Friday, September 26, 2003

Mass Medication – The Practice and Problems

Mass medication programs are useful when used appropriately in food animal production. But your goal should be kept in focus when deciding the method, route of administration and product to be used.
   The treatment may be preventive or therapeutic, or a combination of the two, depending upon the stage of the disease in question in the individuals comprising the group treated. When utilized effectively, mass medication is a medically and economically sound procedure, combining veterinary science with practical production economics. On the other hand, when misused or misdirected, it can be an inefficient additional expense and a confounding factor to satisfactory therapy. Mass medication is defined as the administration of a pharmaceutical product to an entire group of food animals for disease control purposes.This treatment usually includes antibiotics directed at bacteria, mycoplasmas or rickettsia and compounds controlling
coccidial infections.

Goals of Mass Medication
   Two main goalsmorbidity and mortality controlare most often the focus of mass medication programs in food animals. Morbidity control is more easily and effectively achieved; mortality control is more difficult.

   Morbidity is defined as the cumulative sum or percentage of animals that must be removed from their pen or herdmates for individual treatment. Costs incurred on these animals include not only direct medical costs, but also the time and money spent in removing and holding them in a separate location for treatment and returning them back to the group.
   By controlling morbidity, at least one of the following  three objectives are realized:
   1. Health costs are minimized when treating the entire group with mass medication (plus the remaining sick individuals after mass treatment), resulting in less total dollars spent than treating all sick animals on an individual basis from the start.
   2. Facilities are inadequate to handle a large number of sick animals on an individual basis, thus making mass treatment more cost effective than facility construction or expansion.
   3. Personnel are lacking in time or capability to handle a large number of sick animals on an individual basis, thus making mass treatment more cost effective than hiring more or better capable personnel.
   On a strictly medical cost return example, lets assume that the mass medication of a group of 100 animals undergoing a disease outbreak costs $2 per head for a total of $200. And assume that the cost to treat an individual animal for the disease is $15. Using these figures, mass medication in order to  be cost effective, would have to prevent or stop the disease in at least 14 animals that otherwise would have required individual treatment. Remember, this solely assesses the return on a medical cost basis and does not include facility or personnel costs, or additional losses occurring when an animal must be separated  from the group.
   Mortality, defined as the sum or percentage of dead cattle out of the subject group, is more difficult to alter directly with mass medication. Certainly when indirect factors such as inadequate facilities or poor ability to identify sick individuals early are a consideration, then mass medication may improve the final mortality rate.
   However, when all aspects of individual cattle identification and treatment are adequate and uncompromised, mass medication as a rule does not decrease overall mortality. Some sick individuals require more therapeutic care and supportive management than what can be provided in a mass medication program. Additionally, mass treatment can make sick animals harder to identify by temporarily abating the clinical signs but allowing a relapse back into clinical disease one to several days after the program.

   Any medical procedure, including mass medication, can be evaluated by four criteria:
     1. Cost. Is the expense of the mass treatment justified as compared to the results expected or observed with less expensive products or combinations?
     2. Stress. How stressful is the mass treatment on the cattle? Does clinical benefit compensate for the stress involved?
     3. Efficacy. How effective is the mass treatment (in vitro and in vivo)?
     4. Convenience. How easy is the mass treatment and does the convenience compensate for any shortcomings?

Route Of Administration
   Several types and forms of products are available utilizing various routes of administration. The route  chosen depends upon the disease being treated, the facilities and husbandry conditions and the economics of the delivery system or procedure. Here are four  alternative routes:
   1. Feed. Several feed ingredients are available and approved for mass medication in beef cattle. The key factor in successful group medication is consumption of adequate levels of the ingredient by all or most of the group. As simple as this sounds, it often is overlooked. Either uneven mixing practices, behavioral eating patterns or individual animal anorexia due to disease may  influence the outcome of mass medication.
   Sick animals often go off feed. So mass medication should be geared as a preventive approach early if respiratory disease control is the focus.
   Oxytetracycline and chlortetracycline are available as feed additives for disease control. Additionally, oxytetracycline is available in combination with neomycin, and chlortetracycline is available in combination with sulfamethazine. Indications for use and withdrawal times vary with the level or dose of the product included.
   Besides being included into mixed feed in a microingredient or premix form, these products are also available in a crumbles or pellet form to be top dressed over feed. The crumbles and pellets have shown to be especially palatable to cattle and may stimulate increased consumption as a secondary benefit.
   For control of coccidiosis, four feed ingredients have been approved: amprolium, decoquinate, lasalocid and monensin. In determining which product to use, its important to know (a) the life cycle of the coccidial organism, (b) the duration of time it must be fed, and (c) how to include it in a feeding program. Also, each product differs in approvals to be fed with other ingredients and this must be considered.
   Tylosin is also approved as a feed ingredient with a primary role of liver abscess control in feeder cattle.
   2. Water. Fewer products are available to medicate water than for feed. Sulfonamides are the antibacterial compounds available for medicating water. The same principle applies to water medications as with feedthe animals must drink the water in order to receive a benefit. Water medications can decrease the palatability of the water, and this may increase the uncertainty of adequate delivery of the medication to appropriate animals. In an attempt to overcome this, flavored gelatin powder has been added with the medication to alter the smell and taste of the water. Practitioners vary in their preference of flavor to be added. To achieve the effective dose required, the mechanics of water medication must be monitored closely to ensure that the proper amount is added initially and maintained through the medicating period. Continuous flow or automatic refill tank systems prove unmanageable, so all sources of water must be manually filled and medicated.
   3. Oral. Individual oral medications require that the animal be caught and restrained for administration of the product. Liquid and bolus forms are available. The liquids include neomycin sulfate and some sulfonamides. These are primarily for bacterial enteritis and absorption through the GI tract is limited. The liquid medications are administered through a drench wand or hook.
The boluses available consist of one or a combination of sulfonamides and neomycin sulfate. They are approved for the treatment of enteritis, respiratory disease and foot rot. Absorption across the GI tract must occur at significant levels in order to reach target tissues of lung and feet.
Long-acting, sustained release boluses containing a sulfonamide are available, giving 48 to 72 hours of therapeutic blood levels from a single administration. Boluses are time-consuming to administer and adequate head restraint must be obtained. Multi-dose balling guns are frequently used to administer boluses but have been shown to result in a higher incidence of pharyngeal trauma and abscessation than single dose equipment. This may be a consideration during mass medication of a large group when time becomes a factor.
   4. Injectable. Antimicrobials alone or in combination represent a high percentage of all the mass medication regimens performed on food animals. However, increasing concerns over injection site trauma and scarring in muscle tissue has led to the reevaluation of many habitually routine procedures, not the least of which is intramuscular mass medication.
   The intramuscular, subcutaneous and intravenous routes of administration have all been used for mass medication purposes. The intramuscular route has been the method of choice until recent concerns about carcass quality. The neck area is the site for both intramuscular and subcutaneous injections. A disadvantage of intramuscular injection of mass medications is the muscle soreness that can develop with some products or combinations. The propylene glycol-based products and 200 mg/ml products are especially noted for this. In extreme cases, the stress caused by muscle soreness precludes any therapeutic benefit achieved from the injection.
   The subcutaneous route of injection becomes increasingly more popular when compatible with the medication being administered. Though some scarring may occur, the muscle trims at carcass fabrication are minor compared to intramuscular injections. Large volumes of medication are more easily accommodated. Technique is critical to obtain a true subcutaneous injection, and it is preferable to manually tentthe skin prior to needle insertion to avoid abrasion of underlying muscle tissues.
   The intravenous route of administration is desirable for compatible products due to negligible impact on carcass quality. But like the oral boluses, this often proves too time-consuming and inconvenient  for mass medication purposes. If injectable sulfonamides are used, however, this route must be utilized as it is the only approved route of administration  for these products.
   Long-acting injectable antimicrobial formulations are currently available. Long-acting oxytetracycline is available in a 200 mg/ml and 300 mg/ml preparation. Long-acting
combinations of procaine penicillin G and benzathine penicillin are also being marketed commercially. Another parenteral administration is the use of Tilmicosin at the label dose of 10 mg/kg.
   Previously, bioavailability and convenience were the major concerns regarding mass medication routes of administration. However, recent pressures from the beef packing industry, and subsequent response and investigation by production-oriented veterinarians and producer organizations, have prompted new research and focus on injection site dynamics and tissue characteristics.
   Mass medication techniques are especially suspect when a majority, or all, of the food animals in a particular group are medicated. It is critical that all animals medicated are somehow identified so appropriate withdrawal times may be observed and potential carcass trims at slaughter may be traced back to the problem procedure.

Specific Program Applications
   In the feedyard. Mass medication programs are widely utilized in receiving programs on high risk stressed or sick cattle. Injectable antibiotics or combinations are the most common form of treatment.
   Respiratory disease is the main focus and these programs are geared toward morbidity control. Intramuscular and subcutaneous routes of administration are the norm and programs vary from one to three days in duration.
   Occasionally during prolonged wet or dry periods, foot rot reaches epidemic proportions in a feedyard. Individual therapy is effective; however, many of these cattle are in the finishing phase of the feeding period. So it is costly (in lost performance) to remove them from their home pen and inconvenient to a follow a withdrawal period.
   Mass medication with a feedgrade tetracycline has proven effective in stopping epidemic foot rot. Oxytetracycline fed at just less than two grams per head per day has no withdrawal requirement and is an effective prophylaxis against further cases; also, its therapeutic in mild to moderate cases already present.
   Tylosin is available in feed additive form for control of liver abscesses. Prior to the introduction of this practice, it was common to feed one of the tetracyclines at high levels (2-4 grams) three days a month for the same purpose.
   Decoquinate, lasalocid, or monensin are commonly fed as a coccidiostat in receiving and starting rations. Factors affecting the choice as to which is fed include (a) the degree of challenge, (b) concomitant approvals with other additives and (c) feeding program.
   Amprolium also has been approved and used as a treatment for clinical coccidiosis, as well as being apreventive compound.
   In stocker operations. Mass medication in stocker cattle is widely utilized, much as in high risk stressed or sick feeder cattle. But many stocker operations dont have holding and working facilities to handle sick cattle. Thus, individual animals must be roped and thrown or driven long distances to facilities in order to be treated. Either scenario is highly stressful and may not be conductive to a satisfactory treatment response.
   Therefore, it often is cost effective to aggressively mass medicate received cattle in order to minimize, if not prevent morbidity. Parenteral aminoglycosides, particularly neomycin, require extremely long and somewhat unpredictable withdrawal periods200 days or more in some casesand should not be used to avoid a violative residue.
   Surfactants, though not antimicrobials, are commonly placed in the water of stocker cattle for bloat prevention. This is especially useful in high moisture, rapidly growing legume pastures where bloat potential is high. Of course, enough surfactant must be ingested, within tolerable palatability limits, to prevent a frothy bloat in the rumen. When they quit drinking, you have added too much.
   In cow-calf operations. Antimicrobial mass medication in cow-calf herds usually is directed at calf disease. Antibiotics may be included in creep feed as prophylaxis against respiratory disease, although this is generally unsuccessful since sick calves usually back off the creep feed. Individual calves are often caught and handled one time during an outbreak and given long-lasting oxytetracycline injection and longacting sulfa boluses.
   Weaned calves also can be medicated through the water with sulfonamides. This proves too costly in sucking calves, however, because they share a common water source with the cow and most of the medication goes to the cow.
   Anaplasmosis control in cows has been achieved with mass medication in endemic or problem areas. For prophylactic purposes, constant feeding of a tetracycline at low to moderate levels has been utilized. During an acute outbreak, herds can be medicated with intramuscular long-lasting oxytetracycline at 9 mg/lb body weight.
   For prevention of grass tetany and milk fever, magnesium and calcium can be provided to cows on a mass medication basis. This is usually in the form of free choice mineral licks or blocks.          
   Additionally, prostaglandins have been injected on a mass basis for estrus synchronization in cow herds.

Mass Medication Criteria
   Since the decision to mass medicate a group of animals is quite subjective, here are several criteria to consider:
   1. Clinical appearance and past performance of similar cattle. This requires a key person to evaluate the animals upon arrival and daily thereafter in determining the need for mass medication. A knowledge of the morbidity/mortality patterns of previous animals from the same origin is helpful. A keen ability to observe and clinically evaluate the group also is helpful.
   2. Morbidity patterns. This criterion proves useful for deciding when to mass medicate for respiratory disease in the feedlot. When morbidity exceeds predetermined percentages, either on a daily or cumulative basis, mass medication is indicated. For example, a pull rate out of a pen of 10% any one day or a cumulative 25% over a three-to-five day period indicates mass medication.
   3. Feed consumption. When routinely measured, feed consumption can serve as an early indicator of an impending disease break, before observable clinical signs appear. A sudden drop in feed consumption suggests mass medication should be considered, particularly in high risk cattle.
   4. Body temperature. When cattle are being worked as a group, rectal temperature has been used as a judgment criterion to selectively medicate individuals. Individuals below the selected temperature point receive either no antibiotic or a less expensive, less efficacious one.
   However, it must be recognized that (a) temperature elevations occur for reasons other than infection and (b) animals harboring a bacterial infection do not always maintain a fever.
   The ambient environmental temperature, the animals disposition, and the order in which the animal is worked in the group can all elevate the body temperature. Conversely, extended disease progressing to a weak moribund animal or previous treatment with corticosteroids can lower the body temperature.

Choosing the Product
   Product choices are reasonably clear cut for the feed, water and oral routes of mass medication. The injectable route is not so clear.
   Here are some characteristics to consider when selecting an injectable mass medication program:
   1. FDA approved for use in beef cattle. Extralabel drug usage currently is left to the discretion of the veterinarian under some general guidelines. Abuse of this privilege may jeopardize the veterinarians position.
   2. Inexpensive. Return on the money spent is the key here. Will an expensive but highly efficacious drug afford results that justify its use over a less expensive and possibly less efficacious drug?
   3. Effective against respiratory and GI pathogens. These conditions are common and frequently found simultaneously in the same animal.
   4. Active in small volumes. Injection mechanics and tissue damage are more likely and of more concern with large volume formulations.
   5. Non-irritating upon injection. Injection site scarring and the stress of muscle soreness must be weighed against clinical benefit.
   6. Wide safety margin. Accurate dosing may prove difficult in a group with variable weights. Narrow safety margins increase the chance of overdosing and causing adverse reactions or toxicity.
   7. Easy to administer. The intramuscular and subcutaneous routes remain the easiest methods of delivery.
   8. No interference with subsequent antibiotic use. There are many theories and questions exist as to resistant bacterial strains after antibiotic administration. Most likely, resistance develops against antibiotics after previous treatment with a different one.
   9. Does not mask effects of disease condition. The alteration of an infection from clinical to subclinical adversely affects sick animal identification. Also, early or continued treatment can facilitate the development of a chronic disease.
   10. Short withdrawal time. Extended withdrawal times preclude the option to recognize and pull poorly performing animals. Also, it increases the risk of violative residues and, in extreme cases, may delay the marketing of a finished animal. 
   When choosing a specific injectable product or combination for mass medication, bacterial cultures and sensitivity determinations are of value, if time permits.
   Some antibiotics show 100% efficacy continuously over time, i.e. ceftiofur, sulfachlorpyridazine, and trimethoprim/sulfa on isolates of Pasteurella-Mannheimia/Hemophilas. Unfortunately, however, 100% cure rates are rarely experienced because effective antibiotic therapy is just one aspect of achieving a cure. The best results come from ongoing culture and sensitivity monitoring.
   In summary, mass medication is a health management tool that, when used appropriately, results in cost savings and sound economic return to the food animal producer. Careful planning and consideration should precede the implementation of a mass treatment program, clearly defining the goal to be achieved and a detailed plan of execution. For economic as well as professional reasons, indiscriminate administration of antibiotics to large groups of
food animals should be avoided.