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Is One Leptospirosis Vaccine

Dose Size Really Right For All Dogs ?

 

 

 

What Happens After My Pet Receives His Leptospirosis Vaccination ?

How Frequently Do Leptospirosis Vaccine Side Effects Occur And What Is In These Vaccines That Cause Them To Have So Many Side Effects ?

Is The Dynamics Of Every Bad Vaccine Reaction The Same ?

Can You Tell Me More About The Really Bad Reactions – The Ones Called Anaphylaxis or Cytokine Storms ?

Is It True That All Vaccines Should Be Given At The Same Dose Regardless Of The Size Of My Dog ?

What Can Ten Hamsters Tell Us ?

Is The Chance Of A Bad Reaction To Vaccines A Simple Matter Of The Size Of The Dose and The Weight Of My Dog ?

 

 

Well, Experts Know That Anaphylactic Reactions Are An All-Or-Nothing Event - So It Wouldn’t Make Any Difference If My Pet Got A Smaller Vaccine Dose – Right ?

Are These Vaccine Problems Or Regulatory Problems. Is Mr. Fox Guarding The Chicken Coop ?

 

Are There Factors Other Than Dose Size That Could Make My Pet More Susceptible To Vaccine Reactions ?

Can You Propose A Way That Too Large A Dose Of Killed-antigen Vaccine Like Leptospirosis, Given To My Pet , Might Increase Its Likelihood  For Side Effects ?

Are You One Of Those Anti-vaccination Guys ?

 


What Can I Do To Minimize My Pet’s Risk When Its Time For His Booster Vaccinations ?

Is Checking My Dog’s Leptospirosis Antibody Titer A Good Way To Decide If My Dog Needs A Booster Leptospirosis  Vaccination ?

 

If you would like to read some sad experiences of people who have contacted me about this problem, go here.

 

 

 

Ron Hines DVM PhD

Lots of my articles are plagiarized and altered on the web to market products and services. There are never ads running or anything for sale with my real articles. Try to stay with the ones that begin with http://www.2ndchance.info/ in the URL box or find all my articles at ACC.htm.

This is a difficult article for most of the people for whom I write my articles. It is long-winded and technical. If any of it is unclear, send me an email and I will do my best to explain it

September of 2013 was a noteworthy month for me. Two dog owners wrote to me expressing their grief at loosing their pets subsequent to having received leptospirosis vaccine boosters. (Veterinarians know that lepto vaccines are the most likely products to give vaccine reactions [ref] )  It troubled me that they asked questions that I could not answer.

While that was still on my mind, my veterinary newsletter ran a clip about a Connecticut veterinarian’s legal predicament for scaling vaccine dose to his patient’s body weight. (ref)   Later that month, I saw an AVMA quote from a Department of Agriculture's vaccine regulator describing vaccine manufacturers as his “clients”. How strange – I had thought pet owners and practicing veterinarians were the clients of the CVB ? (ref)
It seemed to me that the time had come to have a closer look at the whole situation.

The East Coast dog had received Merial’s Recombitek® 4LEPTO. So I called the Merial veterinarian's hotline. The nice young veterinarian who answered seemed to know little more about the subject of vaccine reactions than I did. The vaccine safety studies she promised to send me never arrived.

The second dog belonged to a servicewoman stationed in Japan. It had received Merck’s Nobivac ® Lepto 4 vaccine . My attempts at obtaining vaccine reaction data on that product were equally unsuccessful.

So I called the veterinarian’s inquiry line at the Center For Veterinary Biologics (CVB) in Ames, Iowa. Their Biologics Specialist, a PhD in Molecular Biology, was uninformative. Not only would he not discuss vaccine reactions with me, he told me that all adverse event (bad reaction) reports the CVB receives from the public and veterinarians alike become “proprietary” - property of the vaccine manufacturers and I could not see them. So I asked to view the initial safety studies submitted to the CVB when the vaccines were initially approved. He refused that as well and chuckled that any attempts I might make to obtain any additional information under The Freedom of Information Act would be unsuccessful as well. (A flashback to when my children were young and wouldn’t show me what they were hiding in their hands behind their back.)

Dog owners like you are in a unique situation when it comes to your pet’s vaccine safety and efficacy. Although all human vaccines are reviewed for safety and efficacy by the FDA; animal vaccines are reviewed by the US Department of agriculture under an archaic law, The Virus-Serum and Toxin Act of 1913, that was enacted because of some worthless pig vaccines. (ref) You can see all bad reaction reports on the vaccines you take anytime - they are posted online. But you are not allowed to see the same information when it comes to your pet. I could see I had quite a project on my hands if I wanted to understand the nature and depth of the problem and that it would require examining many facets of the situation.

Over the years, the veterinary establishment has developed a rather inflexible, pyramidal structure – much like the old monarchies of Europe. Their official position is that vaccine dose has nothing to do with bad (adverse event) reactions. The one-size-fits-all vaccine dogma reigns supreme and it is considered blasphemy by many to question it . I had plenty of projects on my "to-do" list and wasn't thrilled to have another - besides, I have enough problems with institutionalized veterinary medicine already (ref) - but the medical student kept asking me questions I could not answer.

So I decided I would write an email to the most knowledgeable person I knew of regarding vaccines, Dr. Stanley Plotkin, I would let his response govern my course. Dr. Plotkin speedily replied  that my “perception that there were no studies that specifically addressed that question [on dose-to-body weight effects] were correct”.

In the discussion that follows, I sometimes use the word vaccine and antigen (its active ingredient) interchangeably. When I say "antigen mass" - I mean the amount of vaccine. But although the primary ingredient in all vaccines is antigen, many vaccines contain other ingredient, either required in their manufacture (like blood extracts [BSA]) or things added to increase the product’s ability to stimulate the immune system (adjuvants).

There are 7 leptospirosis-containing vaccines currently on the market in the United States (ref) All but one combine the leptospirosis part (dead antigen) with attenuated (weakened) live virus (modified live virus or MLV) designed to protect your dog against a variety of other common canine diseases. How dead (inactivated) antigen and live MLV react within your pet’s body are quite different. So do not assume that anything I have to say about killed antigen dynamics has anything to do with how they might react to MLV vaccines.

In the case of MLV vaccines, like distemper or parvovirus vaccine, only enough organisms (antigen mass) need be given to assure that they multiply in your pet’s body and that the resulting (very mild) infection produces protective antibodies and “immunological memory” that guard your pet into the future. In the second type (killed antigen vaccines=bacterins) like leptospirosis, Lyme or rabies vaccine, we count on the mass (the quantity) of dead antigens to produce the antibodies and “memory” that will protect your pet into the future. 

What Happens After My Pet Receives His Leptospirosis Vaccination ?

Within an hour or so of receiving the shot, the antigens in the vaccine will be carried through your pet's lymphatic vessels to the nearest lymph nodes they drain to. The courier cells that carry the antigens are dendritic cells, sentinel guarding cells of your pet’s immune system scattered throughout its body. They are particularly common under the surface of your dog's skin, nose, lungs and intestine – the places invading bacteria and virus are most likely to enter its body.

Dendritic cells deliver (present) the vaccine antigen to another type of lymph node cell, the virgin (“naive”) T-cells (CD4+ T cells), with orders to begin dividing and to produce peptides and combine them with MHCII molecules. The peptide-MHCII complexes will stimulate your pet's CD4+ T cells to divide (proliferate) to their Th1, activated form. Others will become cells (Tfh or T-folicle helper cells) that assist certain B-cells (plasma cells) in your pet’s lymph nodes in producing antibodies against the vaccine antigens that were injected. If this choreographed "dance of the cells” does not go precisely as ordered, your pet will not become immune or your pet will produce antibodies that are not in the best interests of its health. (ref 1 ref 2) If your smaller dog gets a whopping dose of antigen, more than can be processed (opsonized) in those regional lymph nodes, what becomes of the excess is anyone's guess.  

Throughout the process, “memory cells” (B and T types) are also created – cells that will begin the process again in a more rapid fashion if an antigen similar to the one in your pet's vaccine ever enters its body again. Some of those cells live a very long time. Those cells are the reason your dog will never become ill with parvo once a single effective vaccine dose against parvo gets properly processed.  Other antigens, like the antigens that leptospirosis produce (LPS or surface lipopolysaccharides), do not produce as good immunological memory.  Those are the ones that require your veterinarian to periodically “remind” the pet’s immune system with a booster vaccination. (ref)

How Frequently Do Leptospirosis Vaccine Side Effects Occur And What Is In These Vaccines That Cause Them To Have So Many Side Effects ?

A vaccine’s potential for undesirable side effects is often called its potential for “reactogenicity”.

My calls and emails to the USDA Center for Biologics and Merial were an attempt to get that answer for you. Neither would cooperate in providing the information that they have on file. European veterinary regulatory agencies are similarly tight-lipped about providing that data. So I filed my first Freedom of Information Request. In December of 2013, I managed to get those reports.

On Jan 8, 2014, I received an email from the Center For Veterinary Biologics informing me that they plan to change their policy (perhaps this article played a small part in that) and make vaccine manufacturers report all undesirable (adverse) vaccine reactions to them. The pharmaceutical companies will not be pleased.  They have their lobbyists, but there is no one in Washington lobbying for you and your pet.  You need to let the CVB and your congressmen know that you support the CVB's decision. Add that the information needs to be posted on the CVB website in a understandable/readable manner for pet owners like you - just as the FDA posts adverse event reports for the vaccines you and your family receive on their site to help you make wise decisions..

In any case, there are major problems in drawing conclusions from official Adverse Event Reports. Those are the letters that pet owners and veterinarians send, on their own volition, to vaccine manufacturers or the CVB when vaccines cause unwanted reactions. First, experience in human medicine has showed that only a small fraction (~1%) of human adverse events get reported to the FDA. (ref)    The number that get reported to CVB when they concern our pets is quite likely only a fraction of 1%. Some refer to to the causes of that as the Seven Deadly Sins.

Second, vaccine manufacturers don’t dedicate a lot of effort forwarding reports they receive to the CVB -everybody is on the honor system. Ninety percent of human adverse reports get sent to the drug manufacture - not the FDA.

Thirdly, the data is often sketchy, making it hard to find trends or draw conclusions.

The fourth problem is the plethora of leptospirosis vaccines out there. The formulation of each is a closely guarded trade secret. If one vaccine or the other has a bad track record, I will not know which ingredients in it might be responsible. But I can guarantee you one thing: if uncensored adverse event reports were as easily obtained from the CVB as they are from the FDA, veterinary vaccine manufacturers would scramble fast as greased lightening to not be high on that list.

My intuitive feeling is that the leptospira’s own surface proteins (their LPS lipopolysaccharides antigens) have the potential to cause adverse reactions on their own accord. If ancillary ingredients in the vaccine were responsible, the problem would have been corrected by now (lipopolysaccharides are reactogenic in their own right [ref]). Other ingredients in these vaccines have the potential to cause bad reactions (ref); but because of the secretive practices of the CVB, I can not tell you how much they contribute to the problem.

Is The Dynamics Of Every Bad Vaccine Reaction The Same ?

No.

First, every vaccine antigen has its own characteristics that govern how your pet’s immune system handles them. Some, like leptospirosis antigen are highly “reactogenic” – inclined to cause unwanted reactions - some are considerably less so.

Second, there are many places along the immunity road where the process can take a wrong turn – producing the wrong type of antibodies (IgE antibody-class switching, promiscuous antibodies, etc.)   IgE is the class of antibodies that are generally associated with allergy and hypersensitivity. But in some cases, these adverse reactions appear to occur in the absence of circulating antibody – the process is extremely complex and still being figured out.

The likelihood of these reactions in dogs increases with succeeding vaccinations because memory cells are then taking part in the process. The sites that these unwanted reactions occur also vary. In some dogs, the skin and underlying tissue is the primary point – those dogs develop hives and swelling (and sometimes fever) than generally passes with no permanent damage. In some, lung tissue is the central point of reactions – then their ability to breath is affected. In others, their cardiovascular system loses its ability to sustain vital functions (circulatory collapse=shock).

Complicating our understanding is the fact that these are often fleeting, emergency situations with dynamics that change from minute to minute. Some are certainly due to non-key components (bovine albumen, antibiotic additives like neomycin thickening and syringability agents such as gelatin, and adjuvants designed to aid in the antigen presentation process). What percentage, we can not say.

Many factors one might not consider enter into the effectiveness of our vaccines. Overweight children were found to respond poorly to DTP vaccinations. The problem was solved using longer needles – fat does not have adequate lymph supply to get the vaccine antigens to the children’s lymph nodes properly. Perhaps similar things occur in chubby pets – I do not know.

Can You Tell Me More About The Really Bad Reactions – The Ones Called Anaphylaxis ?

There are a group of “first responder” cells (mast cells) in your pet’s body designed to release irritating chemicals (cytokines and histamine) when they detect foreign invaders - a form of chemical warfare. They wear a coat of plasma cell-generated IgE (on their surface FceRI receptors) that was designed to be triggered by only one specific antigen that your pet encountered some time in the past. Things exist for a reason. It is normal for humans and pets alike to produce this form of antibody-coated mast cell; we are just unsure what those normal functions are.  IgE is thought to be important in protecting your pet's intestines from parasites, but it will probably be discovered that it has other much more important functions as well. In any case, IgE “gone awry” usually comes up in discussions of all types of allergy – from a sneezy nose or fleabite sensitivity to life threatening anaphylactic reactions. It is probable that the basophils in your pet’s blood will eventually settle in its tissues as mast cells.

The cytokines and histamines that these mast cells release cause blood vessels in the area of release to expand (dilate) and leak fluid (angioedema). When that is a whole-body occurrence, the pet’s blood pressure can drop dangerously low and its lungs can become critically congested with leaked blood plasma (pulmonary edema). You can read a less simplistic explanation here (ref)

Although that was the classical explanation for anaphylaxis, there are cases where the theory does not hold up – crises occurring on the first exposure to a vaccine antigen and cases that occur in an obvious dose-dependent manner. 

Those cases are called anaphylactoid reactions. They are indistinguishable from true anaphylaxis in their appearance and effects and I cannot tell you which occur subsequent to pet vaccinations. An adverse event occurring the first time a dog received a specific vaccine would most likely be anaphylactoid while one occurring after booster vaccinations, true anaphylaxis.  But there are other ways a pet could be primed for true anaphylaxis. Unlike most things your dog gets vaccinated for, there are over 200 species of leptospira and of them, only 6 are known to cause disease in dogs. (ref) Damp, humid environments, particularly near water impoundments, are full of non-pathogenic leptospira (saprophytic leptospira). Perhaps association with them pre-sensitize certain dogs. When it was obviously the pet's first exposure to a leptospirosis-containing vaccine, it might be more appropriate to call it a Cytokine Storm.

Not every case of leptospirosis in dogs is detected. Many recover naturally without the owners ever realizing the pet was ill. Some veterinarians believe that  those dogs could be more susceptible to anaphylactic reactions on their subsequent vaccinations when the vaccine contains leptospirosis strains (serovars) the dog was naturally exposed to in the past (ref)

Is It True That All Vaccines Should Be Given At The Same Dose Regardless Of The Size Of The My Dog ?

Veterinarians tend to believe that - and that notion is nurtured by the veterinary vaccine industry and their regulators. You can read a typical response to a pet owner who brings a toy breed dog and a giant breed dog to their veterinaran for yearly vaccinations and questions why they both get the same dose here.

I will have to reach far from your neighborhood dog and cat hospital to show you examples why that is untrue. When I cross species lines, it is true that the size-versus-dose relationship can be questioned. At the least, consider them as proof of concept. Almost all vaccines in use in humans to today crossed species lines when their efficacy (effectiveness) was first established. The list I give is long; it may be overkill, but the point needed to be made. Giving an amount of vaccine in proportion to body weight is called dose scaling or allometric scaling.  It doesn’t come up frequently across the spectrum of vaccines because dogs are the only species on the planet whose adult body weight varies in the extreme.

Rabies vaccine

Like leptospirosis vaccines, many rabies vaccines are also killed antigen products that rely on the amount of antigen mass in the syringe to impart protective immunity to your pet.  The CDC worked out a procedure for vaccinating bats against rabies using dog rabies vaccine:
Take a gray wolf, probably similar to the progenitor of all dogs. An adult weighs about 36000 grams. An Egyptian fruit bat weights about 125 grams and a Mexican free-tailed bat 11-14 grams. Is the same 1 ml dose of dog rabies vaccine required to immunize all of them effectively ? .... No. Fruit bats were successfully immunized with 0.1 ml of the dog vaccine and free-tail bats were successfully immunized with 0.05 ml. Read the studies here
and here.   (The CDC considers ≥  0.5 IU/mL of antibody to be protective in all animals.) Rabbits (~4.8 kg) are successfully immunized against rabies with a 0.25 ml dose of dog rabies vaccine. (ref)

Ringling Bros. Circus elephants weight between 1,645 and 4,741 kg. It takes two 4ml doses of bovine rabies vaccine to immunize them against rabies. Even that massive dose was insufficient to reliably sustain  ≥  0.5 IU/mL  titers, (ref)  The need for larger vaccine doses in heavy animals like elephants versus lighter weight animals has been known for over three decades. Since no commercial elephant vaccines exist, horse or cattle vaccines are given at 2-3 times the amount suggested for those species. (ref) ]

Our Feathered Friends

Birds get the flu too. When the veterinarians at the Rotterdam Zoo were concerned that their birds might catch it (avian influenza H7N1), they gave them a bird flu vaccine designed for chickens. The chicken dose was 0.5ml. They found that there was an inverse relationship between the bird’s weight and the protection the vaccine gave. So, subsequently, birds weighing 1.5kg or less received 0.25ml and birds weighing more than 1.5 kg received 0.5ml. However, even that dose was not sufficient to produce antibody protection in their heaviest birds – ostriches, rheas and cassowaries.  You can read about that here , here   and here .

How About When  My Kids Or I Go In For Vaccinations ?

The most problematic vaccine that your children get are their DTP shots. Anaphylactic reactions to DTP vaccinations are quite rare – but fever, malaise and injection-site inflammation are quite common – particularly after the kids immune systems are sensitized by earlier DTP injections. (ref)  

Like leptospirosis , DTP vaccine is a killed antigen product, designed  to protect children against diphtheria, pertussis (whooping cough) and tetanus. In the case of DTP, the quantity of vaccine antigen your children receives definitely does influence the frequency of adverse reactions. Studies have shown that children receiving half the suggested vaccine dose for their last vaccination develop adequate protection to these disease with significantly fewer side effects. (ref)  Every antigen in this 3-disease vaccine has unique qualities, when a somewhat reduced protection was noticed at all, it was for pertussis. (ref)  but over time, half-antigen pertussis protection equaled full dose protection as well. (ref1, ref2ref3)

It’s flu season. If you get Sanofi’s Fluzone vaccine, you will find that it has three suggested dosing schedules. If you’re a mature adult, you will get 45 µg of combined HA antigens. Your child under 3 will get 22.5 µg of combined HA antigens and senior citizens will get 180 combined HA antigens - Clinical trials had found that a one-size- fits-all dose schedule did not work for this product either. (ref)

Americans are rarely vaccinated for tuberculosis. But in areas of the world where that vaccine (BCG) is routinely given, the dose for a child is half the dose given to an adult. (ref

Can We Learn Anything From Bioterrorism Research ?

My best vet tech in Sarasota, FL move to Washington D.C. So I put her in touch with old friends at the NIH. She was quickly hired and emailed me that she was being immunized against anthrax – with a killed antigen product not that unlike leptospirosis bacterin.  But to test their anthrax vaccine, prior to its use in humans, the researchers used rhesus macaque monkeys.

Adult rhesus monkeys weight 5-7 lbs (2.3-3 kg). Pharmaceutical companies often use 120-150 pounds (54.5-68 kg) as an average adult human weight. The anthrax vaccine developers gave various groups of monkeys anthrax vaccine at various doses to see what protection it afforded before the monkeys were later infected with living anthrax.

In this small test, more monkeys survived anthrax when they had been previously immunized with half the human vaccine dose than the full human vaccine dose (100% survival vs 80% survival). Protocols were then modified so that today, all rhesus monkeys receive one-fifth the human dose. So too large a vaccine antigen dose could actually give your pet worse protection than a more refined dose calculated on the animal’s body weight. Read the article here. ( The results reminded me of an early experiment where smaller vaccine doses produced better immunity in monkeys than a larger one - in that case- to rabies vaccine. At the time, the authors theorized that the full human dose was too large for the smaller monkey's immune system to handle efficiently [ref] )

Vaccines In Development

NIH currently invests a great deal of effort looking for an effective vaccine to prevent human AIDS. One promising approach is to link antigen components of the human immunodeficiency virus to a harmless adenovirus vector – something similar to Merial’s canarypox-vectored feline leukemia vaccine. Those researchers have found that the response in mice is better when the dose is reduced by 1-3 logs versus what is used in their human volunteers (a 1 log reduction is a ten times smaller antigen mass, a 3 log reduction is 1000 times smaller amount of antigen).

What Can Ten Hamsters Tell Us ?

They can tell us two things. They can tell us if a particular batch of leptospirosis vaccine is “up to snuff” ie meets quality control regulations and they can tell us that effective leptospirosis immunizing dose should be adjusted to body weight.

You probably thought that all sorts of spectacular analytical machines were used to test the potency of your dog’s next leptospirosis vaccine – right? So did I.

Each batch of leptospirosis vaccine relies on ten hamsters being volunteered for a dangerous assignment.  Every year more than 32,000 hamsters do so. (ref)

These hamsters weigh between 50 and 90 grams. (ref) Five of the hamsters are immunized with dog leptospirosis vaccine and five are not. Fifteen to 20 days later, all hamsters are given a fatal dose of live leptospira. At lease four of the five unimmunized hamsters must die and four out of five vaccinated hamsters must live, for the vaccine batch to pass. (ref)  Now according to the common wisdom, you would think that the hamsters would receive the same vaccine antigen dose suggested for dogs. However, that is not so. The immunized hamsters receive 1/40th of
the recommended dog dose. Testing procedures for European dog leptospirosis vaccines are essentially the same. (ref)

Hamster batch-testing does not tell you if one batch of vaccine is more reactogenic than the next. For that, you would need something like a post-vaccination febrile (fever) test in dogs. 

I am not going to tell pet owners or veterinarians to scale their dog's leptospirosis vaccine doses to its body weight. Until we have hard data release (if ever)- that will be a decision that your personal veterinarian has to make. My personal opinion is that pets need just enough vaccine antigen to prime their individual lymph node memory cells – no more and no less. I hunted for weeks for an article that showed that the mass of those lymphoid cells in the body was proportional to a dog’s body weight but could find nothing one way or the other. The lymphatic system is an organ just like any other organ in your pet’s body – pancreas, liver, etc - and organ weight (mass) is generally proportional to body size. Experimenting with vaccine dose-to-body weight relationships ought to be done within the confines of a veterinary college, the CVB or a licensed vaccine manufacturer – not forced to be done by practicing veterinarians like Dr. Robb out of concern for his patient's welfare.. It is long overdue that they be done. Ask that they be done, or, if you dwell in one of those institutions, do them yourself and prove me wrong.

This morning, a paper arrived from Japan. It showed that veterinarians over there feel the same way I do and have gone much farther in doing the research that we US veterinarians, the CVB and vaccine manufacturers have neglected to do. (ref) My take on the situation is that nothing I present here is news to the dog vaccine industry. Faced with the extreme variation in the weight of our canine pets, the manufacturers and their regulators  had the choice of performing expensive trials to determine the correct (optimal) dose for various size and age dogs or produce a vaccine (by upping the antigen mass) that would protect the largest conceivable dog that would be given their product. They elected to take the second option. However, that meant that the smaller dogs would be vastly overdosed.

Is The Chance Of A Bad Reaction To A Vaccine A Simple Matter Of The Size Of The Dose and The Weight Of My Dog ?

No.

No. They are not simple dose/body weight equations (ie more dose = more reaction). They are related in a much more complicated non-linear way  and can occur over a wide range of doses. Another non-linear event is the weather. If you get up for work and find an overcast sky, you are more likely to take your umbrella because you anticipate the possibility of rain. It may rain and it may not rain – but you know the chances are greater than on a sunny day.

Well, Experts Know That Anaphylactic Reactions Are An All-Or-Nothing Event - So It Wouldn’t Make Any Difference If My Pet Got A Smaller Vaccine Dose – Right ?

That is not entirely true.

First, we do not know the true nature of post-vaccination reactions in dogs. They may be formal anaphylactic events that follow traditional explanations, or they may be anaphylactoid reactions that do not. Most likely many different types are lumped together in one bundle. 

Regarding true anaphylaxis, there is a triggering dose (a threshold dose) that will cause reactions. In very sensitive pets, it can be so low that it could be described as “any dose” But that is not - strictly speaking - correct. Some believe that the greater the dose, the more likely those events are to occur and, possibly, the more violent they will be. That aspect of anaphylaxis is rarely studies. But it was examined in regard to anaphylaxis-triggering antigens that enter through the digestive system. (ref)  The graph from that article below, clearly shows that that particular author found that the larger the dose exposure to those antigens was, the more likely an allergic event was to occur. Click on the graph to enlarge it.

Are These Vaccine Problems Or Regulatory Problems. Is Mr. Fox Guarding The Chicken Coop ?

No, the fox is not guarding the chicken coop, the CVB is, but the fox has gotten his nose inside and is doing his best to arrange the furniture to his liking.

The Center For Veterinary Biologics (CVB)

When you get a vaccination, the folks at the FDA’s (CBER) unit in White Oak, MD  look out  for your safety. (ref)  The CBER has a key professional staff of about 179 individuals. (ref) and had a yearly budget of $172 million dollars. However, your pet’s vaccines are approved and monitored by the US Department of Agriculture’s Center For Veterinary Biologics in Ames, Iowa. The CVB has a professional staff of less than 39 individuals. (ref) It’s 2013 budget was $15 million dollars. The average starting salary for an FDA/CBER employee is estimated to be $91,000. The average starting salary for a USDA/CVB employee is estimated to be $49,000.

The CVB  that approves and monitor’s your pet’s vaccines is staffed by good, honest people – just like you. But their current employment and hope of future employment can depend, in part, on staying in the good graces of vaccine companies and their lobbyists. A similar situation exists in the FDA which you can read about here.

The FDA and USDA also have different philosophies when it comes to vaccine safety. The USDA/CVB focus has traditionally been on agriculture where livestock value is a fixed, emotional attachment to a specific animal is limited and a higher degree of adverse events is more acceptable (ref)

“When somebody says it’s not about the money, it’s about the money.”
H.L. Mencken


Every fall, the powerful  lobbying group for veterinary vaccine manufacturers, the AVBC (ref) , descends on Ames, Iowa like crows during corn harvest.

It is highly unrealistic to expect the little group of Ames, Iowa midwesterners employed by the CVB, no matter how dedicated and well meaning, to protect the interests of pet owners across the Nation when faced with a  multibillion dollar industry ($5.8 billion in 2013 ) intent on maximizing profits. The CVB needs support and protection from you, the pet owner, to allow them to function without fear of retaliation and level the playing field. As things now stand, they have been reduced to somewhat of a lady’s auxiliary to the veterinary vaccine industry - much like the union auxiliaries of bygone times (ref)   They hear from plenty of lobbyists, but they don’t get many letters of thanks and encouragement from dog owners like you or photos of people's treasured pets – why not write and send them one ?

Due to its agricultural past and underpinnings, the CVB also sees its mission as sterilizing every last shedder dogs (like a herd of cows) - not protecting your specific pet from serious infection at the lowest possible risk of side effects. That can lead to vaccine potency overkill on the part of vaccine manufacturers trying to please them. What is important to you is your pet’s health – not herd health. That is the unintended consequence when one protects hot dogs and pet dogs out of the same office. (ref) The CVB, like the FDA, also get conflicting messages. On the one hand, they are told to uphold safety standards – a time consuming procedure - while on the other hand, they are told to speed up the drug approval process (ref)

Money infused into an organization by animal vaccine manufacturers and other special interests has the potential to tilt decision making. In the case of the FDA, 35% of their biological's budget came from the industries they regulate in the form of “user fees” in 2012 . The FDA readily provided that information to me in a friendly email. In the case of the CVB that regulates your pet’s vaccines, even my Freedom of Information Act requests for that information as well as the bad reaction reports regarding your pet's leptospirosis vaccines were simply ignored. That sort of behavior reinforces the perception that there are things that the CVB and the powerful companies that control them would prefer that you and I not know and that their prime concern is not your pet's well-being.

Inappropriate Selection Of Test  Dogs

The test animals, used to develop leptospirosis vaccines are too young to accurately reflect  the dynamics of the vaccine when it administered to the more mature dogs that will constitute the great majority of future patients. As an example, the MSD (aka Merck) leptospirosis vaccine marketed in Europe, Nobivac®DHPPi, was developed in beagle puppies that were 6-10 weeks old. (ref)  Very few practicing veterinarians would inject leptospirosis-containing vaccines into a puppy that young.  The immune system of a 6-10 week old puppy is too immature to be indicative of what occurs when older dogs receive the vaccination. The likelihood of reaction is worst in midyears after several yearly injections that have primed the hypersensitivity (allergic reaction) system. Besides, the threat of contracting leptospirosis at under 3 months of age is close to negligible.

At least with the strains of leptospirosis that Merck tested in Boxmeer, there is considerable room for dose adjustment – One quarter the recommended vaccine dose gave adequate protection to their beagle dogs. (ref)  

Neither the CVB nor Merial would tell me the breed, let alone the weight, of the dogs used in CVB approval testing (although the French contingency of Merial used 8-16 week old beagles to test their Eurican1L canine leptospirosis vaccine [ref])

Major Problems In The Adverse Event Reporting System

Adverse vaccine reaction reports are available for anyone to view on the FDA website. They are a bit difficult to locate and interpret, but their free availability is an enormous incentive for human vaccine manufacturers to produce safe products.  Worldwide reporting systems of that kind are what spur improvements in vaccine formulation and guide vaccination-administration schedules. (ref)

The USDA/CVB has no such program.  Due to drug company pressure, Pet owners and veterinarians are intentionally kept in the dark as to the relative safety of the different vaccines on the market.

Deceptive Vaccine Marketing Techniques

Most veterinarians (and informed pet owners) would assume that a vaccine with the name of Recombitek® 4 Lepto, marketed by Merial, would be a recombinant vaccine. The internet is full of people who have wrongly made that assumption. Recombinant vaccines are those in which genes to produce the desired bacterial antigen have been grafted into a harmless organism – like yeast. For example, that is the technology that most human hepatitis B vaccine use. (ref)

Even Merial press releases stated “Merial's RECOMBITEK® family of canine vaccines have been developed with recombinant technology” (ref)

The pleasant veterinarian I spoke to on the Merial veterinarian’s hot line would not give me a straight answer when I asked if  Recombiteck was a recombinant vaccine. But a renown veterinary school professor, kind enough to answer my email, confirmed that that is not the case.  On other points, we have disagreements - its possible to have the same skill sets and knowlege base and still reach contradictory conclusions. (ref)

Are There Factors Other Than Dose Size That Could Make My Pet More Susceptible To Vaccine Reactions ?

Most certainly so. 

Genetics, environment, nutrition and lifestyle factor into all aspects of your pet’s health and the probability of it becoming ill. Many of those factors do not give us much of a chance to control. The best we can often hope for, is to change the things we can change and hope we have lessened that probability. Read the suggestions in the last heading for some suggestions in doing that when your pet's vaccinations are concerned. Thank Dr. Jean Dodds for most of them.

Can You Propose A Way That Too Large A Dose Of Killed-antigen Vaccine Like Leptospirosis, Given To My Pet , Might Increase Its Likelihood  For Side Effects ?

The accepted institutional line is “ the cause of vaccine reactions is multifactorial (that’s doublespeak for “we know these reactions occur, but we have no idea what the cause(s) are”). “Its just a random act of nature - like being struck by lightening.”

To get beyond that required a deeper understanding of modern immunology than I possess. So I posed the question of a vaccine dose / to body weight relationship to some of the world’s leading immunologists. Many were kind enough to reply. You can read their replies here.

Reduced to the simplest of analogies, the immune process in your pet is similar to the performance of a dance troupe – a well choreographed performance between dendritic cell ladies adorned in IgE antigen costumes cavorting with their T-cell gentlemen - while memory B cells keep a record the performance to play it again  at some later date.  When excessive amounts of vaccine antigens are added, the situation can go out of control - to a point where inappropriate antibodies (class switching) and memory cells are produced in a chaotic manner. 

Rather than that fanciful explanation, you can read about the true process that occurs, as best we understand it here , here, here and here

 Anergy And Antigen Overload

Even when excessive vaccine antigen does not cause a vaccine reaction in your pet, it can have later negative consequences. Vaccine antigen given in excess of lymph node requirements can actually produce a lower, less specific immunity than antigen given in optimal amounts. Perhaps something like that was in play with the CDC's rhesus monkeys I spoke about earlier. Similar things occur when too large a dose of BCG vaccine is given to laboratory animals. (ref)   A similar phenomenon is what dermatologists take advantage of when they give you or your pet desensitization injections. They attempt to shift antibody response from Th2 to Th1 cells. Excessive vaccine antigen is also known to reduce the “affinity” (specificity) of the antibodies produced. Need ref

Are You One Of Those Anti-vaccination Guys ?

I am not at all against vaccines.  I do not believe in great conspiracies. I do not have an axe to grind with the USDA, Vaccine manufacturers or the institutional veterinary medical community. I have enough problems with them already. (ref) During my career, vaccines have been a sizable portion of my income. That income helped me raise six children and saved the lives of many pets. Antibiotics and vaccines are the two greatest health discoveries since the Rambam.   I just think that pet vaccines should be administered in accordance with current medical knowledge and that old practices need to be periodically reviewed in light of advances in our understanding of immunology.

What Can I Do To Minimize My Pet’s Risk When Its Time For His Booster Vaccinations ?

The first thing you can do is to avoid vaccinations that are unnecessary. The economics of veterinary medicine encourage over-vaccination. Recommendations are never made in a vacuum. Veterinarians are caught in an economic squeeze: AVMA policies that encourage an over-abundance of new graduates keep starting salaries low – barely enough to pay off the sizable college loans they have accrued. On line pet medication suppliers compete ruthlessly for the veterinarian’s pet medication sales. Vaccine busses cruse the Country selling their wares. Endless advertising by vaccine manufacturers bombard veterinarians every day and candy bar corporations squeeze out veterinarians less motivated by economics. Vaccine-related revenue is the easiest revenue we veterinarians earn - it subsidizes all the other services your pet depends upon. You can read about some of those pressures here. Vaccine manufacturers have no incentive to provide veterinarians or pet owners with information that would cause them to buy less of their vaccines, neither does the CVB or academic and veterinary hierarchies such as the AVMA.

Do not give multivalent (prevents more than one disease) vaccines to your pet that  containing killed antigen when individual, directed products are available. There is no beneficial effect in giving those combination vaccines and there can be detrimental effects – particularly when they contain known reactogenic ingredients such as leptospirosis antigen.

Those multiple (4-way, 5-way etc.)vaccines that contain leptospirosis as one of their ingredients  have the potential to cause immunosupression whereby less protection is given by vaccines designed to protect against multiple diseases (multivalent vaccines). (ref)    A similar negative effect of multvalent vaccines is seen in human meningococcal vaccine (ref)

It can be confusing to pet owners, some companies use the term “4-way” to describe vaccines, containing only leptospirosis but with ingredients from the four common strains (serovars) of  the organism.

Do not begin your pet’s vaccinations at too young an age. Catching these disease requires exposure. Consider just not exposing your dog to those diseases by avoiding doggy parks, grooming salons and places where dogs congregate until the pet is at least 12-14 weeks old before starting vaccinations. Not all lifestyles allow that and exceptions have to be made for pups obtained from shelters, large breeders and pet stores. Avoid obtaining you pet from the last two, consider the risk worth the good you have done when obtaining it from the first.  I know that there are conscientious people making a living breeding dogs; but there are many who are not.

Be very cautious about vaccinating pets with chronic or acute health conditions. Nothing upsets me more that a pet taken to an animal hospital for a medical problem leaving with vaccine boosters. Also be extra cautious if littermates, parents or dogs in your pet’s family tree have had vaccine reactions, hives or confirmed food and other allergies. If your dog has a vaccine reaction of any sort, write and store the information as to the type of vaccine and brand. Avoid those brands in the future and consider if the possible benefits of future vaccinations really justify the risks. In the future, there will probably be other anti-IgE options for those high-risk dogs (ref)

If you own a smaller breed, consider if a leptospirosis vaccination is really necessary. Ask the veterinarian how many confirmed cases of leptospirosis in dogs of your pet’s size and lifestyle he/she has treated. (Humans are occasionally given a special lepto vaccines too. In us, as in our dogs, lifestyle is the primary risk factor for catching it. Cubans, working in rat-infested sugar cane fields, sewage plant, fish farm workers and those with high exposure to rodent urine are among the few where the vaccine is considered worthwhile.)

Rely on the advice of a veterinarian who has spent considerably more time considering this problem than I have. You can read her suggestions here .

If you are concerned about vaccine risk and over-vaccination, do not use the services of mobile or periodically held “vaccine clinics”. They tend to be overly positive about the need for frequent vaccination and when serious vaccine reactions occur, they rarely have the specialized staff and equipment on hand to treat them.

Remember that your dog is not protected the moment it receives its vaccination, it takes up to several weeks for the full effect of vaccines to develop. In a recent study, it was 21 days after the first lepto vaccination before that the animal's antibodies began to rise and they were not at their highest until 6 weeks after their second injection. (ref) That is the fallacy of requiring things like a kennel cough vaccination the day before your dog enters a commercial boarding facility.

Less Obvious Risks

There might be other, less thought of, risks in unnecessarily exposing your pet to vaccine antigens beyond the amount that is required to safely immunize it or in administering vaccines too frequently. Those dangers might exact a toll in ways that are more subtle than the obvious vaccine reactions I wrote about.  Antigen exposure is now thought to encourage many forms of autoimmune disease. (ref) (Pet-owner response to this article and data I have obtained from the CVB make me quite concerned that leptospirosis-containing vaccines trigger autoimmune phenomena considerably more frequently than acknowleged by the pharmaceutical industry.) Antigens, and the helper chemicals they contain (adjuvants), are not all that selective in the immune processes they encourage. Occasionally, a case of mistaken identity occurs and the body immunizes itself against itself (=autoimmunity). (ref) Perhaps that is what occurred in these three dogs. But more complex ("foggy") reactions are also possible:

I mentioned earlier that antibodies produced by vaccines can be "promiscuous", that is, react with more than one perceived "invader". We know from a 2012 study that leptospirosis vaccine antigen can do that. Cattle vaccinated against leptospirosis can have false-positive reactions for another disease (brucellosis). (ref) Veterinarians do not know if similar cross-reactions occur in dogs. Leptospira is a spirochaete ; so is the lyme disease organism. How things like the in-office "Snap" tests used to diagnose lyme and other such diseases might be affected by leptospirosis vaccinations (particularly when excessive amounts of vaccine are given to small dogs) is unknown. There is also a long-held suspicion that over-administration of vaccine antigens takes a toll on the kidneys (ref)

I have an article that documents autoimmune diseases linked to vaccine adjuvants. If you email me I will send it to you.

 

 

 

Is Checking My Dog’s Leptospirosis Antibody Titer A Good Way To Decide If My Dog Needs A Booster Leptospirosis  Vaccination ?

Veterinarians are still uncertain how much your pet’s immunity to leptospirosis is linked to its antibody titer (ref) That is because of the memory cells I spoke of “sleeping” at various locations in your pet’s body. Once aroused by another exposure to leptospirosis, they can mobilize quickly to effectively defend your pet (ref) even when antibody levels are low or undetectable. There is no clearly defined protective titer for leptospirosis. (ref)  

If you managed to get this far, I have a favor to ask of you:

If you have an online presence, link to this article. If not, pass it along to your friends.

If your dog suffered a serious reaction after receiving a leptospirosis-containing vaccine, please let me know.

If your dog suffered sudden kidney damage or high BUN , Creatinine , C-reactive protein or urine myoglobin lab values, bleeding tendencies or anemia (Evans syndrome) low blood platelets (thrombocytes), a diagnosis of myelogenous leukemia or invasive mast cell tumor within the weeks following a leptospirosis-containing vaccine, I want to know about that as well. Your pet's individual genetics probably play a role in its susceptibility to these reactions. (ref1, ref2)

 

 

Click the ark if you are curious what vaccines non-domestic animals might receive