Malaria and Rome: A History of Malaria in Ancient Italy (4 page)

⁷ For the symptoms see Gilles and Warrell (1993: 35–49); Harinasuta and Bunnag in Wernsdorfer and McGregor (1988: i. 709–34); Marchiafava and Bignami (1894) and Marchiafava (1931) on symptoms of
P. falciparum
malaria in Italy; Armand-Delille
et al
. (1918: 13–77) described the symptoms of
P. falciparum
malaria in Macedonia.

10

Types of malaria

the characteristic periodicity of intense fever recurring on the second day, in the case of
P. falciparum
and
P. vivax
, or on the third day, in the case of
P. malariae
, which distinguishes malaria from other diseases. This feature enables us to be certain that ancient texts do in fact refer to malaria.

There are indeed other diseases which have some periodic tendencies, for example relapsing fever (
Borrelia recurrentis
) transmitted by the human body louse, or brucellosis (undulant fever), which is most commonly acquired by ingesting contaminated milk or cheese. In relapsing fever attacks last for five to nine days, followed by a similar period of intermission, while in some cases of brucellosis there is a daily periodicity more reminiscent of that of malaria.

These diseases certainly existed in Roman times.⁸ However, they lack the characteristic association with certain types of environment, especially wetland environments, which are strongly associated with malaria, because they are not transmitted by mosquitoes.

Similarly all the other major infectious diseases transmitted predominantly either directly by the respiratory route (e.g. tuberculosis, influenza, and smallpox) or by vectors other than mosquitoes (e.g. typhus and bubonic plague) do not have any epidemiological association with wetland environments. In the tropics important viral diseases transmitted by mosquitoes exist (for example, yellow fever and dengue fever). However, mosquito-transmitted diseases caused by viruses cannot become endemic in Europe because they induce complete immunity in survivors and require constant transmission to new hosts. Yellow fever, for example, cannot survive the winter in Europe because its vector mosquito (
Aedes aegypti
) cannot stand European winters.⁹ In Europe malaria was the only major disease transmitted by mosquitoes in the past and so strongly associated with mosquito breeding sites in wetlands. Consequently in the search for ancient malaria in this book the focus will be on texts that give general descriptions of particular regions in which seasonal unhealthiness is associated with certain types of environments. Such descriptions on the whole constitute a better source ⁸ Capasso (1999) has recently demonstrated the presence of brucellosis in a number of the skeletons from Herculaneum.

⁹ Yellow fever caused brief summer epidemics in some Mediterranean cities in the eighteenth and nineteenth centuries. For example, Palloni (1804) described a yellow-fever epidemic at Livorno. It killed over 700 people out of a total population of about 70,000, but did not survive the winter or spread beyond the part of the town closest to the sea. The disease obviously arrived on board a ship.

Types of malaria

11

of evidence for malaria than biographical accounts of the illnesses of individuals, such as Alexander the Great or various Roman or Byzantine emperors, which frequently provide too little detail for a reliable retrospective diagnosis.¹⁰

The periodicity of malarial fevers is caused by the synchronized process of schizogony (or merogony, a type of asexual reproduction unique to parasitic protozoa) at the end of which erythrocytes burst, releasing new merozoites into the bloodstream to invade other red blood cells. However, it is important to bear in mind that in practice the characteristic periodicity is not in fact observed in many cases, owing to infections with multiple generations of parasites whose developmental cycles are not synchronized. Experiments in which malaria was deliberately transmitted by infected mosquitoes to patients suffering from syphilis and afterwards cured with quinine (
Treponema pallidum
, the pathogen of syphilis, cannot tolerate the temperatures generated by malarial fevers inside the human body) were carried out for many years at Horton Hospital in Epsom in England. These experiments proved that in malaria caused by
P. falciparum
, the most dangerous species of malaria, most attacks take the form of subcontinuous or quotidian (peaking every twenty-four hours) fevers. It was also demonstrated that even in the milder type of malaria caused by
P. vivax
the periodicity of the fever is generally quotidian in primary infections throughout the course of the attack. The periodicity of vivax malaria is only tertian from the beginning of the attack in relapses. The tertian and quartan periodicities are the clearest symptoms of malaria found in historical sources. References to quotidian fevers have less diagnostic value because of the possibility of confusion with other diseases, for example typhoid fever (see Ch. 5. 2 below). However, it must be recognized that modern experimental research in medicine indicates that references to the tertian and quartan periodic fevers in ancient sources only reveal the tip of the iceberg of malaria in antiquity. This is a very important conclusion for the interpretation of the ancient evidence. A large proportion of all cases of both P. falciparum
and
P. vivax
malaria, including virtually all primary infections, would have taken a quotidian form in antiquity just as they do today.¹¹

¹⁰ Illustrations of the biographical approach: Engels (1978) on Alexander; Lascaratos and Marketos (1997) on the Byzantine emperor Andronicus III Palaeologus.

¹¹ Covel and Nicol (1951) and Shute (1951) on the work at Horton Hospital, which 12

Types of malaria

As a general rule, it may be said that the longer and the more regular the periodicity, the less dangerous the disease. It was well known in antiquity that quartan fevers were usually not dangerous (although
P. malariae
is now known to cause quartan malarial nephrosis, a severe kidney disease), but nevertheless lasted longer than other malarial fevers.
P. falciparum
infections do not last much longer than a year (but cf. Ch. 5. 4 below for recent modifications to this standard view found in the textbooks), and
P. vivax
infections do not last for longer than three to six years. However, there are cases in modern medical literature of individuals who had recrudescences with clinical symptoms of
P. malariae
over fifty years after the original infection. One woman from Karpathos in Greece was infected with quartan fever at the age of three in 1925, and then had no further attacks until she reached the age of seventy-two, when a recrudescence occurred following treatment for another medical condition with an immunosuppressive drug. Presumably in this particular case the human immune response was strong enough to keep the infection asymptomatic after the initial attack for seventy years, but not powerful enough to eliminate the parasites from the body completely. This suggests that
P. malariae
can effectively persist throughout the entire life span of the human host. The asymptomatic persistence of
P. malariae
infections has been frequently revealed in modern cases by the use of infected blood in transfusions. Celsus affirmed that quartan fevers did not kill anyone, although Antonio Benivieni of Florence (1443–1502), one of the earliest practitioners of pathological anatomy, described one fatal case of quartan fever in the fifteenth century .¹² The periodic episodes of fever during a malarial infection are probably a followed the Nobel Prize-winning discovery of the malaria treatment for syphilis by Julius Wagner-Jauregg in Vienna in June 1917 (Whitrow 1990; see also Ch. 5. 2 below). Recent textbooks on malaria reiterate these conclusions, stating for example that ‘tertian periodicity is rarely seen in falciparum malaria: persistent spiking fever or a daily (quotidian) febrile paroxysm is more usual’ (Gilles and Warrell (1993: 37) ).

¹² Garnham (1966: 275–6) and the monograph of Kibukamusoke (1973) on the kidney disease; L. H. Miller in Wernsdorfer and McGregor (1988: i. 729); Lentini and Tecce (1955), Guazzi and Grazi (1963), Garnham (1966: 271–2), Vinetz
et al
. (1998), and Chadee
et al
. (2000) on longevity of quartan fever; Garnham (1966: 45–9) on definitions of the terms
relapse
, recrudescence
, and
recurrence
in malariology; Celsus,
de medicina
3.15.6:
quartana neminem iugulat (quartan fever kills no one); Oribasius,
synopsis ad Eustathium
6.13, ed. Raeder: toŸß tetarta∏on nosoıntaß pr5wß £gein (those who are sick with quartan fever have a mild disease); Galen 17A.226–7K and 17B.341–3K; Benivieni (1528/9), 59; Carmichael (1989: 34–5) discussed Benivieni.

Types of malaria

13

non-specific immune response by the human body in an attempt to bring the infection under control, by making it too hot for the parasites to thrive.¹³

It is agreed by all those interested in this subject that
P. vivax (and
P. malariae
, generally regarded as insignificant with regard to mortality) was present in the Mediterranean by the fifth century .

This is shown by numerous texts in the Hippocratic corpus and later medical writers. Even if, for the sake of argument, only the presence of
P. vivax
(and
P. malariae
) in Greece in the fifth century 

is accepted, recent research in historical demography (see Ch. 5. 4

below) has demonstrated that
P. vivax
, in synergistic interactions with other diseases, is capable of enormous effects on the mortality regimes of human populations, even though it seldom kills otherwise healthy and well-nourished individuals by itself, according to the general consensus of medical literature.¹⁴ The position with regard to the history of
P. falciparum
, the most dangerous species of human malaria, is more controversial. Some authors (e.g. G. Belios and J. P. Kardamatis for Greece) have regarded
P. falciparum
as present in Mediterranean countries from time immemorial. Similarly Brunt found no evidence in literary sources that malaria was regarded as a new disease in Italy in classical times. Nevertheless others have reached the conclusion that
P. falciparum
malaria was only introduced to the Mediterranean world in the course of the Graeco-Roman period. W. H. S. Jones originally suggested that it was introduced to Italy by Hannibal’s soldiers during the Second Punic War, but later suggested that it had reached Sybaris by the end of the archaic period. He also maintained that the disease played a major role in the decline of classical Greek civilization.

Grmek once argued that malaria flourished in Greece in the Neolithic period, continued to exist at a low level in dispersed locations, and spread again in the fifth century . More recently he declared that the evidence for
P. falciparum
malaria in Neolithic Greece, adduced by J. L. Angel, is no longer compelling, even though it is ¹³ Gravenor and Kwiatkowski (1998), but cf. Hoshen
et al
. (2000).

¹⁴ L. H. Miller in Wernsdorfer and McGregor (1988: i. 713): ‘infections with
P. vivax
are rarely fatal’, cf. Gilles and Warrell (1993: 44): ‘severe vivax malaria has been described in the past (for example, in Europe) possibly related to malnutrition and other intercurrent diseases. However . . . the acute mortality of vivax malaria is very low’.

14

Types of malaria

likely that it was present in small foci. Zulueta is even sceptical about the presence of
P. falciparum
in Greece as late as the fifth century . He dates its spread in the Mediterranean to the time of the Roman Empire. Celli, the author of what remains the only comprehensive survey of malaria in the Roman Campagna

throughout history, sidestepped the debate about the time of introduction of
P. falciparum
by devising a theory of periodic attenuations of the virulence of the disease (‘
grandi attenuazioni periodiche dell’

infezione
’). Celli’s book is still extremely valuable for its collection of historical sources. However, it is inevitably to some extent out of date owing to the steady march of progress in science and medicine during the twentieth century. Tomassetti reckoned that malaria was above all a phenomenon of the early modern period and was not so bad in antiquity, but he did not examine the ancient sources thoroughly. Many modern historians have expressed similar opinions without studying the relevant ancient sources (especially the medical authors—Celsus, Galen, and Asclepiades) in the necessary detail.¹⁵ It is now time to examine some of these ancient sources.

Celsus, writing in the time of Tiberius in the early first century , provides important evidence. The interpretation of his text is easy if it is compared to the very detailed account and case studies of Ettore Marchiafava, who in collaboration with Celli first described
P. falciparum
under the microscope in 1889, in Italy. After describing quartan fevers caused by
P. malariae
(see Ch. 5. 2 below), Celsus continued as follows:

There are two types of tertian fever.The first type commences and terminates in the same manner as quartan fever. Its distinguishing feature is that it disappears for one whole day and returns on the third day. The second type is much more pernicious. It too recurs on the third day. However, out of the forty eight hours, the paroxysm lasts for almost thirty-six hours (sometimes more or less), nor is there any total cessation during the remission, but it becomes less severe. Most doctors call this type of fever semitertian.¹⁶

¹⁵ The Bibliography for this book concentrates on recent literature, although the most important older works are included. Fraccaro (1919) discussed the principal theories which had been proposed up to then; Jones (1907), (1908) and (1909
a
) and (1909
b
); Brunt (1987: 611–24); Corvisier (1994); Grmek (1983: 397–407) and (1994); Zulueta (1973), (1987: 200–3), and (1994); Celli (1933); Tomassetti (1910: i. 68–72, 164–71).