Oriol Mitjà * E-mail: oriol.mitja@isglobal.org Affiliations Skin NTDs Program, Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain, Division of Public ...Health, School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea ORCID http://orcid.org/0000-0003-3266-8868 Michael Marks Affiliations Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom, Hospital for Tropical Diseases, University College London Hospitals NHS Trust, London, United Kingdom ORCID http://orcid.org/0000-0002-7585-4743 Laia Bertran Affiliation: Skin NTDs Program, Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain Karsor Kollie Affiliation: Neglected Tropical and Non Communicable Diseases Program, Ministry of Health, Government of Liberia, Liberia Daniel Argaw Affiliation: Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland Ahmed H. Fahal Affiliation: The Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan Christopher Fitzpatrick Affiliation: Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland L. Claire Fuller Affiliation: International Foundation for Dermatology, London, United Kingdom Bernardo Garcia Izquierdo Affiliation: Anesvad foundation, Bilbao, Spain Roderick Hay Affiliation: International Foundation for Dermatology, London, United Kingdom Norihisa Ishii Affiliation: Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan Christian Johnson Affiliation: Fondation Raoul Follereau, Cotonou, République du Bénin Jeffrey V. Lazarus Affiliation: Skin NTDs Program, Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain Anthony Meka Affiliation: Medical Department, German Leprosy and TB Relief Association, Enugu, Nigeria Michele Murdoch Affiliation: Department of Dermatology, Watford General Hospital, Watford, United Kingdom Sally-Ann Ohene Affiliation: World Health Organization Country Office, Accra, Ghana Pam Small Affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America Andrew Steer Affiliation: Group A Streptococcal Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia Earnest N. Tabah Affiliation: National Yaws, Leishmaniasis, Leprosy and Buruli ulcer Control Programme, Ministry of Public Health, Yaoundé, Cameroon Alexandre Tiendrebeogo Affiliation: World Health Organization Regional Office for Africa, Brazzaville, Congo Lance Waller Affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America Rie Yotsu Affiliation: Department of Dermatology, National Center for Global Health and Medicine, Tokyo, Japan Stephen L. Walker Affiliation: Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom Kingsley Asiedu Affiliation: Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, SwitzerlandCitation: Mitjà O, Marks M, Bertran L, Kollie K, Argaw D, Fahal AH, et al. Research * Validating a clinical algorithm for identification of skin NTDs using key symptoms and signs. * Developing common clinical and laboratory diagnostic platforms for these diseases, which are practical in the field. * Mapping to identify their overlap to allow integrated coordinated control and treatment activities as well as health system strengthening for service delivery. * Piloting the integrated approach in one or several regions. * Better understanding of the epidemiology of these diseases including transmission and interaction with poverty and water, sanitation, and hygiene (WASH). * Understand community resilience and program factors that strengthen community participation.
Scabies outbreaks in residential and nursing care homes for elderly people are common, subject to diagnostic delay, and hard to control. We studied clinical features, epidemiology, and outcomes of ...outbreaks in the UK between 2014 and 2015.
We did a prospective observational study in residential care homes for elderly people in southeast England that reported scabies outbreaks to Public Health England health protection teams. An outbreak was defined as two or more cases of scabies (in either residents or staff) at a single care home. All patients who provided informed consent were included; patients with dementia were included if a personal or nominated consultee (ie, a family member or nominated staff member) endorsed participation. Dermatology-trained physicians examined residents at initial clinical visits, which were followed by two mass treatments with topical scabicide as per local health protection team guidance. Follow-up clinical visits were held 6 weeks after initial visits. Scabies was diagnosed through pre-defined case definitions as definite, probable, or possible with dermatoscopy and microscopy as appropriate.
230 residents were examined in ten outbreaks between Jan 23, 2014, and April 13, 2015. Median age was 86·9 years (IQR 81·5–92·3), 174 (76%) were female, and 157 (68%) had dementia. 61 (27%) residents were diagnosed with definite, probable, or possible scabies, of whom three had crusted scabies. Physical signs differed substantially from classic presentations. 31 (51%) of the 61 people diagnosed with scabies were asymptomatic, and only 25 (41%) had burrows. Mites were visualised with dermatoscopy in seven (11%) patients, and further confirmed by microscopy in three (5%). 35 (57%) cases had signs of scabies only on areas of the body that would normally be covered. Dementia was the only risk factor for a scabies diagnosis that we identified (odds ratio 2·37 95% CI 1·38–4·07). At clinical follow-up, 50 people who were initially diagnosed with scabies were examined. No new cases of scabies were detected, but infestation persisted in ten people.
Clinical presentation of scabies in elderly residents of care homes differs from classic descriptions familiar to clinicians. This difference probably contributes to delayed recognition and suboptimal management in this vulnerable group. Dermatoscopy and microscopy were of little value. Health-care workers should be aware of the different presentation of scabies in elderly people, and should do thorough examinations, particularly in people with dementia.
Public Health England and British Skin Foundation.
Erythema nodosum leprosum (ENL) is a painful inflammatory complication of leprosy occurring in 50% of lepromatous leprosy patients and 5-10% of borderline lepromatous patients. It is a significant ...cause of economic hardship, morbidity and mortality in leprosy patients. Our understanding of the causes of ENL is limited. We performed a systematic review of the published literature and critically evaluated the evidence for the role of neutrophils, immune complexes (ICs), T-cells, cytokines, and other immunological factors that could contribute to the development of ENL. Searches of the literature were performed in PubMed. Studies, independent of published date, using samples from patients with ENL were included. The search revealed more than 20,000 articles of which 146 eligible studies were included in this systematic review. The studies demonstrate that ENL may be associated with a neutrophilic infiltrate, but it is not clear whether it is an IC-mediated process or that the presence of ICs is an epiphenomenon. Increased levels of tumor necrosis factor-α and other pro-inflammatory cytokines support the role of this cytokine in the inflammatory phase of ENL but not necessarily the initiation. T-cell subsets appear to be important in ENL since multiple studies report an increased CD4
/CD8
ratio in both skin and peripheral blood of patients with ENL. Microarray data have identified new molecules and whole pathophysiological pathways associated with ENL and provides new insights into the pathogenesis of ENL. Studies of ENL are often difficult to compare due to a lack of case definitions, treatment status, and timing of sampling as well as the use of different laboratory techniques. A standardized approach to some of these issues would be useful. ENL appears to be a complex interaction of various aspects of the immune system. Rigorous clinical descriptions of well-defined cohorts of patients and a systems biology approach using available technologies such as genomics, epigenomics, transcriptomics, and proteomics could yield greater understanding of the condition.
Skin-related neglected tropical diseases (NTDs) affect nearly 1 billion people worldwide, contributing to significant physical and psychological morbidity. The DLQI suite of patient-reported outcome ...measures is widely used to assess the impact of skin diseases on individuals’ health-related quality of life (HRQoL), but it has not been validated for use in skin-related NTDs. The new strategic framework for the control of skin-related NTDs identified the socioeconomic and mental health impact of skin NTDs as research gaps to be addressed. Robust assessments of HRQoL will be an essential part of this research and will require validated appropriate tools, including the DLQI.
The long-term survival of plasma cells is entirely dependent on signals derived from their environment. These extrinsic factors presumably induce and sustain the expression of antiapoptotic proteins ...of the Bcl-2 family. It is uncertain whether there is specificity among Bcl-2 family members in the survival of plasma cells and whether their expression is linked to specific extrinsic factors. We found here that deletion of the gene encoding the antiapoptotic protein Mcl-1 in plasma cells resulted in rapid depletion of this population in vivo. Furthermore, we found that the receptor BCMA was needed to establish high expression of Mcl-1 in bone marrow but not spleen plasma cells and that establishing this survival pathway preceded the component of plasma cell differentiation that depends on the transcriptional repressor Blimp-1. Our results identify a critical role for Mcl-1 in the maintenance of plasma cells.
CTLA4 gene polymorphism and autoimmunity Gough, Stephen C. L.; Walker, Lucy S. K.; Sansom, David M.
Immunological reviews,
April 2005, Volume:
204, Issue:
1
Journal Article
Peer reviewed
CD28 and cytotoxic T‐lymphocyte antigen‐4 (CTLA4) are two receptors that have critical but opposing functions in T‐cell stimulation. CD28 promotes a number of T‐cell activities, whereas in contrast ...CTLA4 is an essential inhibitor of T‐cell responses. Because of its inhibitory role, CTLA4 is a strong candidate susceptibility gene in autoimmunity and several studies suggest disease‐associated polymorphisms. In this review, we discuss recent progress in relating CTLA4 polymorphisms to disease susceptibility and consider the putative mechanisms by which CTLA4 may act to inhibit autoimmunity.
Leprosy reactions, Type-1 and erythema nodosum leprosum, are immune-mediated complications of leprosy, which play a significant role in the morbidity associated with the disease. A considerable ...amount of literature has been published on the impact of leprosy in general but few studies focus specifically on leprosy reactions. This study aimed to investigate the impact of leprosy reactions on physical, psychological, and social aspects of the lives of people affected by analysing their life experiences and perspectives about leprosy reactions.
This qualitative study involved people affected by leprosy reactions and their family members in two leprosy endemic countries. The data were collected through 66 interviews and 9 focus group discussions (4-6 participants each) in Surabaya, Indonesia, and Purulia, India. Content analysis and conversational analysis were performed. This study found that both types of leprosy reactions were perceived as an unpredictable and painful condition. Leprosy reactions restricted physical activities of the participants, such as going to bathroom, sleeping, eating, and cooking. In the interviews, the respondents expressed a range of emotions and feelings including confusion, sadness, anxiety, and anger. Some recounted that they felt stigmatized and lost opportunities to socialise and earn money. Differences between the two settings were identified. The majority of Indonesian participants preferred to stay at home, and some concealed the diagnosis of leprosy, while most of the Indian respondents continued working up to the time of hospitalization.
Leprosy reactions are a distressing complication of leprosy and adversely affect the lives of those affected. Individuals reported physical discomfort, distress, anxiety, stigma, and financial hardship and these negative impacts in the physical, psychological, and social spheres reinforced each other. These findings provide important information about a need for early detection and sustained commitment to follow-up care for people with a history of leprosy reactions. More research on new drugs for reactional episodes, tools to measure knowledge, attitude, and practice, and costing study on leprosy reactions treatment are needed. We recommend the development and testing of holistic strategies to improve the management of leprosy reactions.
Abstract
Following the acceptance of plate tectonics theory in the latter half of the 20th century, vicariance became the dominant explanation for the distributions of many plant and animal groups. ...In recent years, however, molecular-clock analyses have challenged a number of well-accepted hypotheses of vicariance. As a widespread group of insects with a fossil record dating back 300 My, cockroaches provide an ideal model for testing hypotheses of vicariance through plate tectonics versus transoceanic dispersal. However, their evolutionary history remains poorly understood, in part due to unresolved relationships among the nine recognized families. Here, we present a phylogenetic estimate of all extant cockroach families, as well as a timescale for their evolution, based on the complete mitochondrial genomes of 119 cockroach species. Divergence dating analyses indicated that the last common ancestor of all extant cockroaches appeared ∼235 Ma, ∼95 My prior to the appearance of fossils that can be assigned to extant families, and before the breakup of Pangaea began. We reconstructed the geographic ranges of ancestral cockroaches and found tentative support for vicariance through plate tectonics within and between several major lineages. We also found evidence of transoceanic dispersal in lineages found across the Australian, Indo-Malayan, African, and Madagascan regions. Our analyses provide evidence that both vicariance and dispersal have played important roles in shaping the distribution and diversity of these insects.
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