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Der diesjährige internationale Weltlepratag steht unter dem Motto „United for Dignity“ und ruft dazu auf, gemeinsam die Würde Leprabetroffener, von denen viele nach wie vor unter krankheitsbedingter Stigmatisierung und Diskriminierung leiden, zu achten.

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.

Lepra, nicht was Du denkst ist das Motto des Welt-Lepra-Tages am 27. Januar 2020. Vor nunmehr 20 Jahren vermeldete die WHO, dass Lepra weltweit eliminiert wurde. Zwar gab es beachtliche Erfolge in der Zurückdrängung der Lepra, doch auch heute werden weltweit ca. alle zwei Minuten neue Patienten mit Lepra diagnostiziert. Vor vier Jahren hat die WHO die Globale Leprastrategie 2016 – 2020 „Beschleunigung zu einer Lepra-freien Welt“ verabschiedet. Diese beinhaltet drei zentrale Ziele, die u. a. Grad-2-Behinderungen, Fälle bei Kindern oder Diskriminierungen von Erkrankten betreffen. Dieses Ziel gilt es bis 2020 zu erreichen. Wie das Epidemiologische Bulletin 4/2020 berichtet, werden sie nach aktuellem Kenntnisstand nicht erreicht werden können. Experten sind deshalb zu dem Schluss gelangt, dass neue Initiativen und innovative Ansätze benötigt werden, um die bestehenden Herausforderungen anzugehen und die Triple-Zero-Ziele der Globalen Leprastrategie (Keine Ansteckung – Keine Behinderung – Keine Diskriminierung) zur Realität werden zu lassen.

Salmonella enterica serovar Typhimurium (S.Tm) infections of cultured cell lines have given rise to the ruffle model for epithelial cell invasion. According to this model, the Type-Three-Secretion-System-1 (TTSS-1) effectors SopB, SopE and SopE2 drive an explosive actin nucleation cascade, resulting in large lamellipodia- and filopodia-containing ruffles and cooperative S.Tm uptake. However, cell line experiments poorly recapitulate many of the cell and tissue features encountered in the host’s gut mucosa. Here, we employed bacterial genetics and multiple imaging modalities to compare S.Tm invasion of cultured epithelial cell lines and the gut absorptive epithelium in vivo in mice. In contrast to the prevailing ruffle-model, we find that absorptive epithelial cell entry in the mouse gut occurs through “discreet-invasion”. This distinct entry mode requires the conserved TTSS-1 effector SipA, involves modest elongation of local microvilli in the absence of expansive ruffles, and does not favor cooperative invasion. Discreet-invasion preferentially targets apicolateral hot spots at cell–cell junctions and shows strong dependence on local cell neighborhood. This proof-of-principle evidence challenges the current model for how S.Tm can enter gut absorptive epithelial cells in their intact in vivo context., Author summary Bacterial pathogens can use secreted effector molecules to drive entry into host cells. Studies of the intestinal pathogen S.Tm have been central to uncover the mechanistic basis for the entry process. More than two decades of research have resulted in a detailed model for how S.Tm invades gut epithelial cells through effector triggering of large Rho-GTPase-dependent actin ruffles. However, the evidence for this model comes predominantly from studies in cultured cell lines. These experimental systems lack many of the architectural and signaling features of the intact gut epithelium. Our study surprisingly reveals that in the intact mouse gut, S.Tm invades absorptive epithelial cells through a process that does not require the Rho-GTPase-activating effectors and can proceed in the absence of the prototypical ruffling response. Instead, S.Tm exploits another effector, SipA, to sneak in through discreet entry structures close to cell–cell junctions. Our results challenge the current model for S.Tm epithelial cell entry and emphasizes the need of taking a physiological host cell context into account when studying bacterium–host cell interactions.

Der diesjährige Welt-Lepra-Tag wird am 27. Januar 2019 unter dem Motto "Beendigung von Diskriminierung, Stigmatisierung und Vorurteilen" begangen. Im Epidemiologischen Bulletin 4/2019 werden die aktuellen Daten und Heraus­forderungen der Lepra-Bekämpfung erörtert. Gleichzeitig wird verdeutlicht, warum das Jahr 2018 – geprägt von entscheidenden Impulsen – auch zuversichtlich stimmt, dass langjährige Hürden der Lepra-Kontrolle bewältigt und die Leiden der Betroffenen gemildert werden könnten.

Additional file 1. Ijinga Schistosomiasis control project: School aged Children Questionnaire.

Small interfering RNAs (siRNAs) exhibit strong off-target effects, which confound the gene-level interpretation of RNA interference screens and thus limit their utility for functional genomics studies. Here, we present gespeR, a statistical model for reconstructing individual, gene-specific phenotypes. Using 115,878 siRNAs, single and pooled, from three companies in three pathogen infection screens, we demonstrate that deconvolution of image-based phenotypes substantially improves the reproducibility between independent siRNA sets targeting the same genes. Genes selected and prioritized by gespeR are validated and shown to constitute biologically relevant components of pathogen entry mechanisms and TGF-β signaling. gespeR is available as a Bioconductor R-package., Genome Biology, 16 (1), ISSN:1474-760X

Salmonella enterica serovar Typhimurium (S.Tm) infections of cultured cell lines have given rise to the ruffle model for epithelial cell invasion. According to this model, the Type-Three-Secretion-System-1 (TTSS-1) effectors SopB, SopE and SopE2 drive an explosive actin nucleation cascade, resulting in large lamellipodia- and filopodia-containing ruffles and cooperative S.Tm uptake. However, cell line experiments poorly recapitulate many of the cell and tissue features encountered in the host’s gut mucosa. Here, we employed bacterial genetics and multiple imaging modalities to compare S.Tm invasion of cultured epithelial cell lines and the gut absorptive epithelium in vivo in mice. In contrast to the prevailing ruffle-model, we find that absorptive epithelial cell entry in the mouse gut occurs through “discreet-invasion”. This distinct entry mode requires the conserved TTSS-1 effector SipA, involves modest elongation of local microvilli in the absence of expansive ruffles, and does not favor cooperative invasion. Discreet-invasion preferentially targets apicolateral hot spots at cell–cell junctions and shows strong dependence on local cell neighborhood. This proof-of-principle evidence challenges the current model for how S.Tm can enter gut absorptive epithelial cells in their intact in vivo context., PLoS Pathogens, 16 (5), ISSN:1553-7374, ISSN:1553-7366

Cell Host & Microbe, 18 (5), ISSN:1931-3128, ISSN:1934-6069