Reversing Autoimmunity Combination of Rituximab and Intravenous Immunoglobulin

In this concept paper, the authors present a unique and novel protocol to treat autoimmune diseases that may have the potential to reverse autoimmunity. It uses a combination of B cell depletion therapy (BDT), specifically rituximab (RTX) and intravenous immunoglobulin (IVIg), based on a specifically designed protocol (Ahmed Protocol). Twelve infusions of RTX are given in 6–14 months. Once the CD20+ B cells are depleted from the peripheral blood, IVIg is given monthly until B cells repopulation occurs. Six additional cycles are given to end the protocol. During the stages of B cell depletion, repopulation and after clinical recovery, IVIg is continued. Along with clinical recovery, significant reduction and eventual disappearance of pathogenic autoantibody occurs. Administration of IVIg in the post-clinical period is a crucial part of this protocol. This combination reduces and may eventually significantly eliminates inflammation in the microenvironment and facilitates restoring immune balance. Consequently, the process of autoimmunity and the phenomenon that lead to autoimmune disease are arrested, and a sustained and prolonged disease and drug-free remission is achieved. Data from seven published studies, in which this combination protocol was used, are presented. It is known that BDT does not affect check points. IVIg has functions that mimic checkpoints. Hence, when inflammation is reduced and the microenvironment is favorable, IVIg may restore tolerance. The authors provide relevant information, molecular mechanism of action of BDT, IVIg, autoimmunity, and autoimmune diseases. The focus of the manuscript is providing an explanation, using the current literature, to demonstrate possible pathways, used by the combination of BDT and IVIg in providing sustained, long-term, drug-free remissions of autoimmune diseases, and thus reversing autoimmunity, albeit for the duration of the observation

Current biologics in treatment of pemphigus foliaceus: a systematic review

BackgroundPemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with systemic corticosteroids and immunosuppressive agents (ISAs). More recently, biologics have been used. The current literature on biologic therapy often combines treatment of PF with PV, hence it is often difficult for clinicians to isolate the treatment of PF from PV. The purpose of this review was to provide information regarding the use of current biological therapy, specifically in PF.Materials and methodsA search of PubMed, Embase, and other databases was conducted using keywords pemphigus foliaceus (PF), rituximab (RTX), intravenous immunoglobulin (IVIg), and biologics. Forty-one studies were included in this review, which produced 105 patients with PF, treated with RTX, IVIg, or a combination of both. Eighty-five patients were treated with RTX, eight patients with IVIg, and 12 received both RTX and IVIg.ResultsMost patients in this review had PF that was nonresponsive to conventional immunosuppressive therapies (CIST), and had significant side effects from their use. RTX treatment resulted in complete remission (CR) in 63.2%, a relapse rate of 39.5%, an infection rate of 19.7%, and a mortality rate of 3.9%. Relapse was greater in the lymphoma (LP) protocol than the rheumatoid arthritis (RA) protocol (p<0.0001). IVIg led to CR in 62.5% of patients, with no relapses or infections. Patients receiving both biologics experienced better outcomes when RTX was first administered, then followed by IVIg. Follow-up durations for patients receiving RTX, IVIg, and both were 22.1, 24.8, and 35.7 months, respectively.DiscussionIn pemphigus foliaceus patients nonresponsive to conventional immunosuppressive therapy or in those with significant side effects from CIST, RTX and IVIg appear to be useful agents. Profile of clinical response, as well as relapse, infection, and mortality rates in PF patients treated with RTX were similar to those observed in PV patients. The data suggests that protocols specific for PF may produce better outcomes, less adverse effects, and improved quality of life

Benefit incidence analysis of healthcare in Bangladesh – equity matters for universal health coverage

Background: Equity in access to and utilization of healthcare is an important goal for any health system and an essential prerequisite for achieving Universal Health Coverage for any country. Objectives: This study investigated the extent to which health benefits are distributed across socioeconomic groups; and how different types of providers contribute to inequity in health benefits of Bangladesh. Methodology: The distribution of health benefits across socioeconomic groups was estimated using concentration indices. Health benefits from three types of formal providers were analysed (public, private and NGO providers), separated into rural and urban populations. Decomposition of concentration indices into types of providers quantified the relative contribution of providers to the overall distribution of benefits across socioeconomic groups. Eventually, the distribution of benefits was compared to the distribution of healthcare need (proxied by ‘self-reported illness and symptoms’) across socioeconomic groups. Data from the latest Household Income and Expenditure Survey, 2010 and WHO-CHOICE were used. Results: An overall pro-rich distribution of healthcare benefits was observed (CI = 0.229, t-value = 9.50). Healthcare benefits from private providers (CI = 0.237, t-value = 9.44) largely favoured the richer socioeconomic groups. Little evidence of inequity in benefits was found in public (CI = 0.044, t-value = 2.98) and NGO (CI = 0.095, t-value = 0.54) providers. Private providers contributed by 95.9% to overall inequity. The poorest socioeconomic group with 21.8% of the need for healthcare received only 12.7% of the benefits, while the richest group with 18.0% of the need accounted for 32.8% of the health benefits. Conclusion: Overall healthcare benefits in Bangladesh were pro-rich, particularly because of health benefits from private providers. Public providers were observed to contribute relatively slightly to inequity. The poorest (richest) people with largest (least) need for healthcare actually received lower (higher) benefits. When working to achieve Universal Health Coverage in Bangladesh, particular consideration should be given to ensuring that private sector care is more equitable

Inequalities in Health Status from EQ-5D Findings: A Cross-Sectional Study in Low-Income Communities of Bangladesh

Background: Measuring health status by using standardized and validated instrument has become a growing concern over the past few decades throughout the developed and developing countries. The aim of the study was to investigate the overall self-reported health status along with potential inequalities by using EuroQol 5 dimensions (EQ-5D) instrument among low-income people of Bangladesh. Methods: A cross-sectional household survey was conducted in Chandpur district of Bangladesh. Bangla version of the EQ-5D questionnaire was employed along with socio-demographic information. EQ-5D questionnaire composed of 2-part measurements: EQ-5D descriptive system and the visual analogue scale (VAS). For measuring health status, UK-based preference weights were applied while higher score indicated better health status. For facilitating the consistency with EQ-5D score, VASs were converted to a scale with scores ranging from 0 to 1. Multiple logistic regression models were also employed to examine differences among EQ-5D dimensions. Results: A total of 1433 respondents participated in the study. The mean EQ-5D and VAS score was 0.76 and 0.77, respectively. The females were more likely to report any problem than the males (P<0.001). Compared to the younger, elderly were more than 2-3 times likely to report any health problem in all EQ-5D dimensions (OR [odds ratio]=3.17 for mobility, OR=3.24 for self-care). However, the respondents of the poorest income group were significantly suffered more from every EQ-5D dimension than the richest income quintile. Conclusion: Socio-economic and demographic inequalities in health status was observed in the study. Study suggests to do further investigation with country representative sample to measure the inequalities of overall health status. It would be helpful for policy-maker to find a new way aiming to reduce such inequalities

Integrative Analysis Applying the Delta Dynamic Integrated Emulator Model in South-West Coastal Bangladesh

A flexible meta-model, the Delta Dynamic Integrated Emulator Model (ΔDIEM), is developed to capture the socio-biophysical system of coastal Bangladesh as simply and efficiently as possible. Operating at the local scale, calculations occur efficiently using a variety of methods, including linear statistical emulators, which capture the behaviour of more complex models, internal process-based models and statistical associations. All components are tightly coupled, tested and validated, and their behaviour is explored with sensitivity tests. Using input data, the integrated model approximates the spatial and temporal change in ecosystem services and a number of livelihood, well-being, poverty and health indicators of archetypal households. Through the use of climate, socio-economic and governance scenarios plausible trajectories and futures of coastal Bangladesh can be explored

Ecological Determinants of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh

BACKGROUND: The agro-ecology and poultry husbandry of the south Asian and south-east Asian countries share common features, however, with noticeable differences. Hence, the ecological determinants associated with risk of highly pathogenic avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh and e.g., Thailand and Vietnam. The primary aim of the current study was to establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks at subdistrict level in Bangladesh. The secondary aim was to explore the performance of two different statistical modeling approaches for unmeasured spatially correlated variation. METHODOLOGY/PRINCIPAL FINDINGS: An ecological study at subdistrict level in Bangladesh was performed with 138 subdistricts with HPAI-H5N1 outbreaks during 2007-2008, and 326 subdistricts with no outbreaks. The association between ecological determinants and HPAI-H5N1 outbreaks was examined using a generalized linear mixed model. Spatial clustering of the ecological data was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at subdistrict level considering their first order neighbors, and 2) a multilevel (ML) model with subdistricts nested within districts. Ecological determinants significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level were migratory birds' staging areas, river network, household density, literacy rate, poultry density, live bird markets, and highway network. Predictive risk maps were derived based on the resulting models. The resulting models indicate that the ML model absorbed some of the covariate effect of the ICAR model because of the neighbor structure implied in the two different models. CONCLUSIONS/SIGNIFICANCE: The study identified a new set of ecological determinants related to river networks, migratory birds' staging areas and literacy rate in addition to already known risk factors, and clarified that the generalized concept of free grazing duck and duck-rice cultivation interacted ecology are not significant determinants for Bangladesh. These findings will refine current understanding of the HPAI-H5N1 epidemiology in Bangladesh

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Thalassemias in South Asia:clinical lessons learnt from Bangladesh

Abstract Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world’s thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009–2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries

Levels, Trends and Disparities in Public-Health-Related Indicators among Reproductive-Age Women in Bangladesh by Urban-Rural and Richest-Poorest Groups, 1993-2011

Khan MH, Zanuzdana A, Krämer A. Levels, Trends and Disparities in Public-Health-Related Indicators among Reproductive-Age Women in Bangladesh by Urban-Rural and Richest-Poorest Groups, 1993-2011. PLoS ONE. 2013;8(9): e75261.BACKGROUND AND OBJECTIVES: Although Bangladesh has already achieved noticeable progress in the field of development and health, disparities in public health indicators for several markers are still reported. To assess public health development in Bangladesh during the last two decades, firstly, we analysed levels, trends and disparities in public-health-related indicators by rural versus urban as well as by the richest versus poorest group of women who have ever been married. Secondly, using the most recent data set we performed multiple analyses to check whether urban-rural and richest-poorest disparities were still significant. METHODS: The analysis was based on six nationally representative data sets from the Bangladesh Demographic and Health Surveys (BDHS) conducted in 1993-94 (n=9,640), 1996-1997 (n=9,127), 1999-2000 (n=10,544), 2004 (n=11,440), 2007 (n=10,996) and 2011 (n=17,749). The outcome variables were six selected public-health-related indicators. We performed various types of analyses, including multiple logistic regressions. RESULTS: The trend of all indicators except being overweight (1993-2011) displayed gradual improvements for both markers. However, the urban and richest groups revealed a better situation than their counterparts in both simple and multiple analyses. Disparities between richest-poorest groups were more pronounced than urban-rural disparities. For instance, the prevalence of delivery at any healthcare facility in 2011 was 20.4% in rural areas and 46.5% in urban areas, whereas it was 9.1% in the poorest group and 57.6% in the richest group. CONCLUSION: The public health sector in Bangladesh has achieved some successes over the last two decades. However, urban-rural and richest-poorest disparities are still considerable and therefore more public health strategies and efforts are clearly needed for the rural and poorest groups of women in order to reduce these gaps further