3D virtual histology at the host/parasite interface: visualisation of the master manipulator, Dicrocoelium dendriticum, in the brain of its ant host

Some parasites are able to manipulate the behaviour of their hosts to their own advantage. One of the most well-established textbook examples of host manipulation is that of the trematode Dicrocoelium dendriticum on ants, its second intermediate host. Infected ants harbour encysted metacercariae in the gaster and a non-encysted metacercaria in the suboesophageal ganglion (SOG); however, the mechanisms that D. dendriticum uses to manipulate the ant behaviour remain unknown, partly because of a lack of a proper and direct visualisation of the physical interface between the parasite and the ant brain tissue. Here we provide new insights into the potential mechanisms that this iconic manipulator uses to alter its host’s behaviour by characterising the interface between D. dendriticum and the ant tissues with the use of non-invasive micro-CT scanning. For the first time, we show that there is a physical contact between the parasite and the ant brain tissue at the anteriormost part of the SOG, including in a case of multiple brain infection where only the parasite lodged in the most anterior part of the SOG was in contact with the ant brain tissue. We demonstrate the potential of micro-CT to further understand other parasite/host systems in parasitological research.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Disease and the Extended Phenotype: Parasites Control Host Performance and Survival through Induced Changes in Body Plan

BACKGROUND: By definition, parasites harm their hosts. However, some forms of parasite-induced alterations increase parasite transmission between hosts, such that manipulated hosts can be considered extensions of the parasite's phenotype. While well accepted in principle, surprisingly few studies have quantified how parasite manipulations alter host performance and survival under field and laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: By interfering with limb development, the trematode Ribeiroia ondatrae causes particularly severe morphological alterations within amphibian hosts that provide an ideal system to evaluate parasite-induced changes in phenotype. Here, we coupled laboratory performance trials with a capture-mark-recapture study of 1388 Pacific chorus frogs (Pseudacris regilla) to quantify the effects of parasite-induced malformations on host locomotion, foraging, and survival. Malformations, which affected ~50% of metamorphosing frogs in nature, caused dramatic reductions in all measures of organismal function. Malformed frogs exhibited significantly shorter jumping distances (41% reduction), slower swimming speeds (37% reduction), reduced endurance (66% reduction), and lower foraging success relative to infected hosts without malformations. Furthermore, while normal and malformed individuals had comparable survival within predator-free exclosures, deformed frogs in natural populations had 22% lower biweekly survival than normal frogs and rarely recruited to the adult population over a two-year period. CONCLUSIONS/SIGNIFICANCE: Our results highlight the ability of parasites to deeply alter multiple dimensions of host phenotype with important consequences for performance and survival. These patterns were best explained by malformation status, rather than infection per se, helping to decouple the direct and indirect effects of parasitism on host fitness.Brett A. Goodman and Pieter T. J. Johnso

Crisis resolution and home treatment in the UK: A survey of model fidelity using a novel review methodology

Crisis resolution teams (CRTs) provide treatment at home to people experiencing mental health crises, as an alternative to hospital admission. Previous UK research, based on self‐report surveys, suggests that a loosely specified model has resulted in wide variations in CRTs’ service delivery, organization and outcomes. A fidelity scale (developed through evidence review and stakeholder consensus) provided a means of objectively measuring adherence to a model of good practice for CRTs, via one‐day fidelity reviews of UK crisis teams. Reviews included interviews with service users, carers, staff and managers, and examination of data, policies, protocols and anonymized case notes. Of the 75 teams reviewed, 49 (65%) were assessed as being moderate fidelity and the rest as low fidelity, with no team achieving high fidelity. The median score was 122 (range: 73–151; inter‐quartile range: 111–132). Teams achieved higher scores on items about structure and organization, for example ease of referral, medication and safety systems, but scored poorly on items about the content of care and interventions. Despite a national mandate to implement the CRT model, there are wide variations in implementation in the UK and no teams in our sample achieved overall high fidelity. This suggests that a mandatory national policy is not in itself sufficient to achieve good quality implementation of a service model. The CRT Fidelity Scale provides a feasible and acceptable means to objectively assess model fidelity in CRTs. There is a need for development and testing of interventions to enhance model fidelity and facilitate improvements to these services

Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

© The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

Crisis resolution teams for people experiencing mental health crises: the CORE mixed-methods research programme including two RCTs

Background Crisis resolution teams (CRTs) seek to avert hospital admissions by providing intensive home treatment for people experiencing a mental health crisis. The CRT model has not been highly specified. CRT care is often experienced as ending abruptly and relapse rates following CRT discharge are high. Aims The aims of CORE (Crisis resolution team Optimisation and RElapse prevention) workstream 1 were to specify a model of best practice for CRTs, develop a measure to assess adherence to this model and evaluate service improvement resources to help CRTs implement the model with high fidelity. The aim of CORE workstream 2 was to evaluate a peer-provided self-management programme aimed at reducing relapse following CRT support. Methods Workstream 1 was based on a systematic review, national CRT manager survey and stakeholder qualitative interviews to develop a CRT fidelity scale through a concept mapping process with stakeholders (n = 68). This was piloted in CRTs nationwide (n = 75). A CRT service improvement programme (SIP) was then developed and evaluated in a cluster randomised trial: 15 CRTs received the SIP over 1 year; 10 teams acted as controls. The primary outcome was service user satisfaction. Secondary outcomes included CRT model fidelity, catchment area inpatient admission rates and staff well-being. Workstream 2 was a peer-provided self-management programme that was developed through an iterative process of systematic literature reviewing, stakeholder consultation and preliminary testing. This intervention was evaluated in a randomised controlled trial: 221 participants recruited from CRTs received the intervention and 220 did not. The primary outcome was re-admission to acute care at 1 year of follow-up. Secondary outcomes included time to re-admission and number of days in acute care over 1 year of follow-up and symptoms and personal recovery measured at 4 and 18 months’ follow-up. Results Workstream 1 – a 39-item CRT fidelity scale demonstrated acceptability, face validity and promising inter-rater reliability. CRT implementation in England was highly variable. The SIP trial did not produce a positive result for patient satisfaction [median Client Satisfaction Questionnaire score of 28 in both groups at follow-up; coefficient 0.97, 95% confidence interval (CI) –1.02 to 2.97]. The programme achieved modest increases in model fidelity. Intervention teams achieved lower inpatient admission rates and less inpatient bed use. Qualitative evaluation suggested that the programme was generally well received. Workstream 2 – the trial yielded a statistically significant result for the primary outcome, in which rates of re-admission to acute care over 1 year of follow-up were lower in the intervention group than in the control group (odds ratio 0.66, 95% CI 0.43 to 0.99; p = 0.044). Time to re-admission was lower and satisfaction with care was greater in the intervention group at 4 months’ follow-up. There were no other significant differences between groups in the secondary outcomes. Limitations Limitations in workstream 1 included uncertainty regarding the representativeness of the sample for the primary outcome and lack of blinding for assessment. In workstream 2, the limitations included the complexity of the intervention, preventing clarity about which were effective elements. Conclusions The CRT SIP did not achieve all its aims but showed potential promise as a means to increase CRT model fidelity and reduce inpatient service use. The peer-provided self-management intervention is an effective means to reduce relapse rates for people leaving CRT care. Study registration The randomised controlled trials were registered as Current Controlled Trials ISRCTN47185233 and ISRCTN01027104. The systematic reviews were registered as PROSPERO CRD42013006415 and CRD42017043048. Funding The National Institute for Health Research Programme Grants for Applied Research programme

Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze-dried onto the cortical surface without losing infectivity. We show that combination rAAV-RANKL- and rAAV-VEGF-coated allografts show marked remodeling and vascularization, which leads to a new bone collar around the graft. In conclusion, we find that RANKL and VEGF are necessary and sufficient for efficient autograft remodeling and can be transferred using rAAV to revitalize structural allografts

Compulsory admission at first presentation to services for psychosis: does ethnicity still matter? Findings from two population-based studies of first episode psychosis

Objectives Compared with the majority population, those from minority ethnic groups in the UK are more likely to be admitted compulsorily during a first episode of psychosis (FEP). We investigated whether these disparities in pathways in to care continue. Methods We analysed data from two first episode psychosis studies, conducted in the same geographical area in south London 15 years apart: the Aetiology and Ethnicity in Schizophrenia and Other Psychosis (AESOP) and the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) studies. The inclusion/exclusion criteria for case ascertainment for first episode psychosis were identical across the two studies. We performed multivariable logistic regression to estimate odds of compulsory admission by ethnic group, controlling for confounders. Participants Two hundred sixty-six patients with first episode psychosis, aged 18–64 years, who presented to mental health services in south London in 1997–1999 and 446 with FEP who presented in 2010–2012. Results When the two samples were compared, ethnic differences in compulsory admission appear to have remained the same for black African patients, i.e. three times higher than white British in both samples: AESOP (adj. OR = 3.96; 95% CI = 1.80–8.71) vs. CRIS-FEP (adj. OR = 3.12; 95% CI = 1.52–6.35). Black Caribbean patients were three times more likely to be compulsorily admitted in AESOP (adj. OR = 3.20; 95% CI = 1.56–6.54). This was lower in the CRIS-FEP sample (adj. OR = 1.68; 95% CI = 0.71–3.98) and did not meet conventional levels for statistical significance. Conclusion Ethnicity is strongly associated with compulsory admissions at first presentation for psychosis with evidence of heterogeneity across groups, which deserves further research

Globetrotting strangles: the unbridled national and international transmission of Streptococcus equi between horses.

The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, Streptococcus equi subspecies equi, establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit S. equi to naïve animals initiating new episodes of disease. Here, we report the analysis and visualization of phylogenomic and epidemiological data for 670 isolates of S. equi recovered from 19 different countries using a new core-genome multilocus sequence typing (cgMLST) web bioresource. Genetic relationships among all 670 S. equi isolates were determined at high resolution, revealing national and international transmission events that drive this endemic disease in horse populations throughout the world. Our data argue for the recognition of the international importance of strangles by the Office International des Épizooties to highlight the health, welfare and economic cost of this disease. The Pathogenwatch cgMLST web bioresource described herein is available for tailored genomic analysis of populations of S. equi and its close relative S. equi subspecies zooepidemicus that are recovered from horses and other animals, including humans, throughout the world. This article contains data hosted by Microreact