Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Hippocampal subfield pathologic burden in Lewy body diseases vs. Alzheimer's disease.

AIMS: Lewy body diseases (LBD) are characterized by alpha-synuclein (SYN) pathology, but comorbid Alzheimer's disease (AD) pathology is common and the relationship between these pathologies in microanatomic hippocampal subfields is understudied. Here we use digital histological methods to test the association between hippocampal SYN pathology and the distribution of tau and amyloid-beta (Aß) pathology in LBD and contrast with AD subjects. We also correlate pathologic burden with antemortem episodic memory testing. METHODS: Hippocampal sections from 49 autopsy-confirmed LBD cases, 30 with no/low AD copathology (LBD - AD) and 19 with moderate/severe AD copathology (LBD + AD), and 30 AD patients were stained for SYN, tau, and Aß. Sections underwent digital histological analysis of subfield pathological burden which was correlated with antemortem memory testing. RESULTS: LBD - AD and LBD + AD had similar severity and distribution of SYN pathology (P > 0.05), CA2/3 being the most affected subfield (P < 0.02). In LBD, SYN correlated with tau across subfields (R = 0.49, P < 0.001). Tau burden was higher in AD than LBD + AD (P < 0.001), CA1/subiculum and entorhinal cortex (ERC) being most affected regions (P = 0.04 to <0.01). However, tau pathology in LBD - AD was greatest in CA2/3, which was equivalent to LBD + AD. Aß severity and distribution was similar between LBD + AD and AD. Total hippocampal tau and CA2/3 tau was inversely correlated with memory performance in LBD (R = -0.52, -0.69, P = 0.04, 0.009). CONCLUSIONS: Our findings suggest that tau burden in hippocampal subfields may map closely with the distribution of SYN pathology in subfield CA2/3 in LBD diverging from traditional AD and contribute to episodic memory dysfunction in LBD.

Progression of alpha-synuclein pathology in multiple system atrophy of the cerebellar type.

AIMS: The aim of this study was to identify early foci of α-synuclein (α-syn pathology) accumulation, subsequent progression and neurodegeneration in multiple system atrophy of the cerebellar type (MSA-C). METHODS: We analysed 70-µm-thick sections of 10 cases with MSA-C and 24 normal controls. RESULTS: MSA-C cases with the lowest burden of pathology showed α-syn glial cytoplasmic inclusions (GCIs) in the cerebellum as well as in medullary and pontine cerebellar projections. Cerebellar pathology was highly selective and severely involved subcortical white matter, whereas deep white matter and granular layer were only mildly affected and the molecular layer was spared. Loss of Purkinje cells increased with disease duration and was associated with neuronal and axonal abnormalities. Neocortex, basal ganglia and spinal cord became consecutively involved with the increasing burden of α-syn pathology, followed by hippocampus, amygdala, and, finally, the visual cortex. GCIs were associated with myelinated axons, and the severity of GCIs correlated with demyelination. CONCLUSIONS: Our findings indicate that cerebellar subcortical white matter and cerebellar brainstem projections are likely the earliest foci of α-syn pathology in MSA-C, followed by involvement of more widespread regions of the central nervous system and neurodegeneration with disease progression.

The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012.

On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

Infection control failures in a dental surgery--dilemmas in incident management.

Three separate incidents involving failure of decontamination of dental instruments were reported to our Unit in less than one year. We describe the risk assessment we undertook for the likelihood of detecting transmission of a blood borne virus infection. Even where 4000 patients attended the same dentist for seven years, there was no certainty of detecting even one person infected by the decontamination failure, while several people who had acquired infection by other routes would be identified. We conclude that these findings suggest that notifying patients is not usually justified.

Disposal of syringes, needles, and lancets used by diabetic patients in North East Essex.

To investigate community disposal of contaminated sharps by insulin-treated diabetes mellitus patients, we surveyed 144 patients. Twenty-three (16.0%) were non-contactable, leaving a study sample of 121, of whom 102 (84.3%) responded. Among the respondents 93.1% used lancets and 97.1% needles; 70.6% used lancets once or twice a day and 65.7% used needles twice a day. The majority said they had received no information on safe disposal of sharps. Of those recalling advice, most received it from diabetes nurse specialists. The majority of needle users used needle clippers and/or sharps bins for disposal. Most of the lancet users resorted to drinks cans/bottles or domestic waste. There were statistically significant differences in practices between patients receiving and not receiving advice on sharps disposal (odds ratio [OR] 6.36 [95% CI 2.04-23.28] p = 0.0007 for needle disposal and OR 15.41 [95% CI 3.57-90.12] p = 0.00001 for lancet disposal). There were also statistically significant differences among needle users using and not using needle clippers and/or sharps bins according to the interval since diagnosis and the frequency of needle use per day. This study identifies a need for a standardised approach to sharps disposal supported by an effective method of disseminating information, and a need for advice on auditing its impact.

Description of an HIV patient notification exercise in Essex involving a dental healthcare worker.

During 2000, one of the Consultants in Communicable Disease Control (CsCDC) for North Essex Health Authority was advised that a healthcare worker (HCW) in dentistry had recently been diagnosed as HIV positive. As a result of the HCW's history and taking account the Guidance on HIV infected healthcare workers of the United Kingdom Expert Advisory Group on AIDS, North and South Essex Health Authorities embarked on the largest patient notification exercise in the United Kingdom, to date. This involved an examination of 36,000 patient records and resulted in the identification of 5,929 exposed patients. Of these 5,929 patients, 3,825 contacted the health authority helpline and 3,096 were counselled and screened for evidence of HIV infection. All tests were negative. This was also the first patient notification exercise to use salivary samples for patient screening. The exercise cost in excess of 300,000 Pounds, ignoring the opportunity costs of staff having to devote time to the exercise.

Antibody responses to Hepatitis A vaccine in healthy adults.

Hepatitis A vaccination has been used in a number of settings to control community outbreaks of the disease. Yet United Kingdom guidance for post-exposure prophylaxis continues to promote the administration of human normal immunoglobulin, despite concerns about the administration of human derived blood products. Little is known about the time frame of the antibody response to hepatitis A vaccine which, if rapid, could permit the exclusive use of vaccine for post-exposure prophylaxis. We report the findings of a pilot study in healthy adult volunteers given a single dose of Havrix monodose.

Carriage of Neisseria meningitidis in residents and staff at a residential home for elderly people following a case of invasive disease.

A study of the carriage of Neisseria meningitidis among staff and residents of a 'closed community' (a residential home for elderly people) was conducted after a resident developed invasive meningococcal disease. All 39 other residents and 49 staff who worked at the home during the previous seven days were offered a throat swab and 38 residents and 49 staff consented. Two residents (none in the index case's social group) and one staff member were found to be carrying N. meningitidis, all phenotypically distinct from the infecting isolate. Thus, all four individuals carried different organisms and the index case was sporadic. Our findings suggest that residents or staff in long stay residential settings where a sporadic case occurs need not be offered meningococcal prophylaxis unless they fulfil the existing definition of 'close personal contacts' of the case.

Basis of rabies virus neurovirulence in mice: expression of major histocompatibility complex class I and class II mRNAs.

Expression of major histocompatibility complex (MHC) molecules on cells of the central nervous system (CNS) plays an important role in the pathogenesis of acute viral encephalitis. We have compared the induction of MHC class I and II mRNA transcripts in mice upon infection with the virulent challenge virus standard (CVS) strain of rabies virus and avirulent rabies virus variant RV194-2. Rabies virus antigen was detected with immunoperoxidase staining and 35S-labeled RNA probes were used to detect MHC class I and class II mRNA transcripts by in situ hybridization in infected brains. In CVS and RV194-2 infected animals, MHC class I mRNA expression occurred in the brain in neurons, glia, choroid plexus epithelial cells, ependymal cells, and inflammatory cells; expression was moderately higher in CVS-infected mice. In contrast, MHC class II mRNA expression was minimal in CVS-infected mice and it was markedly upregulated in CNS inflammatory cells upon RV194-2 infection. Both viruses induced an acute inflammatory reaction in the cerebrospinal fluid (CSF), which was more pronounced in CVS-infected mice. Both viruses also induced an antigen specific T and B cell response detectable in lymph nodes and spleen. These studies, which show a correlation between greater expression of MHC class II mRNA in the brain following intracerebral RV194-2 infection and protection against RV194-2 infection in the brain, suggest that recovery from avirulent rabies virus infection of neural cells involves T helper cells produced and/or retained in the brain for reasons that are not entirely clear.

Control of a community hepatitis A outbreak using hepatitis A vaccine.

In an outbreak of hepatitis A infection among children attending a village primary school hygiene measures and prophylaxis of household contacts of initial cases with human normal immunoglobulin did not prevent spread. Over two months 16 pupils and two household contacts were infected, and seven children aged 6 to 10 years were jaundiced. Testing for salivary IgG and IgM among staff and pupils and their household contacts identified asymptomatic cases. Hepatitis A vaccine was offered to staff and pupils. Coverage was 78%. If those with previous infection are included 81% were protected. Two cases arose in the seven days after the vaccination campaign. No further cases were identified in the following 30 weeks. Our experiences illustrate a lack of public and professional awareness of the seriousness of hepatitis A in adults, and suggest that hepatitis. A vaccine alone is a useful outbreak control measure. Salivary antibody testing showed that only a quarter of those over 40 years of age (17/69) were immune to hepatitis A.

Screening child playgroup contacts of an adult with smear negative tuberculosis.

A childcare assistant with smear negative, culture positive tuberculosis worked for four months with 85 children who attended playgroups for 2.5 to 5 hours each week. Eighty-two of the children completed contact tracing procedures. No evidence was found of transmission of disease to any child.

Sustained reduction in the carriage of Neisseria meningitidis as a result of a community meningococcal disease control programme.

The effect of a community intervention programme of antibiotics and meningitis vaccine on pharyngeal carriage of Neisseria meningitidis was investigated. Carriage rates were determined in pupils at both secondary schools (ages 11-18 years) included in the community intervention programme and compared with two schools outside the area matched for socio-economic status. A total of 1869 pupils were studied 6 months after the programmes, and 2457 pupils after 11 months. Six months after the programme was completed there was a 72% reduction in pharyngeal carriage of Neisseria meningitidis in pupils attending the schools in the intervention area compared with pupils in the control schools. After 11 months this difference persisted in the 11-14 age group but not in the 15-18 age group. No resistance to the antibiotics used in the programme was found. A community intervention programme of antibiotics and vaccine for the control of meningococcal disease led to a long-term reduction in Neisseria meningitidis carriage in some age groups.

Community immunization programme in response to an outbreak of invasive Neisseria meningitidis serogroup C infection in the Trent region of England 1995-1996.

Between 8 December 1995 and 16 January 1996 seven laboratory confirmed cases of septicaemia owing to infection with Neisseria meningitidis serogroup C strains and one highly probable case of meningococcal septicaemia occurred in three electoral wards in south Rotherham and the Retford area of north Nottinghamshire. All cases occurred among children aged 1-17 years. One patient died. The public health response to this outbreak was the largest community prophylactic antibiotic and immunization programme against meningococcal infection, to date, in the United Kingdom. The target group for each Health Authority was 8900 for Rotherham Health Authorities and 8000 for North Nottinghamshire Health. Local logistical factors led to differences in the implementation of the programme by each Health Authority. At the completion of each programme, 8320 doses of vaccine had been administered (92.5 per cent coverage) during the Rotherham Health Authorities programme and 7660 (95.7 per cent coverage) during the North Nottinghamshire Health programme. The additional financial cost of the exercise amounted to approximately Pounds 125000 for each Health Authority. This paper describes the evolution of the outbreak, the decision-making process resulting in the immunization programme in each Health Authority, the implementation of each programme, problems identified and lessons learned.

An outbreak of infection with Salmonella enteritidis phage type 4 associated with the use of raw shell eggs.

A community outbreak of Salmonella enteritidis phage type (PT) 4 infection, associated with eating food from a sandwich bar in Colchester, occurred in July 1991. One hundred and forty-four people were reported with food poisoning, of whom 132 met the clinical case definition. Three cohort studies of 92 people showed that illness was associated with the consumption of food containing mayonnaise. S. enteritidis PT4, indistinguishable by plasmid profile analysis, was isolated from stool samples from 83 people, food items including egg shells from the sandwich bar, and birds taken from the egg producing farm which supplied the eggs. This was the largest recorded outbreak of S. enteritidis PT4 infection in recent years associated with eggs produced in the United Kingdom. Existing advice on avoiding the use of raw eggs in uncooked dishes had not been followed. This outbreak highlights the importance of training in the implementation of this advice.