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Transmission of prion brain diseases such as bovine spongiform enecephalopathy (BSE) – also known as mad cow disease – and human variant Creutzfeldt-Jakob disease (vCJD) is generally attributed to the consumption of the brain or organ meat of infected animals but new research demonstrates lambs exposed to milk from prion-infected sheep with inflamed mammary glands can develop prion disease as well. The research, which is published in the January 2011 issue of the Journal of Virology, has major implications for human and livestock health.
“Prions cause devastating, ultimately fatal infections in humans,” says corresponding author Christina Sigurdson of the University of California, San Diego School of Medicine. “This study is the first demonstration of prions from an inflamed organ being secreted, and causing clinical symptoms in a natural host for prion disease.”
Recent research had suggested that human-to-human transmission of prions has occurred via blood transfusions, “underscoring the importance of understanding possible transmission routes,” the researchers write. The misfolded prions that cause vCJD in humans, and BSE in cattle -- which can be transmitted to humans -- commonly accumulate in lymphoid tissues before invading the central nervous system, where they wreak their deadly effects. Inflammation can cause lymphoid follicles to form in other organs, such as liver and kidney, which leads prions to invade organs that normally do not harbor infection. In recent research, this team, led by Ciriaco Ligios of the Istituto Zooprofilattico Sperimentale in Sardinia, Italy and Adriano Agguzi at the University of Zurich, Switzerland, reported sheep with misfolded prions in inflamed mammary glands, also known as mastitis, raising concerns that prions could be secreted into milk.
In the new research, the team infected sheep with a common retrovirus that causes mastitis, and misfolded prions. They bred the sheep, in order to stimulate the females to produce milk, which they then collected and fed to lambs that had never been exposed to prions. The lambs developed prion disease after only two years, a speed which surprised the researchers, and “suggested that there was a high level of prion infectivity in milk,” says Sigurdson.
The research raises several disturbing possibilities.
A common virus in a sheep with prion disease can lead to prion contamination of the milk pool and may lead to prion infection of other animals.
The same virus in a prion-infected sheep could efficiently propagate prion infection within a flock, through transmission of prions to the lambs, via milk. This might be particularly likely on factory farms, where mastitis may be common, and could occur in goats as well as sheep.
Humans with variant Creutzfeldt-Jakob disease (vCJD) might accumulate prions in inflamed organs, and could also secrete prions.
However, “This work cannot be directly extrapolated to cattle,” says Sigurdson. She says that BSE prions do not accumulate to detectible levels in lymphoid organs, and thus would not be expected to accumulate with inflammation. “Nonetheless,” she says, “it would be worth testing milk from cattle with mastitis for prions as there may be other cellular sources for prions entry into milk.”
(C. Ligios, M.G. Cancedda, A. Carta, C. Santucciu, C. Maestrale, F. Demontis, M. Saba, C. Patta, J.C. DeMartini, A. Aguzzi, and C.J. Sigurdson, 2011. Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk. J. Virol. 85:1136-1139.)