New idea for epidemic prevention: giving vaccines to wild animals

From COVID-19 to rabies vaccines, humans have paid a huge economic price for the development and vaccination of vaccines. If we do the work "in advance" and vaccinate wild animals, can we change the situation?

Reporter/Wang Xueying Editor/Ding Lin

New Media Editor/Chen Xuanzhi

From the "Black Death" in the 14th century to the COVID-19 today, countless large-scale infectious diseases have broken out in human society over the past century. With the continuous advancement of science and technology, humans have gradually realized that animals, as hosts of many deadly diseases, are playing an increasingly important role in the history of human epidemics. If vaccinating people is only a "symptomatic treatment", then will vaccinating wild animals to prevent and treat diseases become a new idea for "curing the root cause" of human epidemic prevention work?

How to vaccinate wild animals

Every January, some airports in Texas become extremely busy: cargo planes take off from here and fly to the border area between the United States and Mexico, scattering nearly 1 million "small brown bait blocks" from the air into suburbs and wild areas.

At first glance, these things are inconspicuous. The shell made of fish feed is square and less than half the size of a matchbox, and can easily be submerged in the grass. However, do not underestimate these "dirty" things, because they hide a great mystery - when wild animals cannot resist the temptation of fish feed and take the initiative to bite the bait, the vaccine liquid wrapped in the "capsule" inside the bait will be bitten into its mouth at the moment of being bitten, indirectly achieving the purpose of "vaccinating" the wild animals with rabies vaccine.

▲Oral rabies vaccine bait. (Source: U.S. Centers for Disease Control and Prevention)

Humans had no choice but to come up with this trick.

As we all know, rabies is an acute infectious disease caused by the rabies virus, which is common in animals such as dogs, wolves, and cats. It is a zoonotic disease with a very high mortality rate in humans. Although human knowledge of rabies has made a qualitative leap with the advancement of science, the medical community still has no effective treatment methods. The most common response plan is still passive prevention and treatment, that is, "vaccination with post-exposure prophylaxis" (PEP). In order to cut off the spread of rabies from the source as much as possible, humans have also begun to list animals as the objects of rabies vaccination.

But even if domestic pets can be vaccinated by their owners, what about wild animals that are free? In Western countries such as the United States and Australia, nearly 90% of rabies cases reported each year occur in the wild - wild animals, led by foxes, skunks, coyotes and raccoons, have surpassed domestic dogs and become the main source of rabies virus.

Swiss scientists took the first step to solve the problem of difficulty in vaccinating wild animals. In 1978, they used wild foxes as the first large-scale oral rabies vaccine in the wild.

However, the vaccination program started off badly and did not achieve the expected results. At that time, people did not fully realize that in order to successfully induce wild animals to take the vaccine orally, the size, packaging and even taste of the vaccine bait blocks needed to be adjusted according to the different dietary preferences and living habits of the target animals. In addition, this improved oral rabies vaccine was mainly a (attenuated) live vaccine, which aroused public concerns about its safety, and the project was once stopped.

▲Several common oral rabies vaccines. (Source: Plos One)

By 1995, European countries had begun to release and test oral rabies vaccines. In view of this, the U.S. Department of Agriculture also joined hands with states and the federal government to launch a massive wild rabies vaccine campaign: based on the actual situation of each state, the United States will distribute 6.5 million oral rabies vaccines to state governments each year to protect "high-risk" wild animals such as raccoons - although this move cannot guarantee that all animals will produce antibodies after eating bait vaccines, nor can it guarantee that all wild hosts such as gray foxes, skunks and coyotes will be "induced to breed". However, since the implementation of the plan in 1995, the number of reported rabies cases in Texas, which was once the hardest hit area, has almost been eliminated, and the trend of rabies "moving westward" in the United States due to the movement of wild animals has been effectively curbed [1].

▲Since the introduction of oral rabies vaccines in 1995, the number of reported cases of rabies in wild animals in the United States has continued to decline. (Source: AVMA Journals)

Should we fight people or beasts? Let’s do the economic calculation

Not everyone will encounter rabies in their lifetime. So why go to all the trouble to launch veterinary vaccines? Wouldn't it be better to prepare more effective and safer vaccines for human use?

People’s actual choices may have to start with an economic account.

According to the treatment plan recommended by the World Health Organization, a healthy adult who is bitten by a sick animal should be vaccinated with rabies vaccine in several doses according to the "5-shot method" or "2-1-1 method" to protect the patient's life as much as possible. At the same time, the patient should also choose whether to receive additional rabies immunoglobulin according to the injury. Due to multiple factors such as the different production locations, the price of the full course of rabies PEP vaccine varies greatly in different countries.

▲"5-injection method" and "2-1-1" PEP vaccination scheme (Image source: Researchgate)

According to the “Current Status of Rabies Prevention and Control in China” published by the Chinese Center for Disease Control and Prevention in 2009, the price of a full course of rabies vaccine for humans in my country ranges from RMB 250 (domestic vaccine) to RMB 350 (imported vaccine), depending on the place of vaccine production. The price of passive immunization preparations ranges from RMB 300 (antiserum) to RMB 1,200 (anti-rabies immunoglobulin). The total cost for a level 3 exposed person to complete standardized preventive treatment is RMB 1,500 [2].

However, in the United States, the price of a full course of rabies PEP vaccination is higher. According to the data from the Centers for Disease Control and Prevention, although the cost ranges from US$1,200 to US$6,500, the average price for ordinary people to receive a full course of rabies PEP vaccination in a medical institution is as high as US$3,800, which does not include the cost of manual care[3]. Since the US health insurance system bears most of the costs for patients, the US government spends more than US$200 million on human rabies vaccines each year[4].

On the other hand, veterinary oral rabies vaccine is actually not cheap. Its cost not only covers the cost of bait blocks, but also takes into account multiple factors such as the release density, release cycle, and sowing method in different regions.

At present, the cost price of oral rabies vaccine bait blocks in Europe and the United States is not low - the cost of bait blocks that meet the usage standards is about US$1.27 per block. When released in the wild, the number released per square kilometer needs to exceed 75 to achieve the expected epidemic prevention effect.

At the same time, since the different flight paths of pilots will also affect the effectiveness of the vaccine, the cost of delivering oral rabies vaccine bait blocks also fluctuates greatly - the cost of using fixed-wing flights is the lowest, about US$8.62 per square kilometer, while the cost of using multi-rotor flight mode is the highest, reaching US$33.30 per square kilometer.

▲Bait dispenser on the plane (Photo source: ontario.ca)

Taking all of the above factors into account, the U.S. Department of Agriculture pointed out in a recent survey report that the cost of oral rabies vaccines for wildlife ranges from US$58 million to US$148 million, but they can maintain good prevention and control effects over a 20-year period[5]. Although the cost is not low, compared with the financial investment in rabies vaccines for humans, oral rabies vaccines are indeed an "economical and affordable" option.

For many countries, the threshold for oral rabies vaccination is indeed a bit high. However, compared with dealing with exposed patients, even the promotion of injectable veterinary rabies vaccination is beneficial.

Take Africa as an example. Although Africa is not a high-incidence area for rabies, the individual mortality rate of rabies in many countries south of the Sahara is generally high. One of the main reasons is that the rate of rabies vaccination for local stray dogs and domestic dogs is too low, and rural towns are the hardest hit areas. For local villagers, if they want to receive a full course of five rabies vaccinations after being bitten by a sick dog, they need to pay at least US$60 per person, which is equivalent to 25% of the annual income of an ordinary local farmer. What's worse is that local livestock are also affected by rabies. Every year, the number of livestock killed by sick dogs causes losses of up to US$280 million to Africa.

▲Many stray dogs are easily frightened, and it is not easy to get them to get vaccinated. Some people even trained dog catchers to implement vaccinations (Photo source: nytimes.com)

Due to the high transportation cost of the vaccine, the cost of vaccinating dogs against rabies in Africa is as high as US$7.3 to US$11.27 per dog. However, after comprehensive consideration, promoting rabies vaccines for animals seems to be a better choice.

Copy the successful experience: Protecting "neighbors" = protecting yourself

This year’s epidemic has forced us to face a grim reality: our furry animal “neighbors” are exposing humans to a higher risk of disease: of the 1,415 infectious organisms known to cause disease in humans, 61% can cause disease in both humans and animals, and about 175 of these pathogens are believed to be associated with a variety of emerging diseases in the past two decades. At the same time, among the currently known emerging pathogens, humans can determine that about 132 pathogens can cause zoonotic diseases[6].

The US Centers for Disease Control and Prevention pointed out in a report: "(Currently) more than 6 out of every 10 known diseases that can cause illness in humans are transmitted from animals, and this proportion is as high as 75% for emerging infectious diseases." An average of 2.7 million people die each year worldwide from zoonotic diseases[7].

Can we replicate the success of oral rabies vaccines for more types of zoonotic diseases? At least, US Biologic, a well-known American antibody and biochemical reagent supplier, believes that this idea is reliable.

▲Oral Lyme disease vaccine produced by US Biologic. (Source: Tennessean)

Lyme disease is an infectious disease transmitted by ticks, with wild white-footed mice as the main host. After being infected with Lyme disease, the human body will suffer from nervous system damage and cause heart or joint diseases. In recent years, due to the rapid changes in the natural ecological environment, the large increase in white-footed mice has caused human society to continue to suffer from Lyme disease invasion - to this day, there is still a lack of long-term and large-scale supply of human Lyme disease vaccines on the market.

In view of this, US Biologic borrowed the idea of ​​oral rabies vaccine and disguised Lyme disease vaccine into bait blocks, which were scattered in large quantities in observation areas where wild white-footed mice frequently appeared. In order to better suit the preferences of white-footed mice, researchers adjusted the shape and size of the vaccine and upgraded the raw materials for wrapping the vaccine capsules to pet feed mainly composed of bone meal and fish bone meal.

In addition to the more "suitable" shape and taste, scientists have further improved the safety of the vaccine - it only targets the pathogen and not the host. Even if squirrels and chipmunks accidentally eat it, the oral Lyme disease vaccine will not affect the health of these animals. It is encouraging that after a large number of field trials, US Biologic has recently officially announced the success of the vaccine.

▲Mice bitten by ticks (Photo source: lymedisease.org)

"Protecting these furry creatures and their neighbors is actually protecting ourselves," said Tonie Rocke, an epidemiologist at the National Wildlife Health Center of the U.S. Geological Survey. In his opinion, vaccinating the intermediate host is sometimes more effective and easier to operate than directly "sniping" the source. Rocke used the Hendra virus as an example.

The Hendra virus can cause severe respiratory disease in humans. Its source is flying bats, but horses can be infected by eating fruit that flying bats have gnawed. When people come into contact with sick horses, the virus may infect healthy people through the secretions of sick horses.

▲After the Hendra outbreak in Queensland, Australia, some local horses were quarantined (smh.com.au)

Due to the living habits of flying foxes and their important role in the ecology of fruit trees and plants, scientists changed the idea of ​​oral rabies vaccines. Instead of "sniping" flying foxes, they chose to vaccinate horses for prevention. By cutting off the way flying foxes infect intermediate hosts, they not only protect the health of horses, but also indirectly protect the health of humans. Following this line of thought, humans not only hope to protect their own health by protecting their "furry neighbors", but also hope to better protect their wallets - and even their own food.

As we all know, African swine fever is a highly contagious hemorrhagic disease. Although it is not transmitted to humans, it is very deadly to wild boars and domestic pigs. The virus is highly stable and easy to survive. The disease course of infected animals is short and the mortality rate is high. In the production and breeding environment, African swine fever is not easy to identify, and diagnosis is highly dependent on laboratory monitoring. In addition, there are many subtypes of African swine fever virus, and they are constantly mutating. All these have caused African swine fever to become a sharp sword hanging over the head of the breeding industry.

As a notifiable animal disease listed by the World Organization for Animal Health, African swine fever is also a Class I animal disease in my country. The skyrocketing pork prices, the farmers who suffered heavy losses overnight, the indiscriminate slaughter of domestic pigs... In order to protect people's wallets and dining tables at the same time, vaccinating domestic pigs against diseases has become the best choice.

Although there is no African swine fever vaccine that can be marketed in large quantities in the world, it is getting closer: Recently, the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences (hereinafter referred to as the Harbin Veterinary Research Institute) announced that the African swine fever vaccine independently developed by it has achieved a major breakthrough in stages. Its scientific research team has successfully artificially selected a weak live vaccine for African swine fever, and confirmed in experiments that the vaccine can effectively provide safe immunity for domestic pigs to prevent African swine fever. Even if the maximum dose is administered, the vaccine will not have the risk of relapse, and will not cause health effects on pregnant domestic pigs and piglets after delivery.

Saving animals is worse than saving yourself?

Although humans have been studying how to vaccinate wild animals more effectively, there have always been objections within the academic community about the feasibility and cost-effectiveness of this idea.

In recent years, coronaviruses that have caused outbreaks have repeatedly been confirmed to be related to bats. Some experts point out that if bats, a "mobile virus reservoir", can be controlled at the source, the emergence of more new infectious diseases may be reduced. However, unlike raccoons and white-footed mice, which can be directly fed with bait vaccines, scientists can only use intermediaries (such as insects) to vaccinate bats and rely on the social habits of wild bats themselves - this not only increases the work and uncertainty of vaccine development, but also greatly increases the cost of vaccines.

In addition, different types of diseases will manifest themselves differently in different populations of animals, and the prevention and control measures taken by humans for different disease situations will also vary greatly. Therefore, it is naive and almost impossible to block the source of infection by "sniping" wild animals.

"Not to mention that it may take decades to identify the true host, sometimes, for some diseases transmitted by insects such as mosquitoes and ticks, a strategy of directly eliminating the carriers may be more effective," said Melinda Rostal, chief scientist of the US non-profit EcoHealth Alliance. He believes that calling on humans to stay away from potentially dangerous animals as much as possible is more efficient than inducing wild animals to be vaccinated.

▲Common wildlife vaccines. (Source: Cornell University)

However, supporters of veterinary vaccines have also pointed out that the research and development and approval procedures for veterinary vaccines are simpler and faster than those for human vaccines. Especially for some new infectious diseases, veterinary vaccines can sometimes be more effective in quickly controlling the overall epidemic.

"Directly developing vaccines for humans can certainly reduce costs and is easy to implement, but it is only a temporary solution and not a fundamental solution." Dr. Duan Yu, who specializes in poultry and livestock infectious disease detection and kit development, said this in an interview with a reporter from Beijing Science and Technology News | Science Plus Client. Having been at the forefront of poultry and livestock disease detection kit development for many years, he can better understand the significance of the term "human-animal health community."

"We provide oral vaccines to wild animals, which is actually building a protective network around humans," Duan Yu said. "Like COVID-19, it is difficult for humans to predict what kind of viruses will appear in the future and how much impact they will have on human society. So we can't just sit back and think that making a vaccine for ourselves will solve the problem. After all, compared with other species, human power is limited. Only by protecting our neighbors can we better protect ourselves in the long run."

Dr. Joanne Maki, who holds the same view, also called for a change in people's thinking about disease prevention and control. "In the past, wildlife disease prevention and control mainly relied on large-scale killing, through targeted hunting, imprisonment and elimination of certain animals. However, this method is neither humane nor scientific, especially when placed on the entire ecological environment, it has a great negative impact." As the head of veterinary and public health technology for an animal health company, Dr. Maki pointed out that killing and epidemic prevention requires a lot of labor and the effect is difficult to sustain, which is a "double blow" to the economy and ecology: "If we can build an 'immunity wall' for wild animals (such as oral rabies vaccine), everything will be different."

As an important part of the natural ecology, the impact of wild animals on human society is increasing year by year. Vaccinating wild animals to prevent diseases may provide a new way for humans to protect their own health.

References:

[1]aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nwrc/research-areas/SA_Rabies/CT_Orv_vaccination

[2] Current Status of Rabies Prevention and Control in China (2009)

[3]cdc.gov/rabies/location/usa/cost.html

[4]aphis.usda.gov/aphis/ourfocus/wildlifedamage/programs/nrmp/ct_orv_vaccination

[5] Human Conflicts with wildlife: Economic Considerations.US Department of Agriculture, Animal and Plant Health Inspection Service, National Wildlife Research Center; 2000.

[6]Louise H. Taylor, Sophia M. Latham. Risk factors for human disease emergence. The Royal Society Publishing. July 2001, Volume 356, Issue 1411

[7]emro.who.int/in-press/reviews/one-health-operational-framework-for-action-for-the-eastern-mediterranean-region-focusing-on-zoonotic-diseases.html

[8]who.int/rabies/vaccines/oral_immunization/en/

[9]avmajournals.avma.org/doi/full/10.2460/javma.253.12.1555

[10]sciencemag.org/news/2017/01/inside-global-campaign-get-rid-rabies

Produced by: Science Central Kitchen

Produced by: Beijing Science and Technology News | Science Plus Client