Measuring mantled howler monkey (Alouatta palliata) testes via parallel laser photogrammetry: Expanding the use of noninvasive methods.

Parallel laser photogrammetry (PLP), which consists of attaching two or three parallel laser beams at a known inter-beam distance to a camera, can be used to collect morphological measurements of organisms noninvasively. The lasers project onto the photo being taken, and because the inter-beam distance is known, they act as a scale for image analysis programs like ImageJ. Traditionally, this method has been used to measure larger morphological traits (e.g., limb length, crown-rump length) to serve as proxies for overall body size, whereas applications to smaller anatomical features remain limited. To that end, we used PLP to measure the testes of 18 free-living mantled howler monkeys (Alouatta palliata) at La Selva Biological Station, Costa Rica. We tested whether this method could reliably measure this relatively small and globular morphology, and whether it could detect differences among individuals. We tested reliability in three ways: within-photo (coefficient of variation [CV] = 4.7%), between-photo (CV = 5.5%), and interobserver (intraclass correlation = 0.92). We found an average volume of 36.2 cm3 and a range of 16.4-54.4 cm3, indicating variation in testes size between individuals. Furthermore, these sizes are consistent with a previous study that collected measurements by hand, suggesting that PLP is a useful method for making noninvasive measurements of testes.

Sleep Dysfunction in Adolescents With Prolonged Postconcussion Symptoms: A Reciprocal Coupling of Traumatic Brain Injury and Sleep-Related Problems.

CLINICAL SCENARIO: Concussions are often neglected injuries that affect children and adolescents. Two physiological responses to a concussion are an ionic flux and an increased indiscriminate release of glutamate, which leads to an increase of intracellular calcium and extracellular potassium. This can ultimately result in sleep dysfunction, which often occurs after concussion and has long been thought of as simply another concussion symptom. FOCUSED CLINICAL QUESTION: Does the likelihood of prolonged postconcussion symptoms increase with reported sleep-related problems (SRPs) in young athletes (8-18 y) compared to concussed young athletes without SRPs and healthy controls? SUMMARY OF KEY FINDINGS: Four cohort studies with level 2/3 evidence measured subjective and objective sleep dysregulations in concussed and healthy populations. Overall, there was a difference in subjective SRPs between concussed and healthy patients. This correlated with other studies where worse sleep scores during the acute phase of concussion and increased SRPs led to worse ImPACT scores in patients 3 to 12 months postconcussion and longer overall recovery. Objective sleep dysfunction measures were significantly worse in concussed patients than in healthy controls, but no significant difference existed in melatonin measures. CLINICAL BOTTOM LINE: There is strong evidence that sleep dysfunction is both a symptom of concussion as well as a causal factor of prolonged postconcussion symptoms. These studies show that sleep dysregulation is not always evident in objective measurements, leading to the strong possibility of a functional dysregulation of the sleep-wake cycle that is evident solely from subjective reports. STRENGTH OF RECOMMENDATION: While there are strong cohort studies researching the role of sleep in those with postconcussion symptoms, the nature of sleep studies prevents the production of strong, high-level evidence studies such as randomized control trials. Thus, there is level B evidence that the likelihood of prolonged postconcussion symptoms is increased by a higher amount of SRPs.

Chimpanzee (Pan troglodytes schweinfurthii) Population Spans Multiple Protected Areas in the Albertine Rift.

We used mitochondrial DNA to examine gene flow in a region of western Uganda that has received little attention regarding chimpanzee population dynamics. The area is critical to gene flow between isolated Democratic Republic of Congo populations and the rest of East Africa. None of the chimpanzees in each of the 4 protected areas under consideration (Toro-Semliki Wildlife Reserve, Semuliki National Park, Rwenzori Mountains National Park and Itwara Central Forest Reserve) are fully habituated. Therefore, it is not clear whether one or more populations have historically used this fragmented landscape for (1) regular ranging and/or (2) infrequent dispersal. We incorporated the published sequences of the first hypervariable region of the D-loop of the mitochondrial genome from 3 previously sampled sites (n = 39) while also contributing the first extensive genetic sampling of chimpanzees in Toro-Semliki (n = 80). Our goal was to generate a historical baseline model of metapopulation dynamics in this region and determine which, if any, of these protected areas forms a fragmented landscape for a single chimpanzee population. According to a discriminant analysis of principal components, the haplotypes at Toro-Semliki form a central cluster, and Itwara is its nearest genetic neighbor. Rwenzori Mountains National Park is the most distant neighbor of all protected areas. We performed an analysis of molecular variance for 14 different population models that divided the samples from the 4 protected areas into 2, 3 or 4 populations. The best fit model included 3 populations: Toro-Semliki Wildlife Reserve and Itwara Forest Reserve comprised a single population; Semuliki National Park and Rwenzori Mountains National Park formed 2 additional separate populations (variance among = 9%, p = 0.014). The results indicated that some protected areas comprised distinctive populations, while others formed a fragmented landscape for a population's ranging for foraging purposes. Therefore, the edges of a protected area do not always define a chimpanzee population. We propose a closer examination of those dynamics through renewed sampling. Advances in DNA extraction and next-generation sequencing will allow us to compare thousands of single nucleotide polymorphisms in the genomes of unhabituated chimpanzees living in each of these protected areas.

Detecting riparian habitat preferences in "savanna" chimpanzees and associated Fauna with strontium isotope ratios: Implications for reconstructing habitat use by the chimpanzee-human last common ancestor.

OBJECTIVES: Riparian or gallery forests are critical habitats for numerous plants and animals today. Paleoanthropologically, reliance on such habitats informs behavioral and ecological reconstructions; for example, gallery forest habitats likely played a critical role in the transition from ape to hominin in the early Pliocene and may represent a preferred habitat for the last common ancestor of chimpanzees and humans. Direct indicators for gallery forest habitats preference are lacking. The objective of this article is to assess whether strontium isotope ratios are a reliable indicator of habitat preference for fauna living in and around gallery forests. MATERIALS AND METHODS: We report bioavailable strontium isotope ratios from the Mugiri River, its tributaries, and its gallery forest (Toro-Semliki Wildlife Reserve, southwestern Uganda), and compare them to surrounding savanna-grassland values. We compare these environmental values to strontium isotopes ratios in faunal tooth enamel to determine if habitat preferences are accurately reflected. RESULTS: Gallery forest and savanna-grassland vegetations have significantly different strontium isotope ratio profiles. We trace these isotopic differences to the influence of the Mugiri tributaries, which originate on Paleoproterozoic gneiss deposits on top of the surrounding escarpments. These isotopic differences in vegetation are mirrored in the tissues of fauna with habitat preferences for either the gallery forest or the surrounding grasslands. DISCUSSION: This research demonstrates the potential of strontium isotope ratios to identify habitat preferences in modern or fossil fauna under proper geologic variability. It provides a methodological model for future studies seeking to reconstruct habitat preferences in early hominins.

Is genetic drift to blame for testicular dysgenesis syndrome in Semliki chimpanzees (Pan troglodytes schweinfurthii)?

BACKGROUND: We present 3 likely cases of testicular dysgenesis syndrome (TDS) within a community of chimpanzees (Pan troglodytes schweinfurthii). We tested whether genetic drift may be the culprit, as a genetic cause has been suspected to account for TDS among other wildlife. METHODS: We successfully sequenced a 367-bp segment spanning the first hypervariable region within the D-loop of the mitochondrial genome for 78 DNA samples. RESULTS: We found 24 polymorphic sequence sites consisting of 7 singletons and 17 parsimony informative sites. This sample contained 9 haplotypes with a diversity index of 0.78 (SD = 0.03). All tests against the null hypothesis of neutral polymorphisms were non-significant (P > .10). The mismatch distribution of pairwise differences does not fit a Poisson's curve (raggedness index = 0.166; SSD = 0.12; P = 1). CONCLUSIONS: Thus, we found no significant signs of genetic isolation, population expansion, or genetic bottleneck. Alternative causes of TDS and how they might pertain to this population are discussed.

Why are there apes? Evidence for the co-evolution of ape and monkey ecomorphology.

Apes, members of the superfamily Hominoidea, possess a distinctive suite of anatomical and behavioral characters which appear to have evolved relatively late and relatively independently. The timing of paleontological events, extant cercopithecine and hominoid ecomorphology and other evidence suggests that many distinctive ape features evolved to facilitate harvesting ripe fruits among compliant terminal branches in tree edges. Precarious, unpredictably oriented, compliant supports in the canopy periphery require apes to maneuver using suspensory and non-sterotypical postures (i.e. postures with eccentric limb orientations or extreme joint excursions). Diet differences among extant species, extant species numbers and evidence of cercopithecoid diversification and expansion, in concert with a reciprocal decrease in hominoid species, suggest intense competition between monkeys and apes over the last 20 Ma. It may be that larger body masses allow great apes to succeed in contest competitions for highly desired food items, while the ability of monkeys to digest antifeedant-rich unripe fruits allows them to win scramble competitions. Evolutionary trends in morphology and inferred ecology suggest that as monkeys evolved to harvest fruit ever earlier in the fruiting cycle they broadened their niche to encompass first more fibrous, tannin- and toxin-rich unripe fruits and later, for some lineages, mature leaves. Early depletion of unripe fruit in the central core of the tree canopy by monkeys leaves a hollow sphere of ripening fruits, displacing antifeedant-intolerant, later-arriving apes to small-diameter, compliant terminal branches. Hylobatids, orangutans, Pan species, gorillas and the New World atelines may have each evolved suspensory behavior independently in response to local competition from an expanding population of monkeys. Genetic evidence of rapid evolution among chimpanzees suggests that adaptations to suspensory behavior, vertical climbing, knuckle-walking, consumption of terrestrial piths and intercommunity violence had not yet evolved or were still being refined when panins (chimpanzees and bonobos) and hominins diverged.

Dose-dependent exposure and metabolism of GNE-892, a ß-secretase inhibitor, in monkeys: contributions by P450, AO, and P-gp.

(R)-2-Amino-1,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H-spiro[imidazole-4,1'-naphthalen]-5(1H)-one (GNE-892) is an orally administered inhibitor of ß-secretase 1 (ß-site amyloid precursor protein cleaving enzyme 1, BACE1) that was developed as an intervention therapy against Alzheimer's disease. A clinical microdosing strategy was being considered for de-risking the potential pharmacokinetic liabilities of GNE-892. We tested whether dose-proportionality was observed in cynomolgus monkey as proof-of-concept for a human microdosing study. With cryopreserved monkey hepatocytes, concentration-dependency for substrate turnover and the relative contribution of P450- versus AO-mediated metabolism were observed. Characterization of the kinetics of these metabolic pathways demonstrated differences in the affinities of P450 and AO for GNE-892, which supported the metabolic profiles that had been obtained. To test if this metabolic shift occurred in vivo, mass balance studies in monkeys were conducted at doses of 0.085 and 15 mg/kg. Plasma exposure of GNE-892 following oral administration was more than 20-fold greater than dose proportional at the high-dose. P-gp-mediated efflux was unable to explain the discrepancy. The profiles of metabolites in circulation and excreta were indicative that oxidative metabolism limited the exposure to unchanged GNE-892 at the low dose. Further, the in vivo data supported the concentration-dependent metabolic shift between P450 and AO. In conclusion, microdosing of GNE-892 was not predictive of pharmacokinetics at a more pharmacologically relevant dose due to saturable absorption and metabolism. Therefore, it is important to consider ADME liabilities and their potential concentration-dependency when deciding upon a clinical microdosing strategy.

Mitigation of opioid off-target effects and identification of structural drivers of opioid receptor engagement for BACE-1 small molecule inhibitors.

Application of safety lead optimization screening strategies during the early stage of drug discovery led to the identification of a series of CNS-active small molecule inhibitors with opioid off-target effects, as evidenced by potent agonistic activity in functional cell-based assays for mu (MOP), kappa (KOP) and delta (DOP) opioid receptors. The translation of these effects was confirmed in vivo with the following observations: hypoactivity and decreased fecal production in rats (characteristic of MOP agonism); increased urine production in rats (characteristic of KOP agonism); and decreased intestinal transit time in mice, which was partially blocked by the MOP antagonist naloxone, demonstrating that the in vivo effects were specific for MOP. Based on the confirmation of in vitro-in vivo translatability, an in vitro screening strategy was implemented that resulted in the identification of an optimized backup molecule, devoid of in vivo off-target opioid effects. In addition, in silico modeling by docking of the various molecules to the opioid receptors allowed the identification of the structural drivers of these off-target effects, which can be applied to future chemical-design criteria. Thus, implementation of the safety lead optimization strategy described in this article demonstrates the utility and impact of such approaches on risk mitigation and identification of lead small molecules with improved safety profiles.

Elucidating the mechanism of cytochrome P450-mediated pyrimidine ring conversion to pyrazole metabolites with the BACE1 inhibitor GNE-892 in rats.

We investigated an uncommon biotransformation of pyrimidine during the metabolism of GNE-892 ((R)-2-amino-1,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H-spiro[imidazole-4,1'-naphthalen]-5(1H)-one), a ß-secretase 1 inhibitor. Three novel metabolites, formed by conversion of pyrimidine to pyrazole, were observed in the (14)C-radiolabeled mass balance study in rats. Their structures were characterized by high-resolution mass spectrometry and nuclear magnetic resonance. Although these metabolites accounted for <5% of the administered dose, their unique nature prompted us to conduct further investigations. The pyrazole-containing metabolites were formed in vitro with rat hepatocytes and liver microsomes, which supported that they were formed during hepatic metabolism. Further, their generation was inhibited by 1-aminobenzotriazole, indicating involvement of cytochrome P450s. Studies with rat recombinant enzymes identified that CYP2D2 generated the N-hydroxypyrazole metabolite from GNE-892. This biotransformation proceeded through multiple steps from the likely precursor, pyrimidine N-oxide. On the basis of these data, we propose a mechanism in which the pyrimidine is activated via N-oxidation, followed by a second oxidative process that opens the pyrimidine ring to form a formamide intermediate. After hydrolysis of the formamide, a carbon is lost as formic acid, together with ring closure to form the pyrazole ring. This article highlights a mechanistic approach for determining the biotransformation of the pyrimidine to a pyrazole for GNE-892.

Selective insectivory at Toro-Semliki, Uganda: comparative analyses suggest no 'savanna' chimpanzee pattern.

Chimpanzee (Pan troglodytes) insectivory across Africa is ubiquitous. Insects provide a significant nutritional payoff and may be important for chimpanzees in dry, open habitats with narrow diets. We tested this hypothesis at Semliki, Uganda, a long-term dry study site. We evaluated prospects for insectivory by measuring insect abundance along de novo transects and trails, monitoring social insect colonies, and surveying available raw materials for elementary technology. We determined the frequency and nature of insectivory through behavioral observation and fecal analysis. We then compared our results with those from 15 other long-term chimpanzee study sites using a cluster analysis. We found that Semliki chimpanzees are one of the most insectivorous populations studied to date in terms of frequency of consumption, but they are very selective in their insectivory, regularly consuming only weaver ants (Oecophylla longinoda) and honey and bees from hives of Apis mellifera. This selectivity obtains despite having a full range of typical prey species available in harvestable quantities. We suggest that Semliki chimpanzees may face ecological time constraints and therefore bias their predation toward prey taxa that can be quickly consumed. Geographical proximity correlated with the results of the cluster analysis, while rainfall, a relatively gross measure of environment, did not. Because broad taxonomic groups of insects were used in analyses, prey availability was unlikely to have a strong effect on this pattern. Instead, we suggest that transmission of cultural knowledge may play a role in determining chimpanzee prey selection across Africa. Further study is needed to test these hypotheses.

Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.

The development of 1,3,4,4a,5,10a-hexahydropyrano[3,4-b]chromene analogs as BACE1 inhibitors is described. Introduction of the spirocyclic pyranochromene scaffold yielded several advantages over previous generation cores, including increased potency, reduced efflux, and reduced CYP2D6 inhibition. Compound 13 (BACE1 IC50=110 nM) demonstrated a reduction in CSF Aß in wild type rats after a single dose.

Detection of hepatitis E RNA in pork products at point of retail in Ireland - Are consumers at risk?

Hepatitis E (HEV), a zoonotic virus, is the leading cause of acute viral hepatitis in Europe. The presence of HEV in domestic pigs can result in infections in humans through consumption of pork products which are undercooked or where processing methods are insufficient to inactivate the virus. In Ireland, pork accounts for 34 % of all meat consumption (CSO, 2022) and the prevalence of HEV in products at point of retail has not previously been characterised. A sampling strategy was designed in which high pork content sausages, fresh pork liver and raw fermented sausages were systematically purchased from three types of retailers between May 2018 and March 2019. In total, 200 pork products were tested using a lysing agent to release the HEV from the product for detection. RT-PCR for HEV was performed on samples with an extraction efficiency >1 % (n = 188/200) (94 %). Low level HEV RNA was detected in 9/188 (4.8 %) pork products tested. The highest incidence of HEV RNA was in pork liver where 6/25 (24 %) samples were positive. The concentration of HEV ranged from 0.02 - to 9.4 genome copies/g of pork. Based on these data an exposure assessment was performed which found that if consumers followed advice from the Food Safety Authority of Ireland to achieve core temperatures of 70 °C or higher when cooking, the risk was likely to be negligible.

Mechanistic pharmacokinetic-pharmacodynamic modeling of BACE1 inhibition in monkeys: development of a predictive model for amyloid precursor protein processing.

This study was conducted to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of two novel inhibitors of ß-site amyloid precursor protein (APP)-cleaving enzyme (BACE1), GNE-629 [(4S,4a'S,10a'S)-2-amino-8'-(2-fluoropyridin-3-yl)-1-methyl-3',4',4a',10a'-tetrahydro-1'H-spiro[imidazole-4,10'-pyrano[4,3-b]chromen]-5(1H)-one] and GNE-892 [(R)-2-amino-1,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H-spiro[imidazole-4,1'-naphthalen]-5(1H)-one], and to develop a PK-PD model to predict in vivo effects based solely on in vitro activity and PK. GNE-629 and GNE-892 concentrations and PD biomarkers including amyloid ß (Aß) in the plasma and cerebrospinal fluid (CSF), and secreted APPß (sAPPß) and secreted APPα (sAPPα) in the CSF were measured after a single oral administration of GNE-629 (100 mg/kg) or GNE-892 (30 or 100 mg/kg) in cynomolgus monkeys. A mechanistic PK-PD model was developed to simultaneously characterize the plasma Aß and CSF Aß, sAPPα, and sAPPß using GNE-629 in vivo data. This model was used to predict the in vivo effects of GNE-892 after adjustments based on differences in in vitro cellular activity and PK. The PK-PD model estimated GNE-629 CSF and free plasma IC50 of 0.0033 µM and 0.065 µM, respectively. These differences in CSF and free plasma IC50 suggest that different mechanisms are involved in Aß formation in these two compartments. The predicted in vivo effects for GNE-892 using the PK-PD model were consistent with the observed data. In conclusion, a PK-PD model was developed to mechanistically describe the effects of BACE1 inhibition on Aß, sAPPß, and sAPPα in the CSF, and Aß in the plasma. This model can be used to prospectively predict in vivo effects of new BACE1 inhibitors using just their in vitro activity and PK data.

Cronobacter Species in the Built Food Production Environment: A Review on Persistence, Pathogenicity, Regulation and Detection Methods.

The powdered formula market is large and growing, with sales and manufacturing increasing by 120% between 2012 and 2021. With this growing market, there must come an increasing emphasis on maintaining a high standard of hygiene to ensure a safe product. In particular, Cronobacter species pose a risk to public health through their potential to cause severe illness in susceptible infants who consume contaminated powdered infant formula (PIF). Assessment of this risk is dependent on determining prevalence in PIF-producing factories, which can be challenging to measure with the heterogeneity observed in the design of built process facilities. There is also a potential risk of bacterial growth occurring during rehydration, given the observed persistence of Cronobacter in desiccated conditions. In addition, novel detection methods are emerging to effectively track and monitor Cronobacter species across the food chain. This review will explore the different vehicles that lead to Cronobacter species' environmental persistence in the food production environment, as well as their pathogenicity, detection methods and the regulatory framework surrounding PIF manufacturing that ensures a safe product for the global consumer.

Detection of Hepatitis A RNA, Hepatitis E RNA, Human Adenovirus F DNA, and Norovirus RNA in Fresh and Frozen Berry Products at Point of Retail in Ireland.

Soft fruits are at particular risk of contamination with enteric viruses such as Hepatitis A virus (HAV), Hepatitis E Virus (HEV), Norovirus (NoV), Human Adenovirus (HAdV) and Sapovirus (SaV). The aim of this study was to investigate, for the first time, the presence of these biological agents in ready to eat (RTE) berries at point of retail in Ireland. A sampling strategy was designed in which RTE fresh and frozen strawberries and raspberries were purchased from five retailers between May and October 2018. Reverse Transcriptase Polymerase Chain Reaction (RT-qPCR) assays for HEV RNA, Nov RNA, SaV RNA, and human Adenovirus species F DNA (HAdV-F) were performed on 239 samples (25g portions). Viral nucleic acid was present in 6.7% (n = 16) of samples tested as follows: HAV RNA (n = 5), HAdV-F DNA (n = 5), HEV RNA (n = 3) and NoV GII RNA (n = 3). Sapovirus RNA was not detected in any product. No significant differences were found between berry type, fresh/frozen status, or supermarket source. This study suggests a risk that exists across all retail outlets however only low levels of nucleic acid ranging from 0 to 16 genome copies/g were present. Although these findings may reflect non-viable/non-infectious virus the continued provision of risk mitigation advice to consumers is warranted and further work is required to ensure control measures to reduce contamination are implemented and enforced.

Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin. However, how muscle contraction and fast muscle fiber damage contribute to the pathophysiology of DMD has not been well characterized. We explored the role of fast skeletal muscle contraction in DMD with a potentially novel, selective, orally active inhibitor of fast skeletal muscle myosin, EDG-5506. Surprisingly, even modest decreases of contraction (<15%) were sufficient to protect skeletal muscles in dystrophic mdx mice from stress injury. Longer-term treatment also decreased muscle fibrosis in key disease-implicated tissues. Importantly, therapeutic levels of myosin inhibition with EDG-5506 did not detrimentally affect strength or coordination. Finally, in dystrophic dogs, EDG-5506 reversibly reduced circulating muscle injury biomarkers and increased habitual activity. This unexpected biology may represent an important alternative treatment strategy for Duchenne and related myopathies.

A thermodynamic comparison of arboreal and terrestrial sleeping sites for dry-habitat chimpanzees (Pan troglodytes schweinfurthii) at the Toro-Semliki Wildlife Reserve, Uganda.

The nightly construction of an arboreal sleeping platform (SP) has been observed among every chimpanzee's population studied to date. Here, we report on bioclimatic aspects of SP site choice among dry-habitat chimpanzees (Pan troglodytes schweinfurthii) at the Toro-Semliki Wildlife Reserve, Uganda. We placed a portable weather monitor within 1 m of chimpanzee SPs and compared the microenvironment of this site with terrestrial monitors placed 10 cm above the ground directly underneath the simultaneously studied SP. We calculated physical "comfort levels" of monitored sites using the RayMan thermophysiological model that we modified to take ape body proportions into account. The RayMan tool gauges energy balance using wind speed, temperature, relative humidity, and heat index in conjunction with the study subject's mass and stature to determine whether the individual is in energy balance or homeostasis. We found that (1) terrestrial microclimates have greater homeostatic potential than arboreal microclimates, and (2) there is a significant positive linear relationship between wind speed and height of SP in the forest canopy. Advantages of terrestrial sites are that they require lesser energetic expenditure to stabilize the body when the SP is under construction and perhaps during use as well. We found that terrestrial sites also had better homeostatic potentials. This combination of advantages explains why SPs are so often sited terrestrially in habitats where predation risk is low. Early hominins must have had technological or social measures to avoid or deter predators that were significantly advanced over those found among chimpanzees before they began sleeping on the ground.

Risk assessment of enteric viruses along the food chain and in the population.

Food-borne microbial illness contributes up to one third of global disease burden. The largest category of food-borne illness is gastroenteritis, the majority of which is caused by enteric viruses. Viruses like these are transmitted to food either by waste-contaminated waters, or by handling and transfer during processing. An important tool for reducing or controlling food-borne microbial risk is risk analysis. This framework has been adopted globally to manage risks associated with microbial contamination in food. Several hundred microbial risk assessments (MRAs) have been published by different national and international organisations, for different food-hazard combinations. The use of MRAs in controlling and understanding virus risk has, to date, been limited, compared with the efforts made on bacterial pathogens. Given the large disease burden that viruses are responsible for, this disparity should be addressed. The main reasons for the relative lack of risk assessments are the difficulty in detecting and monitoring viruses compared with bacteria. This means less data on prevalence, concentration and inactivation, and allows viruses to remain silent contributors to global disease. There are also key conceptual differences between virus risk assessment and bacterial risk assessment. This project aimed to assess the current state of the art for food-borne virus risk assessment, then to progress the field further by using the data available to produce risk rankings and risk assessments. This was done by a combination of literature reviewing and various risk assessment tools. The result was an assessment of the overall evidence base in the literature, a semi-quantitative ranking comparison between the viruses and foods of most concern, and a survey of inactivation methods, leading to a quantitative ranking of the effectiveness of each in reducing and managing food-borne virus risk.