Malcolm T. Sanford
Before the advent of the Varroa bee mite (Varroa destructor), the biggest challenge to honey bee health was American foulbrood (AFB), caused by the rod-shaped spore-forming bacterium Paenibacillus larvae sub. larvae (formerly classified as Bacillus larvae and Paenibacillus larvae ssp larvae/pulvifaciens). It is the most widespread and destructive of the brood diseases, according to Wikipedia.com: “Larvae up to three days old become infected by ingesting spores present in their food. Young larvae less than 24 hours old are most susceptible to infection. Spores germinate in the gut of the larva and the vegetative bacteria begin to grow, taking nourishment from the larva. Spores will not germinate in larvae over three days old. Infected larvae normally die after their cell is sealed. The vegetative form of the bacterium will die, but not before it produces many millions of spores. American foulbrood spores are extremely resistant to desiccation and can remain viable for more than 40 years in honey and beekeeping equipment. Each dead larva may contain as many as 100 million spores.”
A paper in the 2010 Journal of Invertebrate Pathology provides a history of this fearsome disease: “By 1650 nearly all farms in New England are reported to have had a colony or two of bees. However, the number of bees managed by these colonists rapidly declined after 1670, presumably because of AFB. Substantive documentation of AFB’s presence in the new world, however, did not occur until more than a century later, by the late 1800s and early 1900s. Then, AFB and EFB were a ‘veritable scourge’ in many parts of the country resulting in the passage of many state bee laws and implementation of state apiary inspection programs. These early apiary laws proposed to mitigate the spread of AFB by requiring the destruction of all infected colonies and the burning of infected bee equipment. This effort was not insignificant, for instance, in the state of Pennsylvania over 32,000 colonies were burned between 1930 and 1965, a number that is just shy of the total number of colonies in the state in 2007 according to the Ag Census (PA Dept of Ag, unpublished records; USDA-NASS, 2009c).”
The discovery of antibiotics, materials that stopped vegetative reproduction in a bacteria’s life cycle, has been a boon to humans themselves, as well as their animal husbandry activities. The application of these substances in beekeeping hailed the beginning of honey bee “domestication.” The evolution of treatments includes Sulfathiazole®, a so-called “sulfa” drug (1940s-1950s), followed by oxytetracycline, a broad spectrum tetracycline , Terramycin® (1950s through 1990s). Lincomycin , Lincomix® and more recently tylosin tartrate , Tylan® have all allowed beekeepers to use them to prevent reproduction of the vegetative stage. Unfortunately, these substances are not effective against the spores of Paenibacillus larvae sub. larvae, which represent the biggest challenge to controlling AFB. They are literally indestructible, except by fire and radiation, and can exist almost indefinitely as disease “time bombs” in honey, ready to germinate when liberated through honey-bee-feeding activity.
Beekeepers often have not realized the potential “inconvenient” results of using these antibiotics. Sulfa drugs have mostly been abandoned because of their potential to contaminate honey. The others have been relatively inexpensive and easy to acquire for use in various treatments from dusts, to liquids to something called “extender patties.” The latter provide an extremely long-lasting treatment by mixing the antibiotic in vegetable shortening. However, it is now well known that once use begins, it must continue. AFB simply patiently waits in its spore form to begin growing anew. In addition, these materials have been readily available “over the counter” in several formulations, many of which are then further re-formulated by enterprising beekeepers to use in a “prophylactic,” or preventative manner, keeping AFB at bay, but not eradicating it. Unfortunately, just as their other animal agriculturalist cousins have realized, the continuous use of any one antibiotic over time by beekeepers all too often results in resistance by bacteria, which can evolve into more potent organisms in the long run.
AFB Resistance to antibiotics has indeed been identified in many countries, including the U.S., Canada and perhaps most spectacularly, Argentina. It is now apparent that overuse of antibiotics in both human health and agriculture is leading to a “perfect storm,” which many have called a future disaster of great proportion. The bottom line so far is that these “wonder” substances that have furthered treatment for so many diseases could be rendered useless, with little if any backup substance in the research and/or distribution pipeline to replace them.
Another risk, more specific to beekeeping, is the possibility of contaminating the honey crop with antibiotics. This was expressed by C.L. Farrar as far back as 1960 in American Bee Journal – vol. 100 – Number 5 – May, 1960, pages 192, 193:
“The beekeeper must recognize that Federal food-additive laws now in effect apply to honey as well as all other foods. The large purchasers of honey are requesting suppliers to certify that the honey offered for sale is pure and free of contaminants. Honey, like any food product offered for sale, can be condemned if it contains even traces amounting to less than 1 part per million of a chemical, drug, or antibiotic for which no legal tolerance has been established. One publicized condemned shipment could do great harm to the entire honey market. This situation need not cause a panic in the beekeeping industry, but it does require caution and good judgment in how chemicals and medicants are used.”
Recently the Food and Drug Administration (FDA) has published a draft document for comment, entitled: “Guidance for Industry Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Species: Study Design Recommendations for Residue Studies in Honey for Establishing MRLs and Withdrawal Periods.” The objective of this document is to establish appropriate Maximum Residue Limits (MRLs) or other safe limits in honey following the treatment of honeybees with veterinary drug products, or to justify withdrawal periods in honey for registration purposes when an MRL already exists. Use of veterinary drug products in honeybee production is considered as a minor use in minor species in most jurisdictions. These studies should provide a much more robust guide for antibiotic residues in honey than have been available in the past.
In an announcement that took many by surprise, but was considered by others inevitable, I. Barton Smith at the USDA Honey Bee Laboratory Beltsville, MD stated: “On December 11, 2013, The U.S. Food and Drug Administration (FDA) implemented a plan to help phase out the use of medically important antimicrobials in food animals for food production purposes, such as to enhance growth or improve feed efficiency. The plan would also phase in veterinary oversight of the remaining appropriate therapeutic uses of such drugs.
“Implementation will require a beekeeper to get a prescription or veterinarian feed directive (VFD) from a veterinarian who has a ‘Veterinarian-client-patient relationship (VCPR)’ with the beekeeper in order to purchase and feed antibiotics to honey bees for the prevention and control of American and European foulbrood diseases.” A list of drugs affected by this plan is attached to the document.
This was followed up by: “On June 2, 2015, the FDA announced the Veterinary Feed Directive (VFD) final rule. Drugs included under the VFD will require a veterinarian to write a VFD for a producer that will allow that person to purchase and use the product specifically as written. This will include oxytetracycline. Prescription drugs for bees can only be obtained from a local or on-line pharmacy. Additionally, drugs included in the VFD may only be obtained from a licensed medicated feed mill.”
The deadline for this action it turns out is January 1, 2017. The rather abrupt time line is causing consternation in U.S. beekeeping. Many questions have come up mainly concerning the “Veterinarian-client-patient relationship (VCPR)” mentioned above. A big problem is that many if not most veterinarians have limited if any knowledge of beekeeping or beekeepers. As part of establishing this relationship, the veterinarian must physically visit the apiary to see that one actually keeps bees, is reasonably knowledgeable about the management of honey bees, and has a reason for requesting antibiotics. After that the veterinarian must write either a prescription or something called a “Veterinary Feed Directive (VFD),” depending on the particular situation.
This situation is not unknown for veterinarians who have had to recently add aquaculture and backyard chickens to their repertoire. The exercise could be beneficial in the long run because it forces veterinarians to be much better informed in beekeeping practice in general, something that has not been part of U.S. beekeeping, but is in Europe and Latin America.
The American Beekeeping Federation (ABF) recently sent a series of questions to the Food and Drug Administration (FDA): “ It is our understanding that bees are included in the FDA final rule on antibiotic feed directive. What will be required under the rule for beekeepers to obtain antibiotics for therapeutic use in their beehives? Which currently available antibiotics for use in treating bees are included under the veterinary feed directive? Which antibiotics for treating bees will require a veterinarian’s prescription? Please explain the difference between Rx and VFD under the rule. What constitutes a valid veterinary client/patient relationship? Does this vary from state to state?”
The Response from FDA’s Center for Veterinary Medicine is five-pages long. With respect to various state involvement, a detailed list has been published based on the following: “On June 11, 2015, CVM mailed a letter to the entity with authority over the practice of veterinary medicine in each of the 50 states and the District of Columbia. In that letter, CVM committed to publishing a list indicating whether a state-defined VCPR or a federally-defined VCPR is required for a lawful veterinary feed directive in each state. In addition CVM reported plans to post relevant correspondence received from state regulatory authorities on its Veterinary Feed Directive website. This information is presented in a table listing whether states will adhere to their own or federal rules. Most default to the federally-defined option, but not all. This is a work in progress.”
The above documents are not an easy read. An explanation by a beekeeper who is also a veterinarian might be better understood. Fortunately, one of the new owners of Betterbee is a registered veterinarian and has posted some clarification at beesource.com:
“Starting January 1, 2017, all of the antibiotics that are delivered in feed or water are going to change from being over the counter (OTC) to needing either a prescription or a veterinary feed directive (VFD). These are papers that a veterinarian has to supply with their signature. Prescriptions are fairly easy. The veterinarian or a pharmacy could fulfill this. the water soluble antibiotics would use this. Oxytetracycline, Tylan and Lincomix are the three labeled for bees.
“A VFD could be used also. This paper goes to a feed mill or feed distributor. Prior to this ruling, both of those needed licenses from the FDA. There were limited feed mills in the northeast with that license. Having mostly dairy cows drive the mills in the northeast, there was no need for antibiotics. It is a liability for a mill to even have antibiotics since each tanker of milk is tested and mistakes would be caught easily by the dairy plants. So, a VFD is not a best management thing, it is a law that tells how the antibiotics is to be prescribed. The rule changes are coming about to help prolong the time an antibiotic works for human disease fighting.
“With this rule change, an unlicensed feed mill can get a category I drug and mix it for minor species (like bees) therapeutic uses. Terramycin is the only drug approved for use in bees as a VFD drug. The company that makes it went to great lengths to make it a category I drug by removing approved uses that required withholding in chickens. Category I drugs can be fed with no withholding in the major species while Category II drugs have a withholding period. Prior to this rule change, Terramycin would have been a Category II drug because it was used for bees to control AFB or EFB with a 42 day withholding period. The company may have removed bees from the label in order to protect sales as a Category I drug.
“What is an unlicensed feed mill? Pretty much anyone that mixes feed can be an unlicensed feed mills. A lot of larger farms have their own feed mills. A 50 pound bag of Terramycin will make several thousand treatments, so it may be easier to use prescription drugs anyways as they come in smaller bags. The mill still needs to collect a VFD from the end user to have their paper trail. the FDA will do some auditing of the paper trail, but it is a little harder to do that in unlicensed mills versus licensed mills. I am not sure how they are going to accomplish this part of the regulatory circle. It may be complaint driven, or it may be part of regular FDA food producer inspection. So, bottom line is the beekeeper (or bee supply dealer) may be able to obtain the VFD labeled drug, mix it into sugar, and then sell it or use it when a properly completed VFD from a veterinarian is presented to them.”
And in another post, “I am sure some will say this is too little of a change, but it is a big change and demonstrates the FDA is listening.
“I gave a talk at the American Veterinary Medical Association about beekeepers, bees and veterinarians. After the talk, an FDA official approached me and we had a good talk about how the new antibiotic regulations were going to affect beekeepers. I told him I thought beekeepers were only going to use prescription antibiotics and the VFD drugs would not be used in beekeeping because there were not enough licensed medicated feed mills that would deal with the small quantities of antibiotics beekeepers would need. He thought the beekeepers would be like a large farm where they would mix their own antibiotics and sugar and not use a licensed feed mill anyways. I explained why that was not legal based on the category II status of Terramycin (Category II means there is a withholding time for the antibiotic).
“Yesterday, the FDA announced that for MINOR SPECIES (like honey bees), unlicensed feed mills would be allowed to mix antibiotic feed for therapeutic uses even if they could not for cattle, swine or poultry. A beekeeper could be considered an unlicensed feed mill.
“I still do not think this will clear the issue fully because there is no extra label drug use allowed for VFD drugs. The VFD drug Terramycin will be labeled for the CONTROL of AFB or EFB. CONTROL falls into a spectrum of PREVENTION, CONTROL OR TREATMENT. There is no exact cut off, but when using a drug for CONTROL of a disease, there is an expectation that the disease is active in some part of the population being treated. The veterinarian writing the VFD would have to have medical records supporting that diagnosis. Feeding Terramycin with a VFD for PREVENTION of AFB or EFB would get the veterinarian into trouble. The evidence against the veterinarian for the hearing would be very clear because the veterinarian would have it all written out in the VFD. There have been rumors that the FDA may allow Extra Label Drug Use for MINOR SPECIES of VFD drugs, but that is still just rumor. An example of Extra Label Drug Use would be using Terramycin for prevention instead of control of AFB.
“A beekeeper would still have to have the VFD or prescription written by a veterinarian. That is not going to change.”
Chris Cripps, DVM
Dr. Cripps has also developed a specialized website in an effort to bring veterinarians and beekeepers together. Ohio, Florida, Michigan, Kentucky and a few others are also considering developing similar initiatives. More are sure to come. He also reports there is a group of veterinarians working to form the American Association of Bee Veterinarians, which will exist to educate veterinarians about bees and their diseases, concluding: “The FDA is pushing veterinarians and beekeepers together. Hopefully this is a good thing for both. Neither has invited this change, but both are working to understand how it will work and to make it work. The FDA is still a little unclear on some of the details. Keep informed because there may be changes as time goes on. The FDA is not looking to put beekeepers out of business or to create massive disease outbreaks. The FDA is trying to make sure antibiotics work when people get sick. Hopefully we can overlook some of the small problems created while trying to fix a really big problem.”
Although not intended, the possible ramifications of this new ruling in fact could be quite telling. From both a practical and financial point of view, given the current practices of beekeepers, including purchasing antibiotics over the counter with the only guideline being, “follow the label; it’s the law,” the all-to-emotional response to this new ruling is certainly justified.
Some beekeepers worry that in all the confusion, many will slack off on their use of medication, or stop using it preventatively, leading to a surge in disease. Tony Jadczak, former Maine state apiarist, reports European foulbrood already has been spiking in the past four or five years in several states including Maine. The disease used to be found in 1 to 1.5 percent of hives inspected annually in those states; now the disease rate can reach as high as 5 to 6 percent. He concluded, “We (in Maine) have a rapid response to a disease outbreak, so this (new rule) may slow the process down,” Jadczak said. “We’ll see.” By some estimates this could add $50 to $500 for a vet visit alone to beekeeper costs.
Rusty Burlew of honeybeesuite.com muses on the new ruling: “Since drugs like oxytetracycline will require a veterinary prescription, I speculate that the incidence of infected hives will increase. As a result, people like me, who have never given much thought to AFB, may suddenly be hit with it. Simply put, those beekeepers who were suppressing AFB kept it from spreading. Those suppressors left many small-time beekeepers pretty much free of the disease. Although I’ve never treated for it and have never seen it in my apiary, I wonder how long that will last under the new system. As with other diseases, absconding bees, drifting bees, swarming bees, robbing bees, lost bees, and drones can all carry the disease. Since foulbrood does not affect adult bees, they can easily carry it wherever they go.
“I further speculate that the reappearance of AFB and EFB will not happen immediately. I suspect that beekeepers who have been using the drugs are stockpiling, so for a while, at least, we won’t notice a large uptick in cases. But as stockpiles disappear or lose their effectiveness, the incidence of disease will rise. And once your hive becomes infected, how easy will it be to find a veterinarian who is willing to diagnose your hive and prescribe treatment? And how affordable will that be?”
She concludes: “It’s not getting easier for beekeepers. I really do have mixed feelings about the new laws. Yes, they are most likely a good thing. But with all the problems honey bees face, perhaps we need an exception. Should we be allowed one easy-to-get drug for the brood diseases? I assume that not all beekeepers with AFB will burn their hives or go to a vet. Instead they will try to keep their bees alive, spreading the pathogen far and wide while their colonies collapse. If nothing else, beekeepers should be aware of this potential new problem and be on the lookout for symptoms. Beekeeping is tough and every day seems harder than the one before. Knowing what I know now, would I do it again? I wonder.”
Dr. Cripps agrees there could be a resurgence of AFB because some beekeepers may forgo finding a veterinarian to save time and money. For most large beekeepers, though, the added cost could be quite minimal per hive. This might cause havoc during pollination season. Flatbed trailers bring tens of thousands of hives to places like California to pollinate almonds, and Maine to pollinate blueberries and apples. Orchardists pay up to $200 a hive for a temporary stay to ensure pollination. If infected hives introduce disease to a heavily honey bee-populated area for a short period of time, it could spread rapidly as the hives go to the next crop or home.
“Most commercial keepers know what AFB is and know to prevent or treat it, but less-experienced hobbyists may not,” Dr. Cripps concludes, “One source of infection can be secondhand beekeeping equipment, because spores persist for such a long time. Backyard keepers just starting out may think they’re getting a great deal when buying used equipment runs the risk of an AFB flare-up once a new hive starts up in contaminated equipment and prophylactic feeding is stopped.”
Lost in much of the conversation so far is the role of established bee inspection services. Again, most of these have their roots in controlling AFB, but more recently this has been eclipsed by other issues. Dr. Richard Taylor, long-time beekeeper and columnist writing in 1991, stated: “My own view is, and has for some time been, that mandatory inspection of apiaries is something whose time has long since come, and gone. American foulbrood is a manageable problem that can be left in the hands of beekeepers themselves. This is not going to eliminate American foulbrood, to be sure, but neither is anything else. It is not a proper area for government.”
In response I wrote: “Before doing away with inspection services, some thought needs to be given to alternatives. Many of the traditional inspection services are knowledgeable about and sympathetic to the plight of beekeepers. However, if disbanded there is no assurance that another crop of regulators who are less involved with beekeepers might not arise in the face of future perceived ‘crises.’ This is particularly likely to happen in the face of invasion of Africanized bees associated with sensationalized press coverage. A state inspection service can also intervene to prevent and/or blunt potentially harmful regulations being promulgated at the federal level.
“Finally, it is far easier to get rid of a bureaucracy than to try to re-establish one. It is not a given that some of the same concerns prompting establishment of bee inspection services in the first place, and well supported by the beekeeping industry in the past, will not reappear in the future. The Michigan experience may be instructive. Inspection in that state was done away with for a time, but the industry demanded it be reinstated. However, when it was reestablished, the inspection bureaucracy was not particularly knowledgeable nor sympathetic with industry concerns. As a result, Michigan beekeepers are again reexamining their bee law.
I concluded, “As part of this discussion, some time should be given to analyzing the role of bee inspection in the current beekeeping environment. Is it simply to find and destroy colonies with AFB or to provide other services to the beekeeping community? Is leaving commercial beekeepers alone (except for spot inspections) and concentrating on part- timers and side liners a good strategy? These questions deserve answers as bee inspection continues to reinvent itself becoming more relevant to the modern beekeeping environment.”
Controlling the Varroa mite, for example, something far more responsible for colony losses than AFB, with many of the same risks in terms of sharing mites via something called “Varroa bombs,” is not part of most bee inspection legislation. Given its mandate, providing a licensed honey bee veterinarian on staff to deal with this new ruling promulgated by the FDA, might indeed be Dr. Taylor’s “proper area for government.”
The possibility that antibiotics might not be effective in the future, the root reason for the new law, may mean it’s time to get off this bandwagon in favor of more biologically-relevant approaches to controlling AFB. Dr. Mark Winston, author of the recent book, Bee Time, reflects on the question, “Whatever Happened to Pastoral Beekeeping.” He concludes: “Here’s the present-day irony: honey bees will die if untreated, but relying too heavily on the treatments has accelerated colony demise. We’re trapped in this tragic cycle of increasing chemical use.”
Research also suggests another reason for abandoning antibiotic treatments, the effect on the honey bee’s microbiome, something humans have in common with insects . Yale researchers have found genetic evidence that bacteria, which normally live the bellies of honey bees, have become highly resistant to the antibiotic tetracycline. They play an important role in protecting the honey bee by neutralizing toxins found in their diets while also helping fight off various pathogens.
Eight different tetracycline-resistant genes have been detected among U.S. honey bees that were exposed to antibiotics. Those same resistance genes were missing in bees from countries where antibiotic use is banned (Czech Republic, New Zealand and Switzerland). “It seems to be everywhere in the U.S.,” says Nancy Moran of Yale University, a senior author on the study. “There’s a pattern here, where the U.S. has these genes and the others don’t.”
Reports from Australia are more to the point. Mr. Jeffery Gibbs a forty-year commercial beekeeper and industry spokesperson states: “Antibiotics are yet another toxin for your bees. There is barely a commercial beekeeper in Australia who doesn’t understand the terminology Olley’s Lolly. (Illegal Antibiotics) From my investigations more than eight out of ten beekeepers down south are dosing.”
A hope exists that it might be possible to come to grips with AFB in the form of resistance to the disease from a long-known, but little-used tool, breeding honey bees for “hygienic behavior.” Dr. Walter Rothenbuhler, retired from The Ohio State University (deceased), coined the term, according to Drs. Marla Spivak (now at the University of Minnesota) and M. Gilliam, who have written a detailed review of the subject in Bee World, published by the International Bee Research Association (IBRA). “Resistance to American foulbrood (AFB) consists of the colony’s ability to detect and remove brood before the causative organism reaches the infectious spore state. Early removal of diseased larvae, which contain noninfectious rods only, prevents spread of the disease, but removal of spore-infected larvae also contributes to transmitting the disease. Thus, early removal is paramount and the more bees with the trait the better off is the colony.”
Hygienic behavior is heritable and it can be selected for, Spivak and Gilliam conclude. Unfortunately, most colonies exhibit low levels because of its recessive nature. Thus, selection for the trait should become a routine part of any bee breeding operation. Commercially available lines of hygienic stock would help many beekeepers overcome a multitude of problems, especially those associated with mites and disease. This would reduce operating costs by minimizing use of chemicals, with their concomitant possibilities of bee, colony and product contamination. Finally, standard queen rearing and breeding techniques can be used to produce many hygienic queens from a few mothers using any race of honey bees.
A comment from Steven Taber, author of Breeding Super Bees comes to mind. “Back in the ‘30s Dr. Park at Iowa state showed you could breed AFB-resistant bees in 3 to 4 generations…About 20 years later, Dr. Rothenbuhler determined the genetic method of resistance. And about 20 years ago, I showed how easy it was for any beekeeper to find hygienic bees in his own bees.”
The best example of actually eradicating AFB is currently taking place in New Zealand. The three keys to the success of this program are adequate inspection, proper diagnosis and the elimination of clinical cases. New Zealand’s effort is theoretically possible and appears to be working. Maintaining the low AFB level once it has been achieved, however, will no doubt be the greater challenge.
Research at the University of Minnesota continues to look at this behavior, concluding: “Diligent selection and breeding efforts are required to obtain and maintain hygienic colonies with consistently rapid removal rates. However, the benefits of having colonies resistant to AFB, chalkbrood disease, and partially resistant to Varroa destructor (Spivak and Reuter, 1998b, 2001) are evident. The maintenance of resistant bee colonies is the foundation for effective integrated disease and pest management, and in the long run is the most sustainable alternative to the risks and problems associated with the prolonged use of antibiotics and pesticides.”
It may well be that resistance to Terramycin® without any suitable substitutes could be a prime incentive for beekeepers to finally begin implementing hygienic behavior technology to its fullest potential. The new ruling concerning antibiotics and veterinarians adds fuel to this fire. None of it will be easy or convenient for beekeepers, but as Dr. Winston concludes: “Only a conscious and concerted effort will return us to the beekeeping of yesteryear, when keeping bees was the most natural of pastimes.”
Originally brought to you courtesy of American Bee Journal, the beekeeper’s companion since 1861. “Bringing you the latest in practical bee management and bee research.”
For further information, see a University of Florida webinar published March 28, 2017, 36 minutes long, which is designed as a veterinarian’s guide to honey bee antibiotics, given the new ruling.