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.
PATHOGENESIS
The precise pathogenesis of the trypanosomoses remains far from clear. Three features — anaemia,
tissue damage and suppression of immune responses — dominate the pathology of trypanosomosis.
Infection becomes established at the site of inoculation of metacyclic trypanosomes in the skin, where a
chancre may form. Multiplication of the parasites induces an inflammatory response, the severity of which
depends upon the size of the inoculum, the species of parasite and the breed and species of the host.
These may originate from either the host or the parasites. The chancre reaches a maximum diameter, of
some 100 mm, ten to 14 days after an infective tsetse fly feed, its development preceding invasion of the
bloodstream by trypanosomes, and is accompanied by enlargement of the draining lymph nodes.
Trypanosomes are detectable in the blood 13 to 16 days after an infective tsetse fly has fed. At this time
the chancre begins to regress, and the characteristic series of intermittent parasitaemias begins.
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Bone marrow impression smear from a calf with an acute Trypanosoma vivax infection, showing a
macrophage which has phagocytosed several erythrocytes x1 200. Stained with Wrights-Leishman.
(Unpublished photomicrograph by courtesy of Dr L. Logan-Henfrey, International Laboratory for Research on
Animal Diseases, PO Box 30709, Nairobi, Kenya)
After an infection has become established, a protracted battle ensues as the parasite provokes an
immune response. Anti-VSG antibodies destroy large numbers of trypanosomes. The destruction of large
numbers of parasites releases lysosomal and other enzymes as well as structural proteins. Some of these
enzymes have been identified and are thought to be directly harmful to the host. Many biological
mediators such as the vasoactive amines are released from activated or damaged host cells. Anaemia is
a cardinal sign of trypanosomosis in many domestic animals, and the aetiology is probably similar in all
species. There is no single cause of the anaemia in trypanosomosis; the pathogenesis is complex and
involves a variety of mechanisms. Accompanying anaemia is leukopenia, which possibly arises from
direct inhibition of stem cell differentiation.
There are several possible sequelae to the early phase of infection, which depend largely on the nature of
the parasite and the susceptibility of the animal. There may be spontaneous recovery or death, but very
often there is a chronic phase which is characterized by infrequent, low-grade parasitaemias. Animals
lose weight and condition and, as a result of dyshaemopoiesis, remain anaemic. Extensive
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haemosiderosis occurs as a result of erythrophagocytosis, and the trapping of iron in phagocytes is
believed to contribute to the failure of erythropoiesis. Despite the apparent absence of parasites in the
circulation, red blood cell destruction continues, and insufficient erythropoietic compensation results in
persistent anaemia.
The pathogenesis of tissue lesions varies with the species of trypanosome. Trypanosoma congolense
and T. vivax are mainly intravascular parasites; they induce changes in the endothelium of capillaries,
and so indirectly cause damage to adjacent tissues. Trypanosoma brucei, on the other hand, has an
affinity for tissues. Its presence in the extravascular compartment is associated with marked lesions in
parasitized tissues.
The severity of endothelial injury also depends on the interaction of host and parasite.
Trypanosoma congolense often attaches to erythrocytes and capillary endothelium. Damage to
endothelial cells by parasite products, immune complexes, vasoactive amines and cytokines increases
vascular permeability. In T. congolense infections a generalized dilatation of capillary beds, which alters
the haemodynamics, is observed. The concomitant anaemia and more sluggish tissue perfusion affect
the exchange of metabolites and are associated with intracellular oedema of capillary endothelial cells.
Fibrinous microthrombi form in response to endothelial damage. These changes can be prominent in
T. vivax infections, with which disseminated intravascular coagulation is more commonly associated.
Alterations to the microcirculation produce secondary degenerative changes in tissues. As capillary
permeability increases, phagocytes and products of the parasite extravasate more readily and are
responsible, in part, for some of the tissue lesions. Cytokines and parasite-derived substances, such as
proteases, may directly injure host cells, an effect that is exacerbated by the formation of immune
complexes in tissues. In the case of T. brucei, parasites localized in tissues cause mechanical disruption
of host cells and probably also have some direct toxic effect on host cells, possibly mediated by their
enzymes. The cellular response provoked by parasites within the tissues causes further damage, and
auto-antibodies are also thought to play a role in inducing lesions. The influence of all of these changes
on the course of the disease depends upon their severity and upon the degree of impairment of the
affected organs.
An important feature of the pathogenesis of trypanosomosis is the effect on lymphoid tissue. As the
disease progresses, the volume of tissue in the spleen, lymph nodes and bone marrow inreases
markedly. This hyperplasia of reticuloendothelial cells reduces lymphoid cell density, and eventual
lymphoid depletion can occur.
Chronic disease is associated with progressive emaciation and eventually cachexia. This is usually
accompanied by low levels of parasitaemia but the pathogenesis is poorly understood. The reduced lifespan of red blood cells, the increased catabolism of many proteins, and the associated negative nitrogen
balance of clinically affected animals would appear to be largely responsible for the pitifully thin condition
of animals suffering from chronic trypanosomosis.
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