ANAPLASMOSIS symptoms , lifecycle , pathogenesis, treatment drug of choice in farm animals

                                                          ANAPLASMOSIS

Aetiology

A rickettsial organism, Anaplasma marginale, is the cause of anaplasmosis in cattle. The organism parasitizes red blood cells following infection of susceptible cattle and is transmitted by ticks, biting insects, and introduced mechanically by blood-contaminated instruments that penetrate the skin. Dermacentor andersoni, other Dermacentor species, and B. annulatus are biologic vectors that pass A. marginale through their eggs into the next generation of ticks. Other ticks, tabanids, and mosquitoes may be mechanical vectors of the disease as they inject blood from infected cattle to susceptible cattle while feeding. Needles and veterinary instruments that become contaminated with blood during herd-wide procedures can transmit the infection. 

Similarly, blood-contaminated instruments used for reproductive work such as infusion cannulas, embryo transfer instruments, and insemination equipment occasionally can spread the infection. Chronically infected cattle that usually are asymptomatic act as reservoirs of anaplasmosis and the spread of the disease tends to occur during peak vector seasons or following common surgical procedures that result in the iatrogenic spread. Cattle less than 1 year of age tend to either be resistant to infection or have very mild signs of illness. The opposite is true for adult cattle because susceptible animals more than 2 years of age often have severe illness and possible high mortality. The resistance of young animals to infection may be explained partially by passive antibodies obtained from colostrum. However, other factors appear to be important because infection in susceptible cattle up to 1 to 2 years typically results in mild signs, if any, whereas infection of susceptible cattle older than 2 years frequently causes acute, severe disease. In addition, sources of stress such as shipment, starvation, weather extremes, and experimental splenectomy apparently can overcome the natural resistance of young cattle to anaplasmosis, thereby resulting in acute disease.

 Natural infection of young cattle results in a carrier state that may persist for the life of the animal. A biological balance appears necessary to maintain immunity because clearing of infection eventually may allow susceptibility to reinfection. Seroconversion may occur despite the chronic carrier state, although it does not occur in all infected carrier cattle. Protective immunity requires both humoral and cellular immune components, including antibodies against the outer cell membrane plus macrophage activation. The immune response can clear the acute rickettsemia but fail to completely clear the infection because of the development of antigenic variants of the agent. Seropositive cattle are assumed to be carriers. Seronegative cattle in endemic areas are more difficult to categorize and the subject of much research. Further confusion is added by studies that demonstrate acquired immunity to clinical disease persisting following clearance of infection by chemotherapy.

 This immunity following chemotherapy with imidocarb or tetracycline persisted regardless of the seropositive or seronegative status of the treated cattle. However, in endemic regions harbouring anaplasmosis, seronegative cattle within A. marginal-infected herds appear susceptible to infection and illness. Therefore seronegative cows in positive herds have not necessarily developed effective immunity even if they had been seropositive previously and naturally cleared the infection later. Relative exposure rate, concurrent stresses, vector loads, and length of time between clearance of infection and subsequent reinfection all may influence the susceptibility of seronegative cattle that once had been seropositive.

Clinical Signs

As previously stated, the likelihood of clinical illness associated with A. marginale infection is typically proportional to the age of the susceptible animal. Exceptions do occur, especially when extraordinary stress, heavy infective doses, heavy vector parasitism, or concurrent diseases overwhelm the apparent resistance in younger cattle. Many, if not most, animals less than 1 year of age have an inapparent infection or very mild signs. Incubation in natural infection ranges from 20 to 40 days and is followed by an acute disease characterized by dramatic signs of a fever (104.0 to 107.0° F/40.0 to 41.7° C), depression, anorexia, gastrointestinal stasis, anaemia, dehydration, and cessation of milk flow. The severity of clinical signs is proportional to the degree of anaemia. Icterus is present in many acute cases but may not appear unless the affected animal survives 2 or more days.

 Hemoglobinuria does not occur. Hemolysis results from erythrocyte destruction by the reticuloendothelial system and therefore is primarily extravascular. Mortality varies but may reach 50% in acute cases. Infected cattle that survive acute signs may remain weak, anaemic, jaundiced, and lose significant condition. Susceptible adult cattle introduced into endemic herds may suffer peracute signs and die within 1 to 2 days after the onset of signs. Infected animals are assumed to remain carriers of the organism regardless of the degree of subsequent seropositive status. Recovery from the acute disease may require weeks. Abortion may occur during the acute or convalescent period.

Diagnosis

The CF and rapid card agglutination tests are the most common means of confirmation of infection but may not become positive until 1 week following acute infection. These same serologic tests are very useful to detect chronic carrier cattle that may be free of clinical signs. Diagnosis in acute cases is aided by ancillary tests that verify the severe anaemia (low packed cell volume and regenerative) and also rule out liver disease as a cause of jaundice. Microscopic examination of whole blood smears stained by Wright’s, new methylene blue, or Giemsa stains may allow identification of A. marginale in erythrocytes (Figure 15-7). The organisms appear as one or more spherical bodies in the periphery of erythrocytes and must be differentiated from basophilic stippling and Howell-Jolly bodies. PCR and competitive ELISA are newer and more sensitive tests and should be used to help determine infection and clearance of infection following treatment.

Treatment

Treatment with several chemotherapeutic agents is possible but inconsistently effective in clearing the organism. The most current recommendations in North America indicate oxytetracycline to be the treatment of choice. In Europe, fluoroquinolones could be used. A variety of tetracyclines can be used, and the intensity of treatment may dictate whether the organism is eliminated or simply reduced in number within the host. Imidocarb dipropionate (5.0 mg/kg IM in two doses at 14-day intervals) will sterilize infected cattle, but this drug is not used in cattle in North America. Long-acting tetracycline (20 mg/kg IM four times at 3-day intervals; Liquamycin LA 200, Pfi zer, Inc., Animal Health Division) also eliminates the infection in some calves.

 Lesser numbers of injections of this same long-acting tetracycline may control acute infections but not eliminate the organism completely. Cattle cleared of infection may eventually be susceptible to infection again. Whole blood transfusions also may be necessary when anaemia is judged to be life-threatening in acutely infected cattle. Acaricides and fly control measures always are indicated to reduce the vector population as much as possible. These chemicals must be applied or utilized in approved manners as regards dairy cattle. 

Prevention

When the incidence of infection is low, elimination of infection in acute and asymptomatic carrier cattle (as evidenced by seropositivity) coupled with insect control may allow effective control. Endemic herds or geographic regions present a more difficult challenge for control measures. In addition to vector control and treatment measures, husbandry practices must be modified. Stress should be minimized; animals from nonendemic areas should not be introduced to the herd; and common use of instruments for veterinary procedures, blood collection, and ear tagging should be avoided unless disinfected between animals. Vaccinations have been used but require care because currently, none are completely free of problems. 

In the United States, a killed product has been utilized, and this product is formulated from infected erythrocytes. Therefore anti-red blood cell antibodies may develop in vaccinated cattle and predispose to neonatal isoerythrolysis in calves born to vaccinated cows receiving the recommended yearly boosters. Administration of boosters should not be performed during late gestation. Live vaccines are commonly used in many countries including Australia and countries in Central and South America but are not licensed in the United States because of concerns about pathogen transmission from blood-based vaccines. A product approved in California consists of modified live irradiated A. marginal organisms and is administered to calves less than 1 year of age to cause immunity associated with persistent infection. This vaccine may cause disease if administered to older animals. Recently another purified vaccine has been introduced and is available in the United States.

 This vaccine is reported to minimize the potential for neonatal isoerythrolysis in calves suckling colostrum from vaccinated dams (Am-Vax, Schering-Plough Animal Health, Kenilworth, NJ). Continued advances in vaccine technology hold the best hope for future control of anaplasmosis in cattle.