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2015 ; 93
(6
): 1130-1133
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Considerations for Comprehensive Analyses of Sporozoite-Based Controlled Human
Malaria Infection Studies
#MMPMID26392161
Lover AA
Am J Trop Med Hyg
2015[Dec]; 93
(6
): 1130-1133
PMID26392161
show ga
There has been renewed interest in the use of sporozoite-based approaches for
controlled human malaria infections (CHMIs), 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, with important implications for planning future studies. Analysis of
time-to-event data has had extensive development in recent years, but these
methods have had limited exposure outside biostatistics. Expansion of the
published analyses to include recent methodological approaches optimized for the
types of data used could provide a richer analysis of these studies and may
result in alternative findings. Specifically, in a re-analysis of these data
using survival analysis techniques, the differences recorded in prepatent periods
between the two dosing regimens do not reach statistical significance, and there
is no evidence for statistically significant differences in prepatent periods
between the Dutch and Tanzanian study sites. Although these findings do not
impact the reported safety and tolerability of challange with cryopreserved
Plasmodium falciparum sporozoites (PfSPZ), or invalidate the authors' hypotheses
regarding naturally acquired immunity and its effect on parasite growth rates and
prepatent periods, they highlight important opportunities to more fully use
datasets from these trials and related CHMI experiments in the planning of future
challenge studies.
|*Data Interpretation, Statistical
[MESH]
|*Sporozoites/immunology/parasitology
[MESH]
|Humans
[MESH]
|Kaplan-Meier Estimate
[MESH]
|Malaria/parasitology/*prevention & control
[MESH]