Short Answer: Rabies is an acutely infectious viral disease of the central nervous system (CNS), which is typically transmitted in the saliva of infected animals (especially dogs); transmission is most commonly via a bite.   Britain has been free of classical rabies since 1922 and many western European countries are also now rabies free.   Rabies is still endemic across much of eastern Europe and the majority of infected animals are Red foxes.   There has been some recent data suggesting that rabies viruses are species-specific (i.e. fox rabies is different to, say, dog rabies and as such foxes shouldn’t be able to infect dogs), but spill-over between hosts is not unknown.   In humans, if infection is caught early and vaccination provided then death is unlikely; once symptoms have manifest it is almost always fatal.   Initially, anti-rabies campaigns involved widespread culling of foxes, but this was costly, labour intensive and largely ineffective – success was achieved in a couple of cases, but typically culling could not suppress fox numbers below the estimated one fox per two sq-kilometres required to sustain the disease.   Culling also maintains a state of flux in the fox population, resulting in more fights as newcomers establish territories, and can make the situation worse.   The greatest success has come from widespread vaccination, which began in Switzerland during the late 1970s and stopped the westward progression of the disease, forcing it back eastwards.   Baits containing capsules of the vaccine are dropped in infected areas; these are eaten by the resident foxes, which effectively form a ‘living wall’ of immunised animals that prevent the virus getting a foothold.   In some countries, now rabies has become a minor disease, widespread baiting has ceased (the costs now out-weigh the benefits) and it remains to be seen whether outbreaks arise as the number of immune individuals drops below the threshold. (Image: a healthy, non-rabid, red fox in North America)

The Details: The word rabies (a Latin word meaning ‘madness’), has the ability to strike fear in the hearts of most people.   The origins of this disease are enigmatic, but certainly not recent.   Indeed, rabies may even crop up in Greek mythology in the fate that befell the hapless hunter Acteon more than a millennium ago.   There are many variations on the story, but one -- recounted by David Macdonald in his Running with the Fox -- tells how Acteon happened upon Diana (Goddess of the Hunt) and her nymphs bathing naked; in her fury at his voyeurism, she magically made his hounds rabid and they savaged their master.   This version is presumably a Roman slant on the tale (Diana is the Roman name for the Goddess who, in Greek, was Artemis).   Most Greek versions I know of describe a similar chain of events (Acteon chancing upon Artemis bathing naked in a woodland pond), but they generally agree that she turned him into a stag, where upon his hounds tore him to pieces.   There is no specific mention of rabies but his hounds were said to have attacked their former master with a ‘wolf’s frenzy’, although whether this was just because he was now a stag is a matter of opinion.   Regardless, rabies was known in Aristotle’s time and around the 4^th Century BCE he described how dogs suffered from a madness that caused them to become irritable; crucially Aristotle noted how “all animals they bite become diseased”, thereby recognising that the disease could be passed on in the bite of an infected animal.   Much has changed since Aristotle’s time and not only do we now know what rabies is, we can modify its genetic code to produce a vaccine.

Knowing your enemy   
Rabies is a highly infectious disease caused by a virus; specifically a negative-strand RNA virus.   There are many different strains of the rabies virus (and all mammals are susceptible to one type or another), but they are all members of the same Lyssavirus genus, from the Greek lyssa, meaning ‘frenzy’ or ‘madness’ and the Latin virus, meaning ‘poison’.   The virus has a characteristic bullet shape and is surrounded by a membrane envelope with surface projections.   The virus particles (called ‘virons’) are tiny, only 180 nanometres long by 75 nanometres wide – to put it another way, if you laid them end-to-end, there would be just over 55,500 in one centimetre or 141,000 in an inch.   Rabies, like all viruses, requires a live host cell in which to replicate and, although susceptible to heat, ultraviolet radiation and chemical that breakdown fat cells, it is resistant to drying and freezing.   Rabies is generally divided into two broad ‘groups’ based on their primary hosts.   Epidemics that sweep through humans and domestic animals are referred to as classical rabies, while those that occur in wild animals are called sylvatic rabies.   It should be noted that these categories are based only upon the main reservoir for the virus; the virus causing the infection is the same.   Recent molecular analysis has suggested that many strains are species specific (i.e. only certain species can be a host, such that you have ‘fox rabies’, ‘raccoon rabies’, ‘wolf rabies’ etc.), but spill-over should not be totally discounted. (Image: Rabies virus, purified from an infected cell culture. Negatively stained virions: note their characteristic "bullet shape." Magnification approximately x70,000. Micrograph from F. A. Murphy, School of Veterinary Medicine, University of California, Davis.)

The most common method of infection is the virus entering the body through a bite from an infected animal.   The virus cannot be transmitted through intact skin but it can enter the body across mucous membranes (i.e. through the nose, mouth, eyes etc.) -- indeed, this is how many of the modern vaccines that we shall discuss shortly work -- although sufficiently prolonged contact must be made, making it an unlikely source of infection for most species.   Once in the body, the virus incubates for, on average, between two and eight weeks (up to four months has been reported); how long it takes for the symptoms to develop depend on where the victim was bitten and thus how long it takes for the virus to move into the central nervous system (CNS).   In order to enter the CNS it must first build up sufficient numbers (concentration), which it does by replicating in striated muscle at or near the bite site; as the virus moves through the muscle fibres it takes a peculiar route, making it unlikely that the body will launch an immune response until it’s too late.   The virus then binds to receptors entering nerve cells and is delivered from the peripheral nervous system into the CNS in the axoplasm (nerve fluid).   Once in the CNS it moves along nerves to a suitable replication site within the brain and newly formed virons pass back down nerves to organs, including the salivary glands from where it can be transmitted in a bite.   For an excellent, in-depth discussion of the virus and its behaviour inside the body, the reader is directed to Alex Wandeler’s 1980 review in Biogeographica.

The site of virus replication within the brain is important because it determines the ‘form’ of rabies that an animal contracts.   If the virus establishes itself in the limbic system (inner part of the brain), the victim is subject to agonising muscle spasms that prevent them from drinking; any attempt at swallowing water, even saliva, can trigger muscle spasms and the victim may come to fear water (become hydrophobic).   The victim becomes highly aggressive, biting without provocation, and hence this is often referred to as the furious condition.   If the virus replicates in the neocortex (outer layer), the animal becomes progressively paralysed, often to the point where it cannot bite, and this is known as the dumb condition.   It is important to note that both classical and sylvatic rabies can be either furious or dumb in nature.   Whether or not a rabid animal is likely to bite seems also to depend on the species.   Anecdotal evidence has long suggested that rabid foxes are more likely to bite humans than other rabid animals and in a paper to the Journal of Wildlife Diseases earlier this year (2011) a team of American biologists found that there is some foundation to this rumour.   The team, headed by Kimberly Yousey-Hindes at the New York State Health Department, studied Human Rabies PEP surveillance data collected between 1997 and 2007; they found that Red foxes infected with raccoon rabies were more likely to bite people than infected raccoons were and infected Grey foxes (Urocyon cinereoargenteus) were significantly more likely to bite humans than rabid Red foxes.   Despite furious rabies being the more stereotypical form of the disease, with the infected animals travelling widely and attacking without provocation, the dumb condition is more common.   Regardless of the condition, once the animal is symptomatic, death typically follows within a few days; vaccine administration soon after infection, however, has a high chance of success.

Rabies in Britain and Europe     
Thankfully, Britain is currently free of rabies, but this has not always been the case.   There are mentions of rabies in the UK back as far as 1026, although it wasn’t until much later (1793) that a plan for eradicating the disease (in the form of a total ban on importing dogs) was implemented.   In 1819, the Duke of Richmond reputedly died after being licked on his face by his tame fox (apparently contracting rabies through a cut he sustained shaving) and in 1897 the Victorians passed the General Rabies Order, which required dogs taken out in public to be muzzled and authorised the shooting of any un-muzzled or stray animals in certain districts.   Despite classical rabies being a problem, sylvatic rabies never became established, although there were two incidents in park deer – one in Barnsley during 1856 and a second in Richmond Park during 1886 and 1887, when 257 Fallow deer (Dama dama) were infected and observed biting each other.   Indeed, in 1886, rabies became a notifiable disease under the Contagious Diseases (Animals) Act, meaning that it was an offence not to report suspected cases to the authorities.   Following years of strict stray dog control, the UK was declared rabies free in 1902 (Ireland the following year) and there were no further outbreaks until 1918, when First World War servicemen smuggled rabid dogs back from the European war zone.   The first outbreak was in Plymouth, but the disease quickly spread and eventually most of the south of England was affected.   The disease was subsequently eradicated and Britain was once again rabies free by 1922, when compulsory quarantine was introduced for dogs. (Image: EU Pet Passports were introduced in 2000 to permit free movement of domestic animals between member countries provided certain criteria could be met, including up-to-date rabies vaccination)

Since 1922 there have been several cases of rabies, but all were contained (most within quarantine).   In 2000, following recommendations published in the 1998 Kennedy Report, the quarantine laws were altered and the Pet Travel Scheme (‘PETS’) was introduced; this allows animals entering the UK from member countries to bypass quarantine, provided the animal holds a valid ‘Pet Passport’, which assures various stringent criteria are met, including having been vaccinated against rabies.   Currently, there are 91 countries and islands that are members of PETS.   There were no cases of indigenous rabies in Britain (although several tourists arrived with the disease) until November 2002, when a bat worker was admitted to Dundee Hospital in Scotland suffering from rabies contracted through a bat bite; this was the first death from wildlife rabies in Britain since 1902.   Studies on the Daubenton’s bat (Myotis daubentonii) carcass by the Department of the Environment Food and Rural Affairs (DEFRA) found European Bat Lyssavirus II present in its saliva.   Despite the tragic consequences, this was not considered an epidemiologically significant event, because it did not spread.   Indeed, while fatal to terrestrial mammals, it seems only bats can transmit bat rabies.

Britain has been fortunate – much of Europe and North America have not fared so well with rabies.   The current epizootic (wildlife epidemic) in Europe started just south of Gdansk in Poland during 1939 and spread rapidly westwards at a rate of up to 60km (40 mi.) per year, reaching Germany in 1950, then Austria in 1966.   The first Slovenian outbreak occurred in 1973 and it rapidly spread south, peaking during the early 1980s.   In Europe as a whole, more than 90% of the infected animals were (indeed, still are) Red foxes and by the start of the 1990s the rabies epizootic was at its peak, with most countries reporting infections.   With construction on the Channel Tunnel well underway, fears were raised over the possibility of rabid foxes coming over from France; at the start of the 1990s, France were reporting more than 900 cases of fox rabies.   Fortunately, these fears were unfounded -- not least because of the various defences in place either end of the tunnel -- and, in 1995 (a year after the tunnel opened) France had reduced the number of cases to only 13; the disease has since been eradicated in the country.

North America has seen a shift from the majority of rabies cases being classical prior to 1960 to the majority (92% in 2009) being sylvatic.   Foxes are a problem rabies vector (carrier) in the United States, but significantly less so than raccoons (Procyon lotor).   According to the Center for Disease Control (CDC) in Atlanta, 35% of sylvatic rabies cases reported during 2009 were in raccoons, while 7.5% were in foxes; bats and skunks (Mephitis mephitis) are also significant vectors, each accounting for 24% of the 2009 cases.

The role of Mr. Tod        
The behaviour of the rabies virus has been well studied in the fox and in his 1987 book, Running with the Fox, Prof. Macdonald explained that foxes succumb at a dose one-ten-thousandth of that required to infect a human.   Once infected, the virus incubates in the fox for around 20 days as it travels into the brain where it replicates before migrating to the salivary glands; here it reaches high concentrations, such that a single millilitre could, theoretically, infect 34 million other foxes.   Prof. Macdonald noted that once the virus appears in the saliva the animal is infectious for six days and dies about four days (often 24 hours) later.   In a review on fox behavioural ecology published in the Journal of Veterinary Medicine during 2003, German biologist Ad Vos noted how a fox can be infectious before any symptoms are evident:
 

“… so an apparently healthy fox that behaves completely normal can already transmit the virus.”

Contrary to the image I suspect most people would hold of a rabid fox, Prof. Macdonald pointed out that only around 11% develop the furious strain of the virus, a stance echoed by Dr Vos who, in his 2003 paper, noted that extremely aggressive behaviour is not very common in rabid foxes because the majority suffer the apathetic (dumb) form and that transmission probably involves contact between a rabid ‘passive’ fox and a healthy individual.   We now know that rabies does not have to be transferred in a bite (although it’s by far the most common method); it can be transmitted via tissue and urine contact.   Indeed, some authors have suggested that foxes can catch bat rabies from eating, or even sniffing at, infected carcasses, although the vaccine is susceptible to destruction by gastric acid and Canada-based virologist Alex Wandeler found that foxes were 100,000-times more resistant to oral infection with rabies than they were to injection. (Image: A healthy, non-rabid fox from Britain)

We know little about what happens to the foxes’ behaviour once they are infectious but, in 1985, pathologists Marc Artois and Michel Aubert reported on a study during which they radio-tracked three rabid foxes in an area of Lorraine, north-east France; they found all three remained within their normal range during the incubation period but, during the infectious phase, they appeared disorientated and strayed several hundred metres beyond their normal range, although all three died at the border of their own territory; some had fresh wounds, suggesting they had been fighting.   The overall activity increased, largely as a result of “numerous aimless day-time movements” and the animals spent more time resting at the periphery of their ranges.   It seems probable that this sudden increased movement and increased time spent at territory boundaries would increase contact with neighbouring foxes – it would have been interesting, had the animals lived longer, to see whether they invaded neighbouring territories.   We also have some data on how healthy foxes behave towards rabid animals, albeit from captive individuals.   In a 1975 paper, CDC epidemiologist William G. Winkler described how one of his subjects turned away from an individual with dumb rabies, while another sniffed it all over; when the fox suffered seizures the healthy animals clearly tried to avoid contact.   It is unclear from these observations whether the healthy fox was able to tell the other animal was sick or whether turning away was a reaction to unexpected and frightening behaviour.   Observations elsewhere describe foxes bringing food to injured members of their social group, suggesting they are aware when another fox is ill.

The social system of the fox plays a crucial role in mediating how a rabies epidemic spreads, but is a subject that has received little attention until relatively recently.   Indeed, prior to the studies of Huw Gwyn Lloyd (MAFF, now DEFRA), David Macdonald (Oxford University) and Stephen Harris (Bristol University), little was known about the social behaviour of Red foxes in Britain.   Early theories had these animals as antisocial loners, but many hours of pain-staking research in less than glamorous conditions by the aforementioned biologists slowly started to show a different, more social side, to Reynard.   It quickly became apparent that, when trying to get a handle on how a disease will spread through a population, you need to understand that population.

Fox sociality is covered in reasonable detail in the main fox article, so I will only summarize it here.   Generally-speaking, there are three main social ‘systems’ employed by foxes: pairs (adult male and female) predominate in upland areas where territories are large owing to the distribution of food; family groups (adult male and female with, usually female, cubs from previous litters) are more common in lowland, especially urban, areas where territories are smaller; finally foxes may spend some, or all, of their lives moving around (so-called itinerants) rather than establishing a territory.   The formation of pairs or groups is not only an effect of food availability, it is also associated with density – in richer habitats, territories can be smaller, food is sufficient to support group formation and fox density is higher (i.e. there are more foxes in the area), while the opposite is true in poorer habitats.   The rabies virus can spread faster through high density populations than low density ones.   (Image: A rabid fox photographed in Alaska during 1970)

Mathematical models suggest that, in order for rabies to spread, there is a critical threshold density (CTD), below which the epizootic cannot be sustained.   Most models put the CTD at around one fox per two sq-kilometres, although some early estimates from Europe suggest that rabies can spread at much lower densities and that there must be less than one fox per five sq-kilometres (one every two sq-miles) in order to stop it spreading.   In Britain, densities range from that single fox per five sq-km to more than two animals per sq-km.   Neighbouring territory holders rarely seem to fight, but trespassers are violently expelled, and in high density populations, there is a greater potential for increased contact between foxes and a concomitantly greater likelihood of conflict.   Given that the most likely route of transmissions is through bites or other open wounds, fighting with an interloping rabid animal would seem almost certain to lead to infection.   It should be noted that it is the territory owner who usually initiates the attack, so even though most foxes suffer dumb rabies, this does not preclude them from aggressive encounters.

Waves, peaks and troughs of infection
Rabies epizootics show distinctly seasonal and cyclical patterns in spread and intensity.   In a 2006 review of wildlife rabies in Europe, Finish biologists Katja Holmala and Kaarina Kauhala described the spread of the virus within a population.   When rabies enters a new area there is a peak in reported cases among the main wildlife vector, although it has been estimated that between 90% and 98% of cases may go unrecorded.   Thus, there is a ‘front’ of infection that spreads out into uninfected areas as a band, typically 40km to 100km (27 – 67 miles) wide.   As the front moves forward the infected foxes in the zone behind it begin to succumb and it is estimated up to 80% of the resident foxes die (assuming around 20% avoid the infection).   Such high mortality causes the fox population to crash below the CTD so the disease cannot spread – this leads to what is called a silent phase that typically lasts for two or three years.   During the silent phase the incidence of the disease remains low, allowing the fox population to recover and, as numbers rise, they increase past the CTD and the population becomes re-infected (likely from contact with rabid foxes moving out of nearby infected zones left as the ‘front’ advances).   Thus, countries in the wake of the infectious zone tend to experience rabies epidemics that cycle between epizootic (infectious) and silent phases until the disease is eradicated.

This graph shows a rough approximation of rabies spread through an area, with a disease 'front' (yellow) in which there is high (65-80%) mortality of foxes that advances into uninfected (clear) areas.   As the front passes through the area (taking up to three years to do so), fox populations crash below the normal population density (NPD) until there are too few foxes to support further spread (the rabies population density, RPD) and the disease remains at low levels as the population recovers, this is the silent phase (grey shading).   As fox numbers rise again, the disease begins to spread through the population again, causing another outbreak, or epizootic phase (aqua shading).   The area is subject to periodic silent and epizootic phases, on a roughly six-year cycle, until the disease is eradicated.   Graph modified from that reproduced by Michael J. Delany in his 1982 book Mammal Ecology, published by Blackie, Glasgow.

We also see seasonal peaks in infection that are associated with fox biology and behaviour.   Reported cases tend to show two peaks.   The first peak occurs in late winter and infection is predominantly among male foxes; tracking studies have shown that it is during this time that males trespass into neighbouring territories in search of any vixens still in season, and this brings them into conflict with the territory owner, usually ending in a fight.   Reports of rabies then settle down during the spring as the breeding season draws to a close, and into summer when pregnant females have given birth and adults confine most of their movements to their own range while hunting for the cubs.   The second peak is during the late summer and this time it’s the vixens that form the bulk of reported cases; in his fascinating 2003 review, Ad Vos pointed to research on reproductive stress in ungulates and suggested that this second peak may arise because the energetic costs of pregnancy and maternal care, coupled with the hormones released during birth and lactation that act to suppress the immune system, may make vixens more susceptible to infectious diseases at this time.

In his review, Dr Vos noted that cases of rabies in fox cubs are very rare (and are most likely infections picked up from adult group members) and, during the summer months, the juveniles aren’t a significant rabies risk because they remain within the core area of their parents’ range and don’t participate in territorial defence.   Dispersal then begins in August, peaking in October, and juveniles can potentially serve to spread the disease; they can certainly travel widely and this potentially puts them into contact with other foxes.   Nonetheless, a radio-tracking study of dispersing and non-dispersing foxes in Bristol, by Tom Woollard and Stephen Harris, found no evidence that dispersing juveniles fought more, or were wounded more, than non-dispersers; indeed, an earlier study by Bristol biologists found that dispersers had significantly lower life expectancy (in Bristol death usually comes under the wheels of a car) than non-dispersers.   Thus, the role of dispersing foxes in the spread of rabies remains poorly understood.   Dr Vos concluded that it was ultimately territory holders that controlled the spread of the disease because they attacked intruders (regardless of whether the interloper was itself aggressive) and are, therefore, extremely susceptible to becoming infected.

Kill or Cure?      
Rabies is an old disease and a vaccine against it is a comparatively recent development, thus the traditional European view had always been that rabies could be eradicated if sufficient foxes were killed.   Indeed, in a brief article to the New Scientist during October 1990, Bristol University biologists Stephen Harris and Graham Smith discussed what would happen if sylvatic rabies ever came to Britain and how being too sentimental could have disastrous consequences.   The biologists presented a computer model of how rabies might spread were it to arrive in Bristol under three scenarios: no control; vaccination; and culling.   The model predicted that, without any form of control, the disease would flare up quickly and, within three years, almost all the urban foxes would be dead and the disease would have reached the surrounding countryside.   A vaccination campaign that reached 70% of the fox population (an optimistic percentage) slowed the spread, but it still breached the city and made it to the countryside.   It transpires that only with an intensive cull (i.e. five culling operations at two-monthly intervals that killed 92% of the foxes) was it possible to eradicate the disease within one year.   This approach has been widespread in both Europe and North America and, when rabies hit Albert in 1952 it prompted a massive cull of wildlife with, among many other species, 105,000 coyotes and 50,000 foxes killed.   So, is culling the best, indeed the only option?

The problem with widespread culling is that it is difficult to achieve the desired result.   Decades of persecution through fur trapping, anti-rabies campaigns and more general campaigns to halt the spread of fox populations have generally had little success at reducing colonisation, decreasing numbers or wiping out rabies.   Indeed, in some areas, rigorous culling has actually prolonged the epizootic when compared to similar areas in which there was little or no culling.   There are, of course, some exceptions and in Jutland (on the Danish peninsula) an intensive campaign of shooting, gassing and poisoning of feeding station baits with strychnine nitrate succeeded in eradicating rabies within two breeding seasons on three separate occasions.   Nonetheless, in Europe as a whole (and in most areas where fox control is practiced) culling has had little impact on numbers because the fox population is quick to respond with increased fecundity (see Q/A for more).   Indeed, culling may cause more problems than it solves, if territory holders are principally responsible for rabies transmission.   Culling sends the population into a state of flux; vacant territories arise as the owners die and these are rapidly taken over by dispersing foxes, which then potentially leads to more fighting as boundaries are re-established.   If dispersers do turn out to play a role in rabies transmission, having a mobile population that is predominantly made up of juvenile dispersing foxes could make the situation worse.   Culling must also be long-term, keeping the population low for long enough for the disease to die out; this becomes less cost efficient as the number of rabies cases drops off.

If long-term culling is problematic (not to mention expensive and more difficult as fox numbers decline or animals become more wary), is there an alternative?   In recent years, vaccination appears to have succeeded where culling has failed and, in a 1982 paper, David Macdonald and Philip Bacon presented their Merlewood fox rabies simulation model, which predicted that vaccination against rabies was a realistic alternative to culling provided sufficient bait-uptake could be achieved (the model assumed 60% of the population took the bait).   The basic idea of any vaccination campaign is to create a CTD using immunized animals; in other words it essentially mimics heavy culling by ensuring so many foxes are immune to rabies that it cannot physically spread.   In order to prevent re-infection, it is necessary to establish such ‘immune belts’ (i.e. areas where most, ideally all, foxes are inoculated) along borders.   A subsequent model by Oxford University mathematician James Murray and his colleagues, published in 1986, assessed the spread of rabies among foxes after an introduction near Southampton in southern England.   The model predicts that the epizootic spreads out at a rate of up to 100 km (67.5 miles) per year, travelling fastest through central England where fox densities are highest, to cover the entire West Country in just over two years, Wales in just over three years and reaches Manchester in just under four years; this is followed by periodic ‘waves’ of the disease every six years.   The mathematicians conclude from their model that, in order to halt the spread of the virus, it is necessary to establish “rabies breaks” (immune belts) 10-25km (7-17 miles) wide -- in which at least 80% of the population were vaccinated -- ahead of the advancing ‘front’.

So, what is a vaccine?   Well, essentially it’s something that has enough of the disease causing agent (in this case, the rabies virus) in it to enable the animal’s body to manufacture antibodies that are able to recognise it, bind to it and ultimately disable it, should it be encountered again – the key is that there shouldn’t be enough of the agent to actually cause the disease.   Consequently, weakened viruses may be used, and this is how Louis Pasteur -- spurred on by the widespread occurrence of urban rabies -- developed the first rabies vaccine more than a century ago; he injected rabbits with rabies, killed them, extracted their spinal cords, which he ground down and injected into other rabbits (many repeats of this later, he had a weakened rabies virus that could be used as a vaccine).   Pasteur began administering his vaccine in 1885 and over the following year-and-a-half he had treated 2,500 people, with his successes outnumbering his failures.   Recent advances in biotechnology and genetic engineering meant that we could administer chemicals that essentially kills the virus (although this makes it less effective as a vaccine), or we can now disguise less dangerous viruses as rabies (a sheep in wolf’s clothing, if you like); we can even remove certain genes on the live virus to prevent it being infectious.   The late 1980s and early 1990s saw the development of several vaccines against rabies and a flurry of laboratory studies assessing their effectiveness on captive foxes.

Most vaccines proved successful at providing immunity, although some trials with the SAD ‘strain’ of the vaccine did appear to cause rabies in a few individuals.   Interestingly, there were a couple of individuals that seroconverted (produced antibodies) of their own accord and thus recovered without being vaccinated.   Quite how this natural immunity arose is unclear, but there is evidence that inoculated vixens may pass some of their anti-rabies antibodies to their cubs, although as Dr Vos and his colleagues (writing in a 2003 paper to The Veterinary Record) failed to find any antibody transfer directly to the foetus (i.e. across the placenta), the immunoglobulins are presumably delivered to the cubs in the colostrum.   Regardless of the method of transfer, it appears that these antibodies provide short-term protection.   In a 2003 paper to a Czech veterinary journal, Peter Hostnik and colleagues at the University of Ljubljana in Slovenia found that vixens vaccinated with the Lysvulpen anti-rabies vaccine transferred antibodies to their cubs, which persisted until the cubs were two months old.   This has important consequences for vaccination programmes because these ‘maternally-derived’ antibodies interfere with vaccines, suggesting that any attempt to vaccinate cubs will achieve little during their first eight weeks of life.

To catch (and vaccinate) a fox   
As you might imagine, rounding up foxes and injecting them with anti-rabies vaccine is a rather impractical idea.   Thus, an alternative strategy was needed; this came in the form of bait vaccines.   The basic premise is to conceal the vaccine in something the fox is likely to eat and drop it where the fox is likely to find it.   The problems, however, are many-fold.   The bait must be relatively cheap to manufacture, attractive to the fox (otherwise it won’t get eaten), the bait casing shouldn’t deactivate the vaccine and neither should local weather (e.g. some early vaccines rapidly deteriorated above 4^oC / 39^oF), the vaccine capsule should be easily ruptured and the bait should require chewing – the vaccine must come in contact with the fox’s oropharyngeal mucosa (i.e. tonsils) to stimulate an immune response and trigger the body to produce antibodies.

The first baiting trials were conducted in Switzerland during 1978, where rabies was tracked as it moved along the ‘stalks’ of Y-shaped valleys in the Alps.   In his book, Running with the Fox, David Macdonald explains:

“At the entrance to one arm of each Y every effort was made to kill foxes, while at the other arm chicken heads loaded with oral rabies vaccine were scattered – the foxes ate the chicken heads and thereby inoculated themselves.   In these trials rabies progressed up the valleys until the junction where it met the two types of ‘barrier’.   There, the disease continued up the arm of the valley where foxes had been killed, but was stopped in its tracks by the barrier of healthy inoculated foxes.”

The success of the Swiss Alps trial spurred interest in a more widespread and coordinated vaccination campaign across Europe, but chicken heads were expensive so alternative bait was required.   Trials on captive foxes led to the development of a bait that is widely-used today – it is a square or rectangular fishmeal polymer bait into which a polyethene sachet (similar to the condiment packets you get in restaurants) is placed, sometimes encased in an additional wax casing that prevents it falling out when it’s air-dropped from a light aircraft.   The sachet contains about 1.5 ml of vaccine and is ruptured when the fox bites it, allowing the vaccine to make contact with the lymphatic tissue in the throat.   It is important that it makes contact in the mouth; if the fox swallows the bait whole it is useless, because the vaccine is deactivated by the stomach acid.   Captive studies by biologists in Germany during the early 1980s found that antibodies were present in the fox’s blood about two weeks after bait consumption and maximum protection was recorded a further two weeks later (i.e. one month after the bait was eaten).   It appears that this protection is generally fairly long-lasting and, in a 1997 study, Marc Artois and colleagues found that immunized foxes failed to succumb to challenge (i.e. were still immune to the virus) 18 months later.   It is currently unknown precisely how long the antibodies remain, although if we consider that few foxes appear to exceed two years old, it probably provides life-long protection.

So, is vaccination a magic bullet for rabies eradication?   The short answer is no.   The success rate is heavily dependent upon a bait uptake success of 60% or greater; if too few foxes get the bait it leaves a sufficiently large pool of unprotected animals through which the virus can spread.   This explains why baiting campaigns are more successful during the autumn and winter (when food is less abundant and bait is more likely to be taken); bait drops in the spring or summer are likely to be ignored, cached or brought back to the cubs who are either too small to eat it, or too young to benefit from the vaccine.   Low bait uptake is also the main reason why vaccination could be problematic in urban environments; trials at the University of Bristol suggest that bait uptake by their foxes was only around 40%, because there was so much other food around.   It is conceivable that householders might be persuaded to swap the food they deliberately leave out for vaccine baits, but nobody knows how well this would work.   Hence, in areas where bait is unlikely to be taken and manually vaccinating the population (i.e. trapping and injecting them with vaccine) is impracticable, multiple waves of heavy culling may be the only realistic solution, as distasteful as it may appear at first glance.