An epidemic of porcine diarrhea in North America

pig farmPorcine epidemic diarrhea arrived in the United States in the spring of 2013. The disease, caused by a coronavirus, was first identified in the United Kingdom in 1971, and has subsequently spread throughout Europe and Asia. The disease is a concern for the swine industry because it is associated with high case fatality ratios in suckling pigs.

Porcine epidemic diarrhea virus is a member of the coronavirus family, which also includes the SARS and MERS coronaviruses (CoV). Before 2013 the virus had not been isolated in North America. It was detected on a farm in Iowa in May and subsequently spread to 22 states. It is estimated that between 1-4 million pigs have died of the disease in the US.  Recently the virus was found on a Canadian pig farm in Middlesex County, where it most likely arrived from the US.

PEDV can infect pigs of all ages, but is most serious in nursing pigs in which the clinical symptoms are the most severe. The disease is characterized by acute vomiting and watery diarrhea which in nursing pigs leads to dehydration and frequently death. There is no treatment for the disease other than rehydration; no antiviral drugs are available, but a vaccine was developed in 2013. The virus does not infect humans.

Sequence analysis of genomes from three US isolates of PEDV indicate that they are most closely related to a virus isolated in 2012 in Anhui, China. These data suggest, but do not prove, that the US PEDV originated from China. How the virus might have arrived from that country is a matter of speculation. The virus is believed to move from farm to farm on trucks that are used to carry pigs, as well as on contaminated boots and clothing. Many farms observe strict biosecurity procedures in which trucks are properly washed, disinfected, and heated to inactivate the virus. However these procedures cost money and take time, and may be bypassed in some cases. If older pigs are asymptomatically infected, they might be transported to other farms and spread the virus. Once in a farm, stopping spread of the virus is difficult: it is spread by fecal-oral contamination.

The coronavirus family is divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Several human coronaviruses that cause common cold-like illness, as well as PEDV, are alphacoronaviruses. SARS-CoV and MERS-CoV are betacoronaviruses. Viruses in the alphacoronavirus and betacoronavirus genera are believed to have originated from bats, while birds might have been the origin of viruses in the other two genera. Analysis of the PEDV genome sequence indicate that the 5’-untranslated region is similar to that of a bat coronavirus. Based on this information it has been suggested that PEDV originated from a cross-species transfer of a bat alphacoronavirus into pigs.

National Hog Farmer is not usually on my reading list, but it has a good summary of porcine epidemic diarrhea.

TWiV 268: Transmission is inevitable

On episode #268 of the science show This Week in Virology, Vincent, Alan, Kathy, and Ashlee discuss fomites in physicians offices, plant virus factories involved in aphid transmission, and clues from the bat genome about flight and immunity.

You can find TWiV #268 at www.microbe.tv/twiv.

Fouchier vs the Dutch government on influenza H5N1 research

ferretFrom Martin Enserink at ScienceInsider:

Virologist Ron Fouchier has suffered a loss in a legal battle with the Dutch government over the publication of his controversial H5N1 influenza research. On Friday, a Dutch district court ruled that the government was right to ask Fouchier to obtain an export license before sending two hotly debated papers out for publication.

Readers of this blog will remember the furor sparked by Fouchier’s experiments in 2011 in which he developed an avian influenza H5N1 isolate that could transmit among ferrets by aerosol. When Fouchier was ready to publish the results, the Dutch government required that Fouchier apply for an export license. In so doing they were applying EU regulations that are designed to prevent the spread of biological weapons.

Fouchier applied for and was granted an export license on 27 April 2012. Fouchier’s employer, Erasmus Medical Center, appealed the decision to require an export license for this type of work. It is this appeal that was recently denied by a Dutch district court.

Fouchier rightfully claims that such EU regulations put him at a disadvantage compared with other groups. For example, Kawaoka’s findings on aerosol-transmitted avian influenza H5N1 virus in ferrets were not subject to EU export rules and were published ahead of Fouchier’s paper. I can understand Fouchier’s position; science is very competitive and being the first to publish is a coveted position. I am not sure that this is an issue worth bringing to the courts: even though Fouchier published after Kawaoka, most virologists credit the observations to both laboratories. The Dutch government should recognize that its scientists must be internationally competitive and expedite such future requests.

In my view, there is a larger issue at stake here: what constitutes research that requires an export license? I would argue that the avian influenza H5N1 virus that Fouchier produced is not a biological weapon. Remember that while this virus could transmit among caged ferrets by aerosol, it was markedly attenuated. In other words, gaining the ability to transmit by aerosol came at a fitness cost that reduced the virulence of the virus in ferrets. Such a virus is not a biological weapon, and should not have been subject to EU export requirements.

I do not know who in the Dutch government reviews such export license requests, but hopefully the next time Fouchier or any other virologist applies, there will be knowledgeable virologists involved in making the correct decision.

TWiV 230: Gene goes to Washington, flu chickens out

On episode #230 of the science show This Week in Virology, Vincent, Rich, Alan and Kathy review H7N9 infections in China, the debate over patenting genes, and receptor-binding by ferret-transmissible avian H5 influenza virus.

You can find TWiV #230 at www.microbe.tv/twiv.

Human infections with avian influenza H7N9 virus from wet market poultry

Results of a study of four patients in Zhejiang, China, who developed influenza H7N9 virus infection suggests sporadic poultry-to-human transmission:

We diagnosed avian influenza A H7N9 in all four patients (who were epidemiologically unlinked), two of whom died and two of whom were recovering at the time of writing. All patients had histories of occupational or wet market exposure to poultry. The genes of the H7N9 virus in patient 3’s isolate were phylogenetically clustered with those of the epidemiologically linked wet market chicken H7N9 isolate. These findings suggest sporadic poultry-to-person transmission.

The four patients had occupational contact with poultry: one was a chef, one slaughtered and cooked live market poultry, and two bought live market poultry. Each had contact with poultry 3-8 days before onset of disease, and all were positive for influenza H7N9 virus by polymerase chain reaction of sputum or throat swab samples (virus was cultured from three of the four patients). Two of five pigeons and four of 20 chickens from two different wet markets were also positive for influenza H7N9 virus. Sequence analysis of virus recovered from patient 3 revealed that the HA and NA genes are nearly identical with those of two viruses isolated from epidemiologically linked chickens (1673 of 1683 bases for HA, 1394 of 1398 bases for NA).

While these H7N9 infections might have been acquired from poultry, the origin of other infections in different areas of China (>100) is unclear. According to the Ministry of Agriculture, as of 26 April 2013, only 46 of the 68,060 samples collected from poultry markets, habitats, farms and slaughterhouses across the country have tested positive for H7N9 virus, and none of these positive samples have been from poultry farms.

End of moratorium on influenza H5N1 research

In early 2012 influenza virus researchers around the world decided to stop working on highly pathogenic avian influenza H5N1 virus. This decision came after work from the Fouchier and Kawaoka laboratories revealed the isolation of influenza H5N1 strains that can be passed among ferrets by aerosol. The moratorium on influenza H5N1 virus research has now been lifted, as described in a letter from influenza virologists to Science and Nature.

Lifting the embargo on H5N1 research is an important step forward for understanding what regulates influenza transmission. In my view it was an ill-conceived move, done to quell the growing concern over the adaptation of influenza H5N1 virus to aerosol transmission in ferrets. We now know that these viruses are not lethal for ferrets, and much of the outrage expressed about this work was misguided. In my view the moratorium has accomplished little other than delaying the conduct of important virology research.

According to the influenza virus researchers who signed on to the moratorium, its purpose was to:

…provide time to explain the public-health benefits of this work, to describe the measures in place to minimize pos- sible risks, and to enable organizations and governments around the world to review their policies (for example on biosafety, biosecurity, oversight, and communication) regarding these experiments.

An important consideration is the level of containment that will be required for studying influenza H5N1 transmission. WHO has released recommendations on risk control measures for H5N1 research, and individual countries will decided how to proceed. The US has not yet made a decision on the level of containment needed for H5N1 virus transmission research. Influenza virologists who participated in the moratorium have their own view:

We consider biosafety level 3 conditions with the considerable enhancements (BSL-3+) outlined in the referenced publications (11–13) as appropriate for this type of work, but recognize that some countries may require BSL-4 conditions in ac- cordance with applicable standards (such as Canada).

Their last statement forms the crux of the issue on H5N1 transmission research:

We fully acknowledge that this research—as with any work on infectious agents—is not without risks. However, because the risk exists in nature that an H5N1 virus capable of transmission in mammals may emerge, the benefits of this work outweigh the risks.

Slow motion sneezing

A bit unsettling, but this is what happens when a sneeze is not contained:

If you have a respiratory viral infection, each drop expelled can contain tens of thousands of infectious virions.

Made by South Australian Health.

TWiV 199: Of mice, ticks, and pigs

On episode #199 of the science show This Week in Virology, Vincent, Alan, Rich, and Kathy discuss recent outbreaks of hantavirus pulmonary syndrome in Yosemite National Park and novel swine-origin influenza in the US midwest, and isolation of the Heartland virus from two patients in Missouri with severe febrile illness.

You can find TWiV #199 at www.microbe.tv/twiv.

TWiV 190: The second ferret of the Apocalypse

On episode #190 of the science show This Week in Virology, Vincent, Alan, and Kathy review selection of influenza H5N1 viruses that can transmit among ferrets by aerosol.

You can find TWiV #190 at www.microbe.tv/twiv.

TWiV 177: Live in Dublin

On episode #177 of the science show This Week in Virology, Vincent, Connor Bamford, Wendy Barclay, and Ron Fouchier discussed avian influenza H5N1 transmission experiments in ferrets and novel bunyaviruses at the 2012 Spring Conference of the Society for General Microbiology in Dublin, Ireland.

You can find TWiV #177 at www.microbe.tv/twiv.