Trypanosomosis

Trypanosomosis is a protozoal infection which can occur in dogs and to a lesser extend in cats in many parts of the world. The disease is caused by protozoa of the genus Trypanosoma, which are mainly transmitted by tabanids, stable flies, tsetse flies or triatomines, depending on the species involved. Several domestic and wild animals are also susceptible for clinical infections with trypanosomes. Furthermore some of the pathogens possess a zoonotic potential causing among others sleeping sickness in man. In ruminants and horses the developing disease can be of massive economic importance and is restricting successful cattle farming in large parts of Africa. In dogs, the disease can be chronic or acute with a variety of symptoms and a potential lethal outcome. Some of the trypanosomes infecting dogs also possess an important zoonotic potential – with the presence of dogs as well as cats contributing significantly to increased domestic transmission (here for Trypanosoma cruzi) (Gürtler et al., 1993), causing Chagas disease in the Americas.

Pathogens

Trypanosoma parasites are flagellate protozoa belonging to the family Trypanosomatidae, which includes blood and tissue parasites of vertebrates, usually transmitted by blood-feeding vectors. Six trypanosome species are known to infect dogs: Trypanosoma brucei (brucei), Trypanosoma caninum (unknown pathogenicity), Trypanosoma congolense, Trypanosoma cruzi, Trypanosoma evansi and Trypanosoma rangeli (non-pathogenic). In cats, T. brucei (brucei), T. congolense and T. evansi have been reported as pathogens with possible clinical signs, whereas infection with T. cruzi is reported frequently, but without the clinical situation as described in dogs.

Trypanosomes are characterised by a longitudinal, fusiform appearance, a flagellum which arouses from the basal body moving forwards, an undulating membrane and a kinetoplast, lying behind the basal body.

The developmental cycle of trypanosomes is typically heteroxenous (that is, part of the cycle occurs in a vertebrate and part in an invertebrate host), although the cycle of one species (T. caninum) is still unknown.

A cyclic development takes place in the insect host. Trypomastigote forms are taken up by the insect during feeding. Depending on the species, the trypanosomes multiply within the insect host in different locations. At the end of the development, metacyclic forms are produced which are then transmitted to a new host. Based on the mode of transmission, trypanosomes can be divided into the group of Stercoraria, when the pathogen is passed on through the insect faeces and of Salivaria, when transmitted via the saliva. In some species a mechanical transmission may also occur.

Epidemiology

The single Trypanosoma species affecting dogs and cats possess such different vectors and different geographical distribution as well as clinical appearance so that subdivision by disease complex is the most logical separation.

Tsetse-transmitted Trypanosoma sp. infection

This group affects all domesticated animals, causing so-called Nagana in cattle and sleeping sickness in man. The responsible species of this group, which are of importance in cats and dogs are Trypanosoma brucei (brucei) and Trypanosoma congolense. The distribution of these two Trypanosoma species is correlated with the distribution of the main vector, tsetse flies. Additionally to tsetse transmission, mechanical transmission by tabanids and other biting flies might generally also occur, for example outside the tsetse distribution areas as in Central and South America.

Trypanosoma evansi infection

This infection is especially of importance in horses and camels, causing so-called Surra or Mal de cadeiras. Nevertheless, all domestic animals are susceptible, and the disease can as well be fatal in dogs (Echeverria et al., 2019) and has been reported with clinical signs in cats (e.g., Tarello, 2005; Misra et al., 2016). The distribution in Africa extends into the tsetse area, but the disease is also reported in Middle East, Far East, Asia and Central and South America (Petersen and Grinnage-Pulley, 2016). Transmission is primarily by biting flies, mainly tabanids and Stomoxys. In Central and South America Trypanosoma evansi is also transmitted by vampire bats of the Desmodus rotundus genus, in which the parasites can multiply and survive for a long time (Herrera et al., 2005). Additionally, oral transmission by consumption of affected meat from T. evansi-infected herbivores has as well been demonstrated besides other animals also in dogs (Raina et al., 1985).

Trypanosoma cruzi infection

This infection is known also as Chagas disease or American trypanosomosis, a major neglected tropical disease, especially endemic in continental Latin American countries. According to WHO, about 6 to 7 million people worldwide are estimated to be infected with Trypanosoma cruzi (WHO, 2021). All mammals are considered susceptible to infection, but the disease is best recognized in dogs and humans, with dogs serving as a major domestic reservoir (Petersen and Grinnage-Pulley, 2016). Dogs constitute the main domestic reservoir of T. cruzi in endemic areas of Latin America, where triatomines are present (Crisante et al. 2006; Estrada-Franco et al. 2006; Gürtler et al. 1990). In cats, infection is as well occurring, but usually subclinical. The main transmission is via the excrements of triatomines.

Besides these Trypanosoma species, the following two species have also been detected in dogs:

Trypanosoma rangeli infection

This Trypanosoma species is another human parasite, which has also been detected in dogs in endemic areas of this species in Latin America (D’Alessandro, 1976; Pifano et al., 1948). Trypanosoma rangeli can be transmitted by both saliva and faeces of triatomines (Dantas-Torres, 2008). It is non-pathogenic in dogs, but can be mistaken for T. cruzi during diagnosis in areas of overlapping occurrence (Dantas-Torres, 2008).

Trypanosoma caninum infection

Trypanosoma caninum is another Trypanosoma species, which has been isolated in dogs in Brazil. The species has unique biological characteristics, including e.g. its isolation exclusively from intact skin fragments (Madeira et al., 2009; Madeira et al., 2014). It appears to be non-pathogenic to dogs, in which the infection triggers a mild humoral immune response (Alves et al., 2012; Madeira et al., 2014). Besides unknown pathogenicity, the transmission cycle of this little-known trypanosome species remains also unclear (Madeira et al., 2009).

Distribution

The following distributions of the trypanosomes, important for canines and felines, are reported:

The distribution of Trypanosoma brucei (brucei) and Trypanosoma congolense is correlated with the distribution of the main vector, tsetse flies, which is ranging in Africa from latitude 15°N to 29°S (Petersen & Grinnage-Pulley, 2016), with regional varieties for the single species. Additionally, the pathogens are also reported outside the classical tsetse areas, e.g. in Central and South America where mechanical transmission is of importance.

Trypanosoma evansi and its corresponding disease Surra/Mal de cadeiras is reported within and outside tsetse areas. Besides North Africa, it is also reported in Middle East, Far East, Asia and Central and South America (Petersen and Grinnage-Pulley, 2016). The mainly mechanically through the bite of bloodsucking insects from the family Tabanidae and Muscidae has allowed the trypanosome to move beyond the tsetse fly region and out of Africa.

Trypanosoma cruzi, the agent of Chagas disease or American trypanosomosis, is found mainly in endemic areas of 21 continental Latin American countries (Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela) (WHO, 2021). Furthermore the pathogen is reported in the southern United States and throughout Mexico. In the US, in detail, T. cruzi-infected dogs have been reported from Tennessee, South Carolina, Georgia, Virginia, Louisiana, California, Oklahoma, and Texas (reviewed in Bern et al., 2011).

Dogs are also commonly infected with Trypanosoma rangeli in areas of Latin America that are endemic for this species (D’Alessandro, 1976; Pífano et al., 1948). Overlapping areas with T. cruzi occurrence have been reported, producing mixed infections in vectors, which can make morphological differentiation of species difficult (Vallejo et al., 1988) or which might produce mixed infections in vertebrates , thus causing crossed serological reactions, complicating a specific diagnosis of Chagas infection (Guhl and Marinkelle, 1982; Guhl et al., 1985, 1987). Very few cats have been examined for the presence of T. rangeli. A cat in Venezuela was found to have circulating trypomastigotes of this species in its blood (Pifano, 1954), and in a further study in Venezuela 8.5% of cats were shown to be infected with T. rangeli (Tonn et al., 1983).

Finally, Trypanosoma caninum has been reported in dogs in different areas of Brazil (Barros et al., 2012; de Oliveira et al., 2015; Madeira et al., 2009).

Transmission

Trypanosoma brucei (brucei) and Trypanosoma congolense are two pathogens causing so-called Nagana especially in cattle respectively sleeping sickness in man. Both pathogens are as well of importance in dogs and cats. They are usually transmitted by tsetse flies (Glossina spp.) during blood feeding. The trypomastigote form is inoculated by the insect. Within the vector the parasite multiplies in a different form and finally is transmitted to a new host during feeding of the fly. Apart from this cyclic development and transmission, the pathogens can also be transferred mechanically throughtabanids and other biting flies, for example outside the tsetse distribution areas.

Trypanosoma evansi is the pathogenic agent of the so-called Surra or Mal de Cadeiras in camels and equines, but is also reported as pathogenic agent in dogs and cats. It is primarily transmitted mechanically by tabanids and stable flies (Stomoxys spp.). In Central and South America, T. evansi is also transmitted by vampire bats of the Desmodus rotundus genus, in which the parasites can multiply and survive for a long time (Herrera et al., 2005). Dogs can also be infected by consumption of affected meat from T. evansi-infected herbivores (Raina et al., 1985).

Trypanosoma cruzi and Trypanosoma rangeli are both transmitted by triatomines, also known as kissing bugs

T. cruzi is transmitted to the definitive host through the vector’s excrement. Metacyclic trypanosomes penetrate the organism either through normal healthy mucosa or broken skin, often caused by scratching. Ingestion of T. cruzi-infected bugs may also cause infection of the definitive host (see further down).

T. rangeli can be transmitted through both faeces and saliva of the vector (Dantas-Torres, 2008), the main route of transmission seems to be via saliva, through the bite of an infected triatomine. But there is still a lot of debate on the maintenance of T. rangeli in vertebrates.

Additionally, T. cruzi and T. rangeli have also been detected in different bats in Brazil (e.g., Lisboa et al., 2008; Maia da Silva et al., 2009), representing a potential reservoir.

Regarding T. cruzi, other modes of transmission (here including humans) are blood transfusions, organ transplants, oral transmission by consumption of food contaminated by vectors, and congenital transmission (Camandaroba et al., 2002; Kribs-Zaleta, 2006, 2010a; Roellig et al., 2009). According to Kribs-Zaleta (2010b) these ways of transmission may also be important for sylvatic hosts as well: vertical (congenital) transmission has been verified experimentally among rats (Moreno et al., 2003) and supported by circumstantial evidence among lemurs (Hall et al., 2007) and other animals. Connatal transmission of T. cruzi has also been reported in dogs (Rodríguez-Morales et al., 2011). Oral infection generally is produced by the ingestion of infected triatomines or their faeces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials (Toso et al., 2011). Other likely routes of oral transmission in domestic mammals are the ingestion of faeces-contaminated water or licking faeces-contaminated fur (Coffield et al., 2003).

Regarding the transmission of Trypanosoma caninum, attempts to infect triatomines were unsuccessful. The mode of transmission of this trypanosome species remains unclear (Madeira et al., 2009).

Pathogenesis

Tsetse-transmitted Trypanosoma (Trypanosoma brucei (brucei) and Trypanosoma congolense)

After inoculation of metacyclic trypanosomes into the skin, the pathogens reside for a few days before they enter the lymph and lymph nodes and then the bloodstream, where division by binary fission takes place (Petersen and Grinnage-Pulley, 2016). Depending on the species, different cells and organs are affected: T. congolense attaches to endothelial cells and localizes in capillaries and small blood vessels, while T. brucei (brucei) invades tissues and causes tissue damage in several organs (Petersen and Grinnage-Pulley, 2016). Immune complexes additionally cause inflammation and further signs of disease and lesions.
As consequence, besides anaemia, degenerative, inflammatory and necrotic lesions in diverse organs due to an intensive invasion of lymphocytes, macrophages and plasma cells can be observed.

Trypanosoma evansi

The pathogenesis of T. evansi is complex and the cause of death is still somewhat obscure (Habila et al., 2012). The trypanosomes of T. evansi can be found in intra- and extravascular fluid (Sudarto et al., 1990). They invade the host by multiplying rapidly in the blood and later in the central nervous system (CNS). A typical feature in trypanosomosis is anaemia. There are several reports on the mechanisms of development of anaemia. Haemolytic factors such as haemolysis and free fatty acids, immunologic mechanisms, haemodilution, coagulation disorders, depression of erythrogenesis and release of trypanosomal sialidase have been implicated in the development of anaemia (Adamu et al., 2008; Esievo and Saror, 1991; Igbokwe, 1989; Murray, 1978; Omer et al., 2007). The anaemia seems predominantly the result of haemolytic crises in which the erythrocytes are being destroyed by an expanded mononuclear phagocytic system (Igbokwe and Mohammed, 1991). The haemolysis seems to be triggered by an autoimmune reaction against the erythrocytes (Rickman and Cox, 1983). The infiltration and dissemination of T. evansi in the CNS (Berlin et al., 2009) finally causes severe and potentially fatal clinical symptoms in the second stage of the disease.

Trypanosoma cruzi

After entering the bloodstream as metacyclic trypomastigotes, the pathogens actively invade many cell types, where multiplication by division in the amastigote form takes place. Subsequently transformation back into the trypomastigote form and cell lysis releases the trypomastigotes, which then invade new cells. In the case of T. cruzi, a tropism for cardiac and smooth muscle has been observed besides numerous other tissues (Petersen and Grinnage-Pulley, 2016).
The organ and tissue damage during an acute T. cruzi infection is caused by the parasite itself and by the host’s acute immunoinflammatory response, which is elicited by the presence of the parasite (Andrade, 1999). During the chronic infection, the balance between immune-mediated parasite containment and damaging inflammation of the host tissues probably determines the course of disease (Rassi et al., 2010). Although the pathogenesis of chronic Chagas disease is not completely understood (Rassi et al., 2010), a growing consensus indicates that parasite persistence is needed for the development of the disease (Bonney and Engman, 2008; Kierszenbaum, 2007; Tarleton, 2003). But it is unclear, whether the tissue damage is mostly caused by direct parasite factors, or is indirectly triggered through the immunopathology or the autoimmune mechanisms caused by the parasite (Marin-Neto et al., 2007; Soares et al., 2001; Tarleton and Zhang, 1999).
During the acute stage, all types of nucleated cells in the (human) host are potential targets for the infection with T. cruzi. With development of an immune response, parasitaemia is reduced, but the parasite is not completely eliminated. An infection of specific tissues, such as muscle or enteric ganglia, persists indefinitely for the life of the host (Rassi et al., 2010).

Trypanosoma rangeli

T. rangeli is apathogenic for the vertebrate host.
The presence of some form of reproduction of T. rangeli in a vertebrate host is controversially discussed (Guhl and Vallejo, 2003). An increase in the number of trypomastigotes (Urdaneta-Morales and Tejero, 1985) as well as amastigote forms in different tissues (Urdaneta-Morales and Tejero, 1986) has been described, whereas other researchers have not been successful in detecting intracellular forms or tissue lesions caused by the parasite (Grisard et al., 1999; Herbig-Sandreuter 1955). Thus the possibility of T. rangeli reproduction in the vertebrate host might be strain dependant (Guhl and Vallejo, 2003).

Trypanosoma caninum

Data related to the pathogenesis of this parasite in dogs are still unknown. T. caninum is isolated exclusively from intact skin fragments, an unusual feature of the Trypanosoma genus; it also does not infect triatomine insects, and it grows very well in axenic cultures, with a predominance of epimastigote forms (Madeira et al., 2009).
Apparently, this parasite is not very immunogenic for dogs, even though it is able to stimulate the production of specific antibodies (Alves et al., 2012).

 

Diagnosis

Due to the multisystemic nature of trypanosomosis, the variety of clinical signs, and the indeterminate character of chronic Chagas disease, diagnosis of Trypanosoma infection can be missed (Eloy and Lucheis, 2009). In dogs, a presumptive diagnosis might be based on clinical findings plus a history of having been in Trypanosoma endemic zones and on laboratory findings, but often the clinical pathological aspects are unspecific. In cats, the infection often is subclinical and even less indicative than eventually in dogs.
Generally, diagnosis can be performed by blood culture, through the examination of fresh blood and Giemsa-stained blood smears, and by the detection of anti-Trypanosoma antibodies using different serological tests (e.g., indirect immunofluorescence assay, ELISA). Molecular methods (e.g., polymerase chain reaction [PCR]) have also been used for the detection and characterisation of trypanosomes (Gow et al, 2007).
Cytological examination of blood smears illustrates the different trypomastigote stages of the different Trypanosoma species as following: 20 μm long in T. cruzi (1-2 undulations of the undulating membrane), 26-34 μm long in T. rangeli (with 4-5 undulations of the undulating membrane), 9-18 μm in long in T. congolense (with 3-4 undulations of the undulating membrane). T. brucei will present in a short and stumpy form (12-26 μm long) with no free flagellum and a long and slender form (23-42 μm long) with a free flagellum. T. evansi is morphologically indistinguishable from T. brucei (Bowman et al., 2002).
A conclusive diagnosis of Trypanosoma infection can be established by demonstrating the presence of parasites, but parasitological methods have poor sensitivity. The fluctuating character of parasitaemia and the very low number of circulating parasites, especially in the chronic infection stage, frequently impede their detection, even with the use of concentration methods (Eloy and Lucheis, 2009).
In contrast to the limitations in parasitological diagnosis, serological diagnosis is facilitated by the presence of many early and apparently constant anti-T. evansi and anti-T. cruzi antibodies during the course of infection (Eloy and Lucheis, 2009). But in relation to specificity, serological methods for both antibody and antigen detection present problems due to cross-reactivity. In this context, cross reactivity between T. cruzi and T. rangeli antigens and antibodies (Caballero et al., 2007; Saldaña and Sousa, 1996) and between T. cruzi tests and other trypanosomatid genera, such as Leishmania (Abras et al., 2016; Caballero et al., 2007; Santos et al., 2016) have been reported. Especially for canine test systems, cross reactions of canine Leishmania test systems with T. caninum positive dogs could also be documented (Alves et al., 2012). For the evaluation of the different methods in the diagnosis of T. cruzi infection in dogs and cats see e.g. Enriquez et al. (2013).

 

Clinical Signs

Depending on the species of Trypanosoma, dogs can show anything from non-pathogenic infection to acute or chronic disease with a variety of clinical signs and a potential lethal outcome. In cats, data on clinical signs and seroprevalences are more scarce, but again a wide spectrum from non-pathogenic over moderate to severe disease with fatal outcome is described.

Tsetse-transmitted Trypanosoma (Trypanosoma brucei (brucei) and Trypanosoma congolense)

Dogs and cats are susceptible to T. brucei (brucei) infection.
The experimental disease in dogs has been likened to that in man, in the course, signs, and lesions (Losos and Ikede, 1972). Loss of weight, subcutaneous oedema, keratitis, and conjunctivitis are commonly seen (see Losos and Ikede, 1972 for detailed citations). Fever, emaciation, dullness, and oedema of eye lids and ventral thorax have also been reported in infected dogs (Bouffard, 1908). A detailed description of canine experimental infection with T. brucei can be found in Nwosu and Ikeme (1992) with lethal outcome for two dogs showing acute disease on days 7 and 8 post infection (p.i.), and lethal outcome for two further dogs showing sub-acute disease on days 24 and 28 p.i. Furthermore, in one dog with both acute and sub-acute disease, nervous signs with mild salivation towards the terminal stages of the disease was recorded (Nwosu and Ikeme, 1992).
Clinic of T. brucei (brucei) infection in cats is similar to that in dogs with development of emaciation, intermittent keratitis, conjunctivitis, oedema of eyelids, alopecia, and hypertrophy of the spleen (Losos and Ikede, 1972). Old reports of experimental infections of cats describe a lethal outcome within 22 to 26 days p.i. (Kanthack et al., 1899). These cats developed pyrexia, ocular changes including an aqueous flare and conjunctivitis, oedema of the face and eyelids. At necropsy, they were found to have pronounced wasting with generalized lymphadenopathy, splenomegaly, hepatomegaly, and pleura and pericardium haemorrhage (Kanthack et al., 1899). Natural infection in a cat demonstrated apathy, anorexia, oedema and erythema of the head region, and ocular signs such as photophobia, lacrimation, conjunctivitis, keratitis, as well as pannus, hypopyon, and hypertony (Hill, 1955), with ocular signs also reported by Mortelmans and Neetens (1975).  
T. congolense infection in dogs has been observed with severe clinical signs in the acute cases including keratitis, photophobia, acute ulcerative stomatitis, and oedema of the periorbital space and lower jaw (Parkin, 1935). Jaundice, anaemia, and enlargement of lymph nodes were also reported by Curson (1928). A chronic course reported by Bouffard and Dupont (1912) also described emaciation, anaemia, and subcutaneous oedema as main signs (Joweit, 1910).
In cats, T. congolense infection has been reported to cause anaemia, emaciation and lethal outcome, but no ocular signs (Curson, 1928; Laveran, 1909).

Trypanosoma evansi

T. evansi regularly affects dogs and also cats (Desquenes et al., 2013).
A number of studies report on a wide range of clinical findings as well as high mortality rates in dogs infected with T. evansi (Aquino et al., 1999; Colpo et al., 2005; Echeverria et al., 2019; Franciscato et al., 2007; Herrera et al., 2004; Silva et al., 1995). The clinical signs include generalized lymphadenomegaly, apathy, weight loss, hyperthermia, corneal opacity, hypochromic mucous membranes, cardiac arrhythmia, hepatosplenomegaly, oedema, cutaneous lesions, anorexia, vomiting, hyperaemic mucosa and diarrhoea.
Clinical descriptions of T. evansi infections in cats are less often to be found in the literature. After experimental infection of cats, vomiting, diarrhoea, hyperthermia, progressive weight loss, facial oedema, corneal opacity, lymphadenopathy and hindlimb instability as well as a potential lethal outcome were observed (Costa et al., 2010, Da Silva et al., 2010). Findings furthermore included generalized muscle atrophy, pale mucosae, icterus, lymphadenopathy and splenomegaly, corneal opacity, subcutaneous oedema (mainly of the head) and hydropericardium (Da Silva et al., 2010). These findings were consistent with those found in felines naturally or experimentally infected by T. evansi (Choudhury and Misra, 1972; Misra et al., 2016; Tarello, 2005). Along with the clinical signs a regenerative anaemia was observed (Da Silva et al., 2009).

Trypanosoma cruzi

Dogs infected with T. cruzi may develop acute and chronic manifestations similar to those in humans, including acute myocarditis, arrhythmias, chronic dilated cardiomyopathy, congestive heart failure, and sudden death (Kjos et al., 2008). Barr (2009) even describes three distinct phases of Chagas myocarditis in dogs; acute, indeterminate (or latent), and chronic (Barr et al., 1989, 1991a, b, 1992, 1995). Peak parasitemia coincides roughly with the appearance of generalized lymphadenopathy and acute myocarditis at 17 days p.i. Lethargy, generalized lymphadenopathy, slow capillary refill time with pale mucous membranes, and in some cases splenomegaly and hepatomegaly, are the main presenting signs in young puppies. In dogs older than 6 months, clinical signs are often much less severe and sometimes not apparent at all (Barr, 2009). Although less common than signs referable to cardiac abnormalities, neurologic signs referable to meningoencephalitis may also occur, and include weakness, pelvic limb ataxia, and hyperreflexive spinal reflexes suggestive of distemper (Barr, 2009). Dogs that survive the acute phase enter the prolonged indeterminate phase typified by the lack of clinical signs (Barr, 2009). The dog is the only experimental animal model in which the indeterminate phase progresses to the late phase of severe, chronic myocarditis (Andrade et al., 1997). More detailed data on the intermediate stage, especially regarding cardiac histologic and ultrastructural findings can be found in Andrade et al. (1997). Although not all dogs progress to develop chronic disease, some develop chronic myocarditis with cardiac dilatation over the next 8 to 36 months (Barr et al., 1991a, 1992). With the progressive development of cardiac dilation, ECG abnormalities become more prevalent and may even result in sudden death. Clinical signs referable to right-sided and eventually, in some, left-sided chamber failure occurs, and can include pulse deficits, ascites, pleural effusion, hepatomegaly, and jugular venous congestion (Barr et al., 1991a). Dogs diagnosed at an older age (mean of 9 years) survived between 30 to 60 months whereas dogs diagnosed at a younger age (mean of 4.5 years) survived only up to 5 months after diagnosis (Meurs et al., 1998). For more detailed clinical descriptions see Barr (2009).
The presence of T. cruzi in domestic cats was first reported in 1978 in north-east Brazil (Mott et al., 1978). Since then seroprevalences in cats have been reported in several studies (e.g., Cardinal et al., 2007; McCown and Grzeszak, 2010; Longoni et al., 2012), but clinical disease has nearly not been reported in contrast to dogs. A single cat in Montevideo, Uruguay, has been described as having signs due to T. cruzi including convulsions and transient posterior paralysis (Talice, 1938).

Trypanosoma rangeli

T. rangeli has been reported to be non-pathogenic in dogs as well as in humans. It is as well likely to be non-pathogenic in cats.

Trypanosoma caninum

T. caninum infection is suggested to be asymptomatic in dogs, without specific clinical signs, occurring with low parasitaemia (Madeira et al., 2014). Furthermore, the humoral immune response in the infection by T. caninum has been low or absent (Alves et al., 2012), a fact which may be related to the characteristic of T. caninum in which its presence appears to be limited and restricted to the skin (Madeira et al., 2014). Prevalence data as well as data on potential clinical signs in cats is missing.

 

Treatment & Prevention

For treatment in dogs, several drugs have been used, including e.g., diminazene aceturate, quinapyramin sulfate, benznidazole and nifurtimox. The duration of the therapy is variable, dependent on the Trypanosoma species involved and the response to therapy. The first two compounds date back to the midst of the last century (see Giordani et al., 2016 for detailed history). The current drugs all have small therapeutic indices and can cause local irritancy at the injection site or even more severe side effects. Additionally, extensive utilization in the past has led to the appearance of resistant parasites in the field (e.g., Anene et al., 2006), and the fact that many of these trypanocides are chemically related, has exacerbated the situation with cross-resistance onset (Peregrine, 1994). After treatment, relapses are common.
For cats data on treatment is very scarce.

Tsetse-transmitted Trypanosoma (Trypanosoma brucei (brucei) and Trypanosoma congolense)

T. brucei infection in dogs has been reported to be treated with diminazene aceturate resulting in clearance of parasites within 24 hours after treatment (Egbe-Nwiyi and Anita, 1993). In different studies with diminazene aceturate or isometamidium chloride, apparent recovery was observed, but relapses occurred later on, resulting in more resistant parasite populations (Kaggwa et al., 1988). In further treatment trials with diminazene aceturate or pentamidine isethionate, parasite clearance could first be observed, followed by relapse in the diminazene aceturate group, whereas in the pentamidine isethionate group no relapse was recorded, but death occurred in two dogs (Akpa et al., 2008). Old reports describe the use of prothidium and isometamidium in T. brucei infected dogs (Toure, 1973).
T. congolense infection in dogs has been reported to be successfully treated with isometamidium chloride and additional supportive therapy including intravenous fluids, nonsteroidal anti-inflammatory drugs and corticosteroids at an early disease stage (Davoust et al., 2006; Watier-Grillot et al., 2013). Pentamidine has been used as alternative therapy in a canine case report, with good clinical improvement, but an unclear long-term infection status (Deschamps et al., 2016). Finally, diminazene aceturate plus difluoromethylornithine (DFMO) was tested in experimentally T. congolense infected dogs, but could not prevent relapse (Onyeyili and Anika, 1990).

Treatment reports of T. brucei infected cats are very scarce. Hill (1955) reported on a treatment with quinapyramine sulfate (antrycide methyl-sulphate) in a single case. Improvement of clinical signs was recorded, but relapses occurred despite increasing the dosage and finally resulted in euthanasia. Anecdotal reports of suramin treatment of cats by Mettam (1947) and Unsworth (1954) also exist, but generally the data is scarce and from the midst of the last century.
Treatment of T. congolense infection in cats has not been tried (Bowman et al., 2002).

Trypanosoma evansi

Diminazene aceturate has been shown to be an effective treatment for T. evansi in dogs, with application on two consecutive days (see e.g., Saari et al., 2018). But toxicity in dogs is an issue, which has to be considered (Losos and Crockett, 1969; Oppong, 1969). According to Desquesnes et al. (2013), dogs can also be treated with isometamidium chloride, despite being quite sensitive to both above mentioned drugs. Adequate water supply is recommended to avoid a toxic effect on the kidneys, which can be fatal. Furthermore, case reports on the application of quinapyramine sulphate (and chloride) in T. evansi infected dogs are also published with negative test results three days after treatment in some of the treated dogs, but without any long-term observation (Singh et al., 1993). After suramin treatment of a T. evansi infected dog, trypanosomes could not be detected, but relapse and death were recorded about three months later (Defontis et al., 2012). The efficacy of melarsomine dihydrochloride was also evaluated in dogs. The treatment could clear the parasite from the blood, but was not successful in cases with nervous infection (Desquesnes et al., 2012).
When the infection threat is lethal, such as with T. evansi in dogs, a strategy to kill all parasites, as far as possible, is generally preferred. The objective in this case is to achieve fully curative or “sterilizing” treatment, which requires the use of (i) curative drugs, such as diminazene aceturate or melarsomine dihydrochloride; or (ii) chemoprophylactic drugs, such as quinapyramine sulfate and chloride (Desquesnes et al., 2013). However, in the case of an invasion of the nervous system, none of these drugs have yet been proven to be efficient (Desquesnes et al., 2013).
Generally, toxicity and recurrence of the disease requiring prolongation and repetition of the treatment are two major problems.

In cats, experimental treatment with diminazene aceturate on two time points was reported to clear infection with T. evansi, but again recurrence of parasitaemia was observed about three weeks after treatment (Scheidle, 1982), whereas Sivajothi and Sudhakara Reddy (2018) reported successful treatment with diminazene aceturate along with other supportive medication and negative blood smears after a five-day therapy. According to Desquesnes et al. (2013), cats can also be treated with isometamidium chloride, despite being quite sensitive to both above mentioned drugs. Again, adequate water supply is recommended to avoid a toxic effect on the kidneys, which can be fatal (Desquesnes et al., 2013). Finally, successful treatment of feline T. evansi infection with melarsomine was reported and confirmed by negative blood smears between one week and one month after therapy (Tarello, 2005).

Trypanosoma cruzi

Treatment of dogs in the acute phase of Chagas disease is poorly reported as this phase is seldom recognized (Barr, 2009). The drug of choice for Chagas disease in general is benznidazole, but nifurtimox can also be used (Croft et al., 2005). In dogs, nifurtimox usually in association with corticosteroids (Andrade et al., 1981) and benznidazole have been reported; see Barr (2009) for detailed summary on therapy instructions. But due to severe side effects with nifurtimox, benznidazole finally is the drug of choice in dogs (Barr, 2009), due to less side effects and reports on effective treatment of acute canine infections (Viotti et al., 1994). As antiparasitic treatment in the chronic stage rarely changes the outcome of disease, treatment directed toward the myocardial failure and ventricular arrhythmias is strongly recommended (Barr, 2009; Petersen and Grinnage-Pulley, 2016), even though ventricular arrhythmias seem resistant to drug therapy (Barr, 2006). Medical treatments rarely result in a clinical cure. In severe cases of acute myocarditis coupled with high parasitaemia, prognosis is poor and zoonotic risk is higher (to those handling blood products), so that euthanasia should be considered in these cases (Barr, 2009).

There are no reports of attempted treatment of infected cats (Bowman et al., 2002).


As the main part of the Trypanosoma transmissions is vector-borne, prevention in form of control and removal of the corresponding vectors (triatomines, tsetses, tabanids) is essential. The control of the vectors can be achieved by insecticide spraying, insecticide impregnated screens, insecticide use on livestock etc. But depending on the vector, measures and success can be very different. Awareness campaigns, health education activities, and, in case of triatomines as vectors, upgrading of housing conditions, removal of nesting material and decreasing vector attraction to dwellings at night by turning off outdoor lighting are further control measures (Barr, 2009; Eloy and Lucheis, 2009; Petersen and Grinnage-Pulley, 2016). Oral infection by consumption of infected meat (T. evansi) should be avoided by not feeding infected animal meat, by elimination of dead animals’ carcasses as soon as possible and by containment of dogs, especially stray dogs, around slaughterhouses and on livestock farms (Desquesnes et al., 2013). Oral infection by vector-contaminated food (T. cruzi) should also be avoided. In the case of T. cruzi breeding of positive bitches should be discouraged, blood donor screening is recommended and iatrogenic transmission should also be avoided through disinfecting measures of contaminated surfaces (Petersen and Grinnage-Pulley, 2016). Comparable to prevention approaches in livestock, chemoprophylaxis against T. evansi infection with isometamidium chloride, combined with prophylactic measures, such as ectoparasiticides treatment etc., has also been performed in dogs and demonstrated great efficiency in preventing canine infection (Watier-Grillot et al., 2013). Detailed information on T. evansi prevention in general can also be found in Desquesnes et al. (2013)
In respect to Chagas disease, a multi-pronged approach including community mobilisation and empowerment, intersectoral cooperation and adhesion to integrated vector management principles may be the key to sustainable vector and disease control in the affected regions (Gürtler and Yadon, 2015). The epidemiological complexity forced governments to adopt this approach in which social participation, education, and housing improvement were part of the strategy added to the traditional insecticide spraying (Travi, 2019). As several studies have indicated that the presence of domestic animals, principally T. cruzi-infected dogs, increase the risk of T. cruzi infection in humans (Crisante et al., 2006; Enriquez et al., 2014; Gurtler et al., 1996; Jimenez-Coello et al., 2010; Pineda et al., 2011) and dogs have been defined as ‘‘the driving force of the infection cycle’’ of T. cruzi (Coffield et al., 2013), ectoparasiticidal treatment of dogs has been examined in respect to vector control. Fipronil treatment has not been successful in protecting dogs from contact with triatomines (Gürtler et al., 2009), whereas insecticide impregnated collars reduced fecundity and molting rates of triatomines, ultimately causing the extinction of exposed bug populations (Reithinger et al., 2006). Experimental utilization of a member of the isoxazoline family demonstrated high mortality rates of triatomines. Dogs were not protected against T. cruzi infection, but transmission in households was significantly impaired, due to a sustained lethal activity on the bugs (Laiño et al., 2019), thus representing an additional potential tool in the control of Chagas disease.
Regarding cats, control and prevention is similar to the measures listed above, but the free roaming attitude of cats in the wilds will continue to place them at great risk of acquiring infections due to either bites of vectors or the ingestion of infected meat or rodents (Bowman et al., 2002).

Zoonotic Potential

Of the Trypanosoma species relevant for dogs and cats, especially two have zoonotic character. There have been several human Trypanosoma evansi infections reported in- and outside Africa (Haridy et al., 2011; Joshi et al., 2005; Truc et al., 2007, 2013; Vanhollebeke et al., 2006). And most important, Trypanosoma cruzi, the agent of Chagas disease, possesses zoonotic potential. In detail, Chagas disease affects about 6-8 million people worldwide (Schofield et al., 2006) and causes approximately 12,000 deaths per year (PAHO, 2021). About 70 million people are living worldwide in areas at risk for infection (PAHO, 2021; WHO, 2015). The infection has two successive phases in humans; an acute, usually asymptomatic or oligosymptomatic phase (Prata, 2001), and a chronic phase. About 30-40% of the human patients may progress to the chronic phase with neurological, cardiac, digestive (megacolon or megaesophagus), or cardiodigestive clinical signs (Vago et al., 2000). Chronic Chagas disease is considered a disabling disease responsible for the most significant morbidity and mortality among parasitic diseases (Bonney, 2014), leading to a global expenditure of USD$ 627.5 million per year in health care costs (Lee et al., 2013). The estimated cost per patient at the early stages of the disease is $ 200, but in the chronic symptomatic form, this value can reach $ 4,000 to 6,000 (Abuhab et al., 2013).
Some 150 mammal species are susceptible to T. cruzi, with dogs, cats, rodents, and both domestic and wild lagomorphs constituting an important reservoir for human infection. Several studies have shown that one of the major risk factors for T. cruzi infection in humans is the presence and number of dogs in the home (Acha and Szyfres, 2003). This observation would indicate that dogs are an important source of food and infection for the vectors (Gürtler et al., 1998), thus, participating in the zoonotic cycle of transmission of T. cruzi.

 

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Treatment & Prevention

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Barr SC: American trypanosomiasis. In: Greene CE (ed.): Infectious Diseases of the Dog and Cat. 2nd edn., 2006, WB Saunders, Philadelphia, USA, pp. 676-80

Barr SC: Canine Chagas' disease (American trypanosomiasis) in North America. Vet Clin North Am Small Anim Pract. 2009, 39, 1055-64

Bowman DD, Hendrix CM, Lindsay DS, et al.: The Protozoa. In: Bowman DD, Hendrix CM, Lindsay DS, Barr SC (eds.): Feline Clinical Parasitology. 1st edn., 2002, Iowa State Univ. Press, Ames, USA, pp. 3-81

Coffield DJ Jr., Spagnuolo AM, Shillor M, et al.: A model for Chagas disease with oral and congenital transmission. PLoS One. 2013, 8, e67267

Crisante G, Rojas A, Teixeira MMG, et al.: Infected dogs as a risk factor in the transmission of human Trypanosoma cruzi infection in western Venezuela. Acta Tropica. 2006, 98,247-54

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Deschamps JY, Desquesnes M, Dorso L, et al.: Refractory hypoglycaemia in a dog infected with Trypanosoma congolense. Parasite. 2016, 23, 1

Desquesnes M, Holzmuller P, Lai DH, et al.: Trypanosoma evansi and surra: a review and perspectives on origin, history, distribution, taxonomy, morphology, hosts, and pathogenic effects. Biomed Res Int. 2013, 2013, 194176  

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Gurtler RE, Cecere MC, Castanera MB, et al.: Probability of infection with Trypanosoma cruzi of the vector Triatoma infestans fed on infected humans and dogs in northwest Argentina. Am J Trop Med Hyg. 1996, 55, 24-31

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Laiño MA, Cardinal MV, Enriquez GF, et al.: An oral dose of Fluralaner administered to dogs kills pyrethroid-resistant and susceptible Chagas disease vectors for at least four months. Vet Parasitol. 2019, 268, 98-104

Losos GJ, Crockett E: Toxicity of berenil in the dog. Vet Rec. 1969, 85, 196

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Onyeyili PA, Anika SM: Effects of the combination of DL-alpha-difluoromethylornithine and diminazene aceturate in Trypanosoma congolense infection of dogs. Vet Parasitol. 1990, 37, 9-19

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Peregrine AS: Chemotherapy and delivery systems: haemoparasites. Vet Parasitol. 1994, 54, 223-48

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Pineda V, Saldana A, Monfante I, et al.: Prevalence of trypanosome infections in dogs from Chagas disease endemic regions in Panama, Central America. Vet Parasitol. 2011, 178, 360-3

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Zoonotic Potential

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Haridy FM, El-Metwally MT, Khalil HHM, et al.: Trypanosoma evansi in dromedary camel: with a case report of zoonosis in greater Cairo, Egypt. J Egypt Soc Parasitol. 2011, 41, 65-76

Joshi PP, Shegokar VR, Powar RM, et al.: Human trypanosomiasis caused by Trypanosoma evansi in India: the first case report. Am J Trop Med Hyg. 2005, 73, 491-5

Lee BY, Bacon KM, Bottazzi ME, et al.: Global economic burden of Chagas disease: a computational simulation model. Lancet Infect Dis. 2013, 13, 342-8

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Truc P, Büscher P, Cuny G, et al.: A typical human infections by animal trypanosomes. PLoS Negl Trop Dis. 2013, 7, e2256

Truc P, Gibson W, Herder S: Genetic characterization of Trypanosoma evansi isolated from a patient in India. Infect Genet Evol. 2007, 7, 305-7

Vanhollebeke B, Truc P, Poelvoorde P, et al.: Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I. N Engl JMed. 2006, 355, 2752-6

Vago AR, Andrade LO, Leite AA, et al.: Genetic characterization of Trypanosoma cruzi directly from tissues of patients with chronic Chagas disease: differential distribution of genetic types into diverse organs. Am J Pathol. 2000, 156, 1805-9

WHO: Chagas disease in Latin America: an epidemiological update based on 2010 estimates. Wkly Epidemiol Rec. 2015, 90, 33-44