Analysis of three phage resistance mechanisms and a recA homologue encoded by the lactococal plasmid pNP40

Phage represent a major problem in dairy fermentations Investigation of the phage resistance mechanisms employed by naturally insensitive lactococcal strains should aid m the development of rational strategies to help combat the problem. The lactococcal plasmid pNP40 from Lactococcus lactis ssp lactis biovar diacetylactis confers complete resistance to the prolate-headed 0c2 and the small isometnc-headed 0712 in L lactis ssp lactis MG1614, and has been used successfully to construct commercially valuable starter strains. In this study, the determinants for two independent abortive infection phage resistance systems (AbiE and AbiF) were cloned AbiF was shown to act at the level of phage DNA replication while AbiE operates post-replication, possibly at the level of transcription/translation or phage packaging/release pNP40 was also found to mediate resistance to 0c2 by a novel earlyacting phage resistance mechanism which we propose prevents phage DNA penetration into the host. Sequence analysis of the detemmants for AbiE and AbiF demonstrated that two overlapping ORF's, of 861 bp and 894 bp respectively, are required for expression of AbiE while a single 1026 bp ORF encodes AbiF Two ORF's are located between the abiE and abiF determinants, one of which codes for a RecA homologue. This represents, to our knowledge, the first recA gene located on a plasmid. Using a RecA deficient lactococcal strain, it was established that while the chromosomally-encoded RecA is required for full phenotypic expression of AbiF, the pNP40-encoded RecA has no discernible role in phage resistance. Thus, pNP40-directed phage insensitivity is mediated by three independent phage resistance systems AbiE, AbiF and a novel phage DNA penetration blocking mechanism

The first year counts: cancer survival among Indigenous and non-Indigenous Queenslanders, 1997–2006

Objective: To examine the differential in cancer survival between Indigenous and non-Indigenous people in Queensland in relation to time after diagnosis, remoteness and area-socioeconomic disadvantage. Design, setting and participants: Descriptive study of population-based data on all 150 059 Queensland residents of known Indigenous status aged 15 years and over who were diagnosed with a primary invasive cancer during 1997–2006. Main outcome measures: Hazard ratios for the categories of area- socioeconomic disadvantage, remoteness and Indigenous status, as well as conditional 5-year survival estimates. Results: Five-year survival was lower for Indigenous people diagnosed with cancer (50.3%; 95% CI, 47.8%–52.8%) compared with non-Indigenous people (61.9%; 95% CI, 61.7%–62.2%). There was no evidence that this differential varied by remoteness (P = 0.780) or area-socioeconomic disadvantage (P = 0.845). However, it did vary by time after diagnosis. In a time-varying survival model stratified by age, sex and cancer type, the 50% excess mortality in the first year (adjusted HR, 1.50; 95% CI, 1.38–1.63) reduced to near unity at 2 years after diagnosis (HR, 1.03; 95% CI, 0.78–1.35). Conclusions: After a wide disparity in cancer survival in the first 2 years after diagnosis, Indigenous patients with cancer who survive these 2 years have a similar outlook to non-Indigenous patients. Access to services and socioeconomic factors are unlikely to be the main causes of the early lower Indigenous survival, as patterns were similar across remoteness and area- socioeconomic disadvantage. There is an urgent need to identify the factors leading to poor outcomes early after diagnosis among Indigenous people with cancer

Geocoding cryptosporidiosis cases in Ireland (2008–2017)—development of a reliable, reproducible, multiphase geocoding methodology

Background: Geocoding (the process of converting a text address into spatial data) quality may affect geospatial epidemiological study findings. No national standards for best geocoding practice exist in Ireland. Irish postcodes (Eircodes) are not routinely recorded for infectious disease notifications and \u3e 35% of dwellings have non-unique addresses. This may result in incomplete geocoding and introduce systematic errors into studies. Aims: This study aimed to develop a reliable and reproducible methodology to geocode cryptosporidiosis notifications to fine-resolution spatial units (Census 2016 Small Areas), to enhance data validity and completeness, thus improving geospatial epidemiological studies. Methods: A protocol was devised to utilise geocoding tools developed by the Health Service Executive\u27s Health Intelligence Unit. Geocoding employed finite-string automated and manual matching, undertaken sequentially in three additive phases. The protocol was applied to a cryptosporidiosis notification dataset (2008-2017) from Ireland\u27s Computerised Infectious Disease Reporting System. Outputs were validated against devised criteria

Socio-Economic Factors Associated With The Incidence of Shiga-Toxin Producing Escherichia Coli (STEC) Enteritis and Cryptosporidiosis in the Republic of Ireland, 2008–2017

The Republic of Ireland (ROI) currently reports the highest incidence rates of Shiga-toxin producing Escherichia coli (STEC) enteritis and cryptosporidiosis in Europe, with the spatial distribution of both infections exhibiting a clear urban/rural divide. To date, no investigation of the role of socio-demographic profile on the incidence of either infection in the ROI has been undertaken. The current study employed bivariate analyses and Random Forest classification to identify associations between individual components of a national deprivation index and spatially aggregated cases of STEC enteritis and cryptosporidiosis. Classification accuracies ranged from 78.2% (STEC, urban) to 90.6% (cryptosporidiosis, rural). STEC incidence was (negatively) associated with a mean number of persons per room and percentage of local authority housing in both urban and rural areas, addition to lower levels of education in rural areas, while lower unemployment rates were associated with both infections, irrespective of settlement type. Lower levels of third-level education were associated with cryptosporidiosis in rural areas only. This study highlights settlement-specific disparities with respect to education, unemployment and household composition, associated with the incidence of enteric infection. Study findings may be employed for improved risk communication and surveillance to safeguard public health across socio-demographic profiles

Spatiotemporal Dynamics of Sporadic Shiga Toxin–Producing Escherichia coli Enteritis, Ireland, 2013–2017

The Republic of Ireland regularly reports the highest annual crude incidence rates of Shiga toxin–producing Escherichia coli (STEC) enteritis in the European Union, ≈10 times the average. We investigated spatiotemporal patterns of STEC enteritis in Ireland using multiple statistical tools. Overall, we georeferenced 2,755 cases of infection during January 2013–December 2017; we found \u3e1 case notified in 2,340 (12.6%) of 18,641 Census Small Areas. We encountered the highest case numbers in children 0–5 years of age (n = 1,101, 39.6%) and associated with serogroups O26 (n = 800, 29%) and O157 (n = 638, 23.2%). Overall, we identified 17 space-time clusters, ranging from 2 (2014) to 5 (2017) clusters of sporadic infection per year; we detected recurrent clustering in 3 distinct geographic regions in the west and mid-west, all of which are primarily rural. Our findings can be used to enable targeted epidemiologic intervention and surveillance