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The Spread of Malaria to Southern Europe in Antiquity: New Approaches to Old Problems

Published online by Cambridge University Press:  26 July 2012

Robert Sallares ,
Abigail Bouwman  and
Cecilia Anderung
Robert Sallares
Affiliation:
Dept of Biomolecular Sciences, UMIST, PO Box 88, Manchester, M60 1QD, United Kingdom (e-mail: rsallares@aol.com)
Abigail Bouwman
Affiliation:
Dept of Biomolecular Sciences, UMIST, PO Box 88, Manchester, M60 1QD, United Kingdom (e-mail: rsallares@aol.com)
Cecilia Anderung
Affiliation:
Dept of Biomolecular Sciences, UMIST, PO Box 88, Manchester, M60 1QD, United Kingdom (e-mail: rsallares@aol.com)
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The discoveries in the late nineteenth century that malaria is caused by protozoan parasites, which are transmitted by mosquitoes, quickly led to intense speculation about its history in antiquity. The historiography of malaria has passed through three distinct phases during the last hundred years or so. The first generation of historians to consider the effects of malaria did exaggerate its significance in some respects. The argument by W H S Jones that the Greek doctrine of fevers was based on malaria was generally and rightly accepted. However, it is not surprising that his view that malaria was a major reason for the degeneration of the moral character of the ancient Greeks attracted little sympathy. The eradication of malaria from southern Europe in the 1930s and 1940s contributed to a decline of interest in the subject. Subsequently medical historians and even professional malariologists tended to minimize the historical significance of malaria. The revisionist tendencies of this second phase of research led to attempts to reassess some of the details of the evidence upon which Jones had relied. For example, Leonard Bruce-Chwatt and Julian de Zulueta rejected Jones's belief that Plasmodium falciparum, the most dangerous of the four species of human malaria, was already active in Greece in the fifth century BC. They suggested that it started to spread in southern Europe only during the time of the Roman Empire and attributed all the references to intermittent tertian fevers in Hippocratic texts dating to the fifth and fourth centuries BC to the less virulent P. vivax. Although the literature produced during this second phase of scholarship was in many ways more sophisticated, it still suffered from some of the same weaknesses; in particular, analysis proceeded in a purely qualitative manner, without any consideration of the effects of malaria on historical human populations in quantitative terms. A second weakness was a tendency to make generalizations covering the whole of Mediterranean Europe. Since many types of mosquito are incapable of transmitting malaria to humans, mosquito breeding sites do not occur everywhere, and many mosquitoes do not fly further than a few hundred yards from their breeding sites, malaria can only be really understood by micro-analyses, conducted at a very local level, of geography, hydrology, climate, competition between different species of mosquito for breeding sites, and human activities.

Type
Articles
Information
Medical History , Volume 48 , Issue 3 , 01 July 2004 , pp. 311 - 328
Copyright
Copyright © Cambridge University Press 2004

References

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2 For example, J Ruffié and J-C Sournia, Les épidémies dans l'histoire de l'homme: essai d'anthropologie médicale, Paris, Flammarion, 1984, p. 209.

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5 R Sallares, Malaria and Rome: a history of malaria in ancient Italy, Oxford University Press, 2002, gives much more bibliography on the questions considered in this paper.

6P. ovale is not considered any further in this paper since it was never common in Mediterranean countries.

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11 A survey of recent work in this field is provided by J Mercader (ed.), Under the canopy: the archaeology of tropical rain forests, Piscataway, NJ, Rutgers University Press, 2002.

12 Bruce-Chwatt and de Zulueta, op. cit., note 3 above, pp. 9–11.

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15 Celsus, De medicina, III.3.2: “tertianarum vero duo genera sunt. Alterum eodem modo, quo quartana, et incipiens et desinens, illo tantum interposito discrimine, quod unum diem praestat integrum, tertio redit. Alterum longe perniciosius, quod tertio quidem die revertitur, ex quadraginta et octo horis fere triginta et sex per accessionem occupat (interdum etiam vel minus vel plus), neque ex toto in remissione desistit, sed tantum levius est. Id genus plerique medici appellant.”

16 E Marchiafava and A Bignami, On summer–autumn malarial fevers, transl. J Thompson, London, New Sydenham Society, 1894, pp. 231–2. Bruce-Chwatt and de Zulueta, op. cit., note 3 above, pp. 19, 89, accepted Celsus' evidence but incorrectly dated it to the second century AD. This is symptomatic of an unwarranted general tendency on the part of these authors to shorten the chronology for the spread of falciparum malaria in antiquity. The identification of semitertian fever in Celsus was also accepted by G Corbellini and L Merzagora, La malaria tra passato e presente: storia e luoghi della malattia in Italia, Rome, Università di Roma “La Sapienza”, 1998, p. 14.

17 Celsus, De medicina, III.3.1.

18 Plutarch, Moralia, VIII.9.731b–734c, and Pliny, Historia naturalis, XXVI.1–9, both discussed leprosy as a new disease in Hellenistic and Roman times.

19 Quintus Serenus, Liber medicinalis, 51.932–4, ed. R Pépin, Paris, Presses Universitaires de France, 1950.

20 Hippocrates Epidemiae, I.2, op. cit., note 13 above, vol. 2, pp. 606–9: . On the question, raised by Bruce-Chwatt and de Zulueta, op. cit., note 3 above, p. 18, of the association in the Hippocratic texts of semitertian fever with consumption (tuberculosis), see Sallares, op. cit., note 5 above, pp. 136–9.

21 Hippocrates, op. cit., note 13 above, pp. 624–5: . Julian de Zulueta's argument (mentioned by Corbellini and Merzagora, op. cit., note 16 above, p. 22), that sufferers from semitertian fever died too slowly for falciparum malaria to have been the cause, does not take into account the likelihood, discussed below in this article, that by the fifth century BC at least some populations in northern Greece already had a high frequency of human genetic mutations conferring some resistance to malaria. M Grmek, Diseases in the ancient Greek world, Baltimore, Johns Hopkins University Press, 1989, p. 281, accepted the identi fication of falciparum malaria in the Hippocratic texts.

22 Aetius of Amida, Libri medicinales, VI.3.

23 For the problem of whether Macedonia was severely affected by malaria during the time of its rise to power under Philip and Alexander the Great in the fourth century BC, see E Borza ‘Some observations on malaria and the ecology of central Macedonia in antiquity’, Am. J. Ancient Hist., 1979, 4: 102–24.

24 Hippocrates, op. cit., note 13 above, pp. 618–9: .

25 This is a better approach to the problem than assuming, as W H S Jones (op. cit., note 1 above, p. 76) did, that the silence of very scarce earlier sources proves that malaria was unknown in Attica until c. 430 BC.

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28 Strabo, Geographia, V.4.13.251C.

29 Pliny the Younger, Epistolae, V.6.2.

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31 Marcus Porcius Cato, Origines, II.17; photographs of Graviscae in Sallares, op. cit., note 5 above, pp. 194–5.

32 Asclepiades ap. Caelius Aurelianus, De morbis acutis, II.63–4; Galen, VII.435 and XVIIA.121–2, Opera omnia, ed. C Kühn, Leipzig, C Cnobloch, 1821–33.

33 M McCormick, Origins of the European economy: communications and commerce, A. D. 300–900, Cambridge University Press, 2001, pp. 980–1.

34 Vitruvius, De architectura, I.4.11–12; Strabo, Geographia, V.1.7.213C.

35 Sidonius Apollinaris, Epistulae, I.8.2.

36 M Coluzzi, ‘The clay feet of the malaria giant and its African roots: hypotheses and inferences about origin, spread and control of Plasmodium falciparum’, Parassitologia, 1999, 41: 277–83.

37 On the question of the refractoriness of modern tropical strains of P. falciparum to European mosquitoes, see Sallares, op. cit., note 5 above, pp. 33–6. Refractoriness was probably overcome in North Africa and the Near East in prehistory before P. falciparum had even reached southern Europe.

38 R Miller, S Ikram, G J Armelagos, R Walker, W Harer, et al., ‘Diagnosis of Plasmodium falciparum infections in mummies using the rapid manual ParaSight-F test’, Trans. R. Soc. Trop. Med. Hyg., 1994, 88: 31–2; G Taylor, P Rutland, and T Molleson, ‘A sensitive polymerase chain reaction method for the detection of Plasmodium species DNA in ancient human remains’, Ancient Biomolecules, 1997, 1: 193–203; N Cerutti, A Marin, E Massa, and D Savoia, ‘Immunological investigation of malaria and new perspectives in palaeopathological studies’, Bolletino della Società Italiana di Biologia Sperimentale, 1999, 75 (3–4): 17–20.

39 D Soren, T Fenton, and W Birkby, ‘The late Roman infant cemetery near Lugnano in Teverina, Italy: some implications’, J. Paleopathol., 1995, 7: 13–42; D Soren and N Soren (eds), A Roman villa and a late Roman infant cemetery: excavation at Poggio Gramignano, Lugnano in Teverina, Rome, “L'Erma” di Bretschneider, 1999, pp. 461–651.

40 Sallares, op. cit., note 5 above, pp. 61–3, on the seasonality of malaria in Italy.

41 Unfortunately no corresponding adult cemetery has been discovered.

42 C Shulman, T Marshall, E Dorman, J Bumer, F Cutts, et al., ‘Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae’, Trop. Med. Int. Health, 2001, 6: 770–8.

43 A Barbosa and B López Arjona, El paludismo en el primer año de la vida, Madrid, Sáez Hermanos, 1935, pp. 11–18.

44 R Torpin, ‘Malaria complicating pregnancy’, Am. J. Obstet. Gynecol., 1941, 41: 882–5; C A Gill, The genesis of epidemics and the natural history of disease: an introduction to the science of epidemiology based upon the study of epidemics of malaria, influenza, and plague, London, Baillière, Tindall and Cox, 1928, pp. 74–83.

45 C Luxemburger, R McGready, A Kham, L Morison, T Cho, et al. ‘Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission’, Am. J. Epidemiol., 2001, 154: 459–65; M Cot, J Le Hesran, T Staalsoe, N Fievet, L Hviid, and P Deloron, ‘Maternally transmitted antibodies to pregnancy-associated variant antigens on the surface of erythrocytes infected with Plasmodium falciparum: relation to child susceptibility to malaria’, Am. J. Epidemiol., 2003, 157: 203–9.

46 A Sorgoni, ‘Riflessioni sulla maggior forza, con cui si sviluppano le febbri intermittenti ne' marchegiani abitanti nel territorio di Narni a confronto di quella minore forza colla quale si producono negl'indigeni narniesi’, Giornale Arcadico di Scienze, Lettere ed Arti, 1832, 57: 12–21.

47 For general accounts of Umbria in late antiquity, see G Binazzi (ed.), L'Umbria meridionale fra tardo-antico ed altomedioevo, Perugia, Università degli Studi, 1991; S Bocci, L'Umbria nel Bellum Gothicum di Procopio, Studi pubblicati dall'Istituto italiano per la storia antica, vol. 62, Rome, Istituto italiano per la storia antica, 1996.

48 For details of the methods used, see R Sallares and S Gomzi, ‘Biomolecular archaeology of malaria’, Ancient Biomolecules, 2001, 3: 195–213 (with EMBL/Genbank accession nos. AJ426487–8 for the malaria sequences that were obtained).

49 Determination of the sex of a sample of these infants (see also next footnote) indicated that the infant population had a fairly normal sex ratio (five female and four male). Consequently there is no question of selective exposure of female infants in this cemetery.

50 Only nine out of fifteen of the Lugnano infants that were sampled yielded positive results for sex determination by the amelogenin sex determination system—infant bones cannot be sexed by morphological methods (for details of methods see R Sallares, S Gomzi, A Bouwman, C Anderung, and T Brown, ‘Identification of a malaria epidemic in antiquity using ancient DNA’, in K Robson Brown (ed.), Archaeological Sciences 1999. Proceedings of the Archaeological Sciences Conference, University of Bristol, 1999, Oxford, Archaeopress [BAR S1111], 2003, pp. 120–5). This ratio is comparable to results from other ancient Mediterranean archaeological sites, e.g. M P Evison, ‘Ancient DNA in Greece: problems and prospects’, Journal of Radioanalytical and Nuclear Chemistry, 2001, 247: 673–8; C Vernesi, D Caramelli, S Carbonell i Sala, M Ubaldi, F Rollo, and B Chiarelli, ‘Application of DNA sex tests to bone specimens from three Etruscan (VII–III century B.C.) archaeological sites’, Ancient Biomolecules, 1999, 2: 295–305; M Cipollaro, G Di Bernardo, G Galano, U Galderisi, et al., ‘Ancient DNA in human bone remains from Pompeii archaeological site’, Biochemical and Biophysical Research Communications, 1998, 247: 901–4.

51 Sallares, op. cit., note 5 above, pp. 64–8.

52 Quintus Serenus, Liber medicinalis, 51.935–940, op. cit., note 19 above.

53 Literary evidence for the interaction of magic and religion in Umbria at this time has been discussed by G Bartocci, ‘The cultural construction of the Western conception of the realm of the sacred: co-existence, clash and interbreeding of magic and sacred thinking in fifth- and sixth-century Umbria’, Anthropology and Medicine, 2000, 7: 373–88.

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55 I Hershkovitz, B Rothschild, B Latimer, O Dutour, E Léonetti, C Greenwald, et al. ‘Possible congenital haemolytic anemia in prehistoric coastal inhabitants of Israel’, Am. J. Phys. Anthropol., 1991, 85: 7–13, on the skeleton Homo 25.

56 G Baggieri and F Mallegni, ‘Morphopathology of some osseous alterations of thalassic nature’, Paleopathology Newsletter, 2001, 116: 10–16.

57 F Mallegni and G Fornaciari, ‘Le ossa umane’, in A Ricci (ed.), Settefinestre: una villa schiavistica nell'Etruria romana, 3 vols, Modena, Panini, 1985, vol. 2, pp. 275–7, on skeleton no. 26.203.

58 J C Carter, The chora of Metaponto: the necropoleis, 2 vols, Austin, University of Texas Press, 1998, vol. 2, pp. 527–9, 553–6.

59 Grmek, op. cit., note 21 above, p. 275; M Grmek and D Gourevitch, Les maladies dans l'art antique, Paris, Fayard, 1998, pp. 223–5.

60 G Maat and M Baig, ‘Scanning electron microscopy of fossilized sickle-cells’, Int. J. Anthropol., 1990, 5: 271–6; G Maat, ‘Bone preservation, decay and its related conditions in ancient human bones from Kuwait’, Int. J. Osteoarchaeol., 1993, 3: 77–86.

61 P Hortolà, ‘Red blood cell haemotaphonomy of experimental human bloodstains on techno-prehistoric lithic raw materials’, J. Archaeol. Sci., 2002, 29: 733–9.

62 A Ragusa, M Lombardo, G Sortino, T Lombardo, R L Nagel, and D Labie, ‘βS gene in Sicily is in linkage disequilibrium with the Benin haplotype: implications for gene flow’, Am. J. Hematol., 1988, 27: 139–41.

63 A Kulozik, J Wainscoat, G Serjeant, B Kar, B Al-Awamy, et al., ‘Geographical survey of βS-globin gene haplotypes: evidence for an independent Asian origin of the sickle-cell mutation’, Am. J. Hum. Genet., 1986, 39: 239–44

64 A list of G6PD mutations is given by E Beutler and T J Vulliamy, ‘Haematologically important mutations: glucose-6-phosphate dehydrogenase’, Blood Cells, Molecules, and Diseases, 2002, 28: 93–103.

65 M Cappadoro, G Giribaldi, E O'Brien, F Turrini, F Mannu, et al. ‘Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum may explain malaria protection in G6PD deficiency’, Blood, 1998, 92: 2527–34; K Lang, B Roll, S Myssina, M Schittenhelm, H Scheel-Walter, et al., ‘Enhanced erythrocyte apoptosis in sickle cell anaemia, thalassaemia and glucose-6-phosphate dehydrogenase deficiency’, Cellular and Physiological Biochemistry, 2002, 12: 365–72.

66 Y Abdulrazzaq, R Micallef, M Qureshi, A Dawodu, I Ahmed, et al., ‘Diversity in expression of glucose-6-phosphate dehydrogenase deficiency in females’, Clinical Genetics, 1999, 55: 13–19.

67 For details of the methods used, see Sallares, et al., op. cit., note 50 above. See also A Bouwman and T Brown, ‘Comparison between silica-based methods for the extraction of DNA from human bones from 18th to mid-19th century London’, Ancient Biomolecules, 2002, 4: 173–8. For other work on the G6PD gene in degraded materials, see H Liu, X Huang, Y Zhang, H Ye, A Hamidi, et al. ‘Archival fixed histologic and cytologic specimens including stained and unstained materials are amenable to RT-PCR’, Diagn. Mol. Pathol., 2002, 11: 222–7.

68 F Martinez di Montemuros, C Dotti, D Tavazzi, G Fiorelli, and M Cappellini, ‘Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) variants in Italy’, Haematologica, 1997, 82: 440–6.

69 A Minà La Grua, Memoria sopra l'itterizia e su le malattie ordinarie dei contadini di Castelbuono, Palermo, Vrizi, 1856.

70 Grmek, op. cit., note 21 above, pp. 210–44; E Lieber, ‘The Pythagorean community as a sheltered environment for the handicapped’, in H Karplus (ed.), International symposium on society, medicine and law (Jerusalem March 1972), Amsterdam, Elsevier, 1973, pp. 33–41, on p. 36.

71 G Gaetani and A Ferraris, ‘Biochemistry of G6PD deficiency and molecular genetics of G6PD variants in Italy’, in L S Greene and M E Danubio (eds), Adaptation to malaria: the interaction of biology and culture, Amsterdam, Gordon and Breach, 1997, pp. 9–31, on p. 20. J V Day, Indo-European origins: the anthropological evidence, Washington, DC, Institute for the Study of Man, 2001, pp. 287–9, discusses the hypothesis of Eugene Giles that G6PD deficiency and the taboo on beans arose among the Proto-Indo-Europeans.

72 Tadmouri, et al., op. cit., note 54 above.

73 A Cao, M Gossens, and M Pirastu, ‘β-thalassaemia mutations in Mediterranean populations’, Br. J. Haematology, 1989, 71: 309–12. Earlier discussions by medical historians and palaeopathologists (e.g. Grmek, op. cit., note 21 above, pp. 254–64) did not employ the evidence of DNA sequence data, which was not yet available.

74 Cao, et al., op. cit., note 73 above.

75 P Perrin, R Bouhassa, L Mselli, N Garguier, V Nigon, et al. ‘Diversity of sequence haplotypes associated with β-thalassaemia mutations in Algeria: implications for their origin’, Gene, 1998, 213: 169–77.

76 C Ramsdale and K Snow, ‘Distribution of the genus Anopheles in Europe’, Eur. Mosq. Bull., 2000, 7: 1–26.

77 W Horsfall, Mosquitoes: their bionomics and relation to disease, New York, Ross, 1955, pp. 94, 103, 107.

78 P Sondaar, ‘Palaeolithic Sardinians: palaeontological evidence and methods’, in M Balmuth and R Tykot (eds), Sardinian and Aegean chronology: towards the resolution of relative and absolute dating in the Mediterranean, Oxford, Oxbow, 1998, pp. 45–51.

79 S Moscati, Italia punica, Milan, Bompiani, 1986, pp. 150–2, 181.

80 G Schilirò, E Mirabile, R Testa, G Russo-Mancuso, and S Dibenedetto, ‘Presence of haemoglobinopathies in Sicily: a historic perspective’, Am. J. Med. Genet., 1997, 69: 200–6.

81 This is the explanation of the problem posed by Bruce-Chwatt and de Zulueta, op. cit., note 3 above, p. 15.

82 Sallares, op. cit., note 5 above, pp. 78–85.

83 M McCormick, ‘The imperial edge: Italo-Byzantine identity, movement and integration, AD 650–950’, in H Ahrweiler and A Laiou (eds), Studies on the internal diaspora of the Byzantine Empire, Washington, DC, Dumbarton Oaks, 1998, pp. 17–52, on pp. 25–31.

84 Grmek and Gourevitch, op. cit., note 59 above, pp. 97–9.

85 J L Angel, ‘Porotic hyperostosis or osteoporosis symmetrica’, in D Brothwell and A Sandison (eds), Diseases in antiquity, Springfield, IL, C C Thomas, 1967, pp. 378–89, argued that there was malaria at Lerna in the Middle Bronze Age.

86 J L Angel, ‘Porotic hyperostosis, anemias, malarias, and marshes in the prehistoric eastern Mediterranean’, Science, 1966, 153: 760–3.