Malaria and Rome: A History of Malaria in Ancient Italy (28 page)

North wrote as follows:

Chronic malaria is not infrequently associated with a species of chronic pneumonia, which in the experience of the Roman physicians, is often accompanied by the development of tubercle.⁷⁴

After considering the views expressed by more than fifty doctors and scientists on the question of the interaction of malaria and tuberculosis, Collari concluded that tuberculosis struggles to establish itself in a patient already suffering from malaria (perhaps because of the very high fever). However, a malarial infection of a person already suffering from tuberculosis rapidly exacerbates the effects of tuberculosis:

forme che assumono carattere speciale dall’influenza malarica; cionondimeno, da osservazioni raccolte, ci è permesso di argomentare ad una certa frequenza della complicazione palustre in queste manifestazioni morbose
[
sc. pleuro-polmonite e bronchite
].
’

⁷² Chambers (1865); Blewitt (1843: 466).

⁷³ Hoolihan (1989: esp. 472–3, 476–7, 479–82 on malaria) discussed this nineteenth-century debate about Rome as a health resort, cf. Wrigley (2000).

⁷⁴ North (1896: 273). Sambon (1901
b
: 314–15) expressed the same view: ‘in the Roman Campagna the most frequent complication is pneumonia which occurs in the winter or spring months, during relapses of the intermittent fevers’.

Demography of malaria

139

When patients with chronic malaria become infected with pulmonary tuberculosis, it assumes a slow course with a tendency towards sclerosis; whereas when a patient with pulmonary tuberculosis becomes infected with malaria, the tuberculosis tends to be aggravated and to assume a course which develops rapidly.⁷⁵

A recent review of the question of the interaction between malaria and tuberculosis concluded that repeated malarial infections, even if asymptomatic, cause both quantitative and qualitative depression of the human immune system and thereby increase susceptibility to tuberculosis as well as the rate of development of tuberculosis infections, reiterating Collari’s conclusion seventy years ago. This review considered the possibility that the continuing presence of endemic malaria may be one of the reasons for the persistence of tuberculosis in tropical countries (exacerbated now by its interaction with the HIV virus), in contrast to the gradual disappearance of tuberculosis in temperate countries over the last 150

years.⁷⁶

Baccelli also observed that malaria can aggravate many other diseases.⁷⁷ Malarial interference with the T-cell component of the human immune system diminishes the immune response to other pathogens (e.g. the Epstein-Barr virus in relation to Burkitt’s lym-phoma).⁷⁸ Marchiafava and Bignami illustrated a different type of disease interaction with malaria when they described the case of a thirty-three-year-old epileptic man from outside the Porta del Popolo in Rome in whom a malarial infection brought on an epileptic fit. The interaction between malaria and epilepsy has also attracted attention in recent medical research.⁷⁹ We can hardly leave the topic of synergistic interactions between malaria and other diseases without briefly mentioning what might well become the most important interaction in tropical Africa, namely malaria’s interaction with the HIV virus, even though it is not relevant to antiquity. One study found that ‘HIV-1 infection progressively ⁷⁵ Collari (1932: 324):
quando la tubercolosi polmonare si impianta nei malarici cronici assume un decorso lento con tendenza alla sclerosi; mentre quando la malaria sopravviene in un malato di tubercolosi polmonare, questa tende ad aggravarsi e ad assumere un decorso rapidamente evolutivo
.

⁷⁶ Enwere
et al.
(1999), cf. Hovette
et al
. (1999) for recent research on the malaria–tuberculosis interaction.

⁷⁷ Baccelli (1881: 165–6).

⁷⁸ Whittle
et al
. (1984).

⁷⁹ Marchiafava and Bignami (1894: 120–1); Roy
et al
. (2000).

140

Demography of malaria

leads to an increased prevalence and severity of malaria in semi-immune adults’.⁸⁰

Since the evidence of Galen and Asclepiades suggests that malaria was common in imperial Rome (see Ch. 8 below), the balance of probability in the light of modern medical research is that malaria dominated the mortality regime of the population in at least some districts of the city, just as it did in Grosseto, and in the surrounding countryside, even if a large majority of all deaths might have appeared to doctors in antiquity to be the result of other diseases. In the same way, when Corvisier observes that ‘fever’

(puretÎß) can only be directly connected to malaria in a small proportion of the cases in the Hippocratic
Epidemics
, this is only to be expected under the conditions of endemic malaria, and should not be taken to minimize its importance.⁸¹ The paradoxical yet logical conclusion of modern research is that ‘in very highly endemic centres the amount of sickness [sc. in adults] is greatly
reduced
in comparison with epidemic areas’, because acute illness is concentrated in infants and children.⁸² Nevertheless very highly endemic centres have higher overall mortality (including adult mortality) than areas where malaria has an epidemic character, never mind areas where it does not occur at all. Of course it is quite possible to have excess seasonal mortality patterns without the presence of malaria, but under those circumstances overall mortality for the whole population is lower, as the example of Florence shows.

5. 3 M   

The effects of malaria in antiquity were probably, in their turn, exacerbated by the moderate degree of chronic malnutrition that was arguably endemic among the masses in most if not all ancient populations. If the recent trend towards increasing average height in the populations of modern developed countries is to be attributed to improved nutrition, as seems to be the case, then it is an inevitable conclusion that malnutrition was endemic in historical populations. Specifically in the case of ancient Rome, preliminary reports of research on the skeletal population from Vallerano near ⁸⁰ Whitworth
et al
. (2000).

⁸¹ Corvisier (1994: 305–8); contrast Grmek and Gourevitch (1998: 223–5), using the figurines from Smyrna in the Louvre as evidence for virulent
P. falciparum
malaria in the Hellenistic period.

⁸² Hackett (1937: 174).

Demography of malaria

141

Rome, dating to the second century , have revealed a significant frequency of porotic hyperostosis attributed to iron-deficiency anaemia. Together with palaeodemographic evidence for low life expectancy (unreliable in detail, yet probably still reasonably accurate in respect of the overall impression given), and better-known literary evidence such as Soranus’ comments on the frequency of rickets in the city of Rome (caused by vitamin-D deficiency), it suggests a rather low standard of life in the suburbs of Rome itself with repeated infections and widespread chronic malnutrition, especially of infants and children. Such problems continued, inci-dentally, throughout the history of the city of Rome. The explanation of Soranus’ evidence was provided by Lapi in the eighteenth century. He admitted that rickets was common in Rome in his own time, even though he argued that Rome was healthier than its reputation suggested. Lapi states that rickets manifested itself in babies in Rome between the ages of nine months and two years. He attributed the prevalence of rickets in Rome to the custom of keeping infants inside rooms, with the unintended consequence that they were never exposed to ultraviolet radiation in sunlight, which converts the sterol 7-dehydrocholesterol in skin into cholecalci-ferol, vitamin D3.⁸³ We may infer that infants were kept indoors because of the widespread fear of ‘bad air’ among the Roman population. Evidently their diet did not include fish-liver oils, the most important potential dietary source of vitamin D, and was inadequate to compensate for the lack of exposure to sunlight, but an inadequate diet was not the only reason for rickets in the Roman population, both ancient and early modern.

Malnutrition of the host adversely affects the parasite as well as the host. At the most extreme level, it has been suggested that severe malaria is rare in children suffering from the worst forms of protein-energy malnutrition, but the most recent research indicates that protein-energy malnutrition is indeed associated with increased morbidity and mortality from malaria.⁸⁴ A considerable body of research has found that deficiencies of several different vitamins reduce the reproduction rate of malarial parasites, leading to lower parasite counts in the blood of patients. For example, a ⁸³ Ricci
et al
. (1995); Soranus,
Gynaecology
2.43–4; Lapi (1749: 75):
il tenere i bambini a marcire nelle camere lontanissimi dal sentire l’alito dell’aria esterna
; Levi (1945: 34, 76) on the association of rickets, general malnutrition, malaria and trachoma in Lucania; Davidson
et al
. (1979: 121–4).

⁸⁴ Shankar (2000) gives a detailed survey of all facets of the malaria-nutrition problem.

142

Demography of malaria

shortage of vitamin E, an antioxidant, predisposes erythrocytes to oxidant-induced premature lysis, rupturing the red blood cells before the parasites have completed their development inside.

Deficiency of vitamin C has been reported to have the same effect in experiments on monkeys. Other experiments have shown that a diet deficient in a nutrient essential for the malaria parasite, para-aminobenzoic acid, suppresses infections of rats with the malaria species
Plasmodium berghei
. Para-aminobenzoic acid is a precursor of the important coenzyme folic acid. It has been suggested that a diet of pure breast milk, which contains a very small proportion of this chemical, may increase resistance to malaria among very young human infants, although there is no experimental proof, and human malaria parasites do appear to have some capacity to produce it themselves. Iron deficiency is inimical to the parasites, although its effects on the chances of the host’s developing malaria are unclear; different studies have yielded conflicting results in both humans and animals. Nevertheless iron supplements to the diet do appear to increase the risk and severity of attacks of malaria.

Studies in India have shown that a deficiency of riboflavin (vitamin B2)
in vivo
results in a reduced parasite reproduction rate. The best sources of riboflavin are milk, eggs, and liver. It is relatively scarce in cereals, especially if they are highly processed.⁸⁵

These are all deficiencies in the diet of the human hosts. Natural selection for resistance to malaria can also favour human genetic mutations that produce an
inherited
reduction in the uptake of essential nutrients, even if the nutrients are abundant in the diet. Some recent research in biochemistry at the hospital in Grosseto has produced very interesting results. It has been shown that there is a high frequency of familial flavin-deficient erythrocytes in Grosseto and in Ferrara in the Po delta (which had endemic malaria in the late medieval and early modern periods), but not in Florence, a city with no history of
P
.
falciparum
malaria. This inherited genetic condition causes a reduced uptake of riboflavin by red blood cells even if it is abundant in the diet. It is a product of natural selection for resistance to malaria under conditions of extreme pressure and illustrates the importance of malaria in the past as an agent of natural selection.⁸⁶

⁸⁵ Das
et al
. (1988), with Davidson
et al
. (1979: 140–2); Gilles and Warrell (1993: 64); Har-El and Chevion (1997); Dobson (1997: 336–8).

⁸⁶ Anderson,
et al
. (1994), cf. Anderson
et al
. (1995).

Demography of malaria

143

Nevertheless, even with the help of this trait conferring a degree of resistance to malaria, life expectancy at birth in Grosseto in the nineteenth century was still only twenty (see Ch. 5. 4 below). In other parts of Italy, especially in the Mezzogiorno, Sicily, and Sardinia, where there was also intense pressure from malaria, other genetic traits conferring degrees of resistance to it attained high frequencies, notably glucose-6-phosphate dehydrogenase (G6PD) deficiency and thalassaemia. Research in Sardinia by Siniscalco and colleagues first provided strong support for Haldane’s hypothesis, proposed in 1949, that heterozygotes for thalassaemia have increased resistance to
P. falciparum
malaria. Although that research was later criticized because of problems concerning the geographical origin of some of the populations of the villages which were studied, the new techniques of molecular biology have not only confirmed Haldane’s idea over the last few years, but have also shown that the statistical correlation between high frequencies of thalassaemia mutations and the presence (past or present) of endemic malaria is valid not just in the Mediterranean, but all over the world wherever
P. falciparum
malaria occurs. Grmek has comprehensively studied the evidence for the history of thalassaemia, G6PD deficiency, and favism (which is associated with G6PD

deficiency) in antiquity.⁸⁷ G6PD deficiency reduces the activity of a gene that plays a critical role in a biochemical cycle that eliminates oxidizing agents from erythrocytes. It is thought, in general terms, that this results in the premature lysis of red blood cells before malaria parasites inside have completed their development, although the precise mechanism remains unclear. Thalassaemia (predominantly b-thalassaemia in Mediterranean populations) is caused by mutations in the globin genes which lead to an imbalance in the correct synthesis of the a-and b-globin chains of the haemoglobin molecule. Malarial parasites digest haemoglobin to obtain amino acids for protein synthesis.

Thalassaemia and G6PD deficiency are very common in the modern populations of areas in the Mediterranean which were colonized by Greeks and Phoenicians in antiquity. They also occur ⁸⁷ Siniscalco
et al
. (1961); Weatherall (1997), Grmek (1983: 355–407), Ruwende and Hill (1998), Astolfi
et al
. (1999), and Vezzoso (1946) on thalassaemia; Greene and Danubio (1997) and Battin (1998) on G6PD deficiency. Lieber (1973) suggested that the Pythagorean communities in the cities of Magna Graecia arose from ‘a society of favism sufferers’. This hypothesis is not impossible, but cannot be proved or disproved given the lack of contemporary evidence for the origin of these communities.