A modelling analysis of a new multi-stage pathway for classifying achievement of public health milestones for leprosy.

Several countries have come close to eliminating leprosy, but leprosy cases continue to be detected at low levels. Due to the long, highly variable delay from infection to detection, the relationship between observed cases and transmission is uncertain. The World Health Organization's new technical guidance provides a path for countries to reach elimination. We use a simple probabilistic model to simulate the stochastic dynamics of detected cases as transmission declines, and evaluate progress through the new public health milestones. In simulations where transmission is halted, 5 years of zero incidence in autochthonous children, combined with 3 years of zero incidence in all ages is a flawed indicator that transmission has halted (54% correctly classified). A further 10 years of only occasional sporadic cases is associated with a high probability of having interrupted transmission (99%). If, however, transmission continues at extremely low levels, it is possible that cases could be misidentified as historic cases from the tail of the incubation period distribution, although misleadingly achieving all three milestones is unlikely (less than 1% probability across a 15-year period of ongoing low-level transmission). These results demonstrate the feasibility and challenges of a phased progression of milestones towards interruption of transmission, allowing assessment of programme status. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Diagnosing and treating leprosy in a non-endemic setting in a national centre, London, United Kingdom 1995-2018.

BACKGROUND: Leprosy is rare in the United Kingdom (UK), but migration from endemic countries results in new cases being diagnosed each year. We documented the clinical presentation of leprosy in a non-endemic setting. METHODS: Demographic and clinical data on all new cases of leprosy managed in the Leprosy Clinic at the Hospital for Tropical Diseases, London between 1995 and 2018 were analysed. RESULTS: 157 individuals with a median age of 34 (range 13-85) years were included. 67.5% were male. Patients came from 34 different countries and most contracted leprosy before migrating to the UK. Eighty-two (51.6%) acquired the infection in India, Sri Lanka, Bangladesh, Nepal and Pakistan. 30 patients (19.1%) acquired leprosy in Africa, including 11 from Nigeria. Seven patients were born in Europe; three acquired their leprosy infection in Africa, three in South East Asia, and one in Europe. The mean interval between arrival in the UK and symptom onset was 5.87 years (SD 10.33), the longest time to diagnosis was 20 years. Borderline tuberculoid leprosy (n = 71, 42.0%), and lepromatous leprosy (n =, 53 33.1%) were the commonest Ridley Jopling types. Dermatologists were the specialists diagnosing leprosy most often. Individuals were treated with World Health Organization recommended drug regimens (rifampicin, dapsone and clofazimine). CONCLUSION: Leprosy is not a disease of travellers but develops after residence in an leprosy endemic area. The number of individuals from a leprosy endemic country reflect both the leprosy prevalence and the migration rates to the United Kingdom. There are challenges in diagnosing leprosy in non-endemic areas and clinicians need to recognise the symptoms and signs of leprosy.

Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the 'MTX and prednisolone study in ENL' (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL. METHODS AND ANALYSIS: MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients' reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events. ETHICS AND DISSEMINATION: Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

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

Improving physical health care in a mental health trust.

It is a challenge both to general medicine and psychiatry to develop systems that are better equipped to meet the physical health needs of mental health patients and reduce mortality rates (Hansen et al, 1997). Central and North West London Mental Health NHS Trust is establishing a department of physical health care staffed by nurses with general nursing backgrounds to tackle this problem. This nurse-led department is designed to train nurses and doctors in key aspects of physical health assessment and treatment interventions.

Osler and the skin.

William Osler was the greatest physician of his time. Specialists reading his textbooks agreed that in their own specialities he was accurate and illuminating. His grasp of dermatology was particularly striking and skin changes are prominent in five of the syndromes named after him and in at least 100 of his papers. This paper describes how his early training in dermatology under Tilbury Fox in London and Hebra in Vienna combined with his unusual personal qualities to enable him to make massive contributions to a wide variety of dermatological topics. These include smallpox, cutaneous tuberculosis, nail growth, leprosy, scleroderma, pigmentation and purpuric eruptions as well as the more obvious hereditary haemorrhagic telangiectasia, angio-neurotic oedema and Osler's nodes.

Kellersberger Memorial Lecture 1998: Nerve Damage in Leprosy: a problem for patients, doctors and scientists.

There are interesting challenges in leprosy right now. The last fifteen years have seen the world-wide implementation of multidrug therapy with tangible benefits for patients and doctors. Paradoxically this success has revealed how much we still need to understand about leprosy nerve damage. For patients it is imperative that nerve damage is detected at an early stage when damage is still reversible. They need effective education to prevent the development of disability and to minimise the social and economic effects of nerve damage. For doctors and paramedical workers nerve damage needs effective treatment. We need to use current treatments effectively and also develop new treatments. This lecture looks critically at the pathology, detection and treatment of nerve damage, reviewing our present knowledge and looking to future developments.

Fly me, I'm tropical.

Leprosy, malaria and jigger fleas are all in a week's work for London's Hospital for Tropical Diseases. But some fear that the internal market could bring its 170-year history to a close, reports Annabelle May.

Giant reactions to tuberculin in lepromatous leprosy patients.

A detailed account and definition is given of the previously inadequately described "giant reactions" to tuberculin occasionally seen in leprosy patients. The reaction is an accelerated and exaggerated response to species-specific antigens of Mycobacterium tuberculosis found in both PPD and New tuberculin. Our studies were performed in Malaysia, Uganda, Spain, and England. There was a significantly higher incidence of the phenomenon in Malaysia than in the other centers, but this may have been because there alone previously untreated lepromatous (LL and BL) patients were serially tested for up to three years after starting chemotherapy. Of the 28 patients exhibiting giant reactions, 27 occurred among lepromatous patients (24 LL and 3 BL), of which only 3 (1 LL and 2 BL) were untreated. One treated BL patient had developed, and one untreated BL patient was a family contact of, active tuberculosis. Giant reactions are uncommon in untreated and in very long-term treated LL patients, but may occur in up to a fifth of those receiving their first 1-3 years of chemotherapy. Although the mechanism is not yet understood, it appears to be a coincidence of delayed hypersensitivity of the tuberculin type and a less-delayed phenomenon of excessive local edema associated with local lymphadenopathy and short-lasting symptoms of malaise and pyrexia. It is suggested that the majority of giant reactions occur during a period of temporary lack of immune regulation associated with changing levels of antigenic load.