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Rabies - in animals and in humans - an outbreak in northern Israel

Although not an epidemic disease, rabies is one of the most serious diseases transmitted from animals to humans. How it happens, and how to treat an infected person

In 2017 and at the beginning of 2018, the rabies epidemic broke out in settlements in Gilboa and the northern valleys. In 2017, at least 74 animals became ill with rabies (and were destroyed) - 47 jackals, 14 cows, ten dogs, two cats and one sheep. All the sick domestic and farm animals and 11 people were bitten by sick jackals, some of the biting jackals were not caught. The people who were bitten, and those who were in contact with the animals that got sick (if they sought treatment) were treated with a series of vaccinations, as detailed below, to prevent the outbreak of the disease in them. Without treatment the disease is fatal.

A dog in the Beit Shean Valley, November 2017, with suspected rabies. He was completely apathetic and moved towards the photographer's vehicle without fear. Photography: Avihai Ran
A dog in the Beit Shean Valley, November 2017, with suspected rabies. He was completely apathetic and moved towards the photographer's vehicle without fear. Photography: Avihai Ran

In the current outbreak, no humans became ill with rabies, and if everyone who was affected or was in contact with sick and suspected animals sought treatment, they would not become ill either. In the past, rabies claimed victims in our country as well: in the first decade of the country, 23 human deaths occurred from rabies. Since then four more people have died from the disease - three in 1997 and one in 2004.

rabies disease

Rabies is a fatal and incurable viral disease of the central nervous system, mainly in the brain, in all mammals. Mortality from the disease is about 100%, because once the signs of the disease appear there is no way to overcome it. Most often, a bite or scratch from an animal infected with rabies transmits the virus that causes the disease, but there are also other ways. From the moment the virus enters the body until it reaches the central nervous system - the damage to which causes the symptoms - may take quite a long time. At this time, a combination of injecting antibodies against the virus (tolerant vaccine) and an active vaccine prevents the development of the disease.

It's true - it's not an epidemic disease, and when it occurs, it's isolated cases here and there, but it's one of the scary diseases that accompany us and the animals around us, since the dawn of history.

Rabies virus

The rabies virus, Rabies virus, is a negative RNA virus (in which the genetic information to create the virus proteins is encoded by the complementary strand), belonging to the genus Lyssavirus of the Rhabdoviridae family. Besides the rabies virus, the genus also includes 13 other viruses, all of which infect and reproduce in mammalian cells. It is an enveloped and bullet-like virus, whose dimensions are 180×75 nanometers. The envelope (originating from the host cell) contains the protein lugs of the virus. The protein box of the virus (the virion) contains, in addition to the viral RNA, the enzyme for replication and transcription of the RNA. The host range of the virus is wide and includes most mammals. In the infected animals, the virus multiplies in muscle cells, epithelial cells (the cells that line internal spaces in the mammalian body), connective tissues and cells in the nervous system. The virus is found in saliva, urine, milk and lymph, and probably also in other body fluids. In some hosts, including humans, the virus is not found in the patient's blood. In most hostels the virus is deadly. Exceptions are certain species of bats that carry and spread the virus, some without any signs of illness.

Rabies viruses in an electron microscope photo: CDC/ Dr. Fred. A. Murphy
Rabies viruses in electron microscope photography
Photo: CDC/Dr. Fred. A. Murphy

The names of the disease and the virus

Rabies - most cases of rabies are related to dogs and their relatives from the canine family - hence the name of the disease. The English name Rabies originates from the Latin word rabere which means grumpy, raging. The origin of the Latin word is probably from the word rabhas in the Sanskrit language which means to act violently. Hence the name of the family of viruses in which the cause of the disease is included - Rhabdoviridae. In Greek, the disease is called Lyssa or Lytta, which in Greek mean madness or rampage. Hence the name of the genus in which the virus is included - Lyssavirus.

The disease in humans was also called hydrophobia - fear of water - one of the typical symptoms of patients with the disease.

the development of the disease

After being infected with viruses through some kind of injury - and probably even through the respiratory system - and after the first culture cycle in the epithelial cells or muscle cells near the site of infection, the viruses reach the peripheral nervous system and other structures in the body (including the various excretory glands). From the peripheral nervous system they "advance" towards the central nervous system and when they reach it the signs of the disease begin to appear. In a person it is usually a period between ten days and a year. The time varies depending on the distance between the entry area of ​​the virus and the brain (bite in the face vs. a bite on the leg, for example), the initial amount of viruses and other factors. One extreme case of a girl who became ill eight years after being bitten is also known. The initial signs are not unique, and are similar to other neurological diseases: temperature rise, headaches, dizziness, nausea and vomiting. The animal becomes aggressive, and sometimes on the contrary - too quiet, afraid of water, foamy mucus is secreted from its mouth, swallowing difficulties are revealed and convulsions begin. Paralysis later develops leading to death. The animal usually dies after about 10 days from the appearance of the signs of the disease.

Around the world, tens of thousands of cases a year of people dying from the disease are reported and millions receive treatment after contact or suspected contact with an animal infected with the disease. There is no natural infection between person to person (although theoretically it is possible). So far, five deaths of transplant recipients who contracted the disease and died from it have been recorded: in four of them, corneas were transplanted from donors who died of an unidentified neurological disease (and were not diagnosed as having rabies). The fifth underwent a kidney transplant about two years before his death, and in retrospect it turned out that the donor was bitten by a rabid raccoon several months before his death. Three additional transplantees, who received the organs (heart, liver and the second kidney) of the same donor were treated accordingly.

In Israel - stray dogs, wolves, jackals and foxes are the main reservoir of the virus. Other wild mammals such as raccoons, badgers, skunks, coyotes and bats are a reservoir for viruses in other countries.

The disease in history

Rabies is first mentioned in the scriptures about 4000 years ago in the laws of Eshnunna (Eshnunna - an independent kingdom in the Sumerian period). There is detailed the financial fine that the owner of a mad dog must pay to the families of the people it bit and who died as a result: 40 shekels of silver for a free person and 15 shekels of silver for a slave.

In Greek mythology, two gods were "appointed" as responsible for the disease - Areseus (son of Apollo) to prevent it, and Artemis to cure it.

In the Iliad, Homer compared Hector to a furious dog and mentioned Sirius, the dog star, which has a deadly effect on humans. The Greek philosopher Democritus mentioned it in his writings (420 BC) as a disease of dogs, while Aristotle wrote about dogs suffering from madness, which causes them to growl, and that every animal bitten became ill.

In the first century AD, the Roman Cardanus described the mucus in the mouth of a sick dog as a virus (poison in Latin; he did not know how "right" he was). His contemporary, the philosopher and naturalist Gaius Pliny II, described the cause of the disease as "a worm from the tongue".

The Roman physician and encyclopedist Celsus (Celsus, 25 BC to 50 AD) was the first to study the disease and came to the conclusion that mucus from the sick dog is enough to cause it. He was the one who suggested cleaning the wound thoroughly and even cauterizing it - the treatment that remained for about 1800 years after him (and mostly didn't help).

Many outbreaks of rabies have been described in the last two thousand years, mainly throughout Europe and Western Asia. The first description of rabies in the New World was during the Spanish invasion (~1500) - then one of the Spanish bishops described small animals (probably vampires - blood-sucking bats) biting the soldiers' fingers while they were sleeping and causing them to die. Since then there have been many more reports. In 1789, a tanner from New York was recorded skinning an infected cow that fell ill and died of the disease.

At the beginning of the 18th century, stories and legends about blood-sucking vampires began to appear in Central Europe and the Balkans. The fictional character Dracula was built on the basis of these legends, to which the historical character (Vlad the Impaler) was later adapted. Some believe that the symptoms of rabies (hallucinations and fear of water and light) and the means of its transmission - the bites - mainly by wolves, which were more common then than today. plays a significant role in the development of these legends.

Actual research on rabies began in the early 19th century. In 1804, the German researcher George Zinke published his research on the disease in a book, and other researchers followed suit.

The significant breakthrough in the treatment of rabies was in 1881 in the joint research of Emile Roux and Louis Pasteur. In this study, they developed a vaccine against rabies by drying the spinal cords of sick rabbits, injecting them into dogs and deliberately infecting them with the disease. Thanks to the injection, the dogs were vaccinated against it. Rowe and Pasteur's research reached its peak on July 6, 1885, when they were approached by Joseph Meister, a 9-year-old boy who had been bitten by a sick dog. Pasteur injected him with the vaccine he had developed - 13 injections with time intervals between them, and the boy was saved. Three months later, 15-year-old Jean-Baptiste Jupille, who also survived, was also vaccinated. The vaccine opened a new era in human relations with this terrible disease.

In 1953 it was discovered for the first time that bats can be carriers of the virus. Later it turned out that staying in caves where there is a heavy load of bat secretions can also cause the disease to appear, even without physical contact with the bats.

Diagnosis of the disease:

It is possible to clearly identify that it is rabies, if in the post-mortem analysis Negri bodies are found in the brain tissue (Negri bodies, named after the researcher who discovered them, Adelchi Negri). These bodies are actually clusters of the viruses in the cytoplasm of the cells, and are observed in about 80% of cases.

Microscopic observation of a section of the brain of a rabies victim. The black dots are CDC/Dr. Daniel. Perl
Microscopic observation of a section of the brain of a rabies victim. The black dots are CDC/Dr. Daniel. Perl

Another possibility, when the animal is still alive, is to inject its saliva into the brains of mice. If it is rabies, paralysis of the limbs, encephalitis and death develop in them within a few days.

Another option is the infection of cell cultures, which allow the culture of rabies viruses, in the body fluids of the suspect animal and after a time the virus is identified by unique antibodies.

Can rabies patients be cured? – Milwaukee Protocol

As mentioned, this is a fatal and incurable disease, and the patient's treatment is mainly focused on alleviating the suffering. However, there were several exceptional cases: in October 2004, About a month after a bat bit her finger, 15-year-old Jeanna Giese began to show signs of rabies. Just five days after developing symptoms, she was rushed to Children's Hospital of Milwaukee. There the doctors, led by Dr. Rodney Willoughby, decided to try and save her by anesthetizing her for an extended period and giving her a cocktail of antiviral drugs. The idea of ​​anesthesia was based on the thought that the virus mainly causes disruption of the activity of the brain, and what actually kills the patient are the wrong commands of the brain that disrupt the activity of other vital organs. Stopping the activity of the brain due to the anesthesia may prevent some of the damage and the immune system will have more time to deal with the virus.

The unusual treatment was indeed successful, and after 76 days of hospitalization, Gina was released from the hospital alive and in reasonable condition, but with neurological damage. After about a year of strenuous restorative treatments, she overcame most of the damage.

The unusual treatment, which has since been called the "Milwaukee protocol" has since succeeded in saving five more rabies patients, but failed in another 35 patients. Although there is There is a small chance of recovery with it, but the best way to deal with the disease is to vaccinate before the symptoms appear.

 Vaccines that prevent rabies in humans

In retrospect, we know today that the vaccine that Pasteur and Roe created was actually a vaccine with weakened viruses (viruses were not yet known in their time). The viruses were weakened by drying, for 10-5 days, the spinal cord containing them. The vaccine was injected in 13 doses at regular intervals. The following generations of vaccines were inactivated viruses, also known as "killed". The inactivity was achieved by treating viruses isolated from the brains of animals that died of the disease, with UV radiation or with chemical substances, such as phenol. These vaccines had a side effect, often fatal: damage to the myelin (demyelination) of the nervous system, which occurred in one vaccine out of 3000. In developing countries, these vaccines are still used, but their effectiveness is less than the modern vaccines.

Louis Pasteur saves a man bitten by a rabid dog. On the side, a girl who was bitten is waiting for her turn. Source: Iconographic Collections
Louis Pasteur saves a man bitten by a rabid dog.
On the side, a girl who was bitten is waiting for her turn.
Source: Iconographic Collections

Four main vaccine components are given today to humans who have come into "problematic" contact with animals infected or suspected of being infected with rabies, in North America and Europe, as well as in Israel. The ingredients include killed viruses that are harvested from infected cultures of human cells (Human diploid cell vaccines - HDCV), green gonon cells (PVRV - Purified Vero Rabies Vaccine), chicken embryo cells (Rabipur) or duck embryo cells (Purified duck embryo vaccine). These ingredients have far fewer side effects than the brain-based ingredients, but the relatively expensive price of cultured vaccines prevents their use in developing countries.

Veterinarians, laboratory workers and other workers at risk of contact with sick animals receive an initial preventive vaccination consisting of three doses of HDCV at intervals of one week and three or four weeks after the first vaccination, and then renew the vaccine every two years.

To prevent rabies in those exposed to the virus, the person must be injected with antibodies (produced from the blood of people vaccinated with an active vaccine - Human Rabies Immune Globulin - a tolerant vaccine) against the virus up to ten days after exposure. In addition, an active vaccine (killed or modified virus) is used. given After a bite or scratch by an animal suspected of being infected, the wound is disinfected, the antibodies against the virus are injected and a series of injections of the active vaccine is given. In Israel, Rabipur is used divided into five doses that are given on the day the treatment starts (with the antibodies), 3, 7, 14 and 28 days later. Administering the vaccinations in time, before the symptoms appear, prevents the disease - so you should immediately contact the nearest health office if you are bitten by an animal, and assess the need for the vaccinations. The active vaccine is also given as preventive treatment to populations at risk, veterinarians, wildlife researchers and travelers to countries where rabies is common. It does not provide protection from the disease, but allows for easier treatment in case of exposure and apparently increases the amount of time from the moment of exposure when treatment must be started.

Wildlife vaccination

Another means, which also helped to eradicate the disease from certain and relatively isolated areas, is the genetically modified vaccinia virus (the virus with which we immunized against the smallpox disease), whose outer envelope expresses one of the proteins of the rabies virus (V-RG: vaccinia rabies glycoprotein). This transgenic virus has been in use since 1983 and is given by feeding (live oral vaccine). Baits containing it in a glass capsule (chicken heads or "bonzo cookies" or any other food) can be spread over large areas, vehicles and aircraft, thus vaccinating most of the wild animal population. The glass capsule shatters in the mouth, and through the wounds the virus of the vaccine penetrates the blood and nervous systems.

In the State of Israel this method is indeed used, but its effectiveness is only partial since the neighboring countries do not act in the same way and the virus continues to enter the country with infected animals crossing the border.

Vaccination of domestic animals

Dogs, cats and other domestic and farm animals may be "intermediaries" in the transmission of the disease to us from wild animals or stray animals that are carriers or infected with the disease. That is why it is very important to vaccinate this population and it is done in many countries and backed by legislation. All dogs in Israel must be vaccinated annual In the composition of killed viruses - Rabisin (consider vaccination once every two years). In addition, some of the cats and animals are stored in the compound in animal corners and zoos.

Summary

Although the scope of rabies morbidity is small compared to other diseases, it is a deadly disease, with awareness, desire and resources it is possible to reduce the morbidity from it to a considerable extent and even get rid of it completely in areas where there are no carrier bats (there are none in Israel) and there is no infiltration of infected individuals from neighboring countries.

So what needs to be done in Israel to reduce the damage from the disease.

  1. Continue to vaccinate the wild animals by distributing baits containing a vaccine against the disease. and increase the dispersal on our northern borders, with Jordan, Syria and Lebanon, beyond which we do not stockpile.

  2. Take care and vaccinate our pets, especially dogs.

  3. In any case of incidents with a wild animal, pet or farm animal, whose health and behavior are suspicious, Avoid direct contact with the animal, stay away from the place and report to the Israel Nature and Parks Authority hotline by calling *3639.

  4. Seek a medical diagnosis in cases of bite or scratch by an animal. Instruct children and teenagers to report to their parents or medical personnel any bite or scratch from an animal, even if they are familiar with it.

As long as our neighboring countries do not vaccinate their wild animals against the disease, we will not be able to eradicate it. Just reduce the damage...

for further reading:

Summary of rabies events for 2017 - on the website of the Ministry of Agriculture 

on rabies - on the website of the Center for Disease Control - in the United States

2 תגובות

  1. It is also important to shoot stray dogs and give a ringing slap to the dog lovers - haters of people who oppose this.

  2. Hello, thanks for the comprehensive article.
    You mentioned that the virus is also found in urine. Is it in the same concentration as Brook?
    How many in the world die from rabies a year?
    Thanks

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