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Background: Previous qualitative studies on attitudes towards schistosomiasis demonstrated inconclusive results on the extent of stigma towards schistosomiasis in endemic communities around the world. The Explanatory Model Interview Catalogue–Community Stigma Scale (EMIC-CSS) has been used and validated for the assessment of public stigma across numerous countries in various health conditions. This study tested the performance of the scale in the context of stigma related to schistosomiasis in twelve communities in the three districts of Magu, Nyamagana and Ilemela in Mwanza region, Tanzania. Methodology/Principal findings: The 15-item-version of the EMC-CSS was first translated to Kiswahili language. The translation was discussed within the research team to retain the meaning of the items and implement cultural adaptations. Validation of the adapted EMIC-CSS scale was conducted following the framework of Herdman and Fox- Rushby. A pilot study with 41 participants from two communities provided the basis for testing the performance of each item and assessing the semantic and operational equivalence of the scales. In addition, eight qualitative focus group discussions (FGDs) were conducted to evaluate the conceptional equivalence of the EMIC-CSS. Finally, the performance of the adjusted scale was tested on 200 participants with a 50:50 male-female ratio from ten communities. The mean score of the EMIC-CSS M = 8.35 (SD = 6.63) shows clear indications for public stigma towards schistosomiasis. The EMIC-CSS demonstrated a good internal consistency with Cronbach's alpha α =.857 and no floor and ceiling effects. Conclusion/Significance: The results demonstrate that the EMIC-CSS is a useful instrument in assessing public stigma towards schistosomiasis and allow a clear recommendation of the EMIC-CSS for schistosomiasis in the Tanzanian culture. However, future studies are additionally recommended to address specific aspects and forms of the disease and how they contribute to the development of stigma towards schistosomiasis. Author summary: Schistosomiasis is a common disease in many lakeshore areas across Africa, especially in communities of a lower socio-economic status with inadequate access to clean water and hygienic sanitary facilities. The disease is caused by parasitic worms transmitted by fresh water snails in infested water bodies and can be lethal, if the infection and related chronic morbidities aren't timely treated. Available evidence indicates that people suffering from schistosomiasis experience stigmatization from community members and healthcare providers when seeking health care services. However, this has not been systematically examined. In the present study the EMIC-CSS questionnaire was adapted and validated according to the framework of Herdman and Fox-Rushby in order to investigate the extent of stigmatization due to schistosomiasis in Mwanza region, Tanzania, where the disease is highly endemic. The scale was successfully validated and the results indicate that schistosomiasis-related stigma is indeed common in communities living along the Lake Victoria in Mwanza region. The findings of this study can improve knowledge and create awareness about the existence of community-related stigma towards persons infected with schistosomiasis and, as a result, can be used to contribute to the control and elimination of schistosomiasis in Tanzania. [ABSTRACT FROM AUTHOR]

This protocol describes a study in which we would assess the effect of using community lay counselors, self-help groups (SHGs), and trained frontline health workers to reduce mental disorders and improve quality of life (QOL) of persons affected by leprosy or Buruli ulcer (BU). A cluster randomized controlled study design will be employed. The study will involve persons affected by leprosy or BU. Ten local government areas (clusters) with the highest number of notified leprosy or BU cases between 2014 and 2018 in Southern Nigeria will be purposively selected. The clusters will be randomized into intervention and control groups using a computer-generated list of random numbers. At baseline, data were collected using the following validated questionnaires, Patient Health Questionnaire, Generalized Anxiety Disorder questionnaire, Stigma Assessment and Reduction of Impact Scale, World Health Organization QOL BREF and Warwick-Edinburgh Mental Well-being scale among persons affected by leprosy or BU. The intervention will last for 2 years and will involve use of community lay counselors, SHGs, and appropriately trained frontline health workers in reducing mental disorders and improving QOL of persons affected by leprosy or BU. This project postulates that the reduction of burden of mental health problems and improved QOL among persons affected by leprosy or BU could be achieved through a holistic approach involving SHGs, appropriately trained community opinion leaders, and general health-care workers as well as a functional referral system. If successful, the model will be integrated into the activities of the National Tuberculosis and Leprosy Control Programme and scaled up nationwide. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and burden in leprosy lacks a uniform approach. As a result, the assessment of leprosy endemicity or burden are not comparable over time and across countries and regions. This can make program planning and evaluation difficult. This study aims to identify relevant metrics and methods for measuring and classifying leprosy endemicity and burden at (sub)national level. Methods: We used a mixed-method approach combining findings from a systematic literature review and a Delphi survey. The literature search was conducted in seven databases, searching for endemicity, burden and leprosy. We reviewed the available evidence on the usage of indicators, classification levels, and scoring methods to measure and classify endemicity and burden. A two round Delphi survey was conducted to ask experts to rank and weigh indicators, classification levels, and scoring methods. Results: The literature review showed variation of indicators, levels, and cut-off values to measure leprosy endemicity and/or burden. The most used indicators for endemicity include new case detection rate (NCDR), new cases among children and new cases with grade 2 disability. For burden these include NCDR, MB cases, and prevalence. The classification levels 'high' and 'low' were most important. It was considered most relevant to use separate scoring methods for endemicity and burden. The scores would be derived by use of multiple indicators. Conclusion: There is great variation in the existing method for measuring endemicity and burden across countries and regions. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies. Author summary: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. If left untreated, it could lead to deformity and resultant disabilities. The number of new cases has remained stagnant for the past decade. Additional interventions are required tailored to the level of endemicity and burden of an area. Currently, measuring and classifying endemicity and burden in leprosy lacks a standardized uniform approach, making program planning and evaluation difficult. We did a systematic literature search and Delphi survey, a method to elicit (group) opinion from a panel of experts, to take an inventory of indicators, classification levels and cut-offs that were used to measure and classify endemicity and burden of leprosy. This study highlights the variation in usage of indicators, levels, and cut-off values to determine the endemicity and burden of leprosy across regions and countries. There was agreement that endemicity and burden should be measured separately using multiple indicators, and that the classification levels 'high' and 'low' were most important. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies. [ABSTRACT FROM AUTHOR]

Summary: The peroxisomal sterol carrier protein 2 (Scp2) of the biotrophic maize pathogen Ustilago maydis was detected in apoplastic fluid, suggesting that it might function as a secreted effector protein. Here we analyze the role of the scp2 gene during plant colonization. We used reverse genetics approaches to delete the scp2 gene, determined stress sensitivity and fatty acid utilization of mutants, demonstrated secretion of Scp2, used quantitative reverse transcription polymerase chain reaction for expression analysis and expressed GFP‐Scp2 fusion proteins for protein localization. scp2 mutants were strongly attenuated in virulence and this defect manifested itself during penetration. Scp2 localized to peroxisomes and peroxisomal targeting was necessary for its virulence function. Deletion of scp2 in U. maydis interfered neither with growth nor with peroxisomal β‐oxidation. Conventionally secreted Scp2 protein could not rescue the virulence defect. scp2 mutants displayed an altered localization of peroxisomes. Our results show a virulence function for Scp2 during penetration that is probably carried out by Scp2 in peroxisomes. We speculate that Scp2 affects the lipid composition of membranes and in this way ensures the even cellular distribution of peroxisomes. [ABSTRACT FROM AUTHOR]

Background: Control strategies in Tanzania focus on school children by mass drug administration (MDA) using praziquantel. High risk adults are left untreated although potentially infected. Objective: To understand the prevalence of S. mansoni among the adult population and to find whether Testing and treatment campaign, intensive information campaign and engaging the community improves praziquantel uptake during MDA among high-risk adults in Ilemela and Nyamagana municipality, Mwanza Tanzania. Methods: For three consecutive years (January 2018, January 2019, and November 2019), we implemented three cross sectional prevalence surveys through a test and treatment approach involving adult individuals aged ≥15 years. Participants' age, sex, and history of participating in the study were recorded by using a questionnaire. A single urine sample were collected from each participant and screened for S. mansoni infection using PO-CCA test. Participants who tested positive were treated with praziquantel 40mg/kg bwt. Prior to the implementation of MDA, there was an intensive information campaign and community engagement. MDA were done among adult individuals about one month after each testing and treating campaign. Results: A total of 2,148 (38.3% females), 2,070 (32.8% females) and 2,141 (36.6% female) adult individuals participated in the testing and treatment campaign in January 2018, January 2019, and November 2019, respectively. The respective overall prevalence of S.mansoni based on PO-CCA was 81.7% (95%CI: 79.9- 83.2), 70.9% (95%CI: 68.9-72.8) and 74.1% (CI: 72.2 -75.9); indicating a clear decline in prevalence of S. mansoni infection between the baseline and the two consecutive follow-up testing and treatment rounds. The number of participants of PZQ uptake increased from 18,252(67.6%) in the 1st round in February 2018 to 22,581 (83.6%) in July 2019 and 22,583 (83.6%) in December 2019 during the 2ndand 3rd treatment rounds respectively, of the 27,000 adult individuals aimed to be treated in every treatment round. In all three MDA rounds, male had higher participation rate than female and more than half of the participants were youth aged 15-35 years. Conclusion: There was high prevalence of S. mansoni among adults along shore of the Lake Victoria in Mwanza city, however following testing campaign, engaging the community and intensive information campaign there was a significant increase in praziquantel uptake and improvement in the treatment coverage of MDA. The findings demonstrate the role of multi- strategic approaches on praziquantel uptake when implementing along with treatment and test campaign in high-risk adult population. [ABSTRACT FROM AUTHOR]

Background: Large-scale RNAi screening has become an important technology for identifying genes involved in biological processes of interest. However, the quality of large-scale RNAi screening is often deteriorated by off-targets effects. In order to find statistically significant effector genes for pathogen entry, we systematically analyzed entry pathways in human host cells for eight pathogens using image-based kinome-wide siRNA screens with siRNAs from three vendors. We propose a Parallel Mixed Model (PMM) approach that simultaneously analyzes several non-identical screens performed with the same RNAi libraries. Results: We show that PMM gains statistical power for hit detection due to parallel screening. PMM allows incorporating siRNA weights that can be assigned according to available information on RNAi quality. Moreover, PMM is able to estimate a sharedness score that can be used to focus follow-up efforts on generic or specific gene regulators. By fitting a PMM model to our data, we found several novel hit genes for most of the pathogens studied. Conclusions: Our results show parallel RNAi screening can improve the results of individual screens. This is currently particularly interesting when large-scale parallel datasets are becoming more and more publicly available. Our comprehensive siRNA dataset provides a public, freely available resource for further statistical and biological analyses in the high-content, highthroughput siRNA screening field. [ABSTRACT FROM AUTHOR]

Targeting of permissive entry sites is crucial for bacterial infection. The targeting mechanisms are incompletely understood. We have analyzed target-site selection by S. Typhimurium. This enteropathogenic bacterium employs adhesins (e.g. fim) and the type III secretion system 1 (TTSS-1) for host cell binding, the triggering of ruffles and invasion. Typically, S. Typhimurium invasion is focused on a subset of cells and multiple bacteria invade via the same ruffle. It has remained unclear how this is achieved. We have studied target-site selection in tissue culture by time lapse microscopy, movement pattern analysis and modeling. Flagellar motility (but not chemotaxis) was required for reaching the host cell surface in vitro. Subsequently, physical forces trapped the pathogen for ~1.5-3 s in "near surface swimming". This increased the local pathogen density and facilitated "scanning" of the host surface topology. We observed transient TTSS-1 and fim-independent "stopping" and irreversible TTSS-1-mediated docking, in particular at sites of prominent topology, i.e. the base of rounded-up cells and membrane ruffles. Our data indicate that target site selection and the cooperative infection of membrane ruffles are attributable to near surface swimming. This mechanism might be of general importance for understanding infection by flagellated bacteria. [ABSTRACT FROM AUTHOR]

The food-borne pathogen Salmonella enterica serovar Typhimurium invades mammalian epithelial cells. This multistep process comprises bacterial binding to the host cell, activation of the Salmonella type three secretion system 1 (T1), injection of effector proteins, triggering of host cell actin rearrangements, and S. Typhimurium entry. While the latter steps are well understood, much less is known about the initial binding step. Earlier work had implicated adhesins (but not T1) or T1 (but not other adhesins). We have studied here the Salmonella virulence factors mediating S. Typhimurium binding to HeLa cells. Using an automated microscopy assay and isogenic S. Typhimurium mutants, we analyzed the role of T1 and of several known adhesins (Fim, Pef, Lpf, Agf, and Shd) in host cell binding. In wild-type S. Typhimurium, host cell binding was mostly attributable to T1. However, in the absence of T1, Fim (but not Pef, Lpf, Agf, and Shd) also mediated HeLa cell binding. Furthermore, in the absence of T1 and type I fimbriae (Fim), we still observed residual binding, pointing toward at least one additional, unidentified binding mechanism. Dissociation experiments established that T1-mediated binding was irreversible ("docking"), while Fim-mediated binding was reversible ("reversible adhesion"). Finally, we show that noninvasive bacteria docking via T1 or adhering via Fim can efficiently invade HeLa cells, if actin rearrangements are triggered in trans by a wild-type S. Typhimurium helper strain. Our data show that binding to HeLa cells is mediated by at least two different mechanisms and that both can lead to invasion if actin rearrangements are triggered.