Eradication of rabies – ‘one health approach’ Eric Fèvre Centre for Immunity, Infection and Evolution, University of Edinburgh and International Livestock Research Institute

World Rabies Day September 28 th or thereabout each year “…to raise awareness about the impact of human and animal rabies, how easy it is to prevent it, and how to eliminate the main global sources.”

Is rabies a solvable problem? One of the so called “neglected zoonotic diseases” High case fatality rate Biology is understood Control methods known Elimination is possible

Cases of rabies in humans and vaccinated dogs in Mexico, 1990 – 2004 Vaccinated dogs (Millions) Cases of rabies in humans

Why is rabies important? Rabies is 100% preventable yet at least 55,000 humans die from rabies each year around the world, mostly from exposure to dogs. A person dies of rabies almost every 10 minutes. Almost half of all rabies deaths occur in children under the age of 15 years. Many developed countries have vaccines for animals and humans to prevent rabies. These countries might only have a few deaths each year.

What kind of animals get rabies? The rabies virus can infect all mammals. Mammals are warm- blooded animals that have hair and mammary glands to produce milk for their babies. Animals like frogs, birds, and snakes do not get rabies.

Headache, fever, sore throat Nervousness, confusion Pain or tingling at the site of the bite Hallucinations –Seeing things that are not really there Hydrophobia –“Fear of water" due to spasms in the throat Paralysis –Unable to move parts of the body Coma and death Symptoms (in humans)

The right tools Control of rabies in the main animal reservoir – domestic dogs –Dog vaccination –Dog population control Dog culling – not likely to be successful in the long term due to replacement rate in dogs (dogs have a high fertility rate) –Animal welfare concerns Fertility management –Human pre- and post exposure prophylaxis

Rabies Ancient disease Lyssavirus (ss RNA, negative sense Rhabdovirus) Causes a fatal disease in all mammals Public health problem Economic problem Wildlife conservation Ethiopian wolf

Rabies and rabies-related viruses SerotypeCommon host rangeKnown distribution Rabies 1 Dog, cat, bat, human; wild carnivore, e.g.: fox, skunk, raccoon, jackal; mongoose Worldwide Lagos bat 2 Frugivorous bats, cat, dogAfrica: West, NE, Southern Mokola 3 Shrew, cat, dog, rodent, human Africa; West, NE, Southern Duvenhage 4 Insectivorous bat, humanZimbabwe, S. Africa EBL -1 5 Insectivorous bat (chiefly serotines), human Germany, Poland, Ukraine, Netherlands, France, Spain EBL -2 6 Insectivorous bat (Myotic spp), human Netherlands, Denmark, Switzerland, Finland, UK ABL 7 Flying fox (Pteropus spp), human Australia Lyssaviruses Several new genotypes isolated from bats – Aravan virus (Kyrghyzstan, Arai et al., 2003), Irkut virus and West Caucasian Bat Virus (Russia, Botvinkin et al., 2003)

1. Inoculation by bite 2. Uptake into peripheral nerves 4. Massive replication in brain 3. Spread to central nervous system 5. Spread to salivary glands and excretion in saliva Infection Incubation – very variable Neuronal transport CNS replication Salivary gland replication Virus excretion Clinical signs Death – usually within 7 days of clinical signs appearing The infection cycle

Rabies in Europe

Rabies in Europe -2003

Bat rabies in the USA Most human deaths attributed to two species –<5% of all bat submissions ‘Small vectors’ or high viral infectivity? Silver-haired bat (Lasionycteris noctivagus) Eastern pipistrelle bat (Pipistrellis subflavus))

Rabies in humans Localised pain or paresthesia Change in behaviour, anxiety, fear, aggression Aerophobia Hydrophobia Paralysis, coma, death Full recovery extremely rare Treatment must rely on palliative care –Anxiolytics, pain relief Counselling of family

Recovery from Rabies Recovery from human rabies extremely rare and has resulted in profound disability Recent case of more complete recovery in unvaccinated teenage girl in USA

Diagnosis (post mortem) Negri body in a brain section Immunofluorescence of brain stem cells Both for animals and people….

Children are more likely to be bitten in high-risk sites, such as the head and neck

A neglected disease Clinical rabies results in death Rabies is known to be under-reported Surveillance for rabies is inadequate Poor data leads to poor prioritization Classic “One Health” problem with benefits of integrated human-animal health

What is “One Health”? “…the collaborative efforts of multiple disciplines working locally, nationally and globally to attain optimal health for people, animals and our environment” (American Veterinary Medical Association 2008)…” “…One Health is used to refer to a more integrated or holistic approach to human, animal, and ecosystem health….

One Health and rabies Strong case for integrated control Management of rabies in animals as a key public health intervention Tools are available, they just need to be properly applied Policy makers need to acknowledge the problem

Under-reporting of rabies: why? Many cases do not undergo laboratory confirmation Some cases may not be recognised by medical staff Cases may be recorded locally but not transmitted to central authorities or to the WHO Patients may be aware of the futility of medical treatment and stay at home Patients may seek treatment from local healers Rabies may be perceived as ‘bewitchment’ requiring exorcism rather than medical treatment: problem of stigma.

Rabies elimination The main reservoir is almost always domestic dogs The virus is usually locally transmitted (little evidence of re-introduction from elsewhere) We have pre- and post- exposure vaccines for people We have an efficacious vaccine for dogs We understand dog ecology, including urban dogs We know that we need to cover 60% of the dog population with vaccine on an annual basis to interrupt transmission We have benchmark data on the current burden (or at least models to estimate it), so measuring success of a programme is possible

What is lacking? Better reporting of both rabies cases and dog bites in countries Better communication between the veterinary and medical communities in terms of –Outbreak reporting –Information flow –Joint vaccination programmes –Budgets Scaled up approach across wide regions, rather than a piecemeal one –Big scale interventions over long periods of time, with annual vaccination of dogs –Centralised management Commitment for a sustained budget –This HAS been achieved in South America and Europe