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Even in the absence of transmission precautions, the rate of secondary cases is exceptionally low within the UK.22 The participants will consent to the clinical study team informing the local Health Protection Unit of their involvement in the study. The Unit will be notified of their Oxygenase challenge date and when stool clearance has been completed. Any breach in enteric hygiene precautions that result in another individual coming into contact with infectious material will be reported, with potential cases of transmission to be confirmed by sequence comparison to an isolate of the challenge strain stored at a Public Health England microbiology reference laboratory (Colindale, London). Sample size The selected sample size balances the need for a statistically reproducible attack rate while minimising the number of individuals exposed to paratyphoid infection. To meet the primary objective of a clinically reproducible attack rate of 60�C75%, this careful, dose (de-)escalation protocol will be followed.9 The maximum number of participants required will be 80, with the minimum 20 if the starting dose (1�C5��103 CFU) satisfies our criteria. This is based on the probability that the criteria are satisfied according to the true attack rate. If the attack rate in the first group of 20 participants is greater than 75%, a lower dose will be decided based on the prior attack rate combined with laboratory and clinical findings. De-escalation to a dose lower than 1�C5��103 CFU will also be considered if the target attack rate is reached and the chief investigator, with agreement from the DSMC, decides that a lower dose may achieve a similar attack rate. Statistical analysis The analysis of the primary end point will be descriptive only. The percentage of participants who meet the criteria for diagnosis of paratyphoid will be calculated with a 95% Clopper-Pearson Exact CI. Those individuals who withdraw or are treated prior to day 14 without prior diagnosis of paratyphoid would be excluded from this analysis. A secondary analysis of the primary end point will be conducted using the Kaplan-Meier method which will include all participants. Time-to-event analyses of individual components of the primary outcome (eg, positive blood culture for S. Paratyphi, oral temperature>38.0��C, etc) will be conducted using the Kaplan-Meier method and will include all participants. Participants not meeting the criteria for an individual component of the primary end point will be censored in the analysis at the time of diagnosis or at day 14 for those undiagnosed. Discussion This will be the first S. Paratyphi A human challenge model developed. It is presumed that this study will be similar to the experience of recent typhoid challenge studies based on the literature iterating the similar clinical presentation between typhoid and paratyphoid fever.