²⁷ Grmek (1983: 402).
²⁸ Covel and Nicol (1951), reviewed more recently by Gravenor et al. (1995). Andrew Read pointed out the last reference to the author.
²⁹ Cohen (1983: 28), citing other literature.
36
Evolution of malaria
spreading with humans across the savannah grasslands in what is now the Sahara during the mid-Holocene climatic optimum would first have encountered A. labranchiae in North Africa rather than Italy, the balance of probability is that North Africa is where the ‘European’ strains of P. falciparum malaria evolved. Malaria evolution in North Africa would not have been subject to the constraints of the European climate during the glacial periods. Consequently the argument from mosquito refractoriness is as unconvincing as the other arguments used to support late-introduction theories.
Moreover when the mid-Holocene climatic optimum ended,
populations of P. falciparum in North Africa would have become isolated from the populations in central Africa. The occurrence of evolution in isolated populations is a standard scenario frequently invoked in theories of evolutionary biology. Today the leading edge of the evolution of drug resistance by malaria is in south-east Asia, a geographical area very far removed from the heartland of P. falciparum in tropical Africa.
Grmek identified the disease which afflicted the Athenians camped outside Syracuse in Sicily in 413 , described by Thucydides, as most probably P. falciparum malaria.³⁰ He gave a cogent explanation of the role of malaria in the Syracusan military strategy against the Athenian forces. Unfortunately it is generally ignored by mainstream ancient historians. Grmek argued that the Syracusan generals deliberately confined the Athenian forces to an area which they knew was unhealthy and then waited to let malaria do their work for them. He also discussed the possibility that P. falciparum malaria was a new disease then because it took an epidemic form, attacking large numbers of adults (the Athenian soldiers and their allies), who evidently did not have acquired immunity to it and so presumably had not previously experienced it in childhood. This idea may seem plausible, but yet again the most recent scientific research casts doubt on it, even though it is true that in areas where malaria is hyperendemic, as it certainly has been in many places in Tuscany and Latium in recent times, virtually everyone is infected in early childhood. With constant reinfections in childhood acquired immunity develops, with the result that adults seldom have acute attacks of fever and may not appear to have any parasites in their blood upon microscopic examination. There is still ³⁰ Grmek (1979: 150–61), cf. the non-committal opinion of Villard (1994).
Evolution of malaria
37
some experimental support for the older view that acquired immunity to malaria is short-lived and requires constant reinfection under holoendemic conditions to maintain it. However, the new techniques introduced into molecular biology in the last few years (the polymerase chain reaction (PCR); analysis of microsatellites; analysis of restriction fragment length polymorphisms (RFLP) of DNA) have produced new evidence which sheds further light on the situation.
P. falciparum displays a great deal of genetic variation. All the various stages of development in humans are haploid clones, but in the gut of mosquitoes diploid zygotes are formed, as mixtures of different clones of parasites mate. Recombination of genetic material during meiosis in heterozygotes then yields new genotypes of parasite. Experiments have shown that the extent of recombination in genes coding for cell-surface proteins exported by parasites to the surface of erythrocytes is very considerable. Moreover the genetic diversity generated in this way may date back millions of years, at least partially antedating the split between P. falciparum and the chimpanzee malaria parasite P. reichenowi.³¹ With the mosquito as a secondary host, malaria parasites have access to the evolutionary benefits of sexual reproduction (i.e. the capacity to generate genetic variation to give them the ability to meet new challenges in their environment, e.g. variations in their host’s immune response, new drugs used by modern doctors, etc.). PCR
amplification of VNTR (variable number tandem repeat)
sequences of DNA has shown that most individual cases of malaria in tropical countries today are infected with between two and six different haploid clones at the same time. The larger the number of haploid clones in a mosquito’s blood meal, the greater the degree of recombination that is likely to occur. Much earlier, Marchiafava had already reached the conclusion, from examination of parasites visible under the microscope in blood smears, that it was usual for patients in Rome to be infected with at least two different generations of parasites simultaneously. This explains why quotidian fevers, not tertian fevers, were the norm in cases of P. falciparum ³¹ Conway et al. (1999) found evidence for a high recombination rate in the merozoite surface protein 3 gene coding for a cell-surface protein involved in immunological interactions; Hughes (1993), Taylor et al. (2000), Ayala and Rich (2000), and Okenu et al. (2000) on the antiquity of such polymorphisms; it is the subject of current controversy. Some scientists maintain that genetic polymorphism in P. falciparum is primarily generated by mitotic recombination rather than meiotic recombination.
38
Evolution of malaria
malaria in Rome both in the nineteenth century and in antiquity.
There is now some evidence that acquired immunity to P. falciparum is clone-specific. Differential expression of surface antigens in erythrocytes is controlled by the recently discovered family of var genes. Successful reinfection only occurs when a new
