How rabies is transmitted in animals: from dogs to humans, how you can get infected

Rabies is a vaccine-controlled zoonotic viral disease. At the stage of clinical symptoms, its mortality rate is 100%. Transmission of the rabies virus to humans in almost 99% of cases occurs from domestic dogs. At the same time, not only domestic animals, but also wild animals can suffer from rabies. The infection is transmitted to people and animals through bites or scratches, usually via saliva.

Rabies is present on every continent except Antarctica, with 95% of human deaths occurring in the Asian and African regions. Rabies is a neglected tropical disease (NTD) that predominantly affects poor and vulnerable populations living in remote rural areas. Approximately 80% of human cases occur in rural areas. Although vaccines and immunoglobulins can be used effectively to prevent rabies in humans, they are not always available or accessible to those in need. Worldwide, rabies deaths are rarely reported in official records; Victims of the disease are often children aged 5 to 14 years. With the average cost of a course of post-exposure prophylaxis (PEP) for rabies being US$40 in Africa and US$49 in Asia, such treatment often places a catastrophic financial burden on affected families, whose daily income averages US$1–2 per person [1].

Every year, more than 29 million people worldwide receive rabies vaccinations after animal bites. This is estimated to prevent hundreds of thousands of rabies deaths each year. The global economic burden of rabies transmitted by dogs is estimated at US$8.6 billion per year.

Prevention

Elimination of rabies in dogs

Rabies is a vaccine-preventable disease. The most cost-effective strategy for preventing rabies in humans is to vaccinate dogs. Vaccination of dogs reduces mortality from dog-borne rabies and reduces the need for AEDs in the care of patients injured by dog ​​bites.

Rabies Awareness and Dog Bite Prevention

An important step following the implementation of a rabies vaccination program is public education about dog behavior and bite prevention among children and adults, as this helps reduce both the incidence of rabies in humans and the financial burden associated with treatment for dog bites. To increase public awareness about methods of preventing and controlling rabies, it is necessary to carry out outreach work and disseminate information about the responsibilities of animal owners, ways to prevent dog bites and first aid after a bite. Forming an active position and sense of responsibility among citizens for the implementation of such programs allows for more widespread and effective dissemination of relevant information.

Immunization of people

To immunize people at the stages after exposure to the rabies virus (see PEP) and before it (used less frequently), the same vaccine is used. Pre-exposure immunization is recommended for persons at high risk in the workplace, in particular laboratory technicians handling live rabies virus and related viruses (lyssaviruses); as well as persons who, in the course of professional or private activities, may come into direct contact with bats, predators or other potentially infected mammals (veterinarians, game wardens).

Pre-exposure immunization may also be indicated for ecotourism enthusiasts and persons moving to remote areas with high risks of exposure to the rabies pathogen and limited availability of anti-rabies biological products. Finally, the possibility of immunizing children permanently or temporarily living in remote areas should be considered. When playing with animals, children are at increased risk of serious bites and sometimes do not report bites to adults.

Symptoms

The incubation period for rabies usually lasts 2–3 months, but can vary from 1 week to 1 year depending on factors such as the site of entry of the rabies virus and the viral load. Initial symptoms of rabies include fever and pain, as well as unusual or unexplained tingling, pinching, or burning sensations (paresthesia) at the wound site. As the virus penetrates the central nervous system, progressive, fatal inflammation of the brain and spinal cord develops.

There are two forms of the disease:

• Rabies manifests itself in the form of hyperactivity, agitated behavior, hydrophobia (fear of water) and sometimes aerophobia (fear of drafts or fresh air). Death occurs within a few days as a result of cardiac arrest.
• Paralytic rabies accounts for about 20% of all human cases. This form of rabies is less severe and usually lasts longer than the violent form. It is characterized by the gradual development of muscle paralysis starting from the site of the bite or scratch. Coma slowly develops and death eventually occurs. The paralytic form of rabies is often misdiagnosed, which contributes to underreporting of the disease.

Symptoms of rabies in humans

The virus can exist in the body asymptomatically for 30 to 90 days. Less often, the incubation period is reduced to 10 days, and even less often it increases to a year. The duration primarily depends on the location of the injury. The longer the virus has to get to the brain, the longer a person will remain outwardly healthy. In medicine, cases have been described in which the disease manifested itself even 4 years after the bite of an infected cow.

The disease goes through three stages of development, each of which manifests itself with different symptoms.

The first signs of rabies in humans

The initial stage, which lasts from 24 hours to 3 days, is characterized by the following symptoms:

• The wound is the first to worry the patient. Even if the bite has already healed by this point in time, the person begins to feel it. The damaged area hurts, the sensations are of a pulling nature, localized in the center of the injury. The skin becomes more sensitive and itchy. The scar becomes inflamed and swollen.
• Body temperature does not exceed 37.3 °C, but does not fall below 37 (low-grade fever).
• Headaches occur and weakness appears. The patient may feel nauseous and vomit.
• When a bite was applied to the face, a person often develops hallucinations: olfactory and visual. The victim begins to be haunted by odors that are actually absent, and non-existent images appear.
• Mental abnormalities appear: the patient becomes depressed and is haunted by causeless fear. Sometimes increased anxiety is replaced by excessive irritability. A person experiences apathy towards everything and becomes withdrawn.
• Appetite disappears. Night rest is disrupted, normal dreams are replaced by nightmares.

Symptoms of the second stage of rabies in humans

The next stage lasts from 2 to 3 days, it is called the arousal stage. It is characterized by:

• Due to damage to the nervous system, there is an increase in the excitability of the neuro-reflex system. The tone of the autonomic nervous system predominates.
• A clear symptom of disease progression is the development of hydrophobia. When an infected person tries to take a sip of liquid, a spasm occurs. The respiratory and swallowing muscles are affected, until vomiting occurs. As the disease progresses, a similar spasm will occur in response to the sound of flowing water and even the sight of it.
• The patient's breathing becomes rare and convulsive.
• Facial spasms appear. Any external irritants cause an acute reaction of the nervous system.
• Convulsions become a response even to stimuli that are insignificant for a healthy person: bright light, wind or draft, sharp sound. This causes fear in the patient.
• The pupils dilate, the eyeballs protrude (exophthalmos), and the gaze is fixed at one point. The pulse quickens, profuse sweat appears, saliva flows continuously, its volume increases significantly.
• Mental disorders progress, the patient is overly excited and becomes violent. He poses a threat to himself and others, behaves aggressively and even violently. Infected people rush at others, fight and bite, tear things and hair, and hit walls. In fact, during such an attack, a person suffers terribly from haunting eerie images and sounds. During the peak of the attack, a person may stop breathing and also stop beating.
• When the attack passes, people behave adequately, non-aggressively, their speech is logical and correct.

Symptoms of the third stage

The final phase of the disease is the stage of paralysis. It lasts no more than a day and is characterized by loss of motor function. The patient's sensitivity is impaired, convulsions and hallucinations no longer haunt him. Various muscle groups and organs are paralyzed. Outwardly, the person appears calm. In this case, a significant temperature jump occurs. It rises to 42 °C, the heart rate increases, and blood pressure drops. A person dies due to paralysis of the heart muscle or respiratory center.

From the onset of symptoms of the disease until the patient dies, it takes from 3 days to a week. Sometimes rabies is characterized by rapid progression and an erased clinical picture. In this case, the victim may die during the first day, after the first meager symptoms appear.

Diagnostics

Currently available diagnostic tools are not suitable for detecting rabies infection before the onset of clinical symptoms of the disease, and diagnosis may be difficult until specific signs of rabies such as hydrophobia or aerophobia appear. Intravital and postmortem confirmation of rabies in humans can be carried out using various diagnostic techniques aimed at identifying the whole virus, viral antigens or nucleic acids in infected tissues (brain, skin or saliva) [2].

Incubation period after rabies infection

In the process of large-scale research, it was found that the rabies virus enters the bloodstream through the bite of a virus carrier. The virus spreads from the site of the bite to the brain. Virus cells travel both in the bloodstream and along nerve fibers.

Important! Until the virus concentration in the brain reaches a critical mass and neuronal damage begins, the animal does not appear sick.

The incubation period is the time between the bite and the onset of symptoms. Incubation of the rabies virus can last from several weeks to several months. An animal bite during the incubation period does not carry the risk of infection, since the virus has not yet entered the saliva. At the final stage of the disease, the sick dog produces saliva with a huge amount of virus.

At the stage when the virus cells have multiplied in the brain, almost all animals begin to show the first signs of rabies. Most of which are not obvious. Within 3–5 days, when the virus has destroyed enough neurons, the animal begins to show obvious signs of infection.

In almost all countries, an animal that bites a person or other pet must undergo a mandatory quarantine period.

Some countries require this quarantine to take place at an approved animal control facility, while others allow quarantine at the owner's home.

Transmission of infection

Infection in humans usually occurs as a result of a deep bite or scratch inflicted by an infected animal, with up to 99% of transmission to humans occurring from rabid dogs.

In the Americas, most human deaths from rabies are now caused by transmission from bats, since transmission from dogs has largely been interrupted in the region. In addition, bat rabies poses an increasing threat to human health in Australia and Western Europe. Cases of human deaths resulting from contact with foxes, raccoons, skunks, jackals, mongooses and other species of wild predatory animals that carry rabies are very rare, and there is no information confirming the transmission of rabies through rodent bites.

Transmission of infection can also occur if the saliva of an infected animal comes into direct contact with mucous membranes or fresh wounds on human skin. Extremely rare cases of rabies infection through inhalation of aerosols containing the virus or through transplantation of infected organs have also been described. Transmission from person to person through a bite or through saliva is theoretically possible, but has never been confirmed. The same applies to people becoming infected by consuming raw meat or milk from infected animals.

What is rabies

Rabies is an infectious disease of viral etiology that gradually affects the entire peripheral nervous system. A person becomes infected through contact with the saliva of an infected animal through injuries to the skin or mucous membranes.

Currently, there is no treatment for the disease, but it is possible to prevent the development of rabies symptoms in a person after a cat bite through timely vaccination. If the vaccine was not administered before the first clinical signs appeared, then death is inevitable.

The rabies virus is a neurotropic microorganism whose size ranges from 100 to 150 nm. Bullet-shaped virions gradually penetrate the cerebral cortex through ascending neurons, then descend into the salivary glands and are released into the external environment.

In the cytoplasm of the affected brain cells, during the life of the pathogen, specific inclusions are formed - Babes-Negri bodies. Their detection plays a leading role in the post-mortem diagnosis of the disease in cats and other animals.

Post-exposure prophylaxis (PEP)

Post-exposure prophylaxis (PEP) involves providing first aid to a bite victim after exposure to the rabies virus. It helps prevent the virus from entering the central nervous system, which inevitably leads to death. The PEP is as follows:

• copious rinsing and local treatment of the bite or scratch wound as soon as possible after possible contact;
• a course of immunization with a powerful and effective rabies vaccine that meets WHO standards; And
• if indicated, administration of rabies immunoglobulin (RAI).

Prompt medical care after exposure to the rabies virus is an effective way to prevent symptoms and death.

Copious rinsing of the wound

This type of first aid involves immediately and thoroughly irrigating and washing the wound with soap and water, detergent, povidone-iodine, or other substances that remove and kill the rabies virus for at least 15 minutes.

Risk of exposure and indications for AEDs

Depending on the degree of contact with an animal that may presumably be infected with rabies, a full set of PEP may be recommended according to the following scheme:

A PEP is required for all Category II and III exposures assessed as presenting a risk of developing rabies. The risk increases in the following cases:

• it is known that the mammal that bit a person belongs to a species that is a carrier or vector of rabies;
• the exposure occurred in a geographic area in which rabies is still present;
• the animal appears sick or exhibits abnormal behavior;
• the wound or mucous membrane is contaminated with animal saliva;
• the bite was not provoked;
• the animal is not vaccinated.

If the animal's vaccination status is not definitively established, it cannot be considered as a determining factor in deciding whether to initiate ECP. Such situations are possible when the organization or control of the implementation of dog vaccination programs is unsatisfactory due to lack of resources or low priority of such programs.

WHO continues to actively advocate for the prevention of rabies in humans through the elimination of rabies in dogs, the implementation of strategies to prevent dog bites, and the widespread introduction of intradermal AEDs, which reduce the volume and thus reduce the cost of cultured cell culture by 60-80%. vaccines.

Comprehensive management of bite cases

If possible, the bite should be notified to veterinary authorities, and the biting animal should be identified, isolated, and either quarantined for observation (in the case of healthy dogs and cats) or referred for immediate laboratory evaluation (in the case of dead or euthanized animals with clinical signs). signs of rabies). AED must be continued for a 10-day observation period or until laboratory results are available. Preventive treatment may be interrupted once it is confirmed that the animal is not infected with rabies. The full course of PEP must be completed if an animal with suspected rabies cannot be caught and tested. Veterinary and medical authorities are encouraged to jointly conduct contact tracing to identify other suspected rabid animals and human bite victims so that appropriate preventive measures can be taken.

Treatment of rabies in humans

Once symptoms first appear, the disease becomes incurable. All actions of doctors will be reduced only to making a person feel better. They try to isolate him from external stimuli, administer opioid analgesics, and perform maintenance therapy. Artificial ventilation helps prolong life, however, death is inevitable.

Post-exposure vaccine

Providing first aid to the victim is the responsibility of the surgeon working in the anti-rabies care center. The patient receives an injection on the same day he seeks help.

If previously up to 30 vaccinations were administered in the abdominal area, under the skin, then since 1993, such a scheme for preventing the disease was abandoned. A modern vaccine (COCAV) is currently in use. It is purified and makes it possible to significantly shorten the treatment course, as well as reduce the dosage administered once.

The vaccine is not injected into the buttock! For children it is placed in the thigh (outer surface), and for adults and adolescents in the deltoid muscle. Standard dosage is 1 ml. The effect of the administered vaccine reaches 98%, however, it is important to give the first injection no later than two weeks after receiving an injury or bite.

When a patient first contacts him, even months after dangerous contact, he will be prescribed a course of treatment.

After the vaccination has been done, the first antibodies to the virus will appear after 14 days, their maximum concentration will occur in a month. When there is a risk of shortening the incubation period, the patient is administered rabies immunoglobulin.

When the course is completed, the person will develop immunity, which will begin to work 14 days after the last injection.

The formed protection will operate throughout the year.

Despite existing vaccines and immune globulin, people continue to die from the virus. This occurs as a result of their low awareness of the dangers of the disease and due to their failure to consult a doctor. Some victims refuse medical care and in 75% of cases die due to infection. Sometimes the blame for the death of such patients lies with doctors who incorrectly assessed the degree of threat to human health (up to 12.5%). Some patients (up to 12.5%) die due to interruption of the course or violation of the vaccination regimen.

It is strictly prohibited for patients undergoing treatment, as well as 6 months after its completion: to consume any alcoholic beverages, excessive physical fatigue, being in a bathhouse or sauna, or hypothermia. This is due to a decrease in antibody production and deterioration of immunity. If the patient receives concurrent treatment with immunosuppressants or corticosteroids, monitoring of antibodies to the virus is necessary. If they are produced in insufficient quantities, then additional therapy is necessary.

Typically, most people do not experience any side effects after receiving the vaccine. It is most often well tolerated. Minor allergic manifestations are observed in no more than 0.03% of cases.

There are no contraindications for administering the rabies vaccine, due to the mortal threat of the sick person.

Injections are administered to women carrying a child and to patients with acute pathologies.

In what cases is it not necessary to get vaccinated?

• If an animal gets in contact with saliva or touches the intact skin;
• If an animal bites a person through thick fabric and it is not damaged;
• When an injury occurred from the beak or claw of a bird;
• When bitten by animals living at home, if they have been vaccinated against the virus and have not shown signs of illness for a year.

As for domestic animals, a person is not vaccinated if he has not been bitten on the neck, face, fingers or hands, and also if the bite is single. When the injury is localized in a dangerous place or is multiple in nature, the person is given 3 vaccinations. This is necessary because even vaccinated pets can be carriers of the virus.

The injured animal must be monitored; if it shows signs of illness, vaccination should begin immediately.

If infection is likely to occur. The vaccine must be given if you have received an injury (bite, scratch, saliva on damaged skin) from a wild animal. If it is possible to monitor him, then the person is given only 3 injections.

Prevention is stopped if the animal remains healthy for 10 days after the injury.

Also, 3 vaccines are sufficient if the animal was killed and no rabies virus was found in its brain.

The course is completed in full if:

• The fate of the animal is unknown;
• It had contact with representatives of wild fauna.

If an injured person was vaccinated with a full course earlier, and 365 days have not passed since that time, then he is given three vaccines (first, 3 and 7 days). If the year has already passed, then it is necessary to complete a full therapeutic course.

Anti-rabies immunoglobulin

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Therapy using immunoglobulin is necessary for implementation within 24 hours after injury. This period should not exceed 3 days after possible infection and before the 3rd vaccine was administered. The dose is 20 IU/kg immunoglobulin.

One half of the calculated dose is injected around the damaged tissue (the wound can be irrigated). The rest is injected into the muscle (into the thigh - into its upper third or into the buttock). The vaccine and immunoglobulin are not administered with the same syringe!

They can be combined if there are the following indications:

• The bite is deep, bleeding is observed;
• There are multiple bites;
• Injuries occurred in hazardous areas.

You should remember the deadly danger of the virus. It is necessary to consult a doctor immediately after an injury or after situations involving a risk of infection arise.

WHO activities

Rabies is included in the new WHO roadmap for 2021–2030. The fight against rabies, given the zoonotic nature of this disease, must be carried out within the framework of close interagency cooperation at the national, regional and global levels.

• As part of a comprehensive approach to health, WHO, FAO (Food and Agriculture Organization) and OIE (World Organization for Animal Health) have made rabies control a priority.
• The WHO-led Unite to Stop Rabies initiative serves as a multi-stakeholder platform to mobilize and share rabies resources and coordinate global efforts to eliminate rabies in humans, with the goal of achieving zero dog-borne human deaths by 2030 rabies.
• WHO works with a range of partners to provide guidance and support to countries in developing and implementing national rabies elimination plans.
• WHO regularly reviews and disseminates technical guidance on rabies control issues [3], such as epidemiology, surveillance, diagnostics, vaccines, safe and cost-effective immunization [4], strategies for the control and prevention of rabies in humans and animals, and practical implementation of programs [5 ] and palliative care for people with rabies.
• During rabies elimination, countries can ask the WHO to certify that they have achieved zero mortality from dog-borne rabies [3], submit an application for approval of a canine rabies control program to the OIE, or independently declare the elimination of canine rabies [6].
• In 2021, Mexico became the first country to be certified by WHO as having eliminated deaths from rabies transmitted by dogs.
• WHO's priorities to help strengthen the global movement towards universal health coverage include including rabies biologics on national schedules and promoting increased access to AEDs for poor and rural populations.
• In 2021, the GAVI Alliance included human rabies vaccines in its Vaccine Investment Strategy 2021–2025, which will support increased uptake of EPPs for suspected rabies cases in GAVI eligible countries; WHO will continue to provide advice to the Alliance on strategies and methods for introducing rabies vaccine in countries that request it.
• To evaluate the effectiveness of rabies control programs and to increase public awareness and outreach efforts, monitoring and surveillance of such programs is necessary.

The main document that will guide efforts to combat NTDs in the next decade is the Roadmap to combat NTDs for the period until 2030, which indicates phased regional targets for the elimination of rabies [7].

The following principles are key to sustaining rabies control programs and expanding them to surrounding areas: start small, implement local rabies programs through comprehensive incentives, demonstrate program success and cost-effectiveness, and engage government agencies and affected populations.

Elimination of rabies requires sufficient long-term investment. Effective and proven methods of attracting attention and mobilizing political will in this area are demonstrating success on the ground and publicizing the rabies problem widely.

[1] Zero by 30: the global strategic plan to end human deaths from dog-mediated rabies by 2030 [2] WHO, Laboratory techniques in rabies. Fifth edition. Volume 1 and Volume 2 [3] WHO expert consultation on rabies: Third Report. TRS N°1012 [4] Rabies vaccines: WHO position paper – April 2021 [5] Scientific and operational updates on rabies [6] OIE Rabies Portal [7] Ending the neglect to achieve the sustainable development goals: a road map for neglected tropical diseases 2021–2030