No abstract

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled ‘reservoir’ host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers.

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein–Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10−7) and myosin IIIB (MYO3B; P=5.4 × 10−6). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.

Aims. To profile site of stroke/cerebrovascular accident, type and extent of field loss, treatment options, and outcome. Methods. Prospective multicentre cohort trial. Standardised referral and investigation protocol of visual parameters. Results. 915 patients were recruited with a mean age of 69 years (SD 14). 479 patients (52%) had visual field loss. 51 patients (10%) had no visual symptoms. Almost half of symptomatic patients (n = 226) complained only of visual field loss: almost half (n = 226) also had reading difficulty, blurred vision, diplopia, and perceptual difficulties. 31% (n = 151) had visual field loss as their only visual impairment: 69% (n = 328) had low vision, eye movement deficits, or visual perceptual difficulties. Occipital and parietal lobe strokes most commonly caused visual field loss. Treatment options included visual search training, visual awareness, typoscopes, substitutive prisms, low vision aids, refraction, and occlusive patches. At followup 15 patients (7.5%) had full recovery, 78 (39%) had improvement, and 104 (52%) had no recovery. Two patients (1%) had further decline of visual field. Patients with visual field loss had lower quality of life scores than stroke patients without visual impairment. Conclusions. Stroke survivors with visual field loss require assessment to accurately define type and extent of loss, diagnose coexistent visual impairments, and offer targeted treatment.