Protozoal Diseases

Babesiosis

Babesiosis is a tick-borne, protozoan, hemoparasitic dis­ease of goats that occurs in Africa, Asia, and Europe. In certain areas, the economic losses associated with caprine babesiosis may be significant, notably around the Mediterranean and in the Middle East and India.

Etiology

Two main species of Babesia infect sheep, Ba. motasi and Ba. ovis, but in goats Ba. motasi infection predominates. Ba. motasi is classified as a large Babesia sp. with a length of 2.5-4 μm, while Ba. ovis is a small Babesia sp. with a length of 1-2.5 μm. Another large species, Babesia crassa, has been found in Iran and a few other countries, including Turkey. It is reported to be infective, but probably non- pathogenic, for goats. Using molecular techniques, a new large species, Babesia sp. Xinjiang, producing clinical dis­ease in goats and sheep, has been identified in China (Niu et al. 2017). Another small species, Babesia taylori, infec­tive for goats, was earlier reported from India, but its status as a distinct species is doubtful (Uilenberg 2006). The agents causing bovine babesiosis are not pathogenic for goats, although inapparent infections of goats with Babesia bigemina have been observed. Ticks serve as biological vec­tors, but mechanical transmission is also possible.

Epidemiology

Ba. motasi infection of small ruminants has been reported from much of Europe, the Middle East, the former USSR, India, Southeast Asia, and parts of Africa (Purnell 1981a). The primary biological vector for Ba. motasi is the tick Haemaphysalis punctata, although it is also likely to be transmitted by other species in the genus Haemaphysalis. Reports of transmission by Dermacentor silvarum and Rhipicephalus bursa are probably erroneous (Uilenberg et al. 1980; Uilenberg 2006). Transovarial and transstadial tick transmission occurs. Babesia sp.

Several strains of Ba. motasi exist, with variable infectiv­ity and pathogenicity for goats (Purnell 1981b). The Ba. motasi strain in northern Europe has comparatively low pathogenicity compared to the strain present in southern Europe and the Mediterranean region (Uilenberg 2006). An outbreak of naturally occurring disease in both sheep and goats caused by Ba. motasi was reported from India (Jagannath et al. 1974). A strain of Ba. motasi isolated from sheep in Wales produced fever and anemia in a splenecto- mized goat, but pathogenicity for intact goats was not evaluated (Lewis et al. 1981). Babesiosis was the cause of debilitating disease in sheep and goats in southwest Nigeria, but caused death only in goats (Adeoye 1985).

Ba. ovis is transmitted primarily by R. bursa. The geo­graphic distribution of Ba. ovis overlaps with that of Ba. motasi, but is associated primarily with disease in sheep where it occurs. Subclinical infections of goats with Ba. ovis have been reported from Somalia (Edelsten 1975), Turkey (Zhou et al. 2017), and Iran (Bazmani et al. 2018). There are also reports from Iran that suggest goats infected with Ba. ovis may not show overt clinical signs, but never­theless have abnormal clinicopathologic findings consist­ent with anemia (Esmaeilnejad et al. 2012). Clinical apparent disease in goats resulting from Ba. ovis infection has been reported from India (Muthuramalingam et al. 2014). Clinical disease in goats with mixed infection of Ba. ovis and Ba. motasi has been reported from Iraq (Sulaiman et al. 2010) and India (Tufani et al. 2018). The pathogenicity of Babesia spp. in goats and sheep may be intensified by concurrent infections, particularly other hemoparasites such as Thieleria and Anaplasma. No cross­immunity develops after infection with either Ba. motasi or Ba. ovis.

Pathogenesis

Merozoites introduced by infected ticks during feeding invade host erythrocytes.

Clinical Signs

Affected goats will have fevers, perhaps as high as 41.7 °C (107 °F), and show anorexia, rumen atony, depression, weakness, enlarged lymph nodes, and signs of anemia, including dyspnea, tachypnea, and tachycardia. Coughing, ocular and nasal discharge, and diarrhea have also been reported in acute cases in goats. Abortion can occur in pregnant does. Sheep consistently show icterus and hemo­globinuria, with coffee-colored urine. Goats will also show these signs, but less consistently than sheep (Jagannath et al. 1974). Affected goats should be examined for the presence of hard (Ixodes) ticks, though infective ticks may have dropped off before clinical signs develop. Morbidity and mortality rates can be high. Death can occur within 48 hours of the onset of signs. Chronic infections may occur, with anemia and ill-thrift the prominent findings.

Clinical Pathology and Necropsy

Blood parameters consistently reveal decreases in total RBC count, hemoglobin concentration (Hb), PCV, and platelet count, while variable levels of WBCs and serum proteins have been reported. Giemsa-stained blood smears

should be examined for evidence of piroplasms.

An indirect fluorescent antibody (IFA) test can be used for the serodiagnosis of Ba. motasi infection, with titers of 1 : 640 or more considered as evidence of infection (Lewis et al. 1981).

At the time of necropsy, the predominant findings are splenomegaly, lymphadenopathy, and enlarged liver. Icterus and hemoglobinuria are variable. Peripheral blood should be examined for piroplasms.

Diagnosis

The diagnosis of caprine babesiosis is suggested by signs of anemia, hemoglobinuria, and acute collapse in animals where babesiosis is known to occur. Definitive diagnosis depends on the identification of the organism in blood smears. Theileriosis can be differentiated by the morphol­ogy of piroplasms and a more prominent lymph node enlargement. Anaplasmosis does not normally produce hemoglobinuria. When hemoglobinuria is present, plant poisonings, copper toxicosis, anthrax, and leptospirosis must also be considered.

Treatment

The diamidine derivatives diminazene and imidocarb diproprionate are effective - diminazene aceturate at a dose of 3 mg/kg bw given IM or imidocarb at a dose of 1-2 mg/kg bw given IM or SC.

Control

While effective live vaccines are commercially available for control of bovine babesiosis, this is not the case for small ruminants, though active research into the development of subunit vaccines offers promise for the future. At present, tools for limiting babesiosis in goats are limited to control­ling tick vectors on animals and in the environment.

Theileriosis

Theileriosis encompasses a group of tick-borne, protozoal diseases of ruminants affecting primarily the hemic- lymphatic system. The disease in small ruminants, known as malignant ovine theileriosis, is caused mainly by Theileria Iestoquardi and occurs in the Middle East, Eastern and Northern Africa, India, China, Central Asia, and Eastern and Southern Europe. Theileriosis in sheep and goats has been reviewed (El Imam and Taha 2015).

Etiology and Epidemiology

Theileriosis has received little direct attention in goats and much has been inferred from the disease in sheep. The main pathogenic Theileria sp. infecting both goats and sheep is T. Iestoquardi (earlier known as T. hirci). Two addi­tional Theileria species pathogenic for small ruminants have been identified in China, namely Theileria luwens- huni and T. uilenbergi (Yin et al.

The disease in small ruminants, caused by T. lestoquardi infection, is often associated with high morbidity and mor­tality rates. It produces serious losses in sheep and goats in northern Africa, notably in Sudan, as well as in Asia, the Middle East, southern Europe, and the southern former USSR. In a report from Iraq, however, a strain of T. lesto- quardi, responsible for 100% morbidity and 89.7% mortal­ity rates in a flock of sheep, produced no clinical disease when inoculated in a goat (Hooshmand-Rad and Hawa 1973). Similarly, in an Indian study, the infection was trans­mitted to sheep but not goats (Sisodia and Gautam 1983).

Species of Theileria highly pathogenic for cattle do not cause disease in small ruminants. While Theileria annu- lata can infect caprine and ovine RBCs in vitro, it cannot infect sheep and goats in vivo (Li et al. 2014).

Infections in goats with non-pathogenic small ruminant species of Theileria are also much less common than in sheep, and goats may be refractory to some species infec­tive for sheep.

T Iestoquardi is transmitted by Hyalomma spp. and Rhipicephalus spp. ticks, while the two recently described species in China, T. luwenshuni and T. uilenbergi, are trans­mitted by Haemaphysalis longicornis and Haemaphysalis quinghaiensis (Li et al. 2009). H. punctata is the vector of T. luwenshuni in Great Britain (Phipps et al. 2016). The tick vectors of T. ovis in sub-Saharan Africa are not well estab­lished, while R. bursa is reported as a vector in the former USSR, north Africa, and Asia.

Pathogenesis

Sporozoites enter the host by the bite of infected ticks. The parasites are initially located in the spleen and lymph nodes, where they invade lymphocytes and produce schiz­onts. These schizonts, which early in the infection contain large nuclei and later small ones, are readily identifiable in Giemsa-stained smears of lymph node aspirates or biopsies and are referred to as Koch's Blue Bodies. After lysis of lymphocytes, micromerozoites enter the blood stream as piroplasms and invade erythrocytes. The piroplasm is poly­morphic in RBCs, exhibiting ring, oval, comma-shaped, or rod forms. Additional replication occurs in the RBCs, and the sexual stages of the life cycle occur in the tick. The ane­mia of theileriosis is less severe than that seen in babesio­sis, the other piroplasm of goats. The detailed mechanisms by which Theileria produce extensive tissue damage and high mortality in infected animals are not fully understood but recent advances in that knowledge have been reviewed (El Imam and Taha 2015).

Clinical Signs

In malignant ovine theileriosis (T. lestoquardi infection), clinical signs initially include fever, increased heart and respiratory rates, anorexia, dullness, and depression. Lymph nodes are markedly swollen. Serous nasal dis­charge and lacrimation develop, and the conjunctivae are congested. The clinical course may last from two to three weeks; during that time, the animal may experience a decrease in milk production, coughing, rough haircoat, emaciation, weakness, recumbency, and death. Pregnant animals may abort. A mild to moderate anemia may be observed and, in sheep, icterus has been inconsistently reported. In benign theileriosis, transient fever and mild lymph node swelling may occur and be overlooked under field conditions. Animals that recover may show chronic ill-thrift, decreased milk production, and delayed maturity. They can also become carriers and remain a source of infection.

Clinical Pathology and Necropsy

Anemia and lymphopenia may be noted in the hemogram. Koch's Blue Bodies may be identified in Giemsa-stained smears of lymph nodes or characteristic piroplasms seen in circulating RBCs. On examination after death, lymph nodes, spleen, and liver are all enlarged. The liver is icteric and the kidneys may show patchy hemorrhagic infarcts. Necrotizing ulcers ringed by hemorrhage may be seen in the abomasum and intestine.

Diagnosis

Because of the presentation of swollen lymph nodes, theile- riosis must be differentiated from trypanosomosis where both diseases occur. Diagnosis of acute clinical cases of theileriosis is based on identification of Koch's Blue Bodies in lymph nodes or piroplasms in erythrocytes. The piro- plasms must be distinguished from those of Babesia spp. The detection of Koch's Blue Bodies is more problematic during periods of low parasitemia, such as in the chronic carrier state, and other diagnostic tests are available to detect the immune response or presence of the organism.

Serologic tests for detection of antibody include the IFA test and the ELISA. Molecular-based tests include PCR and LAMP.

Treatment and Control

Treatment can reduce mortality, but will not necessarily eliminate the carrier state. The treatment of choice for theileriosis in sheep and goats is buparvaquone, given once at a dose of 2.5 mg/kg bw IM. Oxytetracycline, given at a dose of 10 mg/kg bw IM daily for five days, has also been used in small ruminants, but two studies indicate that buparvaquone is more effective in clearing the infection than oxytetracycline (Al-Obaidi and Alsaad 2004; Rehman et al. 2010).

Control of caprine theileriosis involves control of the tick vectors, primarily through dipping programs. Attenuated vaccines are used for control of theileriosis in cattle, both for East Coast fever (Theileria. parva) and tropical theileri- osis (T. annulata). The vaccines are produced from Theileria schizonts grown and attenuated in cell culture. Vaccination for East Coast fever must be carried out in conjunction with simultaneous treatment using oxytetracycline, as clin­ical and potentially fatal manifestations of disease can occur with vaccination alone. Schizonts of T. lestoquardi also can be grown and attenuated in cell culture, and while vaccination against malignant theileriosis in sheep and goats is not yet widely practiced, there are reports of cell culture-attenuated T. Iestoquardi vaccine being developed and tested successfully in Sudan and elsewhere in the Middle East (Ahmed et al. 2013).

Trypanosomosis

Trypanosomosis is a major constraint on ruminant live­stock production in Africa, including goat production. The impact of South American trypanosomosis on goats is largely unexplored and is only briefly discussed. Salient characteristics of the important animal and human trypa­nosomes and their pathogenicity for goats are summarized in Table 7.7. Though often referred to as trypanosomiasis, the preferred name for disease caused by trypanosome infections is trypanosomosis (Kassai et al. 1988). Animal trypanosmosis is also known as Nagana.

Etiology

The trypanosomes are flagellate protozoa characterized by a kinetoplast and an undulating membrane. Most trypano­somes require two hosts to complete their life cycle, a hematogenous insect vector and a vertebrate host. In sub­Saharan Africa, cyclic transmission of the parasite to mam­malian hosts occurs via numerous species of tsetse flies (Glossina spp.) during feeding by the flies. Elsewhere in the world, mechanical transmission by other species of biting flies is the primary mode of infection. A detailed and informative review of African animal trypanosomes and the diseases they cause is available elsewhere (Connor and van den Bossche 2004). A review of the disease specifically in goats also has been published (Gutierrez et al. 2006).

Trypanosoma congolense is the most common trypano­some of goats in Africa. Trypanosoma vivax is the second most common. Natural infection of goats with Trypanosoma brucei is also sporadically reported. Goats are susceptible to Trypanosoma uniforme, a trypanosome of the vivax group in Uganda and Zaire, but only mild infections occur. Trypanosoma simiae, a trypanosome of swine and camels, is transmissible to goats by either Glossina spp. or biting flies, but causes mostly mild or subclinical disease.

Goats and other domestic animals are relatively resistant to Trypanosoma gambiense, the cause of West African human sleeping sickness. When infection does occur, the clinical course is chronic. Trypanosoma rhodesiense, the cause of East African sleeping sickness in humans, is an uncommon cause of caprine disease. A non-pathogenic trypanosome, Trypanosoma theodori, is found incidentally in goats in Israel. It is transmitted by a hippoboscid fly, Lipoptena caprina. This organism is morphologically simi­lar to the common, non-pathogenic sheep trypanosome Trypanosoma melophagium.

Information on the pathogenicity of the trypanosomes that occur outside of sub-Saharan Africa, primarily in South and Central America as well as in Asia, is more lim­ited. Trypanosoma cruzi is cyclically transmitted by redu- viid bugs in South and Central America, while Trypanosoma evansi and Trypanosoma equiperdum are mechanically or sexually transmitted, respectively, in Africa, South and Central America, and Asia. These trypanosomes cause dis­ease in various species. Tr. cruzi is primarily of importance for humans; Tr. evansi for camels, horses, cattle, and Asian buffalo; and Tr. equiperdum for horses. Their infectivity for goats is presumed to be low. Based on evidence of antibody detected by IFA testing, natural infection of goats with Tr. cruzi is known to occur, but no clinical disease was noted in infected goats (Herrera et al. 2005). Kids infected experi­mentally with Tr. cruzi showed no clinical signs of disease and carried the infection for 38 days (Diamond and Rubin 1958).

The goat is a natural host for Tr. evansi, but reports of the disease, surra, in goats are rare. Surra was reported to be occurring in goats in Mindanao in the Philippines, but field confirmation has been difficult. It is believed that the cases may involve a particularly virulent strain of Tr. evansi. Experimental challenge of goats with an equine strain of Tr. evansi from Mindanao produced clinical and pathologi­cal changes consistent with surra (Dargantes et al. 2005a, b).

Epidemiology

The distribution and intensity of animal trypanosomosis in sub-Saharan Africa follow the distribution and intensity of the various species of the tsetse fly. Approximately 10 mil­lion km² or 37% of the African continent is tsetse infested. This area includes 38 countries. Various estimates suggest that the livestock-carrying capacity of such areas in West and Central Africa could be increased five- to seven­fold by eliminating or controlling animal trypanosomosis (Griffin 1978).

There are more than 489 million goats in Africa, with a large proportion of them in the tsetse-infested regions of the continent (FAO 2021). Natural infections with Tr. con­golense, Tr. vivax, or Tr. brucei resulting in clinical disease have been known in African goats since the early twentieth century. However, a perception persisted that goats are highly resistant to infection, that caprine trypanosomosis is only sporadic, and that the disease in goats is of little economic consequence (Griffin 1978). This opinion has undergone a critical reappraisal. Regional differences do exist in the prevalence of caprine trypanosomosis, but it can be high in some areas (Kramer 1966; Griffin and Allonby 1979a). In general, caprine trypanosomosis is more common in East Africa than West Africa. This is attributed to differences in feeding preferences between

Table 7.7 Trypanosomosis in various hosts with the emphasis on goats.

Table 7.7 (Continued)

riverine species of Glossina and savannah species; the lat­ter are more inclined to feed on goats. A report from Zambia identified Tr. brucei, Tr. congolense, and/or Tr vivax infections in goats that were naturally transmitted by Glossina morsitans morsitans and Glossina pallidipes (Bealby et al. 1996).

Goats may serve as a reservoir of trypanosome infection for other species. In the Sudan, goats infected with Tr. con­golense developed a chronic form of disease from which many spontaneously recovered. When the organism was passed from goats into calves, however, acute fatal bovine trypanosomosis occurred (Mahmoud and Elmalik 1977). Goats also have been implicated as a reservoir of Tr. rho- desiense, a nosodeme of Tr. brucei transmissible to humans (Robson and Rickman 1973).

The economic impact of trypanosomosis on goat produc­tion is beginning to be studied. A Kenyan analysis demon­strated that goats receiving monthly chemoprophylaxis against trypanosomosis had significantly decreased mor­tality rates, increased weight gains, and improved repro­ductive performance compared to untreated control goats. Differences in performance were also noted between breeds in the study, with indigenous breeds performing better than non-indigenous breeds or cross breeds (Kanyari et al. 1983).

The existence of inherent trypanotolerance in certain goat breeds has been controversial. It is generally accepted that trypanotolerant breeds of cattle exist, notably the N'dama of West Africa and the West African Shorthorn, and that trypanotolerance is measured by the ability to control trypanosome numbers and resist the effects of the disease, independent of pre-existing immune experience. This inherent ability to control parasitemia and minimize disease is not as great in specific goat breeds, despite the general observation that some breeds of goats readily sur­vive in tsetse-infested areas. West African Dwarf (WAD) goats are considered to be inherently trypanotolerant, but that tolerance is seen as relative, and may be compromised when the goats are stressed, for example by concurrent parasite infections. There is also concern that cross breed­ing of WAD goats for improved size and production may be reducing the breed's inherent trypanotolerance through introgression of genes of trypanosusceptible breeds. In East Africa, the Small East African (SEA) goat breed is con­sidered to be inherently trypanotolerant. The subject of trypanotolerance in small ruminants in sub-Saharan Africa has been reviewed (Geerts et al. 2009; Yaro et al. 2016).

In summary, goats are highly susceptible to pathogenic trypanosomes, although the disease commonly follows a subclinical course. Parasitemia is usually low but persistent, and therefore goats should be considered as a potential res­ervoir for most of the trypanosomes affecting other species, including humans, and particularly where goats are com­mingled with cattle or camels (Gutierrez et al. 2006).

Pathogenesis

Trypanosomes fall into two main groups regarding their ability to produce disease. The hematic group, which includes Tr. congolense and Tr. vivax, remains confined to the circulation after introduction into the blood stream by feeding Glossina spp. The disease produced in these infec­tions is characterized by anemia. The humoral group, which includes Tr. brucei, is more invasive, with trypano­somes found in intercellular tissue and body cavity fluids after initial infection. Anemia in these cases is overshad­owed by marked inflammatory, degenerative, and necrotic changes.

Anemia in trypanosomosis may be due to extravascular hemolysis and erythrophagocytosis, as well as decreased erythropoiesis in chronic infections (Kaaya et al. 1977). The destruction of RBCs may result from both non- immune- and immune-mediated mechanisms. Hemorrhage secondary to DIC may also contribute to anemia. Thrombocytopenia, microthrombus formation, and hem­orrhage suggestive of DIC have been observed in caprine trypanosomosis due to Tr. vivax (Van den Ingh et al. 1976; Veenendaal et al. 1976). Anemia may be exaggerated by hemodilution because of expansion of blood and plasma volumes, which increased, respectively, by 29 and 44% in goats with subacute Tr. vivax infection (Anosa and Isoun 1976).

The pathogenesis of inflammation and tissue damage by humoral trypanosomes such as Tr. brucei is complex and is reviewed elsewhere (Soulsby 1982; Connor and van den Bossche 2004). Immunosuppression can occur in trypanosomosis. Tr. vivax and Tr. brucei infection of goats resulted in depressed responses to mitogen stimulation in lymphocyte transformation tests (van Dam et al. 1981a; Diesing et al. 1983), and goats experimentally infected with Tr. congolense produced a weaker antibody response to vaccination with Brucella melitensis vaccine than did uninfected controls (Griffin et al. 1980). Impaired immune function may aggravate the severity of concur­rent infections. This was suggested by evidence of higher mortality rates and parasite loads in goats concurrently infected with Tr. congolense and Ha. contortus than in goats infected with only one parasite or the other (Griffin et al. 1981a, b). Under field conditions, goats with chronic trypanosomosis are more susceptible to helminthiasis and carry heavier helminth burdens, probably as a result of immunosuppression.

Trypanosome infection is associated with ovarian dys­function and irregular estrous cycles (Llewelyn et al. 1987; Mutayoba et al. 1988). Gross testicular atrophy has been reported in bucks with Tr. congolense infection (Kaaya and Oduor-Okelo 1980). There is also a variety of endo­crine abnormalities reported following inoculation of trypanosomes into the blood stream of goats, including depression of circulating thyroxine, testosterone, and cor­tisol levels (Connor and van den Bossche 2004).

One of the most notable features of trypanosomosis is the successive waves of parasitemia that occur every few days in animals that survive initial infection. Each wave of parasitemia is followed by an increase in circulating anti­body that temporarily reduces the parasitemia. The effect is only temporary, however, because cyclically transmitted trypanosomes are capable of repeatedly altering their sur­face antigens and thereby evade the host immune system sufficiently to avoid total elimination of infection. These variant antigens are surface-coat glycoproteins. It is the occurrence of variable antigens that has been the major obstacle in the development of effective vaccines.

Clinical Signs

Goats presenting with clinical disease and naturally infected with Tr. vivax, Tr. congolense, or Tr. brucei are regu­larly observed in Africa. Clinical syndromes produced by these three major tsetse-transmitted trypanosomes are pre­sented separately below. In the early stage of the disease, a prominent skin chancre may be noted at the site of tsetse fly feeding.

Trypanosoma vivax

Acute, subacute, and chronic forms of disease can occur. Acute disease usually results in recovery or death within four weeks. Subacute disease, with a decreased level of parasitemia, may persist for 10-12 weeks, and chronic dis­ease for 17 weeks or longer. The chronic form of the disease is most common. Parasitemia is evident on blood smear within 6-10 days after infection and peaks at approximately 10 days, but identification of the parasite on blood smears in subacute and chronic cases is less reliable. Successive waves of parasitemia occur at four- to seven-day intervals, accompanied by fluctuating fevers as high as 42.2 °C (108 °F). Anemia develops rapidly, coinciding with the first wave of parasitemia.

Clinical signs may include depression, anorexia, lack of rumen motility, enlarged lymph nodes, and weight loss. Anemia can become severe, with signs including pallor, increased heart rate and respiration, exercise intolerance, and marked listlessness. Jaundice and hemoglobinuria are uncommon findings. Severe emaciation is evident in chronic disease, although surviving animals may begin to gain weight again and the severity of anemia diminish as the level of recurrent parasitemia is brought under control.

Trypanosoma Congolense

Acute, subacute, and chronic forms of disease also have been described for Tr. congolense infection of goats (Griffin and Allonby 1979b). The acute phase results in death or recovery within six weeks. Fluctuating temperatures up to 41.1 °C (106 °F) occur and in fatal cases anemia is severe. Weight loss is variable, depending on the duration of dis­ease. In recovered animals, fever and a milder anemia may occur with the initial parasitemia, but PCV returns rapidly to normal. In subacute cases, animals die or recover within 6-12 weeks after infection. In fatal cases, cyclic parasitemia persists and fluctuating fever, progressive emaciation, weak­ness, lethargy, and pallor are evident clinically Recovering animals begin to gain weight and strength as fever and ane­mia subside. Chronic infections, lasting 12weeks or longer, are almost always fatal. Cyclic fever and parasitemia persist, as does the anemia. Animals become emaciated, haircoat becomes rough, superficial lymph nodes are palpably enlarged, and intermandibular and facial edema develop. Animals become recumbent, then comatose, and die.

Trypanosoma brucei

Because Tr. brucei is a humoral trypanosome, clinical signs may be more severe, although pathogenicity varies with the strain. In addition to anemia, fever, and emaciation, keratitis and signs of encephalitis may occur, including head pressing, circling, and opisthotonos. Lymphadenopathy is a consistent finding and may be more pronounced than with Tr. vivax or Tr congolense infection. The typical course of disease is three to five months, and it is usually fatal. Anemia is not as pronounced as it is in infection with the hematic trypanosomes. Parasitemia is also less severe, and detection of trypanosomes on blood smears is more diffi­cult. Examination of lymph node smears may be more rewarding.

Clinical Pathology and Necropsy

In all forms of the disease, the most significant laboratory findings relate to anemia (Edwards et al. 1956). Moderate to severe decreases in PCV, Hb, and RBC numbers can be seen. In the early stages, anemia is macrocytic, while in chronic and terminal cases, a normocytic anemia is more common. This is reflected in the bone marrow, which is often hyperplastic in acute disease and normoplastic or hypoplastic in chronic disease. In experimental infection of goats, all species of trypanosomes produced a significant thrombocytopenia, with platelet counts 65-82% less than the normal mean (Davis 1982). No consistent changes in the leukogram have been noted in caprine trypanosomo- sis. In cattle, a transient leukopenia and rebound leukocy­tosis can occur during the acute phase of disease. Serum chemistry values remain normal. Animals with acute tryp- anosomosis may show laboratory evidence of DIC.

There are no pathognomonic lesions in trypanosomosis. In acute cases, necropsy findings include an anemic carcass, general lymph node enlargement, marked splenomegaly, serosal and mucosal petechial hemorrhage, and hydroperi­cardium. Microscopically, lymphoid hyperplasia is pro­nounced and microthrombi may be evident in vessels of numerous organs. In the hematic forms of disease trypano­somes are present only in vascular spaces, while with Tr. bru- cei extravascular parasites may be seen in tissues such as the cornea and cerebrospinal fluid. In chronic cases, severe ema­ciation, with serous atrophy of fat and muscle degeneration, may be observed in addition to petechiation, lymphadenopa­thy, and splenomegaly (Losos and Ikede 1972).

Diagnosis

Anemia and emaciation in goats from tsetse-endemic areas suggest the diagnosis of trypanosomosis. Definitive diag­nosis is based on identification of trypanosomes in blood smears or tissues. However, chronic infections in goats are common, the level of parasitemia is generally low, and trypanosomes may be difficult to find in the blood, so vari­ous concentration techniques are recommended. Because parasitemia is cyclical, examining smears from numerous animals in a suspect group may improve the chances of diagnosis. In live animals, parasites may be more readily detected in blood samples taken from an ear vein rather than the jugular vein. Thick blood smears examined after lysis of red cells and staining with Romanowsky stain may reveal the presence of parasites, but morphologic identifi- cationisbetter performedonthinsmears.Microhematocrital centrifugation of blood and examination of a wet mount of the plasma-buffy coat interface can improve detection. Other concentration techniques include dark ground or phase contrast buffy coat technique and the miniature anion-exchange chromatography technique (OIE 2021b). Where available, PCR has emerged as the method of choice for identifying and characterizing trypanosomes from blood and tissue samples. Well-validated primer sequences are reported for all the main animal trypanosomes (OIE 2021b).

Serologic tests employed in the diagnosis of trypanoso- mosis include the IFA test and ELISA. Information on interpretation of serologic responses in goats is limited. The differential diagnosis for trypanosomosis should include helminthiasis, malnutrition, and other hemopara­sites, notably anaplasmosis, babesiosis, and theilerosis, which occur in trypanosomosis-endemic areas.

Treatment

A variety of trypanocidal compounds are available for treatment, but no new drugs have been marketed for quite some time. Subsequently, drug resistance has become a significant problem. Compounds and dosages are formu­lated for single-dose use and treatment is usually on a herd-wide basis, because serial treatments on individual animals are difficult to carry out in the semi-nomadic live­stock farming systems prevalent in endemic areas. Several of the drugs are locally irritating, so SC injections should be given in areas of loose skin, and IM injections given deeply, avoiding vessels and nerves. Curative doses used in cattle are also appropriate for goats and sheep on a mg/kg bw basis (Ilemobade 1986). Treatment is reviewed by Uilenberg (1998).

Diminazene aceturate is given as a 7% cold water solu­tion at a dose of 3.5 mg/kg bw IM and is considered effec­tive against the three major trypanosomes. Relapse of infection has been reported in goats treated with dimina- zene aceturate, presumably because of re-emergence of trypanosomes from the central nervous system, where they were inaccessible to the drug during earlier treatment (Whitelaw et al. 1985a). Quinapyramine dimethyl sulfate is little used nowadays, except for treating Tr. evansi in cam­els and horses, because of toxicity and drug-resistance problems. It is given as a 10% cold water solution at a dose of 5 mg/kg bw SC.

Homidium chloride (soluble in cold water) or homidium bromide (soluble in hot water) are given in a 2.5% water solution at a dose of 1 mg/kg bw IM, and are effective against Tr vivax and Tr. congolense. Isometamidium chlo­ride is currently the most commonly used drug in rumi­nants. It is effective against the hematic trypanosomes when given at a dose of 0.25-0.75 mg/kg bw IM as a 1% or 2% solution in water. This drug was shown to produce signs of shock or death in goats if given at doses greater than or equal to 0.5 mg/kg bw IV (Schillinger et al. 1985). All drugs of the phenanthridinium group (homidium and isometa- midium compounds) are potentially carcinogenic and should be handled as such.

The arsenical compound Cymelarsan® (MCI Sante Animale, Mohammedia, Morocco) has been demon­strated to be effective treatment for Tr. evansi in goats (Gutierrez et al. 2008). Goats experimentally infected with Tr. evansi were cured after a single inoculation of 0.3 mg/kg. This is a higher dose than the 0.25 mg/kg bw routinely used in horses and camels. However, in another study conducted to test the efficacy and toxicity of Cymelarsan in Nubian goats with Tr. evansi infection, goats given either a single IM injection of 1.25 mg/kg or repeated IM injections over a period of eight days or two weeks at doses of 0.125 mg/kg or 0.25 mg/kg developed arsenic toxicosis (Youssif et al. 2008). In that study, a sin­gle IM dose of 0.25 or 0.625 mg/kg was effective in treat­ing the Tr. evansi infection and did not produce arsenic toxicosis. Note that in different jurisdictions there may be prohibitions on the use of arsenical compounds in food­producing animals.

Control

There are numerous constraints on control, including res­ervoirs of infection in wild animal populations; the ability of trypanosomes to continuously alter their antigenic char­acter, which confounds the development of suitable vac­cines; a limited availability of effective drugs; the development of resistance to existing trypanocidal drugs; the difficult logistics of widespread tsetse control; lack of economic resources; poorly developed animal disease con­trol programs; limited technical training programs; lack of international cooperation; and political instability (Doyle et al. 1984; Murray and Gray 1984).

Currently, the major fronts in trypanosomosis control in sub-Saharan Africa are reduction or elimination of tsetse populations and chemoprophylaxis of livestock. Tsetse fly control is accomplished by several methods, alone or in combination, including ground or aerial application of insecticides such as chlorinated hydrocarbons and syn­thetic pyrethroids; tsetse trapping with odor-baited, insecticide-impregnated traps; and gamma-irradiated ster­ile fly release. Aerial spraying of insecticides is now less commonly employed for environmental reasons, and trap­ping has emerged as a viable alternative, albeit for more restricted areas of control.

Isometamidium chloride protects against infection with the three major goat trypanosomes for two to four months. The prophylactic dose of isometamidium is 0.5-1 mg/kg bw administered IM in a 1% or 2% cold water solution. Earlier chemoprophylactic drugs (pyrithidium and quinap- yramine chloride) have been discontinued.

Despite intensive research, no effective vaccine is likely in the near future because of the continuing problem of antigenic variation in trypanosomes and antigenic strain differences. Given the obstacles to vaccination, there is a keen interest in identifying and promoting trypanotolerant breeds of livestock in endemic areas, as discussed above in the section on epidemiology.