They show that while the present risk of Creutzfeldt-Jakob disease (vCJD) from eating sheep could be greater than that from cattle, the overall historical risk from sheep is much less than that from cattle.

The research, which is reported in the journal Nature, follows the failure of a recent study to determine whether sheep carry the infectious prion thought responsible for BSE.

The study, by a team from the Department of Infectious Disease Epidemiology at Imperial College, predicts that the future number of deaths from vCJD due to exposure from BSE in cattle alone lies between 50 and 50,000. The upper estimate is lower than previous figures provided by the Imperial team but is substantially greater than estimates from other scientific groups reported in October 2001.

The additional risk from sheep has a limited impact on these figures except in the "worst-case" scenario of a growing sheep epidemic, in which case the range of possible future numbers of deaths increases to between 110 and 150,000.

Professor Neil Ferguson OBE, leader of the research team, said, "Our latest analysis shows that the current risk from sheep could be greater than that from cattle, due to the more intensive controls in place to protect human health from exposure to infected cattle, as compared with sheep. However, more optimistically, our analysis shows that the overall historical risk from sheep was much less than that from cattle."

The authors explore potential risk-reduction strategies similar to those in place for cattle, including restrictions on the age of sheep slaughtered for consumption and enhanced tissue-based controls to reduce the amount of infectivity entering the food supply.

Combining these controls is estimated to reduce current and future risk by up to 90 per cent for all three sheep BSE scenarios they considered.

"We find that if tissue- and age-based risk-reduction measurements, such as those put in place for cattle, were adopted, the current and future risk could be reduced by up to 90 per cent," said Professor Ferguson.

Professor Ferguson acknowledged that many uncertainties remain in performing this type of study, due to the limited data available on BSE in sheep:

"Our estimates are ultimately dependent on the quality and quantity of information that is gathered by other researchers and we feel that large-scale testing of the national flock, and additional experimental research are urgent priorities."

The report concludes by calling for further urgent research to:

1. Screen large numbers of the 40 million strong national sheep flock for BSE-like diseases for infection. Sample sizes must be sufficiently large to be able to detect low prevalence of disease.

2. Discover how infectious BSE in sheep is according to its stage of incubation; the type of tissue it is found in; and the genetic makeup of the sheep.

3. Determine the susceptibility of sheep, cattle and other species to prion diseases at different ages.

4. Measure historical trends in UK consumption of sheep and beef meat.

The mathematical model developed by the research team incorporated data on how infectiousness develops in sheep and was applied to three different scenarios: a "worst-case" in which BSE spreads both within and between flocks; a situation where BSE spreads only within a flock but not between flocks; and a "best case" in which BSE does not spread either within or between flocks.

The research was undertaken in order to pull together the limited and disparate existing information into a single integrated model. This, say the authors, should help prioritize future data collection and inform policymakers.

"We were not trying to evaluate the probability that BSE has entered the sheep flock, but rather, given the pessimistic assumption that infection has occurred, to explore its potential extent and pattern of spread," said Professor Ferguson.

Professor Ferguson and his co-authors are all members of the Department of Infectious Disease Epidemiology, part of the Faculty of Medicine at Imperial College, London. In 2001 they used mathematical and statistical techniques to track Britain's foot and mouth epidemic and evaluated options for control of the disease.

The department carries out research on a wide range of infectious diseases including Foot and Mouth disease, HIV, influenza viruses, pneumococcal and meningococcal bacteria, BSE, vCJD, and a variety of parasitic infections. The department was founded in November 2000 and is headed by Professor Roy Anderson.

The research was funded by the UK Food Standards Agency.

It was published electronically by Nature on January 9, as part of its Advance Online Publication. It will not appear in the 10 January print edition of the journal, but subscribers to Nature can retrieve full text of the article from this URL.

(Reference: Estimating the human health risk from possible BSE infection of the British sheep flock. Neil M. Ferguson, Azra C. Ghani, Christl A. Donnelly, Thomas J. Hagenaars and Roy M. Anderson.)

[Contact: Professor Neil Ferguson OBE, Tom Miller]

10-Jan-2002