Cry me a river...crackdown on Angels' Eyes

Finally.

While having nothing to do with my previous rants on the topic, the FDA has issued warning letters to the manufacturers of Angels' Eyes and similar products that are vaguely disguised antibiotics sold for purely cosmetic reasons, and without a veterinary prescription. These products have been widely available to decrease tear staining (hardly a life-threatening problem) in dogs, fully at odds with any concepts of prudent antibiotic use.

Here’s some of the FDA letter text:

We have determined that your tear stain remover products containing tylosin tartrate are intended for use in the mitigation, treatment, or prevention of disease in animals, and/or to affect the structure or function of the body of animals, which makes them drugs under section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) [21 U.S.C. § 321(g)(1)]. Statements on your labeling, including your website and product labels, that establish these intended uses of your products include, but are not limited to, the following:

• "The active ingredient in Angels' Eyes®, Tylosin as Tartrate, will prevent your dog from contracting Ptyrosporin (Red Yeast) and bacterial infections which causes excess tearing and staining."

• "May help keep tear stains away by reducing oxidation released through tear ducts."

• "Angels' Eyes® is the first product specifically developed for BOTH DOGS & CATS to help eliminate unsightly tear stains from the inside out!"

• "Only ANGELS' EYES® helps give your pets tear stain free eyes and bright coats."

In addition, your tear stain remover products containing tylosin tartrate are new animal drugs, as defined by section 201(v) of the FD&C Act, [21 U.S.C. § 321(v)], because they are not generally recognized among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling. You are using Tylovet Soluble (tylosin tartrate) as an ingredient in the formulation of your product. Although Tylovet Soluble
is an approved drug, your use of Tylovet Soluble in your product is not a use covered by its approved application, and your products are not the subject of an approved new animal drug application, conditionally approved new animal drug application, or index listing under sections 512, 571, and 572 of the FD&C Act [21 U.S.C. §§ 360b, 360ccc, and 360ccc-1]. Therefore, the products are unsafe within the meaning of section 512(a) of the FD&C Act, [21 U.S.C. § 360b(a)], and adulterated under section 501(a)(5) of the FD&C Act [21 U.S.C. § 351(a)(5)]. Introduction of an adulterated drug into interstate commerce is prohibited under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].

We acknowledge the receipt of three written responses submitted after the inspection in December 2013. These responses discuss your facility's compliance with the Current Good Manufacturing Practices for Finished Pharmaceuticals (Title 21 Code of Federal Regulations Part 211 ). However, your responses do not adequately address our concerns regarding the approval status of your products and your use of tylosin tartrate in those products, as discussed above.

Failure to promptly correct the violations specified above may result in enforcement action without further notice. Enforcement action may include seizure of violative products and/or injunction against the manufacturers and distributors of violative products. “

Interestingly, there’s no mention of anything on the Angels' Eyes website. It will be interesting to see what happens, but it’s great to see some attention paid to this completely illogical use of antibiotics. Hopefully the FDA follows through with this and doesn’t leave it at the warning letter stage.

How to fix an iPad

Sorry… nothing to do with zoonotic diseases, but still entertaining. Our two iPads stopped working over one weekend last October. Figuring they were destined for recycling, I came across some internet posts that said “whack it.” I figured that I had nothing to lose and if nothing else, I’d get the satisfaction of beating on an Apple product. However, it worked. They came back to life with some pretty solid impacts (my knee was sore after) and have needed periodic "re-treatments" since. Lately, one has required a pretty solid thrashing with a rubber mallet, as can be seen in the video.

Casual cat causality

The credit (or blame) for the alliteration goes to colleague and frequent blog material supplier Dr. Stephen Page. It relates to an article in the prestigious medical journal Lancet (Kagihara et al. 2014) entitled “A fatal pasteurella empyema.”

The article describes the case of a 60-year-old man from Honolulu who was admitted to hospital in cardiac arrest. He had various health problems and had had a cough and body aches over the past four weeks, then suddenly deteriorated. He was resuscitated and fluid was found in his chest cavity. When they collected a sample of the fluid, it was full of bacteria that were subsequently identified as Pasteurella multocida. Unfortunately, he died shortly after admission.

Pasteurella multocida is a bacterium that can be found in many animal species but is classically associated with cats. It can be found in most (if not all) healthy cats, as well as in large percentages of other species such as dogs and rabbits. It’s an uncommon cause of infection in people, and is most often linked to cat bites or contact of cats with wounds or other breaks in body barriers. However, it can also be carried by people, and cats are certainly not the only source.

Here, the patient cared for several feral cats and they often slept in his bed (which to me, would make them more pets than feral cats, but that’s beside the point). The authors don’t specifically blame the cats, but it’s inferred. However, there was no investigation (for logical reasons, since it wouldn’t change anything).

Was the cat the source?

Probably, but not certainly.

Further, why the infection developed is a bigger, more interesting and more relevant question, since just being in the vicinity with a cat doesn’t mean you’re going to get an infection.

I often get asked about testing cats for Pasteurella multocida. My somewhat flippant (but still accurate) response is “Here’s the test: Does it look like a cat? If so, it’s carrying Pasteurella.” Cheap and highly accurate.

Seriously, though, it’s true. Most cats carry the bacterium so there’s no indication to test for it. If people are worried about Pasteurella infections (which is really uncalled for, since there are many greater risks in life), they should focus on good hygiene practices, bite avoidance and bite/scratch first aid, not determining whether their cat is carrying the bacterium.

Vet clinic infections...who should pay?

The following question was posed to Dr. Patty Khuly in an article she writes for the Miami Herald.

"Our cats had to go to the vet hospital last week to have their teeth cleaned. The procedures went very well and, as predicted, both were back to normal that evening. Unfortunately, two days later they both started sneezing. First Patches and then Stumpy came down with the exact same cold. Patches got better but we had to take Stumpy back to the hospital. We actually had to pay more for his cold than for the teeth cleaning! Shouldn’t the vet have gone easy on us since our cats live safely indoors and they obviously caught the cold there?"

Dr. Khuly provides a good answer that you can find here.

Here’s my take on the subject:

There are two main questions.

1) Did the cats likely get an infection at the clinic?

  • That’s hard to say. Often, it’s straightforward. In a case like this, not so much. It’s possible the cats picked up a respiratory virus in the clinic from another cat that was sick, or from a healthy carrier. However, it’s also possible (and maybe more likely) that the cats had a recurrence of an underlying infection (or one did, then spread it to the other in the household).
  • Feline herpesvirus is a common cause of upper respiratory tract disease in cats, and a large percentage of cats are infected when they are young. Herpesviruses often live dormant in the body after infections and can reactivate at any point, causing disease. Cold sores in people are caused by a human herpesvirus, and they behave this way too. Stress is a major cause of re-activation, and the stress of hospitalization, anesthesia and the procedure could easily have lead to recrudescence of herpevirus infection in these cats.

2) Did the clinic provide the required standard of care to reduce the risk of hospital-associated infection?

  • Even if the cats acquired an infection at the clinic, it’s not necessarily the clinic’s ‘fault’, particularly if the infection came from a healthy cat that was shedding a virus, unbeknownst to anyone who would look at it. Infection is an inherent risk of hospitalization, and clinics have a duty to take reasonable measures to reduce the risk of disease transmission. That’s a bit of a moving target and it’s pretty subjective, but it’s a key point here. If the cat got the infection in the clinic, was it likely because of inadequate practices, such as failure to isolate a cat with respiratory tract disease, poor hygiene practices (e.g. poor handwashing), failure to use routine infection control measures (e.g. use of protective outerwear like a lab coat) and various other basic infection control concepts? If so, then the clinic’s liable (and should pay for the infection). If not, then it’s an unfortunate event but one that’s no one’s fault.
  • We can’t prevent all infections, but we have a duty to try to prevent as many infections as possible. If the clinic had a reasonable infection control program, had this documented, and followed their policies, they’re unlikely to be liable. Beyond providing optimal patient care, this is why vet clinics need to improve infection control practices. Too often, infection control programs are very informal, undocumented and weak, creating risks to patients and staff, and creating liability risks for the clinic. It leaves the door open for someone to claim that a hospital-acquired infection occurred, and makes it hard for the clinic to convince anyone that the infection was non-preventable.

So, was it the clinic’s fault? I don’t know, and it’s hard to prove. It probably wasn’t, but only with a good infection control program could they state with confidence that they did their best to the prevent infection.

EEE alert, Ontario

The Ontario Ministry of Agriculture Food and Rural Affairs (OMAFRA) has issued an Equine Health Advisory in response to diagnosis of Eastern Equine Encephalitis (EEE) in a horse in Stormont/Dundas/Glengarry, in eastern Ontario. The 12-year-old gelding died, which is the typically outcome with this disease in horses.

EEE is a devastating but fortunately rare (at least in Ontario) disease of horses, people and an assortment of other species (including emus, llamas and alpacas). Typically, a few equine cases are identified in Ontario every year, with human cases being rarer. However, since people and horses are infected in the same way - by the bite of an infected mosquito - finding the disease in a horse indicates risk to both horses and humans in the region.

More information about EEE cases in North America can be found at WormsAndGermsMap.  Information for horse owners in Ontario, as well as Ontario-only equine neurological disease cases, can be found on the OMAFRA website.

FDA releases 2011 antimicrobial resistance data

The US Food and Drug Administration has released the 2011 NARMS (National Antimicrobial Resistances Monitoring System) executive report. It's a good-news/bad-news outcome, which may be as good as can be expected, but at least there's some good news.

Here are some areas that were highlighted by the FDA.

  • Eighty-five percent of non-typhoidal Salmonella collected from humans had no resistance to any of the antibiotics tested.
  • In people, the five-drug resistance pattern “ACSSuT” (resistance to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline) in Salmonella Typhimurium has declined to 19.5% in 2011, from its peak in 1997 at 35.1%.
  • During its 16-year history, NARMS has found Salmonella resistance to ciprofloxacin, one of the most common antibiotics to treat Salmonella infections in humans, to be very low (less than 0.5% in humans, less than 3% in retail meat, and less than 1% in animals at slaughter).
  • Multi-drug resistance in Salmonella from humans, slaughtered chickens and slaughtered swine was the lowest since NARMS testing began. However, multi-drug resistance in Salmonella from retail poultry meats generally increased, with slight fluctuations.
  • Erythromycin resistance in Campylobacter jejuni (C. jejuni) has remained at less than 4% in isolates obtained from humans, retail chicken and slaughtered chicken since testing began. The antibiotic erythromycin is the drug of choice for treating Campylobacter infections, more than 90% of which are caused by C. jejuni.
  • Campylobacter resistance to ciprofloxacin has increased slightly in isolates from humans since 2005. Ciprofloxacin is not approved for use in poultry, and the FDA withdrew approval for the use of enrofloxacin in poultry in 2005. Ciprofloxacin and enrofloxacin are both in the same class of drugs (fluoroquinolones).
  • Resistance to third-generation cephalosporins, another important drug class for the treatment of Salmonella infections, rose among isolates from retail ground turkey between 2008 and 2011, and among certain Salmonella serotypes in cattle between 2009 and 2011. In April 2012, FDA prohibited certain uses of cephalosporin drugs in cattle, swine, chickens, and turkeys. NARMS will continue to monitor these trends over time.

(click image for source)

Exotic animals in hospitals

What zoonotic microorganisms do pangolins commonly carry?

Are some pangolins higher risk than others?

What infection control measures should be used?

I don’t know, and from a cursory review of the literature, I don’t think anyone really knows.

So, do we really want to be exposing them to some of our most susceptible individuals - kids who are patients in children's hospitals?

CBSnews.com posted an article earlier this year about exotic animals and hospitals (something that would be contrary to international pet therapy program guidelines published in the American Journal of Infection Control, and various other policies). The cover picture is of a child, presumably quite immunocompromised, touching a pangolin. She’s wearing a mask and gloves, but it looks like she’s also wearing her pajamas (which she is touching with her glove, that maybe just touched the animal).

In reality, the title and pictures don’t have a lot to do with the actual article. It focuses on a great initiative by a group of zoos to create videos about animals and animal care, and to make a TV network that will be provided to children’s hospitals across the US. That sounds like a great idea. The pictures of exotic animals in hospitals are not-so-great.

Pet therapy’s a wonderful thing. I work with pet therapy programs and have been involved in a few initiatives to produce guidelines to make these programs as safe and effective as possible. Part of that involves knowing what you’re dealing with.

Yes, pangolins (sometimes referred to as "walking artichokes") are cool looking critters. I’m sure the kids get a kick out of seeing them. But, is there any additional benefit beyond what the children would get from interacting with a well trained dog? Beyond the cool factor, there’s not a lot of personal connection with a pangolin, I suspect. A happy, friendly dog might actually provide a greater benefit, and since we know a lot about dogs, we are able to manage the risks much more effectively.

The zoo TV initiative sounds great.

Well-run pet therapy programs are similarly great.

Bringing pangolins and other exotic animals into hospitals… not so much.

Photo: Tree pangolin (Manis tricuspis) in central Democratic Republic of the Congo (credit: Valerius Tygart)(click image for source)

Monkey bites and rabies quarantine

"A monkey was placed under a six-month quarantine on Tuesday after it reportedly bit a woman at a Beaumont restaurant on Sunday..."

Oh, where to start...

  1. Why do people feel the need to have monkeys as pets? I realize that they’re fascinating critters, but is it in the best interests of the monkey and the public? (Generally no...)
  2. Why is a pet monkey in a restaurant? Actually, here, it was three monkeys. I have fewer issues with dogs in restaurants since a well trained dog would just sit quietly on the floor. I doubt that the average monkey is going to do the same. Add two more monkeys to the mix and there's not a chance. In this case, problems started when one of the monkeys took off and ran under a parked car.
  3. Why does a monkey that’s allowed out in public bite? I know that extreme circumstances occur and that you can’t 100% guarantee that bites won’t happen, but monkeys tend to bite more than the average pet. That’s just the way they are. As such, why are they out in public? In this case, after one of the monkeys took off, they were retrieved by another person, who was ultimately bitten when she returned to the runaway monkey to her owner.
  4. Why a six month quarantine? Someone definitely dropped the ball here. After an animal bites, there’s supposed to be a quarantine period to give the animal time to develop signs of rabies if it was indeed able to transmit rabies at the time of the bite. That takes a matter of days. A 10 day quarantine or observation period is the standard approach for dogs, cats and ferrets (since we know more about how rabies progresses in those species). For other species, where less is known, the default response on paper is often euthanasia and immediate testing for rabies, but in practice, a 10-30 day observation period is usually applied. California (where this incident occurred) guidelines are consistent with this and state “While isolation of biting animals other than dogs, cats, and ferrets is not recommended for the reasons given above, local health officers have the prerogative to forego euthanasia and testing in rare special circumstances. If the biting animal has a comprehensive and reliable history that precludes opportunity for exposure to rabies virus, and the risk of rabies in the biting animal is judged by the health officer to be acceptably low, the health officer may institute a prolonged (30-day) isolation of the biting animal."

Like many other aspects of this situation, a six month quarantine just doesn’t make sense.  In contrast, if the monkey had been bitten by a potentially rabid animal (for example, a bat), then it would require a six month quarantine to ensure it had not become infected by being bitten.  The difference between the two kinds of quarantine periods is frequently misunderstood.

Image: A 19th-century organ grinder and his capuchin monkey (click image for source)

St. Louis encephalitis in a horse

Hopefully we can chalk this one up on the "weird and not-so-wonderful" list, and not have it emerge as a significant problem. However, there’s something new to pay attention to as St. Louis Encephalitis virus (SLEV) infection was recently identified in a Brazilian horse with neurological clinical signs.

SLEV is a Flavivirus and a relative of some other important viruses such as West Nile virus and Dengue virus. Like its relatives, SLEV is transmitted by mosquitoes.

In a recent paper (Rosa et al. 2013), SLEV was found in the brain of a horse from Minas Gerais, Brazil that had died of neurological disease. Fairly extensive testing was performed to rule out other causes, so the presence of the virus in the brain and the absence of other potential causes is quite suggestive that SLEV was the problem here. It’s an interesting finding because while this virus is widespread in North and South America, from Canada to Argentina, it rarely causes disease in mammals. It circulates between birds via mosquitoes and occasionally spills over into mammals, which are considered "accidental" and "dead end" hosts since they are not part of the virus's normal transmission cycle and once infected, they can’t pass the virus on to anyone/anything else. Most infections are reported in people and they tend to be mild, although serious neurological disease can occur, especially in elderly individuals.

So, this would be the first confirmed report of SLEV-associated disease in a horse. The signs of disease were pretty non-specific and included depression, incoordination and paralysis of the hind limbs. That’s something we can see with a few different neurological diseases in horses, including the much more common EHV-1 encephalomyelopathy (and in Ontario and other parts of North America, West Nile virus).

The infection was diagnosed in a horse that died in 2009 after 72 hours of neurological disease. That’s a long time from disease to diagnosis, but in this case it’s probably also a good sign. No other horses on the farm were affected at the time, and no one has reported changes in neurological disease patterns in the area (or beyond) since then; therefore, this presumably was not the start of a large, rapidly moving new disease, as we saw when West Nile virus hit North America in the early 2000s.

Hopefully this was just a strange one-off infection, but it shows the need for continued infectious disease surveillance and the ever-changing challenges of infectious diseases.

Rare infection, not-so-rare bug

Animal-loving grandmother died from rare infection after her pet dog licked her hand and bacteria spread into her bloodstream.” For me, the first thing I think of when I hear that is Capnocytophaga canimorsus (to which most people respond “Capno-whata cani-whatsis?”).

It’s a tragic but textbook example of what this common dog-associated bacterium rarely can do.  In this case, 53-year-old Sheena Kavanagh developed septic shock from C. canimorsus infection, presumably after the bacterium got into her body when she was licked by her dog.

This bacterium is found in the mouth of virtually all dogs, but rarely causes human infections. The right set of circumstances are required: First, the bacterium has to make it past the body’s skin defenses (usually, it’s via a bite but in this case, the victim had a small cut on her hand and the thought is that saliva got into the cut), and then it has to evade the body’s immune system. Classically, the disease is primarily found in individuals who don’t’ have a functioning spleen (an organ that plays a key role in eliminating some microorganisms from the blood), and that was the case here. As is common, the woman's condition deteriorated very rapidly, and she died before anyone knew what was happening.

People shouldn’t fear their dogs and become germaphobes. However, people need to be aware of the risks, know some basic preventive measures and know when they are at increased risk of infection. Too often, people who are at increased risk because they have lost their spleen, have an immunocompromising disorder or have some other problem don’t know anything about this and similar issues. Communication with (and between) physicians and veterinarians about these risks is often rare to non-existent.

People like to talk about "one medicine," but we need to actually practice it more often.

More information about Capnocytophaga can be found on the Worms & Germs Resources - Pets page.