpopulationcollectivelycalled themicrobiota.Thedensestpopulationofbacteriaonthisplanetliveswithin ourlargeintestine.Thesoilwestandonhasahugemicrobialpopulationas dotheoceans.Witheverybreath,weinhaleaboutamillionbacteria.We haveaboutthesamenumbersofbacteriainourbodyaswehavehuman cells.Almostalloftheseorganismshaveevolvedtomakeuseofthesources ofenergyintheirenvironment.Afewofthem,verymuchinaminority, haveevolvedtoobtaintheirenergyfromthehumanbody.Itistheseselect fewthatcaninvadeandcausediseaseunderappropriatecircumstances.
Bacteria
Asnotedearlier,enormouspopulationsofbacterialiveonourbody surfaces.Theyliveontheskinwheretheyareresponsibleforbodyodor. Theyliveinourrespiratorytract.Theyliveinourmouthwheretheyare responsiblefor,amongotherthings,toothdecayandbadbreath.Theylive inthegenitaltract.Thegreatestpopulationofbacterialiveswithinourintestinaltract.Theyshareourfoodwithus.Theysendchemicalsignalstothe bodyensuringthatitsdefensesstayintip-topshape,andwhenwedie,they makeourbodiesdecompose.
Propertiesandclassification
Theearlymicrobiologistslearnttorecognizebacteriaunderthemicroscope andgrowtheminnutrient-richculturemedia.Thus,thefirstmethodof classifyingwhattheysawwassimplybytheirshape [4].Theround grape-likebacteriatheycalledcocciandtherod-shapedbacteriatheycalled bacilli(Fig.1.1).Thecocciweresubdividedintothosethatformedchains, likethestreptococciandthosethatformedclusters,likethestaphylococci. Thosethatformedpairstheycalleddiplococci.Somebacilliareconsistently
Gram-positive bacilli
Gram-negative bacilli
Gram-positive cocci (Streptococci)
Spirochetes
Gram-negative Vibrios
Fig.1.1 Themajorbacteriaandtheirshapes.Gram-positivebacteriastainstronglywith thedye,methylenebluewhenstainedbyGram’smethod.Gram-negativebacteriado notretainthebluedyesothatitcanbewashedoutandtheycanthenbestainedbya redcounterstain.
curvedintoacommashapeandvibratedastheymovedsotheywerecalled vibrios.Somebacteriapossesslongfilamentousprocessescalledflagellae (Fig.1.2).Whenflagellaearewavedaround,theyenablethebacteriato move,inotherwords,somebacteriaare“motile.”Theprecisearrangement andnumbersoftheseflagellaearealsoanaidtobacterialclassification.
Thenextstepinthediscoveryprocessinvolvedthestainingofbacteria bychemicaldyes.Themostusefulandimportantstainingtechniqueturned outtobeonedevelopedbyHansChristianGram,aDanishmicrobiologist in1884.Hewasexaminingstainedtissuesectionsfromthelungsofpatients autopsiedafterdyingfrompneumoniaandnoticedthathisdyestainedthe bacteriaverystronglybutnotthelungtissue.UponinvestigationGram foundthathecouldstainsomebacteriawithadyecalledcrystalviolet.More importantlyhefoundthatinsomebacteria,afterstaining,thecrystalviolet waseasilywashedoutbyalcohol,whileinothersitpersisted.Thosebacteria thatstainstronglywithcrystalvioletareclassifiedasGram-positivewhile thosethatreadilylosethedyeareclassifiedasGram-negative.Gram-positive bacteriastainbluewhileGram-negativebacteriacanbecounterstainedby, forexample,thereddyesafranin.ThesedifferencesbetweenGram-positive andnegativebacteriaaresignificantsincetheyreflectmajorstructuraland
biochemicaldifferencesbetweentheircellwalls.ThecellwallsofGrampositivebacteriaaresignificantlythickerthanthoseofGram-negative organisms.Somebacteriasuchasthetreponemesthatcausesyphilisdo notstainstronglywithGram’sstain.Thus,confirmingtheirdistantrelationshiptootherbacteria.
AsecondstainingprocedurewasdevelopedbytheGermanchemistand pathologist,PaulEhrlichandmodifiedbyFranzZiehlandFriedrichNeelsen in1882.Thisinvolvestheuseofadyecalledcarbolfuchsintostainthebacteria.Oncestained,certainlipid-richbacteriacanretainthestainafterwashingwithhydrochloricacidinalcoholbecauseitbindstolipidscalledmycolic acids.Inthosebacteriathatlackmycolicacids,thecarbolfuchsinisreadily washedoutandthebacteriaaredecolorized.Thosethatretainthedyeare stainedredandareclassifiedasacid-fastbacteria.Acid-fastnessischaracteristicofthegroupofbacteriacalledMycobacteria.Thesearethecauseofdiseasessuchastuberculosisandleprosy.Thelipidsinthecellwallsofthese bacteriatendtomakethemimpermeabletoGram’sstain.Theselipidsalso protectthemfromdestructiononcetheyinvadethebody.
Inadditiontotheirphysicalproperties,bacteriamaybeclassified accordingtotheirmetabolicneeds.Forexample,somerequirelotsofoxygenandarecalledaerobeswhileothersonlygrowintheabsenceofoxygen andarecalledanaerobes.Itshouldcomeasnosurprisethereforethatan
Flagellum
Pili
Capsule
Cell wall
Cell membrane
Nucleic acid
Cell sap, enzymes, etc.
Fig.1.2 Piliarecellsurfacestructuresbywhichbacteriacanattachtocells.
aerobesuchas M.tuberculosis preferstogrowinwell-oxygenatedtissueslike thelung.Ontheotherhand, Clostridiumtetani,astrictanaerobethatcauses tetanus,preferstogrowindeadtissuesuchasindeepwoundswhereoxygen tensionislow.Somebacteriasuchas V.cholerae preferalowoxygentension andarethereforeconsidered“microaerophilic.”
Bacteria,withrelativelysimplemetabolicsystems,canreadilyusesugars asanenergysource.Theydifferhowever,inwhichsugarstheycanuse.This toocanbeusedtoclassifythem.Forexample,twobacteriathatcausediarrheaare Escherichiacoli and Salmonellaenterica.Theylookexactlythesame, bothareGram-negativebacilli,but Salmonella cannotuselactoseasafood sourcewhile E.coli can.
IthaslongbeenconventiontogivebacteriaaLatinnameusingtwo words(binomial).Thefirstnamedenotesthegenuswhilethesecond denotesthespecies.Forexample,theorganismthatcausessyphilisiscalled Treponemapallidum,whilethebacteriumthatcausestherelateddiseaseyaws, iscalled Treponemapertenue.Otherexamplesaretheorganismsofthegenus Brucella.Allcauseundulantfeverbut Brucellaabortus infectscattle, Brucella melitensis infectsgoats, Brucellasuis,asitsnameimplies,infectspigs,and Brucellacanis infectsdogs.Allcancausediseaseinhumans(Table1.1).
Thesebacterialnamesmayalsochangeasmoreinformationaccumulates abouttheorganismanditsproperties.Forexample,whenAlexandreYersin firstidentifiedthebacillusthatcausedtheplague,hecalledit Bacilluspestis. Severalyearslateritbecameclearthattheorganismdidnotreallybelongin thegenusBacillus,soitwasrenamed Pasteurellapestis.Finally,in1970, anotherreassessmentmovedittoanothergenus,anditisnowcalled Yersinia pestis.
Asmoreislearntaboutbacteria,thisbinomialsystemappearstobe increasinglyinadequate.Forexample,thereareover2500distinctvarieties of S.enterica.Thesevarietiesaredesignatedserovarsorsubspeciesbecause theycanbedistinguishedbytheuseofspecificantibodiesmadeinimmunizedanimals.Theseantibodiesarefoundinbloodserum,hencetheterm serovar.
Thenormalmicrobiota
Asmentionedearlier,animalbodiesarenotsterile.Wehaveenormous populationsofbacterialivinginourintestine,inourupperairways,and onourskin.Thesebacteriabenefitusinseveralways.Thus,theyhelpus digestfood.Theygeneratemetabolitesthatserveasessentialnutrients.They releaseotherwiseunavailableenergyfromfoodsandtheystimulatethe
Table1.1 Thecharactersinthisbook.
NameoforganismNameofdiseaseAgent
Bacteria
Treponemapallidum
Borreliaburgdorferi
Rickettsiaprowazekii
Rickettsiarickettsii
Salmonellaentericaserotype typhi
Vibriocholerae
Mycobacteriumtuberculosis
Yersiniapestis
Legionellapneumophila
Viruses
SyphilisSpirochete
LymediseaseSpirochete
EpidemicTyphusIntracellular coccobacillus
Rockymountain spottedfever Intracellular coccobacillus
TyphoidfeverGram-negative bacillus
CholeraGram-negative vibrio
TuberculosisAcid-fastbacillus
PlagueGram-negative bacillus
Legionnaire’sdiseaseGram-negative bacillus
VariolamajorSmallpoxOrthopoxvirus MeaslesvirusMeaslesMorbillivirus
YellowfevervirusYellowfeverFlavivirus
PoliovirusPoliomyelitisEnterovirus
InfluenzaAvirusInfluenzaOrthomyxovirus
HumanImmunodeficiencyvirusAIDSRetrovirus SARS-CoV-2COVID-19Betacoronavirus
Protozoa
Plasmodiumfalciparum, P.vivax, P.ovale, P.malariae
MalariaHemoprotozoan parasite
developmentofourimmunesystem.Ifthemicrobiotaisdisruptedby,for example,excessiveantibioticuse,theresulting“dysbiosis”canleadto changesintheimmunesystemthatcanprovokeallergies.Theintestinal microbiotaalsoserveaprotectivefunctioninsofarastheyarewelladapted intheintestinalenvironment.Theycanthereforeout-competeandso excludepoorlyadaptedorganismsthatshouldnotbethere.Theintestinal microbiotaareconsideredtobecommensals,withmutuallybeneficialinteractionsbetweenthemandtheirhost [5].
Howbacteriacausedisease
Bacteriathatcausediseasearesaidtobepathogenic.Obviously,thereare degreesofpathogenicityandthisismeasuredbyvirulence.Thus,ahighly
virulentpathogenisonethatcausesseveredisease.Lessvirulentbacteriacan causemilddiseasewhileavirulentbacteriadonotcausedisease.Inallthe majorbacterialdiseasesdescribedinthisbook,thecausalagentswerehighly virulent.
Therearemanyreasonswhyabacteriumwillactasavirulentpathogen. Thesemaybedirectlyrelatedtotheorganism’smodeofgrowthorthelack ofresistanceinitshost.Bacteriathatinvadethebodyineffect,seektofeed onit.Iftheyaresuccessful,theymaygrowrapidly,andthediseasewillprogress.Forexample, Y.pestis,thecauseoftheplaguepossessesenzymesand toxinsthatkillthewhitebloodcellsdefendingthebody.Thesetoxinsalso destroybloodvesselwallssothatbloodleaksintotissuessuchasthelungs. Theorganismmultipliesexplosively,anddeathoccurswithindays.Other bacteriasuchas M.tuberculosis growmuchmoreslowly.Thehostimmune systemkeepsmostsuchinfectionsundercontrolsothatthemajorityofindividualsinfectedwith M.tuberculosis usuallyremainhealthy.Onlyifthehost’s immunityfailsdoesdiseasedevelop.
Afewbacteriacansecretepotentproteintoxinsthatkilltheirhosts.For example,strictanaerobessuchas B.anthracis,thecauseofanthrax,and C.tetani,thecauseoftetanus,benefitbykillingtheirhosts.Insidethedead animal,thereisananaerobicenvir onmentwheretheycanthrive.On theotherhand,mostbacteriadonotbenefitfromkillingtheiranimalhost. Iftheylosetheirhost,theytoomaydie.Thus,anorganismsuchas V.cholerae,thecauseofcholera,simplycausesseverediarrheathatspreadsthe bacteriumthroughouttheenvironment. M.tuberculosis causeslunginfection.Theresultingcoughingbythevictimresultsinthespreadoftuberculosis.Manybacteria,especiallyGram-negativeonespossessacell-surface coatoflipopolysaccharidemolecules. Thislipopolysaccharidecoatisrecognizedbythehostandtriggersadefensiveresponse.Theresponsetriggers behaviorsincludingfever,malaise, andalltheotheruncomfortablesigns weassociatewithsickness.Thus,theselipopolysaccharidesarealsocalled endotoxins.
Resistancetobacterialinfectionsisinherited.Whenapathogenicbacteriuminvadesapopulationthereisgreatvariationbetweenindividuals intheirdefensiveresponses.Someindividualsarehighlyresistantwhile othersareverysusceptible.Mostofthepopulationliessomewhereinbetween.Overtime,repeatedinfectionswillkillthemostsusceptibleand asaresultthepopulationasawholewillbecomemoreresistant.Ifhowever acompletelynewinfectiousdiseaseappearstowhichnobodyhasresistance, thenalethalepidemiccanensue.ThisiswhathappenedintheBlackdeath dueto Y.pestis wherethepopulationofEuropehadneverpreviously
