Spread of deadly pig virus in China hastens vacci...

嵩云洪钟 2019-08-22

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Pigs are big business in China, where many farms are being ravaged by African swine fever.

A highly contagious disease that kills infected pigs has swept across China and is moving through neighbouring countries. Scientists in China are ramping up efforts to study the virus that causes African swine fever and produce a vaccine. But scientists elsewhere fear that political pressure to make a vaccine quickly could risk introducing chronic strains of the virus.

Although the haemorrhagic disease was first recorded in Kenya in 1921, China’s first case was detected only last August, in the north-eastern city of Shenyang. Since then, the government has reported more than 120 outbreaks across some 30 provinces, autonomous regions or municipalities.

Officials had long feared the arrival of African swine fever in China, which is the world’s largest pig producer. The virus is not harmful to humans, and virologists say the risk of it mutating to become infectious to people is low, but the economic cost of an epidemic is enormous.

Counting the cost

With no vaccine or treatment, more than one million pigs have so far been culled in the country to try to contain the outbreaks. An study published in October, two months after the virus was first detected there, reports that the death of some 100,000 pigs — just 10% of the latest figure — had cost the Chinese economy US$20 million¹. A shortage of pigs could also jeopardize worldwide availability of the blood-thinner heparin, warns Paulo Mourão, a molecular biologist at the Federal University of Rio de Janeiro in Brazil.

The drug’s active ingredient is extracted from the mucous membrane of pig intestines, and used to treat heart attacks, among other things; China accounts for almost 80% of worldwide production². Swine fever “has the potential to cause an unprecedented shortage of heparin’s raw material, which may jeopardize the global supply”, says Mourão.

The Chinese government says the outbreaks are under control, but some researchers are sceptical.

There is little information about how the disease is spreading in China, or how effective the control measures have been, says Linda Dixon, a virologist at The Pirbright Institute in the United Kingdom. She suspects that some cases might have gone undetected.

China has roughly 440 million pigs, and unofficial estimates of the proportion currently infected with the virus vary from 10% to 40%, says Dirk Pfeiffer, an epidemiologist at the City University of Hong Kong.

Research investment

The Chinese government is prioritizing research on the virus, setting aside about 100 million yuan (US$15 million) for projects, says George Gao, vice-president of the National Natural Science Foundation of China in Beijing.

The work will help to fill the many gaps in scientists’ understanding of the virus, including its detailed structure and how it transmits to hosts and evades their immune systems. “We know almost nothing about this virus,” says Gao.

Before the outbreaks, researchers in China were banned from studying the live virus in case it escaped from a lab and infected pigs. Now that the virus has entered the country, scientists at the second-highest-level biosafety laboratories can study it in cells, and those at the most secure biosafety laboratory can work with it in animals, says Gao. “Within a couple of months, I expect to see Chinese scientists contributing a lot to the field,” he says.

Vaccine development

The Harbin Veterinary Research Institute (HVRI), part of the Chinese Academy of Agricultural Sciences, is among the few institutions in the country with permission to handle the live virus in cell culture, and the only facility currently qualified to test the infection in pigs, which is essential for vaccine development, says Bu Zhigao, who heads the institute.

Researchers at HVRI are investigating what, if any, natural immunity pigs have to swine fever with a view to making drugs and developing new diagnostic techniques, but how quickly the virus spreads and vaccine development are the priority, says Zhigao, although he declined to comment on the details of the research.

At a symposium on swine fever in Beijing on 9 April, Pfeiffer says that he heard HVRI scientists present research on a potential vaccine. He says that the experimental vaccine uses a less harmful strain of the pathogen to trigger an immune response — known as an attenuated vaccine — instead of an inactivated strain or a portion of the virus. The benefit of attenuated vaccines is that they tend to produce a stronger and longer-lasting immune response than inactive vaccines, says Dixon.

Political pressure

But Pfeiffer and Dixon are concerned about the intense political pressure in the country to come up with a vaccine quickly. “Vaccine development is something one needs to do very cautiously,” Pfeiffer says.

Attenuated vaccines are made using a live virus, and there is a risk that the microorganism could persist and spread throughout the pig population, and cause unacceptable adverse reactions, Pfeiffer adds. “It is a bit like playing with fire,” he says.

One thing to monitor is whether a vaccine prevents replication of the deadly form of the virus in a host, notes Dixon. If it doesn’t, vaccinated pigs, which might show no symptoms, could infect unvaccinated animals.

In the 1960s, a large number of animals in Portugal and Spain were vaccinated with an attenuated vaccine in a field trial, which led to the emergence of chronic forms of the virus that remained infectious⁵.

A vaccine is probably still some years off, says Dixon, whose team was the first to sequence a variant of the disease³ that entered Georgia in 2007, an outbreak that introduced the virus to the Caucasus and spread to Europe.

Other research

Access to the live virus, as opposed to the isolated genes that scientists in China were limited to working with before, also means that groups in the country can study how it survives in the host. In January, researchers at the China Animal Health and Epidemiology Center in Qingdao published the genome sequence of a local strain¹, which they say resembles a variant isolated in Poland in 2015 that is currently circulating in Europe. And, in February, researchers at HVRI reported work that determined that a virus extracted from the spleen of an infected pig was extremely virulent, resulting in certain death, and efficient at passing from pig to pig⁴.

These results will help to improve measures to prevent and control the disease, says Zhigao, the HVRI paper’s lead author. Backyard and small pig farms are an important source of income for millions of Chinese families, he says. “We must control this disease, no matter how big a cost it is,” he says.

Outside China, there is concern that the disease will spread to countries that lack the resources and infrastructure to control it, says Dixon. The virus is already moving through neighbouring Mongolia, Vietnam and Cambodia. “It seems inevitable that Laos and Myanmar will be next,” says Dixon. Officials in Thailand, South Korea, Japan, Australia, the Philippines and Malaysia are also worried, she says.