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Evaluation of Malaria Parasite Transmission Competency Using a Nanozyme-Based Immunodiagnostic Targeting Female Gamete Antigen Release

Abstract:
Preventing malaria parasite transmission to the mosquito vector is a key elimination challenge that could benefit from a diagnostic test that can identify transmission-competent individuals. Only sexual parasite forms, called gametocytes, which activate into gametes (gametogenesis) upon mosquito uptake or blood sampling are responsible for transmission. Herein, we devised a nanozyme-based immunoassay to detect the Plasmodium falciparum female gametocyte activation antigen PfG377, which is released during gametogenesis. Initial validation of our nanozyme assay with cultured parasites demonstrated that levels of PfG377 were higher in supernatants of activated versus nonactivated cultures and those treated with transmission blocking drugs. To define the field potential of this approach, patient samples from a clinical transmission-focused trial were used, including those receiving treatment with the gametocytocidal drug primaquine (PQ) that sterilizes gametocytes and blocks transmission. PQ-treated patient samples showed significantly lower signals of PfG377 2 days after treatment, consistent with an inability of PQ-treated gametocytes to activate and release antigen upon blood sampling. This study serves as a pathfinder for field transmission rapid diagnostics to detect transmission-competent individuals, which could help revive malaria elimination strategies.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1021/acsnano.5c10298

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Institution:
University of Oxford
Division:
SSD
Department:
Divisional Administration
Sub department:
Kavli Institute for Nanoscience Discovery
Role:
Author
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Role:
Author
ORCID:
0000-0003-4868-9364


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Funder identifier:
https://ror.org/029chgv08
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Funder identifier:
https://ror.org/04e3zg361
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Funder identifier:
https://ror.org/011kf5r70
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Funder identifier:
https://ror.org/054225q67


Publisher:
American Chemical Society
Journal:
ACS Nano More from this journal
Volume:
19
Issue:
41
Pages:
36419-36434
Publication date:
2025-10-06
Acceptance date:
2025-09-15
DOI:
EISSN:
1936-086X
ISSN:
1936-0851


Language:
English
Keywords:
Pubs id:
2298730
UUID:
uuid_76116b0b-7f35-4e7d-8f3a-e0df20a7edfd
Local pid:
pubs:2298730
Source identifiers:
3395956
Deposit date:
2025-10-22
ARK identifier:
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