Anaplasmosis in cattle (Proceedings)

Anaplasmosis is a noncontagious, infectious, transmissible hemoparasitic disease of cattle. It is caused by Anaplasma marginale in the United States and A. centrale in parts of Africa. Anaplasma marginale is member of the order Rickettsiales and anaplasmosis is characterized by anemia, fever, and icterus.

Reservoir hosts

The agent is enzootic in both cattle and certain wildlife hosts. The prevalence in cattle varies between region of the U.S. and within regions depending on topography, wildlife hosts, vectors, and management practices. Likewise, the prevalence in wildlife species can vary by region. For example, Columbian black-tailed deer populations in California have near 100% carrier status for A. marginale, while the white-tailed deer of the Midwest and southeastern U.S. have prevalence rates of about 1% or less. Wildlife species such as antelope, elk, and big horn sheep can also be experimentally infected with A. marginale. While ticks are not normally thought of as reservoir hosts—in the case of anaplasmosis, they can "carry" the agent for long periods of time. While they are usually classified as vectors, from a functional state I tend to think of them as potential reservoirs of new infections. The most important mammalian reservoirs in the U.S. are cattle and black-tailed deer; however, this is not to imply that clinical disease is always limited to areas populated by carrier cattle or black-tailed deer.

Transmission

Boophilus ticks can transmit both babesiosis and anaplasmosis and are extremely important vectors in the areas of the world where they exist. The eradication of Boophilus annulatus in the U.S. has eliminated this potential vector in terms of transmission. The importance of maintaining that eradication control is two-fold because of anaplasmosis and babesiosis. In the western U.S. Dermacentor occidentalis and Dermacentor andersoni are both important in the natural transmission of anaplasmosis. They both will feed on deer species and can pass the anaplasmosis organism from stage to stage (larvae, nymph, and adult) and possibly can have transovarian transmission of the agent. Thus, these ticks are potent biological vectors of anaplasmosis.

Mechanical vectors of anaplasmosis include horse flies, stable flies, deer flies, and possibly mosquitoes. The most important of these are the horse flies (Tabanids) as they tend to be interrupted feeders, have large mouth pieces that can contain a relatively large amount of blood, and can fly long distances. These vectors can all transmit blood from an infected (carrier) animal to a susceptible animal under practical conditions. Additionally, mechanical transmission can occur iatrogenically during common management procedures such as dehorning, castration, bleeding, use of nose tongs, ear tagging, vaccination (hypodermic needles) and other surgical procedures. The routine use of disinfection and cleaning of instruments between uses will help eliminate this possible route of transmission.

Pathogenesis

The age of the animal is an important factor in determining susceptibility to clinical disease. Cattle can become infected at any age; but the older they are the more likely they are to have clinical signs of anaplasmosis. Cattle up to 6 months of age can become infected but do not develop detectable clinical signs. Cattle 6-12 months of age rarely develop overt illness, but their PCV will decrease after they become infected. Cattle 12-18 months have a greater chance of developing clinical illness (1%-20%) and cattle over 24 months of age can experience 50% mortality or more if not treated after infection. The disease can be divided into four phases which have clinical significance: incubation (prepatent), developmental, convalescent, and carrier.

After infection with A. marginale, the organism begins invasion of the erythron and the length of time of the prepatent period is dose dependent with a typical range of 3-8 weeks. At the end of the incubation phase the organism can be seen in abut 1% of the red blood cells if a blood smear is examined. However, clinical signs are not apparent at this time. The developmental phase begins at this time and the % parasitemia doubles each day for 4-11 days. At the end of this phase the animal has recognized the infection and begins to destroy the infected RBCs and the clinical signs of fever, anemia, and icterus are apparent. Death losses usually occur during the late developmental phase or early convalescent phase. Convalescence is marked by increased erythropoietin (reticulocytes, polychromatophilia, and basophilic stippling) and improving clinical signs. The carrier phase begins with clinical recovery and the disappearance of detectable parasitemia and usually last the life of the animal. The carrier can thus become a reservoir for infection of other cattle or a source of anaplasma for vector transmission.

Clinical signs, differential diagnosis, pathology, and diagnosis

The typical signs include fever (up to 105-106°F), anemia, weakness, anorexia, dehydration, and icterus. Sudden death is not atypical in cattle managed extensively. Tachycardia and tachypnea is typical. Hemoglobinemia or hemoglobinuria is not seen. Belligerence is often seen. Cows may abort and bulls will be sterile for 60 days and perhaps up to a year. Differential diagnoses include: bacillary hemoglobinuria, anthrax, leptospirosis, babesiosis, Clostridium perfringens, rabies (belligerence), post-partum hemoglobinuria, sweet clover toxicity, and bracken fern toxicity. Pathology typically seen includes anemia, hepatomegaly, splenomegaly, and icterus. Typically, the spleen is grossly enlarged and the liver is enlarged and orange.

The appearance of anaplasma bodies in the peripheral blood is suggestive of anaplasmosis when present with typical clinical signs. On post mortem, an impression smear (very light) of the cut surface of the spleen is the best sample to demonstrate the parasitized RBC's. Complement fixation or ELISA antibody titers are helpful in convalescing cattle.

Treatment

The most important considerations are to avoid stress, excitement or exercise and to provide water, shade, and feed. Blood transfusions are helpful if accomplished without stress and 1-2 gallons are recommended for a 1,000 to 1,500 pound animal. The increase in PCV will be transient after a transfusion. Oxytetracycline (OTC) can be administered subcutaneously (9 mg/lb LA formulations) or intravenously (3-5 mg/lb) to acutely ill cattle. These are extra-label uses and prescriptions and appropriate withdrawal times are necessary. The effectiveness of OTC in clinically ill cattle is of limited value and can be detrimental if treatment necessitates stressing or moving the animal.

Prevention

The prevalence of carrier cattle in the herd or wildlife reservoirs in the environment will often dictate the effectiveness of any anaplasmosis preventive program. In herds and areas where the prevalence of anaplasma carriers is zero, the goal is to prevent the introduction of carrier animals. This is accomplished by testing cattle (CF or ELISA) before they enter the herd or before they leave the herd of origin. Only test negative cattle or cattle cleared from the carrier state by use of tetracyclines should be allowed to enter the herd. For herds that have a high prevalence of carriers there are two important tools: (1) do not allow non-vaccinated or non-immune cattle to enter the herd, (2) consider the use of controlled infection methods to inoculate young cattle retained as herd replacements. For herds with intermediate prevalence rates (30-70%) there are often clinical cases on a yearly basis so prevention is much more of an issue. These herds have a choice of using controlled infection of all young cattle retained as replacements to increase the prevalence rate to near 100% or the routine use of a killed vaccine to provide protective immunity to clinical disease. The majority of situations will fall into one of these three categories.

Vaccines

There are currently no USDA licensed vaccines available for use in the U.S. The Anaplaz vaccine (Fort Dodge) and the Plazvax vaccine (Schering-Plough) have both been removed from the market. A killed vaccine (Anaplasmosis Vaccine, University Products, LLC, Baton Rouge, LA) is approved by the USDA as an experimental vaccine and is available in a number of states on approval of state animal health officials (AR, CA, FL, IL, IN, IA, KS, LA, MS, NV, OK, OR, TN, TX, PR). This vaccine purportedly uses the same antigens and purification procedures used in the discontinued Plazvac product. It has the added advantage of not having had reported cases of neonatal isoerythrolysis when used in pregnant cattle. Protective immunity requires two doses (28 days apart) and booster doses are recommended every 1-2 years depending on herd history. This vaccine does not protect against naturally infection, only against clinical disease.

A live vaccine (Anavac, PHL Laboratories, Davis, CA) is available for use in California and is preserved in liquid nitrogen. This vaccine is safe for use in cattle 11 months of age and younger; however, clinical disease severity increases with the age of vaccinated cattle. This vaccine is used as a method for controlled infection. Vaccination typically produces a lifelong immune carrier status. This carrier status can be eliminated with the continual use of tetracyclines and once the carrier status is eliminated the animal should have protected immunity against clinical disease for approximately 2 years. The vaccine likewise will not prevent natural infection by ticks or other routes of transmission.

Outbreak responses

As with preventive measures, the herd prevalence and herd goals are important considerations in planning an appropriate response to an outbreak or an individual case. In the case of an individual animal in a herd that has a zero prevalence, that animal should be isolated and treated with OTC long enough to eliminate the carrier state before going back into the herd. Most other outbreaks require some measure of "custom fitting" to achieve control of the outbreak and herd goals.

Parenteral injections of OTC at 3-5 mg/lb body weight (6.6-11 mg/kg) administered during the pre-patent (incubation) phase will prolong that phase for 2-3 weeks and the same dose of OTC given during the developmental phase will delay the clinical onset of anaplasmosis for 3-4 weeks. In either instance, the delay in the onset of clinical signs will be about 28 days. Also, the severity of clinical signs will be lessened somewhat—although may severe in both instances. In most cases, the phase that individual cattle are in will not be known with any great certainty. Thus, you will have to manage multiple, unknown phases. Some examples of managing an outbreak are listed below:

1. Use of injectable OTC alone to stop an outbreak: 3-5 mg/lb (6.6-11 mg/kg) and repeat at 28 day intervals through the vector season. Observe for clinical signs at the cessation of injections.

2. Use of injectable OTC plus killed vaccine: 3-5 mg/lb (6.6 mg/kg) at first opportunity plus the first dose of the killed vaccine. Repeat OTC and vaccine in 28 days.

3. OTC plus killed vaccine in previously vaccinated herd: OTC injection (3-5 mg/lb) plus booster vaccine to those cattle previously vaccinated (but not adequately re-vaccinated—greater than 2 years). Cattle not previously vaccinated should receive a second dose of OTC and second vaccination at 28 days.

4. OTC injections plus feeding chlortetracycline (CTC): Immediate injection of OTC at 3-5 mg/lb with feeding of CTC at 0.5 mg/lb (1.1 mg/kg) for 60 days or more.

The examples above assume OTC as the 50 mg/ml or 100 mg/ml formulations. If long-acting OTC is given the dose is 9 mg/lb (20 mg/kg); however, the 28 day retreatment interval stays the same, so there is not distinct advantage in using the long-acting products. The injectable OTC products are not labeled for anaplasmosis treatment or prevention and veterinarians need to write prescriptions with appropriate withdrawal times. Also, CTC in various feeds is currently permitted at (a) 350 mg/head/day for cattle under 700 pounds body weight, (b) 0.5 mg/lb body weight (1.1 mg/kg) for cattle over 700 pounds body weight, and (c) 0.5-2 mg/lb/day (1.1-5 mg/kg). Additionally, complete feeds to accomplish these doses can be fed at rates of (a) 25-100 g/ton for feedlot cattle under 700 pounds on complete mixed rations, (b) 25-2,800 g/ton when hand fed to cattle less than 800 lbs (not to exceed 350 mg/head/day), (c) 25-700 g/ton for pasture cattle 700 pounds or less (not to exceed 350 mg/head/day), and (d) 25-1,100 g/ton for pasture cattle greater than 700 pounds. Prescriptions by a veterinarian to change the concentrations of CTC in feeds are not allowed by the FDA.

Elimination of the carrier state

To eliminate A. marginale from carrier cattle there are a number of treatment regimens: (a) Oral CTC at 0.5 mg/lb (1.1 mg/kg) daily for 120 days, (b) Oral CTC at 5 mg/lb (11 mg/kg) daily for 60 days, (c) OTC (50-100 mg/ml) IV or IM at 5 mg/day (11 mg/kg) for 10 days, (d) OTC (50-100 mg/ml) IV or IM at 10 mg/lb (22 mg/kg) for 5 days, and (e) OTC (200 mg/ml) IM at 9 mg/lb (20 mg/kg) for 4 treatments at 3-day intervals. Once an animal has been cleared of the carrier state they will tend to remain CF or ELISA positive for an extended period of time and will probably be protected against clinical disease for approximately 2 years.