Resistance is not futile

Apivar ...

Apivar …

Amitraz-containing miticides are sold in the UK as Apivar and Apitraz.

Until recently they were only available with a veterinary prescription. I expect – though I have not yet seen data to support this – that their usage in the UK will increase now they are off-prescription. These miticides are now widely available and so there is greater opportunity to use – and misuse – them.

If you’re using Apivar 1 for the first time this year you will soon have to remove the strips from the hive.

That’s assuming you started treating early enough to protect the all-important winter bees from Varroa and its deadly viral payload.

This post is a reminder to remove the strips at the right time. The alternative – leaving them in place until the first Spring inspections – risks help the development of resistance to amitraz, so further reducing our opportunity to control mites effectively.

Leave and let die

Without careful integrated pest management (IPM) 2 Varroa levels build up in the hive. Varroa transmits viruses – most important of which is deformed wing virus (DWV) – to developing pupae. High levels of DWV either kills the pupa or results in emergence with or without significant developmental defects. Even those bees that are apparently normally developed have a reduced lifespan 3.

Winter bees with a reduced lifespan prevent the colony from surviving through the winter until the queen starts laying again. I’ve also proposed recently that high levels of DWV, and the resulting increased rate of winter bee die-offs, probably accounts for some cases of isolation starvation.

So … intervention is needed to reduce mite levels, protect your bees and save your colonies.

Follow the instructions!

Apivar is one solution to reduce mite levels. It is an easy-to-apply chemical treatment that is very effective in reducing the Varroa load by ~95%. For a National hive it is applied as two polymer strips, each containing 500mg of slow-release Amitraz. Strips are hung between brood frames for 6-10 weeks and – for maximum efficacy – should be scratched with a hive tool and repositioned half way through the treatment period.

Amitraz

Amitraz …

Unlike some other miticides (e.g. Apiguard and MAQS) there are no temperature restrictions for Apivar usage. The colony does not need to be broodless (a requirement for trickled oxalic acid-based treatments) as the treatment period covers multiple brood cycles.

Other than not using it with supers present the only contraindication for Apivar is to not use it if Amitraz-resistant mites are present.

How does resistance develop?

When discussing parasites and pathogens, resistance 4 is a consequence of two things:

  1. A selective pressure that kills the pathogen
  2. A population which exhibits genetic diversity

The selective pressure could be anything … heat for example, antibiotics prescribed by your GP, an antiviral against HIV or – of relevance here – Apivar against Varroa.

Killing – at the population level – is not absolute. Some individuals within the population survive longer than others. They could be exposed to a slightly lower dose, or be located in a protected niche for example. However, treat for long enough and the majority will be killed.

But there’s more …

Pathogen populations are not genetically invariant. Actually, many are quite diverse and have replication cycles that – deliberately 5 – generate diversity.

Therefore some pathogens are genetically slightly less resistant and some are genetically slightly more resistant to a selective pressure. We can ignore the former as they’ll rapidly be killed off … but we must be concerned about the more resistant ones.

Keep taking the pills

All of this is a ‘numbers game’, better represented with graphs and equations. However, the take-home message is simple … to effectively control a pathogen you need to treat for long enough and with a high enough dose to kill the vast majority of the population.

That’s why you’re encouraged to “complete the course” of antibiotics … or to remove the Apivar strips after 10 weeks and not leave them in over the winter.

Because both courses of action result in selection of more resistant pathogens.

If you stop taking antibiotics too soon, you won’t have treated for long enough and with a high enough dose. You end up selecting for the more genetically resistant pathogens.

Similarly, if you leave Apivar strips in overwinter you’ll be “treating” the remaining mites 6 with a lower dose of the miticide, which is an ideal situation to favour the growth of the slightly more genetically resistant mites.

How does Amitraz resistance develop?

Resistance to Amitraz in Varroa is well documented. It’s been described in a number of countries including the USA and Europe, Mexico and Argentina 7. Generally resistance is defined in terms of a reduced level of mite killing, or – in laboratory experiments – an increased dose required to kill a certain proportion of mites.

However, I’m unaware of any studies defining the genetic basis of Amitraz resistance in Varroa.

But Amitraz is a widely-used acaricide 8 and the genetic basis of resistance in cattle ticks is well understood. In these, ticks resistant to Amitraz carry a mutation in the RMβAOR gene 9.

What 10 is the RMβAOR gene?

I’m glad you asked 😉

This gene encodes the β-adrenergic octopamine receptor protein and readers with good memories will recall that this is one of the targets that Amitraz binds to and inactivates 11.

If the protein carries a mutation the Amitraz cannot bind to it and so the mite – or more correctly the tick as it’s yet to be formally demonstrated in mites – is therefore resistant.

(Bad) practical beekeeping

What does all this mean in terms of practical beekeeping?

It means use the correct number of Apivar strips for the colony and leave them in for the right length of time.

Do not …

  • Use one strip on a full colony mid-season to ‘knock back the mites a bit’ 
  • Re-use the strips in another colony (yes really!)
  • Use improperly stored strips (or out of date strips) in which the effective Amitraz dose is reduced

I’ve heard examples of these types of misuse this season. All increase the chance of selecting for Amitraz-resitant mites.

And (the real reason for posting this at this time of year) …

  • Do not leave the strips you added in late summer in the colony throughout the winter

Removing the strips takes seconds. Prize off the crownboard, grab the tab projecting above the top bars, gently withdraw the strip and close the hive up again.

Finally, because of the incestuous lifestyle 12 of Varroa the genetic diversity (and therefore potential presence of more resistant mites) in the population is likely to be increased by the high mite levels that prevail late in the season.

All the more reason to use the effective treatments we currently have in a way that helps ensure they remain effective.


Colophon

Resistance is futile

Resistance is futile

Resistance is futile is the title of a 2018 album by the Welsh rock band the Manic Street Preachers.

More specifically, in the context of this post, it was the phrase routinely used by the Borg – the alien cyborgs sharing a collective mind – in the Star Trek franchise. Borgs rarely speak, but when they do they usually include this phrase. For example “We are the Borg. Lower your shields and surrender your ships. We will add your biological and technological distinctiveness to our own. Your culture will adapt to service us. Resistance is futile.” The warning about resistance being futile was usually accompanied by the threat that the target would be assimilated”.

I’d started writing this post using the title ‘Resistance is futile’ but realised late on that – as far as Varroa are concerned – resistance is anything but futile 13.

Resistance – to miticides – gives Varroa a reason to live. Literally.

Let’s not help them 🙂

Footnotes

  1. I’ll use Amitraz, Apivar and Apitraz interchangeably in this article. The active ingredient is the same, the instructions for use are broadly the same and the potential for the development of resistance is therefore similar.
  2. Which might involve a combination of hard and soft miticides and a variety of interventionist beekeeping practices to reduce mite levels.
  3. Amongst a number of other defects.
  4. Which in this context almost always means resistance to being killed or inactivated.
  5. By which I mean that there’s evolutionary selection for a replication strategy that produces diversity.
  6. And there will be remaining mites, as the initial treatment is only ~95% effective.
  7. For example, https://link.springer.com/article/10.1007/s00436-010-1986-8 and https://www.tandfonline.com/doi/abs/10.1080/00218839.2005.11101162?journalCode=tjar20.
  8. A substance poisonous to mites or ticks.
  9. Corley et al., (2013) Mutation in the RmβAOR gene is associated with amitraz resistance in the cattle tick Rhipicephalus microplus. Proc. Natl. Acad. Sci. USA. 110:16772–16777)
  10. Or perhaps WTF?
  11. Formally this is a circular argument built upon the premise that resistance is associated with a mutation in this gene. The real proof of the pudding will require binding studies to be undertaken with Amitraz and the RMβAOR protein to show both inactivation in vitro and a reduced interaction with the mutant protein. These are not trivial studies for a variety of reasons. Don’t hold your breath.
  12. Literally … I’ll discuss this in the future sometime.
  13. Defined as ‘incapable of producing any useful result’ or ‘pointless’.

12 thoughts on “Resistance is not futile

  1. Greg

    Excellent post as usual. Hereabouts we have been discouraging the use Amitraz but I was not familiar with its mode of operation. Plus… I honestly had no idea the so called “active ingredient” for Apivar was the same thing. Makes sense there are protein synthesis mechanisms involved – I just never thought about it. Thanks again.

    Reply
    1. David Post author

      Thanks Greg
      Not sure where ‘hereabouts’ is (and never sure of the accuracy of an IP lookup … Tacoma, Washington?) but presume the advice is based upon suspected resistance in the local mite population? Has it been formally demonstrated?

      In the UK Apistan, a pyrethroid-type miticide, is often ineffective due to resistance (which I’ve discussed previously). Interestingly though there’s evidence that resistance is lost if there’s no selection present e.g.if no-one uses Apistan for a few years. I’ve argued that this would justify selling the stuff once every five years and banning its use otherwise.

      Of course, beekeepers would stockpile it and ignore these ‘rules’!

      What I don’t know is whether resistance to Apivar (in mites or ticks) has a ‘cost’ in the absence of the aracicide. If it does there might be the basis for a rational treatment regime that involved alternating both with something organic in intervening years. Resistance to the latter (OA, formic acid, thymol) isn’t documented and likely more difficult to select. You might end up with a strategy that consistently worked well that way …

      Cheers
      David

      PS Nice Gravatar … I’m picking up a new canoe (not kayak) on Sunday 🙂

      Reply
  2. Bridget Clyde

    You say to leave on for 10 weeks. On the Apivar packet it says minimum of 6 weeks so I just took off after 6. Are you recommending longer than 6?
    Thanks Bridget

    Reply
    1. David Post author

      Hi Bridget
      I was working from the instructions available in the Thorne’s website. I didn’t have a packet to hand when I wrote the post. I’ve now checked a UK purchased pack of Apivar which says 6 weeks if little or no brood is present, or 10 weeks ‘if brood is present’. It’s on page 2 of the peel-open instructions stuck to the packet. Interestingly, the USA instructions linked from the Dadant website state 42-56 days i.e.6 to 8 weeks.

      I’m certainly not recommending 10 weeks. I’ve usually removed it after 6 weeks, but I also usually monitor mite drop quite carefully during the treatment period. If mite drop was still significant at 6 weeks I’d certainly leave it for longer.

      I suspect the different time periods stated on instructions reflect how compounds are licensed (and the supporting data provided when registering a product) as much as real or significant differences in recommended treatment in the USA or UK. Six, eight or ten weeks … but no longer.

      I think the main thing to ensure is that the strips are removed after no more than 10 weeks. Long term exposure to low levels of a selective treatment is a great way to get resistance.

      Cheers
      David

      Reply
  3. Emily

    This sounds like a good alternative to Apiguard for me, especially as I’ve just had a colony build loads of messy comb in the eke space while I was treating with Apiguard. Would alternating it’s use every other year be enough to discourage resistance?

    Reply
    1. David Post author

      Hi Emily
      Alternating treatments is certainly a good idea. The main issue I have with Apiguard is that queens often stop laying when the colony is being treated … at precisely the time of year that you want the colony to rear lots of strong winter bees for the winter. I’ve still regularly used it (though less so in Scotland as the temperature is too low). Whether just using Apivar alternate years is enough to stop resistance developing isn’t known. The main thing is to use the stuff properly, following the instructions …
      Cheers
      David

      Reply
  4. Martin Ainsworth

    Hi David
    All my hives are double brood,and I wonder should I put two strips of Apivar in each box.
    Many thanks.
    Martin Ainsworth
    Bolton
    LancashireM

    Reply
    1. David Post author

      Hi Martin
      Dosage is clear from the instructions. The packet next to me on the desk states The safety and efficacy has only been investigated in hives with a single brood chamber (dose of 2 strips per hive/brood chamber). Use in hives with more than one brood chamber is not recommended.

      Not much help really! Firstly, it doesn’t state the size of the brood chamber. Secondly, what really matters is the access of bees to the strips and the amount of brood present. Overdosing is covered in the instructions and isn’t an issue up to 5 times recommended dose for 6 weeks (other than clustering). At 1.5 times dose for 10 weeks there were no issues. I don’t use double brood. If I did I’d make a judgement about the level of brood and the real size of the cluster. If either were ‘large’ I’d use 4 strips in the box, appropriately spaced. However, in your location the colony is probably not occupying the full double box at this time of the year (which is a bit late to protect the winter bees anyway) sos 2 strips might suffice.
      Cheers
      David

      Reply
  5. Edward

    Nice post well done, As a matter of interest you cannot access your blogs via website it says down for maintenance.

    Reply
    1. David Post author

      Thanks Edward … I suspect this is a caching problem. Could you try again? I’m in the process of making some changes to the site and the server and may have left things set wrongly.
      I was wondering why my huge advertising revenue had fallen. Er, not.
      Cheers
      David

      Reply

Leave a Reply

Your email address will not be published. Required fields are marked *