Despite its similarity to typhoid fever, Baccelli stated that it revealed the true intermittent periodicity of malaria upon careful observation. Moreover it responded to treatment with quinine.
These two features prove that the ‘subcontinuous typhoid’ fevers of Rome were P. falciparum malaria. Besides its frequent similarity to typhoid fever, P. falciparum malaria occasionally presents itself with gastro-intestinal symptoms similar to those of cholera or dysentery, as was observed in cases at Grosseto and elsewhere. In such cases at autopsy a mass of malarial parasites was observed in the blood vessels of the mucous membranes of the stomach and the small intestine, with relatively few parasites in the rest of the body.⁴⁰ Presumably this was caused by a clone targeting a chemical receptor ³⁸ Smith (1982) on the history of the idea of typhomalarial fever among doctors in the USA; Baccelli (1881: 159–60); Hirsch (1883: 235–6); North (1896: 384–5); Sambon (1901 b: 316); Marchiafava (1931: 21–2, 41).
³⁹ Baccelli (1881: 175) employed the definition of a subcontinuous fever given by Francesco Torti. Torti (1755: 190), in his famous book on the use of cinchona bark to treat malaria, defined pernicious periodic fevers (caused by P. falciparum) as follows: Porro generaliter Febris haec Periodica Pernicialis vel talis est, ut perseveranter intermittat, efferamque naturam suam tantum prodat immani quopiam, & peculiari symptomate febrilem Paroxysmum comitante, cuius ferociam exitialem minime tollit intermedia quies, quae caeteroqui securitatem ex Hippocrate pollicetur: vel talis est, ut, intermis-sione paulatim deperdita, ad Continuam, & Acutam saepius quidem lente, nonnumquam & festinanter ten-dat, cum extensione gravium quorumdam, variorumque symptomatum ad tempus ipsum turbulentae quietis.
(Furthermore this periodic pernicious fever generally takes one of two forms: 1. there are persistent intermissions, and it prodigiously displays its own savage nature, and is accompanied by the characteristic symptom of a febrile paroxysm, and the rest periods of intermission, which would in other circumstances offer safety according to Hippocrates, have hardly any effect on its destructive nature; 2. the period of intermission gradually disappears, it develops into a continuous fever, frequently becoming acute slowly, but sometimes rapidly, with the extension of a variety of serious symptoms into the turbulent intermission periods.) ⁴⁰ Marchiafava and Bignami (1894: 111–12, 151–2); Marchiafava (1931: 31); T. Harinasuta and D. Bunnag in Wernsdorfer and McGregor (1988: i. 726).
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found abundantly in the intestinal organs (cf. the explanation of placental malaria given above). In fact, the view has been expressed that a degree of gastro-enteritis occurs in all cases of malaria.⁴¹
The upshot of the discussion so far is that P. falciparum malaria and gastro-intestinal diseases are not alternatives, as Shaw reckoned, but in fact went hand in hand in bringing about high infant mortality.⁴² In the city of Rome in antiquity, gastro-intestinal diseases were undoubtedly very common as a result of grossly inadequate hygiene, for example the fact that most habitations used cesspits (in order to recover faeces for use as agricultural fertilizer) for waste disposal and were not actually connected to the city’s network of sewers. This has been shown beyond reasonable doubt by Scobie’s remarkably detailed account.⁴³ Nevertheless it remains the case that in historical European populations gastro-intestinal diseases alone had less impact on the mortality regimes of human populations than malaria, where it was endemic. The combination of the two in Rome in antiquity should have generated a very high level of infant mortality.
Two major clinical syndromes, namely severe anaemia and cerebral malaria, have long been generally recognized and accepted as major manifestations of P. falciparum malaria when it attacks children. Both can be aggravated by concomitant bacterial infections, as indicated by indirect methods such as increased levels of leucocytes (white blood cells). Evidence is now emerging from research in Kenya in favour of the recognition of a third major syndrome of childhood malaria, namely respiratory distress. The suggestion is now being made that nearly 50% of all children who are diagnosed in hospital as suffering from acute respiratory diseases in that area, the heartland of the evolution of P. falciparum, may actually have malaria instead and should be treated with antimalarial drugs.
This suggests that the effects in terms of morbidity of P. falciparum malaria where it is endemic are even greater than was generally thought until recently.⁴⁴
⁴¹ De Korte (1899), cf. Murty et al. (2000) for a modern case study. The sort of account given by Wilson (1898) is still highly suggestive, even if Widal’s test is no longer believed to be absolutely diagnostic for typhoid fever.
⁴² Writing about Sardinia, Tognotti (1996: 102) described: la vera e propria strage degli inno-centi che la malaria e le malattie gastro-enteriche provocano nell’isola tra i bambini appena svezzati.
⁴³ Amulree (1973: esp. 248–9 on malaria) was much less perceptive than Scobie (1986).
⁴⁴ Modiano et al. (2001) on leucocytosis; research at the Wellcome Trust Tropical Over-seas Unit at Kilifi in Kenya, directed by K. Marsh, and reported in the Wellcome Trust Newsletter Q3 (1997: 12–14). James (1920: 158) described cases of P. falciparum malaria with 130
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P. falciparum malaria can also directly kill non-immune young adults, such as immigrants to ancient Rome from regions where malaria was not endemic. Those were the cases which were most likely to be noticed by ancient doctors, who on the whole showed relatively little interest in the diseases of infants, judging by extant ancient medical literature.⁴⁵ On top of that, P. falciparum malaria can attack elderly people, whose immune systems may be weakening. In such cases it is possible to have severe infections marked by a high parasite count in the blood without any obvious fever, which is often suppressed in the elderly. Marchiafava and Bignami made these observations on cases in Rome in the nineteenth century and described in detail as an example the case of a seventy-year-old man, a watchman on the Rome–Tivoli railway line. Alexander of Tralles described a case of tertian fever in an old man in the sixth century , while a couple of centuries later Alcuin suffered from P. vivax malaria after the age of sixty. W. D. Hamilton, a prominent scientist in the field of evolutionary biology from Oxford, died recently at the age of sixty-three from malaria contracted on a visit to Africa.⁴⁶ Besides its own direct effects on elderly people, P. falciparum malaria can also strongly exacerbate both the heart diseases and the respiratory diseases whose main effects in terms of mortality are often felt most frequently by elderly age-groups.
Marchiafava and Bignami noted several fatal malaria cases in which autopsy revealed not only malaria parasites but also extensive arteriosclerotic changes in the heart. Since they noted that acute dilatations of the heart occur during severe malarial fevers, pre-existing heart disease probably played a synergistic role in the death of these patients.⁴⁷ Malaria also had every chance to interact with the respiratory diseases of winter in central Italy in antiquity, since malarial infections often occurred as late as October or even November, as has been seen, after which the disease could take several months to run its course.
symptoms predominantly in the respiratory system. Chalandon and Kocher (2000) described a case of an adult with acute respiratory distress.
⁴⁵ Bertier (1990).
⁴⁶ Marchiafava and Bignami (1894: 93, 129–31); Marchiafava (1931: 36); Alexander of Tralles 1.5, per≥ trita≤ou, i. 379, ed. Puschmann (1963): ƒndvcetai d’ e”nai ka≥ gvronta nose∏n trita∏on: ƒg° goın aÛtÎpthß ƒgenÎmhn to»twn ƒp≤ tinoß gvrontoß (It is accepted that an old man can become sick with tertian fever; indeed I myself witnessed a case of tertian fever in an old man.); obituary of W. D. Hamilton in The Times, 9 March 2000.
⁴⁷ Marchiafava and Bignami (1894: 107).
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This is clearly illustrated by the chronology of the most detailed malaria cases available from antiquity, namely the cases of Cicero’s
friend Atticus and his wife Pilia. Cicero’s letters suggest that Atticus had contracted quartan fever ( P. malariae) by 19 September 50 , by which time he had an unspecified fever. Although quartan fevers have a longer average duration than other types of malarial fevers, the Horton Hospital experiments showed that P. malariae does not manifest the latency and prolonged incubation periods of up to about nine months displayed by some strains of P. vivax.
Consequently it can be inferred that Atticus was actually infected in August 50 . By 25 November it had become clear that Atticus had had a double quartan fever, although one of the two fevers had ceased, and the second fever was reported to Cicero to have become milder by then. Yet the troubles continued. Another letter, dating to the middle of December, shows that Atticus still had the fever, while his wife Pilia had contracted it as well. Eventually Cicero worked out for himself from Atticus’ letters the periodicity of his quartan fever and knew on which days Atticus would be suffering. A letter of February 49 reports that Atticus’ quartan fever had left him. Nevertheless a recrudescence of the illness must have occurred (more likely than a fresh infection at that time of the year), since letters dating to early March 49 show that Atticus was suffering again. A letter dating to 17 March 49 suggests that the fever was easing again. Another letter dating to 10 May 49 states that both Atticus and Pilia had lost their quartan fevers for good by then, although it is quite possible that some parasites persisted for the rest of their lives without causing any subsequent acute clinical symptoms. The case of Atticus, which ran from September 50
right through the winter to April 49 , demonstrates how easy it was for malarial infections to be running their course at the same time of the year as the respiratory diseases of winter.⁴⁸ Atticus’ case ⁴⁸ Cicero, Letters to Atticus, ed. Shackleton-Bailey (1965–70), nos. 123.1 (Atticus had a fever when he arrived in Rome on 19 September 50 ), 124.1 (by 16 October 50 Acastus had reported that Atticus had recovered), 125.2 (by 25 November 50 Atticus had lost one of his two quartan fevers, while the second was milder, while a second report claimed that the second fever had gone as well), 128.1 (Pilia had contracted quartan fever by mid-December 50), 128.3 (Cicero intended to visit a location in the Pontine Marshes at the end of December), 128.5 (Cicero begs Atticus to shake off his quartan fever), 130.3 (on 19 December 50 Cicero wrote that he did not know on which day Atticus’ fever was due), 131.2 (by 25–6 December 50 Cicero had found out exactly when Atticus’ fever was due), 154.4 (by 20 February 49
Cicero had heard that Atticus had lost his quartan fever, but Pilia still had hers), 168 (on 7
March 49 Cicero mentions Atticus’ bad day, indicating that he still had the fever after all), 132
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history is an absolutely typical example of the chronology of cases of quartan fever in central Italy in the past. In the early eighteenth century Lancisi described as follows the quartan fevers to which those who lived near wetlands were subject:
The inhabitants of marshes . . . suffer from very prolonged illnesses, especially quartan fevers, which generally persist throughout the winter, and the following spring.⁴⁹
Pliny the Elder made a few comments on the epidemiology of quartan fever:
For nature has imposed some laws even on diseases: quartan fever never commences at midwinter or in the winter months. It does not occur in some people after the age of sixty, others, especially women, lose it at puberty.⁵⁰
The case of Atticus shows that a quartan fever contracted earlier could run right through the winter, even if a new infection could not be contracted in the middle of winter. This is confirmed by modern research. In considering Pliny’s other comments, it is necessary to remember that the periodicity of quartan fever can be concealed by the more powerful rhythms of other species of human malaria, and that once a person has been infected, parasites may survive virtually throughout that person’s entire lifetime (Ch. 2
above). Quartan fever is mentioned in historical literature surprisingly often in view of its relative insignificance as an agent of mortality. One reason for this prominence is that it flourished in highly seasonal Mediterranean-climate regions in the past, to which it was highly adapted, more than it does in tropical countries today.
Another reason for its visibility in historical literature is that the quartan periodicity is more regular than the periodicities of P. vivax or of P. falciparum. Celsus noted that quartan fevers were simpler 171.1 (again mentions Atticus’ bad day, on 10 March 49), 173.3 and 175.2 (Atticus’ bad day is mentioned in both these letters of 12 March and 14 March 49), 200.3 (by 3 May 49 Cicero has learnt that Atticus’ fever is easier), 207 (by 10 May 49 both Atticus and Pilia have lost their quartan fevers), 208 (on 14 May 49 Cicero again states that Atticus is free of his fever, and a cold as well). Galen 9.561K described quartan fevers contracted in autumn as very long lasting. Atticus was a good example of this dictum.
⁴⁹ Lancisi (1717: 46): paludum habitatores . . . longissimis morbis implicari, maximeque quartanis, quae per universam hyemem, et proximum ver aegros solent exercere.
⁵⁰ Pliny, NH 7.50.170: morbis quoque enim quasdam leges natura inposuit: quadrini circuitus febrem numquam bruma, numquam hibernis mensibus incipere, quosdam post sexagensimum vitae spatium non accedere, aliis pubertate deponi, feminis praecipue.
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than other fevers.⁵¹ Consequently quartan fevers were more easily diagnosed than fevers caused by P. vivax or P. falciparum, which frequently took a quotidian form that was liable to be confused with typhoid fever, typhus, influenza, hepatitis, and other diseases.
Dante mentioned quartan fever in the Divine Comedy: Like someone so close to the next bout of quartan fever that he already has blue nails, and trembles all over at the mere sight of cool shade, so I became at his words.⁵²
The Jewish king Alexander Jannaeus was one individual whose death in 76 was associated with an infection of quartan fever lasting for three years, but also with excessive drinking and with severe exertions on military campaigns.⁵³ Although quartan fevers were generally not regarded as fatal (at least in comparison to other types of malaria), nevertheless there was a persistent view in the past that they were particularly dangerous for the elderly. Sydenham expressed this opinion in the seventeenth century, while a traditional Sicilian saying ran as follows: ‘Quartan fever kills the elderly and heals the young’.⁵⁴
Quintus Serenus expressed the opinion that quartan fevers could lead to death and should not be underestimated.⁵⁵ Nevertheless quartan fevers were often regarded in antiquity as ‘weaker’
than benign or malignant tertian fevers, even though they lasted longer on average, simply because quartan fevers only recurred every seventy-two hours.⁵⁶ Since Pliny recognized that there was ⁵¹ Celsus 3.3.1: et quartanae quidem simpliciores sunt. Incipiunt fere ab horrore, deinde calor erumpit, finitaque febre biduum integrum est: ita quarto die revertitur (Quartan fevers are certainly simpler.
They generally commence with shivering, then the heat erupts, and after the fever terminates there is an interval of two days; and so it returns on the fourth day.).
⁵² Dante Alighieri, La Commedìa. Inferno. Canto .85–8, ed. Lanza (1996): Qual è colui che sì presso ha ‘l riprezzo | della quartana c’ha già l’unghie smorte, | e triema tutto pur guardando il rezzo, | tal divenn’io alle porte parole.
⁵³ Josephus, BJ 1.105 and Ant. J. 13.398; Kottek (1994: 34).
⁵⁴ Pitrè (1971: 218): frevi quartana li vecchi ammazza e li giuvini sana.
⁵⁵ Quintus Serenus, Liber medicinalis 48.895–8, ed. Pépin (1950): nec tu crede levem dilato tempore febrem, quae spatium sibi dat, magis ut cessando calescat: letali quoque grassatur quartana calore, ni medicas adhibere manus discamus et herbas (Do not believe that this delayed fever is mild, it gives itself a rest in order to return with even greater force: the quartan attacks wit
h a deadly fever, unless we teach you to apply healing hands and herbs.).
⁵⁶ Pliny, NH 30.30.98–9: in quartanis medicina propemodum nihil pollet (in cases of quartan fever medicine has virtually no effect); [Aristotle,] Problems 1.56.866a ej g¤r m¶ Án åsqen&ß, oÛk #n tetarta∏oß ƒgvneto (for if it was not weak, it would not be a quartan fever). Galen 11.18–19K
compared the onset of quartan and of tertian fevers. See also Ch. 2 above on quartan fevers.
Horace, Sat. 2.3.290 also mentioned quartan fever.
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no effective herbal remedy or any other cure for quartan fever, he decided to list a series of magical treatments for it.⁵⁷ It would not serve any useful purpose here to go through all the references in the works of Pliny and other ancient authors to remedies for malaria, except to stress that their sheer number demonstrates once again the frequency of malaria in antiquity and the difficulty of treating it. A typical example is his reference to an otherwise unknown doctor called Icatidas, who claimed that quartan fevers in men were terminated by sexual intercourse with women who were just beginning to menstruate.⁵⁸ Similar beliefs persisted in Italy until recently.
In traditional Sicilian folk medicine bathing with the urine of a pregnant woman was considered a remedy for persistent cases of quartan fever. Several early modern Italian writers recommended eating bedbugs ( Cimex lectularius L.) as a cure for quartan fever, following a tradition stretching back to antiquity. Quintus Serenus had recommended eating bedbugs, with eggs and wine, in cases of both quartan and tertian fevers. Pliny also noted this idea, although he believed that it was useless as a remedy for malaria.⁵⁹ Another recommended method was eating the liver of a seven-year-old mouse. A different approach to the problem was the recommendation to arise on three consecutive mornings at dawn, face a window or door, and then shut it suddenly after reciting a particular prayer.⁶⁰ These ‘remedies’ merely serve to show how helpless doctors were in the face of malaria, but they continued trying. Martial wrote an epigram about a doctor who treated cases of quartan fever.⁶¹
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