Dialog on drug-resistant parasites

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While there is some disagreement on strategies, experts agree on a need to preserve the efficacy of antiparasitic drugs to protect the health of cattle. Back in April 2013, FDA’s Center for Veterinary Medicine (CVM) released a paper titled “Antiparasitic Resistance in Cattle and Small Ruminants in the United States: How to Detect It and What to Do About It.” We posted a summary of the paper to our website, BovineVetOnline.com, and invited veterinarians and parasitologists to offer their thoughts on drug-resistant parasites and the FDA’s recommendations.

The paper outlines the concept of “refugia,” which involves intentionally leaving a portion of the parasite population 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 antiparasite drugs.

The authors list the following management practices they believe contribute to antiparasitic 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 antiparasitic drug without knowing if it will be effective on the farm.

• Using antiparasitic drugs for unapproved uses, such as to increase weight gain.

• Relying solely on antiparasitic drugs to control parasites, rather than changing management practices.

The report also provides treatment tips for managing antiparasitic resistance. These include using clinical signs and diagnostic tests in management decisions, treating animals when infective larvae are at the highest number on the pasture to maximize environmental refugia, using animal weights to determine dosage, and maintaining treatment records and egg-count-reduction results to use in treatment and culling decisions.

Among non-treatment options, the authors recommend quarantining new livestock, rotating pastures with other livestock species, dragging or harrowing pastures to break up manure piles, managing pastures for taller grass during grazing and reducing stocking density.

Response from Lou Gasbarre
Veterinary parasitologist Lou Gasbarre, PhD, sent a detailed response to the article, applauding the efforts of FDA/CVM for bringing attention to the issue but pointing out what he believes are misconceptions in the paper.

Gasbarre says the recommendations in the FDA paper are appropriate for small ruminants but have flaws when applied to the cattle industry. He points out differences in the biology of the cattle-nematode system versus that in sheep and goats. “The parasites, while in some cases are closely related, do not have the same behaviors,” he writes. “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.

“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,” Gasbarre writes. “The simple fact is that in areas where anthelmintic resistance has been a longstanding 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 United States, 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.

“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 a much more sophisticated and precise implementation than the examples alluded to in the article.

“We need to ensure 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.”

Response from FDA/CVM
Soon after Gasbarre’s comments appeared on BovineVetOnline.com, FDA/CVM sent its response, further explaining the publication and its recommendations.

First, FDA/CVM addresses the issue of managing parasites in cattle versus small ruminants. “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,” they write. “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.

 

“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.”

At that March 2012 meeting, titled “Antiparasitic Drug Use and Resistance in Ruminants and Equines,” seven expert parasitologists and  pharmacologists gave presentations on antiparasitic drug use and resistance in grazing species in the United States and worldwide. A transcript of the meeting, the presentations and a meeting overview are available on the FDA/CVM website.

“We welcome drug companies to pursue approval of appropriate antiparasitic drug combinations with highly or completely overlapping indications,” FDA goes on to write. “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 FDAapproved 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.

“Finally, we agree with Dr. Gasbarre’s closing statements: ‘We need to make sure that producers are using sustainable parasitecontrol 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.”

Both FDA and Gasbarre took exception with a statement in the BovineVetOnline article stating that existing antiparasitic drugs generally remain effective in the United States. They each pointed out that resistance to some types of drugs has become widespread among parasites of cattle and small ruminants.


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