Antibiotic Use for Disease Prevention in Animals: A Thematic Paper resulting from the 2nd G7 Chief Veterinary Officers Forum

Susan Vaughn Grooters, MPH, consults for Keep Antibiotics Working regarding consumer advocacy and policy analysis. Susan is also a graduate research associate pursuing a PhD in Veterinary Preventive Medicine.

On October 5th of this last year the 2nd G7 Chief Veterinary Officers Forum took place. At this meeting were the Chief Veterinary Officers (CVOs) from Canada, France, Germany, Japan, Italy, the United Kingdom, the United States of America, and representatives from the European Union, and two intergovernmental organizations – the World Organization for Animal Health (OIE) and the Food and Agriculture Organization (FAO). A full agreement was reached on the strategies and commitments for the fight against Antimicrobial Resistance (AMR), and a thematic paper resulted.

Within this paper, are important definitions. Agreed upon were the definition for antimicrobial, and antibiotics[1].  As well, definitions for administration of an antibiotic for therapeutic use, relating to disease, and non-therapeutic use were delineated. Perhaps telling is that the simplified schematic was noted as being a ‘compromise representation’. (Fig. 1 below)

View fullsize

I write “telling” because in our own coalition of groups working on advocacy around farm antibiotic use, we sometimes struggle to clearly identify the line between judicious and non-judicious use of antibiotics. Likewise, there is consensus among KAW representatives that growth promotion should lie on the non-treatment side, and is non-judicious. However, if the very CVO’s agreed upon definition for treatment is …“the administration of an antibiotic to an individual animal or group of animals with a bacterial disease” (emphasis added), wouldn’t one come to the conclusion that inclusion of prevention/ prophylaxis should therefore not come under this broader grouping of therapeutic?

The answer perhaps lies in the very agreed upon definition for why an antibiotic should ever be administered for treatment – when an animal has a bacterial infection diagnosed. Antibiotics are tools to treat an evident infection; which left untreated would lead to a diseased state. Healthy animals, free from infection, would receive no therapeutic benefit from such administration. Consensus being garnered regarding why growth promotion is clearly a non-therapeutic use. The very designation of healthy animals, being where the line between therapeutic use and production should lie.

Despite the broad brush that many use to paint consumer advocates, we occasionally have differing opinions. Coming to consensus is an arduous task, especially since many of us have disparate backgrounds and interests. My educational background has been in nutrition, food sciences, public health, and veterinary preventive medicine. I’m guessing it’s that last qualifier that many would guess as to what piqued my interest in writing on this topic. However, it’s the public health training.

When I was first learning about disease prevention it was within the context of health behavior and education. The definitions used in public health distinguish between primary, secondary, and tertiary levels of prevention[2]. Primary prevention concerns interventions before there is any disease present. Overall reduction of risk factors to prevent the onset of a targeted condition, are considered primary preventions. These efforts are generally aimed at entire populations, and not individuals. Vaccination to enhance immunity against an infectious disease is often given as an example of an intervention at the primary level. Primary preventions are always prepathogenesis.

Secondary prevention includes screening tests to detect asymptomatic cases. Interventions at this level may include targeting diagnostic testing for those with risk factors for disease onset. Considering animal health in the food production system, this is when quarantine of an animal would be appropriate, after a positive test. Following this same logic, it is also where control / metaphylaxis treatment with an antibiotic would fall. Any treatment at this secondary level is also population focused, applied to prevent disease outbreaks.

Tertiary prevention is directed at managing a diagnosed illness, to reduce complications, and extend the life-span of an individual. With an eye towards bacterial illnesses, treatment with antibiotics to cure an infection would be given at this step.

Perhaps having multiple disciplines’ definitions of prevention is why there is ambiguity in where to draw the line in use of antibiotics. Within the public health paradigm of disease prevention, antibiotics would be given to treat a diagnosed infection at the tertiary level of prevention, and to control illness outbreaks at the secondary level.  Adopting this model for use in production animal health, a public health plan for disease prevention would necessitate increased reliance on non-antibiotic primary preventions, and then secondary preventions both at the population levels. Prophylactic use does not fit in to this paradigm. By the G7’s own definition, prophylaxis is neither used to cure an infection, nor to treat an animal population with clinically diagnosed animals to stop an outbreak.

This primary level of disease prevention is concerned with maintaining health within populations that mitigate all foreseeable risks of infection. The use of vaccinations, biosecurity protocols, and implementation of stringent hygienic husbandry practices are examples of primary preventions. As are inclusion of micronutrients or phytonutrients in feed shown to increase immune status.  Reduction of animal stressors can also work to maintain health at the population-level.  Interventions such as these, implemented in the animals’ environment, provide increased means to stop disease progression before it even starts.

Inclusion of secondary level interventions to detect infections in a subclinical population with aid of rapid diagnostic tests to screen animals that are at risk of bacterial infections, but show no apparent illness is a secondary preventive measure that can be employed to reduce the use of antimicrobials. To control disease onset, limiting or restricting contact with subclinical cases can prevent the occurrence of outbreaks. Reserving treatment only for animals that have a confirmed diagnosis, in conjunction with quarantine can reduce the reliance on metaphylactic use of antibiotics. In the case of disease control with antibiotics, only treating those that are at risk from having had direct contact with animals diagnosed with bacterial infection may also be warranted. Simply relying upon outward signs and symptoms of infection may conflate viral and bacterial illness. Diagnostics distinguish viruses from bacteria; treatment with antibiotics only warranted in the latter.

Administering antibiotics to a group of healthy animals where screened animals with clinical infections diagnosed exist within that same group of animals, would fall under the definition of the G7 CVO’s control / metaphylaxis designation. “The aim of metaphylaxis is to control the spread of the disease from the clinically sick animals to the other animals in close contact and at risk, which may already be subclinically infected”.

A prevention / prophylaxis definition is also given in the G7 CVO’s document. However, just because the use is defined might not mean it is warranted. They state that when no other reasonable alternatives for prevention or intervention exist, should prophylaxis even be considered. In these rare and exceptional cases antibiotics should only be prescribed for a limited duration focused on a specific subset of animals.

In a practical sense I take this agreement from the U.S., in definition and recommendations put forward in this document, to justify requirement of a duration limit set on all drugs that currently fall under usage labeling. And further, it is realistic to believe that a directive should be, if it has not already been, given to producers to carefully define what other reasonable alternatives have been considered in place of prophylactic antibiotic use.

The common vision that is laid out in the G7 document puts forward the decision to prohibit the use of medically important antibiotics for the production use of growth promotion in food animals. This is an important step. However, we’re facing an international public health crisis and many advocates believe that this warrants a stronger response.

I’ll end by echoing what I heard from veterinarians who practice in the U.K. when they attended a One Health meeting, put on by a drug company in D.C. a while back. Their summation was that if an antibiotic is being used prophylactically, the food animal production system where it is being used is in failure. The idea being that all solutions (e.g. at the primary level of intervention) must be instituted and implemented to prevent bacterial disease onset before an antibiotic is ever even considered. The public health paradigm leads us to first work towards eliminating disease risk factors, second to prevent outbreaks, and lastly to treat individual animals if they are ill.

There is consensus that we need stewardship practices so that antibiotics continue to be effective for disease treatment in sick animals, humans included.

If we continue to use them for prevention, will their efficacy remain? I don’t think we should wait to find out.

[1] Agreed definition of antibiotics – “refers to naturally occurring, semi-synthetic or synthetic substances* that exhibit antibacterial activity to kill or inhibit the growth of bacteria, at concentrations attainable in vivo. Biocide substances, such as disinfectants or antiseptics, are excluded from this definition”.

   * Some heavy metals are used as medicinal products due to their antibacterial properties, and co-select for AMR.

[2] Baumann L.C., Karel A. (2013) Prevention: Primary, Secondary, Tertiary. In: Gellman M.D., Turner J.R. (eds) Encyclopedia of Behavioral Medicine. Springer, New York, NY