Infecting dose and severity of typhoid: analysis of volunteer data and examination of the influence of the definition of illness used

Data from volunteers challenged with Salmonella typhi were reanalysed to explore the relationship between challenge dose and severity of disease. Among 120 ill volunteers who received between 10(5) and 10(9) organisms, dose was weakly correlated with peak temperature (r = 0.22, 95% CI 0.04-0.39), duration of temperature above 103 degrees F (39.4 degrees C: r = 0.13, 95% CI - 0.03 to 0.55) and symptom score (r = 0.27, 95% CI 0.09-0.43). The association with symptom score was lost after adjusting for year, and the findings depended on the definition of illness used: with stricter definitions the associations with temperature were also lost. The study shows the need for caution in interpreting the relationship between dose and severity of disease.