World Rabies Day highlights the impact of human and animal rabies and promotes how to prevent and stop the disease by combating it in animals. Sponsors - the Alliance for Rabies Control and the United States Centers for Disease Control and Prevention - report that 55 000 people die every year from rabies, an average of one death every 10 minutes.
There are safe and effective vaccines available for people who have been bitten by an animal that might have the disease, but usage in developing countries is low due to the high cost.
Dear colleague,
On the behalf of the RITA International Steering Committee and the RITA XX Organizing Committee, we are pleased to invite you to the 20th International Conference on Rabies in the Americas (RITA) that will be held from Monday, October 19th to Friday, October 23, 2009 at Loews le Concorde hotel in the old Quebec City, in “La belle province” of Quebec, Canada. RITA is an international event that gathers leaders in rabies research, as well as regulators, program managers and professionals working on rabies, an important public health concern the world over.
RITA provides an opportunity to assess the state of research, the latest discoveries and new prevention, control, and surveillance techniques for this disease. Since its inception, RITA has grown in prominence and is now the largest and longest running annual conference on rabies in the world. RITA XIX in Atlanta, USA, and RITA XVIII in Guanajuato, Mexico hosted hundreds of delegates from more than 20 countries spread over the five continents.
The meeting programme and the abstracts of the presentations will be available at registration. The delegates will have the opportunity to meet and network with colleagues from around the world during events like the Gala Dinner and Fund-Raising Auction. As this year will mark the twentieth anniversary for RITA, special events are also planned in recognition of this milestone.
We hope to greet you in beautiful and historic Quebec, first town in “New France”, for RITA XX.
Best regards,
Denise Bélanger, DVM, PhD President of the RITA XX Organizing Committee Groupe de recherche en épidémiologie de zoonoses et santé publique (GREZOSP) Faculty of Veterinary Medicine University of Montreal
Christine Fehlner-Gardiner, PhD Member of the RITA International Steering Committee Canadian Food Inspection Agency
Rabies
This page provides links to descriptions of activities, reports, news and events, as well as contacts and cooperating partners in the various WHO programmes and offices working on this topic. Also shown are links to related web sites and topics.
MeSH scope note: An acute infectious disease of the central nervous system affecting almost all mammals, including humans. It is caused by a rhabdovirus and usually spread by contamination with virus-laden saliva of bites inflicted by rabid animals. Important animal vectors include the dog, cat, vampire bat, mongoose, skunk, wolf, raccoon, and fox. (From Dorland, 27th ed)
HUMAN AND ANIMAL RABIES Rabies:
A neglected zoonotic disease
Rabies is a vaccine-preventable disease, and it is still a significant public health problem in many countries of Asia and Africa, even though safe, effective vaccines for both human and veterinary use exist. Most of the 55 000 deaths from rabies reported annually around the world occur in Asia and Africa, and most of the victims are children: 30–50% of the reported cases of rabies—and therefore deaths—occur in children under 15 years of age. The main route of transmission is the bites of rabid dogs. Most of the children who die from rabies were not treated or did not receive adequate post-exposure treatment. Although the efficacy and safety of modern cell culture vaccines have been recognized, some Asian countries still produce and use nervous tissue vaccines, which are less effective, require repeated visits to the hospital and often have severe side-effects. Moreover, these patients do not receive the necessary rabies immunoglobulin, because of a perennial global shortage and because of its high price, so that it is unaffordable in countries where canine rabies is endemic.
Due to complete absence of any successful medical treatment for clinical rabies and the horrific nature of the disease, most rabies victims die at home rather than being admitted to a hospital in abysmal conditions. These circumstances add to the notorious lack of surveillance data. Underestimating the health implications of rabies leads many high ranking decision-makers in public health and animal health to perceive rabies as a rare disease of humans resulting from a bite of an uneconomically important animal (the dog). Therefore, rabies usually falls between two stools and is not dealt with appropriately either by the Ministry of Health or the Ministry of Agriculture.
Rabies
Rabies is a zoonotic viral disease which infects domestic and wild animals. It is transmitted to other animals and humans through close contact with saliva from infected animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once symptoms of the disease develop, rabies is fatal to both animals and humans.
Approximately 55 000 people die from rabies each year. The vast majority of these deaths occur in Asia and Africa. Children are at particular risk. Annually, more than 10 million people, mostly in Asia, receive post-exposure vaccination against the disease.
Two types of vaccines to protect against rabies in humans exist - nerve tissue and cell culture vaccines. The nerve tissue vaccines cause more reactions subsequent to administration and are less potent, but also less expensive, than cell culture vaccines. WHO recommends replacement of nerve tissue vaccines with the more efficacious, safer vaccines developed through cell culture. It also advises that cell culture vaccines that have been specifically authorized for intradermal immunization represent an acceptable alternative to standard administration by the intramuscular route. Administration through the intradermal route should be considered in settings where cell culture vaccines are unaffordable and/or in short supply. Periodic booster injections of rabies vaccine for persons whose occupation puts them at continuous or frequent risk of rabies exposure are advised.
Disease Burden
Rabies is a zoonotic viral disease which infects The first written description of rabies can be found in the Babylon Codex, 23 centuries BC. The disease thrived from ancient times to the end of the 19th century when, in 1885, Louis Pasteur succeeded in the first prevention of human rabies by postexposure vaccination. One hundred and twenty years later, this zoonotic viral disease still continues to plague humankind, especially in developing countries in Africa, South and South-East Asia and, to a lesser extent, Latin America. According to WHO, more than three billion people are at risk for rabies in over 85 countries and territories worldwide, and about 50 000–60 000 human deaths from rabies are estimated to occur annually, even though effective vaccines for postexposure prophylaxis (PEP) are available and over 10 million individuals actually receive rabies PEP each year. The true disease burden of rabies is largely under-estimated, especially in Africa. For example, in Tanzania, incidence of human rabies mortality was estimated to be about 1500 deaths per year (4.9 deaths/100 000 persons) when calculated from active surveillance data on bite incidence, but national statistics reported only 193 deaths per year (0.62/100 000).
In Central and Eastern Europe and North America, most human rabies cases are associated with contacts with wild carnivore species (e.g. foxes, raccoons, dogs, skunks and coyotes), which are the main reservoir of rabies virus, or with bats whose role has been considerably increasing in recent years. In contrast, in canine rabies-endemic regions with large stray-dog populations, the overwhelming majority (95–98%) of cases of human rabies occurs following dog bites. Control of disease in these settings often is hampered by cultural, social and economic realities (Buddhist and Hindu ethics restrain culling of the canine population; India and Thailand have prohibited the killing of stray dogs by municipalities). Reduction of the stray-dog population by capture and euthanasia is ineffective in the long term and there is today no convenient tool for dog reproduction control. In addition, vaccines for human PEP too often are not available or not affordable. All these factors are responsible for the high disease burden in these countries.
The risk of rabies to travellers depends on the country of destination, exposure to animals (especially dogs, but also cats, skunks, raccoons, and bats), conditions of travel and length of stay. Long-stay travellers and expatriates may have an incidence of animal bites equivalent to that in the local population, which can be as high as 100–200 suspect bites per 100 000 person-years.
Animal bites introduce rabies virus into tissue and muscle rich with nerve endings by which the virus can invade the peripheral nervous system, reach the neural ganglion and travel through the spinal cord to the brain. This process usually requires weeks or months, depending upon the distance from the bite site to the brain. Replication of the virus in the brain causes hydrophobia, hallucinations and aggressive behavior, eventually followed by paralysis, coma and death. Meanwhile the virus can spread to salivary glands, from where it will eventually be transmitted to a new host, but also to the skin, cornea, nasal and intestinal mucosa and other organs, including the kidneys.
In rare occasions, the virus was shown to be transmitted by aerosols in caves populated by rabies-infected bats. Cases of transmission by organ transplant (cornea as well as solid organs) also have been reported.
Virology
Rabies virus is an enveloped bullet shape virus, which belongs to the genus Lyssavirus in the family Rhabdoviridae. The negative sense RNA genome encodes a small leader sequence followed by the N (nucleocapsid), P, M (membrane), G (envelope glycoprotein) and L (replicase) proteins which are translated from five capped and polyadenylated monocistronic mRNAs, each encoding one of the five viral proteins. Seven virus genotypes have been described, including several bat lyssaviruses (Lagos bat virus, genotype 2, Central Africa Mokola virus, genotype 3, South Africa Duvenhage virus, genotype 4, European bat lyssaviruses, genotypes 5 and 6, and Australian bat lyssavirus, genotype 7). All these viruses, except Lagos bat, can be pathogenic for humans. The G glycoprotein, which forms spikes at the surface of the virion, is responsible for attachment to viral receptors and bears the neutralization epitopes. There seems to be little cross protection between genotypes 1 (rabies virus) and genotypes 2 (Lagos bat) and 3 (Mokola virus).
Vaccine
Several effective inactivated rabies vaccines are currently available worldwide. Nervous tissue-derived vaccines are prepared from rabid sheep, goat (Semple vaccines in Asia) or suckling mouse brains (Fuenzalida Palacios vaccine in South America) by phenol-inactivation. These vaccines are highly reactogenic due to contamination with brain proteins. This type of vaccine is still unfortunately manufactured and used in South-East Asia, but the number of countries doing so has been decreasing during the past 10 years in accordance with the WHO recommendations to replace them by cell-cultured vaccines.
The new generation of rabies vaccines is made of inactivated virus grown in cell cultures, human diploid fibroblasts (HDCV, Chiron Behring, Sanofi-Pasteur), fetal rhesus cells (Bioport), primary Syrian hamster kidney cells (PHKCV, local manufacturers), chick embryo cells (PCECV, Chiron Behring) and Vero cells (PVRV, Sanofi-Pasteur). Manufactured mainly in industrialized countries but distributed worldwide, these vaccines – which are inactivated with -propionolactone or formalin – are safe and immunogenic.
A number of cell-culture based rabies vaccines are being developed in China and India on Vero cells, human diploid cells (HDC), or duck embryo cells. These vaccines however have not yet been prequalified by WHO and may require further assessment in terms of safety and efficacy before they can be traded internationally. Of importance for the supply of rabies vaccine is the use of the intradermal route schedule which reduces the number of vaccine vials and thereby the cost of PEP by up to 80% (US$ 5–10 for vaccine alone).
Oral vaccination of wildlife to prevent the spread of rabies, which relies on the use of baits containing either live-attenuated rabies virus strains or a live vaccinia virus recombinant expressing the gene for the G protein (VV-G), was implemented with great success in Europe. Field vaccination with VV-G has begun in the Eastern USA.
Passive Immunization
It is well known that rabies PEP with vaccine alone is not always sufficient, especially in cases of severe exposure (category 3) where concommittant passive immunization with rabies immunoglobulins (RIG) is strongly recommended. The worldwide shortage of RIG thus represents a real public health threat and a new challenge. According to a WHO survey, the vast majority of the 7.6 million PEP undertaken worldwide in 2000 were without RIG because of their unavailability and/or unaffordability. Two types of RIGs are currently manufactured: a) human IgGs (HRIG) which are used in industrialized countries and Thailand, and b) equine IgGs (ERIG) which are either pepsin-digested (Thai Red Cross, India, and formerly Berna, Chiron, Sanofi-Pasteur) or highly purified (heat treatment and chromatography purification). Highly purified ERIGs were developed by Sanofi-Pasteur in order to meet the highly stringent regulatory environment in Europe and North America.
It is to be noted that, in view of the current cost of HRIG (over US$ 100) and ERIG (over US$ 40), the price of a cocktail of 2–3 mouse monoclonal antibodies (MRIG) might be highly competitive (expected price less than US$ 10). Interestingly, whereas ERIG can in some experimental conditions interfere with vaccine activity, MRIG were not found to be suppressive. Extensive clinical trials are needed to validate the threshold of MRIG potency for their use as adjuvant of vaccines for curative treatment. China, India and the Philippines have already expressed strong interest in developing such a technology.
Rabies is a zoonotic viral disease maintained in domestic and wild carnivores and bats all over the world. It is transmitted to other animals and humans through close contacts with saliva from infected animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once symptoms of the disease develop, rabies is fatal to both animals and humans.
Rabies has been eliminated as a significant public health risk in most parts of the developed world. However, annually 55,000 deaths are reported, most of them in the developing world. Once infected in the absence of post-exposure prophylaxis the disease is fatal. Although post-exposure prophylaxis using modern vaccines and whenever required rabies immunoglobulin is effective in most situations, many people still die. Most of them are children and most of the patients do not receive the necessary rabies immunoglobulin because of a perennial global shortage and because of its high price, so that it is unaffordable or unavailable in countries where canine rabies is endemic.
The animal hosts that maintain rabies virus in nature are carnivores and bats. Other animals do not play a role in the maintenance of the disease, but are victims of the disease. Humans become infected by the bite of an infected animal, mostly a rabid dog. After a bite immediate post-exposure treatment is needed.
In many countries in which the dog is the reservoir of the virus, few activities are underway to prevent rabies occurrence in humans and to control rabies in dogs, even when the number of human deaths is high. Prevention of human rabies must be a community effort involving both veterinary and public health officials. Rabies elimination programmes focused mainly on mass vaccination of dogs are largely justified by the future savings of discontinuing prevention programmes. If rabies is not eliminated, expenses related to prevention of the disease in both humans and animals are likely to increase dramatically in developing countries.
Role of WHO
WHO is working on at least five requirements that need to be fulfilled to control and prevent human rabies:
* consistent availability of modern effective cell culture rabies vaccines for humans and for animals;
* an increased awareness in the public, and in the medical profession of rabies and effective methods of control and prevention;
* implementation of dog control programmes and elimination of canine rabies;
* eliciting political support;
* improved surveillance.
WHO promotes activities for the control and elimination of dog rabies particularly in Asia and Africa. A number of WHO documents dealing with the various aspects of a comprehensive dog rabies control programme have been developped over time.
Fuentes:
http://www.who.int/mediacentre/events/annual/world_rabies_day/en/index.html
http://www.rita2009.org/invi_E.html
http://www.who.int/topics/rabies/en/index.html
http://www.who.int/rabies/en/
http://www.who.int/immunization/topics/rabies/en/index.html
http://www.who.int/vaccine_research/diseases/zoonotic/en/index5.html
http://www.who.int/zoonoses/diseases/rabies/en/