Quantitative Microbial Risk Assessment Applied to Legionella Contamination on Long-Distance Public Transport.

The quantitative microbial risk assessment (QMRA) framework is used for assessing health risk coming from pathogens in the environment. In this paper, we used QMRA to evaluate the infection risk of L. pneumophila attributable to sink usage in a toilet cabin on Italian long-distance public transportation (LDT). LDT has water distribution systems with risk points for Legionella proliferation, as well as premise plumbing for drinking water, but they are not considered for risk assessment. Monitoring data revealed that approximately 55% of water samples (217/398) were positive for L. pneumophila, and the most frequently isolated was L. pneumophila sg1 (64%, 139/217); therefore, such data were fitted to the best probability distribution function to be used as a stochastic variable in the QMRA model. Then, a sink-specific aerosolization ratio was applied to calculate the inhaled dose, also considering inhalation rate and exposure time, which were used as stochastic parameters based on literature data. At L. pneumophila sg1 concentration ≤100 CFU/L, health risk was approximately 1 infection per 1 million exposures, with an increase of up to 5 infections per 10,000 exposures when the concentrations were ≥10,000 CFU/L. Our QMRA results showed a low Legionella infection risk from faucets on LDT; however, it deserves consideration since LDT can be used by people highly susceptible for the development of a severe form of the disease, owing to their immunological status or other predisposing factors. Further investigations could also evaluate Legionella-laden aerosols from toilet flushing.

Human adenovirus in municipal solid waste leachate and quantitative risk assessment of gastrointestinal illness to waste collectors.

Leachate is a variable effluent from waste management systems generated during waste collection and on landfills. Twenty-two leachate samples from waste collection trucks and a landfill were collected from March to December 2019 in the municipality of Rio de Janeiro (Brazil) and were analyzed for Human Adenovirus (HAdV), bacterial indicators and physico-chemical parameters. For viral analysis, samples were concentrated by ultracentrifugation and processed for molecular analysis using QIAamp Fast DNA Stool mini kit® for DNA extraction followed by nested-PCR and qPCR/PMA-qPCR TaqMan® system. HAdV was detected by nested-PCR in 100% (9/9) and 83.33% (12/13) of the truck and landfill leachate samples, respectively. Viral concentrations ranged from 8.31 × 101 to 6.68 × 107 genomic copies per 100 ml by qPCR and PMA-qPCR. HAdV species A, B, C, and F were characterized using nucleotide sequencing. HAdV were isolated in A549 culture cells in 100% (9/9) and 46.2% (6/13) from truck and landfill leachate samples, respectively. Regardless of the detection methods, HAdV concentration was predicted by the quantity of total suspended solids. A quantitative microbial risk assessment was performed to measure the probability of gastrointestinal (GI) illness attributable to inadvertent oral ingestion of truck leachate, revealing the higher probability of disease for the direct splashing into the oral cavity (58%) than for the gloved hand-to-mouth (33%). In a scenario where waste collectors do not wear gloves as protective personal equipment, the risk increases to 67%. This is the first study revealing infectious HAdV in solid waste leachate and indicates a potential health risk for waste collectors.

Cost analysis of extended half-life recombinant factor IX products in the treatment of haemophilia B in Italy: an update.

Haemophilia B (HB) is a rare disease which may lead to chronic disabling arthropathy, resulting in a significant clinical, social and economic impact. In recent years, new extended half-life (EHL) factor IX concentrates produced by recombinant technology (rFIX) have been developed. They have shown significantly prolonged half-life as compared to other rFIX products and improved bleeding control when used as prophylaxis. To date, EHL rFIX products reimbursed in Italy are a recombinant coagulation factor IX produced with Fc technology (rFIXFc) and a recombinant fusion protein containing rFIX fused with recombinant albumin (rIX-FP). The results of extension studies with injection intervals with a median of almost every 14 days for the complete individualized interval prophylaxis (IP) group on rFIXFc and 21 days for a selected subgroup of patients on rIX-FP have recently been published. The aim of this analysis was to estimate the cost of prophylactic treatment with rFIXFc and rIX-FP in adult patients, in the light of new clinical evidence and current average prices in Italy. The cost of therapy was estimated on the basis of the results of extension studies, the average prices reported in regional drug tenders and assuming an average patient weight of 70 kg. The analysis estimated a cost per patient/year between €224,407 and €230,355 for rFIXFc and between €242,259 and €368,587 for rIX-FP. The sensitivity analysis confirmed the robustness of the results. The use of rFIXFc over rIX-FP proves to be the least expensive choice for the treatment of HB in Italy.

Relations between Air Quality and Covid-19 Lockdown Measures in Valencia, Spain.

The set of measures to contain the diffusion of COVID-19 instituted by the European governments gave an unparalleled opportunity to improve our understanding of the transport and industrial sectors' contribution to urban air pollution. The purpose of this study was to assess the impacts of the lockdown measures on air quality and pollutant emissions in Valencia, Spain. For this reason, we determined if there was a significant difference in the concentration levels of different particulate matter (PM) sizes, PM10, PM2.5, and NOx, NO2, NO, and O3, between the period of restrictions in 2020 and the same period in 2019. Our findings indicated that PM pollutant levels during the lockdown period were significantly different from the same period of the previous year, even if there is variability in the different local areas. The highest variations reduction in the PM10 and PM2.5 levels were observed for the València Centre, València Avd Francia, and València Pista de Silla (all of the urban traffic type) in which there was a reduction of 58%-42%, 56%-53%, and 60%-41% respectively. Moreover, consistent with recent studies, we observed a significant reduction in nitric oxide levels in all the air monitoring stations. In all seven monitoring stations, it was observed, in 2020, NOx, NO2, and NO concentrations decreased by 48.5%-49.8%-46.2%, 62.1%-67.4%-45.7%, 37.4%-35.7%-35.3%, 60.7%-67.7%-47.1%, 65.5%-65.8%-63.5%, 60.0%-64.5%-41.3%, and 60.4%-61.6%-52.5%, respectively. Lastly, overall O3 levels decreased during the lockdown period, although this phenomenon was more closely related to weather conditions. Overall, no significant differences were observed between the meteorological conditions in 2019 and 2020. Our findings suggest that further studies on the effect of human activities on air quality are needed and encourage the adoption of a holistic approach to improve urban air quality.

Quantitative Microbial Risk Assessment as support for bathing waters profiling.

Profiling bathing waters supported by Quantitative Microbial Risk Assessment (QMRA) is key to the WHO's recommendations for the 2020/2021 revision of the European Bathing Water Directive. We developed an area-specific QMRA model on four pathogens, using fecal indicator concentrations (E. coli, enterococci) for calculating pathogen loads. The predominance of illness was found to be attributable to Human Adenovirus, followed by Salmonella, Vibrio, and Norovirus. Overall, the cumulative illness risk showed a median of around 1 case/10000 exposures. The risk estimates were strongly influenced by the indicators that were used, suggesting the need for a more detailed investigation of the different sources of fecal contamination. Area-specific threshold values for fecal indicators were estimated on a risk-basis by modelling the cumulative risk against E. coli and enterococci concentrations. To improve bathing waters assessment, we suggest considering source apportionment, locally estimating of pathogen/indicator ratios, and calculating site-specific indicators thresholds based on risk assessment.

Particulate Matter Exposure and Attention-Deficit/Hyperactivity Disorder in Children: A Systematic Review of Epidemiological Studies.

Attention-deficit/hyperactivity disorder (ADHD) is the most common cognitive and behavioural disorder affecting children, with a worldwide-pooled prevalence of around 5%. Exposure to particulate matter (PM) air pollution is suspected to be associated with autism spectrum disorders and recent studies have investigated the relationship between PM exposure and ADHD. In the absence of any synthesis of the relevant literature on this topic, this systematic review of epidemiological studies aimed to investigate the relationship between the exposure of children to PM and ADHD and identify gaps in our current knowledge. In December 2018, we searched the PubMed and EMBASE databases. We only included epidemiological studies carried out on children without any age limit, measuring PM exposure and health outcomes related to ADHD. We assessed the quality of the articles and the risk of bias for each included article using the Newcastle-Ottawa Scale and the Office of Health Assessment and Translation (OHAT) approach, respectively. The keyword search yielded 774 results. Twelve studies with a total number of 181,144 children met our inclusion criteria, of which 10 were prospective cohort studies and 2 were cross-sectional studies. We subsequently classified the selected articles as high or good quality studies. A total of 9 out of the 12 studies reported a positive association between PM exposure to outdoor air pollution and behavioral problems related to attention. Despite these results, we found a significant degree of heterogeneity among the study designs. Furthermore, 11 studies were judged to be at a probably high risk of bias in the exposure assessment. In conclusion, we opine that further high quality studies are still needed in order to clarify the association between PM exposure and ADHD diagnosis.

The application of quantitative microbial risk assessment to natural recreational waters: A review.

This review examines the aims of and approaches to the Quantitative Microbial Risk Assessment (QMRA) of untreated recreational waters. The literature search was conducted on four databases and yielded 54 papers, which were analyzed on a quantitative (time-trend, geographical distribution, water type) and qualitative (aims, source of microbial data, pathogens and their measurement or estimation, ways to address variability and uncertainty, sensitivity analysis) basis. In addition, the parameters, implications, and limitations were discussed for each QMRA step. Since 2003, the number of papers has greatly increased, highlighting the importance of QMRA for the risk management of recreational waters. Nevertheless, QMRA still exhibits critical issues, above all regarding contamination data and dose-response relationships. To our knowledge, this is the first review to give a wide panoramic view on QMRA in relation to recreational exposure to untreated waters. This could be useful in identifying the current knowledge gaps and research needs.

The Association between Lead and Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

The etiology of Attention-Deficit/Hyperactivity Disorder (ADHD) is complex and multifactorial. Although the development of ADHD symptoms remains to be elucidated, in recent years, epigenetic processes have emerged as candidate mechanisms. Lead is one of the most dangerous environmental pollutants, and it is suspected to be associated with ADHD. The aim of the present study was to review the epidemiological literature currently available on the relation between lead exposure and the diagnosis of ADHD. The PubMed and EMBASE databases were searched from 1 July 2018 up to 31 July 2018. The authors included observational studies (cohort, case⁻control and cross-sectional studies) published in English carried out on children within the last 5 years, measuring lead exposure and health outcomes related to ADHD. Seventeen studies met the inclusion criteria: 5 of these studies found no association between lead exposure and ADHD whereas the remaining 12 studies showed positive associations, even though not all of them were homogeneous in terms of exposure periods considered or ADHD diagnosis. To conclude, the evidence from the studies allowed us to establish that there is an association between lead and ADHD and that even low levels of lead raise the risk. However, there is still a lack of longitudinal studies about the relationship between lead exposure and the development of ADHD. Given the potential importance for public health, further research that includes the entire potential risk factors for ADHD in children must be encouraged.

Human adenoviruses as waterborne index pathogens and their use for Quantitative Microbial Risk Assessment.

The current microbial water quality standards are based on the monitoring of fecal indicator organisms, which are mainly bacterial indicators (i.e., Escherichia coli, intestinal enterococci), however epidemiological data indicate that viruses are important etiological agents of waterborne illnesses. Among waterborne viruses, human adenovirus can be considered as an index pathogen, owing to its abundance in sewage and persistence in the environment, as well as its potential infectivity. In this study, data on human adenoviruses from different water matrices (the entrance and exit of a water treatment plant, rivers and seawaters) were analyzed, in parallel with traditional fecal bacterial indicators and somatic coliphages. The results showed a 64% frequency of positive adenovirus samples, decreasing from the sewage system (100% at the entrance and 94% at the exit) to rivers (92% and 72% for different rivers) and seawater (21%). Adenovirus concentrations showed a significant correlation with somatic coliphages in one river and seawater, thus supporting the recent inclusion of coliphages as viral indicators in water safety guidelines. The data collected were used to estimate adenovirus to indicator ratios, which could be used as input in Quantitative Microbial Risk Assessment (QMRA) studies.

Quantitative Microbial Risk Assessment for Workers Exposed to Bioaerosol in Wastewater Treatment Plants Aimed at the Choice and Setup of Safety Measures.

Biological risk assessment in occupational settings currently is based on either qualitative or semiquantitative analysis. In this study, a quantitative microbial risk assessment (QMRA) has been applied to estimate the human adenovirus (HAdV) health risk due to bioaerosol exposure in a wastewater treatment plant (WWTP). A stochastic QMRA model was developed considering HAdV as the index pathogen, using its concentrations in different areas and published dose⁻response relationship for inhalation. A sensitivity analysis was employed to examine the impact of input parameters on health risk. The QMRA estimated a higher average risk in sewage influent and biological oxidation tanks (15.64% and 12.73% for an exposure of 3 min). Sensitivity analysis indicated HAdV concentration as a predominant factor in the estimated risk. QMRA results were used to calculate the exposure limits considering four different risk levels (one illness case per 100, 1.000, 10.000, and 100.000 workers): for 3 min exposures, we obtained 565, 170, 54, and 6 GC/m³ of HAdV. We also calculated the maximum time of exposure for each level for different areas. Our findings can be useful to better define the effectiveness of control measures, which would thus reduce the virus concentration or the exposure time.

Misinformation on vaccination: A quantitative analysis of YouTube videos.

In Italy, the phenomenon of vaccine hesitancy has increased with time and represents a complex problem that requires a continuous monitoring. Misinformation on media and social media seems to be one of the determinants of the vaccine hesitancy since, for instance, 42.8 percent of Italian citizens used the internet to obtain vaccine information in 2016. This article reports a quantitative analysis of 560 YouTube videos related to the link between vaccines and autism or other serious side effects on children. The analysis revealed that most of the videos were negative in tone and that the annual number of uploaded videos has increased during the considered period, that goes from 27 December 2007 to 31 July 2017, with a peak of 224 videos in the first seven months of 2017. These findings suggest that the public institutions should be more engaged in establishing a web presence in order to provide reliable information, answers, stories, and videos so to respond to questions of the public about vaccination. These actions could be useful to allow citizens to make informed decisions about vaccines so to comply with vaccination regulations.

Quantitative Microbial Risk Assessment in Occupational Settings Applied to the Airborne Human Adenovirus Infection.

Quantitative Microbial Risk Assessment (QMRA) methodology, which has already been applied to drinking water and food safety, may also be applied to risk assessment and management at the workplace. The present study developed a preliminary QMRA model to assess microbial risk that is associated with inhaling bioaerosols that are contaminated with human adenovirus (HAdV). This model has been applied to air contamination data from different occupational settings, including wastewater systems, solid waste landfills, and toilets in healthcare settings and offices, with different exposure times. Virological monitoring showed the presence of HAdVs in all the evaluated settings, thus confirming that HAdV is widespread, but with different average concentrations of the virus. The QMRA results, based on these concentrations, showed that toilets had the highest probability of viral infection, followed by wastewater treatment plants and municipal solid waste landfills. Our QMRA approach in occupational settings is novel, and certain caveats should be considered. Nonetheless, we believe it is worthy of further discussions and investigations.