Rabies research in Yan Jiaxin

Rabies is an acute encephalitis caused by rabies virus, and the mortality rate is about 100%. All mammals are susceptible to rabies virus, but the main storage hosts of the disease are only Carnivora and Chiroptera, including dogs, cats, foxes, jackals, wolves, raccoons, mongooses and bats. The disease can be transmitted from the above storage host animals to other mammals and humans. In nature, mammals other than the above storage hosts, such as rats and rabbits, can only be infected under extremely accidental circumstances, which can be collectively called accidental hosts, and they usually do not constitute the source of infection of the virus. More than 99% of human rabies is caused by bites or scratches from sick dogs (a few are cats).

The disease can also be transmitted by direct contact between infectious substances (usually saliva) and the victim's mucosa or newly damaged skin, but this situation is very rare. Humans are occasionally infected by being bitten or scratched by some wild mammals. Virus inhalation, incomplete inactivated vaccine inoculation or transplantation of infected cornea, tissues and organs may also cause infection, but it is extremely rare.

Incubation period (up to six years)

"The incubation period ranges from 5 days to several years (generally 2-3 months, rarely exceeding 1 year), …"

At present, the longest incubation period of rabies recognized by the international mainstream scientific community is 6 years. American scholar 199 1 reported the case in a professional magazine. However, due to the lack of similar cases and incomplete evidence chain, the international academic community still has objections to the case report. The disease can also be transmitted through direct contact between infectious substances (usually saliva) and human mucosa or recent skin damage. Although there is a theoretical possibility of interpersonal transmission due to bites, it has never been confirmed.

Inhaling aerosol containing virus particles or transplanting infected organs may cause rabies, but this is rare. Ingesting raw meat or other tissues of animals infected with rabies is not the source of human infection. Before the clinical symptoms appear, there is no reliable detection method to diagnose whether people are infected with rabies.

The precursor symptoms of rabies are not specific. Early local symptoms include paresthesia, itching and pain at the site of virus invasion, which are considered to be the result of local sensory ganglion infection and inflammation. The initial clinical manifestations of rabies are often fever, tingling or unexplained burning pain. With the spread of the virus in the central nervous system, people's behavior is abnormal, which is manifested as fidgeting and fluctuating consciousness disorder. Patients feel oversensitive, have abnormal aggressive behavior and sexual behavior, have spasms after being stimulated by touch, hearing, vision or smell, have fear of wind and water, have difficulty breathing, swallow and secrete too much salivary glands. Almost all rabies patients who are mainly excited will have this kind of spasm at some stage, and signs such as wakefulness or irritability, confusion and autonomic nervous dysfunction will appear alternately in the middle. After a few days, the patient may die in a coma due to cardiac arrest and breathing. It is difficult to make a clinical diagnosis without specific signs of rabies such as fear of water and wind. Paralytic rabies accounts for 30% of the total number of rabies cases in human beings, showing paralysis or Guillain-Barre syndrome or other atypical clinical manifestations. The onset process is quiet and the excitement is not obvious; Accompanied by quadriplegia and sphincter dysfunction. Typical early signs include muscle edema and hair erect at the percussion site (usually in the chest, deltoid muscle and thigh). The course of disease is usually longer than manic rabies, but it will eventually lead to death. Paralytic rabies is often misdiagnosed, which leads to underestimation of the incidence of the disease. Pathologically speaking, the incubation period of rabies virus is usually long. After the virus enters the dog, it does not directly enter the blood circulation, but slowly reaches the brain along the nerve, proliferates and then returns to peripheral organs such as salivary glands, and then it is contagious. When dogs are contagious, a large number of rabies viruses have been propagated in the brain. After 3~5 days, with the further propagation of the virus in the brain, dogs that bite and have "toxic" saliva will inevitably get sick and die in a few days. This is the theoretical basis of "ten-day observation". Dogs may have to go through a ten-day observation period to get sick, but in this case, the bitten person is still safe, because although the dog got sick later, it proved that the dog did have "poison" in its brain when it bit people, but at this time, the virus has not propagated to a certain number and has not transferred to salivary glands, and the biting fashion is in the incubation period, and saliva is virus-free.

If a person is bitten by a dog and dies of rabies, the biting dog cannot be a healthy dog and will eventually die of rabies. In other words, it is absolutely impossible for a dog that bit him to be alive after a person died of illness.

The official document of WHO has always recognized that the "ten-day observation method" can be adopted: if the animal is a dog or a cat and remains healthy within the observation period of 10 days after exposure, the post-exposure prevention can be terminated. (It should be emphasized that in rabies epidemic areas, after a suspected dog or cat bites a person, it is necessary to immediately start prevention after exposure while adopting the "ten-day observation method", otherwise it may be too late to take preventive measures against the bitten person after observing that the dog or cat has become ill a few days later. Anyone who has been vaccinated with 3 stitches (or more) before should be vaccinated with 1-2 stitches after re-exposure. Moreover, people who have been vaccinated with 3 injections (or more) before will no longer need to be vaccinated with rabies immunoglobulin. After vaccination with 3 doses of rabies vaccine, the antibody titer is much higher than the minimum suitable titer within half a year, so it is usually unnecessary to detect antibodies. After intensive inoculation, the effective protection period is at least 3 years.

The latest WHO regulation is that no matter how long you have been vaccinated, you only need 2 injections after re-exposure.

In 2009, the regulations of the Ministry of Health of our country on the disposal after re-exposure were: 1-3 injections within three years, and 5 injections after three years.

Disposal after re-contact. Wound treatment: after any exposure, the wound should be treated thoroughly in time first. Vaccination: Under normal circumstances, the antibody level in the body can be maintained at least 1 year after the whole vaccination. If re-exposure occurs during immunization, continue to complete the whole vaccination according to the original procedure without increasing the dose; Those who are exposed again within half a year after full immunization generally do not need to be immunized again; Those who are exposed again within half a year to 1 year after the whole immunization should be vaccinated with 1 dose on the 0 th and 3 rd days respectively; Those who are exposed again within 1-3 years should be vaccinated with 1 dose on 0, 3 and 7 days respectively; Those who have been vaccinated for more than 3 years should be vaccinated all the time. Rabies phobia is a unique phenomenon in China. No country in the world attaches so much importance to rabies as China. The general prejudice and fallacy against rabies is one of the important reasons for the massive abuse of rabies vaccine in China.

At present, China people are most afraid of infectious diseases, except AIDS, which is rabies. Rabies phobia, referred to as "phobia", has now become a very popular psychological disease that can almost keep pace with "phobia".

The most common manifestation of phobia is the abuse of rabies vaccine. Even after repeated vaccination, people still have a lingering fear.

Rabies is an infectious disease with the highest mortality and the lowest incidence, and it is easy for people to overreact. At present, unscientific remarks about rabies are rampant on the Internet or in real life, and all kinds of strange opinions are quite common among "experts" and the public, which makes some people who have contacted cats and dogs (even those who have never contacted them at all) stay in fear for a long time, and even develop into obsessive-compulsive disorder or hysteria. Some people have been vaccinated many times, but they still travel thousands of miles to Wuhan for antibody testing every month, fearing that "once the antibody is lowered, rabies will break out." Some people think that the virus has infiltrated their brains, and they will die, lose their jobs, look up information on the Internet all day, and be at a loss in all kinds of contradictory information. Some people suspect that the vaccine is fake, some people suspect that there is a live virus in the vaccine, some people suspect that rabies virus can spread through the air, and some people suspect that nurses and experts are struggling with endless troubles all day.

When it comes to rabies, we must first clarify the most basic fact: the risk of rabies is not the same as that of AIDS (there is no effective vaccine for the latter at present, and the relevant basic immune mechanism is still unclear). The prevention and treatment of rabies has been basically solved in medicine for a long time. Rabies has been effectively controlled in all developed countries and some developing countries in the world, and the number of rabies deaths has remained at or near zero every year for many years. Rabies 100% can be prevented: no matter how serious the exposure is, 100% can be avoided as long as it is treated according to the plan approved by the World Health Organization (WHO).

In this article, the author will list some representative cases and explain how to avoid the abuse of rabies vaccine. The author will provide several simple and practical standards to help phobia patients get out of the shadows as soon as possible.

How long is the incubation period?

The incubation period of rabies may be as long as forty years? Fifty years? Even for life. Is China going to set the Guinness Book of Records again? In some professional magazines and even textbooks in China, the incubation period of rabies is often described as decades.

Are these "cases" in China really rabies? Because there is no laboratory diagnosis basis, or it is impossible to prove that no new infection has occurred recently (for example, through some special or rare ways), these "cases" have not been recognized by international academic circles, and even passed down as jokes internationally, as an example of the low level of related science in China.

Domestic and foreign data show that the incubation period of rabies is usually 1-3 months, and the incubation period of a few serious head and face bites may be as short as 7 days, and the incubation period of a few cases (less than 1% of the total) may exceed one year.

At present, the longest incubation period of rabies recognized by the international mainstream scientific community is 6 years. American scholar 199 1 reported the case in a professional magazine. The deceased was a Filipino immigrant who never left the United States after immigrating to the United States. Because the probability of rabies infection in the United States is extremely small, and the results of partial gene sequence analysis prove that the rabies virus isolated from the brain of the deceased is the same as the strain prevalent in the country of origin of the deceased, this report proves with the most convincing evidence so far that the incubation period of rabies may be as long as 6 years.

Due to the small number of similar cases and the incomplete evidence chain, the relevant academic circles still have objections to the case report. For example, many French scholars believe that cases with incubation period of more than one year, if any, are very few, and the possibility of recurrence after one year is slim. They all laughed at the idea of extending the incubation period.

Too many people have been bitten by dogs in China for decades. If the incubation period of rabies is really that long and so many people have to be vaccinated, then the annual vaccination amount of rabies in China will increase by a considerable amount. Many phobia patients are scared silly by the legend that rabies has a long incubation period.

Popularize the "ten-day observation method"

We must firmly believe that healthy dogs will not spread rabies! Based on the results of field investigation in China, Chinese and American experts jointly wrote relevant papers, which were published in the third issue of American Journal of Vector-borne Diseases between People and Animals in 2008. But physical health is not equal to real health, which must be tested by experiments or identified by "ten-day observation". After a person is bitten by a dog, if the dog can be killed immediately and the brain tissue is taken for testing, it can be determined whether the bitten person needs vaccination according to the test results (whether there is virus or not). If animals are killed unconditionally on the spot for experiments, the "ten-day observation method" recognized by WHO can be applied: "If dogs (or cats) remain healthy during the observation period of 10, ... the treatment can be terminated."

In recent ten years, our laboratory has not found enough evidence to deny the "ten-day observation method" at home and abroad. This method is a simple and practical method to judge whether dogs (or cats) are contagious, and it is also suitable for China.

It should be noted that in the epidemic areas where rabies is prevalent, people who have not been vaccinated before should immediately start post-exposure prevention while starting the "10-day observation method", and then determine whether they can keep the next 2 or 3 shots of vaccine according to the observation results.

At present, the vast majority of dogs or cats kept in cities are pets, and they usually have little contact with the outside world, so it is convenient to implement the "ten-day observation method". If the "ten-day observation method" is popularized in China, it can not only greatly reduce the dose of vaccine (which may be half of the total dose), but also liberate the vast majority of phobia patients more quickly.

What should I do if I am bitten by a mouse or rabbit?

The relevant report of WHO pointed out: "The inspection of thousands of rodents in the wild and residential areas of North America and Europe shows that few rodents are infected with rabies, indicating that these animals are not the storage hosts of the disease." "After exposure to rodents such as rabbits and hares, there is little need for special anti-rabies post-exposure prevention."

There are occasional statistical reports of rabies cases transmitted by rats in China literature, but the identification of injured animals depends entirely on the oral memories of patients or their families, which has limited scientific value and a small total.

According to the author's years of data collection and research, it is considered that the above viewpoints of WHO are basically applicable to China. Especially in non-key epidemic areas, if bitten by rats or rabbits, the possibility of rabies is extremely small, and rabies vaccine is usually not needed.

There are many opportunities for people to be bitten by rats-3% of all animal injuries-10%. If you don't vaccinate in this case, you can save up to 65,438+0/65,438+00 per year.

Regarding the disposal of rats after biting, China's Ministry of Health has not yet issued relevant work norms. It is suggested that patients should weigh whether they need to be vaccinated with rabies vaccine while objectively publicizing that the probability of rabies caused by rat bites is extremely small.

In addition, birds (such as chickens, ducks and geese), reptiles (such as lizards, turtles and snakes), fish and insects have never suffered from rabies, so it is impossible to be infected with rabies.

Correctly treat "indirect communication"

The source and transmission route of rabies are relatively simple, mainly through being scratched or bitten by dogs or cats. Who clearly stipulates that post-exposure prevention is divided into three levels of management. For class I exposure, that is, touching or feeding animals, or licking the whole skin of animals, no preventive measures need to be taken. The so-called "indirect transmission" mode that many other phobia patients are worried about is actually very unlikely, so it can usually be ignored. If some people have a particularly heavy psychological burden and seriously affect their daily work and study, they can also be vaccinated with 3 needles. After vaccination, you can basically sit back and relax-neutralizing antibodies may last for years or even decades, during which they are sufficiently resistant to so-called "indirect transmission".

We should fully understand the important role of wound cleaning. Correct wound irrigation can reduce the incidence by more than 50%. For many specious "indirect transmission" or slight exposure in non-epidemic areas, wound cleaning is actually enough to completely rule out the possibility of a minimal infection, and there is no need to insist on vaccination.

Regarding the important role of wound management, there is a typical example: the earliest recorded rabies in Europe occurred in Lyon, France in 900 AD: a bear went crazy, bit 20 people at a time, and then fled to the other side of a small river. Among the bitten people, 14 people swam across the river to hunt bears, probably because the river naturally washed away the virus in the wound, and none of these 14 people was infected with rabies virus; Those six people who didn't chase the bear (and therefore didn't clean the wound) all died of rabies later (it seems that brave people have good results).

Viruses in the central nervous system

Many patients with "phobia" like to ask such a question: after rabies virus enters nerve cells, does the antibody triggered by the vaccine not work? Can antibodies kill viruses in the central nervous system (CNS)?

A large number of original and newly discovered evidences show that rabies virus antibodies can not only neutralize viruses in peripheral nerve cells, but also completely eliminate viruses in the central nervous system under certain conditions. After rabies virus enters the central nervous system, it will either be cleared or become ill within 3-5 days. Under any circumstances, it is impossible for rabies virus to lurk in the central nervous system (including the brain and spinal cord) for a long time.

Once rabies breaks out, people will die within ten days. Therefore, if any symptom is suspected to be related to rabies, ten days later, the patient will definitely die of rabies (at least he has been admitted to the intensive care unit for rescue). If this is not the case, the symptoms are definitely not related to rabies (it should be transferred to other specialties as soon as possible). Some phobia patients firmly believe that they have rabies, claiming that the typical rabies performance has lasted for several months or even longer. I hope no one will make fun of themselves like this again.

A large number of examples have proved that it may be effective to treat the virus after exposure for several days or even months, indicating that antibodies may also remove rabies virus from the central nervous system.

Some patients who have been actively rescued by modern life support system for a long time have found that the rabies virus in the whole body (including the central nervous system) has been completely removed after autopsy, which can indirectly prove that antibodies can enter the central nervous system and remove the virus in the central nervous system.

In fact, most vaccination failures occurred within 20 days after the first injection, mainly in patients with severe head and face bites. If you don't get sick this time, the possibility of getting sick again is almost nonexistent.

Rabies virus does not cause morphological changes of brain cells. The whereabouts of rabies virus in human body can not be detected before the onset, and whether brain function is damaged can only be judged according to symptoms. High enough antibodies were detected before the onset, which proved that his brain function was not damaged, at least not seriously damaged, and he would not get sick again in the future.

In short, as long as the rabies virus is vaccinated before the onset and antibodies are produced, it is impossible to "lurk" in the body (including the central nervous system) and it will not happen again. Searching the relevant literature at home and abroad, no cases violating this standard were found. This is another simple and practical criterion, which helps to liberate patients with "phobia" from their blind fear of rabies. At present, the instructions for the use of domestic rabies vaccine include the following "precautions":

"Avoid alcohol, strong tea and other irritating foods and strenuous exercise."

Many netizens have raised questions:

"Why can't you drink alcohol and exercise vigorously after vaccination against rabies?"

Patients with "phobia" are more worried: "Do drinking alcohol, drinking strong tea, eating irritating food and strenuous exercise inhibit antibody production during vaccination? Will it invalidate the vaccine? Will it kill you? "

The vaccine instructions are formulated by the National Pharmacopoeia Committee, and the above quotation in the "Notes" of the instructions comes from the latest edition of People's Republic of China (PRC) Pharmacopoeia and China Pharmacopoeia (20 10 edition).

Careful netizens found that there is no such taboo on the instructions of rabies vaccine produced abroad. For example, the Chinese and English instructions for imported VERO cell rabies vaccine (Wilbaut) and chick embryo cell rabies vaccine (Rebir) do not mention the taboos in diet and exercise (the only taboo mentioned is "use of immunosuppressants and antimalarials should be avoided during vaccination").

At present, rabies vaccines at home and abroad are produced according to the unified quality standards of WHO.

Why is it that only the Pharmacopoeia of China has stipulated so many taboos after rabies vaccine, but the foreign instructions have not mentioned them at all? Some netizens asked: "Why are people all over the world not afraid? Only people in China are afraid of this and that?"

Looking through the existing literature at home and abroad, there is no scientific basis to stipulate the above dietary or exercise restrictions.

It is estimated that even if the alcohol concentration in blood reaches the level that makes animals (or people) drunk or even die of alcoholism, it will not have a significant impact on the production and activity of antibodies.

Therefore, drinking alcohol after rabies vaccine may die of alcoholism or drunk driving, but it will not die of rabies.

If you exercise too hard after rabies vaccine, you may only die of excessive or sudden exercise, not rabies.

Therefore, such a "ban" should be written into "common sense of citizens" and should not be written into "instructions for vaccine use".

A large domestic vaccine manufacturer also believes that "we have not found any cases that affect the vaccine because of eating spicy food" and "irritating food will not affect the immune effect of antibodies, but it may aggravate the adverse reactions, that is to say, whether domestic or imported vaccines are used, if adverse reactions occur, eating spicy food may aggravate the adverse reactions."

The rabies vaccine produced in China 30 years ago was made from animal brain tissue. It is necessary to inject 14-2 1 time within half a month, and 2ml of coarse brain tissue should be inoculated each time. The side effects are great, and drinking and strenuous exercise may increase the side effects. Therefore, the vaccine instructions at that time clearly stipulated: "Don't drink alcohol, strong tea or spicy food, and avoid catching a cold or strenuous exercise or labor" (quoted from 66

In recent 30 years, all rabies vaccines in China were produced by cell culture. After concentration and purification, only 5 or 4 injections were given, with minimal side effects. But now the instructions for domestic vaccines are still copied from 30 years ago.

The above dietary and exercise taboos should be kept in the instructions of rabies vaccine currently used, and there is no experimental evidence.

It is suggested that when the Pharmacopoeia 20 15 is published, the regulations on diet and exercise restrictions in the "Notes" of rabies vaccine instructions should be deleted.