[A global core outcome measurement set for snakebite clinical trials]. / Définition d'un jeu universel de critères de décision de base pour les essais cliniques sur les morsures de serpent.

Background: Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. Method: A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Results: Five universal core outcome measures should be included in all future snakebite clinical trials: mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. Conclusion: This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

Optimization of high-throughput 16S rRNA gene amplicon sequencing: an assessment of PCR pooling, mastermix use and contamination.

16S rRNA gene sequencing is widely used to characterize human and environmental microbiomes. Sequencing at scale facilitates better powered studies but is limited by cost and time. We identified two areas in our 16S rRNA gene library preparation protocol where modifications could provide efficiency gains, including (1) pooling of multiple PCR amplifications per sample to reduce PCR drift and (2) manual preparation of mastermix to reduce liquid handling. Using nasal samples from healthy human participants and a serially diluted mock microbial community, we compared alpha and beta diversity, and compositional abundance where the PCR amplification was conducted in triplicate, duplicate or as a single reaction, and where manually prepared or premixed mastermix was used. One hundred and fifty-eight 16S rRNA gene sequencing libraries were prepared, including a replicate experiment. Comparing PCR pooling strategies, we found no significant difference in high-quality read counts and alpha diversity, and beta diversity by Bray-Curtis index clustered by replicate on principal coordinate analysis (PCoA) and non-metric dimensional scaling (NMDS) analysis. Choice of mastermix had no significant impact on high-quality read and alpha diversity, and beta diversity by Bray-Curtis index clustered by replicate in PCoA and NMDS analysis. Importantly, we observed contamination and variability of rare species (<0.01 %) across replicate experiments; the majority of contaminants were accounted for by removal of species present at <0.1 %, or were linked to reagents (including a primer stock). We demonstrate no requirement for pooling of PCR amplifications or manual preparation of PCR mastermix, resulting in a more efficient 16S rRNA gene PCR protocol.

Applications to medical and surgical specialist training in the UK National Health Service, 2021-2022: a cross-sectional observational study to characterise the diversity of successful applicants.

OBJECTIVES: To compare success of applicants to specialty training posts in the UK by gender, ethnicity and disability status. DESIGN: Cross-sectional observational study. SETTING: National Health Service, UK. PARTICIPANTS: All specialty training post applications to Health Education England, UK, during the 2021-2022 recruitment cycle. INTERVENTION: Nil. PRIMARY AND SECONDARY OUTCOME MEASURES: Comparison of success at application to specialty training posts by gender, ethnicity, country of qualification (UK vs non-UK) and disability. The influence of ethnicity on success was investigated using a logistic regression model, where country of qualification was included as a covariate. RESULTS: 12 419/37 971 (32.7%) of applicants to specialty training posts were successful, representing 58 specialties. The difference in percentage of successful females (6480/17 523, 37.0%) and males (5625/19 340, 29.1%) was 7.9% (95% CI 6.93% to 8.86%), in favour of females. Segregation of applications to specialties by gender was observed; surgical specialties had the highest proportion of male applicants, while obstetrics and gynaecology had the highest proportion of female applicants. The proportion of successful recruits to specialties largely reflected the number of applications. 11/15 minority ethnic groups (excluding 'not stated') had significantly lower adjusted ORs for success compared with white-British applicants. 'Mixed white and black African' (OR 0.52, 95% CI 0.44 to 0.61, p≤0.001) were the least successful minority group in our study, while non-UK graduates had an adjusted ORs for success of 0.43 (95% CI 0.41 to 0.46, p≤0.001) compared with UK graduates. The difference in percentage of success by disabled applicants (179/464, 38.6%) and non-disabled applicants (11 940/36 418, 32.8%) was 5.79% (95% CI 1.23% to 10.4%), in favour of disabled applicants. No disabled applicants were accepted to 21/58 (36.2%) of specialties. CONCLUSIONS: Despite greater success by female applicants overall, there is an attraction issue to specialties by gender. Further, most ethnic minority groups are less successful at application when compared with white-British applicants. This requires continuous monitoring and evaluation of the reasons behind observed differences. TRIAL REGISTRATION: Not applicable.

Colonization and transmission of Staphylococcus aureus in schools: a citizen science project.

Aggregation of children in schools has been established to be a key driver of transmission of infectious diseases. Mathematical models of transmission used to predict the impact of control measures, such as vaccination and testing, commonly depend on self-reported contact data. However, the link between self-reported social contacts and pathogen transmission has not been well described. To address this, we used Staphylococcus aureus as a model organism to track transmission within two secondary schools in England and test for associations between self-reported social contacts, test positivity and the bacterial strain collected from the same students. Students filled out a social contact survey and their S. aureus colonization status was ascertained through self-administered swabs from which isolates were sequenced. Isolates from the local community were also sequenced to assess the representativeness of school isolates. A low frequency of genome-linked transmission precluded a formal analysis of links between genomic and social networks, suggesting that S. aureus transmission within schools is too rare to make it a viable tool for this purpose. Whilst we found no evidence that schools are an important route of transmission, increased colonization rates found within schools imply that school-age children may be an important source of community transmission.

A global core outcome measurement set for snakebite clinical trials.

Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK.

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organization as Alpha. Originating in early autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK and the imposition of new restrictions, in particular, the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages that preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically infected individual. We conclude that the latter provides the best explanation of the observed behaviour and dynamics of the variant, although the individual need not be immunocompromised, as persistently infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs and find that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations and a lack of the rapid evolutionary rate on its ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms), it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission.

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission.

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.

The role of viral genomics in understanding COVID-19 outbreaks in long-term care facilities.

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.

Donor acquired visceral leishmaniasis following liver transplantation.

Patients who undergo solid organ transplantation are at risk of opportunistic infection associated with immunosuppression. We report a case of confirmed donor derived visceral leishmaniasis (VL), in a patient following liver transplantation causing fever and pancytopenia. The diagnosis was confirmed by bone marrow biopsy, with confirmed positive donor serology, with no other route of transmission. To our knowledge, this is the first case report in the United Kingdom and Europe, of confirmed organ donor transmission of VL. This case report highlights an important consideration of donor derived infections, in the context of solid organ transplantation.

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review.

BACKGROUND: Snakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite. METHODS: All randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160. RESULTS: This systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain ('venom antigenaemia') was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies. DISCUSSION: Significant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials.

Large-scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management.

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organizations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1565 positive samples (172 per 100 000 population) from 1376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6 % of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. In total, 1035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore, 100 genetically distinct UK lineages were detected demonstrating local evolution, at a rate of ~2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a discrete sublineage associated with six care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients, indicating infection control measures were effective; and found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.

Failure of rapid diagnostic tests in Plasmodium falciparum malaria cases among travelers to the UK and Ireland: Identification and characterisation of the parasites.

OBJECTIVES: Our objective was to systematically investigate false-negative histidine-rich protein 2 rapid diagnostic tests (HRP2-RDT) in imported Plasmodium falciparum malaria cases from travelers to the UK and the Republic of Ireland (RoI). METHODS: Five imported malaria cases in travellers returning to the UK and RoI from East Africa were reported to the PHE Malaria Reference Laboratory as negative according to histidine-rich protein (HRP2)-RDT. The cases were systematically investigated using microscopic, RDT, molecular, genomic, and in in vitro approaches. RESULTS: In each case, HRP2-RDT was negative, whereas microscopy confirmed the presence of P. falciparum. Further analysis revealed that the genes encoding HRP2 and HRP3 were deleted in three of the five cases. Whole-genome sequencing in one of these isolates confirmed deletions in P. falciparum chromosomes 8 and 13. Our study produced evidence that the fourth case, which had high parasitemia at clinical presentation, was a rare example of antigen saturation ('prozone-like effect'), leading to a false negative in the HRP2-RDT, while the fifth case was due to low parasitemia. CONCLUSIONS: False-negative HRP2-RDT results with P. falciparum are concerning. Our findings emphasise the necessity of supporting the interpretation of RDT results with microscopy, in conjunction with clinical observations, and sets out a systematic approach to identifying parasites carrying pfhrp2 and pfhrp3 deletions.

Genomic epidemiology of COVID-19 in care homes in the east of England.

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.

Delayed diagnosis of spinal cord schistosomiasis in a non-endemic country: A tertiary referral centre experience.

BACKGROUND: Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre. MATERIALS/METHODS: A retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected. RESULTS: Four cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16-74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation. CONCLUSION: We observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis.

Clinical utility and cost-effectiveness of bacterial 16S rRNA and targeted PCR based diagnostic testing in a UK microbiology laboratory network.

16S ribosomal-ribonucleic acid polymerase chain reaction (PCR) and targeted PCR aid microbiological diagnosis in culture-negative clinical samples. Despite routine clinical use, there remains a paucity of data on their effectiveness across a variety of clinical sample types, and cost-effectiveness. In this 4 year multicentre retrospective observational study, all clinical samples referred for 16S PCR and/or targeted PCR from a laboratory network serving seven London hospitals were identified. Laboratory, clinical, prescribing, and economic variables were analysed. 78/607 samples were 16S PCR positive; pus samples were most frequently positive (29/84; p < 0.0001), and CSF least (8/149; p = 0.003). 210/607 samples had targeted PCR (361 targets requested across 23 organisms) with 43/361 positive; respiratory samples (13/37; p = 0.01) had the highest detection rate. Molecular diagnostics provided a supportive microbiological diagnosis for 21 patients and a new diagnosis for 58. 14/91 patients with prescribing information available and a positive PCR result had antimicrobial de-escalation. For culture-negative samples, mean cost-per-positive 16S PCR result was £568.37 and £292.84 for targeted PCR, equating to £4041.76 and £1506.03 respectively for one prescription change. 16S PCR is more expensive than targeted PCR, with both assisting in microbiological diagnosis but uncommonly enabling antimicrobial change. Rigorous referral pathways for molecular tests may result in significant fiscal savings.

The use of biomarkers as a tool for novel psoriatic disease drug discovery.

INTRODUCTION: Psoriatic disease is a relatively new term which encompasses psoriatic arthritis, psoriasis, and associated comorbidities. In this heterogeneous condition, the study of biomarkers is necessary to direct best therapy. Resulting in significant disability and socioeconomic burden, recent recommendations stress the need for tight control in psoriatic disease. Areas covered: The authors outline recent advances in the understanding of psoriatic disease pathogenesis which has highlighted multiple biomarkers that have been pursued as drug targets with varying degrees of success. Current drugs targeting biomarkers and therapies in development are evaluated. The methods of biomarker discovery through genomics, transcriptomics, proteomics, metabolomics, and study of the microbiome are also discussed. Expert opinion: Targeting biomarkers for therapeutic benefit appears to a promising field with multiple success stories, notably those associated with signaling through T-helper-17 cells. The use of genomics, transcriptomics, proteomics, and more recently metabolomics will help individualize targeted biomarker therapies, assist in monitoring therapeutic success, and ultimately yield novel therapeutic targets. Advances in the development of novel biologic molecules targeting more than one cytokine may offer additional gains in therapeutic response.

Administración de esteroides y talidomida para el control del eritema nodoso leproso durante 17 años en el hospital para enfermedades tropicales de Londres / No disponible

Objetivos: La prednisolona y la talidomida se administran frecuentemente en el control del eritema nodoso leproso (ENL) y proporcionan alivio a los pacientes con esta condición en todo el mundo. Sin embargo, tanto el ENL como sus tratamientos causan gran morbilidad. Este trabajo describe el espectro del ENL observado en el Hospital para Enfermedades Tropicales de Londres (HTD), la utilización de esteroides y el uso de esteroides y talidomida en su control y las consiguientes complicaciones. Metodología: Se llevó a cabo una revisión retrospectiva de los pacientes diagnosticados con ENL entre 1996 y 2013. Los datos se obtuvieron de los archivos clínicos, incluyendo la severidad y duración del episodio, además del tratamiento y efectos adversos. Resultados: Entre 1996 y 2013 se diagnosticaron 30 pacientes con ENL. El índice bacteriológico (IB) promedio en el momento del diagnóstico fue > 4.65, superior al aceptado en otros estudios. La mayoría de los pacientes desarrollaron ENL durante el tratamiento (67%) y presentaron ENL crónico (57%). La duración media del ENL fue de 60 meses (rango 9-192); los pacientes con IB > 4.5 presentaron períodos de tiempo más largos. El 87% de los pacientes recibieron prednisolona durante 9 meses; 33% desarrolló efectos adversos, incluyendo diabetes e hipertensión; el 87% de los pacientes recibió talidomida durante 16 meses y el 65% presentó efectos adversos. No hubo casos de embarazo o tromboembolismo. El 77% de los pacientes dejó la prednisolona a los dos meses de iniciar la talidomida. No hubo casos de fallecimiento en nuestro grupo. Conclusión: Describimos el curso clínico del ENL en un país no endémico con acceso a la talidomida y prednisolona. El ENL puede durar mucho más que el tiempo descrito anteriormente y tiene un gran impacto sobre la salud del paciente. En el Reino Unido, la talidomida es esencial para cesar la administración de los esteroides, prevenir efectos adversos y la mortalidad por esteroides, lo cual esté documentado en otros trabajos

Objectives: Prednisolone and thalidomide are commonly used in the management of erythema nodosum leprosum (ENL) and bring relief to patients with this condition worldwide. However, both ENL and its treatments can cause significant morbidity. This study describes the spectrum of ENL seen at The Hospital for Tropical Diseases, London (HTD), the use of steroids and thalidomide in its management and the complications of their use. Study Design: We conducted a retrospective audit of patients diagnosed with ENL between 1996 and 2013. Data were obtained from hospital records including severity and length of disease, together with treatments received and adverse effects. Results: Between 1996 and 2013, 30 patients were diagnosed with ENL. The median bacillary index (BI) at diagnosis was 4.65, higher than in previous studies. Most patients developed ENL during leprosy treatment (67%) and had chronic ENL (57%). The median length of ENL was 60 months (range 9-192); patients with BI. 4.5 had significantly longer duration of disease. 87% patients received prednisolone for median nine months; 35% developed adverse effects including diabetes and hypertension. 87% patients received thalidomide for median 16 months; 65% complained of side effects. There were no pregnancies or venous thromboembolisms. 77% patients stopped prednisolone within two months of starting thalidomide. There were no deaths in our cohort. Conclusion: We describe the clinical course of ENL in a non-endemic country with access to thalidomide and prednisolone. ENL may last far longer than previously described and has significant impact on a patient’s health. In the UK, thalidomide is essential as a steroid-sparing agent, to prevent the adverse effects and mortality of longterm steroids which have been documented elsewhere