Genomic heterogeneity of Dichelobacter nodosus within and between UK sheep flocks and between age groups within a flock.

BACKGROUND: Footrot and interdigital dermatitis are endemic infectious diseases in all sheep farming regions, impairing welfare and production. The development of efficacious vaccines against the primary causative pathogen has been hampered by the extensive antigenic diversity of Dichelobacter nodosus. Understanding the heterogeneity of the pathogen within and between flocks is essential if the feasibility of bespoke vaccine production is to be assessed for use in the U.K. RESULTS: In this study 56 ewe and lamb isolates from 9 flocks were compared by D. nodosus serogroup and Multi Locus Sequence Type which provides significantly enhanced discriminatory power for molecular epidemiology. Serogroup heterogeneity between flocks ranged from two to five unique serogroups per flock. Three flocks contained isolates of two serogroups, two flocks contained isolates of three serogroups and one flock included isolates of five serogroups. Analysis of 25 isolates from one flock with high prevalence of lameness, identified that serogroup and sequence type was significantly correlated with age. Significantly higher proportion of lambs were infected with serogroup B (principally ST85) as opposed to serogroup H (principally ST86), which predominated amongst adult sheep. CONCLUSIONS: Genomic heterogeneity of the pathogen was significantly lower within flock compared to heterogenicity observed between flocks. Furthermore, this study indicates that within a flock, the host-pathogen dynamics and susceptibility to particular D. nodosus strains may be age dependent.

Determinants of the Doppler flow velocity profile through the mitral valve of the human fetus.

OBJECTIVE: A normal fetal flow velocity profile through the atrioventricular valves early in gestation is characterised by a higher late peak (A) than early peak (E) velocity waveform, whereas the E/A ratio is known to increase throughout pregnancy. This study aims firstly to identify which of the two variables, E or A, is the contributory factor to the increased E/A ratio and secondly to assess the relative influence of gestational age, heart rate, and stroke volume on the flow velocity profile through the fetal mitral valve. DESIGN: Eighty normal fetuses from 18 to 38 weeks of gestation were examined by Doppler echocardiography. The variables measured were E and A waves, the early and late flow velocity integrals (EI and AI), and the total filling velocity integral (TI). The ratios E/A and EI/AI were also calculated. Transvalvar flow was obtained by multiplying TI by mitral area. Associations between Doppler variables and gestational age, heart rate, and stroke volume were assessed by multifactorial Anova and simple or multiple stepwise regression analyses. RESULTS: The results showed that the heart rates found did not affect flow velocity variables. There were only weak correlations between both A and AI values and gestational age (negative) and volume load (positive). With the advance in gestation, a significant increase in the early filling E wave was found. The E wave was also positively correlated with stroke volume. CONCLUSION: Contrary to the accepted concept that changes in fetal E/A ratio are related to an improvement in ventricular compliance, this study shows that only the E wave changes. Although these results cannot establish whether changes in the ventricular relaxation process or volume load are responsible for the progressive increase of the E wave, indirect evidence suggests that ventricular relaxation is in fact the most important contributory factor.