The following questions were raised by “Xinmin Weekly”, answered by Prof. Vincent Deubel, Principal Investigator, Unit of Biology of Emerging Diseases, Director General, Institut Pasteur of Shanghai, Chinese Academy of Sciences.
Xinmin Weekly Journalist(Jounalist): There are more and more rabies cases in China these years, especially this summer. What are the factors to cause rabies? What cause animals to be infected and be sick? What cause humans to be sick? Is it related to the seasons?
Vincent Deubel (VD): Rabies is transmitted by a virus present in the saliva of infected and sick animals and transmitted most often by a bite of rabid animal. Individual can also be infected with infectious tissue, such as saliva through mucous membranes. Rabies virus is mainly carried and transmitted by dogs, but other mammals either wild like foxes, raccoons, rodents, and bats, or domestic like cats, or any bovine ,ovine, equine cattle or camels can be infected and transmit the virus to humans or to other animals.
Dogs are fighting animals and infected dogs are more fearful and on defensive when excited, prone to bite.
Rabies is transmitted all year long without specific season. However, outdoor activities in summertime are favorable to promiscuity between human population and infected errant dogs, and to virus transmission.
Journalist: In my view, the rabies virus is a terrible virus to erode neural system. Would you describe how the rabies virus erode human’s neural system and cause them dead?
VD:Rabies virus infects the central nervous system(CNS). It perturbs neurons, and in particular cells that regulate cardiac activity and breath, causing encephalopathy and death.
The incubation period lasts generally one to three months. Dissemination of virus within the CNS is rapid, and includes early involvement of limbic system. Individuals develop symptomatic clinical outcome which often starts with difficulty to swallow, followed by various neuropsychiatric troubles like hallucination, anxiety,agitation, confusion, and hydrophobia and ultimately paralysis and death by respiratory failure. In few days or weeks, patients go into coma and die, generally by respiratory shock.
Journalist: Can we prevent the rabies virus eroding the neural system? How soon will the human have the ability to cure rabies?
VD:Post-exposure specific treatment, well tolerated consists of vaccination and in some cases (animals tested positive for rabies and bites at body extremities and at the head) of serotherapy. It should be initiated as soon as possible after exposure to presumed or declared infected animal, before apparition of symptoms. Vaccinotherapy consist of 4 to 6 injections of anti-rabies vaccine injected within one month.
Journalist:How did physicians treat rabies before Mr. Pasteur developed the vaccine?
VD:There was no therapy against rabies. It was well known that being bitten by a sick animal was fatal.
Journalist:What would rabies develop if there was no vaccine?
VD:Without vaccine, rabies would be one of the most worldwide spread disease which could be contained only by killing rabid dogs or cattle showing typical neurological symptoms like problems swallowing, an increase in drool or saliva, animal biting at everything if excited, difficulty in moving or paralysis, and death. Hundred of thousands people would die of rabies annually.
Journalist: What’s the variability of rabies virus? What difficulties has variation brought to the development of vaccine? What’s the difference between the vaccine developed by Mr. Pasteur more than 100 years ago and the vaccine we use now?
VD:There is a large diversity of viruses that may cause rabies, grouped in a genus called Lyssavirus which includes seven genotypes. The isolates are grouped according to their geographical origin, historical context, and type of vector. Vaccine strains are elaborated from genotype 1 most commonly transmitted by dogs and offer little or no protection against the other genotypes. Thus, it would be necessary to develop new vaccines to extend the vaccine coverage, in particular to protect against rabies viruses transmitted by bats..?
Journalist: Would you tell me the development and application of gene vaccine? Please tell me the immunity theory of the gene vaccine.
VD:The most common gene vaccine or DNA vaccine is so called because the gene coding for the immonogenic protein(s) is under a DNA form (a plasmid prepared in bacteria) under the control of a promoter recognized by cellular polymerase. The protein(s) will be synthesized inside the cells by the cellular machinery after penetration of the DNA inside the cell. The DNA` will first be transcribed in RNA and translated into protein. The protein is then processed by the host cell and presented to the immune system for T cell activation (infected cell lysis) or B cell activation (neutralizing antibodies). The immune response will kill the infected cells and block virus penetration into new cells, respectively.
Journalist: Can the person who has inoculated rabies vaccine be infected rabies virus?
VD:If one person has received the vaccine before being infected with rabies virus, the antibodies and cellular immunity will prevent infection and dissemination of the virus. If one person is vaccinated post-exposure, there is a race between wild virus infection and immune response elicited by the vaccine. Earlier the vaccinehas been delivered, more chance is given to the infected person to block virus progression to the CNS.
Journalist: Why someone infected rabies virus doesn’t show the symptoms of rabies?
VD:Some rabies virus do not infect human or do not show symptoms because their level of replication is low and the host will have the capacity to eliminate the virus more easily and before any damage in CNS occur. In some rare cases, individual infected with rabies virus has not developed the disease yet since the virus may take several years to provoke acute disease. In vary rare cases, genetic resistance to virus infection may occur in some individual, but there is no scientific data available to explain this resistance yet.
Journalist: Is it possible for a rabies virus infected from person to person? Why there are seldom rabies cases about infection from person to person?
VD:Rabies virus is generally transmitted by saliva, through bite or mucous infection. Rabies virus is not transmitted by aerosol or fluids like blood or urine. In addition, it is an enveloped virus highly fragile to chemical (detergent) and physical (temperature, UV). Therefore, chance of virus transmission is very low. In very rare case, like tissue transplantation, the virus has been transmitted from person to person.
Journalist: Has the Institut Pasteur traced the change of rabies of hundred years? If so, what’s your result?
VD:Phylogenetic trees of rabies virus have been extensively been studied and have shown that rabies are evolving similarly to other RNA viruses, may be due to constraints imposed by the need to replicate in multiple cell types within the host, or because viral proteins are not subject to immune selection. Authors, including researchers from Institut Pasteur in Paris and from Oxford, estimated that the current genetic diversity in lyssavirus genotype 1 (including street virus) may have arisen during the last 500 years.
Journalist: Why not inoculate every new-born baby against rabies just as the vaccinia?
VD:Rabies vaccines are presently prepared in cell culture, purified, and inactivated. This makes the vaccine costly and requesting several injection and boosts. In addition, vaccination is not innocuous and should be reserved to exposed personnel or to people who have been potentially infected. .The prevalence of the disease does not justify to include the vaccine in an enlarged vaccination program in children.
Journalist: The rabies is the earliest virus disease that human knows, but why rabies can’t be extinct just as smallpox?
VD:Rabies is a zoonosis, which means that it is carried by animals, and in particular wild animals. It is very impossible to reach all animal population carrying the virus. Smallpox is a disease transmitted only from human to human, like poliovirus or measles, other diseases that WHO expect to eradicate in the future.
Journalist: If a person shows the symptom of rabies, it is sure he will die later. But in history, why there was no epidemic death of rabies just as smallpox and flu?
VD:There were epidemics but by involving a lower amount of people, because rabies is not transmitted by aerosols like flu or by direct contact trough the skin like smallpox. This reduces considerably the risk of human to human transmission.
Journalist: One source says there are 60 countries without rabies in 1988. What’s the standard of “without rabies”?
VD:Countries without rabies mean without notified rabies human or veterinary case. This is based on a reporting system by hospitals and veterinarian clinics, a confirmed diagnostics in medical and veterinarian reference centers, a enforced policy of vaccination of domestic animals (and even wild animals in zoos and in nature), and of vaccination of personnel at risk. In recent years, rabies have been notified in countries declared without rabies, but there were imported cases or cases due to bats originated from neighbor countries.
Journalist: Rabies is epidemic in more than 2/3 of the world nowadays. But 98% rabies cases are in Asia. Why?
VD: Enforced policies of vaccination and of reporting described above helps to reduce and or prevent virus transmission. Governments should be engaged in a sustaining policy to enforce the population to vaccinate their domestic cats and dogs, and to prohibit errant animals. Information of the population about the risk and the disease should also be implemented. This has a cost that Asian countries have difficulties to allocate to the prevention this disease.
Journalist: There was a movement to kill dogs in 1950’s in China and less rabies cases since then. But there are more rabies cases procedures China these years, why?
VD: Virus transmission can be reduced only through a sustaining action by reducing the number of errant dogs which are major carriers and vectors of the virus.
Journalist: When there is a rabies case in a certain area, is it necessary to kill dogs in this area? Why?
VD:In the case of emergency like the situation in China, when an area is known infested with rabies virus, I think that measures of information-education of the population to prevent contact with errant dogs/cats and wild animals (foxes, rodents, bats, raccoons…), of vaccination of domestic animals, and of elimination of errant dogs/cats should be implemented. In some countries endemic for rabies, animals that have bitten individuals are killed and tested for rabies virus before implementing a therapeutic vaccination for the bitten patient. But in epidemic situation, culling wild and errant animals may be recommended to reduce rapidly the risk of transmission. However, a quarantine may be decided for domestic animals if infrastructure in veterinary centers exist. But this has a cost.