Jun 8, 2009 (CIDRAP News) Government officials and researchers may have underestimated the potential role of pigs as "mixing vessels" for influenza viruses and the importance of swine surveillance for identifying new pandemic threats, veterinary experts from Mexico asserted recently.
The group based their conclusions on two genetic analyses tracing the evolution of the novel H1N1 virus that lend support to the mixing vessel theory. Their findings appeared in the Jun 4 issue of Eurosurveillance.
Following virus protein clues
In the first analysis, the group used more than 400 protein sequences from the novel virus and those from previous flu seasons to explore the genetic evolution of the new virus. The closest homologous proteins for the novel H1N1 virus were in swine influenza viruses that have been circulating in the United States and Asia for the past 10 years, suggesting that the new virus probably evolved from recent swine viruses.
In the second part of the study, the group conducted phylogenetic analyses of thousands of protein sequences of H1N1 viruses that circulated in North America over the last 20 years. They found that the novel H1N1 virus has "genetic distinctness," which appears to be a hallmark of previous influenza A viruses transmitted between pigs and humans.
Though the sample size was limited, the authors said the analyses are useful for understanding the evolution of influenza viruses and for detecting emerging viruses with pandemic potential early.
A gap in threat tracking
They wrote that the mixing vessel theory has been around for more than a decade and that influenza experts in 1998 proposed swine surveillance to serve as an early warning system, but that this task was to some extent overlooked. As evidence, they said the number of swine influenza A sequences that were in the database they used for the study was 10 times smaller than the number of human and avian influenza A sequences.
"In some countries, such as the United States, the national strategy for pandemic influenza assigned the entire preparedness budget ($3.8 billion US dollars) for the prevention and control of avian A (H5N1) influenza, overlooking the swine threat," the report said. It referred to a 2006 report on pandemic flu appropriations.
The novel flu outbreak presents new challenges for animal and human health experts, the group wrote. They said their institution, the College of Veterinary Medicine at the National Autonomous University of Mexico, is establishing a surveillance system for pigs and birds to identify novel flu viruses circulating in Mexico. "This effort prioritizes the use of genetic distinctness as a marker for the detection of novel viruses that could lead to influenza pandemics," they wrote.
How real is the mixing vessel threat?
Rodney B. Baker, DVM, president of the American Association of Swine Veterinarians and senior clinician in Iowa State University's College of Veterinary Medicine in Ames, told CIDRAP News that the authors appear to have based their findings about novel flu virus evolution on incomplete data, which may have prevented them from considering all of the possibilities. For example, he said their findings don't seem to factor in the documentation of "parental reassortment" in Asia or the distance of the novel H1N1 virus from North America's endemic strains.
Baker also questioned the group's emphasis on the mixing vessel theory, which he said came about when scientists discovered that pigs have both avian-like and mammalian receptors on their respiratory epithelium. He said the theory remains unproved, though it has been around for many years.
"When discovered, it was believed to be unique to pigs, but now we know that humans, quail, turkeys, and likely many, many species have both receptor types, any of which could serve as a 'mixing vessel,'" he said.
Generally, human flu viruses have triggered the genetic changes in swine influenza viruses since 1918-1919, but none of the genetic shifts or virus introductions from people to pigs has created a pandemic virus or one that transmitted human-to-human, Baker said. "So historically, the pig has never served as a mixing vessel, unless the current virus actually came directly from a pig. If so, it most likely occurred in traditional-style pig farms in Asia," he added.
Funding shortfalls limit surveillance
The authors, however, are correct in pointing out that health officials have underestimated the importance of swine surveillance, and that the efforts suffer for a general lack of food-animal research dollars, Baker said. Most swine surveillance has been conducted by a few dedicated scientistssuch as those at Iowa State, the University of Minnesota, and St Jude Children's Research Hospitalwith few resources, he said.
Fortunately, a small swine surveillance collaboration between the US Centers for Disease Control and Prevention (CDC) and the National Animal Disease Center in Ames had just begun when the new virus was first detected, Baker said.
Last week, John Clifford, the chief veterinarian for the US Department of Agriculture (USDA), announced plans to launch a pilot surveillance program in swine to detect new influenza strains, according to a Jun 2 Reuters report. The program will analyze isolates, submitted by government and private labs, from sick pigs and from herds exposed to workers that have H1N1 infections
Nava GM, Attene-Ramos MS, Ang JK, et al. Origins of the new influenza A (H1N1) virus: time to take action. Eurosurveillance 2009 Jun 4;14(22): [Full text]