However, even if this were the case, it would not prove that P. falciparum was a newcomer in classical times. Since the new data for its remains from Akhziv in Israel. For hippopotamus and papyrus in the region see Sallares (1991: 26, 370, 400–2). Theophrastus, HP 9.7.1–2 also mentioned the marshes.
²² Hershkovitz et al. (1991).
²³ Ramsdale and Coluzzi (1975); Zulueta, Ramsdale, and Coluzzi (1975). Earlier experiments at Horton Hospital in England had shown that the English malaria vector A. atroparvus is similarly unable to transmit tropical African strains of P. falciparum, although it can transmit Italian strains of P. falciparum. However, it could transmit all strains of P. vivax that were tested, although it is very inefficient at transmitting P. malariae (Shute (1940) and (1951)).
²⁴ Zulueta (1973), (1987), and (1994).
34
Evolution of malaria
presence in Egypt in the fourth millennium suggest that P. falciparum was already present in the Mediterranean world thousands of years before classical times, a long period of time was indeed available for the refractoriness of European species of mosquitoes to be overcome. Moreover the experiments yielded no information about the critical factor of the length of time required for refractoriness to be overcome. It is not clear at the moment whether in this particular case overcoming refractoriness required evolution in the mosquito, evolution in the malaria parasite, or coevolution.
Mosquitoes certainly have several defence mechanisms against intruding foreign bodies in general, and may have genes that specifically respond to invasion by malarial parasites. Melanotic encapsulation or melanization is the most well known of these processes. This process is employed by mosquitoes and other insects to surround and inactivate pathogens. A thick layer of melanin is deposited around the malaria parasite when it tries to cross the mid-gut epithelium of the mosquito, en route to the salivary glands for the formation of sporozoites for transmission to another human. Cross-breeding experiments suggest that it is under fairly simple genetic control (no more than about three major loci being involved), with the implication that the expression of the process of melanotic encapsulation can be increased or diminished rapidly in mosquitoes.²⁵
However, there is the complication in the Mediterranean case that the mosquitoes, which transmitted Mediterranean strains of P. falciparum in the past, are refractory to modern tropical strains, as has just been seen. This suggests that differences between various strains of P. falciparum were also important in some as yet un-defined way. Evolutionary processes tend to be very rapid among micro-organisms and, as will be seen shortly, P. falciparum has the capacity for very rapid genetic change. If it did not exist in the western hemisphere before Columbus, several species of mosquito indigenous to the western hemisphere quickly became effective vectors of P. falciparum, a pathogen which they had never encountered before 1492. The failure of Amerindian populations to develop high frequencies of any of the wide range of genetic mutations that confer degrees of resistance to P. falciparum malaria in ²⁵ Lombardi et al. (1986); Collins et al. (1986); Richman and Kafatos (1996); Yan et al.
(1997); Zheng et al. (1997); Billker et al. (1998); Feldman et al. (1998); Paskewitz and Gorman (1999); Barillas-Mury et al. (2000); Oduol et al. (2000).
Evolution of malaria
35
many Old World human populations suggests that they have only recently been exposed to it.²⁶ Grmek rightly observed that the different responses of European mosquitoes to strains of parasite from different geographical areas in fact suggest a long period of separation between the tropical and the subtropical/temperate strains of P. falciparum.²⁷ The experiments at Horton Hospital in England suggested that Italian strains of P. falciparum from Sardinia and Salerno were more severe and more virulent and exhibited a faster growth rate than strains originating in tropical countries (with the proviso that the sample sizes in these experiments were small).²⁸
A faster progression of the infection on the part of European strains of P. falciparum might well have been an evolutionary adaptation to the shortness of the season each year that was suitable for its reproduction because of the climatic constraints in Europe.
Another crucial argument is that since the western Mediterranean mosquito vector-species A. labranchiae is common in North Africa, which in fact is its main area of distribution, as well as in Italy, while A. sacharovi, the second major Mediterranean vector with a more easterly distribution, also occurs in the Near East as well as in Greece, P. falciparum had every opportunity to evolve adaptation to its European vectors in Africa and in the Near East before even arriving in Europe. The nature of P. falciparum malaria in North Africa in the past is an important unresolved question.
The French colonists in North Africa in the nineteenth century had severe problems with malaria. Of course it was in North Africa that Alphonse Laveran discovered malarial parasites, at the hospital in Constantine in 1880. In 1832–3 two earlier French army doctors, Antonini and Maillot, working at the hospital of Bône in Algeria, found that giving high doses of quinine and a generous diet and ending the practice of bleeding reduced
