The design and statistical power of treatment re-infection studies of the association between pre-erythrocytic immunity and infection with Plasmodium falciparum
Author(s)
White, MT
Griffin, JT
Ghani, AC
Type
Journal Article
Abstract
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.
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.
Date Issued
2013-08-08
Date Acceptance
2013-07-01
Citation
Malaria Journal, 2013, 12
ISSN
1475-2875
Publisher
BioMed Central
Journal / Book Title
Malaria Journal
Volume
12
Copyright Statement
© 2013 White et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
G0600719B
G1002284
MR/K010174/1B
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Parasitology
Tropical Medicine
PARASITOLOGY
TROPICAL MEDICINE
ANTIBODY-RESPONSES
CIRCUMSPOROZOITE PROTEIN
EFFECTOR MECHANISMS
ANOPHELES-GAMBIAE
MALARIA VACCINE
KENYAN CHILDREN
ANTIGENS
TRANSMISSION
PROTECTION
SPOROZOITES
Publication Status
Published
Article Number
278