Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland.

BACKGROUND: In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. METHODS: We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012. RESULTS: By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women. CONCLUSIONS: To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.

Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types.

BACKGROUND: In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12-13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12-13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%. METHODS: To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV. RESULTS: From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated. CONCLUSIONS: This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake.

Measles in Scotland, 2013.

In 2013, Wales and England experienced large outbreaks of measles, a disease that has been targeted by the World Health Organisation for European elimination by 2015. Unfortunately, measles-mumps-rubella vaccine uptake declined to less than 80% in Wales and England after the Wakefield publicity and this resulted in increased population susceptibility to measles. In Scotland, measles-mumps-rubella vaccine uptake dropped to 87% in 2003. Scottish public health efforts in response to this decline aimed to maximise uptake of MMR1 by two years; ensure at least 95% uptake of one dose of measles-mumps-rubella before starting school at age five; and maximise uptake of the second dose of measles-mumps-rubella by age six. Although Scotland has not had any large outbreaks reported to date, transmission of measles from healthcare workers to patients has occurred and reiterates the importance of all healthcare workers accurately knowing their immune status and, when needed, to be fully immunised.

The outcome of the movement disorder in methcathinone abusers: clinical, MRI and manganesemia changes, and neuropathology.

BACKGROUND AND PURPOSE: There is limited knowledge regarding the long-term outcome of the methcathinone/manganese-induced movement disorder. Our purpose was to define prognosis in intravenous methcathinone abusers affected by this distinctive disorder attributed to manganese (Mn) toxicity. Also, neuropathology from a globus pallidus region biopsy from a former user is reported. METHODS: Eighteen methcathinone abusers were categorized as active (five), discontinued (four) or former (nine) users. They were reassessed after a median of 32.5 months (range 3.4-59.6) clinically, on rating scales, and with MRI and blood Mn levels. The biopsy was examined ultrastructurally. RESULTS: Overall the group showed a slight tendency to deterioration at follow-up on clinical assessment of motor functioning, especially the active users. No significant change occurred on parkinsonian rating scale reassessment. Significant reduction in Mn levels occurred in former users, and decreased T1-weighted hyperintensity on basal ganglia MRI occurred in 3 of 4 former and 2 of 3 discontinued users, despite lack of clinical improvement. The biopsy consisted of white matter showing decompacted myelin sheaths and frequent abnormalities of mitochondria. CONCLUSIONS: No improvement in this Mn-induced movement disorder occurs after cessation of methcathinone abuse despite improvement of Mn blood levels and/or MRI abnormalities. Ultrastructural abnormalities in a former user confirm structural damage to white matter is associated with the disorder. Methcathinone/Mn toxicity is an important, disabling and permanent medical sequel of intravenous drug abuse in the former Soviet Union.

Cluster of Legionnaires disease cases caused by Legionella longbeachae serogroup 1, Scotland, August to September 2013.

We report six confirmed cases of Legionnaires' disease in Scotland caused by Legionella longbeachae serogroup 1, identified over a four-week period in August­September 2013. All cases required admission to hospital intensive care facilities. All cases were amateur gardeners with frequent exposure to horticultural growing media throughout their incubation period. L. longbeachae was identified in five samples of growing media linked to five cases. Product tracing did not identify a common product or manufacturer.

High uptake of HPV immunisation in Scotland--perspectives on maximising uptake.

In September 2008, Scotland introduced a national human papillomavirus (HPV) immunisation programme with bivalent HPV vaccine, to prevent cervical cancer. This school-based programme routinely vaccinates girls aged between 12 and 13 years. A catch-up campaign, running over three years, also began at this time, offering vaccination to all girls aged 13 years to under 18 years old. The HPV immunisation campaign presented challenges due to this vaccine being targeted to girls in school and older girls who had left school. Following a long and comprehensive planning process, this campaign was successfully implemented across Scotland, delivering high vaccine uptake of 91.4% for three doses of vaccine in the first year (September 2008 to August 2009) for the routine cohort and 90.1% in the second year (September 2009 to August 2010) for the routine cohort. We describe the planning process, challenges and implementation strategies employed to achieve this high uptake.

Public health response to an outbreak of Legionnaires' disease in Edinburgh, United Kingdom, June 2012.

We report an outbreak comprising 50 confirmed cases of Legionnaires' disease in Edinburgh, Scotland, June 2012. In addition, there were 49 suspected cases. Epidemiological evidence suggests that a common outdoor airborne exposure occurred over south-west Edinburgh. This probably emanated from cooling towers in the north-east of the affected area, although not yet clearly linked by scientific evidence. The co-ordinated public health, environmental and clinical response helped prevent ongoing exposure and mitigated associated mortality and morbidity.

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Tick-borne encephalitis in Latvia 1973-2009: epidemiology, clinical features and sequelae.

BACKGROUND AND PURPOSE: To report a 37-year observational experience in Latvia relating the incidence of human tick-borne encephalitis (TBE) and its clinical manifestations, to the field abundance of ticks. METHODS: Tick abundance was measured by standard flagging techniques. Incidence of human tick-borne disease was derived from Public Health reporting data. Clinical and follow-up data were determined from hospital cohorts from 1973 to 2009. RESULTS: Two TBE incidence peaks in the mid-1970s and the 1990s correlated with increased field abundance of ticks. Increased human TBE in the 1970s was associated with higher field abundance of both Ixodes ricinis and I. Persulcatus. The 1990s peak was particularly associated with I. ricinus, the species predominating in western/central Latvia, and with other factors, including changed agricultural land usage. Proportions of patients with meningitic or focal forms of TBE were similar in the two outbreaks and the intervening periods. Meningeal irritation occurred in 90%, altered consciousness in 19%, ataxia in 34%, seizures in 9%, bulbar features in 2-3% and limb weakness in 15% with shoulder amyotrophy predominating in 5%. Annual mortality varied from 0 to 1.3% and was not related to the overall incidence of TBE. Follow-up for 1-13 years of a cohort of 100 patients revealed long-term sequelae in over 50%, more commonly in those suffering focal forms of acute TBE. CONCLUSIONS: Clinical features and mortality of the 1970s and 1990s TBE outbreaks were similar and did not point to a change in virulence.

A survey of community exercise programmes for stroke survivors in Scotland.

Stroke is the most common cause of complex disability in the community. Physical fitness is often reduced after stroke, but training can improve fitness and function. UK and international stroke clinical guidelines recommend long-term exercise participation for stroke survivors. However, there has been no previous research into what services are available to support this. In 2009, we conducted the first European survey of community Exercise after Stroke services. A link to our web-based survey was emailed to health, leisure service and stroke charity contacts in Scotland with email and telephone follow-up to non-respondents. The overall response rate was 64% (230/361). A total of 14 Exercise after Stroke services were identified, the majority of which were run by charity collaborations (7/14), followed by leisure centre services (4/14) and health services (3/14). We sought information on session content, referral and assessment processes, and the qualifications of exercise instructors. This information was cross-referenced with current clinical and exercise guidelines to determine whether existing resources were sufficient to meet stroke survivors' needs for safe, effective and sustainable access to exercise. The results indicated a shortage of stroke-specific community exercise programmes. Further service development is required to ensure appropriate instructor training and referral pathways are in place to enable stroke survivors to access exercise services in accordance with current guidelines.

TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.

OBJECTIVE: To improve understanding of TRPV4-associated axonal Charcot-Marie-Tooth (CMT) neuropathy phenotypes and their debated pathologic mechanism. METHODS: A total of 17 CMT2C phenotypic families with vocal cord and diaphragmatic involvement and 36 clinically undifferentiated CMT2 subjects underwent sequencing analysis of the coding region of TRPV4. Functional studies of mutant proteins were performed using transiently transfected cells for TRPV4 subcellular localization, basal and stimulated Ca(2+) channel analysis, and cell viability assay with or without channel blockade. RESULTS: Two TRPV4 mutations R232C and R316H from 17 CMT2C families were identified in the ankyrin repeat domains. The R316H is a novel de novo mutation found in a patient with CMT2C phenotype. The family with R232C mutation had individuals with and without vocal cord and diaphragm involvement. Both mutant TRPV4 proteins had normal subcellular localization in HEK293 and HeLa cells. Cells transfected with R232C and R316H displayed increased intracellular Ca(2+) levels and reversible cell death by the TRPV channel antagonist, ruthenium red. CONCLUSION: TRPV4 ankyrin domain alterations including a novel de novo mutation cause axonal CMT2. Individuals with the same mutation may have nondistinct CMT2 or have phenotypic CMT2C with vocal cord paresis. Reversible hypercalcemic gain-of-function of mutant TRPV4 instead of loss-of-function appears to be pathologically important. The reversibility of cell death by channel blockade provides an attractive area of investigation in consideration of treatable axonal degeneration.

HPV type-specific prevalence using a urine assay in unvaccinated male and female 11- to 18-year olds in Scotland.

BACKGROUND: We conducted a baseline prevalence survey of unvaccinated 11- to 18-year olds to inform effectiveness studies for the new human papillomavirus (HPV) immunisation programme in Scotland. METHODS: Participants were recruited from schools and colleges and invited to provide demographic data and an anonymous urine sample for type-specific HPV testing. RESULTS: Among females aged 11-14 years, the weighted prevalence was 1.1% overall; 0.9% for high-risk types and no infections were associated with types 16 and 18. Among 15- to 18-year old females, the weighted prevalence was 15.2% overall; 12.6% for high-risk types and 6.5% for types 16 and 18. Among females aged 16-18 years, infection was more frequently associated with attending college and rural schools, and showed a trend towards increasing prevalence with increasing social deprivation (P=0.045). Among males aged 11-14 years, the weighted prevalence was 1.4% overall; 1.0% for high-risk types and 0.7% for types 16 and 18. Among 15- to 18-year old males, the weighted prevalence was 3.9% overall; 2.4% for high-risk types and 0.7% for types 16 and 18. CONCLUSIONS: Human Papillomavirus prevalence is low among 11- to 14-year olds, which includes the age group targeted for routine vaccination. The prevalence in males and correlation with deprivation require further investigation.

Should practitioners promote physical activity as a treatment for depression?

For many years, experts have been debating the pros and cons of exercise for depression. Proponents of exercise for depression point to those clinical trials which have shown that exercise improves mood, while sceptics point out the methodological problems in many of the apparently positive trials, and the uncertainties around the acceptability of exercise as a treatment for depression. Here two experts critically review the evidence around exercise for depression, provide arguments for and against the promotion of physical activity as a treatment for depression, explore issues around the generalisability of exercise as a treatment for depression and look to the future by discussing ongoing trials that will provide more evidence to inform this important debate.

Investigation of a Q fever outbreak in a Scottish co-located slaughterhouse and cutting plant.

Outbreaks of Q fever are rare in the UK. In 2006, the largest outbreak of Q fever in Scotland occurred at a co-located slaughterhouse and cutting plant with 110 cases. Preliminary investigations pointed to the sheep lairage being the potential source of exposure to the infective agent. A retrospective cohort study was carried out among workers along with environmental sampling to guide public health interventions. A total of 179 individuals were interviewed of whom 66 (37%) were migrant workers. Seventy-five (41.9%) were serologically confirmed cases. Passing through a walkway situated next to the sheep lairage, a nearby stores area, and being male were independently associated with being serologically positive for Q fever. The large proportion of migrant workers infected presented a significant logistical problem during outbreak investigation and follow up. The topic of vaccination against Q fever for slaughterhouse workers is contentious out with Australasia, but this outbreak highlights important occupational health issues.

A multi-data source surveillance system to detect a bioterrorism attack during the G8 Summit in Scotland.

In 18 weeks, Health Protection Scotland (HPS) deployed a syndromic surveillance system to early-detect natural or intentional disease outbreaks during the G8 Summit 2005 at Gleneagles, Scotland. The system integrated clinical and non-clinical datasets. Clinical datasets included Accident & Emergency (A&E) syndromes, and General Practice (GPs) codes grouped into syndromes. Non-clinical data included telephone calls to a nurse helpline, laboratory test orders, and hotel staff absenteeism. A cumulative sum-based detection algorithm and a log-linear regression model identified signals in the data. The system had a fax-based track for real-time identification of unusual presentations. Ninety-five signals were triggered by the detection algorithms and four forms were faxed to HPS. Thirteen signals were investigated. The system successfully complemented a traditional surveillance system in identifying a small cluster of gastroenteritis among the police force and triggered interventions to prevent further cases.

Treatment of vasculitic peripheral neuropathy: a retrospective analysis of outcome.

BACKGROUND: Vasculitis of the peripheral nervous system (PNS) is rare. There are no controlled treatment trials, and clinical practice is guided by experience from case series and indirectly by analogy with systemic vasculitis. METHODS: We identified patients (n=212) with possible vasculitic peripheral neuropathy (VPN) from the neuropathology and neurophysiology records of two centres over 28 years. Case-notes were available for 181, from which, 106 cases of clinicopathological VPN were identified. Adequate treatment data were available in 100; follow-up data, in 93. RESULTS: Of 106 cases, 95 had systemic vasculitis and 11 had vasculitis confined to the PNS. Pharmacological treatment (94/100 cases) was corticosteroid-based, and included cyclophosphamide in 54; 17 received additional agents. Initial stabilization was achieved in all but six. One-year survival was 90.3%. Of the nine who died in the first years (mean age 73 years), seven had received cyclophosphamide, and all but two had severe, multisystem vasculitis. The neurological relapse rate was 10%. Only one relapse occurred after cyclophosphamide treatment. Outcome was reported as good in 72% (78% in those who relapsed). DISCUSSION: Death and relapse were infrequent in treated patients. Relapse occurred almost exclusively in patients treated with prednisolone alone. Aggressive early treatment with cyclophosphamide may prevent relapse. The current management approach to VPN appears largely effective, especially if cyclophosphamide is used.

Causes of lumbosacral plexopathy.

The lumbosacral plexus represents the nerve supply to the lower back, pelvis and legs. This review will focus on diseases and disorders affecting the pathway as demonstrated by magnetic resonance imaging (MRI) and computed tomography (CT). We stress the need to review the lumbosacral plexus in patients with non-specific symptoms such as back, hip, pelvic pain, and in those who present with sciatica unaccompanied by demonstrable intervertebral disc prolapse. We illustrate that the imaging appearances may be non-specific and re-inforce the importance of the clinical history and the use of tissue sampling to achieve an accurate diagnosis.

Clinical features of double infection with tick-borne encephalitis and Lyme borreliosis transmitted by tick bite.

BACKGROUND: In Latvia and other endemic regions, a single tick bite has the potential to transmit both tick-borne encephalitis (TBE) and Lyme borreliosis. OBJECTIVE: To analyse both the clinical features and differential diagnosis of combined tick-borne infection with TBE and Lyme borreliosis, in 51 patients with serological evidence, of whom 69% had tick bites. RESULTS: Biphasic fever suggestive of TBE occurred in 55% of the patients. Meningitis occurred in 92%, with painful radicular symptoms in 39%. Muscle weakness occurred in 41%; in 29% the flaccid paralysis was compatible with TBE. Only two patients presented with the bulbar palsy typical of TBE. Typical Lyme borreliosis facial palsy occurred in three patients. Typical TBE oculomotor disturbances occurred in two. Other features typical of Lyme borreliosis detected in our patients were distal peripheral neuropathy (n = 4), arthralgia (n = 9), local erythema 1-12 days after tick bite (n = 7) and erythema chronicum migrans (n = 1). Echocardiogram abnormalities occurred in 15. CONCLUSIONS: Patients with double infection with TBE and Lyme borreliosis fell into three main clinical groups: febrile illness, 3 (6%); meningitis, 15 (30%); central or peripheral neurological deficit (meningoencephalitis, meningomyelitis, meningoradiculitis and polyradiculoneuritis), 33 (65%). Systemic features pointing to Lyme borreliosis were found in 25 patients (49%); immunoglobulin (Ig)M antibodies to borreliosis were present in 18 of them. The clinical occurrence of both Lyme borreliosis and TBE vary after exposure to tick bite, and the neurological manifestations of each disorder vary widely, with considerable overlap. This observational study provides no evidence that co-infection produces unusual manifestations due to unpredicted interaction between the two diseases. Patients with tick exposure presenting with acute neurological symptoms in areas endemic for both Lyme borreliosis and TBE should be investigated for both conditions. The threshold for simultaneous treatment of both conditions should be low, given the possibility of co-occurrence and the difficulty in ascribing individual neurological manifestations to one condition or the other.