Thank you so much, Antony, for that lovely introduction. And, to everybody joining the webinar, I'm really delighted to have been invited to give this presentation to talk about progress towards elimination of canine rabies, and particular thanks to MSD Animal Health for making it possible. So if you've heard, I'm, from the University of Glasgow, and much of my research has focused on the epidemiology of rabies and particularly in East Africa.
And what I'm really hoping in this presentation is that I can convey really where and why rabies still presents such a problem in many parts of the world. But more optimistically, why we are really confident that it's feasible to achieve elimination and the key role that vets have to play in this. So, just some introductory slides about rabies.
Rabies is a very ancient disease and as has long been associated with domestic dogs. And really ever since people have been writing, people have been writing about rabies. The first, documented record was more than 2000 years BC, in the Ishana Code.
And one of these laws explicitly deals with the subject of mad dogs and prescribes what the owner of a rabbit dog must pay in compensation if the dog bites a person. So the link between human rabies and the signs of rabies, and the bite of a mad dog has long been understood. And it's also been recognised that how fatal and incurable the disease is.
And this has led to numerous superstitions and proposed remedies. And, and in fact, Flya the Elder described a cure, which was to insert into the wound the hairs from the tail of the dog that had inflicted the bite. And this actually lives on today in our expression, hair of the dog, which refers to an equally dubious hangover remedy or, dubious efficacy as much of hair of the dog to cure rabies.
So, just some brief introductory points to key features of rabies. The disease rabies is an acute progressive encephalomyelitis, and it's caused by several viruses, all in the genus Lissavirus. These are those bullet-shaped virus particles that you can see in the top right-hand corner of the slide.
It has the highest case fatality of any disease. Essentially, once clinical signs appear, death is virtually always the outcome. But it is 100% preventable and I'm going to come back to that several times in this presentation.
All mammals can be affected and can die from rabies. and, several different, mammalian hosts can also be reservoirs of the disease. But a very key point and when we're thinking about the public health burden of rabies is that the vast majority of human deaths, more than 99% of these are caused by domestic dogs.
So I mentioned that the disease rabies, this acute progressive encephalomyelitis can be caused by several Lisaviruses. And the genus, Lisairus is an expanding sort of day by day, and I, every time I talk about Lisaviruses, I have to update this table because as, as more and more of these viruses are detected. But coming back to my point about the the rabies virus, although these are really interesting group of viruses, and, and several of them have caused rabies in, in humans, worldwide, when we talk about rabies, we're really dealing in terms of the public health problem with the rabies virus itself.
So, just briefly to mention some of these other lyssaviruses, or what some people refer to as the rabies related viruses. In the UK, where, so excuse me, in the UK where I'm speaking from, for example, European bat lyssavirus 2 is endemic in Dor Benton's bats and has caused a human death in the UK. European bat Lisairus one occurs widely across mainland Europe and Was detected for the first time in the UK in 2018 and in the south of England.
But most of these, lysaviruses and when they're detected tend to be found, and occur in bats, and it's like, very likely that, the Lissavirus, genus, that the viruses within the genus, originated in bats. So the genus currently falls into 3 or possibly 4 different phyloros with the rabies virus seen at the bottom of the slide, the European batlisa virus and the Juvenhagen virus in, in this phylo group 1. We have viruses such as Lagos bat virus, and Maola virus and phyler group 2.
And some of the more recently discovered Lisaviruses, including at the top of the slide a coma Lisairus, which actually was a virus we recently detected in Tanzania in group 3 or possibly 4. I think there's still some debate about the precise, classification of, of these more recently discovered viruses. But this yo grouping is important when we think about the effectiveness of rabies vaccines.
There's some excellent vaccines available. For preventing, classic rabies virus. And they also provide good protection against other viruses in phylo Group one, but less so to those in yo Group 2, and, and they probably protect very little against phylo Group 3 and 4.
So while these lyssaviruses are of great interest, and we need to be aware about it, and particularly in countries where we're free of the classic rabies virus, in many cases that there will be some of these lysaviruses circulating. So we need to be alert for the disease rabies and potential causes of that. But I, the rest of my presentation this evening is going to be talking very much about the rabies virus, the classic rabies virus, which, as I mentioned, is overwhelmingly the primary cause of public health concern.
So rabies virus is capable of infecting many mammals, as I mentioned, but paradoxically, it's actually tends to be maintained in distinct epidemiological cycles, which tend to be associated. Only 10 minutes late, with few mammalian hosts almost exclusively from within the carnivore and bat taxa. When we think about, excuse, excuse me, when we think about the infection cycle, it follows a, a, a very similar pattern in all mammalian hosts.
I'm using the dog here as a sort of schematic exemplar. But it's, the, the same pattern occurs in people as well. So typically, rabies virus is transmitted in the saliva of an infected animal through bite inoculation.
There are other routes of transmission, but most commonly, it's a bite inoculation. And the virus remains at the site of inoculation for a variable period of time. And it's at this point that the virus is actually vulnerable to attack by the immune system, and that forms the basis for post-exposure prophylaxis, which I'll talk about later.
But a critical point in the infection cycle is the uptake into the peripheral nerves, probably mediated by nicotinic acetylcholine receptors at the neuromuscular junctions. And once it gets into the peripheral nerves, it's at this point, the virus is protected from the immune system. And essentially the die is cast.
Medical interventions cannot now change the outcome. The virus then hijacks the cellular transport machinery to progress to the CNS where there's a phase of massive replication, and it's at this stage that the disease signs usually start, to appear. So, from the brain, from the CNS, there's rapid then spread to many other parts of the body, but critically to the salivary glands, where there's another phase of replication, and, excretion, the saliva and onward transmission through bite inoculation.
So several key points. Firstly, that the incubation period is very variable during this time, depending on the time of uptake of the virus, but then it's tracking to the central nervous system. And the second key point is that, once clinical signs develop and and that's usually, as I said, by the time of replication of virus in the brain, death is almost always the outcome and usually within 7 days of the onset of clinical signs.
Signs of the disease are associated with nervous system damage and dysfunction, and actually manifest in, in pretty similar ways in all species. Of course, human cases are incredibly harrowing and traumatic disease, obviously for the patient, but also very much for families and for healthcare workers. In most species and in people as well, you typically will see a change of behaviour.
This can often be misdiagnosed as a psychiatric disorder. But it can be really distressing as people go through sort of periods of fear and anxiety, interspersed with periods of complete lucidity. And change of behaviour is a really typical sign in animals as well.
So although aggression is often associated with rabies, in fact, aggressive animals can become docile. When you see cases of rabies and wild animals, it's often an animal that may look Superficially behaving sort of appearing or moving normally or quite alert, no obvious sort of neurological signs, but the behaviour will be strange. So nocturnal animals, appearing confident and calm sort of in the middle of the day.
A non-aggressive species like a bat eared fox, for example, you see suddenly sort of attacking vehicles, jackals trotting into houses or attacking elephants, which is totally not a usual thing for jackals to do. So anytime an animal in a rabies endemic area is behaving abnormally, that's certainly an alert that rabies may be a cause of the problem. But we see problems such as agitation, biting, and it's not just a kind of a a nipping kind of bite.
It's a really a gripping bite and animals can hang on, it's almost tearing, when, when they're biting, and this can obviously cause very serious, injuries and trauma, to animals and people that are, that are also bitten. Muscle tremors, in coordination, seizures are all seen. One of the distinct features of human rabies in comparison to animals is the occurrence of hydrophobia and aeropphobia.
And these are very distinctive signs, and not very well understood, but likely to be a result of a malfunction of the limbic system. And in aerophobia, which is shown in this still from a video of a child in South Africa with rabies, the paediatrician here is just breathing very gently over the skin of the, the, the child. And as in response is eliciting a really sort of sharp, sort of inspiratory, fearful kind of spasm.
It's, it's a really terrible response. And this is the same that's seen in hydrophobia. So people may feel thirsty and may want to drink.
But as soon as they take and try to swallow the same fearful inspiratory reaction occurs and eventually can be elicited just at the sign of, of water. So it's, it's a really terrible disease to witness. And, although there has in the past in recent years been quite some optimism about potential treatments and cures for the clinical disease, none of these have ever shown consistent effectiveness, and palliative care is really the only recommended intervention.
But it's tragic that in many healthcare settings, even the drugs for sedation, anxiolytics for pain relief are not always present. And you still hear really harrowing stories where, patients may be turned away from hospital because of the, there's nothing much that can be done for them. They may be isolated in rooms, sometimes tied and restrained in the beds, to prevent aggressive behaviour or the outcomes of that, sometimes, not allowed contact with family members.
And this all adds to just the really harrowing and traumatising nature of the disease. And I'm sorry you'd have to start with such a kind of terrible part of the disease, but I think it's really important that we know what we're talking about when we're dealing with this disease. It's not just numbers.
I'm gonna be talking more about numbers, but these are really terrible, harrowing, traumatic cases. And the real tragedy of it is that they're 100% vaccine preventable. There should be nobody in this world who is dying such a terrible death as rabies.
It's because we've got some great tools and we've had some great tools at our disposal for many, many decades. And vaccines are the mainstay of human rabies prevention. They've been available for more than 100 years since the time that Louis Pasteur first developed, the first vaccines, and he recognised this window of opportunity, even though he didn't, know exactly of the mechanism.
He knew the time course of from, transmission to, clinical science developing, and he knew there was a window of opportunity after exposure, when immunity could be induced before the agent had reached the brain. And so in this image here, it's showing the vaccine being given to Joseph Meister with Louis Pasteur looking on. And to work at the Pasteur Institute for many years.
And this basic principle of rapid implementation of a post-exposure prevention or post-exposure prophylaxis is still the basis of human preventive strategies today when people are bitten by by rabid animals. Of course, the vaccines today are much more highly purified. They're very safe, they're extremely efficacious, and they can be used also for pre-exposure people, for people at high risk, usually those, at occupational risk.
But they come at a cost. These are very high quality vaccines. They are very costly.
We estimate that around 30 million people every year need to be treated, with, these post-exposure regimens, that in direct costs alone costs around $1.7 billion. And critically, when we're thinking about where rabies is now affecting people, which is mostly in poorest and marginalised communities, the course of vaccine to be sure of being effective, has to be given within 24 hours of exposure.
And I will come back to that and why that period of time is so problematic in some parts of the world. We have a second arm, to rabies prevention, which is vaccinating at source, preventing infection in the animal reservoir. So all transmissions come from an animal source.
And where the rabies is maintained, we talk about the animal reservoir. As I mentioned, domestic dogs, in terms of the public health burden are by far the most important reservoir of, of rabies worldwide, and we have excellent vaccines for dogs. We also have vaccines, oral vaccines for some of the wildlife reservoir species, that maintain rabies in some parts of the world.
So I'm gonna be talking rather little about wildlife rabies specifically and focusing on canine rabies, because of the predominance of canine rabies as the cause of human death. And so when we see these highly effective tools that we've had at our disposal, it's interesting to kind of look at where we stand today with rabies. And canine rabies has been controlled or eliminated from many parts of the world, shown in this map in the yellow.
Mostly more prosperous regions of the world or islands, states, or peninsulas. But the disease still occurs widely, particularly across Africa and Asia. And while great progress has been made in Latin America, there's still pockets where the disease still occurs.
And so why is it that we see these disparities? Why is it that rabies still is an enduring problem in many parts of the world? Why is it that children are still dying on a daily basis from this totally preventable disease?
Well, we sort of set out trying to tackle some of these, and I looked at some key questions quite sort of early on in my research on rabies. And, and one of these really related to sort of awareness of the disease burden. And when I first set out, cases of rabies were reported, human rabies were reported every year to the WHO and published in what was known as the World Survey of rabies.
And typically, in Africa, what we'd see were around 200 human deaths for the continent, every year. And obviously, when set against the backdrop of so many health challenges in Africa, really gave the impression of rabies as a totally insignificant problem. There are many reasons why human cases are unreported, even though it's a very distinctive clinical disease.
there are many reasons why those, records, are not, the disease can be misdiagnosed, the records may not be transmitted, to central authorities and may not reach WHO. So we had the idea really to use the incident of bite injuries. When people are bitten, they often really recognise the risk of rabies.
They recognise the need to get to a clinic for PEP as quickly as possible. And those, records are well maintained in many countries. And so they provide a really useful source of information, for us, both sort of tracking, patterns of disease epidemiologically, but also from using that as a starting point to estimate, the burden of human diseases.
So we used a very simple sort of probability tree model, which started looking at the incidence of bites from suspected rabbit dogs, looking at the sight on the body where people are bitten. And that really is an important determinant of whether somebody will develop rabies after a rabbit dog bite. So bites around the head and the neck are extremely high risk, highly innovative areas close to the central nervous system, and they may carry a 30-40% chance of that person without PP developing rabies, whereas a bite, perhaps on the foot or the trunk and less well innervated area may be as low as 5%.
So overall, we think around 15% of people who are bitten by rabid dogs without PP are likely to go on to develop clinical disease. And then we looked at the probability that the person in a particular area would be able to receive PP and made a conservative assumption that anybody that received PP, which is usually given as a course of vaccines, even receiving a single vaccine at any point in time, we made the conservative assumption that that person would not die of rabies. And using that approach, we predicted around 1500 human deaths in Tanzania, which was around 100 times more than officially reported.
And we took that forward, in several surveys, to try and look at the burden across Africa and Asia. And then Katie Hanson, a colleague of mine here at the University of Glasgow, led a much more detailed study, using generally the same approach, but to generalise global estimates. And this is the map showing the incidence of human rabies deaths from dog rabies in different parts of the world.
And you can see that there are highest incidents in the darkest red colour in, in Africa. The highest number of cases in any country is actually in India, but somewhere around 20,000 deaths. But the incidence, the per capita number of rabies deaths is, is highest in sub-Saharan Africa.
So we came up with an estimate of around 37,000 deaths in Asia, 21,000 in Africa, and about 180 or so in Latin America. And so each year, we think that close to 60,000 people, die of dog mediated rabies each year. And that is, is a figure that when you think of it every day, sort of 150 people every day, it's really quite a horrifying statistic.
There are quite wide confidence intervals around these estimates. We're making predictions, based on different sources of data and different types of assumptions. And other studies have carried out other, used other approaches to estimate the global burden of disease, and but we all come up with tens of thousands of deaths a year.
So we feel very comfortable. This precise figure may not be absolutely accurate, but we're very comfortable about talking about tens of thousands of people dying every year. But it's not just the deaths, the deaths are terrible and harrowing, but they are only one element of the disease burden.
Rabies affects many, many more people who are bitten by rabbit dogs. And when you're living in one of these communities where you may not be able to guarantee availability of PP PEP, it's really a terrifying situation. A bite of a rabbit dog is a life-threatening emergency and you need to get high quality care very quickly.
And when we translate the PPE exposure or dog bite figures around the world, it's something like every hour, more than 3000 people are faced with these life-threatening emergencies. And I mentioned the high cost of rabies vaccine. And that's costly not only to health authorities, but can be very costly also for people who have to seek, the treatment.
And it's probably no surprise to see that your probability of actually being able to get PP really depends on not only the economic and sort of the prosperity of your, of the country that you're in, but also of your community. So when we look at the, the graph in the middle of this slide here, it shows the Human Development Index. In the wealthier countries, if you get bitten by a rabid animal, you're pretty sure that you'll be able to get to a clinic and be able to get the PP in time.
In poorer countries, with a lower HDI, those probabilities can become very low indeed. And it's not just At a national level, even within er middle income countries, it's the poorer communities that are suffering the most hardship. And I think, I'm gonna give a couple of case histories now, because, again, when we talk about numbers, it's quite easy to glaze over.
But these are really terrible and, and awful incidents for families, exposed or if a family members exposed to rabies. The gentleman here on the right is from Tanzania. I think you might be able to see on his back there he has a scar, and that scar is from a, a wound that was inflicted by his daughter when she had rabies.
And she was bitten by a neighbor's dog. The neighbour denied responsibility and didn't provide any support or help for this gentleman. He's a very poor subsistence farmer.
He doesn't have access to ready cash. And this is one of the problems that it takes time when you're not living, in a sort of cash economy, you're in a subsistence economy, it can take time to get the money that you need to, for the travel to the clinic and to pay any of the medical costs. He was able to eventually raise some funds, but it took him 3 days, and that was 3 days.
That delay, was, sufficiently life threatening that his daughter, ended up contracting rabies. After that point, actually, the dog owner did, help provide support for PP for him and, and he was OK. But this just gives you an example of, of the, the type of situation that people are facing.
And this is another case history. This is a family, a mother with her 6 children living in Northwest Tanzania. Again, they're almost very much dependent on subsistence farming.
Like many households in this part of the world, they keep dogs for guarding purposes, also for companionship in, in, in some sense. And, the, the family had just acquired a puppy. The puppy was brought in.
All of the children had touched and played with the puppy. And the puppy, developed rabies, and either licked or bit every single one of her children. And she knew rabies.
When the dog got sick, she recognised the signs. She knew the risks. She knew she had to get her children to the clinic.
But she could only afford to take one child. And so what an incredibly ghastly choice that is for somebody in that situation. Again, I'm pleased to say that actually this family was living in one of our study areas and we were able to provide support, ensuring that all the children receive PEP.
But it's just an example. These are two, just two case histories from the thousands and thousands, that we hear about, occurring every year, and I think we often forget that when we talk about the burden of rabies and focus only on, on human deaths. So, if we don't do anything about rabies now, I say we have got good tools, it's considered a priority, zoonosis, in many parts of the world.
But if we don't do anything more than we're doing now, what's going to happen? Well, some recent modelling work, which was carried out and led again by Katie Hampson as part of the WHO rabies modelling Consortium, estimated that If we maintain the status quo, over a million people will die of rabies before 2030 in 67 rabies endemic countries. And It will just continue apace, demand, the number of cases will continue to increase, and the demand for human PP, the costly human PP will continue to escalate because we still will have rabies endemic and circulating in the domestic dog reservoirs.
So what can we do? Well, I've focused a lot on the inequalities of vaccine provision and access to vaccine, and to human vaccine and, particularly in our discussions. And so improving access to the most poorly served communities of PP would be a very valuable approach, and the consortium estimated it would save almost half a million deaths by 2035.
There are new regimens that have been approved by WHO which are highly cost-saving, in reducing the amount of vaccine that has to be given and the duration of the course, which can be quite an important constraint on people completing the course. And in WHO terms, and when we look at sort of health priorities, we talk about dally, the disability adjusted life years. And so this allows the comparison of different types of intervention, and the cost effectiveness of those.
And on standard metrics, human PP is highly cost effective, in terms of what can be achieved, in disability adjusted life year saved. So, the work of the consortium, was very influential in providing evidence that now allows GAI, the Global Vaccine Alliance, to include human rabies vaccine in their new investment strategy. And this is really a major breakthrough for us working on the rabies problem.
And so now this is, allows the opportunity for countries potentially to apply for vaccine, to be deployed in the more remote areas where vaccine is inaccessible, where people are struggling, and at the moment kind of falling through the cracks in the system in terms of accessing vaccine. It's predicated on using high quality, pre-qualified vaccines, using this abbreviated one-week intradermal regimen, which is highly efficacious. And it's also hopefully going to help countries with challenges faced in forecasting, procurement and accountability.
And when we talk about dog rabies and veterinary vaccines, this is also absolutely the case that when it comes to scaling up, And there are real challenges still in countries being able to forecast appropriately. And that has real consequences in terms of vaccine provision, vaccine production, and by the pharmaceutical companies, and the type of costs that, and, and cost savings that can be achieved. And in terms of global health priorities and the sustainable development goals, there's a major imperative at the moment towards achieving universal health coverage.
So for every person in the world, ensuring that they have access to the most essential medicines. So, ensuring access of human PP would very much sort of contribute to achieving those goals. So we talked about one of the major arms of prevention, and I've been talking quite a lot about human PP, but I now want to really shift to 11 health approach and where dog vaccination comes into this.
And I mentioned that, the huge savings that could be achieved. Simply by improving PP access. But, and this is shown quite nicely on the graph here when we look at the number of deaths that are projected.
So under the status quo, the red line shows human deaths continuing, in a rather unremitting fashion to increase. If you improve PP access, as with we hope the GAI investment, human deaths will go down. But the absolute optimum scenario, fewest deaths are going to occur when we are able to improve PEP access alongside scaling up of mass dog vaccination.
And this really demonstrates kind of the value of a one health approach, because even with improved access, it's still going to be the poorest people, people in the poorly served communities, those with the least access to PP who will be dying, of rabies. And what mass dog vaccination does, it essentially provides a really important safety net. So it will protect everybody from infection at the animal source, regardless of where they live, who they are, how poor they are, how influential they are, whether they can get to hospital or not, they will be protected.
And when we think about mass dog vaccination, it's going to be the only way that we'll get to elimination. And unless we can get to elimination, when we look at those costs, and they're going to continue to increase and increase, over time. So there are a lot of reasons why this combined approach is absolutely the optimum, and it's well recognised by Gay.
And their decision to invest in human vaccine is really contingent upon a parallel commitment and energy from the veterinary side to scale up mass dog vaccination. So, as a veterinary profession, this is really our opportunity. Our opportunity is now.
We have a fairly small window of time where I think we can make such a difference. But we have to find ways to scale up in all our countries and really make it happen, and I'll be talking a bit more about how we might be able to do that. And so, really, sort of one of the .
Over the past 10 years, there's really been sort of enormous momentum in developing partnerships strategies, for rabies control and elimination. And this has been led very much by the tripartite partnership of the World Health organisation, the World Animal Health organisation, and FAO and catalysed by the Global Alliance for Rabies Control. And a really key step, that has now sort of allowed us to move to the next stage in 2015, was setting an agreed target of 2030, and now that's only 10 years away now, for the elimination of human deaths from dog-mediated rabies.
So no more people dying because of transmission from domestic dogs. And it builds on a, a large body of evidence that demonstrates the feasibility of this objective. And I want to talk a little bit about why we think it is actually feasible to do that.
And it draws on some of my work from East Africa, but also examples from other parts of the world. And one of the best examples is is from Latin America. And we really can look to Latin America to learn about some of the key factors in success.
So here, human rabies is transmitted from dogs in only 7 of 35 countries, and just in a few pockets in these areas as well. And a really critical factor in the success has been the investments that have been made in mass dog vaccination. And I just want to show some figures now on the costs of rabies prevention and control.
I mentioned we had 182 human deaths in Latin America and around 37,000 human deaths in Asia. This is not because of a relative lack of investment and prioritisation of rabies in Asia. In Asia, actually.
Our governments are spending more per capita on human PP than they do in Latin America. But there's a key difference. In Latin America, about 20% of the rabies prevention budget is allocated to dog vaccination.
That has been sufficient to allow vaccination of around 60 to 70% of the dog population, in the continent. And that has made the difference and is why that continent now is on the brink of zero human deaths. When we look at Asia, there's major investments.
It's not a disease that we, it's clearly a disease of concern. But there's very little proportionately spent on dog vaccination. And so much of the human PP is being used for people, perhaps in richer parts of communities who are bitten by dogs that probably don't have, have rabies, and often in cities.
So there's a very high expenditure on PP because, of course, clinicians need to kind of play safe. And if there's any possibility of it being rabies, the person receives vaccine. But dog vaccination is still at quite low levels.
And so where we see people dying is particularly in rural areas, in remote areas, in the poorer communities. I've said it before, but it's, it's clearly a point that I think, needs to be given attention. So much of my own research has been about what I might describe as challenging the dogma.
And when I first came to work on rabies, I became aware of phrases I was hearing time and time again, which I was interested in setting out to challenge and actually have been shown to be real common misperceptions. So the first one is that It's really futile to try and control rabies or eliminate rabies and dogs because of rabies and wildlife, and particularly in Africa, of course, where we have so much wildlife. You hear all the time there are too many stray dogs.
It's a problem of stray dogs in Africa and Asia. And I'll come back to that. It would be impossible to vaccinate enough dogs, and particularly because of all these stray dogs.
It would be too expensive to vaccinate enough dogs. And so, really, a lot of my career has been about trying to generate evidence to examine the validity of these perceptions, and to challenge them and test them with data. So we set out to tackle this question first in the Serengeti ecosystem, which has been a great privilege to have been working in, for much of my career in, northwestern Tanzania.
There's a map of the Serengeti here, the national park, and, adjacent wildlife protected areas. As everybody is probably aware, the Serengeti is home to a highly diverse and abundant, populations and communities of carnivores. And that poses challenges in terms of trying to identify what the reservoirs of infection are.
And we've really had to draw and integrate sort of several different lines of evidence. We sometimes describe it as sort of weaving a tapestry, that you'll have a thread of evidence that will give you a little tiny insight, but you don't see the whole picture. And gradually, you just put together these patches, a rather patchy information, that gradually a consistent picture emerges.
And so one of the key, approaches, was developed by my colleague Katie Hampson, in relation to contact tracing, and we're all hearing about contact tracing now, of course, with respiratory infections. But in this case, she had the great insight that in fact, rabies is one of the few diseases where you can really time transmission. You can't do it for many infections, but rabies is a really distinctive, it's a very memorable, disease.
When there's a rabies incident in a household or a village, it can usually be recalled quite precisely. And people have a very strong recollection of it. And so it allows you to go back and retrospectively collect quite detailed data on that event, and Katie's then been following that through looking at, the transmission, chains, following on from, from those exposures in, in a lot of detail.
And she's generated some incredible empirical evidence and data around patterns of infection. We just see a, a fragment of some of her data showing domestic dog cases of rabies here in the red and wild carnivore rabies, in blue. So in the Serengeti, we see carnivores able to move freely outside protected areas.
There are no fences at the moment in this part of Tanzania. And so, but the key question really is, can those wildlife populations maintain separate independent cycles of rabies from domestic dogs? And so looking at the spatial and temporal pattern of cases here, we see domestic dogs shown in the blue.
We see a lot of different wildlife species affected. As I mentioned, rabies can affect a very wide, range of species. But those chains of transmission tend to be quite short and, are not sustained for very long.
So we, we only see the consistent and persistent, sustaining of infection in domestic dog populations. When we look at the genetic data, the early phylogenetic analyses were carried out on partial sequences, of the rabies viruses, but they were still very illuminating. They showed firstly that there was a single major variant that belonged to a Southern African, group of viruses.
But critically, there was no evidence for species-specific groupings. So that variant was able to infect many different host species. And carrying out this, this work was led by Titzana Lambo, who carried out a statistical parsimony analysis, to construct the inter and intraspecies relationship.
So looked at those patterns of transmission within and between host species. And the patterns that she generated shown here, in this figure are consistent with domestic dogs that are shown in grey, and the square shows the sort of the origin host species, in these transmission chains. And that invariably, was the domestic dog.
Wildlife cases shown in red here, fall at the end of transmission chains. . And, similarly, livestock, which we know are dead and hoes also, quite reassuringly in this analysis, also fell at the at the end of these chains.
So all of these data, on their own, would provide some evidence, but would not be, entirely, confirmatory. But they all point to a consistent interpretation, which is that there's no evidence for independent wildlife cycles in the Serengeti, despite the abundance of potential reservoir hosts. And I'm just gonna show you the sequence of photographs taken by colleague Ingela Jansen, which I think are really remarkable, actually.
This is a lion, on the edge of the Serengeti National Park, being attacked by a rabid domestic dog. And that one picture shows you an awful lot about both rabies epidemiology and its natural history. So the directionality of transmission is dog to wildlife.
That's the dominant directionality. It shows the unusual manifestation of the, well, the unusual behaviours that animals show when they have rabies. It's really not normal for dogs to attack lions.
And, and you can actually see slight startled expression on this lion's face. He, he doesn't really know what's quite happening to him. I mentioned the fierceness of the bite, and, and here's the dog now with this gripping bite hanging on, to, to the lion's head.
And the strength that can come with that. It's a, it's a really fierce attack, bringing the lion down, onto the ground. And eventually, the lion shakes him off and, and is able to run away.
But, but you can also see in the background of this picture, the giraffe also looking quite surprised and by this, this rather unusual incident, again emphasising this is not a normal occurrence. But for me, that tells a, a, a picture paints 1000 words. And, and so for me thinking about sort of the pattern of rabies in, in, in, Serengeti, that's a, a good summary of the situation.
But here, I'll show schematically what we think's happening. So the evidence is, the dogs here on the right-hand side are maintaining, infection, in reservoir populations. There's some spillover transmission from dogs into wildlife.
There are short chains of transmission in different wildlife host species and between different wildlife host species and potentially some spill back transmission from wildlife to domestic dogs. But the key point is that if you can disrupt transmission in domestic dogs, the maintenance host, you will just disrupt these transmission chains. You'll break that spillover transmission.
The short wildlife to wildlife chains of transmission will die out. And then we should have a situation where we're able to eliminate rabies from the ecosystem entirely. And so we set out to test this hypothesis using a large scale intervention, in this case, mass dog vaccination, and carried out mass dog vaccination campaigns in villages surrounding the national park.
So essentially to create a sort of cordon sanitaire around the park, to prevent transmission from dogs to wildlife and use that intervention. To tell us, and, and to see if we could confirm our hypothesis that it was really all being driven by domestic dogs. And also, importantly, to gain some operational insights into, mass dog vaccination.
So one of the first questions we wanted to ask is, what level of vaccination coverage do we need to control rabies and dogs? And I'm sure I, you've probably all been hearing about this epidemiological parameter R naught. And it, this really describes the transmissibility of a pathogen.
And the key point is, the more transmissible a pathogen in this case of virus, the higher the value of our naught, and this is why everyone's getting so exercised at the moment about what is the value of our naught, for the novel coronavirus outbreak. For rabies and for other vaccine preventable diseases, we have vaccines. So the objective of our vaccination is to bring the value of our naught down below one.
The higher the value of our naught, the higher the proportion of the population that we need to vaccinate to control the disease. And the key sort of threshold is are not less than one. At that point, while you still might get a few sporadic cases, infection will die out.
It cannot, sustain itself in the population. And so if we look at some of indicative values of our naught for different infections, smallpox, we know, is the first disease ever to be eradicated, but also rinderpest. The Arnot valleys are between sort of 3 and 5.
Measles, which is a target for elimination, much higher valleys, 10 to 15, polio, also a target for elimination, 5 to 7. When we look at rabies, we see actually very low valleys, only 1 to 2. And the low value of our north suggests that elimination of KN rabies through mass dog vaccination should be feasible.
And that's one of the sort of cornerstones for our optimism about elimination. We've, as a profession, achieved one of the greatest successes of the profession in eradicating rinderpest. That was a much tougher job epidemiologically than it's likely to be for rabies.
When we look at these values of our naught, another intriguing feature of rabies transmission that the values of our n are very consistent across a range of settings. And that was something that was very surprising. We know our naught depends on, host communities, contact patterns, and so it's quite context-specific.
And for reasons that we still don't understand entirely, what we see in very differing types of demographic and cultural settings, we see very consistent values of our north. It almost always falls somewhere between 1 and 2. And, even in countries such as Bali and Indonesia, where you have very high density dog populations, you see an R of 1.2 in very low density communities in Tanzania around the Serengeti.
You also see valleys of 1.1 and 1.2.
And that has important implications, but first of all, . 70% vaccination coverage we think should be effective to control rabies across all the dog populations we've looked at in the world should be sufficient, irrespective of dog density. And that's a really useful rule of thumb.
The other corollary of that is that. Dog dog rabies transmission is not at all dependent or very little dependent on the density of dogs. And so that means that reducing dog density is not an effective way to control rabies.
And one of the ways that authorities often approach rabies, and particularly in the face of a sort of perceived crisis, when you have an outbreak, when there's huge public demand for action, indiscriminate culling can often be the first response. With, if, if there are no vaccines available, it can be a, an approach that seems to be doing something to responding to community concerns. But it's a particularly ineffective way to control rabies, because we know that you're aren't able to reduce density sufficiently in a way to control rabies.
We know that dogs are wanted by people. Dogs are only tolerated because people are tolerating them and wanting them around. There's a very strong and long cultural association between people and dogs.
And so dogs that are culled will be rapidly replaced. That can lead to more infected dogs moving into an area, spreading disease. It can lead to people moving and hiding dogs away.
And resulting in the spread of disease, and we've certainly seen that in some parts of the world, where actually implementation of culling has exacerbated the spread and the the the the increase in the outbreak. It's often the case that the dogs are easiest to colour also those easiest to handle may in fact, you may be culling a lot of vaccinating dogs. It invariably generates animosity, mistrust, bad will.
And one of the key factors in the success of dog vaccination campaigns, dog rabies control programmes, is you need to have effective community engagement. You need to be working with communities, bring communities with you to tackle this disease. And in many cases, it has major animal welfare implications as well.
So there are simply no situations where it's likely to be an effective, or an appropriate response to a rabies outbreak. So what talked about sort of theoretical predictions, our values of R0 between 1 and 2 means that during annual campaigns, and from what we know of the turnover dog population, 70% coverage should be sufficient to control outbreaks. And indeed, that's exactly what we've seen in the Tanzanian data.
Where we have achieved between 60 and 70% coverage, we see no further cases. The lower the coverage, the bigger the outbreak, as shown in, in this figure here. And it turns out that that 70% figure is also the optimal economic scenario.
So if you're looking at centralised sort of community campaigns where perhaps a team goes out and sets up a mass vaccination campaign, that 70% coverage is also economically optimum and allows and achieves these very cost-effective levels of investment when we're talking about human lives saved or cost per human life saved. And what we find also in Serengeti is that where we've been able to control dog rabies, and this has tended to be actually in the wildlife rich parts of the ecosystem, rabies and wildlife also disappears. And, we, we haven't had cases of wildlife in the Serengeti National Park for long periods of time, and where they have come in, we are able to trace most of those two, introductions.
So the question really is, in terms of, you know, scaling up is how do we do this? Can we reach the 70% coverage on a large enough scale? We know that if we, we need it to be quite a homogeneous coverage, if we have patchy coverage and we have pockets where dogs aren't being vaccinated, that can really delay our progress towards control and elimination.
Well, I think my message to you all is that, yes, I'm absolutely confident that we can reach 70% coverage. And the key message is that the majority of dogs, and I speak mostly from experience in rural Africa, the majority of dogs are accessible for parental vaccination. It's really common to hear this problem about stray dogs, but The vast majority of dogs are owned or have some close association with the household.
There will be somebody in the community that is taking some care of that dog, and will have some ability to restrain that dog and to be able to handle the dog for vaccination. So if you were just going to come into this village, you'd see these typical village dogs running around. You might think that they're stray dogs.
But you can see from the green spray marks on the back that all of those have been vaccinated. They were all brought by this one young man, and he was able to handle them all. And so we, we believe that accessibility is much higher than is often perceived.
I often say to people, just try and see. Don't take my word for it. Just go and try in your communities.
Try it out, see if these dogs are accessible. And I think, in many times people are surprised that it is much simpler than that the, may appear at the at the outset. We also have had some important findings in terms of the age of dogs that can be safely vaccinated.
And typically, dogs and puppies are generally not vaccinated till about 3 months of age. But the age structure of dogs, in many parts of Africa and Asia is a very young population, and a large proportion of dogs are young puppies under 3 months of age. So we were keen to know whether these puppies would, we could vaccinate them safely and efficaciously, and it turns out that that is the case.
They mount a very effective immune response. We don't seem to have any problems with maternal antibody. And they can be safely vaccinated, and they're actually quite accessible.
So you can see there's buckets of, or there's bowl of puppies being brought. It's a very quick way to, to vaccinate quite a large number of dogs. But there are still clear perception problems around that.
Owners often think you can't vaccinate puppies of that age. It's often quite a widespread perception among veterinarians as well. But all our data suggests that if you're going to a community once a year, for example, for an annual campaign, just vaccinate every dog you can.
Regardless of its age, and these, these puppies, have mounted extremely, effective immune responses. And that will also, if we miss these puppies, then there's going to be quite a large proportion of unvaccinated dogs and our vaccination coverages over time are going to, drop quite rapidly. So I mentioned that the vast majority of dogs are owned.
Again, in rural Africa, in this situation, they can mostly be bought for vaccination. And here's a very orderly queue of well-behaved dogs. And we're very pleased we have these very orderly lines.
I wonder whether this would be achievable if we tried it in a village in, in the UK for example. But most of these dogs have names. Here's just a snapshot from one of our regis registers.
You can see names, I think, perhaps on the screen like Simba, which means lion or chewy, which means leopard. This sort of reflects, dog's role in guarding and the idea of dogs being fierce. but actually, we also find that global figures, are often very prominent.
And, and I think the dog names over time have provided a fascinating reflection of sort of the global political landscape. And I just wanted to show you this quite light-hearted figure in some ways to look at the names of dogs, or the frequency at which the dog names appear in the register. So we can see, sort of, in the early 1990s, that Saddam was actually quite prominent, at the time of just after the First World War, and then kind of declined a bit.
And then after the second Gulf War, it came shooting back in prominence. Osama, you might, it has been a very popular name in recent years, but less so now, but reached a, a really high peak, sort of 2002 03. which again, obviously reflects a global prominence, .
Of that name. And then you can see that Bush appeared sort of in the, the 2000s, and the president's names are often quite popular. So, in, in good time, Obama came along and has actually now outcompeted the Osama.
And it might not surprise you to know that Trump is now appearing in the registers. And actually, it was a couple of years ago I met my first Trump. This is the first Trump I met.
And I found it quite entertaining, actually. He's a very friendly dog, actually. But for some reason, and, rather unusually for this community, the owner decided that it would be a good idea to have him castrated.
So I don't know the reason, but she probably had a good reason. So I talked about accessibility of dogs, and the, the point about dogs' names is a serious one, because it reflects there is a relation, a strong relationship between people and their dogs. They are not stray animals.
And the accessibility we find applies across Africa. These are some images from campaigns in Malawi, the excellent work that's been done by Mission rabies in many parts of Africa and Asia. And, and showing again with well organised, coordinated campaigns, it's really feasible to, vaccinate 70% of dogs.
I appreciate in Asia that the situation is more challenging. They are generally more, what we might term as street dogs. But again, with well-trained teams, with coordinated campaigns, we know that they are, it's also possible, to achieve sufficient vaccination coverages.
There are prospects for oral vaccines that are likely to be able to help support, the more traditional parental campaigns, and they may be critical as we get to the end stages of elimination. To reach those sort of last pockets of hard to reach dogs. So, I think this figure for me sums up kind of, the cause for optimism that we feel about rabies elimination.
There are many challenges that have faced the rabies control programmes in Sri Lanka. And, when I visited, more than 10 years or so ago now, there was very much perception that it was really difficult to access sufficient dogs. To control and eliminate rabies.
But this shows that it really is feasible. It shows that human, as dog rabies vaccinations increase, shown here in the dark blue, human rabies deaths come down. But I think what's really exciting here as well is that if you look at the pale blue columns, human, vaccine costs are also coming down.
And so we're we're getting a win-win, with rabies control. I apologise, I'm, I think I'm slightly running over. I don't have very many more slides to go, so I maybe can just ask the, chair if, it's OK to carry on.
Yeah, no, I'm OK, I apologise to people if you've got other things planned at this time, but I'll try and raise sorry I just checked my watch. I just really wanted to talk about the sort of global, strategic plan. I mentioned this target of 0 by 30, 0 human deaths from canine rabies by 2030.
And the global strategy has now been developed, which proposes a sort of phased approach, starting countries which there is already political will and momentum, for implementing plans. And then followed by a scaling up in other countries, which are earlier on in the process. And so when we look at Kenya, for example, they're already implementing a national plan that was developed in 2014.
The idea is to start small and scale up and use those first few sort of, smaller, Campaigns to develop the expertise, build confidence. For me, it's all about confidence. When I've worked with teams, there's so many uncertainties, there's so many questions, there's so many perceived barriers, and people actually start to do it, find that really can be done.
And it's so exciting. There can be few things we do as vets that can be more rewarding than dog rabies vaccination. We're preventing this terrible disease.
We're really improving lives of people in communities, and it happens very fast. The results can be seen, excuse me, very fast. But we do need, additional support.
We need technical support for countries to develop the plans. There are some areas of training. There's sometimes a lack of expertise in and handling of dogs, and for, planning and implementation of these larger scale programmes.
There's a lot needed in terms of surveillance and monitoring. And one of the barriers has been sort of procurement and reliable procurement of high quality vaccines. But there are initiatives like the OIE vaccine bank that can really help with that.
And we're very much working with partners now to look at sort of global initiatives where we can provide better and more coordinated and more Tangible support for countries to do this. But there's no reason to wait. Every country can start this, can start building their capacity, can start building the expertise and enfuse and motivate the veterinary professionals within the country to achieve something that's incredibly worthwhile and meaningful.
But through our work in many more disadvantaged communities, I'm also increasingly aware of the additional added value of rabies vaccination, the potential for dog vaccination to really achieve broader benefits. And there's so much talk in public health and global health about the critical importance of community engagement and trust. The Ebola crisis and DRC is a case in point.
We, we really can't hope to be effective in communities if we only ever respond to emerging health threats that concern us. We have to start building from the ground up and tackling diseases that are of concern to people day in and day out. And rabies is just one example, but a disease that I think fits the bill really well.
People in endemic areas see this disease. They're confronted with rabies exposures in communities all the time. And when you go in and implement a mass vaccination campaign, you see the results between, after about 2 years, and it's very visible, it's very noticeable, and it's appreciated.
And increasingly we think that this provides a platform for many other interventions as well. And I'm involved now in the Looking at the challenge of certifying eradication of guinea worm, which is now affecting dogs in some of the remaining endemic countries. We've also been looking at ways to integrate mass dog vaccination with treating people against all transmitted helmins and found that people are very accepting and appreciative of efforts to try and link these programmes.
So I think there are an awful lot of opportunities, and One Health gives us this framework and this platform, to think about how we might look at synergies. And there are of course many other dog transmitted diseases, zoonoses, like cystic chinococcosis. A really emerging major livestock disease problem that we're seeing in East Africa is neurosis caused by the tapeworm, parasite, with dogs as definitive host.
Neosporra as a major cause of cattle reproductive losses, all of which can be linked in some way with dogs. So, how can we, what are the sort of final steps we need in terms of our research efforts? Well, I see these falling into three main areas.
That's improving surveillance, trying to understand elimination dynamics, particularly in that end game, and then implementation science. I think we need a lot of work, and, and this is where I think we can all combine doing something on the ground practically in implementation and recording what works, trying to understand the reasons of what works and what doesn't work. And just in this schematic from Latin America, we can get a sense of timelines.
But in the endemic phase, you have a lot of dog rabies around human deaths reflecting that high burden. You start implementing mass dog vaccination control measures. Do rabies comes down very quickly, and human deaths fall, in line with this.
And so you can reach zero human deaths, in a short space of time. And that's why we think the 2030 target is actually feasible. It will take longer to eliminate canine rabies entirely.
But we can reach zero human deaths, by 2030, but we have to get moving now. In terms of surveillance strategies, they're going to be critical, particularly as we reach the endgame, and we need to identify where new incursions are coming from, and to be sure that we're maintaining, a, a rabies-free zone. And this is where new technologies and tools like genomic, whole genome sequencing can come to play, and colleagues have been using and already applying in real time genomic surveillance through these portable whole genome sequencing devices.
To generate whole genome sequences that can actually pinpoint in areas which are free of rabies when you have new incursions, where they've come from. And this is my colleague Kirsten Brunker, who set up a, a, a Meine whole genome sequencing facility, as you can see in quite simple, facilities in basic field conditions, and she can move from collection of that sample, in the field, to generating a whole genome in a, in a very short space of time. So, I'm just gonna end there and really just, go back to a citation or a quote from Louis Pasteur, who recognised when he developed his first vaccines, he really recognised their potential, and the blessing that it would be for humanity to be able to solve the problem of rabies.
We've had these tools for a long time. We have very good evidence now. We've got excellent partnerships.
We know what strategies work. We know what strategies don't work so well. We have everything at our disposal to eliminate canine and human rabies.
We've got high-level commitment. We have and we are continuing to generate new support and new advocates. But we still have a, a lot of work to do.
We have to scale up. We have to coordinate activities. This is not a trivial task.
Eliminating infections and diseases is never trivial. It's going to be hard work. It's going to require organisation.
It's going to require commitment from all of us. But as a profession, I can think of nothing that's more worthwhile that we should be striving towards at the moment. It can be done.
I think it must be done. And I really would like to involve as many of you as we can in our global efforts. So just to finally to thank so many people who've been involved in much of the research, working together and, and, and taking things forward, from the University of Glasgow, from collaborating institutions in Tanzania and across the world.
And then, of course, for many different, donor agencies, it reflects, I think, the one health, the breadth of the concern about rabies from human health, animal health, livelihoods, poverty, inequalities, and also wildlife, health and conservation. And just finally to thank you all very much for your time, for joining me today. Sorry, I ran over a bit, but I tend to get a bit, involved and I start talking about rabies, and you can probably tell it's, very much something that I care deeply about, and I'd be very happy to answer your questions.
So thank you very much. Thank you, Sarah, that was, that was splendid, really, really good and really interesting. How, how, you know, perhaps a couple of practical things, how can we as, as vets, you know, perhaps who aren't in, in the countries, although, you know, very interestingly, we've got Derek here saying he's been involved in a project in a companion association in the Masai Mara, thanks to help from the Serengeti initiative, he said.
We've also found that when these campaigns are done during school holidays, they're more successful because children are the key to getting large numbers of dogs in. The, the dogs are very easy to vaccinate with the children handling them, and that's from Derek in. In Kenya, so obviously Derek's doing a great job, but how can we help, perhaps as vets, you know, in the UK and in, in other, you know, European countries, perhaps who, you know, obviously aren't seeing rabid dogs as such, although interestingly I saw somebody else from Spain, Portugal saying that they've had, A case of rabies, you know, but how can we help, you know, in this crusade.
Well, I think the first is, is, is really showing that we care as a profession. For me, that's really important, that there are many, roles and responsibilities that vets have. But public health is a really important role that we have and I think at any kind of fora where sort of roles and responsibilities of vets are being talked about, I would really like to, you know, kind of ensure that this is a priority, and not just a priority that's put down on paper, but that we can really try and understand sort of what the barriers and constraints are.
There are, it's a, partly, but not entirely to do with funding. We do need to try and encourage funding support for veterinary services in low middle-income countries. Many colleagues I know are doing a fantastic job.
We've got really passionate, committed individuals on the ground trying to make things happen. But there are really, really low level of resources available for veterinary services. And it's dominated so much by, the livestock sector, the economic needs around the livestock trade, which are really important.
But it does mean that zoonotic diseases, can often sort of falls through the, the gaps. And so I'm, I'm passionately convinced that we, as vets, as a profession, need to be speaking more loudly about this, and talking about this as the, as a responsibility of our profession, that's something that we're committed to do. And to encourage funding support for these under-resourced veterinary services, specifically to help with, with dog rabies.
So that's one thing we can do. There are schemes in different parts of the world. So in North America, there are schemes where there are very direct links, between veterinary clinics, and certain veterinary practises, with funding that, is generated through, and linked with dog vaccination in country, and those have been very successful in raising funds for some of the campaigns.
There are some organisations like Mission rabies, which take volunteer vets and do a fantastic job in country. And again, providing this really critical catalyst to, generate confidence, build the expertise, build capacity, to try and encourage, the scaling up. But for me, it sort of does go to a bigger and a more important question around veterinary services.
And, our need to shout more loudly about what we can do, in terms of public health. And I think the One Health platform allows us to do that, but we really need to see it operationalized. We have to not just talk about One Health, we really have to do it, and we have to find collectively, the resources and the technical capacity to allow us to do that.
