Identifying patients at increased risk of non-ventilator-associated pneumonia on admission to hospital: a pragmatic prognostic screening tool to trigger preventative action.

BACKGROUND: Non-ventilator healthcare-associated pneumonia (NV-HAP) is an important healthcare-associated infection. This study tested the feasibility of using routine admission data to identify those patients at high risk of NV-HAP who could benefit from targeted, preventive interventions. METHODS: Patients aged ≥64 years who developed NV-HAP five days or more after admission to elderly-care wards, were identified by retrospective case note review together with matched controls. Data on potential predictors of NV-HAP were captured from admission records. Multi-variate analysis was used to build a prognostic screening tool (PRHAPs); acceptability and feasibility of the tool was evaluated. RESULTS: A total of 382 cases/381 control patients were included in the analysis. Ten predictors were included in the final model; nine increased the risk of NV-HAP (OR between 1.68 and 2.42) and one (independent mobility) was protective (OR 0.48; 95% CI 0.30-0.75). The model correctly predicted 68% of the patients with and without NV-HAP; sensitivity 77%; specificity 61%. The PRHAPs tool risk score was 60% or more if two predictors were present and over 70% if three were present. An expert consensus group supported incorporating the PRHAPs tool into electronic logic systems as an efficient mechanism to identify patients at risk of NV-HAP and target preventative strategies. CONCLUSIONS: This prognostic screening (PRHAPs) tool, applied to data routinely collected when a patient is admitted to hospital, could enable staff to identify patients at greatest risk of NV-HAP, target scarce resources in implementing a prevention care bundle, and reduce the use of antimicrobial agents.

The role of pandemic planning in the management of COVID-19 in England from an infection prevention and control perspective: results of a national survey.

OBJECTIVES: This national survey aimed to explore how existing pandemic preparedness plans (PPP) accounted for the demands placed on infection prevention and control (IPC) services in acute and community settings in England during the first wave of the COVID-19 pandemic. STUDY DESIGN: This was a cross-sectional survey of IPC leaders working within National Health Service Trusts or clinical commissioning groups/integrated care systems in England. METHODS: The survey questions related to organisational COVID-19 preparedness pre-pandemic and the response provided during the first wave of the pandemic (January to July 2020). The survey ran from September to November 2021, and participation was voluntary. RESULTS: In total, 50 organisations responded. Seventy-one percent (n = 34/48) reported having a current PPP in December 2019, with 81% (n = 21/26) indicating their plan was updated within the previous 3 years. Around half of IPC teams were involved in previous testing of these plans via internal and multi-agency tabletop exercises. Successful aspects of pandemic planning were identified as command structures, clear channels of communication, COVID-19 testing, and patient pathways. Key deficiencies were lack of personal protective equipment, difficulties with fit testing, keeping up to date with guidance, and insufficient staffing. CONCLUSIONS: Pandemic plans need to consider the capability and capacity of IPC services to ensure they can contribute their critical knowledge and expertise to the pandemic response. This survey provides a detailed evaluation of how IPC services were impacted during the first wave of the pandemic and identifies key areas, which need to be included in future PPP to better manage the impact on IPC services.

Top research priorities in healthcare-associated infection in the UK.

BACKGROUND: There is a mismatch between research questions which are considered to be important by patients, carers and healthcare professionals and the research performed in many fields of medicine. No relevant studies which have assessed research priorities in healthcare-associated infection (HCAI) that have involved patients' and carers' opinions were identified in the literature. AIM: The Healthcare-Associated Infections Priority Setting Partnership was established to identify the top research priorities in the prevention, diagnosis and treatment of HCAI in the UK, considering the opinions of all these groups. METHODS: The methods broadly followed the principles of the James Lind Alliance (JLA) priority setting activity. FINDINGS: In total, 259 unique valid research questions were identified from 221 valid responses to a consultation of patients, carers and healthcare professionals after seeking their opinions for research priorities. The steering committee of the priority setting partnership rationalized these to 50 unique questions. A literature review established that for these questions there were no recent high-quality systematic reviews, high-quality systematic reviews which concluded that further studies were necessary, or the steering committee considered that further research was required despite the conclusions of recent systematic reviews. An interim survey ranked the 50 questions, and the 10 main research priorities were identified from the top 32 questions by consensus at a final priority setting workshop of patients, carers and healthcare professionals using group discussions. CONCLUSIONS: A priority setting process using JLA methods and principles involving patients, carers and healthcare professionals was used to identify the top 10 priority areas for research related to HCAI. Basic, translational, clinical and public health research would be required to address these uncertainties.

Combined cognitive-behavioural and mindfulness programme for people living with dystonia: a proof-of-concept study.

OBJECTIVES: To design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population. DESIGN: A proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia. SETTING: Participants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community. PARTICIPANTS: 14 participants consented to take part (2 withdrew prior to the starting of intervention). The average age was 60 years (range 44-77), 8 of whom were female. After drop-out, 9 participants completed the 3-day programme. INTERVENTION: A 3-day group residential programme. PRIMARY AND SECONDARY OUTCOME MEASURES: Process evaluation and interviews were carried out before and after the intervention to explore participant's views and expectations, as well as experiences of the intervention. Select questionnaires were completed at baseline, 1-month and 3-month follow-up. RESULTS: Although participants were not sure what to expect from the programme, they found it informative and for many this together with being in a group with other people with dystonia legitimised their condition. Mindfulness was accepted and adopted as a coping strategy. This was reflected in the 1-month follow-up. CONCLUSIONS: We successfully delivered a 3-day residential programme to help those living with dystonia manage their condition. Further improvements are suggested. The quantitative outcome measures were acceptable to this group of patients with dystonia.

epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England.

National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were originally commissioned by the Department of Health and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were first published in January 2001(1) and updated in 2007.(2) A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective for the prevention of HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. The Department of Health commissioned a review of new evidence and we have updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the epic2 guidelines published in 2007 remain robust, relevant and appropriate, but some guideline recommendations required adjustments to enhance clarity and a number of new recommendations were required. These have been clearly identified in the text. In addition, the synopses of evidence underpinning the guideline recommendations have been updated. These guidelines (epic3) provide comprehensive recommendations for preventing HCAI in hospital and other acute care settings based on the best currently available evidence. National evidence-based guidelines are broad principles of best practice that need to be integrated into local practice guidelines and audited to reduce variation in practice and maintain patient safety. Clinically effective infection prevention and control practice is an essential feature of patient protection. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of health care in NHS hospitals in England can be minimised.

How mental health nursing can best improve service users' experiences and outcomes in inpatient settings: responses to a national consultation.

Despite a number of national developments in the past few years, concerns remain about the experience and outcomes for service users in inpatient care settings. As part of a national review of mental health nursing in England, a consultation exercise was carried out to ascertain the opinions of a wide range of stakeholders in order to inform subsequent recommendations. The consultation question specifically related to inpatient care was 'How can mental health nurses best improve service users' experiences, and outcomes, in inpatient care settings?' The consultation generated a total of 326 written responses, mostly from groups and organizations. Responses were subject to content analysis and the three largest categories were 'Service users influencing services' (n = 80, 31%), 'Service users involved in own care' (n = 74, 29%) and 'Direct clinical time' (n = 68, 26%), including respondents citing the need for protected therapeutic engagement time. Many of the themes raised in the consultation were subsequently reflected in the recommendations made in 'From values to action; the Chief Nursing Officer's review of mental health nursing'.

Regulation of TNF-related apoptosis-inducing ligand-mediated death-signal pathway in human beta cells by Fas-associated death domain and nuclear factor kappaB.

Transfectants of human CM and NES2Y beta cell lines and primary islets transfected by FADD-DN (dominant-negative form of Fas-associated death domain), a mutant of FADD and/or a superrepressor of nuclear factor kappaB (NF-kappaB) (AdIkappaB(SA)2), were examined for their susceptibility to the TRAIL (TNF-related apoptosis-inducing ligand)-induced death signal pathway, compared with controls, wild-type cells, and vector transfectants in caspase fluorescence, Western blot, electrophoretic mobility shift, apoptosis, and cytotoxicity assays. FADD-DN inhibited caspase-8 activation induced by TRAIL in the transfectants of CM and NES2Y cells. TRAIL-induced apoptosis and cytotoxicity to the FADD-DN transfectants were decreased in comparison to those responses in controls (CM, p < 0.01 and p < 0.01; NES2Y, p < 0.05, and p < 0.02, respectively). When CM, NES2Y, and primary islet cells were transfected by AdIkappaB(SA)2, TRAIL-induced IkappaB degradation and nuclear translocation of NF-kappaB p50/p65 were blocked. TRAIL-induced apoptosis and cytotoxicity to AdIkappaB(SA)2 transfectants of these cells were also reduced (CM, p < 0.02 and p < 0.02; NES2Y, p < 0.01 and p < 0.01, respectively, and islet p < 0.01 for cytotoxicity). Finally, cytotoxicity induced by TRAIL in CM and NES2Y cells transfected with both FADD-DN and AdIkappaB(SA)2 was reduced, compared with that observed in these cells transfected with either FADD-DN alone or AdIkappaB(SA)2 alone, suggesting that FADD and NF-kappaB have synergistic proapoptotic regulatory effects on the susceptibility of beta cell lines and islet cells to TRAIL-induced destruction.

Continuing education opportunities for recently qualified mental health diplomates.

While successive reports concerned with mental health services have emphasized the importance of continuing professional development for mental health nurses, there have been long-standing concerns about the provision of appropriate courses and opportunities for attendance. Drawing from a longitudinal study of the careers of a cohort of mental health diplomates, this paper focuses on fulfilment of their continuing education plans in the early post-qualification period. During the first 6 months, just under half the cohort had wanted to start a course but been unable to do so. For some, even at this early career stage, dissatisfaction with continuing education opportunities was cited as reason for leaving, or considering leaving, a first job. Reasons for starting courses included career progress and meeting the care-giving needs of the immediate work situation. Diplomates may need guidance on their continuing education needs; there was much uncertainty about plans to take courses and moreover, demand for courses which they had wanted to start but been unable to do so, was not always sustained.

TNF-related apoptosis-inducing ligand death pathway-mediated human beta-cell destruction.

AIMS/HYPOTHESIS: The aim of this study is to investigate whether apoptosis in human beta cells can be related to the induction of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway. METHODS: We examined the expression of TRAIL and TRAIL receptors in two human pancreatic beta-cell lines and in human primary islet cells using RT-PCR assays and flow cytometric analyses and tested TRAIL-mediated beta-cell destruction in (51)Cr release cytotoxicity assays, Annexin-V and APO-DIREC assays. RESULTS: Most of the human beta cells express TRAIL receptors-R1, -R2, -R3, -R4 and/or TRAIL. TRAIL induced much stronger cytotoxicity and apoptosis to beta-cell lines CM and HP62 than did FasL, TNF-alpha, LTalpha1beta2, LTalpha2beta1, LIGHT, and IFN-gamma. The cytotoxicity and apoptosis induced by TRAIL to beta-cell lines CM were inhibited competitively by soluble TRAIL receptors, R1, R2, R3 or R4. Treatment of these beta cells with antibodies against TRAIL receptors was able to block the cytotoxicity of TRAIL to these cells. Beta-cell antigen-specific CTL (CD4(+) and CD8(+)) clones express TRAIL, suggesting that these cells are potential sources of TRAIL-inducing beta-cell destruction. Normal primary islet cells from most donors are resistant to the cytotoxicity mediated by TRAIL. However, treatment with an inhibitor of protein synthesis (cycloheximide) or with an enzyme (PI-PLC) that can remove TRAIL-R3 from the islet-cell membrane was able to increase the susceptibility of TRAIL-resistant primary islet cells to the TRAIL death pathway. CONCLUSION/INTERPRETATION: The TRAIL death pathway is present and can function in human islet beta cells, but unidentified inhibitors of the TRAIL death pathway are present in normal islet cells.

Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus.

AIMS/HYPOTHESIS: To examine the cross-reaction between viral and beta-cell protein determinants and to further understand the potential role of this mechanism in Type I (insuline-dependent) diabetes mellitus. METHODS: Immune responses to a panel of 28 viral and beta-cell protein peptides representing selected sequences of rubella virus (RV), Coxsackie virus, human 38 KDa31G and glutamic acid decarboxylase (GAD 65 and 67) proteins in proliferation or cytotoxicity assays have been studied using uncloned and cloned T-cell cohorts from a group of 60 Type I diabetic patients. RESULTS: Peptide GAD65(252-266) induced the responses of patients with recent onset diabetes in proliferation assays at the highest frequency (77%), whereas GAD67(212-226) stimulated the cellular responses at the highest rate (61%) in patients with late-onset diabetes. RVE1(157-176) was recognised by all groups of patients at the highest frequency and the largest amplitude among the viral peptides tested. T-cell clones specific to GAD65(252-266), GAD65(274-286) or GAD67(212-226) were tested in cytotoxicity assays for their responses to rubella virus peptides. Each of these T-cell clones cross-reacted with two to four rubella virus peptides, including RVE1(157-176) and RVE2(87-107). Analysis of the sequences of cross-reactive viral and glutamic acid decarboxylase antigens showed that these epitopes shared similar peptide binding motifs to HLA DR3/DR4. There is a statistically significant correlation between the response amplitude of patient's peripheral blood mononuclear cells to RVE1(157-176), RVE2(87-107) and GAD65(274-286) in patients with recent onset diabetes, and to RVE1(157-176) and GAD67(212-226) in patients with late onset diabetes. CONCLUSION/INTERPRETATION: Cross-reactive glutamic acid decarboxylase and rubella virus determinants identified by T-cell clones were also recognised at high frequencies by general T-cell populations of Type I diabetic patients.

Rubella virus vaccine associated arthropathy in postpartum immunized women: influence of preimmunization serologic status on development of joint manifestations.

OBJECTIVE: To measure preimmunization rubella virus (RV)-specific IgG levels and to relate these to the development of acute and chronic (persistent or recurrent) joint manifestations following rubella vaccination. METHODS: Specific IgG was determined by whole RV enzyme immunoassays (EIA) (Abbott Rubazyme and M33, an in-house method), immunoblot, neutralization domain peptide (BCH-178c) EIA, and neutralization bioassay in prevaccine samples of 268 RV seronegative women (Abbott absorbance < 0.999 units) who had received monovalent live attenuated RA27/3 strain RV vaccine in a clinical trial that recorded joint manifestations. RESULTS: Of rubella vaccinated women tested for prevaccine antibodies, 21.7% were actually positive (> or = 10 IU/ml) by M33 EIA, 33.2% had Abbott values > or = 0.250 units, and 47.6% had RV protein-specific antibody (immunoblot), while only 17.6% were positive (> or = 10 IU/ml) by neutralization domain peptide EIA and 12.7% had neutralization titers > or = 1:8. Seropositivity by the various methods was compared to recorded occurrence of acute and chronic arthropathy (arthralgia and/or arthritis) after RV vaccination. Relative to women who had no joint manifestations, prevaccine seropositivity rates for subjects with acute arthropathy were significantly (p < 0.05) lower in the Abbott test (< 0.250 units), BCH-178c peptide EIA, and neutralization bioassay, while those who also developed chronic arthropathy had significantly lower prevaccine seropositivity rates for the Abbott (< 0.250 units) and M33 EIA and neutralization bioassay. CONCLUSION: Results suggest that risk for arthropathy following RA27/3 rubella vaccination may be higher in women who have very low prevaccine levels of antibody, particularly in assays measuring functional (neutralizing) antibodies.

CD4+ and CD8+ T-cell clones from congenital rubella syndrome patients with IDDM recognize overlapping GAD65 protein epitopes. Implications for HLA class I and II allelic linkage to disease susceptibility.

To fully characterize human glutamic acid decarboxylase (GAD)65 protein T-cell epitopes associated with insulin-dependent diabetes mellitus (IDDM), CTL clones specific to GAD65 protein antigens were isolated from two congenital rubella syndrome (CRS)-associated IDDM patients. Overlapping nonamer T-cell epitopes recognized by both CD4+ or CD8+ CTL clones within peptides GAD65(252-266) and GAD65(274-286) were identified as sequences bounded by GAD65(255-266) with 6/9 overlapping residues, and GAD65(276-285) with 8/9 overlapping residues, respectively, using two panels of overlapping peptide analogs in cytotoxicity assays. HLA restrictive elements of the T-cell clones were also identified using a panel of B cell lines with different HLA phenotypes as targets in cytotoxicity assays. The antigenic GAD65 peptides elicited cytotoxic responses of peptide-specific CD4+ T-cell clones in the context of HLA DRB1*0404. The CD8+ T-cell clone specific to GAD65(255-263) was found to be restricted by HLA A3 and A11. Similarly, the CD8+ T-cell clone specific to GAD65(277-285) killed peptide-sensitized target cells expressing HLA B35 and B15. The observed HLA restriction of these overlapping epitopes implies that a tandem of [DRB1*0404-A11(3)] and/or a tandem of [DRB1*0404-B35(15)] might predispose CRS patients to development of IDDM.

Identification of rubella virus T-cell epitopes recognized in anamnestic response to RA27/3 vaccine: associations with boost in neutralizing antibody titer.

Rubella virus (RV)-specific cell-mediated immunity (CMI) and antibodies were measured in healthy adolescents reimmunized with measles-mumps-rubella (MMR) vaccine. Lymphocyte proliferation to RV synthetic peptides was determined before and at 2, 4 and 10 weeks after, MMR. After MMR, increased CMI was observed with 16 peptides, including six containing antibody neutralization (NT) domains. Positive CMI (stimulation index > or =2.0) to E1(254-285) and C(1-29) before vaccination was significantly associated with a boost in NT titers, while positive CMI at weeks 2 or 4 to E1(254-285), E1(301-314), E1(389-408), E1(462-481), E2(134-150), E2(140-156), E2(168-179), C(1-29) and C(88-111) showed the same association.

Studying the careers of nurse diplomates: the importance of branch-specific questionnaires.

Questionnaire design is considered in the context of a longitudinal panel study focusing on the careers of people qualifying from all four branches of the UK nurse diploma course. Separate, but comparable, questionnaires were developed for each branch in order to produce information which reflected the differences between branches, and the experiences of the cohort as a whole. This approach ensured that participants from the smaller branches did not feel their interests and concerns were overshadowed by those of the largest (adult) branch, as is often the case during the diploma course's Common Foundation Programme. The elements that needed to be tailored to each branch emerged during a three-stage piloting process used to develop and test the questionnaires. Differences were found between branches in their use of terminology; in certain issues being more relevant to some branches than others; and in questions which concerned all branches benefiting from the inclusion of branch-specific examples. The effectiveness of this approach to questionnaire design is borne out by the study's high response rates.

Serologic responses to measles, mumps, and rubella (MMR) vaccine in healthy infants: failure to respond to measles and mumps components may influence decisions on timing of the second dose of MMR.

Measles, mumps, and rubella-specific IgG antibodies were evaluated in 134 healthy infants routinely immunized with trivalent live attenuated measles-mumps-rubella (MMR) vaccine at one year of age. Blood samples were collected just before, and at 1, 3, and 12 months after MMR. Specific IgG was measured by commercial enzyme immunoassays. Before vaccination, 98.5%, 99.2%, and 98.5% of the infants tested were seronegative for measles, mumps, and rubella, respectively. One year after MMR, 16.4% and 22.4% of vaccinees lacked demonstrable antibody to measles and mumps while none were found to be seronegative for rubella. Response profile analysis revealed primary failure rates of 12.1% (measles) and 8.6% (mumps) while 4% (measles) and 13.8% (mumps) of the infants responded initially but became seronegative within one year. These observations suggest that earlier administration (at age 18 months) of the second dose of MMR may be more desirable than revaccination at school entry.

A new categorization of HLA DR alleles on a functional basis.

In this analysis, we introduce a new categorization of HLA DR alleles which are important members of HLA class II genes encoding cell surface glycoproteins that function to present antigenic peptides to T cells. We have grouped all HLA DR molecules into seven different functional categories on the basis of their ability to bind and present antigenic peptides to T cells and their association with susceptibility or resistance to disease. This novel categorization of DR alleles on the basis of function allows for the prediction of seven similar subregion structures (supertypes or supermotifs) within pocket 4 of HLA DR peptide binding groove as the molecular basis for grouping these alleles. The physicochemical characteristics of HLA DR supertype residues, charge in particular, may influence the selectivity for binding peptide, dominate promiscuous T-cell recognition of antigenic peptides, and affect HLA DR disease associations. To rationalize the functional categories of DR alleles, we have further combined the seven DR supertype patterns into three groups based on the charges of residues within the supertypes. Grouping HLA DR alleles into functional categories may assist in understanding the mechanistic basis of autoimmunity, resolving current paradoxes in HLA disease associations, and developing new immunotherapy strategies.

Point mutation of a rubella virus E1 protein T-cell epitope by substitution of single amino acid reversed the restrictive HLA-DR polymorphism: a possible mechanism maintaining HLA polymorphism.

The influence of single amino acid substitutions within a rubella E1 protein T-cell epitope, E1(273-284) on T-cell recognition was studied. Substitutions of an uncharged amino acid A for an E or for a T and substitution of a T for S were found to not significantly reduce the T-cell responses. However, substitution of a charged residue such as E for hydrophobic residues (I, V, or W); D for Q; or a relatively larger size amino acid for polar residues completely abolished the cytotoxicities mediated by E1(273-284)-specific T-cell clone. A set of single amino acid-substituted peptide analogs of E1(273-284) not eliciting cytotoxicity of the T-cell clone was used to test the influence of point mutation of the epitope on HLA DR restrictions. A panel of B-cell lines with different DR4 subtypes was used as targets in cytotoxicity assays to determine the restrictive HLA molecules. Results showed that modification of the T-cell epitope by point mutation could reverse the HLA DR restriction from one allele to other alleles. A model based on these results has been proposed to explain the mechanism balancing major histocompatibility complex (MHC) polymorphism in outbred populations.

Promiscuous T-cell recognition of a rubella capsid protein epitope restricted by DRB1*0403 and DRB1*0901 molecules sharing an HLA DR supertype.

Two T cell clones derived from different donors with HLA-DRB1*0403 or DRB1*0901 phenotype recognize a rubella capsid peptide, C(265-273) in the context of several different HLA-DR molecules in addition to DRB1*0403 and DRB1*0901. All DR molecules restricting the T-cell clones have in common residues, R or Q at position beta 70, R at position beta 71, and E at position beta 74 in pocket '4' of the DR peptide binding groove, suggesting that a DR subregion structure or supertype, "Q/RRE" underlies the promiscuous T-cell recognition of this peptide. Single amino acid substituted analogs of peptide C(263-275) at anchor position 4 for natural residue R were tested for their ability to induce clonal T-cell cytotoxic responses. The results indicated that a positively charged residue, R or K, was required for T-cell recognition, suggesting a possible mechanism of electrostatic interactions between the negatively charged residue E at position beta 74 of these DR molecules and the positively charged residue at anchor position 4 of the peptide in T-cell recognition.

HLA-DR class II associations with rubella vaccine-induced joint manifestations.

HLA class II (HLA-DR) frequencies were examined in relation to incidence of acute arthralgia or arthritis in 283 white women who had received RA27/3 rubella vaccine (n = 146) or placebo (n = 137) postpartum. Leukocyte DNA was molecularly typed for HLA-DRB1 gene expression. Univariate analysis revealed higher frequencies of DR2 (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.2-18.8) and DR5 (OR, 7.5; 95% CI, 1.5-37.5) but lower frequencies of DR4 (OR, 2.3; 95% CI, 1.1-4.9) and DR6 (OR, 2.8; 95% CI, 1.4-5.8), in rubella vaccinees compared with placebo recipients with arthropathy. Logistic regression modelling of DR, treatment, age, time postpartum, and arthropathy revealed that the odds of developing arthropathy was 1.9 times greater (95% CI, 1.07-3.44) after rubella vaccine than placebo. Risk for arthropathy (regardless of rubella vaccination) was also influenced by DR interactions: odds were 8 times greater in individuals with both DR1 and DR4 (95% CI, 1.45-44.02) and 7.1 times greater with both DR4 and DR6 present (95% CI, 1.85-27.52), suggesting that coexpression of these specificities may predispose to postpartum arthropathy.

Characterization of an overlapping CD8+ and CD4+ T-cell epitope on rubella capsid protein.

A synthetic peptide corresponding to rubella virus capsid protein residues 263 to 275 which contains an epitope recognized by a cloned CD4+ cytotoxic T-lymphocyte (CTL) line was used to induce CD8+ T-cell lines specific to this peptide. A peptide-specific CD8+ CTL clone was derived and characterized. This peptide-specific CD8+ CTL clone exhibited cytotoxicity against target cells infected by a vaccinia recombinant virus expressing rubella virus capsid protein, but not by target cells infected by vaccinia recombinant virus expressing rubella virus E1 or E2 envelope proteins. Analysis of HLA class I restriction of the CD8+ CTL clone revealed that A11 and A3 were restrictive elements. Fine mapping with truncated and overlapping peptide analogs revealed a nonamer sequence, C(264-272), as the T-cell epitope eliciting stronger cytotoxicity. Two anchor residues for binding to HLA A11 and A3 were identified at position 2 (isoleucine) and at position 9 (histidine) or at position 8 (arginine) of the epitope sequence. The identification of overlapping CD4+ and CD8+ T-cell epitopes within the capsid protein sequence C(263-275) implicates a strategy for using such epitopes in a candidate peptide-based rubella vaccine.