Silent spread of H5N1 in vaccinated poultry.

International debate on the merits of vaccinating poultry against the H5N1 influenza A virus has raised concerns about the possibility of an increased risk of between-flock transmission before outbreaks are detected. Here we show that this 'silent spread' can occur because of incomplete protection at the flock level, even if a vaccine is effective in individual birds. The use of unvaccinated sentinels can mitigate, although not completely eliminate, the problem.

Detection of mortality clusters associated with highly pathogenic avian influenza in poultry: a theoretical analysis.

Rapid detection of infectious disease outbreaks is often crucial for their effective control. One example is highly pathogenic avian influenza (HPAI) such as H5N1 in commercial poultry flocks. There are no quantitative data, however, on how quickly the effects of HPAI infection in poultry flocks can be detected. Here, we study, using an individual-based mathematical model, time to detection in chicken flocks. Detection is triggered when mortality, food or water intake or egg production in layers pass recommended thresholds suggested from the experience of past HPAI outbreaks. We suggest a new threshold for caged flocks--the cage mortality detection threshold--as a more sensitive threshold than current ones. Time to detection is shown to depend nonlinearly on R0 and is particularly sensitive for R0<10. It also depends logarithmically on flock size and number of birds per cage. We also examine how many false alarms occur in uninfected flocks when we vary detection thresholds owing to background mortality. The false alarm rate is shown to be sensitive to detection thresholds, dependent on flock size and background mortality and independent of the length of the production cycle. We suggest that current detection thresholds appear sufficient to rapidly detect the effects of a high R0 HPAI strain such as H7N7 over a wide range of flock sizes. Time to detection of the effects of a low R0 HPAI strain such as H5N1 can be significantly improved, particularly for large flocks, by lowering detection thresholds, and this can be accomplished without causing excessive false alarms in uninfected flocks. The results are discussed in terms of optimizing the design of disease surveillance programmes in general.

Quantification of Peyer's patches in Cheviot sheep for future scrapie pathogenesis studies.

Peyer's patches (PPs) are the most probable sites of intestinal uptake of the transmissible spongiform encephalopathy (TSE) agent. The amount of PP tissue varies considerably between different age groups of individuals, and whether this variation is related to susceptibility to TSE infection raises an intriguing possibility. The purpose of this study was to determine the surface area of PP tissue and the number of associated lymphoid follicles in different age groups of Neuropathogenesis Unit (NPU) Cheviot sheep. Terminal ilea were obtained from 33 sheep of different ages. Samples of ileal tissue were collected for immunocytochemistry and immunolabelled for prion protein (PrP). Specimens were then fixed in acetic acid, stained with methylene blue and transilluminated. Image analysis software was used to calculate the area of intestinal and PP tissue. The number of associated lymphoid follicles was determined using a dissecting microscope. Results showed a marked fall in surface area of PP tissue and lymphoid follicle density around puberty (about 8-9 months of age in NPU Cheviot sheep) and both measures remained low throughout adulthood. Using the Spearman's rank correlation coefficient, r(s), these two measures were found to be closely correlated (r(s)=0.899, n=33, P<0.0001). There was also a significant (negative) correlation between age and the two respective measures (surface area of PP tissue versus age, r(s)=-0.879 (n=33, P<0.0001); lymphoid follicle density versus age r(s)=-0.943 (n=33, P<0.0001). Immunolabelling for PrP was observed primarily in the light zone of lymphoid follicles. Results obtained from this study are useful for future oral pathogenesis studies of the NPU Cheviot flock. They may also offer a possible biological explanation for the apparent age-susceptibility relationship observed in natural cases of TSEs and might help to explain the young age-distribution of cases.

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

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.

Effect of penethamate hydriodide treatment on bacteriological cure, somatic cell count and milk production of cows and quarters with chronic subclinical Streptococcus uberis or Streptococcus dysgalactiae infection.

A randomized, controlled field trial was performed in The Netherlands to determine the therapeutic efficacy of parenteral penethamate hydriodide (Leocillin) against naturally occurring, chronic, streptococcal mastitis during lactation. Quarter milk samples were collected from subclinical cases of Streptococcus uberis or Streptococcus dysgalactiae mastitis to determine the effect of treatment on bacteriological cure and somatic cell count (SCC) at quarter level. A quarter was considered to be cured when the bacterial species, isolated prior to treatment, was not isolated from the quarter milk samples taken on days 10 and 20 post-treatment (bacteriological cure), or when a quarter milk SCC (QMSCC) was <250000 cells/ml on days 10 and 20 post-treatment (SCC cure). Longitudinal data analysis was performed to determine the effect of antibiotic therapy on SCC and milk yield at cow level. Bacteriological cure occurred in 59% of 29 treated quarters, while no cure was observed in any of the 21 untreated control quarters. Treatment resulted in a significant decrease in SCC at cow and quarter level in comparison with untreated controls. There was no significant effect of treatment on milk production. Antibacterial treatment of subclinical streptococcal infections during lactation also prevented clinical mastitis. Furthermore, the treatment may contribute to reduction of bulk milk SCC and to prevention of pathogen spread in dairy herds.