Long-term trends in helminth infections of wood mice (Apodemus sylvaticus) from the vicinity of Malham Tarn in North Yorkshire, England.

Helminth infections in wood mice (n = 483), trapped over a period of 26 years in the woods surrounding Malham Tarn in North Yorkshire, were analysed. Although 10 species of helminths were identified, the overall mean species richness was 1.01 species/mouse indicating that the helminth community was relatively depauperate in this wood mouse population. The dominant species was Heligmosomoides polygyrus, the prevalence (64.6%) and abundance (10.4 worms/mouse) of which declined significantly over the study period. Because of the dominance of this species, analyses of higher taxa (combined helminths and combined nematodes) also revealed significantly declining values for prevalence, although not abundance. Helminth species richness (HSR) and Brillouin's index of diversity (BID) did not show covariance with year, neither did those remaining species whose overall prevalence exceeded 5% (Syphacia stroma, Aonchotheca murissylvatici and Plagiorchis muris). Significant age effects were detected for the prevalence and abundance of all higher taxa, H. polygyrus and P. muris, and for HSR and BID, reflecting the accumulation of helminths with increasing host age. Only two cases of sex bias were found; male bias in abundance of P. muris and combined Digenea. We discuss the significance of these results and hypothesize about the underlying causes.

International consensus on terminology to be used in the field of echinococcoses.

Echinococcoses require the involvement of specialists from nearly all disciplines; standardization of the terminology used in the field is thus crucial. To harmonize echinococcosis terminology on sound scientific and linguistic grounds, the World Association of Echinococcosis launched a Formal Consensus process. Under the coordination of a Steering and Writing Group (SWG), a Consultation and Rating Group (CRG) had the main missions of (1) providing input on the list of terms drafted by the SWG, taking into account the available literature and the participants' experience; and (2) providing independent rating on all debated terms submitted to vote. The mission of the Reading and Review Group (RRG) was to give an opinion about the recommendation paper in terms of readability, acceptability and applicability. The main achievements of this process were: (1) an update of the current nomenclature of Echinococcus spp.; (2) an agreement on three names of diseases due to Echinococcus spp.: Cystic Echinococcosis (CE), Alveolar Echinococcosis (AE) and Neotropical Echinococcosis (NE), and the exclusion of all other names; (3) an agreement on the restricted use of the adjective "hydatid" to refer to the cyst and fluid due to E. granulosus sensu lato; and (4) an agreement on a standardized description of the surgical operations for CE, according to the "Approach, cyst Opening, Resection, and Completeness" (AORC) framework. In addition, 95 "approved" and 60 "rejected" terms were listed. The recommendations provided in this paper will be applicable to scientific publications in English and communication with professionals. They will be used for translation into other languages spoken in endemic countries.

TITLE: Consensus international sur la terminologie à utiliser dans le domaine des échinococcoses. ABSTRACT: Les échinococcoses impliquent l'intervention de spécialistes de presque toutes les disciplines et une standardisation de la terminologie utilisée dans le domaine est donc cruciale. Pour harmoniser la terminologie des échinococcoses sur des bases scientifiques et linguistiques bien étayées, l'Association Mondiale de l'Échinococcose a entrepris un processus de « Consensus Formalisé ¼. Sous la coordination d'un Groupe de Pilotage et de Rédaction (GPR), un Groupe de Consultation et de Classement (GCC) a reçu les missions suivantes : (1) fournir un avis sur une liste de termes établie par le GPR, en prenant en compte les références scientifiques disponibles et l'expérience des participants ; (2) fournir un classement indépendant sur tous les termes débattus et soumis au vote. La mission du Groupe de Lecture et de Revue critique (GLR) était de donner un avis formel sur l'article de recommandations en termes de facilité de lecture, d'acceptabilité et d'applicabilité. Les principales avancées obtenues au terme de ce processus sont les suivantes: (1) une actualisation de la nomenclature actuelle des espèces d'Echinococcus ; (2) un accord sur les noms des trois principales maladies humaines dues aux espèces d'Echinococcus : l'échinococcose kystique (EK), l'échinococcose alvéolaire (EA) et l'échinococcose néotropicale (EN), à l'exclusion de toute autre dénomination ; (3) la restriction de l'usage de l'adjectif « hydatique ¼ au kyste et au liquide/fluide produit par E. granulosus sensu lato ; et (4) une description standardisée des interventions chirurgicales pour l'EK, selon le système AORC (pour « Approche ¼, « Ouverture ¼, « Résection ¼ et « Complétude ¼). De plus, 95 termes « approuvés ¼ et 60 termes « rejetés ¼ ont été listés. Les recommandations données dans cet article seront applicables aux publications scientifiques en anglais et à la communication avec les professionnels. Elles seront utilisées pour la traduction dans les autres langues parlées dans les zones d'endémie.

Long-term retrospective assessment of a transmission hotspot for human alveolar echinococcosis in mid-west China.

BACKGROUND: Human alveolar echinococcosis caused by infection with Echinococcus multilocularis is one of the most potentially pathogenic helminthic zoonoses. Transmission occurs involving wildlife cycles typically between fox and small mammal intermediate hosts. In the late 1980s/early 1990s a large focus of human AE was identified in poor upland agricultural communities in south Gansu Province, China. More detailed investigations in 1994-97 expanded community screening and identified key risk factors of dog ownership and landscape type around villages that could support susceptible rodent populations. A crash of the dog population (susceptible domestic definitive host) in the early 1990s appeared to stop transmission. METHODOLOGY/FINDINGS: We subsequently undertook follow-up eco-epidemiological studies based on human population screening and dog survey, in 2005/6 and in 2014/15. Our observations show a decrease in human AE prevalence, especially marked in the 11-30 year old age category. In 2015, although the dog population had recovered and in addition, forest protection and the reforestation of some areas may have favoured red fox (wild definitive host) population growth, there was no evidence of infection in owned dogs. CONCLUSIONS/SIGNIFICANCE: Those observations suggest that over decades socio-ecological changes resulted in a cascade of factors that exacerbated and then interrupted parasite emergence, with probable elimination of peri-domestic transmission of E. multilocularis in this area, despite the relative proximity of large active transmission foci on the eastern Tibetan Plateau. This study case exemplifies how anthropogenic land use and behavioural changes can modify emergence events and the transmission of endemic zoonotic parasite infections, and subsequently the importance of considering processes over the long-term in a systems approach in order to understand pathogen and disease distribution.

Naturally occurring Toll-like receptor 11 (TLR11) and Toll-like receptor 12 (TLR12) polymorphisms are not associated with Toxoplasma gondii infection in wild wood mice.

Toxoplasma gondii is a highly successful parasite with a worldwide prevalence. Small rodents are the main intermediate hosts, and there is growing evidence that T. gondii modifies their behaviour. Chronically infected rodents show impaired learning capacity, enhanced activity, and, most importantly, a reduction of the innate fear towards cat odour. This modification of host behaviour ensures a successful transmission of T. gondii from rodents to felids, the definitive hosts of the parasite. Given the negative fitness consequences of this behavioural manipulation, as well as an increased mortality during the acute phase of infection, we expect rodents to evolve potent resistance mechanisms that prevent or control infection. Indeed, studies in laboratory mice have identified candidate genes for T. gondii resistance. Of particular importance appear to be the innate immune receptors Toll-like receptor 11 (TLR11) and Toll-like receptor 12 (TLR12), which recognise T. gondii profilin and initiate immune responses against the parasite. Here we analyse the genetic diversity of TLR11 and TLR12 in a natural population of wood mice (Apodemus sylvaticus), and test for associations between TLR11 and TLR12 polymorphisms and T. gondii infection, as well as for epistatic interactions between TLR11 and TLR12 on infection status. We found that both TLR11 and TLR12 were polymorphic in wood mice, with four and nine amino acid haplotypes, respectively. However, we found no evidence that TLR11 or TLR12 genotypes or haplotypes were significantly associated with Toxoplasma infection. Despite the importance of TLR11 and TLR12 in T. gondii recognition and immune defence initiation, naturally occurring polymorphisms at TLR11 and TLR12 thus appear to play a minor role in mediating qualitative resistance to T. gondii in natural host populations of A. sylvaticus. This highlights the importance of assessing the role of candidate genes for parasite resistance identified in a laboratory setting in an ecologically meaningful context to quantify their role in mediating host-parasite interactions in the wild.

Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-/- mice.

AIM: To investigate the influence of Trichuris muris (T. muris) infection in a mouse model of genetic susceptibility to inflammatory bowel disease, Mdr1a-/-. METHODS: Mdr1a-/- mice were housed under specific pathogen free conditions to slow the development of colitis and compared to congenic FVB controls. Mice were infected with approximately 200 embryonated ova from T. muris and assessed for worm burden and histological and functional markers of gut inflammation on day 19 post infection. RESULTS: Mdr1a-/- mice exhibited a marked increase in susceptibility to T. muris infection with a 10-fold increase in colonic worm count by day 19 pi compared to FVB controls. Prior to infection, Mdr1a-/- exhibited low-level mucosal inflammation with evidence of an enhanced Th1 environment. T. muris infection accelerated the progression of colitis in Mdr1a-/- as evidenced by marked increases in several indicators including histological damage score, mucosal CD⁺ T-cell and DC infiltration and dramatically increased production of pro-inflammatory cytokines. CONCLUSION: These data provide further evidence of the complex interaction between T. muris and an inflammatory bowel disease (IBD)-susceptible host which may have relevance to the application of helminth therapy in the treatment of human IBD.

Dog ownership, dog behaviour and transmission of Echinococcus spp. in the Alay Valley, southern Kyrgyzstan.

Echinococcosis is a re-emerging zoonotic disease in Kyrgyzstan, and the incidence of human infection has increased substantially since the collapse of the Soviet Union in 1991. Domestic dogs are hosts of Echinococcus spp. and play an important role in the transmission of these parasites. The demography, ecology and behaviour of dogs are therefore relevant in studying Echinococcus spp. transmission. Dog demographics, roles of dogs, dog movements and faecal environmental contamination were assessed in four rural communities in the Alay Valley, southern Kyrgyzstan. Arecoline purge data revealed for the first time that E. granulosus, E. canadensis and E. multilocularis were present in domestic dogs in the Alay Valley. Surveys revealed that many households had dogs and that dogs played various roles in the communities, as pets, guard dogs or sheep dogs. Almost all dogs were free to roam, and GPS data revealed that many moved outside their communities, thus being able to scavenge offal and consume rodents. Faecal environmental contamination was high, presenting a significant infection risk to the local communities.

A translational bridge between mouse and human models of learned safety.

BACKGROUND: Learned safety is established by negatively correlating the occurrence of a neutral stimulus and a noxious stimulus, which renders the previously neutral stimulus a 'safety signal'. While the neurophysiological and molecular mechanisms have been characterized in mice, it is currently not known how the neural substrates involved compare between mice and people. METHODS: Here we attempt to adapt the original animal protocol to humans and use functional magnetic resonance imaging to examine neural responses to the conditioned stimulus in safety conditioned and fear conditioned subjects. Diffusion tensor imaging (DTI) was used in a parallel group of subjects as a first approach to delineate the underlying neural circuitry. RESULTS: Learned safety is associated with dampened amygdala and increased dorsolateral prefrontal cortex and caudate responses and paralleled by pupillary constriction. A neural connection between the amygdala and the dorsolateral prefrontal cortex is suggested by DTI. CONCLUSION: We present a translational bridge between mouse and human models of learned safety in which cellular and molecular insights from animal experiments are extended to the human neural circuitry. This study provides an example of how animal experiments can be used to inform and target human studies, which in turn can corroborate results obtained in experimental animals.

Hydatid cysts: does every picture tell a story?

Ultrasound imaging is an effective aid to the detection of abdominal cystic echinococcosis. Recently, the images produced have provided more information than just a diagnosis. Different cyst morphologies have been classified into types, and such classifications can be considered to represent a natural history of cyst development. Understanding how cyst structures alter with time is crucial to evaluating the effectiveness of different treatment regimes and to understanding natural degeneration of cysts that can occur. However, the developmental events seen in ultrasound need to be matched more closely to immunological and cellular events if we are to have a fuller appreciation of disease progression and regression. At a community level, the relative proportions of cyst types could also provide epidemiological information on disease transmission.

Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse.

The ability to identify, develop, and exploit conditions of safety and security is central to survival and mental health, but little is known of the neurobiology of these processes or associated positive modulations of affective state. We studied electrophysiological and affective correlates of learned safety by negatively correlating an auditory conditioned stimulus (CS) with aversive events (US). This CS came to signify a period of protection, reducing fear responses to predictors of the US and increasing adventurous exploration of a novel environment. In nonaversive conditions, mice turn on the CS when given the opportunity. Thus, conditioned safety involves a reduction of learned and instinctive fear, as well as positive affective responses. Concurrent electrophysiological measurements identified a safety learning-induced long-lasting depression of CS-evoked activity in the lateral nucleus of the amygdala, consistent with fear reduction, and an increase of CS-evoked activity in a region of the striatum involved in positive affect, euphoric responses, and reward.

Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces.

Responses to threat-related stimuli are influenced by conscious and unconscious processes, but the neural systems underlying these processes and their relationship to anxiety have not been clearly delineated. Using fMRI, we investigated the neural responses associated with the conscious and unconscious (backwardly masked) perception of fearful faces in healthy volunteers who varied in threat sensitivity (Spielberger trait anxiety scale). Unconscious processing modulated activity only in the basolateral subregion of the amygdala, while conscious processing modulated activity only in the dorsal amygdala (containing the central nucleus). Whereas activation of the dorsal amygdala by conscious stimuli was consistent across subjects and independent of trait anxiety, activity in the basolateral amygdala to unconscious stimuli, and subjects' reaction times, were predicted by individual differences in trait anxiety. These findings provide a biological basis for the unconscious emotional vigilance characteristic of anxiety and a means for investigating the mechanisms and efficacy of treatments for anxiety.