Mathematical models of the interaction of P. malariae and P. falciparum in the human bloodstream suggest that P. malariae struggles to establish itself if P. falciparum is already present in an individual.
This explains the situation in tropical countries today. P. malariae has often been judged to be quite rare in environments where P.
falciparum is active all the year round, using the traditional diagnostic technique of microscopic examination of blood smears on slides (although the modern techniques of molecular biology now suggest that it is in fact commoner even in tropical environments than used to be thought). However, the same mathematical models also yield the very important result that if a P. malariae infection occurs before an infection with P. falciparum, then P. malariae can establish itself, very significantly reduce the severity of a subsequent infection with P. falciparum because of cross-species immunological reactions, and outlast P. falciparum.³⁶ The interaction of the two diseases is very significant. Livy tells us that many of the survivors of an epidemic (doubtless involving other diseases as well as malaria) in 174
ended up with quartan fever.³⁷ This constitutes evidence for the presence of endemic quartan fever in Latium by then. It is likely that frequent infections with P. malariae earlier in that particular year reduced the severity of a major epidemic of falciparum and vivax malaria in the late summer and autumn of that year. The survivorship rate might have actually increased in the short term, contrary to what would have been expected if P. malariae had not been present at all. However, it must be remembered that malarial infections as a whole did substantially reduce life expectancy in European historical populations in the long run (see Ch. 5. 4
above). Galen observed that quartan fever generally followed other ³⁶ Mason et al. (1999) wrote a very interesting article on the epidemiology of P. malariae and its interaction with P. falciparum.
³⁷ Livy 41.21.5: qui superaverant, longinquo, maxime quartanae, implicabantur morbo (the survivors were ill for a long time, particularly with quartan fever).
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fevers instead of occurring on its own. This statement can only mean that multiple infections were normal.³⁸
for the most part quartan fever does not appear immediately at the beginning of the illness, but occurs after other fevers have manifested themselves³⁹
Cicero gives a specific example of this phenomenon, namely the case of Tiro:
since the essence of the disease has changed into a quartan fever (for so writes Curius), I hope that you [Tiro], with due diligence, will be even stronger⁴⁰
This letter is dated 12 January 49 , precisely the right time of year for that development. Scepticism is always possible with regard to the value of the evidence provided by an author like Juvenal, although in this particular case his words make perfectly good sense in the light of modern medical knowledge. Recent research in tropical countries employing the techniques of molecular biology to detect very low population densities of malaria parasites has shown that mixed infections (as well as subclinical chronic infections) are more frequent than was often thought previously when examination of blood smears under a microscope was the only means of detecting parasites. The ancient medical writers provide very important evidence confirming that P. falciparum malaria was indeed common among the population of the city of Rome from the second century to the second century . Caelius Aurelianus quoted Asclepiades of Bithynia, a Greek doctor who enjoyed great success at Rome (in spite of Cato’s condemnation of Greek medicine) in the late second century , according to ³⁸ Other ancient texts which mention this phenomenon include: Hippocrates, Airs, Waters, Places 10: to»ß te perigenomvnouß ƒß tetarta≤ouß åpoteleut$n (the survivors ended up with quartan fevers); [Aristotle,] Problems 1.19.861b tetarta∏oi g≤nontai to∏ß swzomvnoiß (those who were saved had quartan fevers); Galen 11.114K: πsti d’ oÍsin oÛk øl≤goisin ƒx £llwn puret0n ka≥ noshm3twn åpost3sieß ƒß tetarta≤ouß ƒg≤nonto (in many cases there was a transition from other fevers and diseases to quartan fevers). Galen is quoting Hippocrates Epidemics, 1.6. Mixed infections were the norm in the town of Sermoneta in the Pontine region in the early twentieth century, according to Hackett (1937: 243). Similarly mixed infections were common in Greece (Balfour (1935: 312) ). Galen recognized mixed infections and wrote about them e.g. 7.464–5K and 9.646K.
³⁹ Galen 11.18K: mhd’ eÛqŸß åp’ årc[ß t¤ poll¤ tÏn puretÏn toıton [sc. tetarta∏on]
ejsb3llein, åll’ ‰tvrwn proshghsamvnwn sump≤ptein.
⁴⁰ Cicero, Epist. ad familiares 16.11.1: cum in quartanam conversa vis est morbi (sic enim scribit Curius), spero te, diligentia adhibita, etiam firmiorem fore.
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Rawson’s redating of his floruit. Asclepiades may have invented the idea of seeds of disease that was employed by Lucretius.⁴¹
Asclepiades states that a persistent quotidian fever is not without danger . . . at Rome, he says, we notice that these fevers with a violent seizure of the body and mind, resembling lethargy, are frequent . . . he writes similar comments about these fevers, not once but frequently, saying that for a certain reason this seizing of the mind occurs in attacks of intermittent fevers, and that this is common at Rome.⁴²
Asclepiades states that quotidian fevers, the most dangerous manifestation of P. falciparum malaria, were common in Rome, frequently exhibited the symptoms of cerebral involvement called catalepsy or lethargy by ancient medical writers, and could be fatal.
He made these remarks repeatedly, emphasizing the importance of the phenomena under discussion. Similarly, Marchiafava and Bignami noted that ‘lethargic and comatose “complicated” fevers’
with cerebral symptoms were the forms of P. falciparum malaria most frequently encountered by doctors in hospitals in Rome in the nineteenth century. Baccelli also noted that lethargy was a dangerous condition in some forms of the disease.⁴³ Francesco Torti, the author of an important treatise on (the use of quinine in) cinchona bark, described lethargy as one of the seven symptoms of pernicious periodic fevers that were particularly liable to lead to death, and noted that it did not occur in tertian fever (caused by P. vivax).
Finally the seventh lethal symptom of any intermittent pernicious fever, not characteristic of a simple tertian fever, is an extremely sleepy state of mind, or deep lethargy, which very frequently tends to accompany the febrile paroxysms . . . if it is neglected, and its progress is not inhibited, I would almost say that lethargy, if not conquered by any medical art, will be fatal, like a major stroke, during one or other of the periodic episodes of fever. When this state of mind commences, the patient first falls into a deep sleep. If he is awoken, he immediately goes back to sleep. Shortly afterwards he cannot remember what had happened immediately before.
Consequently he frequently asks for a pot, then forgets to pass urine, and ⁴¹ Rawson (1982) and the speculative arguments of Polito (1999); Nutton (1983: 10–11).
⁴² Caelius Aurelianus, On acute diseases 2.63–4, ed. Drabkin (1950): Item Asclepiades ait cotidianum perseverantem non sine periculo esse . . . apud Romam vero, inquit, frequentare advertimus has febres cum corporis atque mentis oppressione in similitudine lethargiae . . . item similia de his scribit, et non semel sed frequenter, dicens certa ratione mentis apprehensionem typorum in accessionibus fieri, atque hoc apud Romam frequentare.
⁴³ Marchiafava and Bignami (1894: 93, 123–6, 150–1); Baccelli (1881: 180). Caelius Aurelianus II.65–6 described catalepsy as a condition predominantly occurring in the autumn.
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is drowsy in the meantime. Sometimes he answers a question, but is unable to express himself coherently. It may be the case that he understands his own error, but nevertheless cannot correct himself, or continue, but babbling instead, he either cuts short his words, or uses the wrong word, just as if he were affected by a slight stroke causing paralysis
of the tongue. Eventually, as his drowsiness intensifies, he is completely immobile, and snores through his nostrils. He cannot be awakened by any sound, physical force or contact, ligatures or tourniquets, affixing of cupping-glasses or of vesicants, or even fire at any time whatsoever, and if he does become conscious for a time, he immediately relapses into the same sleep, or falls into an even deeper coma, and does not begin to awaken until the periodic attack of fever is coming to an end. Even if he begins to awaken after the first or second period of fever, it is always with a little more difficulty, and if spasmodic gasping is added to the lethargy, he succumbs to his inevitable fate during the third or fourth periodic attack of fever at the latest.⁴⁴
The fact that lethargy was frequently a term applied in antiquity to cerebral malaria caused by P. falciparum is demonstrated by a text of Aetios of Amida, quoting Archigenes and Poseidonius.⁴⁵ Aetios states that lethargy could arise in various ways, but goes on to say that it was a common effect of quotidian and semitertian fevers. It was also possible in quartan fevers, according to Aetios. However, it is significant that he does not mention tertian fever (caused by P. vivax) here. P. vivax does not cause cerebral malaria because it does not (unlike P. falciparum) induce cytoadherence of parasitized erythrocytes to the endothelium of capillaries in the brain.⁴⁶
⁴⁴ Torti (1755: 195–6): Septimum denique lethale symptoma Perniciosae cuilibet Intermittenti, non uni Tertianae familiare, est gravis affectus soporosius, seu profundus Lethargus, qui paroxysmos febriles saepe-saepius comitari consuevit . . . si negligatur, nec inhibeatur progressus, Lethargum una, vel altera accessione mortiferum, ac omni arte invincibilem, fortis Apoplexiae instar, fere dixerim certo portendit. Cum huiusmodi affectus incipit, aeger primo est in soporem pronus, a quo excitatus, statim in sommum relabitur; paulo post fit immemor rerum immediate ante gestarum, unde non raro matulam poscit, deinde mingere obliviscitur, atque interim dormitat; nonnumquam obloquitur, nec suos conceptus valet exprimere; & licet sui erroris sit compos, se tamen nequit corrigere, aut continere: immo quandoque balbutiens, vel verba mutilat, vel unum pro alio pro-fert, non secus ac si levi Apoplexia in linguae paralysim degenerante foret detentus. Ingravescente tandem sopore omnino iacet, ac stertit naribus, neque ulla voce, ulla vi, frictione, ligatura, cucurbitularum, aut vesicantium appositione, immo nec igne quandoque actuali valet excuti; & siquidem excutiatur aliquantisper, statim in eumdem soporem, immo in profundiorem recidit, nec nisi declinante accessione incipit expergisci. Quod si una, vel altera vice resipiscat quidem, sed semper paulo difficilius, aut si soporosae affectioni adjungatur singultus, tertia ad summum, vel quarta accessione, inevitabili fato succumbit. Marchiafava and Bignami (1894: 13–18, 96 n.1) discussed Torti’s classification of intermittent fevers.
⁴⁵ Aetios of Amida 6.3: [Ø l&qargoß] ƒn≤ote d† ka≥ ƒp≥ t0n cron≤wn puret0n sumba≤nei kat¤ per≤odon bapt≤zesqai aÛtoŸß t‘ pn8, oÍon poll3kiß g≤netai ƒp≥ åmfhmerin0n puret0n ka≥ Ómitrita≤wn, πsti d’ Òte ka≥ ƒp≥ tetarta≤wn.
⁴⁶ This is the conventional explanation of the pathology of severe P. falciparum malaria. An 222
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The situation described by Asclepiades lasted throughout the Principate (and most probably throughout late antiquity as well), since Galen made very similar comments in the second century .
Galen wrote pages and pages on forms of ‘fever’ (puretÎß) that can now be identified as malarial fevers. Since it would take a very long time to scrutinize all his writings on the subject in detail, it is only possible to mention a few of the most important points here.
Galen described semitertian fevers as very common in Rome, more familiar to men in the capital of the Roman Empire than anywhere else.⁴⁷ This passage also shows clearly that Galen recognized that different places had different pathocoenoses, and this implies a diversity of mortality patterns in different parts of the Roman Empire.
That there is such a fever, as I have stated, does not require the evidence of Hippocrates or anyone else as a witness, since we observe it every day, especially at Rome. For just as other diseases are common in other places, so this evil is frequent in this city.⁴⁸
The fever arising from yellow bile on its own is called tertian, but the fever which requires an equally strong share of the raw humour is strictly called semitertian. It is most frequent at Rome, being very familiar to men in the city.⁴⁹
He explicitly states that semitertian fevers were extremely dangerous, much more dangerous than tertian fevers: ‘this type of fever [semitertian] is malignant and extremely dangerous’;⁵⁰ ‘Semitertian fever . . . is . . . much worse than tertian fever.’⁵¹ Galen also discussed mixed infections, which are only to be expected where malaria is endemic, as noted above. His comments on the various alternative view, expounded most recently by Clark and Schofield (2000), is that the severe pathological effects are the result of an inflammatory state caused by a toxin released by the malaria parasite.
⁴⁷ Martial 2.40 and 4.80 also mentioned semitertian fevers, cf. 2.16 and possibly 3.93 for less specific references to fevers. Rodrígues (1985/6) and Wittern (1989) discussed Galen on fevers.
⁴⁸ Galen 7.435K: Òti g¤r ka≥ toioutÎß tiß g≤netai puretÏß, Øpo∏on e”pon, oÛkvt’ ƒn t‘de m3rturoß oÇq’
⁴⁹ Galen 17A.121–2K: Ø m†n oˆn ƒp≥ mÎn7 t∫ toia»t7 [sc. xanq∫ col∫] sunist3menoß ønom3zetai trita∏oß, Ø d† ka≥ tÏn ∑mÏn cumÏn jsosqen[ proslab*n, åkrib¶ß Ómitrita∏oß g≤netai, ple∏ston ƒn
⁵⁰ Galen 7.467–8K: [Ø Ómitrita∏oß] . . . £griÎß tv ƒsti ka≥ kindunodvstatoß o˜toß Ø t»poß.
⁵¹ Galen 17A.235K: Ø d’ Ómitrita∏oß . . . πstin . . . polŸ ce≤rwn toı trita≤ou.
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age-groups, which were characteristically targeted by different types of malarial fevers, are of great significance for establishing the epidemiology of malaria in the second century . Galen says that semitertian fevers struck men in the prime of life in autumn, when it was very dangerous, while tertian fevers attacked young men, and quotidian fevers, the most dangerous of all, attacked young children in particular.⁵²
Tertian fever, caused by P. vivax, becomes a disease of childhood when P. vivax is hyperendemic, as it was on Sardinia, for example, in the nineteenth century. However, to interpret all these texts it is necessary to remember that ancient Rome (like early modern Rome) was constantly receiving large numbers of adult immigrants who would have been vulnerable (see Ch. 11 below). All the literature on malaria in early modern Rome states that adult immigrants or visitors were more vulnerable than people who had been born and had lived all their lives in Rome.⁵³ This was because the indigenous inhabitants knew what had to be done in the way of avoidance behaviour, as will be seen later (Ch. 11 below). They might also have had acquired immunity following childhood infection, or even inherited innate immunity. Galen’s observation on the epidemiology of quotidian fevers is extremely important because it shows that primary attacks of P. falciparum malaria frequently occurred in infancy or early childhood in the second century .⁵⁴
⁵² Galen 7.468K: [Ø Ómitrita∏oß] . . . pleon3zei d† ƒp≥ m†n t[ß f»sewß t[ß kat¤ toŸß £ndraß, Ólik≤aß d† t[ß kat¤ toŸß åkm3zontaß, ¿raß d† m$llon t[ß fqinopwrin[ß, Òte ka≥
l≤an kindun*dhß tugc3nei ([semitertian fever] . . . is common in men, particularly those in the prime of life, most frequently in autumn, when it is exceedingly dangerous); 17B.642
[trita≤oi] . . . o˜toi g¤r colwdvstato≤ te puret0n Åp3ntwn ejs≥ ka≥ ple∏stoi to∏ß nean≤skoiß g≤nontai . . . oÈ presbıtai t0n nvwn t¤ m†n ple∏sta nosvousin �
�tton ([tertian fevers] . . . are the most bilious of all fevers and most frequently occur in young men . . . in most cases old men are less affected than young men); 11.23K: pa∏deß d† ka≥ m3lista oÈ mikrÎteroi ka≥ Òsoi t0n tele≤wn flegmatik*tero≤ tv ejsi ka≥ t¶n 1xin toı s*matoß pace∏ß ka≥ årgÏn tÏn b≤on πconteß ƒn plhsmona∏ß ka≥ mvqaiß ka≥ loutro∏ß sunecvsi ka≥ m3lista to∏ß ƒp≥ trof∫
åmfhmerino∏ß eÛ3lwtoi (children, especially younger children, and adults who have more phlegm and are fat and lead an idle lifestyle with excessive eating and drinking and continuous bathing, and most of all those who are being cared for by a nurse, are easily affected by quotidian fevers).
⁵³ e.g. Aitken (1873); Baccelli (1881); Rey and Sormani (1881); North (1896); Bercé (1989).
Similarly Dobson (1994: 47) and (1997: 318) ) noted that P. vivax malaria was more dangerous to immigrants than to the indigenous inhabitants of the English marshlands.
⁵⁴ M. Greenwood (1921) considered Galen as an epidemiologist. In many other instances, for example in relation to the Antonine plague, Galen’s epidemiology turns out to be very disappointing. Grmek (1994: 4) accepted Galen’s epidemiological evidence, speaking of une expansion hyperendémique aux temps de Galien. However, the idea of an expansion in Galen’s time does not take account of the earlier evidence of Asclepiades.
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The inference is that the transmission rate of P. falciparum malaria was very high; high enough to create a situation in which acute clinical illness and direct mortality as a result of malaria was concentrated among children. In relation to the fact that the Romans continued to use the Greek word semitertian and had not coined a specific Latin word for the disease, Quintus Serenus stated that mothers did not want to use a specific word for it for fear that by speaking of it it would be attracted to their own children. This fascinating observation confirms that P. falciparum malaria was regarded as typically a disease of childhood during the time of the Roman Empire. It also illustrates the importance of sympathetic magic in Roman popular thought:
Malaria and Rome: A History of Malaria in Ancient Italy Page 31