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Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials

Pre-existing and intervening low-density Plasmodium infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and their immunological effects may detract from intended vaccine-induced immune responses. Historically, these infections were o...

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Autores principales: Owalla, Tonny J., Hergott, Dianna E. B., Seilie, Annette M., Staubus, Weston, Chavtur, Chris, Chang, Ming, Kublin, James G., Egwang, Thomas G., Murphy, Sean C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531235/
https://www.ncbi.nlm.nih.gov/pubmed/36203582
http://dx.doi.org/10.3389/fimmu.2022.1003452
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author Owalla, Tonny J.
Hergott, Dianna E. B.
Seilie, Annette M.
Staubus, Weston
Chavtur, Chris
Chang, Ming
Kublin, James G.
Egwang, Thomas G.
Murphy, Sean C.
author_facet Owalla, Tonny J.
Hergott, Dianna E. B.
Seilie, Annette M.
Staubus, Weston
Chavtur, Chris
Chang, Ming
Kublin, James G.
Egwang, Thomas G.
Murphy, Sean C.
author_sort Owalla, Tonny J.
collection PubMed
description Pre-existing and intervening low-density Plasmodium infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and their immunological effects may detract from intended vaccine-induced immune responses. Historically, these infections were often unrecognized since infrequent and often analytically insensitive parasitological testing was performed before and during trials. Molecular diagnostics now permits their detection, but investigators must weigh the cost, complexity, and personnel demands on the study and the laboratory when scheduling such tests. This paper discusses the effect of pre-existing and intervening, low-density Plasmodium infections on malaria vaccine trial endpoints and the current methods employed for their infection detection. We review detection techniques, that until recently, provided a dearth of cost-effective strategies for detecting low density infections. A recently deployed, field-tested, simple, and cost-effective molecular diagnostic strategy for detecting pre-existing and intervening Plasmodium infections from dried blood spots (DBS) in malaria-endemic settings is discussed to inform new clinical trial designs. Strategies that combine sensitive molecular diagnostic techniques with convenient DBS collections and cost-effective pooling strategies may enable more thorough and informative infection monitoring in upcoming malaria clinical trials and epidemiological studies.
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spelling pubmed-95312352022-10-05 Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials Owalla, Tonny J. Hergott, Dianna E. B. Seilie, Annette M. Staubus, Weston Chavtur, Chris Chang, Ming Kublin, James G. Egwang, Thomas G. Murphy, Sean C. Front Immunol Immunology Pre-existing and intervening low-density Plasmodium infections complicate the conduct of malaria clinical trials. These infections confound infection detection endpoints, and their immunological effects may detract from intended vaccine-induced immune responses. Historically, these infections were often unrecognized since infrequent and often analytically insensitive parasitological testing was performed before and during trials. Molecular diagnostics now permits their detection, but investigators must weigh the cost, complexity, and personnel demands on the study and the laboratory when scheduling such tests. This paper discusses the effect of pre-existing and intervening, low-density Plasmodium infections on malaria vaccine trial endpoints and the current methods employed for their infection detection. We review detection techniques, that until recently, provided a dearth of cost-effective strategies for detecting low density infections. A recently deployed, field-tested, simple, and cost-effective molecular diagnostic strategy for detecting pre-existing and intervening Plasmodium infections from dried blood spots (DBS) in malaria-endemic settings is discussed to inform new clinical trial designs. Strategies that combine sensitive molecular diagnostic techniques with convenient DBS collections and cost-effective pooling strategies may enable more thorough and informative infection monitoring in upcoming malaria clinical trials and epidemiological studies. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9531235/ /pubmed/36203582 http://dx.doi.org/10.3389/fimmu.2022.1003452 Text en Copyright © 2022 Owalla, Hergott, Seilie, Staubus, Chavtur, Chang, Kublin, Egwang and Murphy https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Owalla, Tonny J.
Hergott, Dianna E. B.
Seilie, Annette M.
Staubus, Weston
Chavtur, Chris
Chang, Ming
Kublin, James G.
Egwang, Thomas G.
Murphy, Sean C.
Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials
title Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials
title_full Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials
title_fullStr Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials
title_full_unstemmed Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials
title_short Rethinking detection of pre-existing and intervening Plasmodium infections in malaria clinical trials
title_sort rethinking detection of pre-existing and intervening plasmodium infections in malaria clinical trials
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531235/
https://www.ncbi.nlm.nih.gov/pubmed/36203582
http://dx.doi.org/10.3389/fimmu.2022.1003452
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