<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Annefleur D.O. Hensen</style></author><author><style face="normal" font="default" size="100%">Maria J.G.T. Vehreschild</style></author><author><style face="normal" font="default" size="100%">Dale N. Gerding</style></author><author><style face="normal" font="default" size="100%">Oleg Krut</style></author><author><style face="normal" font="default" size="100%">Wilbur Chen</style></author><author><style face="normal" font="default" size="100%">Vincent B. Young</style></author><author><style face="normal" font="default" size="100%">Saul Tzipori</style></author><author><style face="normal" font="default" size="100%">Philipp Solbach</style></author><author><style face="normal" font="default" size="100%">Malick Mahdi Gibani</style></author><author><style face="normal" font="default" size="100%">Christopher Chiu</style></author><author><style face="normal" font="default" size="100%">Sigrid C.J. De Keersmaecker</style></author><author><style face="normal" font="default" size="100%">Dasyam, Dileep</style></author><author><style face="normal" font="default" size="100%">Sandra Morel</style></author><author><style face="normal" font="default" size="100%">Jeanne-Marie Devaster</style></author><author><style face="normal" font="default" size="100%">Nicoletta Corti</style></author><author><style face="normal" font="default" size="100%">Ed J. Kuijper</style></author><author><style face="normal" font="default" size="100%">Meta Roestenberg</style></author><author><style face="normal" font="default" size="100%">Wiep Klaas Smits</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">How to develop a controlled human infection model for Clostridioides difficile</style></title><secondary-title><style face="normal" font="default" size="100%">Clinical Microbiology and Infection</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Cdiff</style></keyword><keyword><style  face="normal" font="default" size="100%">CHIM</style></keyword><keyword><style  face="normal" font="default" size="100%">vaccine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan-08-2024</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Background:&lt;em&gt; Clostridioides difficile (C. difficile) &lt;/em&gt;remains the leading cause of healthcare-associated diarrhoea, posing treatment challenges due to antibiotic resistance and high relapse rates. Fecal microbiota transplantation (FMT) is a novel treatment strategy to prevent relapses of &lt;em&gt;C. difficile&lt;/em&gt; infection (CDI), however the exact components conferring colonisation resistance are unknown, hampering its translation to a medicinal product. Development of novel products independent of antibiotics, which increase colonisation resistance or induce protective immune mechanisms are urgently needed. &amp;nbsp;&lt;/p&gt;

&lt;p&gt;Objectives: To establish a framework for a Controlled Human Infection Model (CHIM) for &lt;em&gt;C. difficile&lt;/em&gt;, in which healthy volunteers are exposed to toxigenic &lt;em&gt;C. difficile&lt;/em&gt; spores, offering the possibility to test novel approaches and identify microbiota and immunological targets. Whereas experimental exposure to non-toxigenic &lt;em&gt;C. difficile&lt;/em&gt; (NTCD) has been done before, a toxigenic &lt;em&gt;C. difficile&lt;/em&gt; CHIM faces ethical, scientific, logistical and biosafety challenges.&lt;/p&gt;

&lt;p&gt;Sources: Specific challenges in developing a &lt;em&gt;C. difficile&lt;/em&gt; CHIM were discussed by a group of international experts during a workshop organized by Inno4Vac, an IHI-funded consortium.&lt;/p&gt;

&lt;p&gt;Content: The experts agreed that the main challenges are: developing a clinically relevant CHIM which induces mild to moderate CDI symptoms but no severe CDI, determining optimal &lt;em&gt;C. difficile&lt;/em&gt; inoculum dose and understanding the timing and duration of antibiotic pre-treatment in inducing susceptibility to CDI in healthy volunteers.&lt;/p&gt;

&lt;p&gt;Implications: Should these challenges be tackled, a &lt;em&gt;C. difficile &lt;/em&gt;CHIM not only provides a way forward for the testing of novel products but also offers a framework for better understanding of the pathophysiology, pathogenesis and immunology of &lt;em&gt;C. difficile &lt;/em&gt;colonisation and infection.&lt;/p&gt;
</style></abstract></record></records></xml>