Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.
Description
see page 68 of notes 00002. 65% had grade 3 adverse events. Nice cyclical growth and good pictures of it.
%0 Journal Article
%1 Roestenberg2012
%A Roestenberg, Meta
%A O'Hara, Geraldine A.
%A Duncan, Christopher J A.
%A Epstein, Judith E.
%A Edwards, Nick J.
%A Scholzen, Anja
%A van der Ven, André J A M.
%A Hermsen, Cornelus C.
%A Hill, Adrian V S.
%A Sauerwein, Robert W.
%D 2012
%J PLoS One
%K malaria safety falciparum immunization
%N 6
%P e38434
%R 10.1371/journal.pone.0038434
%T Comparison of clinical and parasitological data from controlled human malaria infection trials.
%U http://dx.doi.org/10.1371/journal.pone.0038434
%V 7
%X Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.
@article{Roestenberg2012,
abstract = {Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.},
added-at = {2012-10-11T22:56:48.000+0200},
author = {Roestenberg, Meta and O'Hara, Geraldine A. and Duncan, Christopher J A. and Epstein, Judith E. and Edwards, Nick J. and Scholzen, Anja and {van der Ven}, André J A M. and Hermsen, Cornelus C. and Hill, Adrian V S. and Sauerwein, Robert W.},
biburl = {https://www.bibsonomy.org/bibtex/28a87c8249ab311f5c7a3987ec671ccc1/aorchid},
description = {see page 68 of notes 00002. 65% had grade 3 adverse events. Nice cyclical growth and good pictures of it.},
doi = {10.1371/journal.pone.0038434},
groups = {public},
institution = {Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. M.Roestenberg@lumc.nl},
interhash = {5ff93ee41a5e94c6335628c6ba6afa6f},
intrahash = {8a87c8249ab311f5c7a3987ec671ccc1},
journal = {PLoS One},
keywords = {malaria safety falciparum immunization},
language = {eng},
medline-pst = {ppublish},
number = 6,
pages = {e38434},
pii = {PONE-D-12-05609},
pmid = {22701640},
timestamp = {2012-12-19T00:46:27.000+0100},
title = {Comparison of clinical and parasitological data from controlled human malaria infection trials.},
url = {http://dx.doi.org/10.1371/journal.pone.0038434},
username = {aorchid},
volume = 7,
year = 2012
}