Transmission_dynamics_of_C__difficile_in_asymptomatic_patients. Transmission_dynamics_of_C__difficile_in_asymptomatic_patients

Clostridium difficile is the leading cause of healthcare-associated infectious colitis. Unlike other common healthcareassociated pathogens, C. difficile produces highly resistant and transmissible spores that confound standard infection control measures. A recent transmission study of C. difficile in a UK hospital helped resolve the transmission dynamics of Clostridium difficile infection (CDI) between symptomatic hospital patients (Kumar et al., 2015) and indicates the importance of whole genome SNP based phylogenetic methods to discriminate the clonal population of C. difficile that cannot be distinguished by conventional methods such as Multilocus Sequence Typing (MLST). In this study we will apply our genome based infection tracking method to understand the transmission dynamics of CDI in a US based hospital as we speculate that every hospital has a different transmission rates of CDI. Moreover, the sample collection includes samples from colonized patients who do not manifest symptoms of CDI at admission (asymptomatic patients) represent an underappreciated source of ongoing transmission of CDI within hospital units. This potential reservoir for CDI would unlikely be remedied by current CDI mitigation strategies. Therefore, a better understanding of the transmission dynamics of C. difficile for this potential CDI reservoir is required. Aim: whole genome sequencing of 77 genomes (1 HiSeq lane) would allow us to comprehensively assess the genetic diversity of the C. difficile and to infer the phylogenetic relationship within the distinct monomorphic clades of C. difficile. This phylogenetic relationship would be used to identify transmission events occurred between highly immunocompromised patients admitted to hospital units. Strategy: We initiated a prospective stool collection protocol for all immunocompromised patients admitted to two inpatient units in a US hospital in 2015. Admission samples were then screened for Clostridium difficile by PCR and DNA was isolated from positive samples. Also, we collected detailed patient movement data related to these positive samples. DNA will be sent to the Sanger from our collaborator. Analysis will be done by Nitin Kumar (Lawley Lab) and Elizabeth Robilotti (Memorial Sloan Kettering Cancer Centre, USA) to produce a whole genome SNP based phylogeny and construct a detailed CDI transmission network. Importantly, this genome project would allow us to infer the source and spread of ongoing transmissions of CDI between highly immunocompromised hosts in two inpatient units.