Comparison of clinical and parasitological data from controlled human malaria infection trials.
BACKGROUND: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 worl...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3372522?pdf=render |
id |
doaj-1fde73bcfd874d738085865cb108d48b |
---|---|
record_format |
Article |
spelling |
doaj-1fde73bcfd874d738085865cb108d48b2020-11-25T02:33:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3843410.1371/journal.pone.0038434Comparison of clinical and parasitological data from controlled human malaria infection trials.Meta RoestenbergGeraldine A O'HaraChristopher J A DuncanJudith E EpsteinNick J EdwardsAnja ScholzenAndré J A M van der VenCornelus C HermsenAdrian V S HillRobert W SauerweinBACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.http://europepmc.org/articles/PMC3372522?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meta Roestenberg Geraldine A O'Hara Christopher J A Duncan Judith E Epstein Nick J Edwards Anja Scholzen André J A M van der Ven Cornelus C Hermsen Adrian V S Hill Robert W Sauerwein |
spellingShingle |
Meta Roestenberg Geraldine A O'Hara Christopher J A Duncan Judith E Epstein Nick J Edwards Anja Scholzen André J A M van der Ven Cornelus C Hermsen Adrian V S Hill Robert W Sauerwein Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS ONE |
author_facet |
Meta Roestenberg Geraldine A O'Hara Christopher J A Duncan Judith E Epstein Nick J Edwards Anja Scholzen André J A M van der Ven Cornelus C Hermsen Adrian V S Hill Robert W Sauerwein |
author_sort |
Meta Roestenberg |
title |
Comparison of clinical and parasitological data from controlled human malaria infection trials. |
title_short |
Comparison of clinical and parasitological data from controlled human malaria infection trials. |
title_full |
Comparison of clinical and parasitological data from controlled human malaria infection trials. |
title_fullStr |
Comparison of clinical and parasitological data from controlled human malaria infection trials. |
title_full_unstemmed |
Comparison of clinical and parasitological data from controlled human malaria infection trials. |
title_sort |
comparison of clinical and parasitological data from controlled human malaria infection trials. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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. |
url |
http://europepmc.org/articles/PMC3372522?pdf=render |
work_keys_str_mv |
AT metaroestenberg comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT geraldineaohara comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT christopherjaduncan comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT juditheepstein comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT nickjedwards comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT anjascholzen comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT andrejamvanderven comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT corneluschermsen comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT adrianvshill comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials AT robertwsauerwein comparisonofclinicalandparasitologicaldatafromcontrolledhumanmalariainfectiontrials |
_version_ |
1724815554044231680 |