Open Access Highly Accessed Research article

Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

Suzanne G St Rose1*, Nora Hunter2, Louise Matthews3, James D Foster2, Margo E Chase-Topping1, Loeske EB Kruuk4, Darren J Shaw5, Susan M Rhind6, Robert G Will7 and Mark EJ Woolhouse1

Author Affiliations

1 Centre for Infectious Diseases, University of Edinburgh, Ashworth Laboratories, King's Buildings, West Mains Road, Edinburgh EH9 3JF, UK

2 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK

3 Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK

4 Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK

5 Division of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK

6 Division of Animal Health and Welfare, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK

7 The National Creutzfeldt-Jakob disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

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BMC Infectious Diseases 2006, 6:5  doi:10.1186/1471-2334-6-5

Published: 11 January 2006

Abstract

Background

Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut.

Methods

Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age.

Results

There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014).

Conclusion

Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.