Abstract

iCatCare
Award for Barcelona-based welfare work
Agnès Dufau is the first recipient of the International Cat Care Welfare Award launched this year by iCatCare and Ceva, and presented at the Ceva Awards for Animal Welfare event held in Birmingham, UK, prior to the BSAVA Congress in April.
The International Cat Care Welfare Award was open to anyone working internationally and not in paid employment by a charity.
The International Cat Care Welfare Award winner, Agnès Dufau
Agnès is president of Plataforma Gatera, a collaboration of 19 charity groups in Barcelona and the surrounding area working to protect animals and, in particular, street cats. She has been instrumental in bringing and keeping together the groups, and introducing educational meetings for those involved in rescue. In 2013, Plataforma Gatera presented the municipal management programme of feral colonies in Barcelona to the Parliamentary Association in Defense of Animals in Madrid, presented ‘Gato Paco: cat responsible ownership’ during the Barcelona Festival and spoke at the International Companion Animal Welfare Conference (ICAWC).
‘Vet and Cat’
This image, captured by Dr Roongrat Maitreejittawon, won ‘the best creativity’ category of the ‘Vet and cat photo contest’ organised by the Thai Society of Feline Practitioners, a National Partner to ISFM
CFP
New AAFP videos for veterinary teams
Did you know that 83% of cats are taken to the veterinarian in the first year of ownership, yet over half of them don’t return? This is why it’s important for veterinary teams to educate cat owners on the value of routine veterinary care. The AAFP has many resources to help veterinary teams, including a new eight-part video series that outlines the ways a practice can minimize stress for both the cat and client during visits.
The series offers a glimpse into the AAFP’s Cat Friendly Practice Program, as well as information about providing the highest quality of care while showing owners a commitment to address the distinct health needs and special considerations of feline patients.
The videos also feature guest appearances by AAFP leaders Drs Ilona Rodan and Elizabeth Colleran. Dr Rodan recommends a number of techniques that can make visits much easier for everyone involved, including making a cat feel more safe and secure, talking softly and using minimal restraint, and changing your approach to each cat’s different needs. Dr Colleran explains the need for understanding feline behavior cues and that, with proper care, routine procedures that used to be done in the ‘back of the hospital’ can be performed right in the exam room.
To watch the video series, visit www.catvets.com/education/online/videos.
CFC
Online application available for ISFM accreditation
Veterinary clinics in Europe, Australasia, Asia and Africa can now apply for their International Society of Feline Medicine (ISFM) Cat Friendly Clinic (CFC) accreditation online. The scheme is run in partnership with Purina in Europe, Royal Canin in Asia and Africa, and Royal Canin and Ceva in Australasia. Previously a printed application form had to be completed and sent to the ISFM’s headquarters.
There are now nearly 150 accredited CFCs in the UK, and others appearing around the globe in Australia, the Czech Republic, Greece, Ireland, Hong Kong, Italy, Germany, Japan, the Netherlands, Poland and Spain.
Clinics that have become accredited have reported that cats are much more relaxed and that fear-related aggression has been greatly reduced. Owners have also found a huge difference with this approach and are enthusiastic about the positive changes for cats.
Find out more by visiting www.wellcat.org. Clinics can register for further information by filling in a short web form and this will give immediate access to electronic resources, and the online application process. Accredited vets are listed at www.icatcare.org/cat-friendly-clinic.
Feline advocates
In conversation: Os Jarrett
As part of a series of interviews with key figures in feline medicine, Nicolette Joosting, of the Vancouver Feline Hospital, Canada, talks tovirologist Professor James Oswald Jarrett.
ABoth of my elder brothers were veterinarians, one of them as a veterinarian in general practice, and the second one, Bill, who had already started in a research career as a veterinary pathologist. Bill was very enthusiastic about it and he really encouraged me to study veterinary medicine. I decided to study virology.
At that time, in the middle 1960s, there were few viruses known to cause disease in cats. Feline panleukopenia virus and feline calicivirus had just been discovered a few years earlier. Whilst there certainly was interest throughout the world, especially at the University of Bristol, at our own veterinary school in Glasgow there was no real virology associated with cats. In fact, at that time, there was very little interest in cats compared with the dog, and nothing like the amount of effort that went into looking at dog diseases. When my brother Bill discovered feline leukaemia virus (FeLV) it certainly was quite a big event and created a lot of interest, both in veterinary and medical circles, because here was a virus in a species that was quite similar to man in many ways, which caused leukaemia. At that time there was an interest in the ability of viruses to cause human cancer as well. So that was a start and, in a way, it did put feline virology on the map because a lot of people throughout the world began studying it at that time.
AMy proudest achievement is having helped build up a group of colleagues, in our own lab and around the world, who have made such a major contribution to cat welfare. A recent proud moment last year was being invited to give the Weipers Lecture, a public lecture at the University of Glasgow, which commemorates Sir William Weipers, a distinguished dean of the veterinary school. The subject ‘Curiosity saved the cat, and others’ was how FeLV research changed the world!
AA great achievement has been the decline in the prevalence of FeLV since the 1970s. We estimate that in the years when the greatest decline was observed (between 1980 and 2000), over 1.5 million cats were saved from death by FeLV in the UK. We did this by actively promoting control measures and supporting veterinary practitioners throughout the UK to test cats and isolate FeLV-positive animals.
Another significant milestone was when my colleague James Neil discovered the molecular mechanisms by which FeLV, by activating cellular oncogenes, causes leukaemia and lymphoma.
My colleague Diane Addie made a remarkable contribution to our understanding of the epidemiology of feline coronavirus in pet cats under natural conditions, and defined the conditions under which the virus causes feline infectious peritonitis. She developed methods to establish coronavirus-free households.
With colleagues, including James Neil, Margaret Hosie, Brian Willett, Julia Beatty and Norman Flynn, we defined the mechanisms on immunity to feline immunodeficiency virus (FIV) and why protection by vaccination is extremely difficult to achieve.
AI find FeLV, in particular, interesting because we now know so much about it. It may well be the best understood of all viruses. Now that we know how it operates in the field, we can prevent its spread and the diseases that it causes. We have developed and are using effective vaccines against it, because we know it can induce a strong immune response. We know the molecular mechanisms by which it produces leukaemia and lymphoma, and can use the virus experimentally to detect genes involved in cancer in general. FeLV research has strongly influenced human medicine – for example, in the discovery of the human retroviruses, HTLV and HIV.
By looking into how it causes pure red cell aplasia, we have a better understanding of molecular mechanisms involved in erythropoiesis. In the past few years there has been a lot of interest in FeLV-C, which when it does occur in cats, almost immediately causes a form of fatal anaemia – a pure red cell aplasia, in which the differentiation of erythrocytes in the cat is blocked. One of the ways this was studied was using transgenic mice in which the FeLV-C receptor has been eliminated. Researchers in the US and Italy found that a large proportion of these mice die in utero of all sorts of lethal conditions because tissues are not being oxygenated as a result of this deficiency in the erythrocyte cells as the foetus develops. It is thought that perhaps mutations in the gene for this receptor are responsible for various human conditions like Diamond-Blackfan anaemia in children and other lethal conditions seen in the human foetus.
Another interesting example is how we are using retroviruses as a tool in gene therapy. One of my closest colleagues, James Neil, is currently working on using FeLV of certain types to try to deliver genes to human cells. At one time it was thought that FeLV might be a hazard to human health but eventually it was found that wasn’t the case at all. So there is the possibility to use FeLV as a vector to introduce genes into human cells. You have to be careful with this approach because you don’t want a system where there is a replicating leukaemia virus in human patients, as happened with using murine leukaemia viruses for this purpose in children, when several cases of leukaemia developed in these children because the virus integrated in the child’s cells and activated oncogenes causing tumours.
A lot of interest is now in these sort of conditions rather than conditions in the cat. The problem now is that the virus has been eliminated from vast proportions of the cat population and, therefore, getting funding to study feline leukaemia virus infection as a disease in cats is quite difficult. There is really, I think, now very little research going on in feline leukaemia virus and this disease in the cat.
AIt would be nice to find out why some cats, but not others, suffer from the pathogenic effects of FIV. I would also like to know more about the spread of FIV in cats into Europe. This is linked to wanting to know how cats spread from the Middle East into Europe during the period 5000–2000 BCE; and how the association with humans has influenced the viruses that cats carry.
Rapid sequencing is being used to look at many isolates of feline leukaemia viruses in Japan, and they find a quite a lot of variety within the isolates. They can construct phylogenetic trees and look at the relationship between viruses, trying to understand how the viruses spread in the community, where they come from and try to predict where they are going. We have a little evidence from the distribution of FIV subtypes that cats may have spread into Western Europe by two distinct pathways, following farming practices. This is an interesting way of using the sequencing of viruses to show how they spread and perhaps how cats spread as well. I think, what is interesting now, is the capacity to do this based not just on the virus but also in the cat. Now that we have the possibility of doing deep sequencing of cat DNA, it is possible to go and look at the cats themselves and see if we can discern geographical spread of cats in this way. Patterns of endogenous viruses could be used to some extent for this purpose.
Mitochondrial DNA has been used quite extensively looking at migrations of human populations based on the frequency of the haplotypes that we find in people and it is something that hasn’t been done yet to a large extent in the cat, but it would be very interesting to do this. We have to ask why cats (and their viruses) have spread in this way and what has been the relationship between the cats and the humans whilst this has been going on. If we look at the way that viruses evolved with cats, that’s obviously been influenced by the way cats have been maintained by people. An example of how the development of cats and their relationships with people has influenced the outcome of infection and our ability to control it is demonstrated by our knowledge of the evolutionary ‘mistakes’ that FeLV made, which I discuss separately in an article on pages 603–604.
AThe first is the difficulty in obtaining funding for research on feline diseases. I’ve been very fortunate, throughout my career, in having quite substantial funding for our research. When we first started in feline virology research, in Britain it was rather pretty straightforward obtaining funding for research on domestic animals and pet animals. A lot of our funding came from ‘human’ sources such as Cancer Research UK and The Wellcome Trust, because of the interest that feline viruses might inform the equivalent human diseases. Subsequently we obtained substantial funding from the Medical Research Council for our work on FIV as a model for AIDS vaccination. Previously the Wellcome Trust had ring-fenced funds for veterinary research, which supported many of the big discoveries of the 1970s and 1980s, but this practice has been discontinued. I think that clinical research and veterinary medicine has suffered because there isn’t quite as much research going on as there used to be. It is very difficult to know how to change that.
The second is population control and its impact on welfare. If I had to campaign on any particular feline issue, this is it. I am chairman of The Cat Group, an enterprise begun some years ago by Claire Bessant when International Cat Care (iCatCare) was the Feline Advisory Bureau (FAB). The Cat Group brings together the major charities and organisations involved with cats in the United Kingdom, to pool experience and develop common, evidence-based approaches to improving cat welfare. We also respond to new issues about cats and give sensible advice to the media and the public.
AYou must be observant, and want to discover the basis of how your chosen subject works. You need to find the best place to conduct your research. Having found good colleagues to work with, you should be very generous to them with your time and ideas.
Disease control
The decline of FeLV
To mark the 50th anniversary of the discovery of feline leukaemia virus at the veterinary school in Glasgow by his brother, Bill Jarrett, Professor Os Jarrett considers the impact better understanding of the virus has had on the prevalence of disease.
The remarkable volume of research carried out by scientists throughout the world on feline leukaemia virus (FeLV) since its discovery in the 1960s, has made it one of the best understood of all viruses, and has had very significant benefits for cat welfare, comparative medicine and cancer.
FeLV is an important pathogen of cats because the diseases that it causes are all fatal. These include several types of leukaemia and lymphoma, anaemia and immunodeficiency. Thankfully, in many cat populations the prevalence of FeLV infection has been reduced to the extent that, from being common in 1964, it is now quite rarely diagnosed.
Shortly after the discovery of the virus, development of methods to diagnose the infection opened up avenues to determine how FeLV is transmitted in cats in nature, and how we can prevent that transmission. Like all retroviruses, FeLV can establish a lifelong infection in which the virus is continuously present in the blood (viraemia), saliva and other secretions. (Happily, after exposure to the virus, many cats resist the infection and become immune.) The blood of persistently infected cats contains several viral elements that can be targeted by diagnostic methods: infectious FeLV can be detected by isolation of the virus in cell culture; antigen within the white blood cells by immunofluorescence; free FeLV antigen in the plasma by enzyme immunoassay; and viral DNA in the nucleus of white blood cells by the polymerase chain reaction (PCR). It is very fortunate that this number of different tests is available: each has its place in the diagnosis of infected cats, as well as in the unravelling of the pathogenesis of the infection.
Two ‘evolutionary errors’
Despite being a very successful virus, FeLV has made two ‘evolutionary errors’ which have contributed to its demise. First, it has evolved to survive within groups of cats: the virus can only be transmitted effectively by direct transfer of infectious saliva from one cat to another in intimate contact. This is facilitated by the fact that cats produce very large quantities of saliva for self- and social grooming; and each millilitre of saliva from a persistently infected cat may contain over 100 infectious doses of the virus. In contrast, indirect transmission of the virus appears to be very inefficient. Consequently, by preventing the spread of the virus, we can eliminate the infection from groups of cats.
Decline in the prevalence of FeLV from 1980–2000. It is estimated that over this period, 1.7 million cats were saved from death due to an FeLV-related disease
FeLV’s second evolutionary error is that the common form of the virus that is transmitted in nature exists as a single antigenic type. This means that a vaccine made from one virus isolate should protect against all other isolates.
The first diagnostic test that we used detected infectious virus in a sample of blood, with which we showed that a positive result indicated that the cat was infected and could transmit the virus. Bill Hardy in New York then developed a rapid test for FeLV, by immunofluorescence, which gave identical results to virus isolation. With it he made two very important observations. First, in households of cats where the virus was present, by identifying viraemic cats and separating them from non-viraemic cats, further transmission of the infection was prevented. Secondly, the non-viraemic cats, which presumably had been exposed to the virus but had recovered and were immune, remained healthy and had a normal life span. Based on those findings, his programme to control the infection was simple and robust. If an index FeLV-positive cat was found in a household – often because the cat was presented with lymphoma – all the cats in the house were tested. Viraemic and non-viraemic cats were then separated, and re-tested 12 weeks later to ensure that they still had the same status. There was a slight possibility that a viraemic cat could have been in the early stages of infection at the time of the initial test and might have recovered; or that a non-viraemic cat had only recently been infected, and was incubating the infection at the first test but had now become viraemic. In our lab we found that recovered cats which mounted an immune response did not transmit the virus. Therefore, new cats can be brought into a household as long as they do not mix with viraemic cats. Of course, any new cats must be tested for the virus before being introduced.
Development of control measures
In the Netherlands, Kees Weijer and his colleagues used this diagnostic test in a systematic way to control FeLV infection in infected households of cats, in association with the cat breeders’ association Felikat. They recorded a threefold fall in the overall prevalence of FeLV infection from 1974 to 1985; and, when targeting households of pedigree cats, from 11.5% to zero. Later, between 1993 and 2002, Katrin Hartmann’s group in Munich recorded a fall in prevalence from 6% to 1% in cats in southern Germany.
In a long-term study in the UK, using virus isolation to identify viraemic cats but applying the same control measures, we showed that the prevalence of the infection could be dramatically reduced in the whole cat population. From surveys conducted by our diagnostic laboratory, we estimated that, in 1980, around 5% of healthy cats carried FeLV; by 2000 this figure was less than 0.5%. In pedigree cats, whose guardians and their breed associations had rigorously implemented these measures, the infection had essentially been eliminated. The remarkable consequences of this fall are illustrated by Dominic Mellor’s estimate – based on these figures, together with the population of cats in the country at the time, and a period from infection to death of 3.5 years – that around 1.7 million cats were saved from dying from the effects of FeLV infection during that 20-year period.
Four components of the virus are released from the bone marrow, a major site of FeLV replication, and are found in the blood. Infectious virus is detected by virus isolation, viral protein by immunoassay, cytoplasmic protein by immunofluorescence, and proviral DNA by PCR
From the 1980s, in-practice methods of diagnosis became available, based on immunoassays to detect virus antigen in the blood, developed by Hans Lutz and Niels Pedersen at Davis. These tests are very useful because they are so rapid, giving a result in a few minutes, allowing the veterinary practitioner to take a direct part in the venture to eradicate the infection. While they have added a new dimension to control, the tests pose a few problems. In the majority of cases the results from an antigen test agree with the result from a test for virus, like virus isolation or immunofluorescence. However, on occasion a cat may be found to be positive for antigen but negative for virus.
More recently, laboratory tests that detect FeLV DNA in white blood cells by the very sensitive PCR became available. Again, some cats are found that have low levels of viral DNA, but not infectious virus, in the blood.
Probably the reason for these anomalies is that, although many cats recover from exposure to FeLV and become immune (as mentioned earlier), the extent of that recovery is variable. The majority of cats keep the virus under control and probably eventually eliminate it from the body. However, in a small minority, immunity may be incomplete and virus-infected cells can persist: thus, viral antigen may be detected in the plasma, or low levels of FeLV DNA may be found in the white blood cells, in the absence of infectious virus. Consequently, it is strongly recommended that a positive antigen test should be confirmed by a test that detects virus. Laboratories offering quantitative PCR will advise on the significance of the level of DNA detected. If a cat is in this discordant category, it should be carefully monitored to ensure it does not subsequently become viraemic.
Vaccination is the other control measure for FeLV which became available in the 1980s. There is now a range of vaccines available, containing either inactivated virus, recombinant proteins, or live canarypoxvirus–FeLV recombinants. These have been shown to provide substantial protection against natural challenge from viraemic cats. Vaccination is strongly recommended for cats that may be exposed to the virus from an unknown source in the field, which essentially means all free-ranging cats.
Is eradication possible?
These successful results raise the question of whether we can eradicate the infection completely. My thesis is that if the infection is eliminated from multi-cat households, it should die out in the general cat population because the conditions for transmission occur only among groups of cats that live together. Of course, there are problem populations, such as feral or semi-feral cats, which are not amenable to testing or control. But gradually, if we continue to apply the present measures, we should continue to see a further fall in prevalence, and possibly eradication, of FeLV infection.
