Worms and Germs Blog : Animal Health & Diseases : University of Guelph : Ontario Veterinary College : Zoonotic Diseases : Guelph, Hamilton, Ontario

The British Small Animal Veterinary Association (BSAVA) has updated its practice guidelines for management of MRSA and MRSP.

Overall, there’s good information in the document with an emphasis on routine infection control as the key measure to reduce the impact of MRSP and MRSA. I’d like to see more emphasis on developing an overall infection control program, but the emphasis on basic principles such as hygiene is good.

Like any guideline document, there will be some disagreements in recommendations. I agree with the majority of what's written, although there are some recommendations that I wouldn’t make, and some additional areas that I’d address. That’s not surprising since most of the recommendations are based on opinion rather than evidence because we don’t have solid evidence for most areas, and there isn’t necessarily a single "right" answer to many questions at this point.

Typically, guidelines assess and report the level of evidence on which recommendations are based, but that’s not done here. Letting people know the evidence (or here, the relative lack of evidence) is a useful part of guidelines. How the recommendations are worded can also play a role. Here, they perhaps overstate the strength of evidence through use of wording such as saying something "will" have an impact, when we really should say it "might." In the absence of evidence, good common sense measures can be recommended and implemented, however we need to remember that we have major limitations in our knowledge. We need to figure out which infection control practices are effective.

I have a major problem with one recommendation: "Colonised animals should be treated with a chlorhexidine shampoo and intranasal fusidic acid or mupirocin once daily." There is simple no evidence supporting the use of active measures to eliminate MRSA and MRSP.

• For MRSA, there is reasonably good evidence that dogs and cats eliminate it on their own in a reasonably short period of time.
• For MRSP, we simply don’t know how long they can be carriers. I suspect that long-term carriage can happen in some animals, so decolonization might be attractive, but we don’t know what to do yet.
• There is absolutely no evidence that intranasal antibiotics are effective in dogs and cats. I have serious doubts that someone can adequately administer a topical antibiotic to the nasal passages of a dog, and particularly a cat.
• If this recommendation is adopted and widely used in the UK, I suspect the country will be an international leader in fusidic acid- and mupirocin-resistant bacteria.

Overall, there are some good recommendations in the guidelines, including the general infection control sections. We need to improve our baseline level of infection control and hygiene to reduce the impact of MRSA, MRSP and a variety of other concerning microorganisms. At the same time, we need to acknowledge our limited knowledge in a lot of areas and the fact that we are really working based on common sense and extrapolation from human medicine, with little direct evidence from veterinary medicine. Much more research is necessary, a major limitation of which is the limited priority given to companion animal infection control by research funding agencies.  This has to change to help control the impact of bugs like MRSA and MRSP on both animals and people.

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A paper in the Journal of Neurooncology (Redelman-Sidi et al, 2011) describes "kitten-transmitted Bordetella bronchiseptica infection" in a cancer patient. The patient in question had a brain tumour that was surgically removed. The 56-year-old man was then started on chemotherapy, which in addition to killing cancer cells can also cause significant impairment of the immune system, which puts chemotherapy patients at high risk for infections of many kinds. This particular patient developed a persistent cough during treatment and was eventually diagnosed with B. bronchiseptica infection. This bacterium is one of the causes of kennel cough in dogs, and can cause respiratory infections in other species, including cats.

The man had acquired a kitten three weeks before he developed the cough. The kitten had (at some undefined time) conjuncitivitis and signs of respiratory disease. Unfortunately, as is too often the case in reports of supposed pet-associated disease in the medical literature, the kitten was not actually tested.  Bordetella bronchiseptica is classically an animal-associated organism, the kitten was newly acquired and it had respiratory disease.  These factors strongly suggests the kitten was the source.  However, without testing of the kitten and investigation of other potential sources of infection, it's hard to be as definitive as the title suggests. The suspicion of the kitten being the origin is reasonable nonetheless.

Some statements from this report are contrary to my typical recommendations for pets and immunocompromised individuals.

Getting a young animal

• Kittens and puppies are entertaining, but they are also higher-risk animals compared to adult dogs and cats. They are more likely to harbour a variety of infectious agents. They are also more likely to bite or scratch through playful or rambunctious behaviour, and it's harder to properly assess their temperament. If an immunocompromised person wants to get a new pet, getting an mature animal is ideal.

Source of the kitten

• The paper unfortunately doesn't mention from where the kitten was obtained and whether there was a respiratory disease problem in other animals at the source. Animals in shelters, humane societies and pet stores are more likely to carry various infectious diseases because they are densely populated facilities, often have infection control challenges, house many high-risk animals and are stressful environments. Getting new animals from these places is not ideal for a high-risk person.

Veterinary care

• The kitten had signs of respiratory disease and was seen be a veterinarian. It doesn't appear that any testing was done and the kitten was just treated with antibiotics. That's pretty common, but in a situation where there is a high-risk person in the house, it's wise to be more aggressive with diagnostic testing to determine whether there may be any concerns for the person.

A pet can be a wonderful thing for a person living cancer, by providing social and emotional support, along with other benefits. Pet ownership always carries some risk of zoonotic infections, and the risk is higher in people with compromised immune systems. Rarely, if ever, is pet ownership inappropriate for a cancer patient, although certain pets and certain situations might be, and high-risk individuals need to think about possible risks and measures to reduce those risks.

People with cancer or other problems affecting their immune system should ensure that their physician knows that they own pets. Veterinarians need to play a role as a member of the overall healthcare team too. Optimizing pet health can help reduce the risk of human infection. Prompt and proper diagnostic testing can identify potential issues. Proper counseling can reduce risky situations from inappropriate pets, inappropriate contacts and other factors that might make exposure to a nasty infection from a pet more likely.

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Rabies is pretty rare in horses, but there have been a few reports this summer.  Though rare, rabies is still a major concern because it's invariably fatal in horses, and almost always fatal in people.

Rabies was recently diagnosed in a horse in Eddy County, New Mexico. It started showing undefined signs of rabies and was euthanized two days later. Several people who worked with the horse are undergoing post-exposure treatment.

While rabies can potentially be spread from horses to people, I'm not aware of any confirmed cases of such transmission. Since rabies usually kills people, even a plausible risk is cause for concern. Additionally, and perhaps more importantly, rabid horses can be very dangerous, and multiple people have been killed by aggressive rabid horses. 

Rabies should be a core component of a horse's vaccination program in any part of the world where rabies is present in the wildlife population. Unfortunately, that's not always understood. One area resident stated she'd never heard of rabies in horses, and while she has her dogs and cats vaccinated, she hasn't vaccinated her livestock. No vaccine is 100% preventative, but rabies vaccination is a cheap and very effective way to reduce the risk of this fatal disease significantly.

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A recent case of canine rabies in France showed yet again the risks posed by illegal importation of animals. This case is somewhat unusual since it seems to involve ignorance of the rules and lax enforcement, compared to rampant animal smuggling, but the end result was the same.

The animal in question was a puppy that was brought to France by a family that had been vacationing in Morocco. They found the puppy on July 11 and returned to France on July 31. European Union regulations require that imported dogs be vaccinated against rabies and microchipped. Neither was done to this puppy, and it was in fact too young to vaccinate against rabies according to standard protocols. The family traveled back to France by ferry and car, and either met no customs officials or at least no officials who asked any questions about the puppy.

They day after they returned to France, the puppy started to exhibit behavioural changes and progressive sleepiness, with subsequent development of aggression. Five days later, it was taken to a veterinarian and it died the next day. Rabies was confirmed a few days later, and testing of the virus strain indicated that it was of the Africa-1 lineage and closely related to strains previously isolated in Morocco.

An investigation into possible rabies exposure ensued. Typically, it is assumed that animals can be infectious for up to 10 days prior to showing signs of rabies. Often, this is extended by several days for added confidence and because it's not always possible to determine exactly when the earliest, mildest signs might have developed. In this case, they considered the period that rabies could have been transmitted to be from July 18 until the puppy's death.

Multiple people had close contact with the puppy. Three family members had been bitten, a clear indication for post-exposure treatment. One other person (a friend of the family, it appears) was also bitten and received treatment. Another person reported being licked on non-intact skin (i.e. an area of skin with a cut, abrasion or other break in the normal barrier) and was also treated. The attending veterinarian, who had been previously vaccinated, received two booster shots.

This isn't the first time that rabies has made its way from Morocco to France, and it's concerning that it was so easy for it to happen. Nine rabid dogs have been illegally imported to France from Morocco since 2001. In 2008, one such dog subsequently transmitted rabies to several other dogs, resulting in France losing its rabies-free status until February 2010. It's not surprising that no questions were asked of the family traveling from Spain to France because of the open nature of borders between EU countries, but the ability to enter Spain from Morocco with no flags being raised is a concern. Hopefully there's an investigation into how this puppy was able to get into Europe so easily and how to reduce the chances of this happening again.

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The mosquito-borne diseases eastern equine encephalitis (EEE) and West Nile (WNV) continue to rear their ugly heads in the northeast as we get further into the late summer season during which they are most common.

On August 13 there was an unconfirmed report of a case of West Nile in a horse at Woodbine Racetrack, just north of Toronto.  No additional details have been forthcoming regarding the severity of the infection or the status of the horse, if WNV infection has in fact been diagnosed.  Nonetheless, the Ontario HBPA is urging horse owners to ensure the vaccination status of their animals for West Nile is up-to-date.  Unfortunately, if horses are not already vaccinated at this point, even vaccinating them immediately may still leave them susceptible to virus for the next few weeks until they are able to fully respond to the vaccine.  This news follows close on the heels of news reports regarding increased numbers of WNV-positive mosquito pools in various regions north of Toronto, and thus is not altogether surprising.

The first case of West Nile in a human in New Jersey was recently diagnosed in a man from Mercer County.  Again, no additional details about the severity of the infection or the man's condition are available, but the public is once again being urged to protect themselves against mosquitoes by wearing long sleeves and pants, using insect repellant, and eliminating standing water in which mosquitoes may breed on their property.  Elsewhere the death on August 14 of a four-year-old girl in New York from infection with EEE has been reported.  She is the fifth person in New York state to die from the disease in 40 years.  The girl first began showing signs of infection earlier this month, but the diagnosis of EEE infection was only reached last week.  EEE has a high mortality rate in humans as well as horses.  Just as infection in animals can act as sentinel indicators for disease risk in humans, these human cases indicate that WNV and EEE are active in these respective areas, and humans and horses alike are at risk of infection.  Mosquito avoidance can help protect both, and in addition timely vaccination of horses can help decrease the risk of disease.

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A paper that will be published in the September edition of Emerging Infectious Diseases (Mead et al 2011) talks about the potential for dogs to act as indicators of Lyme disease activity and risk for people. The use of animals as sentinels for human disease is well established. Sometimes it's because animals are more readily affected. Sometimes it's because the disease is easier to diagnose in animals. Sometimes it's because getting access to samples from animals is easier than from humans.

Because of the distribution of ticks that transmit the causative bacterium (Borrelia burgdorferi) and wildlife that act as the reservoir, the occurrence of Lyme disease is highly variable geographically. Knowing the amount of Lyme disease activity in a specific region is important for understanding the role of this disease in humans, and for implementing preventive measures.

Like people, dogs can get Lyme disease. Dogs are NOT sources of human infection, but since both dogs and people get Lyme disease the same way (from Ixodes ticks), infections in dogs can indicate the potential for infections in people (and vice versa). Since dogs may be more prone to being exposed to ticks, and since ticks are most likely to stay on dogs for the 24 hours or so that is required for ticks to transmit the bacterium, dogs may be more likely to be exposed to Borrelia spp. in endemic regions.

That's the reasoning in the Mead paper which suggests that dogs, because of their potentially greater chance of exposure and tendency to produce a good immune response after exposure, might be good indicators of human Lyme disease risk. To examine this premise, the authors compared data about B. burgdorferi antibody levels in dogs to human infection data. (Note: These are two different things: In dogs, they looked at antibodies, which indicate exposure but not necessarily disease. In people, they looked at disease. It's not inappropriate to compare the two, but you have to be aware of what they were comparing).

Overall, they showed (not surprisingly) that there was a relationship between antibody levels in dogs and Lyme disease in people. Some key findings were:

When the percentage of dogs with antibodies against B. burgdorferi was <1%, there were extremely low rates of disease in people in the area.

• This makes sense since it would indicate that there's little or no transmission occurring in the area. Low levels of B. burgdorferi in dogs or people don't necessarily indicate that Lyme disease is active in the area, since some cases could have been acquired during travel, and false positive results are possible with current testing.

The risk of disease is generally low to non-existent outside the highly Lyme-disease endemic areas: Northeast, mid-Atlantic and upper Midwest regions of the US.

• These are the areas where ticks capable of spreading the bacterium are common and where the bacterium is resident in wildlife, so that's not surprising.

Where 5% of more dogs had B. burgdorferi antibodies in their blood, there was always an above-average incidence of Lyme disease in people in the state, with a lesser association at the county level.

• Again, this makes sense. If most dogs are exposed, more people are going to be exposed, and more people will develop disease.

In 15% of counties where dogs had a >5% rate of antibodies, people did not have above average disease rates. However, in half of them, the incidence of disease in people increased to above average in the following 3 years.

• This is quite interesting and perhaps the most important finding of this study. It suggests that monitoring rates in dogs may predict trends in people.
  

What does this all mean? Well, a lot of these results would be expected based on what we know about Lyme disease. However, the apparent close linkage between human disease rates and dog antibody rates, and particularly the potential that dog rates could predict human rates, is intriguing and could be useful. By routinely monitoring for antibodies in dogs, areas where Lyme disease might be on the rise or might be emerging in people could be identified, leading to more focused educational efforts directed at both the public and healthcare personnel. Getting the dog data (or at least getting good dog data) is perhaps the problem, since testing would need to be done on a subset of the dog population that's not biased and is of adequate size to say something useful. There are ways to do this, but it takes time and money to do it right. Taking advantage of blood samples collected for heartworm testing is one possible approach, but careful thought needs to go into what could be done and whether it would be better than more intensive surveillance of humans or ticks.

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A recent paper about toxoplasmosis in the journal Biology Letters (Thomas et al. 2011) has attracted a lot of attention because it reports a possible link between this cat-associated parasite and brain cancer in people.

Toxoplasma gondii is a protozoal parasite. Cats are the natural host and can (but rarely do) pass the parasite oocysts (eggs) in their feces. People can be infected by ingestion of Toxoplasma oocysts that have been outside of the cat long enough (24 hours or more) to develop into an infectious form. Human Toxoplasma exposure is common, although this is typically not acquired directly from pet cats.  Adult cats rarely shed oocysts, whereas exposure from contaminated soil (e.g. from working in a garden and not washing ones hands afterward) or undercooked meat of various kinds are also important sources in different areas. Almost always, when a person gets infected, disease does not occur. Rather, the immune system contains the parasite, but is unable to kill it completely.  The parasite therefore often enters a dormant state forming small cysts in various body tissues, including in the brain.

Most concern regarding Toxoplasma involves pregnant women who have not been previously exposed to the parasite (and therefore have no antibodies to fight it off quickly). If they become infected during pregnancy, serious infection of the fetus can occur. Another problem in people is Toxoplasma encephalitis, a severe brain condition that occurs most commonly in people with compromised immune systems (e.g. HIV patients), typically from re-activation of dormant Toxoplasma. 

The recent paper by Thomas et al raises an additional concern: brain cancer. The basic premise of the paper is that some types of persistent infections might be able to induce mutations at the cellular level, resulting in cancer. Since Toxoplasma can cause longterm but dormant infection in the brain, they investigated a possible linkage.

The researchers took international statistics about malignant brain cancer from the International Agency for Research on Cancer database to determine brain cancer rates in different countries. They then compared these to Toxoplasma antibody rate data from 37 countries (from a 2006 paper that collected data from other papers). They found that the prevalence of antibodies against Toxoplasma in a country was related to the prevalence of brain cancer in the country (that's an oversimplification of what they did, since they did various kinds of statistical analyses, but that was their basic conclusion).

Some things to consider, though, before you ask for an MRI because you're a cat owner:

• This is a pretty superficial study. When I started reading it, I assumed they had done a case-control study, whereby they took a group of people with brain tumours and an equivalent group of people without brain tumours, and compared Toxoplasma antibody rates. That's not what was done. Rather, what they are essentially saying is that the incidence of brain tumours is higher in countries with a higher incidence of Toxoplasma antibodies in people. There are potentially a lot of other factors that might be involved. For example, they also showed that the incidence of brain cancer increased with increased gross domestic product (GDP) of the country, i.e. brain cancer rates are higher in wealthier countries. This could be because brain cancers are most often diagnosed as a result of more advanced medical care or that there are other lifestyle issues that might be risk factors for cancer. Toxoplasma antibody rates may be higher in high GDP countries (possibly because more people own cats, or for a number of other reasons) and thus the statistics shown an association between brain cancer and Toxoplasma antibodies.  It does NOT mean that Toxoplasma infection is necessarily causing brain cancer.  As the authors say, "This leaves open the possibility that brain cancers and T. gondii are both affected by a third correlated factor."
• This study included all brain tumours. It's hard to believe that Toxoplasma would be a risk factor for all of the various brain tumour types, if there is actually an association.
• The Toxoplasma prevalence data weren't obtained in a standard manner by the researchers. Rather, they took data from a paper written in 2006. That paper obtained the data from various other published papers, some decades old. It doesn't mean that the data are not valid, but using data from studies that collected the information in different ways and from vastly different time periods creates some weaknesses.
• Studies that are looking at a subject from a high level don't necessarily tell you what the risk is at the individual level. As the authors state "...analyses of data aggregated at the population level may not pertain to individual risk." (In epidemiology, this is called the ecological fallacy.)
• A large percentage of the human population (~1/3) has antibodies to Toxoplasma, indicating previous infection. That's a huge number, yet the incidence of brain cancer is very low overall. Certainly, even if there is a true association, the likelihood of an individual developing cancer from Toxoplasma is very low.
• Pet cats rarely shed Toxoplasma. They usually only shed for a couple of weeks of their life, typically when they're kittens. Also, the Toxoplama oocysts must live in the environment for 24 hours or longer to become infectious and a person has to ingest them to get infected. Therefore basic hygiene practices should reduce the chance of exposure even if a cat is shedding oocysts.

This is an example of a study that is great for generating questions that need to be answered, but not answering the questions. They've shown a crude association between toxoplasmosis and brain cancer. What that means is more detailed study is needed to see if the association is real (i.e. not the result of some other correlated factor) and furthermore to try to determine if the association is actually causative. Unfortunately, the press and internet don't understand that aspect and freak people out with statements such as "Cat parasite linked to brain cancer. A parasite spread by cats could almost double their owner's chance of developing brain cancer, research suggests."

One of the paper's concluding statements sums it up nicely: "Clearly, further research is necessary to determine the proximate links between T. gondii and different types of brain tumours and to investigate a mechanism of action." That means we need to work to determine what the true nature of the association is, and not panic at the possibilities.

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Dusty, the dog who tested positive for Hendra virus exposure on a Queensland farm, has been euthanized. The owners confirmed through their Member of Parliament that their pet had been euthanized voluntarily, rather than waiting for Biosecurity Queensland to compel them to do so.

Based on publicly available information, this seems like an illogical and unnecessary response, as well as an unethical approach by the government because it did not explain the implications of a positive result when they ask for voluntary testing of the dog.

The family said Dusty was euthanized because "most recent blood tests confirmed that he carried Hendra virus antibodies, which meant he was able to shed the virus to other animals." However, that's false. If government officials told them that, that's incredibly frustrating, disappointing and concerning. Antibodies have nothing to do with being infectious. I carry antibodies in my blood to a wide range of viral diseases that I've had over the course of my life. That doesn't mean that I still have the viruses in m. The presence of antibodies simply means the body has been exposed and mounted an immune response.

All information that I've seen so far indicates that there's no evidence that the dog was shedding virus and therefore no evidence that it posed a potential infectious risk. Furthermore, an experimental study from 1994 showed that infected dogs did not shed the virus. So, unless there are new data that aren't being released, euthanasia is a completely unnecessary and illogical response, probably based more on fear of liability than any evidence or reasonable assessment of risk. It would have been better to quarantine and monitor the dog, to prevent unnecessary euthanasia and to learn more about this virus in dogs.

If evidence indicating a true risk of transmission of Hendra virus from pets exists, this information needs to be released so that other pet owners in Queensland know what the situation is. If not, more common sense needs to be used when dealing with this disease in such animals.

(click image for source)

This Worms & Germs blog entry was originally posted on equIDblog on 01-Aug-11.

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