The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.

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SUMMARYMicrofilariae of Brugia malayi were obtained from the peritoneal cavities of infected gerbils and were then injected intravenously into mice. A sub-periodic, nocturnal microfilaraemia was produced. The level of microfilaraemia was proportional to the number of parasites injected, with approximately 1–3% of microfilariae being found in the peripheral circulation. The duration of microfilaraemia was proportional to the number of parasites injected; it subsided by 30 days after injection of 104 microfilariae but was still present at a low level 120 days after injection of 2 × 105 microfilariae. A transient splenomegaly developed after injection of microfilariae. Histopathological examination revealed large numbers of microfilariae free in the lumens of pulmonary small blood vessels and without any accompanying inflammatory reaction. Lesser numbers of microfilariae were seen in the cardiac blood and hepatic and renal blood vessels for the first few days after injection. There was cellular proliferation in the splenic white pulp and vascular congestion of the red pulp. Microfilariae labelled with 51Cr were injected intravenously; 57% of radioactivity was found in the lungs, 8·5% in the liver and 2·9% in the spleen. Mice developed immediate hypersensitivity reactions to B. malayi antigen by 4 weeks after injection, but Arthus and delayed hypersensitivity reactions were not seen at any time. When mice which had been injected 5 months previously were challenged with a 2nd injection of microfilariae, there was an accelerated clearance of parasites over 2 weeks and a marked peripheral blood eosinophilia developed. In contrast with natural infections, in which the continuous production of microfilariae complicates assessment, this model provides a system in which factors controlling the circulation of microfilariae in the bloodstream can be studied independently.

A study was undertaken to define the sensitivity and specificity of serological tests in bancroftian and malayan filariasis and correlate the findings with clinical disease. Sera were collected from subjects on three different islands in the Philippines: one endemic for bancroftian filariasis, another endemic for malayan filariasis and the third without endemic filariasis. Antibodies were measured, using Brugiamalayi as the source of antigen. Antibodies against adult worms measured by indirect immunofluorescence were found at a titer of 1 :8 or greater in all patients with bancroftian or malayan filariasis but not in the control subjects. There was no relationship of antibody titer to clinical status. Antibodies against microfilariae

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Young people in out-of-home care are at increased risk of developing a range of posttrauma mental health difficulties, including PTSD, but more commonly anxiety, depression and externalising symptoms. Cognitive models of PTSD indicate that trauma-related maladaptive appraisals, coping strategies and trauma memory qualities are key processes in the development and maintenance of PTSD, yet there has been limited investigation of the potential role of these processes in broader posttrauma psychopathology, particularly in young people who have been exposed to complex, rather than acute, trauma. We recruited 120 10–18 years olds in out-of-home care, and their caregivers, who completed assessments at two time points: baseline and 12-month follow-up. Young people completed self-report measures of trauma-related maladaptive appraisals, coping strategies and trauma-memory qualities, as well as reporting on PTSD, anxiety, depression and externalising symptoms. Carers also reported on internalising and externalising symptoms. We found that all three cognitive processes were associated with baseline self-reported internalising symptoms, with maladaptive appraisals most robustly associated with both anxiety and depression. Changes in all three processes over 12-months predicted a change in self-reported internalising and externalising symptoms, with maladaptive appraisals and coping predicting anxiety symptoms, and coping uniquely predicting depression and externalising symptoms. Effects remained after controlling for co-occurring PTSD symptoms. Findings were not replicated when using carer-reported symptoms. These findings suggest that existing cognitive models of PTSD may also usefully explain broader posttrauma depression, anxiety and externalising symptoms in young people who have experienced maltreatment and live in out-of-home care. Clinical implications are discussed.

Introduction Young people in out-of-home care have often experienced trauma, such as direct maltreatment or witnessing violence. There is good evidence that rates of mental health difficulties are high in this group, including posttraumatic stress disorder (PTSD), a trauma-specific mental health outcome. There remains less evidence to guide how to effectively address elevated PTSD symptoms (PTSS) in these young people, particularly in ways that are feasible and scalable for stretched social-care and mental health services. Methods and analysis This protocol describes a feasibility study comprising a pilot two-arm randomised controlled trial (RCT). Participants (N = 50) will be randomised to either (a) a group-based trauma-focused programme (Teaching Recovery Techniques), delivered by mental health practitioners both online and in-person, or (b) care-as-usual. Primarily, the trial aims to explore the key feasibility and protocol acceptability questions, including rates of recruitment and retention, as well as the acceptability of the intervention (particularly the online delivery format) to participants and services. In addition, outcomes including PTSS (primary clinical outcome), depression and functioning will be assessed at baseline (pre-randomisation), post-intervention and at a 3-month follow-up. Ethics and dissemination Ethical approval has been received from the Health Research Authority (Wales REC1 Ref 20/WA/0100) and University, with further approval from the host trust and social care site. The results will inform the design of a definitive RCT. Dissemination will include peer-reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries. Trial registration ClinicalTrials.gov, NCT04467320. Registered on 13 July 2020.