Trypanosomoses
Author: Vincent Delespaux
Adapted from: R.J. CONNOR and P. VAN DEN BOSSCHE, 2004, African animal trypanosomoses, in
Infectious diseases of livestock, edited by J.A.W. Coetzer & R.C. Tustin. Oxford University Press, Cape
Town, 12: 251 – 295
Licensed under a Creative Commons Attribution license.
EPIDEMIOLOGY
Trypanosomes are protozoan parasites of the genus Trypanosoma, order Kinetoplastida, and have, as
characteristic organelles, a kinetoplast and a flagellum. Typically, trypanosomes are digenetic parasites
and thus require two hosts to complete their life cycle: they multiply in the blood, tissues or body fluids of
a vertebrate host and, with the exception of T.equiperdum which is venereally transmitted, are ingested
by a haematophagous invertebrate vector. With a few notable exceptions, a cycle of development and
maturation occurs in the vector, after which the parasites are transmitted to another vertebrate host as the
vector feeds. Transmission is either by inoculation of trypanosomes with saliva or by contamination of
mucosa or broken skin with trypanosomes in the vector's faecal material, voided during the blood meal.
The type of development cycle within the vector determines whether or not infective, metacyclic parasites
are present in saliva or faeces. On this basis mammalian trypanosomes are classified into the two broad
sections of ‘salivaria’ and ‘stercoraria’.
In Africa, the pathogenic trypanosomes that cause sleeping sickness in humans and nagana in domestic
animals are salivarian, and cyclical development occurs in tsetse flies. Transmission of any trypanosome
species can take place mechanically without cyclical changes occurring in the vector. In nature, this is
effected by biting flies, such as Tabanus, Stomoxys and Lyperosia spp., which feed on more than one
animal before repletion.
Surra is a disease that affects a wide range of host animals, and it occurs in North Africa, the Near and
Far East, Central and South America, Philippines and Mauritius. It is caused by Trypanosoma evansi, a
dyskinetoplastic form of which — known as Trypanosoma equinum — also causes disease in equids in
Central and South America where it is known as ‘mal de Caderas’ or ‘Murrina’. These parasites have
adapted to an entirely mechanical, non-cyclical mode of transmission by blood-sucking flies other than
tsetse. Trypanosoma theileri is a stercorarian parasite of cattle which deserves greater mention. It was
first reported by Theiler in South Africa in 1903, and has since been found to occur in cattle throughout
the world. It is transmitted by tabanid flies and is widely regarded as being non-pathogenic, but in certain
circumstances it has been associated with disease.
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Human sleeping sickness is caused by T. brucei gambiense and T. b. rhodesiense. Whilst these two
subspecies do infect some domestic and wild animals, there are other, more significant pathogens of
livestock.
The remarkable alternate adaptations of these extracellular parasites to mammalian and insect hosts are
reflected in morphological changes which are readily detectable by light microscopy. Bloodstream forms
are trypomastigotes; from the posterior portion of an elongated body, some 8 – 35 µm long, arises a
flagellum which extends anteriorly, and which is connected to the body by an undulating membrane.
Beyond the anterior extremity of some species, the flagellum may extend free of attachment to the
undulating membrane. The beating of the flagellum pulls the trypanosome forwards, imparting
characteristic motility. Within the cell, in a posterior position and at the base of the flagellum, a kinetoplast
is found, and a single nucleus is located almost halfway along the body. In the tsetse fly, trypomastigotes
transform to epimastigotes in which the kinetoplast has migrated anteriorly, to a position adjacent to the
nucleus. Differences in the morphology of the trypomastigote stages of the various species form the basis
for differential diagnosis. The major characteristics are clearly seen in thin blood smears, stained with
Giemsa's, Leishman's or other Romanovsky stains.
a
b
c
d
Trypanosomes in thin blood smears, x1 000 stained with Diff-Quick. a = Trypanosoma congolense: note
absence of free flagellum; b = Trypanosoma vivax : note long free flagellum and large kinetoplast; c =
Trypanosoma brucei : note polymorphism, prominent undulating membrane and free flagellum; d =
Trypanosoma brucei dividing by longitudinal binary fission. (Unpublished photomicrographs by courtesy of
Dr L. Logan-Henfrey, International Laboratory for Research on Animal Diseases, PO Box 30709, Nairobi,
Kenya)
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Electron microphotograph of Trypanosoma congolense: cross-section showing flagellum (F), nucleus (N),
mitochondrion (M) and variable surface glycoprotein coat (VSG), x86 000. Bar represents 0,2 μm.
(Unpublished electron micrograph by courtesy of Dr P. Webster, Yale University School of Medicine,
Department of Cell Biology, New Haven, CT)
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Electron micrograph of Trypanosoma brucei : section through the flagellar pocket (FP) region of the cell.
Microtubules are longitudinally sectioned, x44 000. Bar represents 0,4 μm. (Unpublished electron micrograph
by courtesy of Dr P. Webster, Yale University School of Medicine, Department of Cell Biology, New Haven,
CT)
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Scanning electron micrograph of an intermediate (bloodstream) form of Trypanosoma brucei from the blood
of a mouse. Note the prominent undulating membrane, pointed posterior end and long, free flagellum. A
‘streamer’ or filopodium can also be seen. (By courtesy of Dr P. Gardiner and reprinted by kind permission of
Vinand Nantulya and Parasitology Today )
Trypanosomes show remarkable adaptation. They survive not only in the turbulent blood stream, where
they face vigorous immunological assault, but they also withstand the digestive enzymes of the tsetse
fly's alimentary tract.
Trypanosomes reproduce by longitudinal binary fission, both in the bloodstream and in the fly, although a
sexual process can apparently occur in the tsetse fly. Multiplication in each host culminates in the
presence of mature trypanosomes, which stop dividing and are pre-adapted to the conditions that they
will encounter in the next cyclical host. As a tsetse fly takes its blood meal from an infected host it ingests
trypanosomes. Pre-adapted parasites survive in the fly, but trypanosomes that are not metabolically
adapted to the new physiological conditions die. The transformation of bloodstream trypanosomes into
procyclic or midgut forms within the fly’s midgut is a crucial first step in the establishment of a
trypanosomal infection. The mechanism of maturation of a midgut infection is complex and, once
established does not always progress to maturation. Before the infection is mature, procyclic forms
transform into epimastigote and then to metacyclic forms. From the midgut, trypanosomes migrate to the
mouthparts or salivary glands.
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As the infective tsetse fly feeds, metacyclic trypanosomes and saliva pass through the hypopharynx and
are inoculated intradermally; it is here that infection is established. From the skin, the trypanosomes
reach the blood via the draining lymphatics within a few days. Trypanosomes multiply in the bloodstream,
and although initially their low numbers make detection difficult, the generation time of only a few hours
soon leads to high levels of parasitaemia. Trypanosomes may leave the bloodstream to reach various
extravascular sites.
The ability of trypanosomes to establish prolonged infections is attributable to the phenomenon of
antigenic variation. Each bloodstream trypanosome is completely clad in a dense surface glycoprotein
coat. Within a population of trypanosomes originating from a single infection, almost all bear the same
glycoprotein coat and are thus of the same antigen type. As parasitaemia rises, a swift antibody response
is elicited against the antigen type exposed on the surface of the bloodstream trypanosomes. These
specific antibodies attach to the surface glycoprotein and produce complement-mediated lysis of all
trypanosomes of that antigen type. However, before antibodies reach trypanolytic levels, some
trypanosomes — as few as one in 100 000 — switch off the gene that controls the production of the initial
surface glycoprotein and activate a gene that codes for a different protein. Trypanosomes which bear the
new surface glycoprotein are of a different antigen type and are not destroyed by antibody against the
first antigen type; they survive to produce another parasitaemic wave, which in turn is removed by
antibody specific for that antigen type. By this time a third variant has arisen, and, escaping the effect of
host antibody, it survives to produce the next parasitaemic peak. This antigenic variation is the result of
sequential expression of variable surface glycoproteins (VSGs) which constitute a repertoire of variable
antigen types (VATs). Infections arising from a single trypanosome may have a repertoire of more than
100 VATs. Thus shielded from total destruction, trypanosome infections usually run prolonged courses,
since each VAT is present for several days before being removed. Although within a parasitaemic peak
there is a mixture of a small number of VATs, the sequence of expression of VATs tends to be quite
stable in clonally-derived trypanosomes. This imparts immunologically distinct characteristics to a strain of
trypanosomes, the distinct strain being called a ‘serodeme’. In the course of successive parasitaemic
waves, some trypanosomes stop dividing and transform to the pre-adapted form able to survive in the
tsetse.
After ingestion by the tsetse, pre-adapted trypanosomes shed the glycoprotein coat, transform, multiply
and finally mature. Infective tsetse then transmits metacyclic trypanosomes to another host. Irrespective
of the VAT of the bloodstream trypanosomes ingested by a fly, the metacyclic VATs of a serodeme are
relatively constant. The antigenic diversity within a species leads to the possibility of animals in a tsetseinfested area being exposed to a large number of antigenically distinct trypanosomes, but although
trypanosomes within a species may be antigenically dissimilar, they are morphologically indistinguishable.
The characterization of trypanosomes relied for a long time on comparisons of their morphology, motility,
host specificity, tsetse transmissibility and their development within the fly, but more recent
characterization methods include isoenzyme typing, analysis of kinetoplast DNA by polyacrilamide gel
electrophoresis, pulsed field gradient electrophoresis of chromosomal digests and DNA hybridization.
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The sequel to infection with salivarian trypanosomes is not always disease. The outcome is determined
by many factors, frequently related to the susceptibility of the host and the pathogenicity of the
trypanosome. In the case of wild animals, a natural cycle of trypanosome transmission occurs which is
not associated with disease. Similarly, in some breeds of domestic animals, infection with salivarian
trypanosomes is tolerated, and host and parasite reach an equilibrium. Disturbance of the equilibrium
may precipitate disease a long time after establishment of the infection. Thus, although the tsetsetransmitted trypanosomes are aetiological agents of African trypanosomosis, infection is not always
synonymous with disease. The occurrence of T. theileri in healthy cattle throughout the world exemplifies
a well-developed host-parasite relationship.
Similar events occur in many wild animals which harbour tsetse-transmitted trypanosomes. Infected
animals show no clinical signs, but when they are subjected to the stress of capture, for example, their
immunity is reduced, parasitaemia flares up and clinical disease may be precipitated.
The epidemiology of African trypanosomosis is almost entirely dependent on tsetse flies. African
trypanosomes are well-adapted parasites of many species of wild animals, and sylvatic cycles of
trypanosome transmission occur throughout the 10 million square kilometres infested by this unique
vector. The natural hosts of salivarian trypanosomes usually show no clinical signs of infection, host and
parasites being in equilibrium. The large numbers of naturally infected wild animal hosts constitute a huge
reservoir of trypanosomes. Once infected, tsetses remain so for life and thus they too form a reservoir of
infection. Consequently, when domestic animals are introduced into areas in which sylvatic cycles of
trypanosome transmission occur, trypanosomosis always emerges as a serious disease. Wild animals are
the natural hosts of T. brucei rhodesiense, the aetiological agent of human sleeping sickness in central,
eastern and southern Africa. Thus, people living and working in tsetse areas are at risk of contracting the
disease, but for animal trypanosomosis to occur it is not always necessary for livestock to enter tsetseinfested areas; tsetse also move.
Changes in land use may also alter the extent of tsetse infestation. The abandonment of cultivation, for
various reasons, permits the regrowth of vegetation, which may then provide suitable tsetse habitat.
Conversely, the intensive settlement and cultivation seen in some areas destroy tsetse habitat.
The trypanosomal infection rate in tsetse is of prime importance. The ease with which infections develop
in tsetse depends upon the fly’s vectorial capacity and specific factors related to the blood of host
animals. Generally speaking, the duration of the development of trypanosomes in tsetse increases with
increasing complexity of the developmental cycle.
The prevalence of trypanosomal infections in tsetse is also affected by host preference. Two aspects are
important in this context: first, there is diversity of host preference among Glossina and, second, different
species of hosts vary in their susceptibility to infection with the different species of trypanosomes. Of
particular importance is the relationship between absolute tsetse density and biting rate. A good
understanding of this relationship is essential when predicting the impact of tsetse control interventions.
Usually the challenge increases with the tsetse population density but even at low densities tsetse can
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still cause a substantial disease problem. This is partly attributed to the often observed, increased
frequency with which flies that have metacyclic infections in their mouthparts probe.
Management practices may also alter the challenge to which livestock are subjected, and in this sense
management is central to the epidemiology of trypanosomosis. The different management of calves and
adult cattle can reduce significantly the level of challenge to which young animals are subjected.
Observations on the grazing ranges of livestock in West Africa showed that while cattle foraged widely in
tsetse-infested habitat, sheep, goats and donkeys remained closer to the villages. As a result, small
ruminants and equids were less exposed to attack by tsetse than cattle.
A major influence on the epidemiology of trypanosomosis is the use of trypanocidal drugs. Whilst
permitting the use of tsetse-infested land, chemotherapy may alter the prevalence of trypanosome
species in the area. In Zimbabwe, it was reported that the use of diminazene increased the prevalence of
T. vivax in cattle. Furthermore, the repeated use of trypanocides may result in the emergence of drug
resistant strains of trypanosomes, and the epidemiological picture then changes.
Wild animal hosts of tsetse, such as kudu, warthog, bushbuck, bushpig, buffalo, elephant and rhinoceros,
are vital to sylvatic cycles of trypanosome transmission and they form a major reservoir of infection. The
increasing popularity of game ranching or farming frequently entails the translocation of these animals
from tsetse habitats to tsetse-free areas. As a result, clinical disease may occur in animals normally
regarded as ‘immune’, in the absence of the tsetse vector. There is also the possibility that trypanosomes
could be mechanically transmitted from these species to livestock.
Wild animal hosts of tsetse and certain West African taurine cattle are tolerant of tsetse-transmitted
trypanosomes. Carefully controlled experiments have shown that the trypanotolerance of N’Dama cattle
and of African buffalo (Syncerus caffer) is an innate characteristic. This trait also occurs in some breeds
of sheep and goats. Lower trypanosomal parasitaemias and less severe anaemia occur in trypanotolerant
livestock than in trypanosusceptible animals. The epidemiological significance of this trait lies in the lower
morbidity and mortality due to trypanosomosis in tolerant breeds. Although trypanosome-infected
animals may effect self-cure, the usual sequel to infection in tolerant animals is the establishment of a
balance between host and parasite. If the host is stressed, the equilibrium is disturbed and a clinical
episode of variable severity is precipitated. Stress takes many forms. Animals in late pregnancy or which
are lactating are more susceptible to trypanosomosis. Overwork also constitutes a stress, which in
infected trypanotolerant stock may precipitate disease. This has serious consequences for animal traction
and for hard-working bulls used in restricted breeding seasons in tsetse-infested areas. In a similar
manner, intercurrent disease is stressful; trypanosome-infected animals with helminthosis or other
diseases are more severely affected than those with either disease alone. The combined effect of poor
nutrition and increased exercise is often associated with an increased incidence of trypanosomosis in the
dry season.
Age also has a significant effect on resistance to trypanosomosis. It is widely recognized that cattle born
in an infested area do not immediately succumb to disease, even though they acquire trypanosomal
infections when young, whereas cattle brought into the area readily succumb.
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Despite the antigenic complexity of trypanosomes, infected animals do mount immune responses which,
especially when supported by chemotherapy, can confer specific protection against homologous
serodemes. Thus, within a defined area, animals may acquire protective immunity against locally
prevalent serodemes. However, the movement of these animals to another area may expose them to
different strains, or serodemes, to which they may succumb. This type of tolerance requires continuous
challenge and explains the low mortality of cattle in high challenge, endemic areas (such as the Eastern
Province of Zambia) where trypanocidal drugs are used to prevent animals from succumbing to nagana.
The introduction of tsetse control measures in such areas would result in a loss of immunity that would
render the population highly susceptible to infection and disease. If tsetse control measures breakdown
severe outbreaks of trypanosomosis would ensue, probably with high mortality.
The African continent is experiencing considerable environmental changes as a result of an
unprecedented demographic growth.The increasing human pressure and the demand for arable land is a
major driver of land-use change resulting in deforestation, erosion and loss of biodiversity and suitable
habitats for tsetse flies Like many other arthropods, tsetse flies rely for their survival on habitats with
suitable conditions.The destruction and fragmentation of habitats has had important repercussions for the
density and distribution of tsetse flies. Insome instances,the drastic changes have resulted in the
disappearance of certain species In many cases, however, tsetse flies persist at lower densities in what
might appear to be unsuitable environments probably occupying microclimatic niches. The effects of
anthropogenic environmental changes on the epidemiology and impact of livestock trypanosomosis are
largely driven by the degree with which the tsetse flies adapt to an environment where domestic animals
are becoming increasingly important for their survival.These changes have been demonstrated in
southern Africa where epidemiological studies have clearly revealed the effect of such anthropogenic
changes on the impact of the disease on livestock and the appropriatenesss of particular control
strategies.
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