Specific Diseases of the Hemic-Lymphatic System

Rickettsial Diseases

Anaplasmosis

Anaplasmosis is an arthropod-borne, rickettsial, hemopar- asitic disease of ruminant animals that causes hemolysis. It is usually a subclinical disease in goats and sheep, with goats more likely to manifest clinical signs.

Etiology

In goats and sheep, the principal causative agent is Anaplasma ovis. Goats and sheep may also be infected with Anaplasma mesaeterum, but the geographic distribution of this organism is more restricted and it is even less likely to cause clinical disease, especially in goats. A new species of Anaplasma, named Anaplasma capra, has been identified as infecting goats in China and preliminary reports suggest that it may be zoonotic, with the same organism being con­firmed in Ixodes persulcatus ticks and humans with a his­tory of tick bites (Li et al. 2015; Yang et al. 2017).

Cattle are infected by Anaplasma marginale and Anaplasma centrale; and wild ruminants by A. marginale and A. ovis. Goats may be transiently infected with A. mar­ginale, but do not become clinically ill and are unlikely to be a reservoir of A. marginale infection for cattle (Maas and Buening 1981). Tick-infested goats co-grazing with cattle in Brazil were found to have a high prevalence of A. mar­ginale infection, suggesting that competent ticks feeding on goats and cattle may transfer the pathogen between the two livestock species (da Silva et al. 2018).

The discussion here is limited to Anaplasma organisms that produce erythrocytic anaplasmosis in ruminants. Some other rickettsial organisms that infect WBCs have been transferred to the genus Anaplasma (Dumler et al. 2001), as discussed further in this chapter in the sec­tion on tick-borne fever.

Epidemiology

Anaplasmosis occurs in tropical and subtropical regions worldwide. More particularly in goats, anaplasmosis due to A.

This arthropod-borne disease is spread by a variety of ticks, particularly Rhipicephalus and Dermacentor spp., while Haemaphysalis and Ornithodoros spp. have also been incriminated. Ticks become infected by feeding on infected animals; transmission is probably transstadial and intrasta- dial, as it is in bovine anaplasmosis. The role of other insects, contaminated syringes, and other veterinary equip­ment in the mechanical transmission of A. ovis in goats has not been investigated, although such transmission is known in bovine anaplasmosis. In utero transmission of A. ovis has been established in sheep, and also confirmed in goats (Barry and van Niekerk 1987b).

The severity of clinical disease in cattle increases with advancing age. In experimental infection of goats with A. ovis, no correlation of disease severity with age was dis­cernible, although older animals did have a greater reduc­tion in red cell mass (Splitter et al.

Pathogenesis

The disease produced by A. ovis is primarily an anemia resulting from erythrophagocytosis of parasitized RBCs by the reticuloendothelial system in the spleen, lymph nodes, bone marrow, liver, and lungs. The severity of anemia gen­erally correlates with the percentage of parasitized cells. However, immune-mediated destruction of non-parasitized cells may also contribute to the degree of anemia. In experi­mentally infected goats, the prepatent period was 8-23 days, with parasitized erythrocytes first evident at an average of 15 days post inoculation. Maximum parasitemia occurred 15-30 days post inoculation and the lowest RBC counts occurred from 23 to 34 days after inoculation. On average, RBC count, PCV, and Hb decreased by more than 50%.

Complement-fixing antibody began to appear anywhere from eight days before to one week after the appearance of parasitized erythrocytes, and remained detectable in carrier animals for as long as one year (Splitter et al. 1956).

Clinical Findings

While A. ovis infection is often subclinical in the goat, con­current disease problems, malnutrition, and other stressors may precipitate clinical anaplasmosis. The most consistent clinical finding may be exercise intolerance, but other signs may be observed, including a fever up to 41.9 °C (107.5 °F), anorexia, depression, weakness, pallor of mucous mem­branes, dyspnea, and increased heart rate. If anemia is extreme, jaundice may be present, but hemoglobinuria is an uncommon event. Subclinically infected animals may show only pallor. Diagnosis of anaplasmosis requires labo­ratory confirmation.

Clinical Pathology and Necropsy

Unless there is concurrent disease, the leukogram is likely to be unchanged. Erythrocyte parameters are reduced dur­ing clinical and, to a lesser extent, subclinical disease.

A number of tests are available to confirm either acute infection or the carrier state. For detection of antibody, complement-fixing antibody titers are highest during and immediately after active parasitemia, but persist with vari­able intensity during the subsequent carrier state. False­negative tests can occur in some carriers. Other serologic tests include a capillary tube agglutination test, a rapid card agglutination test, a fluorescent antibody test, and a competitive enzyme-linked immunoabsorbent assay test. The capillary tube agglutination test has been reported to be reliable in the diagnosis of caprine anaplasmosis (Mallick et al. 1979). For detection of the organism, histori­cally the most definitive test was the inoculation of a sple- nectomized goat with blood of the suspected carrier.

Necropsy may reveal thin, watery blood, pallor, and jaundice of tissues. The liver may be enlarged and orange in color.

Diagnosis

Anaplasmosis occurs in regions where other caprine hemoparasitic diseases also occur, including babesiosis, eperythrozoonosis, cowdriosis, and theileriosis. In fact, it is not unusual for some of these conditions to occur simulta­neously in the same animal, and laboratory confirmation of anaplasmosis is essential to establish infection. Clinically, the absence of hemoglobinuria distinguishes anaplasmosis from babesiosis, leptospirosis, copper toxico­sis, and other causes of intravascular hemolysis.

Treatment

The stress of handling ill animals for repeated therapy may be fatal when anemia is severe. Individuals with advanced anemia may require supportive care in the form of fluids and hematinics. Treatment aimed at controlling the infection is most effective during the parasitemic phase of disease. Treatment administered during the pre­patent period slows but does not prevent the onset of para­sitemia. Oxytetracycline and tetracycline hydrochloride have been used successfully to treat clinically affected goats at an intramuscular (IM) dose of 10 mg/kg bw given once a day for one or two days. However, this dose given once a day for three to five days will not eliminate the car­rier state. In cattle, the use of long-acting tetracycline preparations at a dose of 20 mg/kg given once a week for two to four weeks has been effective in this regard. Imidocarb diproprionate may be useful in caprine ana- plasmosis, but information on dosage and treatment schedules for goats is limited.

Control

In general, efforts to control the spread of anaplasmosis by controlling tick vectors are not practical except on a local basis through repeated dipping or spraying.

Eperythrozoonosis

This hemoparasitic disease of goats is of little clinical and economic significance. It is caused by the organism Mycoplasma ovis, previously known as Eperythrozoon ovis.

Epidemiology

While M. ovis infection of sheep is known to occur widely in Europe, Africa, Australia, the Americas, and the Middle East, reports specific to infection in goats have come from Pakistan, South Africa, Australia, Cuba, and, more recently, Hungary (Hornok et al. 2012), Malaysia (Jesse et al. 2015), Egypt (Mahran and Ghattas 2016), Turkey (Aktas and Ozubek 2017), China (Wang et al. 2017), Brazil (Machado et al. 2017), and the Philippines (Galon et al. 2019). As M. ovis cannot be cultured, the spate of recent reports of infection in goats from diverse geographic locations may be more likely due to the availability and application of sensi­tive molecular identification techniques such as PCR rather than to an expansion of the range of infection. As in the past, these newer infections reported in goats are infre­quently associated with clinical disease.

Transmission of M. ovis may be by ticks, other ectopara­sites, mosquitoes, biting flies, contaminated needles, ear tagging, and surgical instruments, with the specific vectors varying by location or not being fully known. In Tasmania, a serologic survey indicated widespread infection in sheep with M. ovis, but virtually no infection in goats, suggesting the possibility of different vectors for the two animal species, or a difference in host susceptibility to chronic infection (Mason et al. 1989). A similar situation was reported from Tunisia, where PCR testing of sheep and goats revealed an overall prevalence of 6.28% in sheep with no infections identified in goats (Rjeibi et al. 2015). In con­trast, the infection was demonstrated to occur in both sheep and goats in Egypt and both species showed clinical signs of anemia and ill-thrift, most notably in weaning-age animals (Mahran and Ghattas 2016).

Etiology and Pathogenesis

The same organism, M. ovis, is infective for both sheep and goats, though a dimorphism has been noted. On Giemsa- stained smears, the organism on sheep erythrocytes dem­onstrates a large ring form, while in goats smaller ring and coccoid forms predominate (Daddow 1979a, b). In both small ruminant species, subclinical or latent infection is the rule; when clinical disease appears, it is often triggered by concurrent problems such as malnutrition or gastroin­testinal parasitism. In experimental infection the prepatent period is six days for both species, but the degree and length of parasitemia are shorter in the goat, lasting four weeks compared with six in the sheep. A carrier state develops in goats, with blood infective as long as 14 months after infection (Daddow 1979a).

Clinical Signs

In sheep, the disease is characterized by weakness, unthrift­iness, anemia, and mild icterus. Staggering and stiffness of the hindquarters have also been reported in sheep. Clinical disease is rarely observed in goats. In a report of clinical disease involving both goats and sheep in Egypt, clinical signs included fever, inappetence, emaciation, anemia, icterus, and ill-thrift. Hematologic analysis of affected animals showed macrocytic hemolytic anemia, as well as anisocytosis and poikilocytosis with reduced hemoglobin, PCV, and RBC values (Mahran and Ghattas 2016).

Diagnosis

The organism can be found on erythrocytes in Giemsa- stained blood smears during the parasitemia. However, clinical signs of anemia may not be recognizable until the waning stages of parasitemia. Antibody may also be detected with the complement fixation (CF) test for up to three weeks after clinical signs are observed. However, false-negative results may occur (Daddow 1977). Low lev­els of antibody may also be intermittently detectable dur­ing subsequent carrier states. It is recommended that the CF test be used on a herd basis rather than for individual diagnosis. Additional serologic tests for detecting antibody to M. ovis include direct and indirect immunofluorescence assays, the modified antiglobulin (Coombs) test, and ELISA. Various PCR techniques are now being used for identification of the organism from whole blood samples (Song et al. 2014; Rjeibi et al. 2015). Differential diagnoses of eperythrozoonosis include other hemoparasites, espe­cially anaplasmosis, malnutrition, gastrointestinal parasit­ism, and cobalt deficiency.

Treatment and Control

Treatment may alleviate clinical disease, but may not clear the carrier state. Single-dose therapy with either neoars- phenamine at a dose of 30 mg/kg, antimosan at 6 mg/kg, or oxytetracycline at 6.6 mg/kg has been recommended for sheep. No specific therapeutic evaluations have been reported in goats. Control involves good preventive medi­cine programs to avoid predisposing conditions, as well as the single-animal use of needles and surgical equipment.

Tick-Borne Fever

Tick-borne fever is a tick-transmitted rickettsial disease of goats, sheep, and cattle caused by the organism Anaplasma phagocytophilum, formerly classified in the genus Ehrlichia (E. phagocytophila). There are several strains of this organism that differ in host pathogenicity - the zoonotic HGE agent that causes human granulocytic ehrlichiosis (or human ana- plasmosis), strains formerly called Ehrlichia equi that cause equine ehrlichiosis (or equine anaplasmosis), and others more adapted to cattle and/or small ruminants that cause pasture fever or tick-borne fever. Dogs can also be infected. The condition is characterized in all ruminant species by fever and leukopenia. Abortions commonly occur in affected sheep and cattle, but less commonly in affected goats. Tick-borne fever in endemic areas causes noticeable losses in goats because of decreased milk production and secondary infections resulting from impaired immune responses.

Epidemiology

The disease occurs in cattle and sheep throughout Europe, wherever its tick vector, Ixodes ricinus, occurs. I. persulcatus in eastern Europe is also a vector. Strains causing human and equine ehrlichiosis (or anaplasmosis) in the United States are transmitted by Ixodes scapularis. Reports of naturally occur­ring, clinical tick-borne fever in goats have come only from Scotland (Gray et al. 1988), Norway (Melby and Gronstol 1984), Germany (Langenwalder et al. 2019), and Switzerland (Pusterla et al. 1999). It is reasonable to assume, however, that where the disease occurs in sheep, goats are susceptible. In Europe, the tick vector I. ricinus favors wet, cool, woodland pastures, and forest. The infection has been identified in feral goats in Scotland (Foster and Greig 1969) and Northern Ireland (Harrison et al. 2012), and in various wild cervids, including red, roe, and fallow deer (Billinis 2013), all of which may serve as a reservoir of infection. The inci­dence of disease increases in spring and autumn, with greater tick activity. With the advent of molecular identification techniques, A. phagocytophilumm, including genetic variants of the organism, is being identified in goats in a wider geographic range, including China (Zhan et al. 2010), but infection is usually not associated with clinical disease.

Etiology and Pathogenesis

The causative agent of tick-borne fever in cattle and small ruminants is Anaplasma (Ehrlichia) phagocytophilum, but bovine and ovine strains are recognized. Strains isolated from sheep readily produce the disease experimentally in goats and vice versa. The infectivity of the bovine strains can be less in small ruminants than in cattle. Cross­immunity between strains is not always complete. Related organisms, with other tick vectors, are Anaplasma or Ehrlichia bovis in cattle and Ehrlichia ovina in sheep.

Infected ticks introduce the organism into host animals in their saliva during blood feeding. Because the organism is passed transstadially and not transovarially in the tick, only nymphal and adult-stage ticks can transmit the infec­tion to ruminants. When entering the host's blood stream, the organism invades neutrophilic granulocytes, and to a lesser extent macrophages, where it replicates. In experi­mental infection of goats, high fever and granulocyte inclu­sions are seen by day three after infection. By day seven after infection, the total WBC count may drop to 27% of the level before infection. There is a transient lymphopenia and a persistent neutropenia, with no left shift. A transient eosinophilia is also observed around day five after infection (Van Miert et al. 1984).

It is believed that the invasion of leukocytes stimulates IL-1 (endogenous pyrogen) release that accounts for the high fever, rumen stasis, and other signs seen in clinical disease. The transient lymphopenia and neutropenia may impair immune defenses and predispose affected animals to serious secondary infections and increased risk of mortality.

There is limited information on morbidity and mortality rates in goats. In a report from Scotland, 25 goats were at risk: 13 had detectable antibody responses to tick-borne fever, 7 showed clinical signs of disease, and 1 died (Gray et al. 1988). In a Norwegian report, 50 of 103 goats in a dairy herd were affected by tick-borne fever, including all goats younger than 1 year of age (Melby and Gronstol 1984). While a low level of immunity develops after infection, the organism has been reported to persist in the blood stream of infected sheep for as long as two years.

Clinical Signs

Clinical signs reported in goats include a fever often higher than 41 °C (106 °F) that persists for three to six days accom­panied by dullness, anorexia, decreased rumen motility, tachycardia, tachypnea, occasional shivering, and cough­ing. In lactating does, there is a significant drop in milk production and pregnant does may abort. Animals should be examined for the presence of Ixodes ticks. Complete recovery may take several weeks and recovered goats may remain carriers

Clinical Pathology and Necropsy

By day three of infection, the organism should be readily apparent in neutrophils in peripheral blood smears stained with methylene blue. The organism is located within vacu­oles in the cell cytoplasm. Leukopenia is marked, with WBC counts commonly less than 3500 by day seven. Initially there is a reversal of the neutrophil-to-lymphocyte ratio because of a transient lymphopenia. Subsequently, lymphocyte numbers return toward normal and neutrophil numbers continue to decrease. A decrease in serum alka­line phosphatase has been observed in the acute phase of tick-borne fever in goats, but the cause is unclear. There are no remarkable necropsy findings.

Diagnosis

A presentation of high fever in tick-infested goats should suggest tick-borne fever in endemic areas. In the acute phase of disease, identification of the organism in neutro­phils in peripheral blood smears is diagnostic. Serologic evidence of infection may be obtained by CF test or counter-immunoelectrophoresis (Webster and Mitchell 1988), as well as an indirect immunofluorescent test (Jongejan et al. 1989). Molecular techniques such as PCR will detect the organism in heparanized whole blood sam­ples (Zhan et al. 2010). Louping-ill, a viral disease, is also transmitted by I. ricinus and can produce fever. The two diseases can occur concurrently in endemic areas. Louping- ill produces neurologic signs, and serologic evidence of infection can be obtained.

Treatment and Control

Several drugs have been evaluated for treatment of goats (Anika et al. 1986a, b). A single intravenous (IV) injection of oxytetracycline at a dose of 10 mg/kg resulted in a return to normal body temperature in six hours and killing of intracellular organisms. A single IV dose of trimethoprim (20 mg/kg) in combination with sulphamethylphenazole (50 mg/kg) and sulphadimidine (50 mg/kg) was also effective, as was chloramphenicol in a single IV dose of 50 mg/kg, where its use is permitted. Spiramycin and ampi­cillin were not effective against tick-borne fever.

Control of tick-borne fever involves controlling exposure of goats to ticks. Pasturing young goats in tick-infested areas during seasons of low tick activity may promote immunity and reduce the severity of disease that develops during periods of increased exposure. The use of acaricides during seasons of high tick activity may also be beneficial.