Nadine Harrison

The immune response to primary EBV infection: a role for natural killer cells

The role of antigen‐specific CD3+CD8+ cytotoxic T cells in the control of primary Epstein–Barr Virus (EBV) infection is well established. However, time is required for the antigen‐specific immune response to develop and expand. In contrast, innate immune responses, such as natural killer (NK) cells, are considered vital early in the infection process. We analysed the scale, phenotype and function of the NK cell response during symptomatic primary EBV infection, infectious mononucleosis (IM) and showed that NK cell numbers were significantly elevated both at diagnosis of IM and in the first month following diagnosis. There were also significant changes in cell phenotype and function, an increase in the proportion of CD56bright cells at diagnosis, and freshly isolated cells showing an enhanced ability to kill EBV‐infected cell lines. Moreover, in our cohort of IM patients higher NK cell counts were associated with significantly lower viral load in peripheral blood. Our results suggest NK cells have an important role in the control of primary EBV infection by eliminating infected B cells and augmenting the antigen‐specific T cell response via release of immunomodulatory cytokines. The magnitude of the NK cell response may ultimately determine whether primary EBV infection has a clinical outcome.

Sexual History and Epstein-Barr Virus Infection

To determine the role of sexual contact in transmission of Epstein-Barr virus (EBV) and occurrence of infectious mononucleosis (IM), a cross-sectional study was undertaken of EBV serologic testing and histories of IM and sexual behavior among 1006 new students at Edinburgh University. Prevalence of EBV seropositivity was significantly greater among women (79.2%) than among men (67.4%; P<.001) and among those who had ever been sexually active (82.7%) than among those who had not (63.7%; P<.001). Having a greater number of sex partners was a highly significant risk factor for EBV seropositivity. Two thirds of IM cases, but only a tenth of asymptomatic primary EBV infections, were statistically attributable to sexual intercourse. The findings suggest that EBV transmission occurs during sexual intercourse or closely associated behaviors. Transmission in this way appears to account for most cases of IM but for only a minority of cases of asymptomatic EBV infection, which mainly occur at younger ages.

Analysis of Immune Activation and Clinical Events in Acute Infectious Mononucleosis

The symptoms of infectious mononucleosis (IM) are thought to be caused by T cell activation and cytokine production. Surface lymphocyte activation marker (SLAM)-associated protein (SAP) regulates lymphocyte activation via signals from cell-surface CD244 (2B4) and SLAM (CD150). We followed T cell activation via this SAP/SLAM/CD244 pathway in IM and analyzed whether the results were associated with clinical severity. At diagnosis, SAP, SLAM, and CD244 were significantly up-regulated on CD4 and CD8 T cells; expression decreased during IM, but CD244 and SLAM levels remained higher on CD8 cells 40 days later. There were significantly more lymphocytes expressing CD8 and CD244/CD8 in patients with severe sore throat. The expression of CD8 alone and CD244 on CD8 cells correlated with increased virus load. We suggest that T cells expressing CD244 and SLAM are responsible for the clinical features of IM but that the control of activation is maintained by parallel increased expression of SAP.

A study of risk factors for acquisition of Epstein‐Barr virus and its subtypes

BACKGROUND Risk factors for primary infection with Epstein-Barr virus (EBV) and its subtypes have not been fully investigated. METHODS Questionnaires and serum samples from a total of 2006 students who entered Edinburgh University in 1999-2000 were analyzed to examine risk factors for EBV seropositivity, both overall and by EBV type. RESULTS The prevalence of EBV seropositivity was significantly increased among females, older students, those who had lived in tropical countries, those with siblings, and those who were sexually active, particularly if they had had numerous sex partners. Risk was lower (1) among students who always used a condom than among those who had sexual intercourse without one and (2) among female oral-contraceptive users than among sexually active nonusers. Risk factors for type 1 EBV infection were similar to those for EBV overall. No associations were found between nonsexual risk factors and type 2 infection. Sexual activity increased the risk of type 2 infection, but the increase in risk with number of sex partners was less consistent than for type 1 infections. Dual infection was uncommon, but the patterns of risk appeared to be similar to those of type 1 infection. CONCLUSION This study provides further evidence that EBV may be sexually transmitted and some suggestion that the risk factors for type 1 and type 2 infection differ.

Infectious Mononucleosis in University Students in the United Kingdom: Evaluation of the Clinical Features and Consequences of the Disease

BACKGROUND Infectious mononucleosis (IM) is common among university students. We undertook to analyze the clinical features and sequelae of the disease in a cohort of students at Edinburgh University. METHODS Consecutive IM case patients were recruited from 2000 through 2002 at the University Health Service after diagnosis of IM. RESULTS IM resulted in marked reductions in student study time, physical exercise, and non-exercise-related social activities, and sustained increases in reported number of hours of sleep. The disease profile differed between the sexes, with significantly more females reporting fatigue, which was more likely to be prolonged (P = .003) and to lead to loss of study time (P = .013). Female case patients were more likely to discontinue their studies following IM (16% vs 0%; P = .056). Within the typically elevated lymphocyte counts in IM, we identified an elevated gammadelta T cell component that may contribute to the disease pathogenesis. CONCLUSIONS IM results in substantial morbidity among university students, reported as more profound in females, and affecting academic studies, physical exercise, and social activities. Immunization to prevent IM and strategies to reduce post-IM disability would be beneficial in this population.

Are UK primary care teams formally identifying patients for palliative care before they die

BACKGROUND The palliative care approach has the potential to improve care for patients with progressive life-threatening illnesses from the time of diagnosis. Policy and clinical directives in the UK advocate early identification. AIM To determine the extent to which practices identify patients for palliative care, including factors influencing early identification and possible effects on place of death. DESIGN AND SETTING Qualitative and quantitative data were collected from six general practices from three Scottish NHS boards and analysed. METHOD Records of patients who had died in the previous 6 months were analysed and interviews with practice staff (n = 21) and with patients currently on the practice palliative care register and bereaved relatives (n = 14) were conducted. In addition, a practice meeting was observed. RESULTS In total, 29% of patients who died were recorded as being on the practice palliative care register before death. Two-thirds of patients with cancer were recorded on the register, but for those with non-malignant conditions only around 20% had any palliative care documented. This was a result of GPs not finding the current guidelines useful and being reluctant to discuss palliative care overtly with patients early in their illness. Palliative care services and documentation were geared towards patients with cancer. More district nurses than GPs saw the benefits of inclusion on the palliative care register. Only 25% of patients on the register died in hospital. CONCLUSION Most patients with advanced progressive illnesses, especially those with non-malignant disease, are not being formally identified for a palliative care approach before they die. Those identified are more likely to benefit from coordinated care and may be more likely to die at home.

Understanding the barriers to identifying carers of people with advanced illness in primary care: triangulating three data sources

BackgroundApproximately 10% of the UK population have an unpaid caring role for a family member or friend. Many of these carers make a significant contribution to supporting patients at the end of life. Carers can experience poor physical and psychosocial wellbeing, yet they remain largely unsupported by health and social care services. Despite initiatives for general practices to identify carers and their needs, many remain unidentified. Neither are carers self-identifying and requesting support. This study set out to explore the barriers to, and consider strategies for, identifying carers in primary care.MethodsWe integrated findings from three data sources – a review of the caregiving literature; a workshop with researchers who have undertaken research with those caring at the end of life, and focus groups with carers and health professionals.ResultsThree categories of barrier emerged. 1) Taking on the care of another person is often a gradual process, carers did not immediately identify with being a ‘carer’ – preferring to think of themselves in relational terms to the patient e.g. spouse, sibling, son or daughter. Often it was health and social care professionals who encouraged carers to consider themselves as an unpaid carer. 2) As the cared-for person’s condition deteriorated, the caring role often became all-encompassing so that carers were managing competing demands, and felt unable to look after their own needs as well as those of the cared-for person. 3) There was ambiguity about the legitimacy of carer needs and about the role of the primary health care team in supporting carers, from both the perspective of the carers and the health professionals. GPs were thought to be reactive rather than proactive which discouraged carers from asking for help.ConclusionsThe needs of carers have to be legitimised to ensure primary care staff are proactive in their approach and carers are empowered to utilise the support available. Strategies to identify carers have to be sensitive to the complex dynamics of a caring relationship as well as the primary care context. Identification is a key factor in improving support for carers themselves and to enable them to support the patient.

Michael Arthur Sansbury

Michael Sansbury (“Mike”) was born and brought up in Aberystwyth but returned to his grandfather’s country to study medicine in Edinburgh. His preregistration jobs were in Fife and in Longmore Hospital, Edinburgh. After his general practitioner training in …

Improving care and support for people with progressive illness in primary care

Abstract Introduction and aims The Palliative Care Directed Enhanced Service (DES) was introduced in Scotland in 2008/2009 to stimulate anticipatory care by GP practice teams. We aimed to evaluate how practices were implementing this by assessing how they were ▶ identifying patients for their palliative care register (PCR), ▶ assessing/reviewing needs, ▶ sharing information with out of hours (OOH) providers, ▶ using the Liverpool Care Pathway (LCP). Methods Six practices were recruited from three Scottish Health Boards. Data were collected on current palliative care patients and on patients dying in the previous 6 months; semi-structured interviews were conducted with GPs, district nurses (DN) and administrative staff (total 20) and with patients and bereaved relatives (total 11); the researcher observed multidisciplinary practice meetings. Results Only 29% of patients were on the PCR prior to death (range 10–38% between practices). Of these, 69% had cancer, 17% organ failure and 14% dementia or physical frailty and 25% died in hospital (cf. 44% of all deaths). 52% on the current PCR had a record of preferred place of care and 35% of resuscitation status. Practices valued better focused and structured palliative care, improved communication with OOH providers and introduction of the LCP but raised some difficulties in including non-cancer patients on the PCR. Patients and relatives appreciated pro-active care. Conclusion Despite this initiative few patients were identified for palliative care. However when identified, their multidisciplinary and OOH care improved and hospital admissions to die decreased. Practices must identify more patients earlier for palliative care.