The dark art of syphilis serology - an analysis of testing algorithms at a UK reference laboratory.

Introduction. Due to the complex nature of treponemal serology interpretation, testing algorithms vary across the UK.Gap statement. There is currently no gold standard method for interpretation of discordant serology results.Aim. To analyse serological response in early infection and to determine the best approach for discordant total antibody EIA and TPPA samples.Methodology. National reference laboratory serology and PCR (genital ulcer swabs) results from 2010 to 2017 were extracted from an electronic laboratory database.Results. A total of 24149 sera underwent analysis. Of syphilis PCR positive cases with contemporaneous sera, 33% (17/52) were IgM positive/equivocal, whilst all were EIA and TPPA positive. No sera with isolated IgM positivity (0/90) demonstrated seroconversion consistent with early treponemal infection, in contrast to 17% (2/12) of sera with isolated TPPA positivity. Isolated EIA positivity was observed in 6.2% (1499/24149) samples with the same result on repeat testing in 73% (154/211). In 100 samples with discordant EIA/TPPA results, IgG Immunoblot was more commonly positive (12/41, 29%) or equivocal (24/41, 59%), in those with a higher EIA antibody index, compared to those with a low antibody index, of which none tested positive and 2/3 (67 %) were equivocal.Conclusion. Isolated IgM positivity was not helpful in identifying early infection; isolated total antibody EIA positivity is unlikely to be a significant finding. IgG immunoblot testing was unable to determine clear treponemal antibody status in nearly half of all EIA/TPPA discordant samples.

The changing epidemiology of diphtheria in the United Kingdom, 2009 to 2017.

BackgroundDiphtheria is a potentially fatal disease caused by toxigenic strains of Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis.AimOur objective was to review the epidemiology of diphtheria in the United Kingdom (UK) and the impact of recent changes in public health management and surveillance.MethodsPutative human toxigenic diphtheria isolates in the UK are sent for species confirmation and toxigenicity testing to the National Reference Laboratory. Clinical, epidemiological and microbiological information for toxigenic cases between 2009 and 2017 are described in this population-based prospective surveillance study.ResultsThere were 33 toxigenic cases of diphtheria aged 4 to 82 years. Causative species were C. diphtheriae (n = 18) and C. ulcerans (n = 15). Most C. diphtheriae cases were cutaneous (14/18) while more than half of C. ulcerans cases had respiratory presentations (8/15). Two thirds (23/33) of cases were inadequately immunised. Two cases with C. ulcerans infections died, both inadequately immunised. The major risk factor for C. diphtheriae aquisition was travel to an endemic area and for C. ulcerans, contact with a companion animal. Most confirmed C. diphtheriae or C. ulcerans isolates (441/507; 87%) submitted for toxigenicity testing were non-toxigenic, however, toxin positivity rates were higher (15/23) for C. ulcerans than C. diphtheriae (18/469). Ten non-toxigenic toxin gene-bearing (NTTB) C. diphtheriae were also detected.ConclusionDiphtheria is a rare disease in the UK. In the last decade, milder cutaneous C. diphtheriae cases have become more frequent. Incomplete vaccination status was strongly associated with the risk of hospitalisation and death.

Antimicrobial stewardship: an evaluation of structure and process and their association with antimicrobial prescribing in NHS hospitals in England.

BACKGROUND: Rigorous antimicrobial stewardship programmes (ASPs) are an essential strategy against antimicrobial resistance. OBJECTIVES: To evaluate and score ASPs in acute English NHS hospitals and determine association of ASP scores with antimicrobial prescribing. METHODS: ASP structure and process were evaluated through an online survey in 148/152 acute hospitals in 2017. Scores were assigned to quality indicators based on resource- and labour-intensiveness, and their association with total and modified WHO-categorized 'Access', 'Watch' and 'Reserve' (AwaRe) prescribing was analysed. RESULTS: The survey response rate was 97% with 78% of trusts submitting antimicrobial prescribing data. Over 80% of ASPs contained stewardship teams, policies and access to outpatient parenteral antimicrobial therapy, whilst less than 50% scored well for leadership or funding. High process performance was observed for antimicrobial pre-authorization, prescribing review and feedback, restricted susceptibility reporting, antimicrobial consumption monitoring, adherence to guidelines and junior doctor training. Low process attainment included education of senior prescribers and lack of resistance surveillance data distribution. Between 2016 and 2017, there was no difference in total trust prescribing (P = 0.117) although carbapenem prescribing fell (incidence rate ratio = 0.93, 95% CI 0.88-0.98) in non-teaching hospitals; 'Watch' prescribing also increased for specialist hospitals (OR = 1.10, 95% CI 1.01-1.20), as did 'Reserve' category prescribing in teaching (OR = 1.58, 95% CI 1.23-3.02) and specialist hospitals (OR = 3.09, 95% CI 2.02-4.74). A high process score was associated with lower 'Reserve' prescribing (OR = 0.82, 95% CI 0.67-1.01). CONCLUSIONS: All responding trusts had established ASPs. The association of a scoring system with total and 'AWaRe' prescribing to assess effectiveness of ASPs merits further study.

Mortality risk factors for listeriosis - A 10 year review of non-pregnancy associated cases in England 2006-2015.

LISTERIOSIS: is a foodborne illness that can result in septicaemia, Central Nervous System (CNS) disease, foetal loss and death in high risk patients. OBJECTIVES: To analyse the demographic trends, clinical features and treatment of non-perinatal listeriosis cases over a ten year period and identify mortality-associated risk factors. METHODS: Reported laboratory-confirmed non-pregnancy associated cases of listeriosis between 2006 and 2015 in England were included and retrospectively analysed. Multivariate logistic regression analysis was performed to determine independent risk factors for mortality. RESULTS: 1357/1683 reported cases met the inclusion criteria. Overall all-cause mortality was 28.7%; however, mortality rates declined from 42.1% to 20.2%. Septicaemia was the most common presentation 69.5%, followed by CNS involvement 22.4%. CNS presentations were significantly associated with age < 50 years, and septicaemia with older age. Age > 80 years (OR 3.32 95% CI 1.92-5.74), solid-organ malignancy (OR 3.42 95% CI 2.29-5.11), cardiovascular disease (OR 3.30 95% CI 1.64-6.63), liver disease (OR 4.61 95% CI 2.47-8.61), immunosuppression (OR 2.12 95% CI 1.40-3.21) and septicaemia (OR 1.60 95% CI 1.17-2.20) were identified as independent mortality risk factors. CONCLUSIONS: High risk groups identified in this study should be the priority focus of future public health strategies aimed at reducing listeriosis incidence and mortality.