Malaria and Rome: A History of Malaria in Ancient Italy (25 page)

It is interesting to go beyond statistics such as those from Grosseto in the nineteenth century to examine in more detail exactly how malaria interacts with other diseases, especially the gastro-intestinal diseases and the respiratory infections which were assigned the primary role in excess seasonal mortality in Rome in the fourth century  by Shaw. Interactions between different species of pathogens can be synergistic, antagonistic, or neutral in terms, first, of their effects on each other and, secondly, of their effects on the human host. It is also possible, for example, that a human genetic mutation which confers a degree of resistance to one pathogen might also make the host more susceptible to another pathogen at the same time. An example of an antagonistic interaction between two pathogens is that between malaria and syphilis (see Ch. 2 above). The sequencing of the entire syphilis genome has shown that the syphilis spirochaete (
Treponema pallidum
) cannot tolerate the intense body temperatures generated during malarial fevers because it lacks a factor responsible for transcription of heat-shock proteins in other bacteria and so cannot respond to heat shock.²⁶ The interaction between malaria and syphilis was artificially created in hospitals in Europe and North America as a treatment for syphilis in the central nervous system before the development of drugs against syphilis. However, it is probably not very important in nature, so to speak, in regions with endemic ²⁵ Fracastoro (1530),
syphilis. sive morbus Gallicus
2.81–3:
In primis ego non omni te assuescere coelo
|
Exhorter: fuge, perpetuo quod flatur ab Austro,
|
Quod coeno, immundaeque grave est sudore paludis
.

²⁶ Fraser
et al
. (1998).

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Demography of malaria

malaria, since syphilis is predominantly a sexually transmitted disease (although congenital transmission through the placenta also occurs) affecting mainly adults. In holoendemic regions people develop acquired immunity to malaria in infancy and childhood and consequently do not have severe malarial fevers during the years of sexual maturity when they are most likely to encounter syphilis. Whether or not syphilis existed in pre-Columbian Europe is a controversial question which need not be considered here.

A possible example of a ‘neutral’ interaction, according to the perceptions of contemporary observers, was that between malaria and smallpox in early modern Rome. Lapi wrote that if women with tertian fevers touched or suckled children with smallpox they were liable to develop the relatively mild discrete form of smallpox (rather than the more dangerous confluent form). He maintained that in such cases the two different diseases would run their courses separately without getting confused with each other. Although Lapi seemed to believe that the two diseases were not interacting with each other, it is possible that what happened is that malaria depressed the immune systems of the women to the extent that they could develop secondary infections of smallpox (presumably following earlier primary attacks in their own childhood which generally conferred immunity).²⁷ Since smallpox certainly arrived in Italy during the Antonine ‘plague’ in the second century , if it was not present earlier, this interaction was possible from then onwards.²⁸ The focus of the rest of this section will be on definite synergistic interactions between malaria and other pathogens which endanger humans.

The gastro-intestinal diseases were indeed major causes of infant and child mortality in historical populations. In ancient Rome Celsus observed that most of the victims of diarrhoea and dysentery were children up to the age of ten.²⁹ However, the first point that needs to be made is that in European history populations with endemic malaria had higher overall mortality than populations with no experience of malaria (detailed demographic analysis in Ch. 5. 4 below). This can readily be seen by comparing the population of Florence in the thirteenth to fifteenth centuries with ²⁷ Lapi (1749: 48); Fenner
et al
. (1988: 51–2) on secondary smallpox infections. Endemic smallpox was finally eliminated from Italy in 1947.

²⁸ Duncan-Jones (1996) discussed the Antonine ‘plague’.

²⁹ Celsus 2.8.30.

Demography of malaria

125

nineteenth-century Grosseto. In Florence, which had no history of endemic malaria, gastro-intestinal diseases, operating principally from July to September inclusive, were indeed the leading cause of infant deaths (outside years of epidemics of bubonic plague), the sort of pattern noted by Shaw. In spite of the effects of gastro-intestinal diseases on children, Herlihy and Klapisch-Zuber reached the conclusion that the average duration of life in Florence in the period in question was as high as forty, if years of major plague epidemics are excluded from consideration.³⁰ In contrast, life expectancy at birth in Grosseto much more recently was only twenty. This comparison shows that children assaulted by gastro-intestinal diseases alone have better survival chances than when malaria is present as well. It is also important to note that infant mortality is virtually unrepresented in the funerary inscriptions from the city of Rome in the fourth century  used by Shaw. Since direct mortality from
P. falciparum
malaria principally falls on infants and children where it is endemic, the bulk of its effects in terms of seasonal mortality would not be expected to be visible in those inscriptions in any case.

How does malaria exacerbate the effects of gastro-intestinal infections?
P. vivax
and
P. malariae
undergo the process of schizogony in erythrocytes in the peripheral blood vessels of the human body, but
P. falciparum
merozoites export proteins to the surface of infected erythrocytes which make them adhere to the capillaries of internal organs. Fixation inside internal organs in this way enables the
P. falciparum
parasites to undergo schizogony under a lower oxygen tension, which favours this process in this particular species of malaria. The most severely affected internal organs are the brain (causing cerebral malaria), the kidneys and the heart and the liver, and (most importantly for the discussion at this point), the placenta in pregnant women (especially primigravidae), in whom any acquired immunity to
P. falciparum
malaria tends to break down in the second and third trimesters. Lancisi noted that women were particularly badly affected during the malaria epidemic in Rome in  1695.³¹ In tropical Africa pregnant women are bitten twice as frequently as non-pregnant women by the mosquito
Anopheles ³⁰ Herlihy and Klapisch-Zuber (1985: 83–4, 276–9). They refrained from constructing life tables for the population of Florence for reasons which will be considered in Chapter 11

below.

³¹ Lancisi (1717: 210–11).

126

Demography of malaria

gambiae
, increasing their chances of being infected by malaria, perhaps because pregnant women produce a larger volume of exhaled breath on average.³² Since mosquitoes are generally believed to locate their prey by detecting chemicals emitted in human breath, European vectors of malaria may also have responded in a similar way to pregnant women in the past (although it is also possible that mosquitoes detect chemicals in human sweat). A new idea which is currently attracting attention among researchers in medicine is that placental malaria is caused by a specific population (or set of haploid clones) of
P. falciparum
with a special affinity for certain chemical receptors generally found only or predominantly in the placentae of pregnant women.³³ The presence of large numbers of plasmodia in the placenta frequently causes miscarriages in non-immune women, or fetal anaemia and intrauterine growth retard-ation in women with some degree of immunity, leading to low birthweight infants who are particularly susceptible to diseases in general and gastro-intestinal infections in particular. Desowitz, a specialist in tropical diseases, put it as follows:

The babies that are born to the malarious usually have a birth weight 200

grams or more below normal. A low-birth-weight baby who doesn’t ‘catch up’ has a puny immune system, and these children frequently die during childhood of all sorts of infections. The death certificate . . . may read diarrhoea or pneumonia, but the real cause of death was malaria of the mother.³⁴

This is how malaria can enormously exacerbate the effects of gastro-intestinal diseases on infant and child mortality without even being present in the children. Average birth weight of infants in fact increased significantly in areas of former malaria endemicity following modern eradication campaigns. Maternal infections with P. vivax
may possibly reduce the severity of subsequent infections with
P. falciparum
during pregnancy, owing to immunological cross-reactions, but
P. vivax
itself causes birthweight reduction in all pregnancies, not just in primigravidae, in areas with endemic malaria. It has been estimated that up to 50% of low-birth-weight babies in some populations in tropical countries may be caused by ³² Lindsay
et al
. (2000).

³³ McFalls and McFalls (1984: 101, 107–8); Fried and Duffy (1996), discussed by Matteelli et al
. (1997); Marchiafava (1931: 50–1) on placental malaria in Italy; Gilles and Warrell (1993: 46); Reuben (1993); Fried
et al
. (1998).

³⁴ Desowitz (1992: 118); Brabin (1992); Newby and Lovel (1995); and Brabin
et al
. (1996).

Demography of malaria

127

maternal malaria.³⁵ In Sardinia, in areas where the transmission rate of
P. falciparum
malaria was extremely high, fertility rates were higher than in areas where the transmission rate was lower. This proves a degree of adaptation by women to intense malaria, as a result of both acquired and inherited immunity (e.g. thalassaemia and glucose-6-phosphate dehydrogenase deficiency in Sardinia), but it has to be remembered that overall mortality was much higher and life expectancy much lower in the areas with a very high transmission rate. Higher fertility was required to balance higher mortality. Even with such increments in fertility, the mortality profile of populations exposed to endemic malaria was extremely poor.³⁶

Besides the indirect effects on infants caused by maternal infection,
P. falciparum
malaria can also be present in infants and children themselves alongside gastro-intestinal infections. In Macedonia during the First World War it was observed that malarial infections readily coexist with typhoid fever, paratyphoid fever, and amoebic dysentery, for example. Of particular interest is the observation that when patients in Macedonia were infected with both typhoid fever and
P. falciparum
malaria, as was proved by examination of blood smears for malaria and microbiological techniques for typhoid fever, the clinical symptoms observed were principally those of typhoid fever. The implication of this with regard to ancient sources is that cases, for example in the books of
Epidemics in the Hippocratic corpus, which look like cases of typhoid fever, could very easily have been infected with malaria as well, but this would not be apparent from the description given in the ancient text. Such dual infections are very likely to happen in areas where malaria is endemic. Malaria may also directly interact with gastro-intestinal infections, since there is some evidence that malaria suppresses the immune response to typhoid fever and other types of salmonella.³⁷ Malarial fevers do in any case strongly resemble the ³⁵ I. A. McGregor in Wernsdorfer and McGregor (1988: i. 757); Brabin and Piper (1997); Nosten
et al
. (1999) on
P. vivax
.

³⁶ Zei
et al
. (1990) observed that placental malaria is in fact more severe in women in areas of low transmission (and so less acquired/innate immunity) than in areas of high transmission (and so a higher degree of immunity).

³⁷ Armand-Delille
et al
. (1918: 79). Corvisier (1985: 117) lists six probable cases of typhoid fever in the Hippocratic
Epidemics
; Mabey
et al
. (1987). Urban
et al
. (1999) described one mechanism by means of which
P. falciparum
suppresses the human immune response to infection. Faccini (1984) discussed typhoid fever in early modern Italy.

128

Demography of malaria

fever of typhoid in the early stages of infection, before the classic periodicity is established (if it is established), but usually without the severe gastro-intestinal symptoms of typhoid fever. Before the true aetiology of malaria was established, this similarity between
P. falciparum
malaria and typhoid fever led many doctors to assimilate the two in the form of a syndrome, called
typhomalarial fever
, whose reality is no longer accepted by modern doctors. The similarity was noted in Rome, too. Baccelli stated that the malaria of Rome frequently took the form of what he called a
subcontinua tifoide
.³⁸ He reckoned that Lancisi had observed the same form of the disease in the Trastevere district of Rome during the great epidemic in 1695.³⁹ This was the most dangerous type of malaria for Baccelli.

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).