Malaria and Rome: A History of Malaria in Ancient Italy (6 page)

²⁹ Galen 17A.222K: oÛ per≥ pr3gmatoß, åll¤ per≥ shmainomvnou ka≥ ønÎmatÎß ƒstin Ó

z&thsiß, oÙß t0n proeirhmvnwn puret0n ønom3zein pros&kei trita≤ouß, Ómitrita≤ouß ka≥

tritaiofue∏ß.

³⁰ Jarcho (1987), contrast Sambon (1901
b
, 305–10).

20

Types of malaria

endemic in London in his own time during the climatic conditions of the ‘Little Ice Age’ (see Ch. 4. 5 below), although he undoubtedly did recognize ‘ague’ or ‘marsh fever’, the indigenous English malaria caused by
P. vivax
(see Ch. 5. 4 below). Even as late as the nineteenth century, Littré in his great edition of the Hippocratic corpus had to insist that the diseases described in it had to be searched for among those present in Greece, not among the diseases of northern Europe.³¹

Any attempt to trace the history of
P. falciparum
malaria in Greece before the fifth century  encounters the perennial problem of the shortage of evidence, which bedevils the historiography of archaic Greece. There is no reason whatsoever for supposing that authors such as Hesiod or the lyric poets ever envisaged producing ancient equivalents of Pauly’s
Realencyclopädie
. Consequently arguments from silence based on such sources are just as worthless in respect of malaria as they are in respect of other problems in Greek history. There is one passage in Homer which has attracted attention. The reference to ‘fever’ (puretÎß, a
hapax legomenon
in Homer) in such an early source is by itself inadequate to prove that this text is a reference to malaria. Although there is no doubt that specialist medical literature such as the writings of Celsus and Galen does refer specifically to malaria, there will always be room for doubt whether the vocabulary of authors who were not specialists in medicine was used in the same way as doctors used it.³² The meaning of the Homeric text was already debated in antiquity, as shown by the scholiast.³³

³¹ Celli (1933: 47);
Œuvres complètes d’Hippocrate
, ed. Littré, ii. 538–84; Bruce-Chwatt (1976) on the history of the term
ague
.
Pace
Jarcho, there did continue to be some recognition of semitertian fevers in literature in northern Europe in the early modern period (e.g. Black (1789: 46, 49).

³² The brief reference to an epidemic attributed to ‘bad air’ during the summer in Virgil, Aeneid
3.137–42 raises similar problems of interpretation. There is no detailed description of the symptoms. Livadas (1959: 301) quoted a passage from the ‘Orphic’
Lithika
as ‘pre-Hippocratic’ evidence for malaria in Greece in the sixth century , but this poem is now regarded as a late work of the fourth century  (so West (1983: 36) following R. Keydell in Pauly-Wissowa,
RE
xviii.2 (1942), cols. 1338–41): ej d† puriflegvqwn ‰ter&meroß £ndra qam≤zwn | ∂ kruerÏß m3rptwn puretÏß paradhq»n7sin, | ]† tetarta≤hß p[ma brad», m& pote l&gein | Boulomvnhß, åll’ ajvn, Òp7 pel3s7si, meno»shß, | tÎnde s» g’ j$sqai di’

åm»monoß åntiac3tou: | o˜toß g¤r puret0n polŸ fvrteroß (If a fever blazing like fire on alternate days regularly attacks a man, | or a fever creeps in while the man is in the grip of an icy chill, | or a quartan fever, never wishing to cease, but always remaining, | brings slow misery to a man as it approaches, | you cure this fever with an excellent agate[?]. | This stone is much better than fevers.) (
Lithika
633–8, ed. Abel (1885) ).

³³ Òti ‹pax ƒntaıqa Ø puretÎß, AAext ka≥ Òti puretÏß kur≤wß lvgei, oÛc ¿ß tineß dvcon-Types of malaria 21

The old man Priam was the first to see him [sc. Achilles] with his eyes, as he hurried across the plain, shining like the star which rises at harvest time [sc. Sirius]. Its rays are conspicuous among the numerous stars in the dead of night, and it is called the dog of Orion by men. It is the brightest star, but its appearance is a sign of evil, for it brings much fever to wretched humans.³⁴

Nevertheless, if the circumstantial details provided in this passage are approached with an open mind, without any preconcep-tions as to when
P. falciparum
reached Greece, the whole context is much more suggestive of
P. falciparum
malaria than anything else.

The parallel with Achilles, avenging the death of Patroclus, suggests a disease capable of causing very high mortality rates.³⁵ The rising of Sirius (in late July) was definitely associated with malarial environments in Etruria by Tibullus:

Remain by the water which flows from Etruscan springs, a stream not to be approached during the heat at the time of the dog star, but now second only to the holy waters of Baiae, when the ground thaws during the varie-gated spring.³⁶

The association with the harvest recalls the name ‘aestivo-autumnal fever’ that was frequently given to
P. falciparum
malaria by Italian doctors, such as Marchiafava and Bignami in the late nineteenth century. In contrast
P. vivax
only requires temperatures of 15–16ºC to complete its cycle of development inside the mosquito and has a tendency to cause spring relapses following primary infections in the previous autumn. Consequently vivax malaria was tai t¶n di3kausin toı åvroß: prÏß g¤r tÏ fqoropoiÏn Ó parabol&. ka≥ Òti deilo∏sin ånt≥ toı deila≤oiß (The word ‘fever’ only occurs once [sc. in Homer]. Moreover it really means ‘fever’, not ‘burning of the air’ as some maintain, for the comparison is with something which causes destruction):
Scholia Graeca in Homeri Iliadem
[
Scholia Vetera
], ed. H. Erbse (1972), v. 268–9. The same pair of alternative explanations is found in Eustathius,
Commentarii ad Homeri Iliadem pertinentes
, ed. van der Valk (1987), iv. 566, writing in the twelfth century .

³⁴ Homer,
Iliad
22.25–31: tÏn d’ Ø gvrwn Pr≤amoß pr0toß ÷den øfqalmo∏si, |

pamfa≤nonq’ ¿ß t’ åstvr’ ƒmpess»menon ped≤oio, | Òß Â3 t’ øp*rhß e”sin, år≤zhloi dv oÈ

aÛga≥ | fa≤nontai pollo∏si met’ åstr3si nuktÏß åmolg‘: | Òn te k»n’ ∞Wr≤wnoß ƒp≤klhsin kalvousi. | LamprÎtatoß m†n Ò g’ ƒst≤, kakÏn dv te s[ma tvtuktai | ka≤ te fvrei pollÏn puretÏn deilo∏si broto∏sin.

³⁵ The rising of the dog-star was regarded as an important time in the development of seasonal disease epidemiology by Hippocrates,
Airs, Waters, Places
11.

³⁶ Tibullus, 3.5.1–4:
Vos tenet, Etruscis manat quae fontibus unda,
|
unda sub aestivum non adeunda Canem,
|
nunc autem sacris Baiarum proxima lymphis,
|
cum se purpureo vere remittit humus
.

22

Types of malaria

observed from March onwards under Mediterranean environmental conditions and was not especially associated with the harvest as such, although it certainly was frequently transmitted during the harvest in the past (see Ch. 5. 4 below). Grmek rightly noted that acute enteric diseases are also prevalent in summer and autumn, as seen, for example, in the population of Florence at the time of the
Catasto
(census) of  1427 (see Ch. 5. 2 below).³⁷ However, the association with the harvest is very significant. Peasants often slept out in the fields during the harvest, where they were very vulnerable to mosquito bites but far from stagnant sources of water in urban areas, the commonest source of enteric diseases. A very important practical reason for farmers in Lazio to stay in their fields at night was to prevent their crops being stolen. The vulnerability of farm workers to malaria infection during the harvest has frequently been noted in Italy and other Mediterranean countries, and indeed all over the world, wherever malaria occurs. In the village of Lodé in northeastern Sardinia, where in the 1930s the morbidity rate from malaria was 90%, 50% of the population slept outside the village during the summer.³⁸

Besides this Homeric text, there is another, completely different, but much stronger line of argument for the presence of
P. falciparum malaria in Greece by the eighth century . The B+ IVS nt 110

mutation for b-thalassaemia, which confers some resistance to P. falciparum
malaria, reaches its highest frequencies in Greece and was spread by Greek colonization. It is also common in the modern populations of those parts of southern Italy which were colonized by the Greeks in the seventh and eighth centuries . This indicates that the mutation was already present in human populations in Greece by then. The implication is that
P. falciparum
was already active in Greece by the eighth century  (see Ch. 5. 3 below for further discussion).

³⁷ Marchiafava and Bignami (1894); Grmek (1983: 65–6).

³⁸ For infection of harvesters see M. E. Danubio in Greene and Danubio (1997: 328) on Lodé; Bercé (1989: 242); Celli (1900: 176); North (1896: 243–4) on Lazio; Desowitz (1992: 111–12) on south-east Asia; M. T. Gillies in Wernsdorfer and McGregor (1988: i. 473) for Turkey; McNalty (1943) for infection of harvesters by
P. vivax
in Scotland in the eighteenth century. Plutarch,
Moralia
137c, discussed by Jones (1908: 545), does not describe any symptoms of the ailments of harvesters. The Chronicle of Joshua the Stylite, ed. Wright (1882), ch. 85, p. 67, shows that in Syria at the end of the fifth century  it was normal for farmworkers to sleep outside on the threshing floor at the time of threshing.

3

Evolution and prehistory of malaria

Several quite different arguments have been proposed in favour of the theory of a late introduction (or reintroduction) of
P. falciparum malaria to Greece and Italy. W. H. S. Jones was looking for an explanation for the decadence, as he saw it, of ancient Hellenic civilization. This approach can be safely dismissed now without further discussion. Zulueta and Grmek and other authors exploited a series of much more scientific arguments which certainly merit extensive discussion, one by one. These ideas are briefly summarized here, before discussion: (1) the hypothesis that
P. falciparum
must be a human pathogen of recent origin because its extreme virulence suggests that it has not had time to adapt to humans as a host;

(2) the hypothesis that large human population sizes would have been needed before malaria could become endemic in Greece and Italy;

(3) the hypothesis that the species of mosquito which were the most effective vectors of malaria in Europe would have taken several thousand years to spread into southern Europe after the end of the last Ice Age;

(4) the hypothesis that because these species of mosquito are refractory to tropical strains of
P. falciparum
a long period of evolution would have been required before they could become efficient vectors of the parasites.

It was once widely believed, as a general principle of parasite ecology and epidemiology, that parasites tend to evolve towards symbiosis or commensalism with their hosts, because in the long run it would not be in the interests of a parasite to kill its host.

This is frequently given as a reason why
P. falciparum
malaria, an extremely virulent disease, must be a human disease of recent origin, which might only have evolved during the last few thousand years. This theory bolstered the conclusions of A. P. Waters and co-workers, who argued on the basis of phylogenetic analyses of 24

Evolution of malaria

0.02

0.044

0.018

Babesia

0.042

0.050

9,998

Theileria

0.069

0.022

Eimeria

0.056

9,998

Toxoplasma

0.048

P. malariae

0.042

7,782

P. ovale

0.012

10,000

9,963

P. vivax

8,802

0.026

P. cynomolgi

0.014

6,120

10,000

P. knowlesi

6,123 0.015

P. fragile

0.029

0.024

P. lophurae

0.064

0.026

0.013

10,000

P. gallinaceum

9,993

0.009

0.034

P. reichenowi

10,000

P. falciparum

0.056

P. berghei

Figure 1. Evolutionary relationships of selected
Plasmodium
species indicated by neighbour-joining analysis of 18S ribosomal gene A sequences in a ClustalX alignment (Thompson
et al.
(1997) ), modified manually in the BioEdit sequence editing program (Hall (1999) ). The apicomplexan species
Toxoplasma gondii
,
Eimeria mitis
,
Babesia bigemina
, and
Theileria annulata
were used as outgroups, with 10,000 bootstrap replications. Bootstrap values are shown below the branches and branch lengths above the branches.

DNA sequences that
P. falciparum
is closely related to avian malarias, but not to other primate malarias, with the implication that P. falciparum
malaria is the result of a lateral transfer of a malaria parasite from birds.¹ It remains controversial whether or not P. falciparum is more closely related to avian malaria species than it is to other primate malaria species. Settling this phylogenetic question is not essential for the purposes of this book, since the evolutionary relationships in question date back to over a hundred million years ago. However, the ecological problem is important for current purposes. Research in ecology in recent years has reached the conclusion that it is not inevitable that a parasite or other pathogen will evolve towards avirulence. It all depends on the precise circumstances, in particular it depends on the factors favouring transmission of the parasite to new hosts, which is what will determine its evolutionary fitness.

¹ Waters
et al
. (1991), discussed by Brooks and McLennan (1992) and McCutchan
et al
.

(1996).

Evolution of malaria

25

Since all the species of human malaria depend on
Anopheles mosquitoes to convey them from human to human, it is not in the interests of the parasite to harm its vector. That might adversely affect transmission of the parasite to new hosts. Consequently none of the species of human malaria causes any great harm to mosquitoes, or at least mosquito immune defence systems appear to be adequate to limit damage. However, the situation with regard to the human host is much more complicated. In an environment where transmission from host to host is possible all the year round, as in the tropics, the type of parasite which will achieve the greatest evolutionary fitness is the one which achieves the highest rate of reproduction in the host, irrespective of what that does to the host.