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Economic Evaluation The aim of the economic evaluation was to examine the cost effectiveness of the two screening models tested in the Chlamydia Screening in Ireland Pilot (CSIP) study: (a) Clinical Setting screening, and (b) ’Pee-in-a-pot’ periodic screening in third level institution/college settings. The methodological approach comprised of a dynamic transmission model paired with an economic model. In both analyses, screening was compared to a control strategy of no organised screening, that is existing care in Ireland. A public health system or provider perspective was adopted with respect to costs. The analysis considered the cost of screening to the health service, and the costs of infection and complications, not any additional costs reported by young people in accepting a chlamydia screening test. Health outcomes were assessed in terms of major outcomes (MOs) averted and quality adjusted life years (QALYs) gained. The costs of Clinical Setting screening were presented in terms of the cost per offer (€26 ), the cost per negative case (€66), the cost per positive case (€152), and the cost per partner notified and treated (€74). The costs of ’Pee-in-a-pot’ screening were presented in terms of the cost per negative case (€39), the cost per positive case (€125), and the cost per partner notified and treated (€74). In both analyses, screening was estimated to result in fewer major outcomes, fewer QALYs lost, and higher healthcare costs compared to the control strategy. The incremental cost effectiveness analyses indicated that screening in the Clinical Setting would result in an incremental cost per MO averted of €6,093 and an incremental cost per QALY gained of €94,717. ’Pee-in-a-pot’ screening was estimated to result in incremental cost effectiveness ratios of €2,294 per MO averted and €34,486 per QALY gained respectively. In Ireland, there is no fixed and generally agreed cost effectiveness threshold below which health care technologies would be considered by policy makers to be costeffective. Nonetheless, on the basis of other technologies that are currently funded, it is not likely that screening delivered in the Clinical Setting, given an incremental cost per QALY in the region of the €94,717 found in this study, would be considered cost effective. ’Pee-in-a-pot’ screening in third level institution/college settings may be considered cost effective if a cost effectiveness threshold in the region of €45,000 per QALY gained is used. This is open to question, however, given the current economic climate and its resulting impact in terms of imposing further constraints on future healthcare budgets. It is also important to note that this strategy would have minimal in impact in reducing overall chlamydia prevalence in the population, if not supported by general population screening and prevention strategy.

Summary A series of background studies in 18 to 29 year olds were conducted in a range of primary care settings in Dublin and Galway, 2007-09, to assess the acceptability and feasibility of opportunistic screening for chlamydia: - semi-structured interviews with 35 women who had never been tested for a sexually transmitted infection (STI) - similar interviews with 30 men and women who had had a STI test - a questionnaire survey of 5685 students and 400 primary care patients - four focus group discussions with university students - semi-structured interviews with eight doctors and 10 practice nurses. The most important barrier to seeking or taking a STI test was the stigma young Irish men and women associated with chlamydia and other STIs, and the fear of being seen doing this. This fear was greater among young women. Young people, especially women, were aware that chlamydia infection was often asymptomatic and were conscious of the danger of complications such as infertility and the consequences of transmitting chlamydia to other women. Factors that would encourage acceptance of a chlamydia screening test, which were common to women and men, were: - normalising STI testing, by portraying it as a responsible practice that adults should engage in - not being asked questions by staff about their sexual history - being offered screening by younger non-judgmental female healthcare professionals - being offered screening in private or general health care settings, where others would not be aware that they were getting an STI test There was a high level of acceptance of chlamydia screening among young people: 95% said it would be acceptable to be offered a test, and 90% of health facility attendees and 75% of students said they would accept a test if offered. The most acceptable setting for chlamydia screening was a General Practice where respondents were most comfortable with being offered screening by a doctor or nurse. Other primary care settings were also acceptable, whereas pharmacies were not because they were seen as public settings. 80% said they would inform their current partner if they tested positive for chlamydia, though this fell to 55-60% in the case of previous partners. Health care providers (doctors and nurses) viewed chlamydia screening as a priority, because young people are sexually active and are at high risk because of alcohol. Providers anticipated high chlamydia test offers and uptake rates. Providers viewed chlamydia testing as a core activity to undertake in primary care, but they would need support for partner notification and easy access to laboratory tests, especially urine-based ones. Conclusion: Most 18-29 year old men and women would respond positively if offered a test for chlamydia, when attending a health care facility for other reasons. They recognise the risks and the importance of their sexual contacts being tested, if they themselves test positive for chlamydia. However, sexual health services in Ireland need to minimise stigma and ensure the confidentiality and acceptability of STI testing of young people.

This report summarises the findings of the Pilot Screening Intervention conducted in Ireland between 2008 and 2009 as part of the Chlamydia Screening in Ireland Pilot study. The studies aimed to pilot screening models and to evaluate their feasibility and effectiveness. The study was commissioned by the Health Protection Surveillance Centre (HPSC) and overseen by the Health Research Board (HRB). It was carried out by a team from the Division of Population Health Sciences at the Royal College of Surgeons (RSCI) in Ireland, the College of Medicine, Nursing and Health Sciences at the National University of Ireland Galway, and Consultants in Public Health Medicine from the Health Service Executive (HSE). ² Ethical approval for study components was provided by Research Ethics Committees of the RCSI, NUI Galway and the Irish College of General Practitioners (ICGP).

Background and aimThe trend in reported case counts of invasive Listeria monocytogenes (Lm), a potentially severe food-borne disease, has been increasing since 2008. In 2015, 2,224 cases were reported in the European Union/European Economic Area (EU/EEA). We aimed to validate the microbiological and epidemiological aspects of an envisaged EU/EEA-wide surveillance system enhanced by routine whole genome sequencing (WGS). Methods: WGS and core genome multilocus sequence typing (cgMLST) were performed on isolates from 2,726 cases from 27 EU/EEA countries from 2010-15. Results: Quality controls for contamination, mixed Lm cultures and sequence quality classified nearly all isolates with a minimum average coverage of the genome of 55x as acceptable for analysis. Assessment of the cgMLST variation between six different pipelines revealed slightly less variation associated with assembly-based analysis compared to reads-based analysis. Epidemiological concordance, based on 152 isolates from 19 confirmed outbreaks and a cluster cutoff of seven allelic differences, was good (sensitivity > 95% for two cgMLST schemes of 1,748 and 1,701 loci each; PPV 58‒68%). The proportion of sporadic cases was slightly below 50%. Of remaining isolates, around one third were in clusters involving more than one country, often spanning several years. Detection of multi-country clusters was on average several months earlier when pooling the data at EU/EEA level, compared with first detection at national level. Conclusions: These findings provide a good basis for comprehensive EU/EEA-wide, WGS-enhanced surveillance of listeriosis. Time limits should not be used for hypothesis generation during outbreak investigations, but should be for analytical studies.

Nanotechnology is an emerging technology that has the potential to impact on all aspects of life and the economy and is expected to form the basis of several technological innovations and advances in the 21st century. The European Commission defines a nanomaterial as “a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm–100 nm”. The production of and demand for products containing nanomaterials has increased significantly in recent years. The Nanodatabase developed by the Technical University of Denmark is a “living” inventory of commercially available products in the European consumer market that claim to contain engineered nanomaterials (ENMs) and currently lists 3037 products. Nanomaterials have a wide range of potential applications, from everyday uses (such as improvements in fabrics, paints, cosmetics and packaging) to medical applications, water and soil remediation and renewable energy production. Nanomaterials include both nanoparticles and nanosynthesised materials. Nanomaterials can be naturally occurring, inadvertently generated or engineered. ENMs are intentionally produced and exhibit unique electrical, magnetic, optical, antimicrobial and other properties. Silver nanoparticles (AgNPs) are among the ENMs most often incorporated in nanofunctionalised consumer products. AgNPs have been incorporated into a diverse range of consumer products including plastics, soaps, pastes, metals and fabrics and have applications in water and soil remediation. In the Nanodatabase, currently 539 of the 3037 products listed contain silver. Although advances in nanotechnology and the continued development of novel ENMs are expected to lead to significant societal benefits, there is increasing concern that the unique properties of ENMs may result in potential hazards for both humans and the environment. ENMs can be released into various environmental matrices during their production, use and disposal. ENMs pose a potential risk to human health through ingestion, inhalation and contact. To date, the concentrations of AgNPs in the aquatic environment have primarily been estimated through modelling, with predicted environmental concentrations in the ng/l range. This is largely because of a dearth of appropriate detection methods. The aims of this 3-year research project were to (1) develop and implement methods for the detection of AgNPs in water; (2) determine the toxicological properties and environmental fate of AgNPs in the aquatic environment and (3) develop risk assessment protocols that can be used to evaluate the environmental fate of and likely risk from AgNPs in aquatic pathways. The suitability of activated charcoal as a capture material for AgNPs from water was examined. Samples of 100 μg/l of AgNPs were initially generated and exposed to activated charcoal for 24 hours to examine the ability of charcoal to capture AgNPs. The decrease in silver concentration was measured using an inductively coupled plasma mass spectrometer. Following initial investigations, the surface area of the charcoal was increased, first, with a pestle and mortar and, second, by milling. The increased surface area of the milled charcoal increased the capture of the AgNPs from 11.9% to 63.6%. A hydrochloric acid leaching procedure was developed that successfully removed the captured silver, allowing the fraction captured by the charcoal to be quantified, with an average recovery rate of 94.8%. The results show that milled activated charcoal can successfully capture AgNPs from water samples. Activated charcoal therefore represents a cost-effective material for the remediation of waters impacted by AgNPs or other nano-wastes. A multi-trophic test battery that included three trophic levels was adopted to assess the ecotoxicity of AgNPs and silver nitrate (AgNO3) to the algae Pseudokirchneriella subcapitata, the crustacean Daphnia spp. and the cnidarian Hydra attenuata. The standard medium (Jaworski’s medium) and an ethylenediaminetetraacetic acid (EDTA)-free medium (Chu#10) were tested concurrently. An approximately 10-fold improvement in test sensitivity using EDTA-free medium was observed overall. No significant difference between the toxicity of AgNP and x Detection, Toxicology, Environmental Fate and Risk Assessment of Nanoparticles in the Aquatic Environment (DeTER) the toxicity of AgNO3 was observed. Both Daphnia pulex and Daphnia magna were compared using AgNO3 and AgNPs. Daphnia pulex, with a 24-hour half-maximal inhibitory concentration (IC50) of 9.3 μg/l, was less sensitive to AgNO3 than Daphnia magna, with an IC50 of 1.22 μg/l. When tested with AgNPs, both species yielded similar results, with an IC50 of 7.85 μg/l for Daphnia magna and 4.2 μg/l for Daphnia pulex. As these IC50 values were substantially higher than the predicted environmental concentrations, sub-lethal end points were investigated. Fecundity was assessed in Daphnia magna, with the number of offspring reduced by 50% after 14 days and 75% after 28 days when cultured in 100 ng/l of AgNPs. This demonstrates that the effects of AgNPs may be seen at close to environmentally relevant concentrations on population numbers rather than single individual organisms. Assessment of the ecotoxicity of AgNPs using Hydra attenuata gross morphology as the end point yielded a 96-hour half-maximal effective concentration (EC50) of 29 μg/l for AgNPs. The effect of silver on the regeneration of Hydra attenuata was the most environmentally relevant bioassay investigated as it is very sensitive and robust and Hydra attenuata represents benthic dwellers likely to be exposed to higher concentrations of AgNPs. The risk assessment involved a number of interlinking stages. Stage 1 included a review of the state of the art regarding natural attenuation processes that affect ENPs in the natural aquatic environment and a review of current risk assessment strategies. In stage 2 a suite of laboratory-scale studies were conducted to better characterise the aggregation potential of AgNPs. The behavioural indications derived from stages 1 and 2 were used to develop an aquatic risk model (stage 3), which was used to characterise the likely residual levels of AgNPs in surface waters. Estimated initial values indicated a mean AgNP concentration of 4.34 × 10–2 μg/l and this was assumed as a worst-case scenario for surface water concentrations in Ireland and used as an initial input value in the risk model. Seasonal factors were incorporated in the risk model to account for potential fluctuations in organic matter and ionic strength, which have been identified as key influencers of particle stability and eventual fate in natural water systems. The predicted results from the model developed indicate that citrate-coated particles underwent greater removal than polyvinylpyrrolidone (PVP)-coated AgNPs in both stream water and lake water, with predicted removal rates after 7 days of ≈70% (stream water) and ≈67% (lake water) for citrate-coated particles and ≈45% (stream water) and ≈50% (lake water) for PVP-coated AgNPs. Predicted aquatic concentrations of AgNPs were compared with toxicity data from project partners to establish if a risk is posed by current estimated concentrations of AgNPs in natural waters. The EC50 values from primary producer (algae) to primary consumer (Daphnia pulex) to secondary consumer (Hydra attenuata) exposed to PVP-coated AgNPs were compared with persistent concentrations of AgNPs in freshwater systems. The concentrations of AgNPs used in the model were at levels deemed unlikely to have toxicity concerns to aquatic organisms (mean levels in water of 4.34 × 10–2 μg/l). Therefore, at current predicted water concentrations, AgNPs are unlikely to present a toxic concern to the aquatic food chain. Stages 4 and 5 used information generated to assess potential human exposure through drinking water. The model incorporated estimated removal rates for the differing treatment processes. Risk to human health was calculated based on water consumption and potential exposure to residual AgNPs using the hazard quotient (HQ). The HQ is a ratio of the possible exposure to a particular substance and the level at which it is expected that no adverse effects will occur. If the calculated HQ is less than 1 then it is expected that no adverse health effects will result from exposure. The predicted HQ indicated that there was no existing risk through the consumption of drinking water (HQ of 3.24 × 10–7 for males and 3.84 × 10–7 for females). However, the increased industrial usage of nanomaterials in many sectors, in conjunction with the persistence of AgNPs during drinking water treatment, suggests the need to constantly monitor levels and re-assess exposure through drinking water into the future. yes