History of Human Parasitic Diseases

History of human parasitic diseases
Francis E.G. Cox, PhD, DSc

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical
Medicine, Keppel Street, London WC1E 7HT, UK
Strictly speaking, any infectious agent can be described as a parasite but
the term is usually restricted to the protozoa and helminth worms. These are
highly evolved and opportunistic organisms that can be found as parasites in
all classes of the animal kingdom. It is not surprising that humans should
harbor some parasites but what is remarkable is the number of dierent
species that can infect us; nearly 300 helminth worms and about 100
protozoa. Not all of these are pathogens but some are responsible for about
20 human diseases or disease complexes and these are among the most
important diseases in the world, mainly in the tropics. Until the end of the
nineteenth century, parasitologists were mainly concerned with the discovery
of parasites in a range of hosts and unraveling their complex life cycles
mainly for their zoologic interest. All this changed when the roles of parasites
in human disease became apparent; this altered the whole approach to the
subject and switched the emphasis from zoology to medicine. The history of
parasitic diseases is now mainly concerned with trying to understand the
events leading up to the identication of parasites and the subsequent
incrimination of parasites in the etiology of the disease. In this article it is
only possible to cover some of the most important parasites, those that cause
disease and give rise to characteristic signs and symptoms (Table 1),
although other parasitic infections are mentioned in passing.
Prehistory and early history
It has long been assumed that humans ancient ancestors must have
harbored several species of parasites, particularly the larger worms, but until
recently there has been no direct evidence to support such an assumption.
Studies of archaeologic artifacts, however, such as the presence of helminth
eggs or protozoan cysts in coprolites and preserved bodies, are nowproviding
E-mail address: frank.cox@lshtm.ac.uk
0891-5520/04/$ - see front matter 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.idc.2004.01.001
Infect Dis Clin N Am 18 (2004) 171188
researchers with some direct information about parasitic diseases in the past
[1]. Coprolites, desiccated or fossilized feces, are the most important source of
parasitologic material, particularly the eggs of helminth worms that preserve
their characteristics very well. Unfortunately, many of the helminth eggs
associated with human coprolites, and attributed to human infections, are
almost certainly eggs from nonhuman parasites from animals eaten for food
that have passed undamaged through the intestine. The earliest records of
helminth eggs from human coprolites tend to be rather ambiguous and are
much debated as is the actual dating of the specimens. Eggs of the lung uke,
Paragonimus, dating from about 5900 BC, have been found in human
coprolites from northern Chile; if this date is correct (although 2500 BC is
more likely), this makes these the earliest records of any human parasite [2].
There is a disputed record from Brazil of hookworm eggs from circa 5000 BC
and eggs of the large roundworm Ascaris lumbricoides have been found in
coprolites dated fromcirca 2330 BC fromPeru. As one moves into more recent
times such records become more frequent and there is now considerable
evidence that most of the common intestinal worms were present throughout
the world in prehistoric times. Mummies and other preserved bodies are also
useful sources of parasitologic material. Egyptian mummies from circa
2000 BC and 1250 to 1000 BC have been found to contain the eggs of tape-
worms, Taenia sp. and Schistosoma haematobium, respectively, and the
presence of the Dracunculus in Egypt has been conrmed by nding a
well-preserved female worm and a calcied worm in mummies [3].
Despite its limitations, paleoparasitology has become a very useful branch
of parasitology and has the potential to develop into a very sophisticated
science combining the use of the well-tried tools of archaeologic research with
molecular techniques, such as the use of DNA. One example of the use of
DNA has been the identication of the protozoan Trypanosoma cruzi in
Table 1
Parasitic diseases
Disease Parasite Numbers infected
Malaria Plasmodium spp 300500,000,000
Amoebiasis Entamoeba histolytica 48,000,000
Sleeping sickness Trypanosoma brucei gambiense
and T b rhodesiense
300,000
Chagas disease Trypanosoma cruzi 18,000,000
Schistosomiasis Schistosoma spp 200,000,000
Hookworm Ancylostoma duodenale
and Necator americanus
150,000,000
Lymphatic lariasis Wuchereria spp 120,000,000
Brugia spp
Loiasis Loa loa No accurate gures
Onchocerciasis Onchocerca volvulus 18,000,000
Guinea worm disease Dracunculus medinensis 80,000
Larval cestodiasis Taenia spp Echinococcus granulosus No accurate gures
172 F.E.G. Cox / Infect Dis Clin N Am 18 (2004) 171188
Chilean mummies dating back to 2000 BC [4]. Studies on parasites in
archaeologic remains are also throwing light on the ways of life of the people
in early civilizations [1]. One problem with the identication of parasites from
human remains is that it depends on the preservation of bodies or body parts
and this only occurs where the climatic conditions are appropriate or where
past civilizations have preserved bodies that can now be examined. For this
reason, for much of the world, there is little or no evidence of the presence of
parasites, whereas certain sites have been particular productive. Nevertheless,
from the available fragmentary information, one can be fairly certain that
human ancestors harbored most of the common helminth parasites known
today.
Parasitic worms: early written records from antiquity to circa AD 1000
The eggs and cysts of parasites found in coprolites, mummies, and other
human remains tell very little about parasitic infections and diseases in the
past, so most historians prefer to place more reliance on the written record.
The rst such records come from a period of Egyptian medicine from 3000
to 400 BC, particularly the Ebers papyrus from about 1500 BC, which
mentions worms clearly identiable as roundworms (A lumbricoides);
threadworms (Enterobius vermicularis); Guinea worms (Dracunculus medi-
nensis); and tapeworms that cannot be identied with any certainty. The
literature from ancient Greece is a source of useful information, especially
the works of Hippocrates. Hippocrates (460375 BC) is widely regarded as
the father of physic and his works have been collected together, added to,
and reassembled a number of times until a denitive version, known
variously as the Corpus Hippocratorum, Corpus Hippocraticum, or Corpus
Hippocraticus, ended up in the library at Alexandria in about 250 BC [5].
Hippocrates and Aristotle (384322 BC) wrote about worms from shes,
domesticated animals, and humans. Bladder worms, the larval stages
(cysticerci) of the tapeworm Taenia solium, which cause a condition known
as measly pork in pigs, were well known to the ancient Greeks and are
referred to by the playwright Aristophanes (380375 BC) as hailstones.
Aristotle, in the section on diseases of pigs in his book History of Animals,
also gives a detailed and accurate account of bladders that are like
hailstones. The massive hydatid cysts of the tapeworm Echinococcus
granulosus, particularly in the liver, were well known in ancient cultures and
there are references to such bodies in ritually slaughtered animals in the
Babylonian Talmud and, in animals slaughtered for food, in the works of
Hippocrates, Arataeus in the rst century AD, and Galen in the second cen-
tury AD. Roman physicians from 700 BC to AD 400, including Celsus (25 BC
AD 50) and Galen (129200), were familiar with Ascaris and Enterobius and
tapeworms belonging to the genus Taenia. Following the decline of the
Roman Empire, the study of medicine was taken up by Arabic physicians.
Avicenna (9801037) in his great work, Al Canon Al Tib, recognized
Ascaris, Enterobius, and tapeworms and also Guinea worms, which had
been recorded in parts of the Arab world, particularly around the Red Sea,
for over 1000 years. Rhazes (850923) was also familiar with the Guinea
worm. At the end of the rst millennium there are numerous written records
of parasitic worms from other parts of the world suggesting that physicians
from dierent civilizations from all over the world were aware of, and wrote
about, the most common parasitic worms [6]. With the possible exception of
dracunculiasis, however, there was no suggestion of any connection between
parasites and disease.
Parasitic diseases: early written records from antiquity to circa AD 1000
Few parasitic infections produce signs and symptoms that are specic
and unambiguous but references to some of these that do, particularly
dracunculiasis, hookworm disease, elephantiasis, schistosomiasis, malaria,
and amebiasis, frequently appear in the early literature.
Of all the diseases caused by parasitic worms the best documented from
the earliest times is dracunculiasis caused by the Guinea worm D medinensis.
The large female worm emerges from the skin, usually of the leg, and causes
such intense inammation and irritation that it cannot have been ignored.
The signs of the infection are so unambiguous that it is possible to interpret
ancient texts with a degree of certainty that is not possible with any other
parasitic infection. Dracunculiasis is the only disease that is accurately
described in the Bible and it is widely accepted that the ery serpents that
struck down the Israelites in the region of the Red Sea after the Exodus from
Egypt, somewhere about 1250 to 1200 BC, were actually Guinea worms.
Although there have been other suggestions it is now widely accepted that
the most authoritative interpretation of this biblical text, thought to have
been written in the eighth century BC, is by Gottlob Friedrich Heinrich
Ku chenmeister, a parasitologist, theologian, and Hebrew scholar [7].
Assyrian texts in the library of King Ashurbanipal from the seventh century
BC also refer to conditions that are obviously dracunculiasis, as do later
Arabic and Greek medical texts, although the disease was never present in
Greece. Descriptions of dracunculiasis occur in all the major Greek and
Roman texts including those of Pliny in the rst century AD, Galen in the
second century, Aetius of Amida in the sixth century, and Paulus Aegineta
of Alexandria in the ninth century. Arab physicians were also aware of the
disease and there are good descriptions of it in works by Rhazes in the tenth
century and Avicenna in the eleventh; both comment that the worm occurs
everywhere (in the hands, in the sides, and thighs) [6]. In the Arab literature
as there is reference to Medina vein, and the impression given by some
authors is that the Arab physicians, including Avicenna, may have thought
that the worm was actually a rotten vein [8]. This may have been caused by
misunderstandings and problems with translations, however, and most
observers now agree that Rhazes and Avicenna and other Arab physicians
were fully aware of the worm-like nature of the parasite and the association
with, but not necessarily the cause of, the disease.
The classical signs of hookworm disease, caused by infection with
Ancylostoma duodenale and Necator americanus, are anemia accompanied
by greenish yellow pallor and lassitude both of which can be attributed to
a number of causes. Geophagy is exhibited by some individuals but this is
not necessarily associated with disease. The disease, which is now assumed
to have been present in many civilizations, would have gone unreported and
any accounts of it must be treated with caution. The greenish pallor called
Egyptian chlorosis, observed by nineteenth century scientists to be asso-
ciated with hookworm infections, is not recorded in the early Egyptian
papyri. Some authorities have suggested that the enigmatic condition, aaa,
which occurs in many Egyptian papyri including the Ebers papyrus, might
refer to hookworms but there is no real evidence for this [3]. Hookworm
infections almost certainly occurred in Greece and in the works of
Hippocrates there are references to a yellowish pallor and geophagy.
Lucretius noted the pallor seen in miners in about 50 BC and this could well
have been caused by infection with hookworms, as discussed later [6]. In
China there are third century BC references to laziness and a yellow disease
that could be caused by hookworm infections [6].
One parasitic disease that could not have escaped attention in the past is
lymphatic lariasis, particularly the bancroftian form caused by infection
with Wuchereria bancrofti. The disease is characterized by gross swellings of
the limbs, breasts, and genitals, a condition known as elephantiasis, and
these have been described and depicted in drawings and sculptures from the
earliest times [9]. Such pathologic changes could be caused by a number of
conditions including tuberculosis and it is dicult to interpret some of the
early records from Greece, Rome, and China. Lymphatic lariasis still
occurs in Egypt and along the Nile and it is tempting to look at the swollen
limbs of a statue of the Pharaoh Mentuhotep II from about 2000 BC and to
deduce that he was suering from elephantiasis, and small statuettes and
gold weights from the Nok culture in West Africa from about AD 500 show
what are clearly enlarged scrotums [9]. The earliest written records are those
of Arabic physicians, including Avicenna, who were obviously familiar with
the condition and even noted the dierences between leprosy and
elephantiasis.
Schistosomiasis, also known as bilharzia and a number of local names
including Katayama disease, red water fever, snail fever, and big belly, is
caused by infection with trematode worms belonging to the genus
Schistosoma of which the most important are S haematobium, S mansoni,
and S japonicum. The pathology of the disease is mainly caused by
immunologic reactions to eggs in various tissues and organs and the nature
of the disease depends on the tissues involved. There is nothing specic about
any form of schistosomiasis that would have attracted the attention of early
observers except the bloody urine (hematuria) associated with S haematobium
infections. Shaematobiumis currently present throughout much of Africa and
the Middle East, including areas along the Nile, and it is known from direct
evidence of nding eggs in mummies that schistosomes were present in ancient
Egypt. There have been numerous attempts to nd descriptions of hematuria
in the medical papyri [10,11]. The most contentious word is aaa, which occurs
only in the medical papyri; the initial hieroglyph suggests a penis discharging
blood and is widely illustrated in historical and parasitologic textbooks. There
are problems with this interpretation, however, and this subject is discussed in
detail by Nunn and Tapp [3] who conclude that we must nowabandon aaa as
a possible ancient Egyptian word for schistosomiasis. It is curious, however,
that the Egyptians did not have a word for this condition, unless it was so
common that it was ignored in the same way that Greek and Roman writers
ignored coughs and colds. In this context, it should be mentioned that there
have been a number of other suggestions as to what aaa might be including
hookworm.
There are numerous references to fevers in the early literature and it is
very dicult to interpret some of these that might or might not have
indicated malaria. The earliest references to what almost certainly was
malaria occur in a Chinese document from about 2700 BC attributed to the
Emperor Huang Ti in his medical treatise, Nei Ching (Canon of Medicine),
which lists not only headaches, chills, and fevers but also distinguished
between tertian and quartan fevers [6]. Clay tablets from Mesopotamia
dating from 2000 BC mention intermittent fevers and there is a mention of
fevers and splenomegaly in the Egyptian Ebers papyrus. In India, the Hindu
texts the Caraka Samhita and Susruta Samhita, collections of texts and
verses dating back to the sixth century BC, refer to tertian and quartan fevers
and enlarged spleens [12]. There are frequent references to the characteristic
malarial fevers in the writings of the early Greeks including Homer in about
850 BC and the philosopher Empedocles of Agrigentum in about 550 BC [13].
The most accurate accounts of malarial fevers from this early period are
those of Hippocrates who, in Epidemics, classied the fevers as quotidian,
tertian, semitertian, and quartan and recorded that the quartan fevers were
the most persistent but that the other fevers were more dangerous [5].
Hippocrates associated poor health, fevers, and enlarged spleens with
marshy places. The belief in the association between fevers and marshy
places was widely acknowledged in the years running up to the beginning of
the rst millennium AD and the Roman author Marcus Terentius Varro
(11627 BC), in his book De Re Rustica, advised against siting houses in
swampy places because of the disease that could pass through the air [12,13].
Diarrhea and dysentery are among the most common manifestations of
intestinal infections today so it is not surprising that there are numerous
references to these conditions in the early literature, but most of these were
probably caused by bacteria. The only important parasitic dysenteric disease
is amebiasis caused by infection with the amoeba Entamoeba histolytica.
Amebiasis involves ulceration of the intestinal wall and abscesses in
extraintestinal sites elsewhere in the body, particularly the liver, and
descriptions of epidemics of dysentery associated with disorders of the liver
are likely to be amebiasis. What is possibly the earliest record is from the
Sanskrit document, Brigu-samhita, written about 1000 BC, which refers to
bloody, mucosal diarrhea [6]. It is also possible that the descriptions of
hepatic and perianal abscesses in the Corpus Hippocratorum are references
to amebiasis. A number of Assyrian and Babylonian texts from the library
of King Assurbanipal refer to blood in the feces and this has been
interpreted by several authors as indicating the presence of amebiasis in the
Tigris-Euphrates basin before the sixth century BC [14]. In the second
century AD both Galen and Celsus describe liver abscesses that are probably
amoebic and there are also good accounts of both dysentery and hepatic
involvement in the works of Aretaeus, Archigenes, Aurelanus and, later,
Avicenna toward the end of the rst millennium [14,15].
The Middle Ages
The Middle Ages refers to a period of European history from about AD 500
to 1500. It is convenient to consider the later period between about AD 1000,
when the period described in the previous section comes to an end, and AD
1500, when the period of European exploration opened up previously
unknown regions with diseases that Europeans had never before seen. The
scientic and medical literature of this period tends to reect the culture,
beliefs, and ignorance of the time not only in Europe but elsewhere. Although
there are scattered references to parasitic worms, and in some cases
suggestions that they were possible causes of disease, it is dicult to interpret
these texts especially because many of these worms were ctitious.
Suggestions that they caused such conditions as toothache and heart attacks
are very far-fetched [6]. Progress in understanding helminth infections was
also held back by adherents to the dogma of spontaneous generation,
although doubts had already been raised about the validity of this concept,
particularly the belief that worms arose de novo from rotting or diseased esh
[16]. There was, however, one discovery of great signicance that has often
been ignored in medical texts because it relates to an animal disease,
fascioliasis or liver uke infection. Fascioliasis is caused by infection with the
trematode Fasciola hepatica, which occurs predominantly in sheep, in which
it causes a condition known as liver rot, and in other animals including
humans. F hepatica occupies a special place in the history of parasitology,
being the rst parasitic worm to be recognized and unambiguously associated
with any disease of livestock. The worm itself was discovered by Jehan (Jean)
de Brie in 1379 and there are references to liver rot in sheep in a number of
works published in the fteenth and sixteenth centuries, of which Anthony
Fitzherberts A Boke of Husbandry published in 1523 is by far the best. In his
book he describes the jaundice and condition of the wool and skin in a way
that might be taken from a modern textbook [10,15,17]. The discovery of the
worm and the subsequent unraveling of, and the implication of snails in, the
life cycle are of great signicance in later studies on the importance of
intermediate hosts and vectors in the life cycles of worms of medical
importance.
The only other information from this period comes from the increasing
numbers of records of the parasitic worms that had been known for over 10
centuries, and these written records are conrmed by discoveries of eggs in
medieval cesspits and latrines; there is no doubt that Europe at that time
was a very wormy world. With the growth of substantial human settlements,
increased travel, and primitive sanitary arrangements, amebiasis, which had
hitherto been sporadic, became widespread and there are numerous records
of bloody ux, widely interpreted as amebiasis, in Europe, Asia, Persia,
and Greece throughout the Middle Ages [14,15]. There are also numerous
references to fevers, clearly relating to malaria and its association with
marshy places, known and feared by a variety of local names including ague
[12,13]. Some of the explanations for this disease were bizarre and included
planetary and lunar movements, earthquakes, and, increasingly, miasma
arising from marshes. It is interesting to note, though, that malaria was
taken so seriously that it was one of the principal diseases studied at the
great medical schools in Europe [12].
The age of exploration: 1500 to 1800
From the earliest times humans have been interested in travel and
exploration and from the point of view of the European colonial powers the
most important period of exploration covered a period from the end of the
fteenth to the end of the eighteenth centuries. In the context of this article it
is convenient to consider the period from 1500 to 1800. This period was
marked not only by the great explorations but also by the great explorers
who brought back to Europe news of new countries, new animals, new
plants, and new diseases, some of which were caused by parasites. Interest in
dracunculiasis re-emerged when the condition began to be recognized by
travelers visiting Asia and Africa, hence its common name, Guinea worm
[6,8,10]. One of the most signicant reports is that of the Dutch navigator
Jan Huygen van Linschoten, who at the end of the sixteenth century noted
the infection in the Persian Gulf and recorded the perceived association with
drinking water [10]. In 1768 an English naval ocer, James Lind,
recommended the purication of drinking water to prevent the infection.
Linschoten was also the rst person to give an accurate description of
lymphatic lariasis (elephantiasis) and, on a visit to Goa between 1588 and
1592, recorded . . .legs and one foot from the knee downwards as thick as
an elephants leg [18]. Thereafter there are numerous references to
elephantiasis especially in Africa but also in Asia including China where
Manson was later to discover the life cycle of the parasite [9,10,15].
Two new parasitic diseases, loiasis and onchocerciasis, were also recorded
for the rst time during this period of exploration. The worms responsible
for loiasis and onchocerciasis both aect the eye and must have attracted the
attention of physicians interested in the eyes and blindness but there are no
early reliable records of these conditions. Loiasis is caused by infection with
the larial worm Loa loa, which moves across the eye under the conjunctiva.
This alarming experience must have been obvious to both suerers and
physicians but early records are sporadic and unconvincing. There is
a mention of this condition by a French surgeon, C. Guyon, who in 1864
identied an engraving by J.T. de Bry, made in 1598, and suggested that it
depicted the extraction of a worm from the eye but this has now been
disputed [19]. The literature of the eighteenth century is dominated by
French workers, mainly ships surgeons. The rst denitive record is that of
a French surgeon known only as Mongin who, in 1770, described the worm
passing across the eye of a woman in Santa Domingo, in the Caribbean, and
how he tried unsuccessfully to remove it [10]. In 1778 another French ships
surgeon, Francois Guyot, recorded that slaves in transit from West Africa to
America suered from recurrent ophthalmia and that he had successfully
removed a worm from the eye of one of them. The history of knowledge of
onchocerciasis is very short and there is nothing about it in the early
literature [20]. This is not really surprising because the causative agent,
Onchocerca volvulus, is mainly found in Africa and South America and it
was only when these continents were opened up by explorers that the disease
began to be recognized. The most important signs of onchocerciasis are
blindness, which might have been caused by a number of factors, and scaly,
itchy, nodular skin, which did attract attention as something unusual and
was known locally in West Africa as kru kru, which has been transliterated
as craw craw [20].
African trypanosomiasis or sleeping sickness was also unknown to
scientists and clinicians until the opening up of Africa during the explorations
of the continent in the sixteenth century. There is, however, one earlier record,
the death of the Emperor Mansa Djata (Jata or Diata) of Mali who died from
the sleeping illness, a disease which frequently aicts the inhabitants of that
climate. . . in 1373 or 1374 [21]. The rst authoritative account of the disease
is that of an English naval surgeon, John Atkins, who wrote in his 1734 book,
The Navy Surgeon, of the sleepy distemper of blacks. Atkins thought that
the disease occurred only in blacks and was caused by excess phlegm or serum
in the brain, diet, and the natural weakness of the brain [22]. In 1803, in
ignorance of these two earlier reports, Thomas Masterman Winterbottom,
a physician working in Sierra Leone, described a newdisease, Negro lethargy,
with a number of local names including those meaning sleepy sickness,
and identied the characteristic enlarged glands in the neck that now
commemorate his name, Winterbottoms sign. Neither Winterbottom nor
anybody else had any real idea about the nature of the disease and a number
of bizarre explanations were oered to explain it [21,22].
South American trypanosomiasis, or Chagas disease, is another disease
rst recorded in this period. Most cases of Chagas disease show few or no
obvious signs or symptoms and the disease itself only becomes apparent long
after the initial infection so knowledge of the disease before the discovery of
the trypanosome responsible for it, Tcruzi, is very limited. Enlarged viscera in
South American mummies dating back 2000 years or more and DNA studies
on the parasite indicate the antiquity of this disease but there is nothing in the
early written records. The rst fragments of information relate not to
the disease but to the blood-sucking bugs that transmit it and come from the
writings of a Dominican missionary, Reginaldo de Lizarraga y Ovando,
between 1608 and 1611 [23]. Thereafter there are numerous references to
blood-sucking bugs mostly by missionaries. The signs of Chagas disease are
so vague that it is very dicult to interpret many of the early writings, which
in any case do not date back further than the seventeenth century.
Infections caused by larval tapeworms: 1500 to 1855
It is convenient to consider two diseases caused by larval tapeworms here.
Hydatid disease, caused by the larval stages of the dog tapeworm, E
granulosus, is common in temperate regions and there are occasional records
of the massive tumorlike cysts associated with this condition in European
medical texts in the sixteenth and early seventeenth centuries [10,15]. They
were variously thought to be sacs of mucus, enlarged glands, distorted blood
vessels, lymphatic varices, or accumulations of lymph, however, and it was
not until the second half of the seventeenth century that their real nature
began to be appreciated. Francesco Redi, in 1684, had realized that the
structures he had found in a hare were living entities but thought that they
were related to infection with the liver uke, F hepatica, and it was not until
1760 that Pierre Simon Pallas discovered that they were tapeworm larvae
[10,15]. Humans can also be infected with the larval stages (cysticerci),
normally found in pigs, of the human tapeworm T solium. There are
accounts of what are possibly cysticerci in humans by Johannes Udalric
Rumler in 1558, Domenico Panaroli in 1652, and Thomas Wharton in 1656,
but as for hydatid disease, none of these realized that the structures they
described were parasites. The rst accounts of cysticerci as parasites are
those of Philip Hartmann in 1688 and Marcello (Marcus) Malpighi in 1697
but it was not until 1784 that Johann August Ephraim Goeze realized that
they were tapeworms [10,15]. By the end of the eighteenth century the true
nature of both the important larval tapeworm infections in humans had
been established. This story continues into the nineteenth century and by
1853 it had nally been established by a number of workers, in particular
Ku chenmeister, that human cysticercosis was caused by the ingestion of the
eggs of T solium and that hydatid disease was caused by the ingestion of eggs
of the dog tapeworm E granulosus [7].
The nineteenth century and subsequent discoveries
The nineteenth century can be considered as the golden age of
parasitology because during this century many of the life cycles of parasites
were elucidated and the various discoveries of previous centuries pulled
together into coherent stories. This was also a period dominated by some of
the greatest names in parasitology, all of whom made many contributions
often in several dierent elds. Of these, one man dominated the eld of
parasitic diseases, Patrick Manson, who is still acknowledged as the father of
tropical medicine [24]. There were too many important discoveries in this
century to do justice to them all and here it is only possible to draw on those
that consolidated themes that have already been discussed. A number of the
discoveries made toward the end of the nineteenth century continued into the
twentieth century and it is logical that these should also be mentioned.
Dracunculus medinensis was one of the parasites described in the earliest
literature but it was not until 1819 that Carl Rudolphi discovered that the
adult female worms contained larvae and in 1836, Forbes found the larvae
in water. Over the next few years it was thought that humans became
infected through the skin, as had already been shown for hookworms (see
later), and it was not until 1870 that Alekej Pavlovitch Fedchenko began to
suspect that small crustaceans belonging to the genus Cyclops were involved
in the life cycle and that infection was acquired by accidentally consuming
them [25]. Fedchenkos discoveries were controversial and remained so until
they were conrmed by Manson in 1894 and Dyneshvar Atmaran Turkhud
who, in 1913, successfully infected human volunteers with Cyclops
containing the larval worms [8,10,15].
Fedchenkos discovery led directly to one of the most signicant events
during this period: the discovery that the larial worms responsible for
elephantiasis were transmitted by mosquitoes. The larval stages, now known
as microlariae, live in the blood and other body uids and were rst seen
by the French surgeon Jean-Nicolas Demarquay in hydrocele uid in 1863
and, independently, in the urine by Otto Henry Wucherer in 1866 [10]. The
adult worms were described 10 years later by Joseph Bancroft in 1876
[9,10,15]. The discovery of the life cycle by Patrick Manson in 1877 is widely
regarded as the most signicant discovery in tropical medicine with
implications that went far beyond helminthology into such diverse areas
as malaria and the arboviruses [24]. Manson, aware of Fedchenkos work on
the life cycle of D medinensis and the role of an intermediate host its
transmission, began to look for an intermediate host for the related larial
worms responsible for elephantiasis. Having found microlariae in the
blood of dogs and humans he hypothesized that they might be transmitted
by blood-sucking insects and proved this by feeding mosquitoes on the
blood of his gardener, who was harboring the parasites, and nding larval
stages in the mosquitoes [26]. Manson, however, possibly misled by
Fedchenkos discoveries, thought that the parasites escaped from the
mosquito into water and that human infections were acquired by drinking
this contaminated material. The real role of mosquitoes in the life cycle and
transmission of lariasis was later established by the Australian parasitol-
ogist Thomas Bancroft and Mansons colleague George Carmichael Low in
1899 and 1900 [9,10,15]. The history of lariasis is discussed in more detail
elsewhere in this issue.
Loiasis (eye worm) and onchocerciasis (river blindness) are also caused
by larial worms and the discovery of their life cycles owes much to the
discoveries made by Fedchenko and Manson. The larvae, microlariae,
were discovered by an ophthalmologist, Stephen McKenzie, in 1890 and
sent for identication to Patrick Manson who, after a number of false starts,
suggested that the microlariae might be stages in the life cycle of L loa
[10,24]. The transmission by ies of the genus Chrysops was discovered by
Robert Leiper in 1912. The rst account of the removal of L loa from the eye
in English is that by William Loney in 1848 and this and a number of
subsequent records are listed by Grove [10]. It is generally agreed that the
microlariae of O volvulus were rst discovered by an Irish naval surgeon,
John ONeill, who found them in skin snips from patients suering from
craw craw in Ghana in 1874 [20]. Some years later, in 1890, the adult worms
were also discovered and by a circuitous route identied by Patrick Manson
[27]. The connection between the presence of the adult and larval worms and
the disease, river blindness, was established by Rodolfo Robles in
Guatemala in 1917, although it was then thought that the disease was
caused by toxins produced by the adult worms. Although the role of
microlariae in river blindness had been established by Jean Hissette in
Zaire in 1932 it was not until the 1960s that there was general agreement
that the pathologic changes in the eye were caused by inammatory
reactions to the microlariae. The importance of microlariae in causing
skin lesions was established by Montpellier and Lacroix in 1920. The role of
blackies, whose larvae live in streams and rivers, in the transmission of
onchocerciasis was demonstrated by Breadablane Blacklock in Sierra Leone
in the mid 1920s and this discovery explained why this disease was called
river blindness and opened up the possibility of control by eliminating the
blacky larvae.
The written record of hookworm disease really took o in the nineteenth
century with increasing numbers of records from the West Indies and South
and Central America. The Italian physician Angelo Dubini found the
worms in a human in 1838 and the connection between the worms and the
disease was nally established by Theodor Bilharz in 1852 and Wilhelm
Griesinger in 1854 [10,15,28]. The conditions in mines are particularly
favorable for the development of hookworms and, although the association
between pallor and working in mines had been made by Lucretius in the rst
century BC it was not until 1879 that the Italian veterinarian, Edoardo
Perroncito, established the real connection while investigating episodes of
disease and mortality among workers in the St Gothard tunnel [29]. The
percutaneous mode of transmission was not elucidated until the experiments
of Arthur Looss at the end of the century. It is appropriate to mention that
suggestions in many historical, parasitologic, and medical texts that
hookworm disease existed in the Americas before 1492 have been
questioned [30]. This is not the place to discuss the various claims and
counter claims but increasing numbers of paleoparasitologic studies suggest
that hookworms were present in the Americas before 1492 and supported by
such authorities as Robert Desowitz [31].
If one accepts that there is no authoritative description of schistosomiasis
in the earliest medical literature the rst denitive record is that of an
epidemic among soldiers in Napoleons army in Egypt in 1798 [10,15,32].
Thereafter there are increasing numbers of reports of illnesses characterized
by hematuria particularly among armies. The worm itself was discovered by
the German parasitologist Theodor Bilharz in 1851 who, with Wilhelm
Griesinger, also made the connection with the urinary disease a year later
but it was not until 1915 that the roles of the snail intermediate host was
discovered by Robert Thomson Leiper. The history of schistosomiasis is
discussed in more detail elsewhere in this issue.
Knowledge of the causes of malaria only became possible after the
discovery of the parasite itself by Charles Louis Alphonse Laveran in 1880
and the elucidation of the life cycle, incriminating the mosquito as the
vector, as suggested by Manson, rst for avian malarias by Ronald Ross in
1898 and then for human malarias by the Italian scientists Battista Grassi,
Amico Bignami, and Giuseppe Bastianelli in the same year [12,13,33]. In
1947, Henry Shortt and Cyril Garnham found that there was a phase of
division in the liver preceding the development of parasites in the blood and
knowledge of the life cycle was completed in 1982 when Wojciech Krotoski
and his colleagues discovered latent stages, hypnozoite, of the liver forms
[34]. The history of malaria is discussed in more detail elsewhere in this
issue.
Sleeping sickness had been known in Africa for centuries but little was
known about the condition, which was thought to be a disease of the natives
of little signicance. By the 1880s, however, epidemics of sleeping sickness
had begun to worry the colonial powers and matters came to a head in 1901
when an epidemic sweeping across Uganda persuaded the British
government to investigate the situation. At rst it was suspected that the
disease was caused either by a streptococcus or, on Mansons suggestion, by
a larial worm, Filaria perstans (Mansonella perstans). The real cause
became apparent in 1901 when Aldo Castellani discovered trypanosomes in
the cerebrospinal uid of patients suering from sleeping sickness [21,22].
The trypanosome responsible for Gambian sleeping sickness, Trypanosoma
brucei gambiense, was discovered by a Colonial surgeon, Robert Michael
Forde, working in Gambia, and identied and named by Everett Dutton in
1901. The second subspecies of human trypanosome in Africa, Trypanosoma
brucei rhodesiense, was discovered by John William Watson Stephens and
Harold Benjamin Fantham in 1910. The tsetse y vector of T gambiense,
Glossina palpalis, was identied by David Bruce and his colleagues in 1903
and the vector of T b rhodesiense, Glossina morsitans, was discovered a few
years later [35]. The history of sleeping sickness is discussed in more detail
elsewhere in this issue.
In 1875 Friedrich Lo sch (also known as Fedor Lesh) discovered the
causative organism of amebiasis, E histolytica, setting the scene for the
elaboration of the etiology of this ancient disease and, in 1883, Robert Koch
discovered peculiar amoeboid structures in intestinal ulcers of patients
with dysentery and also in capillaries surrounding liver abscesses [15].
Although Kochs observations are open to other interpretations, Cliord
Dobell, probably the worlds greatest authority on the subject, believed that
Koch was the rst to demonstrate primary amoebic lesions in the bowel and
secondary lesions in the liver [36]. Denitive proof that amoebae from
dysenteric stools could cause dysentery and extraintestinal abscesses came in
1887 from the work of Stephanos Kartulis, a Greek physician, using cats
[14,15,36]. In 1891 William Thomas Councilman and Henri Laeur,
working at the Johns Hopkins Hospital, wrote a denitive statement of
what was known about the pathology of amebiasis at the end of the
nineteenth century, much of which is still valid today [37]. Attention then
turned to the parasites themselves. Humans harbor several species of
amoebae, three of which, including E histolytica, are morphologically very
similar but only E histolytica causes disease. The rst clues that not all of
these cause amebiasis came from the work of Quincke and Roos in 1893 and
Roos in 1894, who observed that cats could only be infected with cysts with
one form of amoeba, the kind that contained ingested red blood cells and
not the kind that did not (ie, Entamoeba coli) [36]. Thereafter the arguments
relate to the various species and strains of Entamoeba and their relationship
to disease and whether the amoebae alone were the cause of disease or if
bacteria were also required.
The twentieth century
The twentieth century was not merely a period during which nishing
touches were added to what was already known but was marked by the
discovery of the cause of what is now called Chagas disease and the
discovery of a new important parasitic disease, toxoplasmosis, in the early
years of the century and a number of opportunistic parasitic infections in
immunodepressed patients, especially those with AIDS toward the end of
the century.
South American trypanosomiasis, or Chagas disease, is now known to
infect about 12 million people but at the beginning of the twentieth century
was virtually unknown. The rst indisputable and accurate accounts of one
of its main manifestations, megaesophagus, known locally in Brazil as mal
de engasco, are those by Kidder and Fletcher in 1857 and Chernoviz in
1879 [23]. The discovery of the causative organism, T cruzi, the mode of
transmission by bugs, and the role of the trypanosome in the disease are all
because of the eorts of one man, Carlos Chagas, between 1907 and 1909
[38]. T cruzi is now known to be a natural parasite of many species of wild
mammals in the Americas and is transmitted by blood-sucking bugs. It
aects humans if bitten by infected bugs, often early in life, although the
disease may not become apparent until many years later; hence early
diculties in recognizing it. The history of Chagas disease is discussed in
more detail in elsewhere in this issue.
Toxoplasma gondii is the most common human parasite worldwide and
also infects the widest range of hosts but its history has received relatively
little attention [39]. The parasite was discovered in 1909 by Charles Nicolle,
while searching for a reservoir host of Leishmania in a North African rodent
Ctenodactylus gondi, and at about the same time by Alfonso Splendore in
rabbits. Subsequently there have been numerous records from mammals and
birds all over the world. Although T gondii is a common parasite of humans
it was not recognized as a cause of disease because, in most cases, infections
were without symptoms. It can be a serious cause of mortality and
morbidity, however, for the fetus or immunodecient individuals. The
association with human congenital disease and the realization that the
parasite could cross the placenta and damage the fetus was not recognized
until 1937 [40] and it was only toward the end of the twentieth century that it
also became clear that toxoplasmosis can be fatal in immunocompromised
individuals, such as those with AIDS. The nature and life cycle of T gondii
remained elusive until 1970 when it was discovered that this parasite was
a stage in the life cycle of a common intestinal coccidian of cats [41]. This
information enabled pregnant women to be advised to avoid infection by
reducing or eliminating contact with cats or uncooked meat that might be
infected with this parasite. The history of toxoplasmosis has been reviewed
by Dubey and Beattie [39] and Moulin [42].
Cryptosporidiosis and Cyclospora infections, both caused by coccidia
related to Toxoplasma, are late twentieth century diarrheal diseases largely
conned to AIDS and other immunosuppressed patients. The rst cases of
human cryptosporidiosis, caused by Cryptosporidium parvum, were de-
scribed in 1976 by Nime et al [43] and Meisel et al [44] and Cyclospora
infections, caused by C cayetanensis, were described 10 years later by Soave
et al in 1986 [45]. More information about the history of cryptosporidiosis
can be found in McDonald [46].
The twenty-rst century
History does not end at any particular date in the past and the history of
parasitology has continued into the twenty-rst century with developments
based on discoveries made over previous centuries. Guinea worm is now
virtually eradicated as a result of eliminating the copepod intermediate
hosts from water supplies; onchocerciasis is now well on its way toward
eradication through antiblacky larva measures coupled with the avail-
ability of cheap and eective drugs; and there is the hope that the elimination
of lymphatic lariasis as a disease, if not as an infection, will follow. There is
also the expectation that Chagas disease will be eliminated as a result of
successful antibug campaigns in the Southern Cone countries of South
America. The situation is not so promising for other diseases. Malaria is on
the increase because of the development of drug resistance on the part of the
parasites and insecticide resistance on the part of the mosquito vectors.
Sleeping sickness is also on the increase but there are no cheap and eective
drugs or simple control measures to combat it. Despite a vast amount of
eort, there are no vaccines against any of the human parasitic diseases and
no realistic expectation of any in the foreseeable future. Any future history of
parasitology will be concerned with these successes and reasons for failures.
The history of human parasitology is not yet nished.
Envoi
The history of parasitology is an immense subject and the study of
parasites has attracted the attention of zoologists, clinicians, and
veterinarians for centuries. This article adopts a chronologic approach to
a number of diseases caused by parasites. In a short article such as this it is
only possible to touch on the most important aspects of the subject and
some, such as the history of malaria or trypanosomiasis, warrant whole
books on their own and some of the individuals involved have had, or
deserve, their own biographies. Fortunately the subject is well served in the
literature and the reader is referred to the encyclopedic work on parasitic
helminthes by Grove [10]; selected parasitic infections in the books by
Foster [15], Scott [47], Kiple [48], and Cox [49]; and a briefer but more
comprehensive review by Cox [50]. It has also been necessary to be selective
in the choice of diseases covered and the decision was made to concentrate
on the diseases best known from antiquity together with a brief
consideration of a number of diseases more associated with the twentieth
century. There are major omissions including Old World and New World
leishmaniasis, giardiasis, ascariasis, trichinosis, and intestinal and lung
ukes and there are comprehensive accounts of these in Cox [49]. The ukes
and ascariasis are also covered in considerable detail in Grove [10].
Acknowledgments
This study was carried out while in receipt of a Leverhulme Trust
Emeritus Fellowship and the author is grateful to the Trust for its support.
The author also thanks the London School of Hygiene and Tropical
Medicine for accommodating him as a Senior Visiting Research Fellow.
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History of Human Parasitic Diseases

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History of human parasitic diseases

Francis E.G. Cox, PhD, DSc

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