Just Scut'n along

[D Grade]

My friend and I recently participated in a venom study regarding range variations in venom composition from C. Scutulatus (Mojave's Rattlesnakes) from a particular area in Southeast Arizona performed by Wolfgang Wuster, a world renowned herpitologist and snake venom biologist (more on Wolfgang can be found here: Dr Wolfgang Wüster | School of Biological Sciences | Bangor University (http://www.bangor.ac.uk/biology/staff/wuster.php) ). Last night we set out to release some of the specimens we found and I snapped a few pics. All were released without injury, trauma, and in close approximate to the gps location in where they were found. In fact they shook out hand and thanked us kindly for the experience that they wold tell all their friends about. :)

One of three neonates we released:
http://img.photobucket.com/albums/v147/Dieselboy/Mobile%20Uploads/20150925_230042.jpg

Biggest one we had out of five adults, just under 5ft and very happy:
http://img.photobucket.com/albums/v147/Dieselboy/Mobile%20Uploads/20150925_230237.jpg

Two more, the one on the left had the largest venom yield recorded by Wolfgang at over 600mls (typical C. Scutulatus yield is around 300mls):
http://img.photobucket.com/albums/v147/Dieselboy/Mobile%20Uploads/20150925_230225.jpg

[EL Ziggy]

Wow, sounds like quite an adventure D. Beautiful critters you guys found. Stay safe brother.

[D Grade]

Definitly alot of fun, I love working with Crotes. Thanks El. :)

[Venomhunter]

They have a nasty pre synaptic neurotoxin on them, i wouldn't like to take a whack from one of these.
Well, i wouldn't like to take a whack from any species of Crotalus!

[D Grade]

I couldn't agree more, especially C. Scutulatus and C. Tigris.

My buddy who was the main point of contact with Wolfgang said he plans to return next year to to conduct a study on C. Molossus venom which I am highly interested in since I keep one. There's not much detail on the venom composition beside being hemotoxic and the fact CroFab does not counter act it as well as other Crote venom. I believe he plans to conduct tests on various Crotalus venom using AnaVip (the new antivenin that was approved for use against Crotalus bites).

[prairiepanda]

So pretty! I don't think I've ever seen an ugly hot. It's like venom automatically means beautiful.

[Venomhunter]

I couldn't agree more, especially C. Scutulatus and C. Tigris.

My buddy who was the main point of contact with Wolfgang said he plans to return next year to to conduct a study on C. Molossus venom which I am highly interested in since I keep one. There's not much detail on the venom composition beside being hemotoxic and the fact CroFab does not counter act it as well as other Crote venom. I believe he plans to conduct tests on various Crotalus venom using AnaVip (the new antivenin that was approved for use against Crotalus bites).

That sounds very interesting, i believe CroFab also didn't counter act the venom of C. oreganus helleri as well as for other Crotalus sp.
I will do some searching on AnaVip, have heard of it but haven't read anything about it.
Please keep me posted as the research continues!

[MDT]

CroFab did (does) not. You are correct.

[D Grade]

It'll be interesting to start seeing how AnaVip will counteract venom in relation to CroFab. I think CroFab was built around the most common of snake bites which are obviously from C. Atrox. Obviously it won't counteract other venom as well, especially much more rare bite cases such as C. Molossus, C.O. Lutosis, C. Cerberus, etc... It'll be interesting to see if AnaVip evens up the playing field a bit, especially cost wise.

[D Grade]

So pretty! I don't think I've ever seen an ugly hot. It's like venom automatically means beautiful.

Couldn't agree more!

[MDT]

I think at the minimum, the cost competition will be nice. Medically speaking, if it does at least what CroFab does, it'll be a hit. While CroFab may not hit some of those species as well as it does others, it still is beneficial and light years ahead of the Wyeth polyvalent horse serum. Fortunately in the US, we don't have really nasty players. Some are pretty rough, and morbidity/mortality does occur, it doesn't approach Africa, India, Indonesia, etc.

[D Grade]

I agree 100%. I think CroFab is up to $2500ish per vial and AnaVip is supposed to be half of that. Still not cheap by any means but Id certainly rather have two vials for the price of one if I ever get bit.

[MDT]

The next step is to get providers to actually use the stupid stuff.

I was (unofficially) consulted on a case recently...patient was bitten by unknown pit viper in SE Oklahoma. Based on Snakebite Severity Score, patient needed CroFab. Let's just say that there may have been some indecision. By several hours. This drives me insane. Envenomation is a dynamic process, with frequent re-evaluation required and modification of treatment plan at a moment's notice. Just give the *%^$&!@# medicine if it is clinically warranted. We don't jack around with heart attacks (time is muscle)...we shouldn't be jacking around with pit viper envenomation (time is tissue).

[D Grade]

Couldn't agree more, time becomes even more crucial when an allergic reaction or anaphylactic shock come into play.

Did they find out what species of snake the bite was from?

[MDT]

No ID was made, but it really wouldn't matter. CroFab would be adequate for all players in that part of the state.

[Venomhunter]

CroFab is a serum derived from sheep from what i've read, i don't know what animal AnaVip is derived from but if it's cheaper then CroFab and it works on more species of Crotalus (or crotalid) then i will contact an old friend if mine who works in the Antivenom distribution centre here in The Netherlands, to see if he has any plans to ship it over here.

[Venomhunter]

The next step is to get providers to actually use the stupid stuff.

I was (unofficially) consulted on a case recently...patient was bitten by unknown pit viper in SE Oklahoma. Based on Snakebite Severity Score, patient needed CroFab. Let's just say that there may have been some indecision. By several hours. This drives me insane. Envenomation is a dynamic process, with frequent re-evaluation required and modification of treatment plan at a moment's notice. Just give the *%^$&!@# medicine if it is clinically warranted. We don't jack around with heart attacks (time is muscle)...we shouldn't be jacking around with pit viper envenomation (time is tissue).
If there is certainty that that it was from a local pit viper species and there is a systemic envenomation you should never doubt using CroFab (unless allergies etc.)
Like you said: "Time is tissue" also for muscles.
The more muscle tissue is destroyed, the higher the CK levels in the blood are (eventually clogging up the kidneys.)

[MDT]

If there is certainty that that it was from a local pit viper species and there is a systemic envenomation you should never doubt using CroFab (unless allergies etc.)
Like you said: "Time is tissue" also for muscles.
The more muscle tissue is destroyed, the higher the CK levels in the blood are (eventually clogging up the kidneys.)

Trust me, I give lectures to physicians, med students, paramedics about this. I just don't get "not giving it". The ovine component reduces the antigenicity of the product SUBSTANTIALLY. Allergic rxn's are not common, and those are typically mild.

I have never seen an allergic reaction giving CroFab in all the times I have administered it. I actually had to give the Wyeth product once, immediate allergic reaction.

[D Grade]

No ID was made, but it really wouldn't matter. CroFab would be adequate for all players in that part of the state.

Of course, I just like to know which species was the culprit. :)

[Venomhunter]

Trust me, I give lectures to physicians, med students, paramedics about this. I just don't get "not giving it". The ovine component reduces the antigenicity of the product SUBSTANTIALLY. Allergic rxn's are not common, and those are typically mild.

I have never seen an allergic reaction giving CroFab in all the times I have administered it. I actually had to give the Wyeth product once, immediate allergic reaction.

The ovine component sure does help alot!
The chance is always there, even with CroFab however, far less likely.
Wyeth just like L. Mactans AV (Black widow AV) can be very tricky stuff!
It's pretty interesting, why would a Black widow (Latrodectus spp.) bite trigger a allergic reaction whilst Poecilotheria spp. (Tarantula) bite doesn't? Some proteins in the venom are bigger then the proteins in tarantula venom so it's easily detected by our immune system.
That's why i always keep epinephrine and diphenhydramine in my "emergency" drawer!
It's also the case for the AV i guess, plus alot of antigens so that combined makes a risky AV.

[Venomhunter]

Of course, I just like to know which species was the culprit. :)

Same here!

[MDT]

just like L. Mactans AV (Black widow AV) can be very tricky stuff!

I actually had an honest-to-God Widow envenomation several years ago. My only one. Patient was a young pregnant woman and she brought in the spider to be identified. Black Widow for sure. Minimal symptoms, but w/ the neuromuscular stuff, she was at risk for uterine contraction and spontaneous loss of the fetus. We really deliberated on giving the anti-venom. In the end, we did not (after extensive consultation) based on the fact her symptoms were pretty mild and the risk for allergic reaction from the drug was so high. She and the baby ultimately did well.

[Venomhunter]

I actually had an honest-to-God Widow envenomation several years ago. My only one. Patient was a young pregnant woman and she brought in the spider to be identified. Black Widow for sure. Minimal symptoms, but w/ the neuromuscular stuff, she was at risk for uterine contraction and spontaneous loss of the fetus. We really deliberated on giving the anti-venom. In the end, we did not (after extensive consultation) based on the fact her symptoms were pretty mild and the risk for allergic reaction from the drug was so high. She and the baby ultimately did well.
Great to hear that she did allright without it, alpha-latrotoxin together with some other Polypeptides in Latrodectus venom cause alot of uncomfortable symptoms.. Whilst L. Mactans would give a person abdominal cramps (bad when pregnant), nausea, swollen eyelids etc. L. Hasselti would give a person typically back cramps.. CSL limited makes an effective antivenom and it's currently the only Latrodectus antivenom we got here in The Netherlands.
I'm also planning to buy 2 vials of Redback antivenom since i keep two species of Latrodectus (European black widow and The redback spider) just in case, i have epinephrine and diphenhydramine in my emergency drawer so should i ever get bitten again (happend to me once, minor effects) and the envenomation would be moderate to severe then i would be able to treat myself.
Your story made me think about an incident that happend this summer in Leeuwarden, the city i live in.
A man was bitten by a stowaway spider from a package out of Australia, the man thought it was a Redback because the next day his face was a little bit numb.
I was in Mexico at the time so my co workers at the shelter couldn't get my help, but they gave me a call nonetheless.
The symptoms didn't belong to Latrodectus hasselti venom, and the reaction would be pretty late so i knew it wasn't a L.hasselti.
It turned out to be a crabspider (Thomisidae spp.) harmless little spiders! But the doctors in our hospital went crazy because they couldn't tell the diffrence between redback and crabspider, luckily my colleagues were able to determine te spider at last.
This is one of the reasons why i started my venom project, the medical community here in The Netherlands knows very little about venom, even that from local species, yet about 100 venomous bites are reported every year.
I hope to help doctors understand the wide variety of toxic effects caused by venom, and hope to find some answers about the venom composition etc.

[Venomhunter]

It's getting a little bit off topic, sorry D! I think it might be a good idea to start a venom discussion thread!

[MDT]

Yes!!! Sorry D!!!! Back to originally scheduled topic!

[D Grade]

No sweat guys, this is exactly what I was hoping for. :)

[Aaron_S]

So in my non-medical mind I have a question, why is the new stuff cheaper? Is it due to how it's made? I would have thought that a new one would cost the same if not more if it was better, no?

Also, Matt, why did the horse serum give a reaction so quick? That ovine thing you mentioned? As I understood from your posts, doctors are hesitant to administer CroFab because they are worried about allergic reactions? I find it odd considering it could save the life and I'm wildly guessing here, that it's better to deal with the reaction than to let an envenomation go on for too long?

[Venomhunter]

So in my non-medical mind I have a question, why is the new stuff cheaper? Is it due to how it's made? I would have thought that a new one would cost the same if not more if it was better, no?

Also, Matt, why did the horse serum give a reaction so quick? That ovine thing you mentioned? As I understood from your posts, doctors are hesitant to administer CroFab because they are worried about allergic reactions? I find it odd considering it could save the life and I'm wildly guessing here, that it's better to deal with the reaction than to let an envenomation go on for too long?
Did some research on it, this is what i've learned about AnaVip:
It's an equine derived antiserum (derived from horses), there is no ovine component and the initial dose/additional* dose is 10 vials and the maintenance dose is 4 vials.
CroFab's initial/additional dose is 4 to 6 vials and the maintenance dose is 2 vials.
The ovine component makes it more expensive to make plus it's derived from sheep which are less frequently used.
The snake species used for the standardization are the Crotalus durissus (South American Rattlesnake) and the Bothrops asper (Fer-de-lance.)
So, CroFab is more effective because less is needed but Anavip works on more species of crotalid.
The chance of allergic reaction however is greater with non ovine serums so time will tell how this AV will do!
I'm quite curious, i hope that people with snakebites that aren't entirely covered by CroFab will get better resulrs out of this AV :)

*initial dose is meant to get initial control, that means that the progressive swelling stopped and blood values stay around the same value.
After this you get the patient on the maintenance dose, this is 2 vials every 6 hours, repeat this 3 times.
(CroFab)

[MDT]

Yeah, pretty much what VH said...

From an antigenicity standpoint, the Wyeth product utilized the entire antibody, and this was derived from hyperimmunizing horses. Imagine a molecule that looks like the letter "Y". That's what the molecule looks like. So this whole thing was injected and circulating in your blood stream. Your own immune system is really good at recognizing things that "don't belong", especially foreign proteins. So, upon seeing this circulating letter Y, in a lot of folks, that triggered an immune response (which manifests in wheezing, swelling, hives, hypotension, and cardiovascular collapse, which leads to you dying from anaphylaxis). This was a relatively common occurrence, but severity was variable, and clearly, was a life saving product. So you had to use it with care.

The ovine products (sheep derived) are made similarly, only that letter "Y" is chopped into pieces, for CroFab, 3 pieces (imagine cutting the Y into \, |, / ) and Anavip is carved into 2 pieces (thing of a V and | ). So they seprate and keep the "slanty" parts and get rid of the "stick" portion. Getting rid of the "stick" portion seems to significantly reduce the antigenicity of the antivenom. So, the result is a much cleaner product.

CroFab is made with 4 US pit viper species. AnaVip made with 2 SA species. I have not reviewed any pharmacokinetic data, and in full disclosure, I have not had an opportunity to use Anavip.

I do understand that the circulating level of each product is different. In my mind (again, not having read any kinetic data), it would seem that the US specific compound would be more effective in the US (each venom being genetically/molecularly different). Also, the relative cost...CroFab was the first guy out there. They can "name their price" so-to-speak. Now that there is some (apparently good) competition, CroFab will adjust prices and hopefully, everyone will be a little more sane.

As far as administering the med, that is a good question. Seriously...I don't get it. Maybe because of the reputation that the Wyeth product had? We give thrombolytics (clot busters like tPA) in the ED on a relatively common basis. This is pretty tricky stuff, in that it basically stops your ability to clot your blood. We give medications to paralyze people before we intubate them. Nothing like taking an awake, talking patient and removing all muscular control and stopping their breathing, only to insert an endotracheal tube into them and we breath for them. That is a pucker time for sure. We give all kinds of really gnarly stuff and don't bat an eye, because we know that's part of taking care of a particular disease process. So it's not like we aren't familiar with giving tricky stuff. But when it comes to antivenom, it seems like the medical community wets their collective pants.

Oh well, not sure if this answered your question, but I tried to hit the high points...

[Venomhunter]

Yeah, pretty much what VH said...

From an antigenicity standpoint, the Wyeth product utilized the entire antibody, and this was derived from hyperimmunizing horses. Imagine a molecule that looks like the letter "Y". That's what the molecule looks like. So this whole thing was injected and circulating in your blood stream. Your own immune system is really good at recognizing things that "don't belong", especially foreign proteins. So, upon seeing this circulating letter Y, in a lot of folks, that triggered an immune response (which manifests in wheezing, swelling, hives, hypotension, and cardiovascular collapse, which leads to you dying from anaphylaxis). This was a relatively common occurrence, but severity was variable, and clearly, was a life saving product. So you had to use it with care.

The ovine products (sheep derived) are made similarly, only that letter "Y" is chopped into pieces, for CroFab, 3 pieces (imagine cutting the Y into \, |, / ) and Anavip is carved into 2 pieces (thing of a V and | ). So they seprate and keep the "slanty" parts and get rid of the "stick" portion. Getting rid of the "stick" portion seems to significantly reduce the antigenicity of the antivenom. So, the result is a much cleaner product.

CroFab is made with 4 US pit viper species. AnaVip made with 2 SA species. I have not reviewed any pharmacokinetic data, and in full disclosure, I have not had an opportunity to use Anavip.

I do understand that the circulating level of each product is different. In my mind (again, not having read any kinetic data), it would seem that the US specific compound would be more effective in the US (each venom being genetically/molecularly different). Also, the relative cost...CroFab was the first guy out there. They can "name their price" so-to-speak. Now that there is some (apparently good) competition, CroFab will adjust prices and hopefully, everyone will be a little more sane.

As far as administering the med, that is a good question. Seriously...I don't get it. Maybe because of the reputation that the Wyeth product had? We give thrombolytics (clot busters like tPA) in the ED on a relatively common basis. This is pretty tricky stuff, in that it basically stops your ability to clot your blood. We give medications to paralyze people before we intubate them. Nothing like taking an awake, talking patient and removing all muscular control and stopping their breathing, only to insert an endotracheal tube into them and we breath for them. That is a pucker time for sure. We give all kinds of really gnarly stuff and don't bat an eye, because we know that's part of taking care of a particular disease process. So it's not like we aren't familiar with giving tricky stuff. But when it comes to antivenom, it seems like the medical community wets their collective pants.

Oh well, not sure if this answered your question, but I tried to hit the high points...
Great explanation MDT!

[D Grade]

An abundance of info and great discussion, Thanks MDT and VH!