INTERNATIONALJOURNAL OF ANTHROPOLOGY

L. Capasso

Vol. 13 - N. 3 - 4 (165-175) - 1998

The origin of human malaria

Dipartimento di Antropologia,
Universitgl degli Studi di Chieti,
Chieti, Italia

Introduction
"Do not get out the house after sunset during the weeks following the flooding". The
advise is given in a hyeroglyphic in the temple of Denderah, in Egypt. To my knowledge, this
is the most ancient written document of anti-malaric prophylaxis.
The history of human malaria is certainly very ancient, so ancient that the study of written
documents does not allow to approach the origin of the disease. In fact, malaria did certainly
originate prior to writing and it is very probable that some form of malaria was already present
in the ancestors of the genus Homo.
The plasmodia presently causing malaria are nothing more than descendants of ancient
endocellular protozoic parasites of the intestinal tract of a common ancestor of reptiles,
amphibians and birds, all presently infected by some type of plasmodia (Figure 1). These
endocellular parasites "arose from a free-living form, for it is normal for the phagocytic cells
of the host to engulf invaders, and some of these that find themselves inside the phagocyte
might be preadapted to survive there. That such a proceeding is not too uncommon is well
demonstrated by the numerous bacilla that can survive in this fashion, including the tubercle
bacillus, the meninogococcus, and the gonococcus" (Cockburn, 1963).
Having become endocellular parasites, the ancestors of present day plasmodia developed
the ability to be transported from intestinal to hepatic cells via the portal circulation (Figure 1).
Thus the protozoal parasite, having completed its vital cycle within hepatic cells, could have
been released into the host's bloodstream, from where it might have been retrieved by a
bloodsucking arthropod and later reinjected in the blood stream of a new host.
This cycle probably developed millions of years before the first Primates ever appeared
on earth.
Cockburn's theory on the parallel host-parasite evolution (Cockburn, 1963), together with
the evidence that the oldest fossil mosquitoes date back to the time when the first Primates
began their evolution (Lower Tertiary Period), may allow to conclude that "the early ancestral
Primate was already infected with malaria parasites when it first separated from other animals
millions of years ago: subsequently, as the various Primate stocks split off', the parasites would
accompany them and vary in parallel with their hosts. Man is quite a newcomer on earth, so

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that his parasites would have had less time to evolve separate features than those parasites of
the lower Primates, so that his plasmodia would resemble closely those of the other higher
Primates. Furthermore, he appeared in Africa alongside many other Primates, occupying much
the same habitat as they did, especially the baboons which he hunted. Therefore, there would
be a continual interchange of parasites between the various species of Primate and man that
would prevent the selection of distinctive strains of Plasmodium. In his later travels over the
world, he would occupy territories with monkeys and apes other than those found in Africa,
and some places with no Primates at all, and the scene would be set for speciation by Plasmodium
and the appearance of the forms of human malaria paraside known to us today".
Obviously, it is difficult to found direct evidences of the most ancient phases of the history
of malaria. However, some informations can be gained from studies of comparative pathology
and from the analysis of fossil mosquitoes.

Figure 1 - Possible origin of plasmodia causing malaria in the first Primates from a free living protozoon.

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Comparative pathology
Altogether, plasmodia are parasites which are very diffuse among extant Primates. Several
species of simian plasmodia have been identified: all cause similar diseases wich are also
closely related to human malaria.
The clinical characteristics common to all forms of primate malaria are two, namely fever
and splenomegaly; but infection may also occurr in an asymptomatic form.
For these reasons, malaria - - in its various forms - - may be considered a typical disease
of Primates, maintained by specific intermediate hosts, namely mosquitoes of the genus

Anopheles.
Various types of plasmodia have been identified in the main genera of extant Primates. It
is of interest to note that some of these may cause disease in different Primate species (Capasso,
1987). For example, the african chimpanzee is frequently infected by Plasmodium malariae
which can be transmitted to humans, causing a form of malaria (Figure 2). Several malaysian
Primates are affected by malaric fever caused by distinct types of Plasmodiun cynomolgi. It
has been proved (Clarck, 1930) that these plasmodia may sporadically infect humans, causing
a form of malaria similar to benign terzana fever (Figure 2).
Plasmodium infections axe also diffuse among non-human american Primates. For example,
Plasmodium brasilianum is the usual parasite of several species of monkeys and it has been
proved that it may passed to humans by mosquitoes and cause a quaternary type fever (Figure
2).
The bulk of data indicates that plasmodia diffused among Primates since a very distant
past. In favour of this idea is the fact that malaric infections are generally well tolerated by
Primates, with one exception: human malaria caused by Plasmodiumfalciparum. In fact, this
is a very serious disease, but it represents an exception among infections caused by plasmodia
(Capasso, 1987).
It would therefore appear that a sort of equilibrium, through a negative selection of more
reactive hosts and of more virulent parasites resulted from a long contact between host and
parasite (Kim, 1985).
On the other hand, it should be considered that the intermediate arthropod hosts move
freely and permit the circulation of plasmodia among distant populations of non-human and
human Primates, thus allowing the development of crossed immunities, which may slowly
decrease the virulence of the parasites (Lambrecht, 1967). An epidemiologic equilibrium has
not yet been reached. However, it is well known that human populations developed a type of
genetic resistance to Plasmodiumfalciparum infection based on the maintainance of genetic
polymorphysms of the globin genes. In the case of human malaria caused by Plasmodium
falciparum, sickle cell anemia and the thalassemias, such as genetic hemoglobinopathies, result
in conditions which are very unfavourable to life for plasmodia within erythrocytes.
It is universally accepted that the high incidence of heterozygotic gons sickle cell trait
(which is present in up to 40% of the population in some african regions) resulted from the
selective pressure of endemic plasmodial infections (Lambrecht, 1967).
This supports the view that Plasmodium falciparum has been in contact with humans
since a very long time, a period of time sufficient to allow the diffusion of the genetic mutations

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linked to hemoglobinopathies (Capasso and Di Tota, 1990).

Man is not the only mammal which may be infected by Plasmadium falciparum. This
species of plasmodium has been isolated from the blood of gorilla and chimpanzee, in which
infection results in a mild disease associated with splenomegaly (Figure 2). This would suggest
Plasmodiurn

Plasmodiuln

brasilianum

Plasmodiurn

cynornolgi

malariae

Plasmodium

falciparurn

Figure 2 - Species of extant plasmodia infecting both humans and Primates.

that Plasmodium falciparum has been in contact with these Primates species since a very
distant past, which would have resulted in the acquisition of a certain degree of resistance to
the infection (Capasso, 1991).
Now, the question is: in which occasion Plasmodium falciparum passed from its wild
resewoirs to humans? All authors agree that this occurred with the introduction of agriculture
and of sedentary life habits (Brothwell, 1967). Apart from the change of habitat, these are
other reasons which support a link between malaria and agriculture. For example, the clearing
of forests in East Africa probably facilitated the development of endemic malaria, allowing

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169

the proliferation of mosquitoes not adapted to life in wooded ares (Brothwell, 1967). According
to this opinion, mosquitoes representing intermediate hosts quickly adapted to the new ecologic
niche rich in marshy wathers resulting from human activity (Figure 3). Thus some mosquito
species abandoned the humid underwoods and started to reproduce in wathers near villages,
which in turn allowed inter human circulation, excluding hosts in woods, represented by wild
Primates. These non-human Primates only minimally consewed their primordial role of
reservoirs of human malaria after the introduction of agriculture, as presently documented by
the sporadic occurrence of human infections caused by simian protozoa (such as Plasmodium
brasilianum, Plasmodium simium and Plasmdium cynomolgi).

Figure 3 - Plasmodium vivax, Plasmodium malariae, and PIasmodium ovale probably represent species
which coevolved with humans and with the Primate ancestor of man, infecting the ancestor of our
species during the hunters-gatherers phase (group A). Plasmodiumfalciparum, on the contrary, infected
our species more recently, possibly from wind primate resorvoirs, during the acquisition of sedentary
habits and agricolmreal technologies (group B).
On the basis of the comparative pathology, we could therefore conclude that:
1) Malaria coexisted with our species since a very distant past and also appears to be an
infection of very remote origin in non-human Primates.
2) Several species of plasmodia reached a state of equilibrium with humans, so that
infections from these species cause relatively mild forms of disease. It is also possible that
some infections may not result in disease.

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3) The selective pressure of Plasmodiumfalciparum maintained a high frequency of genetic

hemoglobinopathies in human populations exposed to the infection.
4) The clearing of forests and agriculture probably caused an extensive contact between
man and Plasmodiumfalciparum, which was already endemic in the large african anthropoids
(gorilla and chimpanzee).

Fossil mosquitoes
Indirect informations on the history of malaria can be deduced from the study of fossil
mosquitoes. Fossil mosquitoes have been discovered in several geological formations from
various parts of the world (Edwards, 1923). Thousands of specimens of Eocene fossil
mosquitoes have been discovered at some sites, in particular the limestones of the Green River
Formation in Colorado (Grande, 1980). The majority of these fossils can be assigned to the
genus Culex (Cockerell, 1916; 1920), which is nowdays responsible for plasmodial infections
of birds. Instead, the mosquitoes responsible for trasmission of Primate plasmodia pertain to
the genus Anopheles.
Mosquito fossils of the Anopheles genus are restricted to the Old World (Krumbiegel,
1959). It is possible that these fossil forms, structurally similar to extant forms, were already
able to transmitt malarial plasmodia to mammals of the Old World, Primates included, as far
back as the Lower Terziary. The scarcity of fossil forms of the Anopheles genus in Tertiary
sediments and the vast diffusion of plasmodia in present day vertebrates, lead us to suppose
that, during the Lower Terziary, the circulation of these pathogens occurred via some other
genus of mosquito. The probable candidate is the Culex genus (Capasso, 1991), which appeared
at the beginning of the Tertiary with a variety of species and territorial diffusion indicating that
its evolutionary history was already very old (Edwards, 1923). Mosquitoes of the Culex genus
may have played a fundamental role in the transmission of malaria to Mesozoic ancestors of
Primates. It was only later, during the Tertiary Era, that the circulation of plasmodia among
Primates was assured by the Anopheles genus mosquitoes (Capasso, 1991).
The absence of Anopheles fossils in Tertiary sediments of the New World assumes a
particular palaeontological significance because this is associated with a great abundance of
fossils of the Culex genus (both in number of specimens and in number of species). This leads
to suppose that the plasmodia which are typical of present day Primates evolved during the
Tertiary Era in the Old World, where they circulated by means of mosquitoes of the Anopheles
genus. This could not have occurred in the New World in absence of Anopheles mosquitoes.
In these circumstances we must admitt that either the plasmodia, circulating today among
american Primates (man included), arrived in the New World with the Anopheles or, more
probably, that during the plasmodia were circulated among the Primates by mosquitoes of the
genus Culex (Capasso, 1991). Therefore, we could imagine a separation of mosquito
evolutionary present in the Old and New Worlds during the Lower and Middle Tertiary, which
re-traces the separation between the Primate populations of the Old and New Worlds that
occurred in the same period. A remix between these distinct populations of mosquitoes and
plasmodia occurred with the emergence of the Beringia, which allowed man's access to Ame-

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171

rica (Figure 4). Therefore, on the basis of fossil data, we must admitt that the plasmodia, which
were present on earth, at least since the appearance of vertebrates circulated among the earliest
Primates via mosquitoes of the genus Culex. This situation remained unchanged during the
Lower and Middle Tertiary of the New World, in the absence of Anopheles which made its
appearance during the Oligocene and assumed the role of vector of plasmodia for Primates at
the end of the Lower Tertiary. When, during the Lower Pleistocene, man made his appearance
in Africa, he became involved in the epidemiological chain of plasmodial infections. Both in
the Old and in the New World, the mosquitoes of the Culex genus had been vectors of arboviruses
for birds, and mammals since the Cenozoic Era: the first Primates, and later humans, did
nothing more than fit within a pre-existing epidemiological chain.
The Culex mosquitoes of the Upper Tertiary were the first to meet the earlier representatives
of the genus Homo. From this point of view the most interesting species are obviously those
which lived in Africa where, during the Upper Tertiary, human evolution was taking place. A
recently discovered form designated Culex tanzaniae (Capasso at al., 1998), had the opportunity
to feed from the blood of our first african ancestors. It lived on the East African coast during
the Upper Pliocene and the Lower Pleistocene (Schluter and Von Gnielinski, 1987), where the
evolution of the Homo genus was happening. It is very probable that Culex tanzaniae, possibly
with other Culex species, had a role in the transmission of blood parasites among the mammals

Figure 4 - The evolution of Culex and of its vertebrate hosts in the Old and New Worlds (from Capasso,
1991).

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then in existence in that part of Africa. A direct ancestor of man might have been among these
mammals.
It is difficult to think that the speculations exposed here are susceptible as direct
confirmation. However, the development of studies concerning the origin of malaria is rapid.
For example, the recent identification of DNA in ancient human bones could allow the study
of mutations of globin genes in archaeologic material, with the possibility of detecting mutations
linked to the selective pressure of malaria. Moreover, there are other, almost incredible, options.
It could be theoretically possible to search for traces of plasmodia in the blood of fossil
mosquitoes preserved in amber. This research is difficult in view of the very limited amount of
samples available.

Evidence of malaria on ancient bones

Malaria leaves few, not specific, and inconsistent traces on bones. These traces can be
summarized by the morphological aspect defined hyperostosisporotica, which has been the
object of paleopathologic studies since 20 years (Angel, 1967; 1978).
The cranial vault is punctuated by numerous small orifices, which are more frequent in the
parietal and occipital regions and on the frontal aspect of the orbit (so called cribra orbitalia),
and more rarely, on the palatine arch (Figures 5, 6).

Figure 5 - Typical aspect of porotic hyperostosis in a precolumbian child from Ancon, Peru (National
Museum of Anthropology, Florence).

THE ORIGIN OF HUMAN MALARIA

17 3

ANAEMIA

HYPOXEMIA

MEDULLARY
MEDULLARY

STIMULATION

HYPERPLASIA

(POROTIC HYPEROSTOSIS)

Figure 6 - Processing towards porotic hyperostosis by malaria

Micromorphologically, the external table is eroded and the internal table appears thin, but
the bone is overall thickened because of the relative and absolute expansion of the diploe,
whose trabeculae assume radial orientations. This may result in the development of parietal
and frontal thickening, while the loss of the external table and the radial orientation of the
diploic trabeculae causes the typical radiological aspect of the bruch-and/or protein (Weaver,
1980; Van Endt and Ortner, 1982) deficiency or to intestinal parasites (Figure 7).

1 - CHRONIC

ANAEMIA

A-Congenital

THALASSEMIAS
SICKLE-CELL ANAEMIA
MINKOWSKI-CHAUFFARD'S ANAEMIA
B - Acquired

INTESTINAL PARASITES
IRON-DEFICENCY
RICKETS
MALARIA
2 - POLYGLOB

ULIA

Figure 7 - Main causes of chronic hypoxemia

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But, was malaria really absent in the New World in the pre-Columbian period? Nothing is
more controversial. According to authoritative opinions (Dunn, 1965; Zaino and Zaino, 1975),
there are no ind!cations of the presence of the disease prior to the arrival of European colonists.
However, other students favour the opposite hypothesis, highlighting evidences which would
suggest that cbinin was used by precolumbian Incaic populations (Hare, 1954).
Altogether, the presence of malaria in the precolumbian Americas would seem highly
dubious. The evidence of porotic hyperostosis in precolumbian Americans could indeed be
related to iron deficiency or to diet or to other diseases which could have had an important role
in the past (for example, bartonellosis). This is supported by the ideas that malaria, as yellow
fever and smallpox, was introduced through the slave trade or through contact with Spain
(Behar, 1968; E1 Najjar, 1976).
Some studies on the subject advance a sort of possible compromise, which appears to be
biologically sound. It could be supposed that Plasmodium malariae and Plasmodium vivax
represent forms of plasmodia originating in the New World which passed to the Old World
before the practicability of the Berig strait; contacts with the Old World during historical times
(after the Viking and Columbian travels) could have introduced Plasmodiumfalciparum, which
originated in the Old World, into the Americas. A support to this view derives from the study
of an area of high malaric endemism in the Amazon basin (Sultzer et al., 1978). Other authors
demonstrated the occurrence of malaria from Plasmodium malariae and Plasmodium vivax,
but not from Plasmodiumfalciparum, in isolated tribes of Amazonic aborigens. This situation
probably represents a pathocenotic relict, in other words, an ancestral epidemiologic condition
which reflects the situation which prevailed in the precolumbian Americas (Grande, 1980)

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