Short Report: Study variability in recent human challenge experiments with Plasmodium falciparum sporozoites (PfSPZ Challenge)

TL;DR

This study reanalyzes recent human challenge experiments with Plasmodium falciparum, revealing that previous conclusions about dose-dependence and site differences were based on suboptimal methods, emphasizing the need for improved analysis in future research.

Contribution

The paper demonstrates that more appropriate analytical methods negate previous claims of dose-dependence and site differences in PfSPZ challenge studies, refining understanding of variability in human malaria challenge experiments.

Findings

No evidence for dose-dependence within 10,000-25,000 sporozoite doses

No significant differences in event times between Tanzanian and Dutch sites

Highlights importance of analytical methods in interpreting challenge study data

Abstract

There has been renewed interest in the use of sporozoite-based approaches for malaria vaccination and controlled human infections, and several sets of human challenge studies have recently completed. A study undertaken in Tanzania and published in 2014 found dose-dependence between 10,000 and 25,000 sporozoite doses, as well as divergent times-to-parasitemia relative to earlier studies in European volunteers. However, this analysis shows that these conclusions are based upon suboptimal analytical methods; with more optimal analysis, there is no evidence for dose-dependence within this dose range; and more importantly, no evidence for differences in event times between Dutch and Tanzanian study sites. While these finding do not impact the reported safety and tolerability of PfSPZ, they highlight critical issues that should be comprehensively considered in future challenge studies.