Published in:
Open Access 01-12-2013 | Research
The design and statistical power of treatment re-infection studies of the association between pre-erythrocytic immunity and infection with Plasmodium falciparum
Published in: Malaria Journal | Issue 1/2013
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Background
Understanding the role of pre-erythrocytic immune responses to Plasmodium falciparum parasites is crucial for understanding the epidemiology of malaria. However, published studies have reported inconsistent results on the association between markers of pre-erythrocytic immunity and protection from malaria.
Methods
The design and statistical methods of studies of pre-erythrocytic immunity were reviewed, and factors affecting the likelihood of detecting statistically significant associations were assessed. Treatment re-infection studies were simulated to estimate the effects of study size, transmission intensity, and sampling frequency on the statistical power to detect an association between markers of pre-erythrocytic immunity and protection from infection.
Results
Nine of nineteen studies reviewed reported statistically significant associations between markers of pre-erythrocytic immunity and protection from infection. Studies with large numbers of participants in high-transmission settings, followed longitudinally with active detection of infection and with immune responses analysed as continuous variables, were most likely to detect statistically significant associations. Simulation of treatment re-infection studies highlights that many studies are underpowered to detect statistically significant associations, providing an explanation for the finding that only some studies report significant associations between pre-erythrocytic immune responses and protection from infection.
Conclusions
The findings of the review and model simulations are consistent with the hypothesis that pre-erythrocytic immune responses prevent P. falciparum infections, but that many studies are underpowered to consistently detect this effect.