Development of a Core Outcome Measure Instrument; "LeishCOM_LCL", for Localised Cutaneous Leishmaniasis.

BACKGROUND: Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL. METHODOLOGY & PRINCIPAL FINDINGS: A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders' meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. "Clinical Cure" was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach. CONCLUSION: LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future.

First Evidence from Sri Lanka for Subphenotypic Diversity within L. donovani-Induced Classical Cutaneous Leishmaniasis.

Sri Lanka reports a large focus of Leishmania donovani-induced cutaneous leishmaniasis (CL) with CL as the main clinical entity. Two independent, long existed, and clinicoepidemiologically different transmission foci in the northern region (NR) and southern region (SR) were recently reported. Current project is an extension to this previous study. Clinical diversity within a profile of classical cutaneous leishmaniasis (CCL) in a focus of L. donovani-induced CL is described for the first time. Patients with laboratory confirmed CCL (n = 550) from NF and SF were evaluated. Lesions in both foci were found to have all classical developmental stages (small and large nodules, ulcerating nodules, and ulcers) and other identified changes (multiplication, ulceration, and enlargement). Main difference was in the proportions of lesions progressing in to each different stages, proportions of lesion undergoing the main changes, and in timing of these changes during the course of a lesion. Northern focus reported a smaller proportion of lesions showing enlargement and ulceration, and a longer period of time was also required for these changes when compared to same in southern focus. In northern focus, most lesions remained small and nonulcerating and showed a higher tendency to multiply while most lesions reported in southern focus enlarged and ulcerated rapidly and remained single. Current study also evidenced a wider spectrum in the rate and pattern of progression of a skin lesion and high individual variation which could mask these region-based differences. Parasitic, vector-related, or a host etiology is suggested. Slow progressing nonulcerating infections in North may be the result of a well-adopted parasite strain that coevolved with its host for a long period while inducing only a minimal host response. This could be one among many reasons for previously observed silent expansion in northern focus while southern focus remained more confined and stable over time. Small nonprogressive, nondisturbing lesions can play a major role as silent parasite reservoirs in a community. In addition, the laboratory detection rate declined significantly when lesions multiplied and enlarged indicating the need for early laboratory confirmation. Usefulness of identified features in clinical screening and management needs to be considered.

Trends in Recently Emerged Leishmania donovani Induced Cutaneous Leishmaniasis, Sri Lanka, for the First 13 Years.

Sri Lanka reports a large epidemic of cutaneous leishmaniasis (CL) caused by an atypical L. donovani while regional leishmaniasis elimination drive aims at achieving its targets in 2020. Visceralization, mucotrophism, and CL associated poor treatment response were recently reported. Long-term clinico-epidemiological trends (2001-2013) in this focus were examined for the first time. Both constant and changing features were observed. Sociodemographic patient characteristics that differ significantly from those of country profile, microchanges within CL profile, spatial expansion, constant biannual seasonal variation, and nondependency of clinical profile on age or gender were evident. Classical CL remains the main clinical entity without clinical evidence for subsequent visceralization indicating presence of parasite strain variation. These observations make a scientific platform for disease control preferably timed based on seasonal variation and highlights the importance of periodic and continued surveillance of clinic-epidemiological and other characteristics.

First Evidence for Two Independent and Different Leishmaniasis Transmission Foci in Sri Lanka: Recent Introduction or Long-Term Existence?

Cutaneous leishmaniasis caused by a genetic variant of L. donovani is being reported from Sri Lanka since year 2001. Patients presented from different geographical locations (600 patients from North or South and a minority of cases from other foci, 2001-2013) were studied. Analysis revealed two different sociodemographic and clinical profiles of leishmaniasis in Northern and Southern Sri Lanka. Also, the same different profiles were present in these foci since the onset of the recent outbreak and had independently propagated within each focus over the time. A profile of 14 parameters identified in the Northern focus was further examined with regard to other locations. Northwestern (10/14) and Central parts (9/14) of the island were more similar to Northern focus (14/14). Infection would have originated in one focus and spread to other 2 in Northern Sri Lanka. Southern focus was different from and appeared older than all others (2/14). Western focus that accommodates a large transient population had a mixed picture of North and South features (4/14). Lesions in North showed a slow progression and a nonulcerative nature (128/185, 69.2%), while those in South showed a rapid progression and less nonulcerative lesions (193/415, 46.5%). Clinical analysis favoured a parasite aetiology (considerable strain differences) rather than a host aetiology (age, gender, or genetics). Both foci demonstrated a biannual seasonal variation since the onset of the epidemic. Two peaks were observed during the early and latter parts of the year. Furthermore, long-term existence and recent spatiotemporal expansion and detection of leishmaniasis in this country rather than a recent introduction and establishment were indicated by these findings. Vigorous antimalarial activities that existed in Sri Lanka until few decades ago, lack of professional awareness, and more recent military activities that brought human population in close contact with a sylvatic cycle would have played a role in silent propagation of Leishmania parasites and subsequent increment in human cases, respectively, in this country.

Leprosy type 1 reactions and erythema nodosum leprosum: [review]

Leprosy reactions are a major cause of nerve damage and morbidity in a significant proportion of leprosy patients. Reactions are immunologically mediated and can occur even after successful completion of multi-drug therapy. This review focuses on the epidemiology, pathology and treatment of leprosy type 1 reactions, erythema nodosum leprosum and silent neuropathy.

As reações hansênicas são a principal causa de dano e morbidade neural em grande parte dos pacientes hansênicos. São imunomediadas e podem ocorrer mesmo após o término bem sucedido da poliquimioterapia. Esta revisão enfoca a epidemiologia, a patologia e o tratamento das reações hansênicas do tipo 1, do eritema nodoso hansênico e da neuropatia silenciosa.