Animal & Veterinary

Detecting and Preventing Drug-Resistant Parasites

   

Detecting and Preventing Drug-Resistant Parasites
Parasitologist Gasbarre Responds to FDA Report
FDA/CVM Responds to Gasbarre on Resistant Parasites


Detecting and Preventing Drug-Resistant Parasites

John Maday, Editor, Bovine Veterinarian, April 10, 2013

Today’s anti-parasitic drugs generally remain effective against cattle parasites in the United States, but occurrence of resistant parasites in other countries and in other livestock species, and signs of emergence of resistant populations here, create a need for prevention measures. A new report from the FDA’s Center for Veterinary Medicine provides tips for preventing and detecting such resistance.

According to the report’s authors, part of the problem could be that veterinarians and producers are too successful in reducing parasites in host populations.

The paper outlines the concept of “refugia,” which is a portion of the parasite population not targeted for treatment. When an animal is treated with an anti-parasitic drug, susceptible parasites are killed but some resistant or tolerant individuals are left behind. Those parasites pass their genetic resistance on to their offspring. If all the parasites affecting a herd of livestock are exposed to the drug, resistant parasites eventually could make up the majority of the population.

The refugia concept creates a “refuge” for some parasites by leaving them untreated. The idea is to maintain a population of drug-susceptible parasites to dilute the population of resistant ones. Refuges can include untreated animals, parasite eggs and larvae on pastures when animals are treated and life stages of the parasite not affected by treatment. The authors suggest, for example, that treating just half the herd at one time could reduce parasite loads while helping retain the population’s susceptibility to anti-parasite drugs.

The authors list the following management practices they believe contribute to anti-parasitic resistance:

  • Treating every animal in the herd.
  • Frequent routine deworming without performing diagnostic tests or determining if treatment is necessary.
  • Deworming when environmental refugia is low.
  • Giving an anti-parasitic drug without knowing if it will be effective on the farm.
  • Using anti-parasitic drugs for unapproved uses, such as to increase weight gain.
  • Relying solely on anti-parasitic drugs to control parasites, rather than changing management practices.

The authors offer these tips for managing anti-parasitic resistance:

  • Use clinical signs and diagnostic test results to determine which parasites are present on the farm, level of infection and level of resistance, and use the information for management and treatment decisions.
  • Use only anti-parasitic drugs that are effective based on recent diagnostic test results and approved for the particular parasites present on the farm. Always follow the directions on the drug’s label and don’t use anti-parasitic drugs for unapproved uses.
  • Ideally, identify and cull the animals that are the highest fecal egg shedders. Otherwise, target treatment toward animals at greatest risk of illness from parasitic infections.
  • Treat animals when infective larvae are at the highest number on the pasture to maximize environmental refugia. This typically occurs when temperature and humidity are high.
  • When practical, weigh animals to avoid under-dosing anti-parasitic drugs.
  • Maintain adequate treatment records and egg-count reduction results to use in treatment and culling decisions.

Non-treatment management practices that can help reduce parasite infections in herds include:

  • Quarantining new livestock.
  • Rotating pastures with other livestock species or horses.
  • Dragging or harrowing pastures to break up manure piles.
  • Managing pastures for taller grass during grazing. Most parasite larvae stay within an inch of the ground, so cattle grazing short grass can have more exposure. (Well-managed rotational grazing systems have been shown to reduce parasite loads in cattle.)
  • Reducing stocking density, especially so animals are not forced to graze near manure piles.

The paper also includes a discussion of using fecal egg count reduction tests (FECRT) to monitor treatment efficacy in a herd. This involves examining fecal samples before and after treatment and counting the parasite eggs. Less than a 90 percent reduction could indicate resistance, as can a decline in percent reduction over a series of treatments. The authors note, however, that several biological factors reduce the sensitivity of FECRT in cattle compared with other livestock such as small ruminants.

The paper lists several other available tests to identify resistant parasites, but these tend to be expensive.

The paper is available online from FDA’s Center for Veterinary Medicine.

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Parasitologist Gasbarre Responds to FDA Report

John Maday, Editor, Bovine Veterinarian, April 29, 2013

In early April, we ran an article titled “Detecting and preventing drug-resistant parasites,” based on an FDA publication outlining possible causes for the development of resistant parasites and potential management solutions.

Knowing drug resistance in parasites is a complex issue with no clear consensus among the experts, we asked for responses from veterinarians and parasitologists to the FDA’s conclusions and recommendations.

Veterinary parasitologist Lou Gasbarre offered the following comments:

I have read with interest your article dated 4/10/2013 in Bovine Veterinarian concerning detecting and preventing drug-resistant parasites. I feel this is a very important topic and applaud your efforts in bringing this topic to the attention of the cattle industry. At the same time I feel it is very important to provide the industry with the best information we can.

I feel that there are a number of misconceptions in the FDA report that if these recommendations were followed by the cattle industry, they could pose very serious problems for the individual producers. I would like to briefly outline several of these misconceptions/over-simplifications and would be more than happy to discuss them in detail with you if you so desire.

First, the information sheet developed by FDA is a very good set of recommendations for the sheep and goat industry, but has serious flaws when applied to the cattle industry. As you are well aware, the cattle industry is not one management system but is stratified into several steps, i.e. cow/calf, backgrounder/stocker, feedlot and dairy. The recommendations in this article refer to only the cow/calf sector, and even here have some very severe errors. It is completely wrong to assume that the basic biology of the cattle-nematode system is the same as that of the sheep/goat- nematode system. The parasites while in some cases are closely related do not have the same behaviors.

For instance the dominant parasites in cattle are cool weather parasites unlike the dominant H. contortus of small ruminants, as such treatment based on “high temperature, high humidity’ in cattle versus sheep can have very different results. Similarly, dragging the pasture at the wrong time would only spread the parasites over the pastures and alleviate the advantage of keeping stocking rates low to avoid having the cattle graze near fecal pats. There are similar errors in thinking, but I hope these two examples outline the danger in assuming the systems are identical.

Secondly, the procedures outlined will only work if the individual producer first ensures a relatively low overall infection rate in the herd. This means that the producer would first need to develop an aggressive program to lower overall parasite resistance, then institute a good quarantine program for cattle coming into the operation, and finally have an active monitoring program for the operation. Without these tools, the adoption of some of the ideas presented could have very severe effects on animal productivity.

Thirdly, the article completely ignores the use of drug combinations to manage resistance. I am sure in great part this is due to FDA’s aversion in principle to such treatments. The simple fact is that in areas where anthelmintic resistance has been a long standing affair (most notably Australia and New Zealand), the use of multiple drug classes at the same time has become the standard procedure for managing resistance. In addition, all mathematical models indicate that this is the best way to prevent the development of resistance.

Here in the US where resistance in cattle is mainly against the macrocyclic lactones it is important for us to protect the other drug classes by using such combinations. In a similar vein FDA does not adhere to the concept of drug treatment to enhance production goals while we know that this has been the main focus of the cattle industry since ivermectin hit the markets nearly 40 years ago. As such, as it is phrased the argument for refugia will fall on deaf ears. The concept of refugia is an important concept and can be inserted into at least some aspects of the American cattle industry, but to do so takes as much more sophisticated and precise implementation than the examples alluded to in the article.

Finally, I do take some exception to the opening statement that here in the US the existing drugs remain generally effective. While this is true for the benzimidizoles and Levamosole there is widespread resistance to the macrocyclic lactones especially when used in a pour-on formulation - which as you know is the most commonly used treatment in the US. We need to make sure that producers are using sustainable parasite control programs. This requires the use of the right classes of drugs at the right times, and proper pasture management again done at the right time. We must be exceptionally careful to give the right information.

Sincerely,

Lou Gasbarre, PhD

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FDA/CVM Responds to Gasbarre on Resistant Parasites

John Maday, Editor, Bovine Veterinarian, June 10, 2013

In early April, Bovine Veterinarian ran an article titled “Detecting and preventing drug-resistant parasites,” based on an FDA publication outlining possible causes for the development of resistant parasites and potential management solutions.

Knowing drug resistance in parasites is a complex issue with no clear consensus among the experts, we asked for responses from veterinarians and parasitologists to the FDA’s conclusions and recommendations.

Soon after, we received a response from veterinary parasitologist Lou Gasbarre, PhD, in which he questioned several of the recommendations in the FDA publication, specifically as they apply to beef and dairy cattle. In response, FDA’s Center for Veterinary Medicine sent the following letter, further explaining the publication and its recommendations:

“FDA’s Center for Veterinary Medicine thanks Bovine Veterinarian for featuring our brochure, “Antiparasitic Resistance in Cattle and Small Ruminants in the United States: How to Detect It and What to Do About It,” in your article published online on April 10, 2013. We also thank Dr. Lou Gasbarre for his comments, published online on April 29, 2013, on both your article and our brochure.

We want to take this opportunity to expand on and clarify some issues raised by Dr. Gasbarre.

Dr. Gasbarre mentions that the brochure is an over-simplification of the complex issues surrounding antiparasitic resistance in the cattle industry. He further mentions that although FDA lumped small ruminants and cattle together in the brochure, the differences between the two industries require fundamentally different strategies to address antiparasitic resistance.

We agree with Dr. Gasbarre that because the U.S. cattle industry is complex and stratified, veterinarians and producers have to manage parasites differently at each step. However, we think the general concepts of managing antiparasitic resistance outlined in our brochure, such as preserving refugia, not treating the entire herd, avoiding under-dosing, and reducing stocking density, can be practically applied to the cattle industry.

We intended for the concepts and recommendations in the brochure to be high-level. By presenting information about antiparasitic resistance in an easy-to-read format, such as a brochure, we hope to reach more veterinarians. We also hope that veterinarians will use our brochure to educate their clients about the emerging problem of antiparasitic resistance.

On the last page of the brochure, we included the links for information from FDA’s public meeting on “Antiparasitic Drug Use and Resistance in Ruminants and Equines,” held March 5 and 6, 2012. At this meeting, seven expert parasitologists and pharmacologists gave presentations on antiparasitic drug use and resistance in grazing species in the United States and worldwide. Dr. Gasbarre was one of those invited speakers. A transcript of the meeting, the presentations, and a meeting overview are available on our website for those seeking more in-depth information on antiparasitic resistance.

We acknowledge that our brochure does not discuss the use of combination antiparasitic drugs as a tool for slowing the development of antiparasitic resistance. Dr. Gasbarre notes that mathematical models as well as international experiences, such as those in Australia and New Zealand, indicate that appropriate combination antiparasitic drugs can help slow the development of antiparasitic resistance. Several speakers at FDA’s public meeting presented similar findings, and the use of combination antiparasitic drugs was an item of considerable discussion at the meeting.

We welcome drug companies to pursue approval of appropriate antiparasitic drug combinations with highly or completely overlapping indications. Contrary to Dr. Gasbarre’s assertion, we do not harbor any aversion to antiparasitic drug combinations. However, a drug company has to show us that the proposed combination is safe and effective.

We did not mention antiparasitic drug combinations in our brochure because, currently, none with highly or completely overlapping indications are FDA-approved for use in cattle or small ruminants in the United States. Without such an approved combination antiparasitic drug available, it would have been irresponsible for us to recommend combination therapy because of the lack of safety and effectiveness data and an established withdrawal period. It would have also been confusing for veterinarians and producers who are left wondering what combinations to use.

Dr. Gasbarre is correct that FDA does not adhere to the concept of antiparasitic drug treatment to enhance production goals. Antiparasitic drugs in cattle and small ruminants are only FDA-approved for therapeutic uses. Using antiparasitic drugs for production purposes, such as increased weight gain, is inconsistent with their labeling and illegal, as federal regulations do not permit extra-label use of any drug for production purposes. Furthermore, studies suggest such usage hastens the development of antiparasitic resistance due to the practices of treating the entire herd and not selecting animals based on therapeutic need.

We recognize that using antiparasitic drugs for production purposes is prevalent in the U.S. cattle industry, as Dr. Gasbarre suggests. We think there needs to be a paradigm shift within the cattle industry away from these illegal production uses. This type of proactive change will help approved antiparasitic drugs remain effective for longer.

We also want to point out that Dr. Gasbarre’s comments address statements made in both Bovine Veterinarian’s article and our brochure. For clarity, the opening statement that Dr. Gasbarre takes exception to (“Today’s antiparasitic drugs generally remain effective against cattle parasites in the United States…”) is the opening statement of Bovine Veterinarian’s article, not our brochure. In fact, like Dr. Gasbarre, we also take exception to this statement, and our brochure clearly states that resistance to antiparasitic drugs is emerging in the United States.

Finally, we agree with Dr. Gasbarre’s closing statements, “We need to make sure that producers are using sustainable parasite control programs. This requires the use of the right classes of drugs at the right times, and proper pasture management again done at the right time.” He gets at the crux of sustainable antiparasitic drug use that we are promoting in our Antiparasitic Resistance Management Strategy (ARMS).

Our goals in publishing the brochure were twofold: (1) to make veterinarians more aware of the problem of antiparasitic resistance in cattle and small ruminants in the United States; and (2) to provide veterinarians with a starting point for managing antiparasitic resistance by using appropriate antiparasitic drug therapy along with good management practices.

We realize antiparasitic resistance is a complex topic and encourage further dialogue between bovine practitioners, producers, members of academia, and FDA.”

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