Chimpanzees
Tertian
P. berghei
Rodents
Quotidian ?
P. chabaudi
Rodents
Quotidian ?
P. girardi
Lemurs
Quartan
P. sandoshami
Colugo
Quartan
P. traguli
Mouse deer
?
P. bubalis
Water buffalo
Quartan
P. atheruri
Porcupines
Quotidian
P. voltaicum
Bats
?
P. relictum
Birds
36 hourly
P. subpraecox
Owls
Quotidian
P. cathemerium
Birds
Quotidian
P. matutinum
Birds
Quotidian
P. giovannolai
Birds
Quotidian
P. gallinaceum
Birds
36 hourly
P. circumflexum
Birds
Tertian
P. lophurae
Birds
Quotidian
P. pinottii
Birds
Quotidian
P. rouxi
Birds
Quotidian
P. elongatum
Birds
Quotidian
P. floridense
Lizards
?
P. mexicanum
Lizards
?
P. wenyoni
Snakes
?
Source: Garnham (1966). There are numerous other species infecting mammals, birds and reptiles belonging to other genera which are closely related to Plasmodium but differ from it in that they are transmitted by vectors other than mosquitoes and in that schizogony does not occur in erythrocytes.
Types of malaria
9
apostrophe that indicated its original meaning was Francesco Puccinotti’s book Storia delle febbri intermittenti di Roma, published in Naples in 1838, although Guido Baccelli’s book La malaria di Roma, published just two years before Laveran’s discoveries, was the first work to apply it to the disease.⁴ The word malaria was introduced into English literature by Horace Walpole in 1740. He made his exit from Rome just before the annual epidemic of P. falciparum malaria started. The English traveller did not expect to be able to get a Christian burial if he died from malaria in Catholic Rome!
You will wonder, my dear Hal, to find me on the road from Rome: why, intend I did to stay for a new popedom, but the old eminences are cross and obstinate, and will not choose one, the Holy Ghost does not know when. There is a horrid thing called the malaria, that comes to Rome every summer, and kills one, and I did not care for being killed so far from Christian burial.⁵
Today there are known to be four species of human malaria belonging to the genus Plasmodium: P. falciparum (malignant tertian), P. vivax (benign tertian), P. malariae (quartan), and P. ovale. P. ovale, a fairly mild type of malaria, was not endemic in Mediterranean countries. Consequently only the first three species will be considered here.⁶ Their common names, such as tertian and quartan fever, are no longer used in modern medical literature, but of course are found in historical sources. All three species generate a variety of clinical symptoms and syndromes, many of which can also be produced by other diseases.⁷ Malaria can easily mimic typhoid fever, hepatitis A, or influenza, for example. It is above all ⁴ Corbellini and Merzagora (1998: 53–4). Baccelli’s work was reprinted in Monografia (1881).
⁵ Letters of Horace Walpole, ed. C. D. Yonge (1889), i. 20, ‘to the Hon. H.S. Conway’, 5 July 1740.
⁶ Garnham (1966: 217) recorded an isolated case of P. ovale malaria in Epirus in Greece.
Qari et al. (1993) identified a new human malaria parasite morphologically similar to P. vivax, but with the same circumsporozoite protein as the monkey parasite P. simiovale, which they termed ‘ P. vivax-like’. Since it occurs in Papua New Guinea (besides Indonesia, Madagascar, and Brazil), where there are no monkeys, it appears to be established now in human populations, although it doubtless arose as a zoonosis, cf. Escalante et al. (1995). Since there is no evidence for its occurrence in Mediterranean countries it is not relevant for current purposes. Other species of malaria which typically infect primates other than man may occasionally cause zoonoses in humans (Fiennes (1967: 70–5) ).
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 import
ant 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).
¹⁶ Celsus, de medicina 3.3.2: 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 autem et octo horis fere triginta et Types of malaria
15
In a later passage, Celsus confirms that the pernicious semitertian fevers were frequently fatal. He ascribed that outcome to mistakes made by doctors, unintentionally suggesting that treatment may often have been worse than no treatment at all.¹⁷ This point of view was explicitly enunciated, in relation to all diseases occurring in Italy, by Latanzio Magiotti, physician to the court of the Grand Duke of Florence in the seventeenth century . Celsus himself recommended blood letting at the beginning of treatment. This is unlikely to have been beneficial to patients with the anaemias typically associated with malaria.¹⁸ Moreover tools used for bleeding could conceivably themselves have been a source of transmission of malaria via contaminated blood, if they were not cleaned thoroughly after each use. The elder Cato’s denunciation of Greek medicine as worthless was probably well founded in practice, especially in relation to malaria, however interesting the Hippocratic approach to medicine may be to modern historians of medicine, although many treatments could have worked as placebos.¹⁹
Malaria and Rome: A History of Malaria in Ancient Italy Page 3
