Comparison of statistical models to estimate parasite growth rate in the induced blood stage malaria model

• Published in: Malaria Journal
• Main Authors: Leesa F. Wockner, Isabell Hoffmann, Peter O’Rourke, James S. McCarthy, Louise Marquart
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2017
• Subjects: Statistical modelling; Fixed intercept regression; Parasite growth rate; Controlled human malaria infection; Induced blood stage malaria; Clinical trial; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic; The ''Y''
• Online Access: https://doi.org/10.1186/s12936-017-1999-1; https://doaj.org/article/835f83ac9e9f435bb01f2aa8dd4bb74f

Abstract Background The efficacy of vaccines aimed at inhibiting the growth of malaria parasites in the blood can be assessed by comparing the growth rate of parasitaemia in the blood of subjects treated with a test vaccine compared to controls. In studies using induced blood stage malaria (IBSM), a type of controlled human malaria infection, parasite growth rate has been measured using models with the intercept on the y-axis fixed to the inoculum size. A set of statistical models was evaluated to determine an optimal methodology to estimate parasite growth rate in IBSM studies. Methods Parasite growth rates were estimated using data from 40 subjects published in three IBSM studies. Data was fitted using 12 statistical models: log-linear, sine-wave with the period either fixed to 48 h or not fixed; these models were fitted with the intercept either fixed to the inoculum size or not fixed. All models were fitted by individual, and overall by study using a mixed effects model with a random effect for the individual. Results Log-linear models and sine-wave models, with the period fixed or not fixed, resulted in similar parasite growth rate estimates (within 0.05 log10 parasites per mL/day). Average parasite growth rate estimates for models fitted by individual with the intercept fixed to the inoculum size were substantially lower by an average of 0.17 log10 parasites per mL/day (range 0.06–0.24) compared with non-fixed intercept models. Variability of parasite growth rate estimates across the three studies analysed was substantially higher (3.5 times) for fixed-intercept models compared with non-fixed intercept models. The same tendency was observed in models fitted overall by study. Modelling data by individual or overall by study had minimal effect on parasite growth estimates. Conclusions The analyses presented in this report confirm that fixing the intercept to the inoculum size influences parasite growth estimates. The most appropriate statistical model to estimate the growth rate of blood-stage parasites in ...