Newsworthy: Banned antibiotics found in feather meal at Johns Hopkins – How did they get there, and why does your press release contain different conclusions?

An article recently published in Environmental Science and Technology details a study conducted at Johns Hopkins where when examining samples of commercially available feather meal (used as a protein supplement feed or fertilizer) they found trace amounts of fluoroquinolones, a class of antibiotics that have been banned for use in animal feed for 6 years. This is an interesting find, and definitely warrants further research before any broad sweeping conclusions can be made. You know…unless you publish a press release condemning the entire industry for breaking the law and trying to kill us all (question, if all the chicken consumers are dead, how does that lead to higher profits?).

The article itself is very well done. The authors collected samples of feather meal from several states and Canada and tested them for various pharmaceuticals. They also autoclaved the samples to see how the heating processes involved in creation of the product affected degradation/digestion of any of the compounds, and exposed E. Coli cultures to the meal to see if the presence of one or more of the compounds was enough to select for antibiotic resistant populations (they were).

The researchers examined each of the compounds of interest and proposed mechanisms for their presence. Some of them are used at various levels legally within the industry, and the presence of many others (such as caffeine) can be explained by their introduction through various feedstuffs (such as coffee pulp and green tea powder) (Love et al., 2012).

Obviously of most interest to the researchers were the levels of fluoroquinolones, and they hesitantly proposed possible mechanisms for their introduction into feather meal.

“Fluoroquinolones (enrofloxacin, norofloxacin, or ofloxacin) were detected in 6 of 10 U.S. samples, which was not expected because fluoroquinolone use in U.S. poultry production has been banned since 2005. These findings may suggest that the ban is not being adequately enforced or that other pathways, for example, through use of commodity feed products from livestock industries not covered by the ban, may inadvertently contaminate poultry feed with fluoroquinolones…To better interpret our findings, corroborating evidence in the form of antimicrobial usage practices and dosing amounts would be needed.” (Love et al., 2012)

Clearly we’re not ruling out the possibility of these antibiotics being fed, but there is no cause and effect relationship here. They also make note that feather’s contain antibiotics in higher concentrations than meat or other tissues, even after legally defined withdrawal times to remove them from edible tissue. The conclusions here are justly cautious, and place no blame or accusations upon the industry.

The other interesting find was that the feather meal tested would select for antibiotic resistant strains of E. Coli when exposed to cultures. However, this was only testable with autoclaved samples of the meal. And did we mention that the only samples tested here were sourced from China (who according to the article use many more antibiotics than we do in poultry production)?

“These initial results suggest, but cannot prove, that the inhibiting substance may be an antibiotic/bacteriostatic. Autoclaving may have attenuated the quantity and bioavailability of antimicrobial drugs originally present.” (Love et al., 2012)

Again, a cautious observation and hardly conclusive. Comparisons were made from standard cultures exposed to low levels of relevant antibiotics to see if the same strains were removed, but this data cannot be correctly compared as the feather meal was not controlled enough to isolate those compounds. The authors finish their discussion with an appreciation for the novel information they found and an invitation for others to verify, replicate, and build upon their results.

“We have previously described risks related to administration of medicated feed to food animals, which may promote selection for antimicrobial resistance. The presence of antimicrobials in feather meal, as determined in this study, is a previously unrecognized source of these drugs in animal feed. Because this is the first study of PPCPs in feather meal, we invite independent verification of our results by others. More work is needed to determine whether the detected levels of PPCPs in feather meal have an impact on the quality of food animal products and the safety of consumers.” (Love et al., 2012)

And there we have it, an exciting new study that presents a lot of questions to be used for follow-up research. So we’ll publish it and make sure to put out a press release so that not only those keeping up with the journals can read and understand what we’re currently researching.

Well…it seems like the authors like to be scientific when submitting journal articles, but prefer big headlines and sensationalizing when trying to popularize their research. In their official press release, these researchers quickly turn from cautious scientists to industry whistleblowers.

“The discovery of certain antibiotics in feather meal strongly suggests the continued use of these drugs, despite the ban put in place in 2005 by the FDA…The public health community has long been frustrated with the unwillingness of FDA to effectively address what antibiotics are fed to food animals.” – David Love, PhD

Comments from Keeve Nachman, PhD, show a level of conviction that I had no idea he possessed in the original article.

“In recent years, we’ve seen the rate of fluoroquinolone resistance slow, but not drop…With such a ban, you would expect a decline in resistance to these drugs. The continued use of fluoroquinolones and unintended antibiotic contamination of poultry feed may help explain why high rates of fluoroquinolone-resistant Campylobacter continue to be found on commercial poultry meat products over half a decade after the ban.” (I guess we know for sure they’re still being used in the US, I must have missed that citation in your introduction)

“A high enough concentration was found in one of the samples to select for bacteria that are resistant to drugs important to treat infections in humans” (Note: the concentration comment is true, however, your study stated that there was not controlled enough testing to prove that any specific compound present caused the bacterial selection)

“We strongly believe that the FDA should monitor what drugs are going into animal feed…Based on what we’ve learned, I’m concerned that the new FDA guidance documents, which call for voluntary action from industry, will be ineffectual. By looking into feather meal, and uncovering a drug banned nearly 6 years ago, we have very little confidence that the food animal production industry can be left to regulate itself.”

Wow, this press release from the actual authors of the article must be legit, after all, they wrote it, and they wouldn’t write/act completely differently so as to both dangle a carrot to the media and still get their research published in a peer-reviewed journal right?

I knew the Colonel was lying to me. Source: kfc.com

Well, the press release did its job, and Nachman can be found interviewing left and right about how he was “floored” by the result, and how that the more he learns, “the more [he is] drawn to Organic”. There’s a severe lack of integrity here, and the misrepresentation of your data and analysis to cater to anti-big-Ag sentiments is irresponsible and unethical.

So, future scientific corespondents for the Daily Mail aside, what are some other proposed mechanisms for the presence of these banned antibiotics? After all, I’m suggesting that they aren’t being fed routinely as the authors apparently really believe. Let me rephrase that, I’m not ignoring multiple unproven mechanisms for the purpose of shock science.

I spoke with James Hermes PhD, a professor and Poultry Science Extension Specialist here at Oregon State University, about the article. He had obviously heard of it and shared with me some discussions he had had with his colleagues. Their proposed mechanism for the introduction of the pharmaceuticals was through groundwater.

“Feather meal is boiled at the rendering plant, it’s processed with a lot of water, so anything in the groundwater can end up in the meal…Just recently near [Corvallis] they did some testing and found nearly everything we use at home. For years they told us to flush our excess medications…It’s always been there, we’ve just only recently been able to look at such small concentrations 1 parts per billion, trillion, or even possibly quadrillion.” – James Hermes, PhD

So in addition to whatever chickens could be exposed to via drinking the water and concentrating pollutants in their feathers, additional water and pollutants are introduced during the rendering of the product. He encouraged me to find some research showing that ground water contains any and all of the things discovered in the feather meal, and I found it.

So is this a possible mechanism for the introduction of these contaminants? I suggest the authors of the study follow their own advice in the article and explore this mechanism. Perhaps see if the levels of the pharmaceuticals change in the feathers both prior to and after rendering/boiling, explore if they are present in organically produced feather meal, and find out if there are still large concentrations of fluoroquinolones in the groundwater of the areas processing feather meal. And hey, if they want to keep on trucking with scare tactics, I think finding this stuff in the water supply will be much more frightening to the public given that we can’t buy organic water (don’t start).

Finally, in evaluating consumer exposure to the present antibiotics in feather meal, we should keep in mind the steps necessary in the shortest route to the consumer. First, there have to be high concentrations of antibiotics in feather meal; second, that feather meal must be fed to an animal used for food, third; those antibiotics must be retained and remain active until slaughter of that animal at a high enough concentration; fourth, they have to survive gastric juices and be absorbed into the small intestine of the person eating the meat/milk. Nevermind that along the way, the authors of the relevant study note that at any point the vector for the antibiotics is heated most of them will degrade.

Obviously, if the feather meal is used as fertilizer instead of a by product feed, then there are a few more steps that need to take place to get those pollutants onto the plate.

Now if you’ll excuse me, I need to finish this compelling article on how those fat cats selling nautral almond extract are trying to murder me .

 

ResearchBlogging.org
D.C. Love, R.U. Halden, M.F. Davis, & K.E. Nachman (2012). Feather Meal: A Previously Unrecognized Route for Reentry into the Food Supply of Multiple Pharmaceuticals and Personal Care Products (PPCPs) Environmental Science and Technology, 46, 3795-3802

Kolpin, D., Furlong, E., Meyer, M., Thurman, E., Zaugg, S., Barber, L., & Buxton, H. (2002). Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999−2000: A National Reconnaissance Environmental Science & Technology, 36 (6), 1202-1211 DOI: 10.1021/es011055j

 

 

Update: following this post I had a chance to talk with one of the Authors of the article, read about our discussion here.

TPS reports stressing you out? Workplace dogs reduce stress for everyone

We’ve known for a long time that owning pets is good for us. They encourage exercise (Epping, 2011), lower blood pressure (Allen Et Al., 2002), and even reduce anxiety (Jerjes, 2007). So the question then is why wouldn’t we want to bring that to work by having dogs in the workplace?

Dogs in the workplace
Just give Luna the open desk when the intern goes back to school

This article looked at just that. In examining a large company with about 550 employees, and comparing their results to the standards of the industry, the authors found that the presence of a dog at work reduced stress for employees throughout the day. The impact was significant enough that not only did employees feel less stressed as the day progressed, but on days when the dog was absent, they experienced levels of stress above the industry standard by the end of the day.

So what are some of the potential HR concerns with having animals at work? One example would be the 20% of participants who perceived that dogs in the workplace hindered their personal productivity. Examples of employee complaints were:

“Some dogs are disruptive”

“Allergy problems for some”

“Dogs should be well behaved and quiet” (Barker, 2012)

The authors suggest that if company policy allows dogs, it should also address these reasonable concerns to maximize the benefit of the program. In this study those with concerns were actually equally matched in size with the the pro-dog population, and both were smaller than the neutral-dog population. This suggests that with the benefits conveyed, if these concerns can be addressed by policy or management of animals a dog-friendly workplace would have a net benefit for the majority of employees.

All employees reported higher scores than the industry standard for job satisfaction and communication. This communication benefit is attributed to the additional conversations between both peers and employees of different status created by the presence of the dogs. Both of these benefits are assumed to be a result of the general trend of reduced reported stress by all employees when dogs are present. Alternatively, all employees reported greater stress levels when those who normally brought their dogs to work left them at home.

Let me say that again, even those people who didn’t bring their dogs to work (or didn’t own one) were more stressed out when the dogs they were used to seeing at work were not present. This demonstrates that the benefits of pets in the workplace are not solely reaped by those who get to be with their personal pets all day.

Now this study (while cool) shouldn’t be an immediate argument for dogs in the workplace, and the results most certainly aren’t applicable to all industries. There are several limitations that the authors acknowledge and use to promote replication of the study. First, the sample size was small (76 employees), and unfortunately there was no real control. The data was compared to the reported industry standards, which make a great model, but comparing a single company against the average isn’t particularly significant to an industry. This company might just be above average regardless, and there was no way to compare the satisfaction of the employees prior to the dog policy. Finally, the authors were unable to conduct a blind study, meaning that participant bias may have been significant.

If I were to change anything in their procedure, it would be the cortisol sampling. The authors collected salivary samples from all participants every morning for the duration of the study, but did not see any trends in non-dog vs. dog present days, or in employees who brought dogs to work vs. those who left them at home. I’m surprised that they chose the morning portion of the day to collect saliva samples, as it would make much more sense to me to collect a sample at the end of the day, when the effects of the dogs’ presence or absence would have had time to affect stress and subsequently cortisol levels. Ideally, in the replication, they will collect samples twice a day, and be able to determine if the stress reported was real or perceived.

On a final note, I would be really interested to see a similar study looking at an industry where animals are naturally present, such as a shelter, veterinary clinic, or boarding facility. It would be interesting to see if the ability to bring your dog from home would convey additional benefits even when dogs or other animals would be present regardless.

ResearchBlogging.org

Allen K, Blascovich J, & Mendes WB (2002). Cardiovascular reactivity and the presence of pets, friends, and spouses: the truth about cats and dogs. Psychosomatic medicine, 64 (5), 727-39 PMID: 12271103

Randolph T. Barker, Janis S. Knisely, Sandra B. Barker, Rachel K. Cobb, & Christine M. Schubert (2012). Preliminary investigation of
employee’s dog presence on stress
and organizational perceptions International Journey of Workplace Health Management, 5 (1), 15-30

JN Epping (2011). Dog Ownership and Dog Walking to Promote Physical Activity and Health in Patients Current Sports Medicine Reports, 10 (4), 224-227

Jerjes W, Hopper C, Kumar M, Upile T, Madland G, Newman S, & Feinmann C (2007). Psychological intervention in acute dental pain: review. British dental journal, 202 (6), 337-43 PMID: 17384613

Urine protein profiles in cats with cystitis are indicative of increased epithelial damage

Cystocentesis - Image from University of Minnesota CVM

Cats and urinary problems go paw in paw, from the obstruction emergency in males, to common urolithiasis. As a cat owner, it is always important to search for a medical problem before blaming behavioral issues for “accidents” in the house. There’s a whole world of disease out there that can manifest itself as litter box trouble. This article in JAVMA discusses the protein analysis of both healthy cats and those with idiopathic cystitis, urolithiasis, or a UTI.

I’ve actually been thinking about performing a similar study now that I’m at a veterinary clinic with digital records, but do not have the control or finances to have as specific inclusion criteria as this study did (each patient that met inclusion criteria had urine cultures, bladder biopsy, and additional lab work to identify components of the urine performed). The results from this simple small study (n=60) are interpreted well and not only identify a protein present in urine correlated with idiopathic cystitis, but propose a mechanism for it’s presence. Clearly simple, specific, and thorough analysis of blood/urine chemistry have been paying off well for identifying these indicators.

The protein of interest the study found was fibronectin, a protein that plays a role in creating the extracellular matrix and adhesion, and is found in abundance around all cells. This adhesion role implies that fibronectin is crucial within epithelial tissues such as those lining the bladder and urinary tract. What’s interesting is that according to the article, while fibronectin plays large roles in wound healing, blood clot formation, and tumor invasion (Lemberger Et Al., 2011), it was not found in the same high concentrations in any of the cats in the study with conditions other than idiopathic cystitis. One would expect with any inflammation or blood present there would be the same abundance of this protein, but that was not the case. The authors proposed the mechanism that, with chronic idiopathic cystitis, there is significant fibrosis in the urinary tract which damages the epithelial walls. This damage is corrected by increased expression of the fibronectin gene so that the tight junctions between epithelial cells in the cell matrix can be repaired. Thus, with an abundance of fibronectin available to repair chronic damage in the urinary tract, some of it is released and flushed out with urine.

Further study is obviously needed with a larger sample size and more variability in cases, but if the authors’ prediction is correct, fibronectin could be an indicator of epithelial damage in other areas of the body as well. I’m not sure how exactly to go about identifying localized damage, but I am interested in the role that fibronectin could play in anticipating chronic renal failure in cats, as urine chemistry will often not yield an obvious diagnosis until loss of renal function is severe.
ResearchBlogging.orgLemberger SI, Deeg CA, Hauck SM, Amann B, Hirmer S, Hartmann K, & Dorsch R (2011). Comparison of urine protein profiles in cats without urinary tract disease and cats with idiopathic cystitis, bacterial urinary tract infection, or urolithiasis. American journal of veterinary research, 72 (10), 1407-15 PMID: 21962285

What your intoor/outdoor cat could be sharing with the local pumas

Image from Pet-peeves.org

Generally not small talk, though I imagine they might be interested in the projections for this year’s salmon run (pause for polite awkward laughter). A new article from PLoS ONE has been discussed, implying that, while direct contact may not be routine, exchange of disease between domesticated and wild cats may be fairly common.

The group of scientists involved were examining the occurrence of Toxoplasmosis, Bartonellosis, and FIV. They went out to rural Colorado and California and trapped 260 bobcats and 200 pumas to take blood samples. They also collected blood from 275 domestic cats that lived in the areas investigated, most of whom were feral and free ranging. They tested the serum of these animals for antigens that indicated infection, and ran a statistical analysis that looked at the prevalence of each disease compared to factors such as age, location, sex, and species. The data was collected over a ten year period.

I’m not going to discuss much of the wild species data, but there are some important trends for those interested in pet health, though it’s not very surprising. The researchers revealed that the prevalence of disease was much higher in domestic animals near urban areas than in those rural. This indicates that even though there is a larger number of hosts and vectors (fleas and ticks primarily) in rural areas, clearly the higher concentration of animals in urban areas and increased interactions between domestic cats and wild species (created by human expansion into undeveloped areas) plays a much larger role in the transmission of infectious diseases.

There are also some cool snippets about FIV here as well. The discussion mentions that male cats were slightly more likely to be carrying FIV, which is to be expected due to the higher rate of sex hormone driven behaviors such as roaming and fighting. The FIV strains found in the wild felids also had greater genetic diversity, suggesting that the FIV we know and vaccinate for may be a relatively new disease (at least in comparison to wild FIV serovars). The data shows that the highest combination of pathogens that the domestic cats tested positive for were FIV and Bartonellosis, and the authors mention that because Bartonellosis and FeLV infection have also been correlated in other studies, this data implies that there may be a relationship between the three. However, that relationship may be as simple as having similar risk factors.

The take home message of the study is that wild populations can serve as an important reservoir for multiple zoonotic diseases, and that exposure to this reservoir is mediated by the domestic cats we frequently come into contact with. Just one more reason to think about convincing your kitten that the outside world is scary, and that they don’t necessarily have to go check out what the big cats are doing. Feel free to check out the paper yourself, its light on jargon and easy to read. I’m actually a little disappointed to see that they collected this data over a ten year span, but chose not to do any comparison of the rates of disease from year to year. It would have been interesting to see how climate differences and population growth may have affected the number of vectors and associated risk. Additionally, because all of the samples were collected opportunistically when wild animals were trapped for other non-related studies, there was no way to ensure sampling without replacement, which may have skewed the data.

ResearchBlogging.org
Sarah N. Bevins1*, Scott Carver2, Erin E. Boydston, Lisa M. Lyren, Mat Alldredge, Kenneth A. Logan, Seth P. D. Riley, Robert N. Fisher, T. Winston Vickers, Walter Boyce, Mo Salman, Michael R. Lappin, Kevin R. Crooks, & Sue VandeWoude (2012). Three Pathogens in Sympatric Populations of Pumas, Bobcats, and Domestic Cats: Implications for Infectious Disease Transmission PLoS ONE

Ovariohysterectomy versus ovariectomy, is removal of the uterus necessary?

Ah, United States’ medicine vs. European medicine, the war rages on. The battleground I’ll discuss today: elective sterilization of the female reproductive tract.

Image from Penn State Virtual Cat Dissection

This discussion came up in JAVMA recently, and I felt it warranted a look from a future vet. Granted I don’t have all the information and education here, but given that I’ve only ever seen ovariohysterectomy performed in practice, I’m interested in why we actually choose to remove the uterus as well.

Much of the article discusses the benefits gained from the simplicity of the ovariectomy procedure. With the potential to use laproscopic techniques, smaller incisions, and less manhandling of the abdominal cavity, post surgical pain and complications can be markedly reduced in both cat and dog patients. More specifically, better exposure of the ovarian pedicle due to the incision location allows for complete excision of the ovary, suggesting that the surgeon will be less likely to leave any remaining endocrine tissue.

Outside of the surgery itself, the authors discussed the often cited benefits of spaying companion animals, and how the two techniques alter the statistics. Unfortunately, there were little to no studies directly examining the incidence of these benefits when comparing groups with or without a uterus, and some of the numbers they did find were inconclusive or conflicting. I found it interesting to see some of the actual odds concerning the prevented conditions we advertize when discussing spays, the most common being mammary and uterine tumors.

The potential for mammary tumors seems to be the most significant of the spay benefits. Their overall incidence is 3.4%, with 41-53% being malignant (DeTora, 2011). If spayed before first estrus, that risk drops to 0.5%, which is huge! Almost all of the benefits from spaying come from the removal of sex hormone cycling, which seems to be largely necessary for many of these tumors to form (not surprising, as I had previously discussed how estrogen appears to have an immune boosting effect, which would promote chronic inflammation that we know to be an important risk factor for many cancers). The authors point out that as hormone cycling is prevented solely by removal of the ovaries, that all of the future medical benefits of sterilization are gained without removal of the uterus.

The only medical benefit correlated with sterilization that is obviously tied to removal of the uterus seems to be uterine neoplasia.  However, most uterine tumors are benign, with only 0.003% being malignant as well as easily treated with hysterectomy (DeTora, 2011). The authors also found no case of uterine neoplasia ever reported in a dog that had had its ovaries removed before 2 years of age, making this benefit of ovariohysterectomy moot.

While I do think that the authors wrote this commentary with an obvious preference for ovariectomy, the assumptions they made seem rational; and even though there wasn’t enough data to declare one technique superior to the other, I agree with the conclusion that the United States’ preference for ovariohysterectomy cannot be supported by the currently available evidence. However, there is no obvious disadvantage to the procedure, and whichever technique that specific surgeon is most proficient with will probably be the best choice in any situation.

 

ResearchBlogging.orgDeTora M, & McCarthy RJ (2011). Ovariohysterectomy versus ovariectomy for elective sterilization of female dogs and cats: is removal of the uterus necessary? Journal of the American Veterinary Medical Association, 239 (11), 1409-12 PMID: 22087712

Newsworthy: Veterinarians Find Infections Faster by Monitoring Nt-pCNP

"Stinger", a dog with sepsis from a bite wound. Image from Valley Center Veterinary Clinic, Valley Center, CA.

N-terminal portion of pro C-type natriuretic peptide. Try to say that one three times fast. ScienceDaily has a cool article detailing a couple new studies showing that this peptide (Nt-pCNP) could be a solid indicator of sepsis as opposed to a generalized inflammatory response. It could potentially be added to current serum chemistry analysis, or packaged as an ELISA snap for quick, in-house diagnostics for pertinent cases.

Overuse of antibiotics has been a long term problem that is being well addressed in human medicine, however they are used much more broadly and liberally in animals due to their non-prescription access (especially in large animal work), and their use as a diagnostic tool for patients who can’t speak and often can’t afford thorough diagnostics. A veterinarian who’s client is unwilling to pay for a culture will often send broad spectrum antibiotics home anyway as a less expensive option in the hopes that they will take care of the problem.

I was unable to find a chemistry profile of Nt-pCNP, but the journal article itself talks a bit about C-type natriuretic peptide. CNP is produced by vascular endothelial cells and immune system macrophages. It “inhibits microbial growth and modifies pathogenicity of microorganisms” (DeClue, 2011). The problem with looking for just CNP as an indicator of sepsis is that it has a very short half life, and tends to degrade even faster in removed serum. Therefore, the researchers decided to use Nt-pCNP as their target molecule.  Nt-pCNP is created in a 1:1 ratio with CNP as a byproduct, and is much more durable and long-lived in both the bloodstream and collected serum.

The results of the study support the hypothesis  that CNP is a good indicator of sepsis, however like anything else, it’s not ideal. CNP was shown to be a poor indicator of sepsis when the infection was peritoneal. This includes gastrointestinal perforations or other possible infections found within the peritoneum (the authors mention that using peritoneal fluid as opposed to serum from a distal point may yield better sensitivity). Taking these false negatives into account, the test had a 65.5% sensitivity, for all other origins of sepsis in the study, sensitivity was 92%. Unfortunately, there appears to be a large potential for ambiguous negatives when peritoneal infection is suspected, but it’s always important to remember to educate clients that medicine is rarely black and white. It’s nice that House is able to identify exactly what’s wrong with each of his patients every week, but most of the time, we’re just going to give them supportive care based on the most likely result. Some of the limitations of the study that the authors mentioned were the small sample size and uncontrolled natures of the ailments that may have influenced the blood chemistry (samples taken from bacterial vs. viral infections, condition as of admission, underlying secondary infection or ailment, etc.).

In the case of this test and many other lab tests, positives are very definitive and help us out, while negatives are ambiguous. This is true whether it’s a heartworm test, fine needle aspirate, fecal flotation, radiology, or any number of other diagnostic tests. Every one is a tool, and hopefully looking at Nt-pCNP levels will give us another way to confirm sepsis while our cultures are growing at the lab, or perhaps offering another faster or less expensive option that the situation necessitates.
This post was chosen as an Editor's Selection for ResearchBlogging.org
DeClue AE, Osterbur K, Bigio A, & Sharp CR (2011). Evaluation of serum NT-pCNP as a diagnostic and prognostic biomarker for sepsis in dogs. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine, 25 (3), 453-9 PMID: 21457321

Risk factors for companion animal (cats, dogs) vaccine reactions

I’m apparently still on this immunology kick, because I seem to be finding it everywhere. Heck, I recently learned that we’ve cured the allergic response to peanuts and eggs in lab mice. Check out the link, the author is hilarious and the material is interesting.

These two articles offer a great look at the overall prevalence and risk factors associated with vaccine-associated adverse events. The components within the vaccine that cause these events are the antigen itself, adjuvants, preservatives, stabilizers, and residues from the tissue culture used to grow the vaccine (Moore, 2005). Vaccine reactions are similar to any acute allergic reaction, and can present with a variety of mild to severe symptoms. The mild being lethargy, anorexia, fever, edema (generalized or local to the injection site), pruitis, uticaria (hives or wheals), and pain at the injection site; the severe being vomiting, dyspnea (labored or shortness of breath), and anaphylaxis. There’s a lot of information about when certain symptoms tended to occur at intervals after the vaccines were given, but any reaction that isn’t within the first 3 days is pretty much never going to be life threatening. If anaphylaxis is going to occur, it’s going to be immediately following vaccination.

The really useful information was the breakdown of risk factors that can be used for client communication. I’ve decided to discuss them here, broken down into cat and dog categories.

Image from meow-cats.com

First, let’s start with cats. I almost like these numbers more because you don’t have to take into account bias based on animal or breed size, as most cats fall into the <20 lbs category. Nonetheless you still have to remember that a 4 pound kitten does way only a fraction of that 5 year old chubby (BCS >5 on a 9 point scale) longhair it will grow to be.

So the first two risk factors require a little bit of thinking in context to explain the numbers. It seems that cats weighing 2-4 Kg (4.4-8.8 lbs) and approximately one year of age are most at risk compared to other weights and ages. The high numbers for these groups can be explained by the number of first encounter events that occur. If you’re recording vaccine reactions, you will record less in older age groups and higher weights (low weight under 10 lbs is going to be suggestive of a young age rather than a smaller cat), because if an adverse event occurred at a young age, either the animal is no longer vaccinated or steps are taken to reduce its risk (medication, strict scheduling, vaccine selection). That being said, just because the numbers are higher by circumstance, this information is very relevant in a clinical setting. Knowing the epidemiology of these events can help technicians at clinics determine when the discussion of vaccine reactions is “routine” or “protocol”, or when it really needs to be a time to educate the client. Vaccine reactions may need to be just a bullet point when Schrodinger is there for his 4th rabies booster and a discussion when he’s receiving his kitten series.

Sex and neuter status have a large impact on reaction risk as well. Intact males actually have a lower risk of adverse events than neutered males and spayed and intact females. Apparently, estrogen has an immune boosting effect, while testosterone has an immune suppressing effect. This benefits intact males when it comes to all allergic reactions (and possibly auto-immune disorders).

Here’s the big one, and the one clinics have the most control over. With each additional vaccine given in a single visit, the risk of an adverse event increases by 28% in cats. That’s huge. Any cases of severe anaphylaxis or death recorded in the study were preceded by the animals receiving 3 or more vaccines in one visit. So clearly the biggest thing any clinic can do to prevent adverse events (or at least severe ones) is to adopt a vaccination schedule that prevents multiple vaccinations from occurring within the same visit. This can be difficult as clients will not want to end up paying for multiple exams throughout the year, but with boosters outside of rabies, exams shouldn’t be necessary unless an annual or other scheduled exam is due. As far as specific vaccines being more prone to adverse events, the only suggestive evidence was when both FVRCP and FeLV were given within the same visit. This is explained by both having two concurrent vaccinations given, and also the theory that vaccines containing multiple antigens or covering multiple serovars (multivalent) are more likely to illicit reactions. Interestingly, while clients are often scared by the potential for vaccine caused neoplasia from the rabies vaccine, it was among the lowest reaction rates observed with the administration of a single vaccine.

Image from peteducation.com

Dogs had much more biased data within the age and breed groups because there is an obvious relationship between body mass and the potential for reaction. When looking at the dog population, a chihuahua can be as little as 6% of the weight of a bullmastiff, yet they receive the same 1ml dose of vaccine. This means that an 8 lb Chihuahua is going to receive proportionally 15 times more vaccine than a 120 lb bullmastiff. Not surprisingly, this causes a bit of inflation in the number of reactions in groups that are smaller in size, such as toy breeds and puppies. The highest risk group in size was 0-10Kg (0-22lbs) and the highest risk age was approximately 2 years of age (with higher rates for <2 than the rates of >2).

Just like I mentioned before when talking about cats, the greatest risk factor for reactions in dogs was the amount of vaccines given in one visit. The difference though, is how the large weight distribution in dogs makes this even more important. Small dogs (<10Kg) are similar to cats in that their risk increases by 24% with every additional vaccine administered that visit, while large  dogs (10-45Kg) increase their risk by 12 percent. All 3 dogs in the study that suffered fatal reactions received 4 or more vaccines at once.

Breed dispositions were difficult to pinpoint, as the suspected breeds are all small breeds which suffer a higher rate of reaction already due to their size. There is suspicion that dachshunds may be predisposed to allergic reactions in general, but so far the evidence is inconclusive concerning vaccines. Only the Lyme vaccine appeared to carry a higher risk than any other, showing again that, with the exception of neoplasia concerns, rabies does not carry with it any additional risk. Spayed and neutered animals, as in cats, are more susceptible to reactions; however the difference between intact and spayed females is much larger in dogs than in cats (where they are nearly identical). Dogs do seem to display an interesting trend where vaccine reactions are more likely to occur on the 3rd booster in a series, likely catching clinicians and clients off guard as they have received the first two without incident. This just states again that the puppy and kitten periods (and new patients) are of much more relevance when discussing vaccine reactions with clients.

The articles are both great, and contain an excellent statistical analysis of millions of animals. They provide a great overall picture of the epidemiology of vaccine-associated adverse events, and are definitely worth a read for both veterinary doctors and staff. Knowing a couple of the more important statistics can reassure the client and lend credibility to technicians that are responsible for discussing these issues.

ResearchBlogging.orgMoore, G., DeSantis-Kerr, A., Guptill, L., Glickman, N., Lewis, H., & Glickman, L. (2007). Adverse events after vaccine administration in cats: 2,560 cases (2002–2005) Journal of the American Veterinary Medical Association, 231 (1), 94-100 DOI: 10.2460/javma.231.1.94

Moore GE, Guptill LF, Ward MP, Glickman NW, Faunt KK, Lewis HB, & Glickman LT (2005). Adverse events diagnosed within three days of vaccine administration in dogs. Journal of the American Veterinary Medical Association, 227 (7), 1102-8 PMID: 16220670

Article review: Effects of early pregnancy diagnosis by palpation per rectum on pregnancy loss in dairy cattle

Image from UPenn

Just a short one here today. Not too much interesting going on in a study that supports the null, but the methods are great.
This study looked at the affect that one or two rectal palpations to determine pregnancy had on embryo viability. I can see why there would be a question, it seems like a highly invasive procedure when you’re shoulder deep in cow rectum and feeling for an amnion several layers of membranes away. But we tend to anthropomorphize, and many dairy cattle require minimal restraint for the procedure. Nonetheless, it does seem likely that there could be a negative effect on the embryo, especially when rupturing or crushing the amnion via rectal palpation has been a historical method of terminating an unwanted pregnancy in cows (before we started using PGF2α) (Romano, 2011).
The study did a great job of identifying factors that have created conflicting results in the past. Whether that was sampling bias, uncontrolled treatments (multiple people and techniques for palpation), or a lack of a true control. They took the time to show how each one of those shortcomings was corrected in this study, and I think they did a great job designing the experiment.
In the end it was surprising to see that there was no difference between the cows subjected to rectal palpation once or twice compared to the control. I didn’t expect to see a significant difference, but potentially a small one. The authors did warn that because this experiment was so controlled, the results may not be similar to every situation. Inexperienced personnel or different techniques could change the pregnancy rates in practice (the study employed a single veterinarian with >25 years experience). One difference they took time to note was the much lower pregnancy rate in dairy cows as opposed to primiparous heifers. The exact etiology of this is unknown, but is commonly found in dairy. The authors mention it as it played a role in their analysis of the two farms involved (other factors affecting rates between the farms were geographic area, rate of twinning, and breed of cattle).

Not especially exciting, but it’s always great seeing researchers identify a conflicted area and tackle it with strict methods/controls and a large sample size.

ResearchBlogging.orgRomano JE, Thompson JA, Kraemer DC, Westhusin ME, Tomaszweski MA, & Forrest DW (2011). Effects of early pregnancy diagnosis by palpation per rectum on pregnancy loss in dairy cattle. Journal of the American Veterinary Medical Association, 239 (5), 668-73 PMID: 21879969

Article review: Mechanisms of Viral Emergence

It’s funny how reading these articles is incredibly relieving for me. They confirm that I actually did learn and do remember principals and details from my classes. Today’s article comes from Veterinary Research, and discusses the mechanisms and variables involved in the emergence of a virus.

A viral emergence is generally defined as the appearance of a new pathogen for a host, such as human immunodeficiency virus (HIV)-1 for humans in the twentieth century. Viral re-emergence often refers to the reappearance of a viral pathogen after a period of absence, such as the periodic human influenza epidemics or pandemics.” (Domingo, 2010)

There’s a huge amount of information on viral evolution and mutation, a concept that (like everything else you haven’t specifically studied) I had greatly oversimplified. It was incredibly fascinating to read how viruses can recombine and splice gene segments from other unrelated infections, and the various pathways new genes can be created or introduced that allow viruses to jump host species. I’m not going to try to summarize all of those, the article explains them much better than I could, but there’s still a few broad topics in the paper worth discussing.

The concept of viral quasispecies is something I’ve never heard about. I’ve discussed viral serovars on here before, but I believe that term specifically refers to antigen variation. Quasispecies refers to groups of virus that are labeled and operate as one species (for example, Influenza H1N1) but contain different genomes. For example, if I get the flu this winter, the virus I am exposed to may contain several quasispecies, that are the same virus, but contain different genes. Now any deleterious mutations or reassortments will probably be wiped out by my immune system, but the ones with a fitness advantage will reproduce and take over. Here’s the extra interesting part, even if I had been infected with just one quasispecies, I could still shed several while I’m infected. There is so much mutation and variation in viral reproduction that I would be generating new ones as a single host.

Quasispecies are important in emergence because they are a major source of viral evolution. We identify the “wild type” gene amongst quasispecies as a distribution of genes that characterize that viral species (consensus gene); even though amongst different quasispecies they may be found in different places in the genome. This is where the existence of quasispecies propels viral evolution forward. When you mix up the genome so much, you can create mutations that change nothing in the functional portions of the genome, but create subpopulations that are fine tuned to conditions that may not yet be occurring. As an example, it’s been assumed that SARS was introduced to humans through Civet cats, when it was originally a virus transmitted by bats. Contact with civets is common in areas surrounding SARS outbreaks (where they are raised for food), where contact with bats is much less common. It is possible that there was a quasispecies subpopulation of SARS carrying a mutation allowing it to jump species to humans long before it was even introduced to civets. When the disease was contained to bats, this mutation has no fitness advantage, but it can sit idle until a change in the environment (higher infection rates in civets, civets brought from more rural areas, there are unlimited possibilities) gives it an advantage. This essentially allows virus to be proactive in its evolution. Instead of waiting for selective pressure, new genes are created spontaneously in the event that they may become useful.

Civet, image from healthjockey.com

The article continued to discuss different factors in emergence, primarily focusing on new host emergence, and brought it all together as an example of biological complexity. My personal favorite example for biological complexity is the realization that we’ll probably never fully understand the complete pharmacology associated with feelings of hunger and satiety. Alternatively you can illustrate this principal by asking someone to model the weather. The idea is that there are so many variables, all interdependent on each other, that it is pretty much impossible to trace all of the factors that led to an event such as the host change SARS made from civets to humans. They illustrate this by showing that even if viral variation is sufficient to promote a host change, there are numerous other roadblocks that have to be surmounted to allow it to take place (interaction with the new host, sufficient amounts of virus introduced to the system of the new host, fitness of the mutated virus, exposure to multiple quasispecies or serovars, future shedding of virus adapted to that host species, etc.). It’s a paradoxal idea, because we have been able to successfully model systems like these through the CDC and WHO, and we have been able to successfully model complex systems like the weather, even when there are countless interactions that we can’t even begin to measure.

Read this article if you have any interest in virology at all. I learned a lot, and it’s interesting and fluid reading if you have a basic understanding of cell biology.

ResearchBlogging.orgDomingo, E. (2010). Mechanisms of viral emergence Veterinary Research, 41 (6) DOI: 10.1051/vetres/2010010

Article Review: Epidemiology of Surgical Castration in the United States

I recently had a professor tell me that if I didn’t let them know if I made it into vet school, they would forever curse me with fat, in heat, Labrador spays for the rest of my career. I can think of few fates worse for a future veterinarian (though I did mention that the owners also had to have  no way to pay, and will forget to mention this until after the procedure). Today’s article is really cool and discusses the prevalence of ovariohysterectomy and orchiectomy (spaying and neutering, fixing, castration, gonad removal,de-nutting, whatever you prefer to call it) in the USA. It breaks the percentages down into region, animal species, animal breed, animal age, and enrollment in wellness plan from Banfield (animal health insurance).

Banfield Pet Hospital is an amazing organization for animal research because all of their records are computerized and kept in a central database (I should mention that the man who made Banfield what it is today is an OSU alum, go beavs). Because of this treasure trove of data, this study was able to get a sample size of over 300,000 cats and over one million dogs. While this represents less than 1% of the US pet population, its still a valuable amount of data, and we can reasonably assume that Banfield has a decent representation of the rest of the pet population that regularly visits private clinics. The article mentions that one of the only large differences is the mean age at clinics (Banfield’s is slightly lower). The numbers found in this study also line up well with previous examinations using distributed surveys to collect data.

I’m very proud to say that the Northwest region (making up Washington, Oregon, Idaho, and Montana) has the highest percentage of castrated cats and dogs compared to any other region (tied with the North Central region for percentage of dogs) according to the study. The region with the lowest percentage was the Southeast region (making up Alabama, Florida, Georgia, Mississippi, North Carolina, South Carolina, and Tennessee). That’s an area of the country I haven’t ever visited, so I can’t comment on cultural factors that may influence the decision to castrate pets, but clearly more outreach could be focused on that area.

The breed distribution is interesting, but doesn’t offer too much information for most breeds. In my own head I see the Labs’ and Retrievers’ high numbers understandable, as you can in some ways consider them “white-collar” or suburban dogs. This would be associated with a higher income and thus one less roadblock to castration. Pit Bulls can maybe be considered a “blue-collar” dog, but that can’t be the only reason their numbers are so low. I’m actually at a loss as to why the castration rate of Pit Bulls is so much drastically lower than all the others. It’s an obvious outlier. I myself love Pits and believe that in the right hands they make great dogs. But considering their stigma, low rate of adoption (and consequently high euthanasia rate), insurance liability, and higher risk, I do believe we should make castrating Pits a priority. I’ll definitely be looking for more literature that attempts to explain the demographics and other factors that create this problem. The second lowest group, Chihuahuas, is also interesting. Again, I’m not sure why the numbers for this breed are so low, but one factor may be that many Chihuahua’s are kept as indoor-only dogs, and that may reduce the motivation to perform the procedure, as the largest benefit is wasted on them (as seen by those owners).

I’m not surprised to see that mixed animals were more likely to be castrated, and I really have no problem with that. There aren’t too many unwanted animals that come from intentional breeding, and purebred animals generally don’t have trouble finding homes (pending behavioral issues). Responsible breeding doesn’t contribute to the pet overpopulation problem significantly, and leaving that option open to purebred owners is acceptable. With cats on the other hand, I’m happy to see the extremely high rate of castration. Cats are allowed to roam unsupervised much more than dogs, and we have enough trouble controlling the feral population without accidental pregnancies also occurring in animals that could have been easily castrated.

One rather frightening statistic was the percentage of dogs and cats from shelters that do not return for castration. This concerns me as in many cases the cost is free or subsidized to less than $50. In a private clinic you can pay upwards of $200, but this seems to be little incentive as 40-60% of animals are returned for the procedure when it is already paid for. To me, this is indicative that some of those owners will provide a low level of veterinary care for the lifetime of that animal, when they already haven’t taken advantage of a free procedure. This is pure conjecture however, and there could be a host of reasons that owners do not return. However, because the rate is so low, I would bet that there is some significant factor that is relatively consistent among owners who adopt from shelters, whether that be income (shelter’s are a very inexpensive option to get a purebred-looking dog) or attitude.

All in all, a good look at where castration is common, and where education and improvement needs to be made.  I do think that many PSA’s, advertizements, and advocacy campaigns are too often directed at groups that are already in agreement. Even looking the statistics from a PSA I made back in high school show that the primary people concerned with animal welfare are women over 35, and it’s clear that similar announcements are marketed at that group. New campaigns should focus on a new approach to educate people why castration is important, and maybe spend less time showing us pictures of sad puppies. Tell me why I personally should do it, because until it’s too late to change anything, there’s no reason I should think I’m part of the problem.

ResearchBlogging.orgTrevejo R, Yang M, & Lund EM (2011). Epidemiology of surgical castration of dogs and cats in the United States. Journal of the American Veterinary Medical Association, 238 (7), 898-904 PMID: 21453178