Part 4 of a six part series on worm control in goats
Dewormers and dewormer resistance
by Steve Hart
Extension Goat Specialist
Anthelmintics dewormers are regulated by the Food and Drug Administration of the U.S. Department of Agricultture. Only two dewormers (Rumatel® and Panacur/Safeguard®) are approved (will have animal species, disease, dose and drug withdrawal period for that species on the label) for use in goats and may be purchased over the counter for this purpose.
All the remaining drugs, while approved for other food animal species are “Extra-label use”. This means that the animal species the drug is to be used in, the purpose for which the drug is to be used, or the dose level is not on label. FDA has specific criteria whereby veterinarians can prescribe drugs that can be used in an “Extra-label” manner.
The six criteria that must be satisfied are:
The veterinarian must have a valid client patient relationship with the producer that he/she is prescribing the drug for (i.e. he/she must have been to your farm and be familiar with your production system). In addition, he/she must have examined the animal.
The veterinarian must determine that there is no approved drug labeled to treat the diagnosed condition, that the recommended dosage for that product is clinically ineffective, or that the approved product is ineffective.
Individual animals to be treated need to be clearly identified and records of the treatment need to be kept.
The veterinarian must establish an extended drug withdrawal period for treated animals (period of time after administration of drug that animals cannot be used for meat or milk for human consumption).
The producer must agree to follow all the veterinarian's instructions on administering the drug, withdrawal period etc.
The drug that was prescribed for “Extra Label” use must have certain information on the label, including name and address of the veterinarian, established name of the drug, dosage, route of administration, frequency of treatment, cautionary statements and the withdrawal period for any food that may be derived from the treated animal.
Dewormers are a class of drugs used to kill gastrointestinal worm parasites in animals. There are two problems with dewormers for sheep and goats: the lack of being labeled for use in sheep/goats and dewormer resistance.
The greatest problem in use of dewormers is that worms have developed resistance to many dewormers due to the overuse and improper use of dewormers. Therefore, in some goat/sheep herds there are only one or two dewormers that are still effective at killing worms, sometimes none. We need to use management techniques which suppress worms and then use dewormers only when management is not adequate to control worms. The second problem is that often an effective dewormer is not approved by the FDA for use in sheep/goats and therefore is not labeled for use in goat or sheep and must be used in an extra-label manner.
Dewormers are divided into three classes based on their mode of action/chemical structure. Because of the chemical similarities and common mode of action, all drugs in a class are similar in many respects, but some members of a class may have unique characteristics as compared to other members of that class.
The first dewormers included phenothiazine which is no longer available. The next generation of dewormers were the benzimadoles. This class is also referred to as white drenches. They include Thiabendazole (TBZ) fenbendazole (Panacur®, Safeguard®), oxfenbendazole (Synanthic) and albendazole (Valbazen®). Since they are the oldest class of dewormers in use, the worms have had a longer period of time to develop resistance to them.
Thiabendazole is essentially useless and is no longer marketed. In more humid areas of the US where dewormers have been used quite a bit, the only one that may be effective is Valbazen® whereas in other parts of the US where there has been less dewormer used, all members of this class may be effective. All three drugs kill roundworms (such as barberpole worm, black scour worm and brown stomach worm), lungworms, worm eggs and tapeworms. In general, they have poor efficacy against arrested L4 larvae which may be improved by using a higher dose. In addition, Valbazen® also kills adult liver flukes, but has poor efficacy against the juvenile and immature stages.
The second class of dewormers are the imidazothiazoles (cell depolarizers). They have also been around quite a while, and may still be effective in many herds, a likely a consequence of not having been used as much in goats due to the narrow margin of safety. Levamisole (Tramisol, Levasole and Prohibit®) are water soluble powders that often require mixing, or may come in an injectable form.
Morantel Tartrate (Rumatel®, Positive Pellet Dewormer) is another member of this class which may be mixed with feed. Rumatel® must be mixed and used as per instructions on the bag because there are no provisions for “extra label” use of feed additives. This class is basically only effective against roundworms, arrested roundworms and lungworms.
Levamisole is typically given to goats at 1.5 times the sheep dose. However, at twice the sheep dose, toxicity can be observed; the animal walks like it is drunk, it may salivate and slobber, its eyes may tear like it is crying, and it may defecate and urinate. If it is only given a mild overdose, it will usually recover on its own in one to three hours.
Therefore, it is important to have a good idea of what your animals weigh before selecting a dose. Also, it would be good to take a break from deworming to watch animals to see how they are behaving 30 minutes after being dewormed. Since other classes of dewormers are quite safe (animals can usually tolerate at least several normal dose), it is easy to get into the habit that if in doubt whether an animals has swallowed the dewormer, give him another dose. However, don’t do that with this class of drugs because a second dose may be toxic and possibly fatal. When worms become resistant to Rumatel®, Levamisole will still work for a time. Since the gene for resistance to this drug in the worms is a recessive, drug resistance will likely be slower to develop as compared to other dewormers.
The third class of dewormers is the macrocyclic lactones (avermectins/milbemycins. Common members of this group include ivermectin (Ivomec®) dormectrin (Dectomax®), eprinomectin (Eprinex®) and moxidectin (Cydectin®). This is the most recently developed class of dewormers, and are effective against roundworms, arrested roundworms, lungworms and sucking lice. However, this class of dewormers are fat soluble and therefore drug withdrawal periods can be long because the drug is trapped in the fat of the animal.
Cydectin® is the most recent member of this class and appears to be the most potent, probably due to its long persistence in the body, but resistance is rapidly developing to this drug because it has been used so frequently.
Since only two dewormers are approved for use in goats, use of all the other dewormers is “off-label” which is described in boxed text. Goats require at least 1.5 times the sheep dose of dewormer due to having a proportionately larger liver to metabolize the dewormer and due to a faster rate of passage through the digestive tract.
Be careful on the dose with the Tramisol/Levasol/Prohibit® in that too much can be toxic as discussed above. The greater dose of dewormer in goats also requires a longer drug withdrawal period than for sheep. There is a list of withdrawal periods for giving the sheep dose to goats at http://www2.luresext.edu/goats/library/field/dawson02b.html. The withdrawal period will need to be lengthened when using a goat dose.
There is a dewormer dose chart for goats (goat dose) based on bodyweight at http://goatconnection.com/articles/publish/article_168.shtml. Administer dewormers over the back of the tongue so that they go to the rumen. There are extensions for syringes to facilitate correct placement of the dewormer. This will provide a prolonged residence time in the digestive trace and be more effective at killing worms than if the animal sucks the dewormer in the front of their mouth where most of it may go into the true stomach (abomasum).
Pour-on dewormers appear to work poorly in goats and should not be used. Injection of dewormers can promote dewormer resistance. If dewormer is given in the feed or in blocks, there is often a problem of non-uniform dosing of animals, feed hogs get a higher dose of dewormer and timid and wormy ones who aren’t able to fend as well for themselves get little dewormer.
There are several strategies for increasing the efficacy of dewormers. These require more labor and may only be practical in special cases. Animals can be dewormed with a full dose of the Benzimidazole class of dewormers twice, 12 hours apart. This keeps a high level of the drug in the blood for a longer period of time, increasing the drug’s effectiveness. Another trick is to fast overnight, deworm the next morning and keep off feed all day. This slows the passage of digesta and dewormer and increases its effectiveness. This should not be done with late pregnant does or ewes because of the risk of pregnancy toxemia.
There are several different strategies for using dewormers that have been used in the past and there are disadvantages to each one.
One strategy is to deworm the herd when animals die or show symptoms of bottle jaw. The disadvantage is that animals are very wormy and the pasture has become heavily contaminated. There has already been a significant loss in animal production and health. It is much better to deworm animals before infection gets bad.
We can deworm at stategic times when worms are most likely to be a problem such as prekidding and weaning. This can work very well. However, if refugia is low at this time, we can be promoting dewormer resistance. This also neglects year to year differences in weather which is a major factor in determining the level of worms.
Deworming animals that don’t need to be dewormed will increase resistance to the dewormer.
We may deworm when weather conditions are favorable for worms. An old recommendation was to deworm 2 weeks after you have a month with more than 2 inches of rain and the mean temperature is over 60°F. While this is a good idea, the pasture infectivity may not be as high as we guess it to be and the animals may be withstanding the worm burden well.
We may deworm at regular intervals such as 30 or 45 days, to make sure that worms do not cause us a problem. This practice is effective at controlling worms in the short term, but is unsurpassed as the quickest way to develop dewormer resistant worms. The best strategy for deworming when the Barberpole worm is the dominant worm is to determine individually if an animal needs dewormed using the FAMACHA© program. This will reduce the development of dewormer resistance, control pasture contamination and prevent lost production due to worms. However, if the Bankrupt worm or Brown stomach worm are causing our worm problems, we must use fecal egg counts of the herd to determine when animals need dewormed and deworm the whole herd on this basis. Fortunately, in the US, these worms do not have as much dewormer resistance as the Barberpole worm.
Dewormer resistance has followed the use of dewormers. Where a given dewormer is used heavily over a period of time, resistance to that dewormer has developed. Resistance to the benzimidazole class of dewormers was documented in the 1960's. Resistance to levamisole was documented in the 1980's. Resistance to ivermectin was documented in the 1990's (was a good useful dewormer for a while). Moxidectin resistance was first documented in the 2000's.
In most of the southeastern US, there is documented resistance in sheep and goats to multiple dewormers. Several factors have contributed to the development of dewormer resistance. Veterinarians have pursued the eradication of worms instead of controlling them (deworming when the level of worms is high enough to impact the health or productivity of animals), producers found it easier to give a dewormer regularly (by the calendar rather than to evaluate whether there was a need for deworming (and dewormers were cheap!).
In addition, producers did not take the time to manage pastures to reduce parasitism. Pharmaceutical companies have encouraged heavy use of dewormers, driven by the profit motive. And, the worms were illiterate; they didn’t read the pharmaceutical company ads to know which dewormers should kill them.
The dewormer resistance on a given farm is unique to that farm due to the history of dewormers that the animals have been exposed to. However, if animals are traded in a local area, the dewormer resistance will be similar to other farms that the animals were traded with due to the sheep/goats carrying their worms and dewormer resistance of those worms to the next farm with them. Most of the information, whether from academia or drug ads was about using dewormers and not about using management to suppress worms. We are now suffering from the consequences of that misguided approach to parasite control.
Six part series
Worm control in goats
Part 1: Meet the enemy
Part 2. Managing the barber pole worm
Part 3. Integrated parasite management with FAMACHA©
Part 4. Dewormers and dewormer resistance
Part 5. Alternative dewormers: do they work?
Part 6. Doing your own research and fecal egg counts
This six part series on worm control in goats was originally published in The Goat Rancher magazine in 2008.
How do worms become resistant to dewormers?
Worms have a very genetically diverse genome. Therefore, one worm in millions of worms will have some genetic characteristic that enables him to be resistant to a specific dewormer. The potential for dewormer resistance exists in at least a few worms before a dewormer is ever used. Repeated use of that dewormer will gradually kill all the non-resistant worms in a specific population, leaving only resistant worms (Figure 1).
Over time, the level of resistant genes (and resistant worms) will increase in your worm population. Basically, resistance is permanent although there are a few rare exceptions. When worms in your sheep/goats become resistant to a dewormer, you can forget about ever using that dewormer again in your management program. Also, resistant worms are spread by animal movement. You may have not have worms that was resistant to a dewormer, but when you buy an animal, you get their worms for free, but worse, you get the dewormer resistance that may come with them.
That is the reason for recommending that all new animals be dewormed with two classes of dewormer (theory being that most worms will be resistant to only one class of dewormer) and a fecal sample of the sheep/goat needs to be checked a week or two later to verify the absence of eggs (Before putting them in the pasture with the rest of your animals!). Sheep and goats that originate in more humid areas, and higher value animals are more likely to have resistant worms due to greater exposure to dewormers.
Dewormer resistance can be detected by fecal egg count reduction test. That is taking a fecal egg count from a sample of animals, preferably 6-10 head, deworming with whatever product and then taking another fecal egg count 7-14 days later. If the dewormer was effective, the second fecal egg count should have only 1 or 2% of eggs of the first fecal egg count (If the dewormer is highly effective, the fecal egg count will be 0). The first sign of dewormer resistance is when the second fecal egg count has more that 5% of the eggs of the first fecal egg count. This means that there is significant resistance to the dewormer.
When the resistance level is this high, it will progress rapidly to where the dewormer kills less than 50% of the worms. When a dewormer only kills 50% or less of the worms, there may be some improvement in the appearance of the animal for a short time when they are dewormed, but they will need dewormed sooner than expected or they may die
Often the great danger is that we think deworming took care of our worm problem and we are surprised by animal deaths and they are often attributed to other causes since animals were just dewormed. Keep a check on eyes and watch for bottle jaw. Dewormer resistance can also be determined using a kit called the Drenchrite test. The test is currently being offered by Dr. Ray Kaplan of the Department of Infectious Diseases of the University of Georgia Veterinary School.
One sobering fact of deworming resistance is that when our animals become resistant to all classes of dewormers, we are either going to have to do very intensive management to suppress worms or go out of the goat business. There is a recorded case of the worms being cleaned out of sheep with multiple doses of different dewormers and then dewormer susceptible worms were used to reinfect the sheep to replace the resistant worms. Also, there is a new class of dewormer which is in the FDA approval process and will likely take 5 more years to get approval. It is very potent against worms that are resistant to our present three classes of dewormers but worms can still develop resistance to it in time.
Dewormer resistance may be slowed down by;
Not import resistant worms as described above
Refugia is defined as the proportion of the worm population that was not exposed to the dewormer. This includes eggs and larvae on pasture at time of treatment and the worms in animals that were not dewormed (reason for selective treatment with FAMACHA©). The importance of refugia can be illustrated by a case in Australia where it was hot and dry for 3 months and animals were dewormed in the dry period.
Deworming was very effective in that no eggs or larvae survived on pasture and only a few worms survived the deworming of the animal. However 100% of those few surviving worms were resistant. It took little time for the worm population to build (remember the barberpole worm can lay 5,000-6,000 eggs per day and every 4-5 weeks there is a new generation of worms producing eggs), but 100% of the worms were resistant because there were no susceptible worms surviving on pasture for them to mate with.
Worms in refugia are more susceptible to the dewormer and dilute out the dewormer resistant genes of the worms that survived deworming. So refugia is very important in reducing the rate of development of dewormer resistance. Note, that we do not prevent the development of dewormer resistance, but it may take two or three times longer for the worms to become resistant to the dewormer, enabling us to use the dewormer for a longer period of time.
There are three management practices that promote the development of dewormer resistance:
Frequent deworming (more than 3 times per year)
Underdosing the dewormer(increases proportion of worms with genes for dewormer resistance)
Reducing refugia. Ways that we commonly reduce refugia are treating all animals at the same time, treating all animals and moving to another pasture that has few worm eggs or infective larvae, and treating when few larvae are on the pasture such as during a severe draught.
Selective treatment is very effective at increasing refugia and slowing the development of dewormer resistance. Figure 2 show the fecal egg counts in a herd. There is one bar for each animal’s fecal egg count. The height of the bar represents the number of eggs in a gram of feces. One thing that jumps out is that a few animals have much higher fecal egg counts than others. In fact, the 6 animals with the highest fecal egg counts have 50% of the total fecal egg count of the herd and the top 12 of 36 total animals have 80% of the total fecal egg count of the herd.
These top 12 animals have fecal egg counts that are at a level that reduces productivity and the animals with higher fecal egg counts are heading towards death.
he 24 animals with lower fecal egg counts do not need to be dewormed because they are able to be productive with a low level of worms. A low level of worms is normal and beneficial in that it keeps the immune system functioning against worms and provides refugia. If we deworm only these top 12 animals, we restore them to health and the result is observed in figure 3. Note that the graph has been magnified 10 times (look at the numbers on the left side of the graph and compare it to figure 3). After dewoming, the animals that were not dewormed contribute 19 times more eggs to the pasture (refugia) than the animals that were dewormed.
Therefore, the resistant worms that arise from eggs produced by dewormed animals will have many worms from eggs produced by animals that did not get dewormed. In this way, genes (for dewormer resistance) from the dewormed animals will be diluted and the resultant dewormer resistance will be increased only slightly. This is why FAMACHA© is so important to help slow the development of dewormer resistance. It is the only practical way that we can selectively deworm our animals and maintain a high level of refugia which slows the development of dewormer resistance.
Because dewormer resistance can put a producer out of business, especially in the more humid areas of the southeastern US, a producer needs to develop a plan to reduce the rate at which dewormer resistance develops. Management practices which suppress worms are going to have to be the foundation of the control program and dewormers are going to have to be used sparingly and intelligently and only when needed (selective deworming). These principles were discussed in the second and third article in this series. Only through this strategy, can small ruminant production remain a viable farm enterprise in the southeastern US in the long term.
Unfortunately, dewormer resistance is inevitable, but how soon it develops it depends on your management. Using FAMACHA© will slow the development of dewormer resistance as compared to conventional deworming management. However, as mentioned already, the quickest way to get resistant worms is to buy them. Of course no one purposely buys resistant worms, but that expensive good looking animal that you just bought brings his worms along and they may be very resistant to dewormers.
Expensive animals tend to be dewormed excessively since the owners do not want to risk worms killing them. This is especially true if the animal comes from a humid area. Therefore, expensive animals are more likely to have resistant worms. Since buying resistant worms is the quickest way to get dewormer resistant worms, it is wise to make sure that those animals that you bring into your herd do not bring resistant worms in. This is done by deworming them two classes of dewormer (such as Valbazen© and Prohibit©; full goat dose of each at the same time) and then a week later, do a fecal egg count on the animal which hopefully will be zero or close to zero.
If not, you may have to resort to a 3-way combination of Valbazen©, Prohibit© and Cydectin©, all given at the goat dose given at the same time. If the fecal egg count is not zero in a week, you don’t want these worms nor the animal on your farm. Highly resistant worms in one animal can become highly resistant worms in other animals in your herd in a short period of time. How are you going to control those worms? Sometimes, unfortunately, the solution is to go out of business although there are some solutions as discussed below.
When you have resistance to all dewormers i.e. none work, there are a few techniques which often require intensive management that can enable a producer to stay in the business for several more years. Hopefully, there will be another class of dewormers available within 5 years that will provide help. One can use a short duration (5 days on a pasture), long rest period (40+days) grazing program so that sheep/goats pick up few worms and therefore do not need to be dewormed.
One may be able to use alternative dewormers (sericea lespedeza, copper oxide wire particles etc.) as discussed in the next article in this series. However, one is going to have to be good at parasite management to stay in the business. It is better to use good management to prevent your animals from getting into this difficult problem. Using a conventional dewormer at a higher dose (Prohibit© should not be given at more than 1.5 times sheep dose due to toxicity), giving combinations of dewormers or giving dewormers (or combinations) for 2 or 3 days in a row are techniques that can kill most resistant worms. You can select your animals for genetic resistance to worms.
All this makes good parasite management program to reduce dewormer resistance sound better all the time.
In conclusion, next time you deworm, do a fecal egg count to determine if your dewormer is working. If not, switch to another dewormer and check to see if it is working. Use a proper dose of the drug and know the drug withdrawal. Use FAMACHA© to slow down the development of dewormer resistance. Do not buy dewormer resistance and worm all incoming animals with two dewormers. Use management to prevent worms which reduces how often you deworm. Deworm only those animals needing it based on FAMACHA©. Cull animals requiring the most deworming.