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Record W4411668986 · doi:10.1101/2025.06.24.660981

Host iron deficiency protects against <i>Plasmodium</i> infection and drives parasite molecular reprofiling

2025· preprint· en· W4411668986 on OpenAlexaff
Danielle Clucas, Cavan Bennett, Rebecca Harding, Anne Pettikiriarachchi, Andrew Baldi, Louise M. Randall, Ryan Steel, Ronan Mellin, Melissa S. Hobbs, Sabrina Caiazzo, Martin N. Mwangi, Katherine Fielding, Peter F. Hickey, Tracey M. Baldwin, Daniela Amann‐Zalcenstein, Samantha J. Emery‐Corbin, Glory Mzembe, Ernest Moya, Sabine Braat, Aaron R. Jex, Ayşe Y. Demir, Hans Verhoef, Kamija S. Phiri, Beverley‐Ann Biggs, Wai‐Hong Tham, Justin A. Boddey, Sant‐Rayn Pasricha, Ricardo Ataíde

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicParasites and Host Interactions
Canadian institutionsNutrition International
FundersNational Health and Medical Research CouncilMedical Research CouncilBill and Melinda Gates Foundation
KeywordsParasite hostingMalariaHost (biology)Iron deficiencyPlasmodium (life cycle)BiologyImmunologyVirologyMedicineInternal medicineGeneticsComputer scienceAnemia

Abstract

fetched live from OpenAlex

Abstract Iron deficiency, anemia and Plasmodium infection represent significant global health challenges with overlapping geographical distributions, particularly affecting pregnant women in Africa, yet the mechanisms underlying their interactions remain poorly understood. We employed a multilayered approach combining clinical data from Malawian pregnant women (n=711) in the REVAMP trial, a genetic mouse model (Tmprss6-knockout), and in vitro P. falciparum cultures to clarify associations between iron status and malaria susceptibility. Iron deficiency was associated with 50% reduced P. falciparum parasitemia in pregnant women (95% CI [30%-64%], p&lt;0.0001), while iron-deficient mice exhibited significantly improved survival against P. berghei (median 15.5 days vs. 7.0 days for WT mice) and protection from cerebral malaria (83% vs 17% survival). Iron chelation induced substantial transcriptomic and proteomic changes in cultured parasites, affecting host cell invasion and nutrient acquisition processes. Importantly, intravenous iron supplementation did not increase subsequent parasitemia when coupled with malaria prevention. These findings demonstrate that iron deficiency protects against Plasmodium infection and support WHO recommendations for iron supplementation in malaria-endemic regions when combined with adequate malaria prevention strategies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.084
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.241
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

Explore more

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