ZOONOTIC DISEASE PREVENTION AND REDUCTION INITIATIVES

by Joseph C. Paige, D.V.M., M.P.H.

The Center for Veterinary Medicine (CVM) is currently reevaluating its role in the 21st Century considering food safety issues that focus on microbial pathogens, foodborne and zoonotic diseases. CVM intends to increase activities in these areas by developing a science-based, strategic, and systematic plan based on epidemiologic principles. These changes will improve decisionmaking within CVM and help increase consumer confidence in the safety of the Nation¹s food supply. This article focuses on CVM programs to reduce exposure to salmonella spp. via the feed, zoonotic concerns inherent in the drug approval process (e.g., salmonella shedding), and enumerate a limited list of zoonotic diseases where therapeutic drugs are available.

CVM is acutely aware of the broad public health consequences that may occur as a result of exposure of human populations to agents or vectors responsible for zoonotic diseases. CVM is actively involved in interagency activities to ensure the continued safety and efficacy of animal drugs, including those drugs used to treat zoonotic diseases in animals.

Overview

The term ³zoonoses² is defined as an animal disease that is transmissible to man. The criteria used to define zoonotic infection varies, depending on how strictly the definition includes a vertebrate intermediate, other than human, in the natural cycle of distribution. Transmission of the pathogen may occur from the pathogen directly to man or from products derived from the host animal or through an arthropod intermediate. As new biomedical knowledge is acquired, new zoonotic diseases are continually being recognized. For example, over the past decade a number of new diseases have emerged globally, and some previously recognized infections have been identified in regions/species where they had not been reported before. A number of natural and human factors individually or collectively impact on the environment and potentially influence where certain zoonoses emerge, persist, or spread. Some of these factors are: geoclimatic conditions; animal, avian and aquatic hosts; migration patterns; arthropod reservoirs and vectors; and, human impact on ecosystem and biosystem. The list of recognized diseases is well documented in many sources of the literature in human and veterinary medicine, virology, and microbiology.

The principles of surveillance have been well instituted in the Center to gather data on zoonotic entities in order to characterize the problem so that prevention and control efforts can be developed and implemented. Surveillance provides information suggesting the need for institution of specific control and prevention measures. Many drugs are currently approved for control of a majority of bacterial and parasitic infections (the primary sources of zoonotic diseases). Therefore, there is very little impact of any regulatory delay in the drug approval process for drugs that treat zoonotic diseases.

One example of a Center activity which utilizes surveillance techniques is the Salmonella Control in Feed and Feed Ingredients Program. The goal of the program is to obtain zero Salmonella contamination in animal feed ingredients and finished feed. Earlier reports by FDA and the U.S. Department of Agriculture (USDA) concluded that salmonella contamination in feed contributed to salmonella in animals and likely contributed to disease in man. (This scenario fits our definition of a zoonotic disease). The next step was to collect and compile available data to demonstrate the potential problem to industry and academia. Where data did not exist or was of poor quality, FDA/CVM initiated a survey to gather such data. Field investigators sampled complete feed as well as animal and vegetable meal ingredients at feed mills and on-farm mixers for salmonella contamination. A number of studies support the link between salmonella in animal feed and human disease. Even though there is no definitive association between salmonella isolated from feed and human disease at this time, there is strong circumstantial evidence supporting this link which raises the public health concern about the need to control the adulterant (salmonella) in feed and feed ingredients.

In order to accomplish the stated goal of zero tolerance of salmonella in feed ingredients and finished feed, CVM supports a quality assurance program. To this aim, CVM is focusing on a Hazard Analysis of Critical Control Points (HACCP) approach, which addresses the root causes of food safety. This approach is preventative and is applicable to both human and animal feed, providing a more efficient means of ensuring feed safety. Several segments of the industry are now developing generic HACCP. From a regulatory perspective, CVM is focusing on taking action against those firms that show a high incidence of positives of salmonella contamination in animal feed. CVM has recently approved two food additives for salmonella control that are expected to aid in accomplishing CVM¹s goal of zero tolerance for salmonella contamination of feed. This program contributes to reducing salmonella exposure to food animals, and, thereby reduces the incidence of zoonotic disease attributable to salmonella species.

Zoonotic concerns are taken into consideration in the drug approval process. User safety is always evaluated. Will this drug pose a human safety problem of public health significance if approved? This may vary from a situation where approval would pose a positive impact on spread of the infectious agent, and thereby increasing risk of human exposure to a condition where there may be the development of resistance leading to compromise of therapy. A classic example is the salmonella shedding issue. When conditions arise where it is known that a zoonotic disease exists in the species, CVM consults with the Centers for Disease Control and Prevention (CDC), which maintains data on the incidence and prevalence of various zoonotic diseases. CVM utilizes this information to assess problems that may exist with a potential approval.

The problems involved in reducing the prevalence of zoonotic disease is more complicated than having available therapeutic drugs. There must be an understanding of the major factors involved in the transmission (agent, host, and environment) of the disease. Another significant area of intervention in reducing the spread of zoonotic diseases is the development of an adequate animal vaccination program to prevent the disease entity. Since the development of infections is multifactorial, designing control measures is complex. Control efforts for zoonotic diseases may best be directed toward controlling or eradicating the agent at its reservoir or source rather than post-infection therapy.

Another example of a regulatory strategy with potential for reducing zoonotic disease is in the approval criteria for subtherapeutic drugs in food animals, where the increase in salmonella shedding is an issue of concern. This criteria demonstrates animal and human safety with regard to the zoonotic agent, salmonella, by demonstrating that the drug under review does not result in an increase in quantity, prevalence, or duration of salmonella shedding in medicated animals when compared with non-medicated controls or increase the quantity or spectrum of drug-resistant salmonella.

CVM is a valuable resource for several Federal agencies directly involved in zoonotic investigations. There is potential for greater involvement in the future and CVM is currently developing the resources to meet that challenge. CDC has the primary responsibility for investigating a zoonotic disease outbreak in humans and is the first Federal agency notified by the involved State. CVM is currently collaborating with CDC and USDA involving antimicrobial susceptibility monitoring.

Zoonotic Diseases

The following table represents a select list of zoonotic diseases where parenteral therapy is available:

* These represent only a partial list of drugs available to treat these diseases.

Future Concerns High priority needs in the future will be to continue efforts to strengthen CVM¹s overall surveillance by developing post-marketing programs to address adverse drug reactions and improve follow-up and prevention efforts to reduce drug residues. Also, CVM will continue applied research efforts and existing prevention and control programs. In addition, CVM intends to expand the cooperative interaction with CDC, USDA¹s Animal and Plant Health Inspection Service Veterinary Services (USDA/APHIS/VS) Centers for Epidemiology and Animal Health, CDC, and USDA¹s Food Safety and Inspection Service (USDA/FSIS). The following efforts are planned:

• Continue to engage in applied research relative to program needs.
  
• Improve surveillance by increasing resources (personnel, etc.) to address future needs in foodborne zoonotic diseases.
  
• Continue current sentinel surveillance systems such as those now being developed with the ³Antimicrobial Susceptibility Monitoring System.²
  
• Continue to increase communications with consumers to provide assurance of the true impact of antibiotic residues, foodborne pathogens, antibiotic resistance, and zoonotic diseases on public health.
  
• Continue to enter into cooperative agreements with CDC, USDA/APHIS/VS Centers for Epidemiology and Animal Health, and USDA/FSIS concerning the drug residue program under a HACCP approach.
  
• Continue to strengthen the epidemiologic approach in evaluation of food safety issues in order to develop appropriate policy strategies.

To meet these future needs in an increasing technological era, CVM has made tremendous progress by expanding its computer technological base. All of these efforts help the Center in responding to our mission to assure the safety and efficacy of drugs approved and to increase CVM¹s responsibility regarding foodborne issues.

References for this article may be obtained from the FDA Veterinarian.