Bad air, amulets and mosquitoes: 2,000years of - Malaria Journal

14 Pages·2013·3.18 MB·English

Bad air, amulets and mosquitoes: 2,000 years of
changing perspectives on malaria
Hempelmann and Krafts
HempelmannandKraftsMalariaJournal2013,12:232
http://www.malariajournal.com/content/12/1/232
HempelmannandKraftsMalariaJournal2013,12:232
http://www.malariajournal.com/content/12/1/232
REVIEW Open Access
Bad air, amulets and mosquitoes: 2,000 years of
changing perspectives on malaria
Ernst Hempelmann1 and Kristine Krafts2*
Abstract
For many centuries, scientists have debated thecause and best treatment ofthe disease now known as malaria.
Twotheoriesregarding malaria transmission –that of“bad air” and that ofinsect vectors–have been widely
accepted atdifferent timesthroughout history. Treatments and cures have varied accordingly over time. This paper
traces theevolution of scientific consensus onmalaria aetiology, transmission, and treatment from ancient times to
thepresent day.
Background Places” [1]. Inancienttimes,longbeforethetermmalaria
There are certain diseases which have been historically wascoined,the diseasewasdescribed variously as “marsh
shroudedinmystery,theircausesattributed tomagicalor fevers”, “agues” (from the Latin febris acuta), “tertian
spiritual forces. Ovarian teratoma, for example, a tumour fevers”, “quartan fevers”, or “intermittent fevers.” Most
named after the Greek τέρας (monster), is a neoplasm termsoriginatedfromthewritingofHippocrates,whode-
composed of hair, teeth, skin and other mature tissues. scribed the unhealthiness of the air in certain environ-
Aristotle attributed teratomas to hair that had been mentsasitrelatedtofataldiseaseswithquartanfevers:
swallowed by the patient and deposited in various body
tissues.Butothertheoristsclaimedmoreominousorigins: Thisdiseaseishabitualtothem bothinsummerand
teratomas werevariously reportedtobe aconsequence of inwinter,and inaddition theyare verysubjectto
sexual relations with the devil, an expression of a night- dropsiesofamostfatalcharacter;and insummer
mare (incubus), evidence of engagement in witchcraft, or dysenteries,diarrhoeas,andprotractedquartanfevers
apunishmentforwickedness. frequently seizethem, andthesediseaseswhen
Malaria has long been a member of this fascinating prolongeddispose suchconstitutionstodropsies,and
group of diseases with veiled origins. For many centuries thus prove fatal[1].
it was believed that certain diseases, such as malaria and
cholera, were caused by miasma (μίασμα, ancient Greek: QuintusSerenusSammonicus
pollution, defilement), a poisonous vapour or mist filled Thesomewhatmysticalconceptofbadairsetthestagefor
with particles from decomposed matter (miasmata). Prior an alchemistic malaria treatment in the third century CE.
to the introduction of the microscope, everything floating Quintus Serenus Sammonicus, physician to the Roman
abovegroundthatwasinvisibletothehumaneye,includ- emperor Caracalla, directed patients suffering from fever
ing dust particles and bacteria, was called “air” – so in a and ague to wear an amulet with the inscription “abraca-
sense, perhaps this early aetiological speculation was not dabra” (Figure 1) in his didactic medical poem “Liber
farfromthetruth. Medicinalis:”
Hippocrates Inscribischartae,quoddicitur Abracadabra,
In 400 BCE, Hippocrates discussed the aetiology of se-
lected diseases in his treatise “On Airs, Waters, and Saepius:et subterrepetas,seddetrahe summae,
Et magisatquemagisdesint elementafiguris
*Correspondence:[email protected] Singula,quae semperrapiesetcoeterafiges,
2DepartmentofOralPathology,UniversityofMinnesotaSchoolofDentistry, Donecinangustamredigatur literaconum.
515DelawareStreetSE,Minneapolis,MN55455,USA
Hislinonexiscollumredimirememento [2].
Fulllistofauthorinformationisavailableattheendofthearticle
©2013HempelmannandKrafts;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsofthe
CreativeCommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,
distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
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ate foods of the onion family – most likely garlic – to
ward off mosquitoes. Herodotus, a Greek historian who
livedintheFifthCentury BCE,describedthepractice:
OnthepyramiditisdeclaredinEgyptianwritinghow
muchwasspentonradishesand onions andleeksfor
theworkmen,and ifIrightly rememberthat whichthe
interpreter saidinreading tomethisinscription, a
sum of1,600talentsof silverwasspent[5].
Insects have been recognized as agents of death and
decay since ancient times. In the Old Testament of The
Bible, the fourth plague of Egypt consisted of swarms of
flies ( ):
Else,ifthou wiltnot letmy people go,behold,Iwill
send swarmsoffliesupon thee,and uponthy servants,
and uponthy people,andinto thyhouses:andthe
housesoftheEgyptiansshallbe fullof swarmsofflies,
and alsotheground whereontheyare.
Exodus8:21 (KingJamesBible,CambridgeEd)
The ancient Hebrew word, , often translated sim-
Figure1Sammonicus’anti-pyreticabracadabratalisman. ply as “flies”, most likely represents a multitude of vari-
ous sorts of insects – not only flies, but gnats, wasps,
Write severaltimesonapieceofpapertheword and hornets – of a more pernicious nature than their
‘Abracadabra,’andrepeatthewordinthelinesbelow, commoncounterparts.
buttake awaylettersfromthecompleteword and let Years later, disease began to be associated not only
thelettersfallawayone at atimeineachsucceeding with insects but with tiny organisms too small to be
line.Take these awayever,butkeeptherestuntilthe seen. Marcus Terentius Varro (116–27 BCE), a Roman
writingisreducedtoanarrowcone.Remembertotie scholar and writer, recognized the importance of tiny
thesepaperswithflaxandbindthemroundtheneck[3]. creaturesinthepathogenesis ofdisease:
After wearing the talisman for nine days, it was to Advertendumetiam,siquaeruntlocapalustria,
be thrown over the shoulder into an eastward-running etproptereasdemcausas,etquodcrescuntanimalia
stream. Failing this treatment, Sammonicus recom- quaedamminuta,quaenonpossuntoculiconsequi,
mended the application of lion’s fat, or the wearing of etperaeraintusincorpusperosacnaresperveniunt
cat’s skin tied with yellow coral and green emeralds atqueefficiuntdifficilismorbos.Fundanius,Quid
around theneck[3]. potero,inquit,facere,siistiusmodimifundus
Some scholars dismiss the word abracadabra as mean- hereditatiobvenerit,quominuspestilentianoceat?Istuc
ingless. Others, however, translate it as, “let the thing be velegopossumrespondere,inquitAgrius;vendas,quot
destroyed”, “Out, bad spirit, out” (from the Hebrew assibuspossis,autsinequeas,relinquas.
words Abrai seda brai), or “Father, Holy Ghost, Word”
(from theHebrewwords Ab,Ruach,Dabar)[3,4]. Precautions must alsobetakenintheneighbourhood
of swamps,bothforthereasonsgiven, andbecause
MarcusTerentiusVarro there arebredcertain minutecreatureswhichcannot
The “bad air” or miasma theory of malaria aetiology be seenbytheeyes,whichfloat inthe airandenter
remainedanaccepted hypothesiswellintothe19thCen- thebodythroughthemouthandnose andtherecause
tury CE, when mosquitoes were found to be the trans- seriousdiseases.“WhatcanIdo”,askedFundanius,
mitting agent of the disease. However, the correlation “topreventdiseaseifIshouldinherit afarmofthat
betweendiseaseandinsectshasitsrootsinantiquity. kind?”“EvenIcananswerthat question”,replied
The avoidance of insects is certainly not a new Agrius;“sellitforthehighestcashprice;or if youcan't
phenomenon. In the 26th Century BCE, the Egyptians sellit,abandonit”[6].
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Over 1,500 years passed before the term “malaria” organism in blood in 1893, intensely disliked the name
came into use. The word malaria has its roots in the malaria. He considered the term unscientific and vulgar,
miasmatheory,asdescribedbyhistorianandchancellorof preferring the name “paludisme” (Latin: palus = swamp)
FlorenceLeonardo Bruni inhisHistoriaFlorentina,which which is still used in France today [10]. Currently, the
was the first major example of Renaissance historical use of the word malaria is restricted to the disease and
writing: itssymptoms(andnotitscausative agent).
Perhaps in part due to the name of the disease, the
ReceptoFlorentinicastello munitissimo praesidioque aetiological concept of bad air prevailed until the latter
imposito,quid iamagendum foretconsultabant.Erant part of the 19th Century. During his many travels, the
quibusoptimumvideretur exercitum reducere, journalist and African explorer Henry Morton Stanley
praesertimmorbis gravitateque coeli laborantem, (1857–1932) erected a glass screen on his boat, which
etlonga difficiliquemilitiaperaestatisautumnique he used for his trips on the Congo River, as protection
ferventissimos ardoresinsalubribuslocisconfectum, againstmiasma [11].
missioneetiammultorum aduce concessadiminutum:
nam postquamdiutius inhislociscommoratumest, JoannesMariaLancisius
multi,veltediocastrorumvelmetuvaletudinis Appointed as physician to three Popes (Innocent XI, In-
adversae,commeatumaduce postulaverant[7]. nocent XII and Clement XI), Joannes Lancisius was one
of the greatest physicians of his time. In his book De
AvutoiFiorentiniquestofortissimocastelloefornitolodi noxiis paludum effluviis, eorumque remediis (“On the
buoneguardie,consigliavanofraloromedesimifosseda noxious emanations of swamps, and their remedies”), he
fare.Eranoalcunia'qualiparevasommamenteutile describes the transfer of deadly diseases by animals, not-
enecessarioaridurreloesercito,emassimamente ing that “Venenata animalia non occidunt vulnere, sed
essendoaffaticatoperlainfermitàeperlamalaaria infuso per vulnus venetico liquido” (Venomous animals
eperlungoedifficilecampeggiareneltempo do not kill by injuries, but they inject a poisonous liquid
dell'autunno e in luoghi infermi, e vedendo ancora throughthewound)[12].
ch'egli era diminuito assai per la licenza conceduta a Lancisius strongly advocated the use of Cortex
molti pel capitano di potersi partire: perocchè, nel Peruvianus (Peruvian bark) for the treatment of periodic
tempo che eglino erano stati lungamente a quello fever.Extractsofthisbarkhadbeenusedtotreatmalarial
assedio, molti, o per disagio del campo o per paura feversincetheearly1600s.However,theuseoffinepow-
d'infermità, avevano domandato e ottenuto licenza der of Peruvian bark, mixed into French wine, was not
da lui[8]. withoutproblems,andmanyphysicianswerenotinfavour
oftheuseofthebark.In1707,AnthonyvanLeeuwenhoek
After theFlorentineshadconqueredthisstronghold, wrote toHeer van Wikhuysen,“Thismedicine is not tobe
afterputting goodguardians onittheywerediscussing usedbutwiththeutmostcaution,forthatotherwiseitmay
among themselveshowtoproceed. For someofthem it be so prejudicial to the body, that tho the fever should be
appearedmostusefulandnecessarytoreducethe removed,thesubsequentinconveniencesmaybeworsethan
army,more soasitwasextremely stressedbydisease thediseaseitself''[13].
and malaaria(bad air),and duetothelong-lasting Neither of the eminent Italian physicians Giovanni
and difficultcampsinunhealthyplacesduring the Lancisi nor Francesco Torti used the term malaria. It
autumn.They(theFlorentines)furtherconsidered that remainedatermusedexclusivelyinItalianfolkmedicine.
the armywasreducedinnumbersduetotheleave
permitsgrantedtomanysoldiersbytheofficers.Infact FrancescoTorti
during the siegemanysoldiershad asked and In1756,FrancescoTortidefinedanewstandardofcarefor
obtainedthepermittoleavedue tothecamp the use of Peruvian bark. Using a drawing of the Lignum
hardshipsand fearof illness.(Translationinto English Febrium tree, Torti used bark-covered branches to repre-
byPaoloArese,personalcommunication) sent conditions for which cinchona was effective. Barkless,
leafless branches were used to represent conditions for
The Italian term “mal'aria” (bad air) was introduced which cinchona was ineffective (Figure 2). His elegantly
into England 300 years later by Horace Walpole in a let- illustrated publication showed that only intermittent fevers
ter he wrote on 5 July, 1740: “There is a horrid thing wereresponsivetotreatmentwithcinchonabark[14].
called the malaria, that comes to Rome every summer,
and kills one.” [9]. John MacCulloch introduced the CarlLinnaeus
word into the English scientific literature in 1827 [9]. Malaria has long been distinguished from other fevers in
However, Charles Laveran, the first to see the malarial twoaspects.First,malariaisassociatedwithauniqueand
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Figure2TortiFevertreeintheshapeofastylizedcinchonaplant.(CourtesyTheJohnCarterBrownLibraryatBrownUniversity).
characteristic periodic fever, and second, only malaria is 38.α.ArgillainUplandia&quidemcircaStockholmiam
curablebyquinine. Upsaliamque,ut&incampisScaniæfrequentissimaest,
In 1735, Swedish botanist Carl Linnæus travelled to the ubietiamfebresintermitt.fræquentissimæ.(α.Clayis
University of Harderwijk in Holland where he earned his verycommoninUppland,aroundStockholmand
medicaldegree.Hisgraduatethesiswasentitled,“Inaugural UppsalaaswellasinthefieldsofSkåne,where
thesisinmedicine,inwhichanewhypothesisonthecause intermittentfeversaremostfrequent.)
of intermittent fevers is presented. By the favour of God, Furtherinhisthesis,he wrote:
threetimesthebestandthegreatest,submittedbyCarolus
LinnæusfromSmåland,Sweden,aWredianscholar”[15]. 77.α.Chinadequamediciomnesvidendi;Tinct.
In his 24-page, 84-chapter thesis, Linnæus compared Chinæfuit arcanummaximeexclamatum.γ.
differentregionsofSwedenandfoundclayandintermittent Artemisia,Centaurium &Gentiana,necnonNux
fevers to be geographically connected. He concluded that vomica,quatenus amara,agunt. (α.Quinineisknown
verysmallclayparticleswereresponsibleforthesymptoms toallphysicians.Tinct.Chinæisaveryimportantand
of the disease, and proposed that intermittent fevers origi- trustworthy remedy.γ.Artemisia,Centaurium&
natedin–andonlyin–placeswithclay-richsoil: Gentiana,butnot Strychnosnux vomica,because they
arebitter,areeffective.)
24.Frigusnonestcausavera,quia:Rarissima est
Febriumintermittentiuminfrigidissimisterrae. The drug quinine is extracted from the bark of a tree
(Coldisnot thetrue cause, sinceintermittent feveris now known as the Cinchona tree [16]. In 1742, Linnæus
very rareinthe coldest partsofthe country.) named the genus of this tree in his seminal textbook
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Figure3Linnæus’listingoftheCinchonagenus.(CourtesyBayerischeStaatsbibliothek,München).
Genera Plantarum [17]. In the second revised and en- vegetable matter necessary for the generation of mi-
largededition,1,021plantgenerawerelisted,including,as asma. In addition, he noted that no chemical analysis
the last entry, the newly described Cinchona genus or microscopic investigation had ever been able to
(Figure3). identify miasma, and that air composition was always
found to be 78 parts nitrogen, 21 parts oxygen, and
AlbertFreemanAfricanusKing one part carbonic acid [18].
In 1851, in his address to the Medical Society of North By 1883, the American physician, Albert Freeman
Carolina, Charles E Johnson refuted the doctrine of the Africanus King, had assembled 19 facts in support ofthe
miasmatic origin of malaria. As evidence, he pointed mosquito astheorigin ofmalarial disease[19]:
to the “sickly” constitution of the residents of
Gibraltar, a town built on a bed of dry red sand with 1 Malariaismostcommoninareas(swamps,fens,
no ponds or marshes to furnish the decomposing jungles,marshes,etc.)wheremosquitoesareendemic;
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2 Malariaismost common attemperaturesconducive 13Thedangerofacquiringmalariaisgreater after
tomosquitogrowth; sleeping inthenightair;
3 Malariadoesnotoccuratcoldtemperatures; 14Fireprotectsagainstmalaria;
4 Malariaismost common inequatorialandcoastal 15Cityairhasaprotectiveeffectagainstmalaria;
regions; 16Malariaismost prevalentinlatersummerand fall;
5 Malariaoccursfrequently inareasofdensefoliage; 17Malariaisarrestedbycanvascurtains,gauze veils,
6 Forestsmay obstructmalariatransmission; and mosquito nets;
7 Malariamay spreadto areasthat aremiles away; 18Malariaaffectsinfantsmuchlessfrequentlythan
8 Malariamay spreadto previouslyunaffectedplaces adults;and
whensoilisexcavated; 19Ofallhuman races thewhiteis most susceptibleto
9 Alargebodyofwater may prevent thespreadof marsh-fevers,theblack least so;
malaria;
10Previously malarialcountries,whenclearedup,may JohannHeinrichMeckel
becomefreeofdisease; Few families have had such an impact on medicine as
11Thethreatofmalariaisgreatestnearthe surfaceof the Meckel family, which for four generations contrib-
theearth; uted greatly to anatomy, pathology and the biological
12Malariatransmissionis greatest duringthenight; sciences. The last member of the Meckel lineage, Johann
Figure4Frerichs’drawingsofthedepositionofpigmentininternalorgansofintermittenspatients.(CourtesyStaatsbibliothekzu
Berlin–PreussischerKulturbesitz).
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Heinrich Meckel (1821–1856), took the instructor’s pos- Heinrich Meckel conducted her autopsy. He found her
ition in pathologic anatomy at the University of Berlin brain to be dark brown, with all capillaries filled with
that his great-grandfather had held at the Charité. After brownish particles which were without Brownian motion.
his untimely death from pulmonary disease, Meckel’s The spleen was enlarged and likewise dark brown, with
position wasfilledbyRudolfVirchow[20]. similarlyfilledcapillaries.Meckelconcludedthatthebrown
In the 1800s, malaria was endemic in all of Central pigment was a blood product (“aus dem Blutroth entsteht
Europe, except Lichtenstein. It was well known that pa- einschwarzesPigment”)[21].
tients who died of malaria had black deposits in their or- Meckel did not associate the pigment with malaria.
gans. AccordingtoHippocrates, theseblack depositswere But only a few years later the causal relationship of this
characteristicofmalaria,andwereattributabletobile.This brown pigment to malaria was established by Virchow
viewprevaileduntilJohannMeckelprovedotherwise. and Frerichs, and malaria was recognized to be a disease
In 1846, a patient named Adelheid B died at the age of of the blood (Figure 4) [22,23]. Meckel had erroneously
43 after 24 years in various hospitals for mentally ill pa- assumedthepigmentwaschemicallyidenticaltomelanin,
tients. Malariahadnotbeendiagnosedpriortoherdeath. but Virchow correctly associated the pigment with
Figure5Laveran’sdrawingofmalariaparasites.
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haematin crystals (“aus Hämatin condensiert sich allmählich Some years passed before Malachowski developed a stain
körnigesoderkrystallinischesPigment”). which allowed for differential identification of blood para-
It is now known that this brown pigment is formed sites[25].
during the digestion of haemoglobin and produced by Laveran agreed with Meckel with regard to the brown
the malaria parasite through biocrystallization [24]. The pigment, maintaining that the pigment was chemically re-
presenceof brownpigment(alsocalledhaemozoin)inor- latedtomelanin:“Melanæmiaisspeciallyverypronounced
gansatautopsyisastrongindicatorofmalarialinfection. in individuals who died from acute paludisme (pernicious
attacks);thecolourwhichitgivestocertainorgans,particu-
CharlesLouisAlphonseLaveran larly to the spleen, the liver, and the grey substance of the
Intheearlyyearsofmicroscopy,stainingtechnologywasin brain, is almost always sufficient to show from microscopic
its infancy. The French army doctor, Laveran, had to use examinationifdeathistheresultofpaludisme”[26].
unfixedandunstainedbloodforhisexperiments,andcould More convincing was his observation of male gameto-
see in the blood of his patients a dark pigment that was, cytes undergoing exflagellation (Figure 5). In 1880 at the
according to Virchow, the result of infection with malaria. Military Hospital at Constantine in Algeria he discovered,
Figure6Ross’DiaryandNotesofResearchesonMalaria,BookI,page107.(CourtesyArchivesService,LondonSchoolofHygiene&
TropicalMedicine).
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ontheedgesofpigmentedsphericalbodiesinthebloodof RonaldRoss
a patient suffering from malaria, filiform elements resem- The first person to provide definitive proof that mosqui-
bling flagella which were moving very rapidly: “I was still toes carried malaria was British army surgeon, Ronald
hesitating whether these elements were parasites, when on Ross. Working in Secunderabad, India, under the tutelage
November6th,1880,onexaminingthepigmentedspherical of his mentor, Patrick Manson, Ross undertook a meticu-
bodies mentioned above, I observed, on the edge of several lous,two-yearsearch,microscopicallyexaminingthousands
oftheseelements,moveablefilamentsorflagella,whoseex- of brindled grey and white mosquitoes fed with malarial
tremely rapid and varied movements left no doubt as to blood,lookingforapathogeninsidethemosquito.In1897,
theirnature”[26]. he obtained a few mosquitoes which belonged to a species
Figure7LetterfromRKochtoGNuttall.