Evidence map›Paper›PMID 37828012›Full record

ArticleNature communications2023

Clinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito.

Victoria A Balta, Deborah Stiffler, Abeer Sayeed, Abhai K Tripathi, Rubayet Elahi, Godfree Mlambo, Rahul P Bakshi, Amanda G Dziedzic, Anne E Jedlicka, Elizabeth Nenortas and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
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  12. Treatment of avian malaria in captive African penguins (International journal of veterinary science and medicine · 2025
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  14. Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024
    Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 2 countries.

Victoria A BaltaW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0003-0685-6697
Deborah StifflerW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Abeer SayeedW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Abhai K TripathiW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0001-9848-0142
Rubayet ElahiW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Godfree MlamboW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Rahul P BakshiThe Johns Hopkins Malaria Research Institute, Baltimore, MD, 21205, USA.
Amanda G DziedzicW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Anne E JedlickaW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0003-3826-2973
Elizabeth NenortasDivision of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, MD, 21205-2186, USA.
Keyla Romero-RodriguezDivision of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, MD, 21205-2186, USA.
Matthew A CanonizadoDivision of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore, MD, 21205-2186, USA.
Alexis MannW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Andrew OwenCentre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L69 3BX, UK.ORCID 0000-0002-9819-7651
David J SullivanW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0003-0319-0578
Sean T PriggeW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0001-9684-1733
Photini SinnisW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.ORCID 0000-0003-2954-7547
Theresa A ShapiroW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. tshapiro@jhmi.edu.ORCID 0000-0002-6823-7536
Johns Hopkins University · USUniversity of Liverpool · GB

Funding

Essential PK/PD relationships of antimalarial drugsR01AI095453 · NIAID · JOHNS HOPKINS UNIVERSITY · PI SHAPIRO, THERESA A · 2012 to 2024
$4.8M
Dual artemisinin action combats resistanceR01AI150763 · NIAID · JOHNS HOPKINS UNIVERSITY · PI SULLIVAN, DAVID JOSEPH, VEKILOV, PETER G · 2021 to 2025
$2.9M
The Skin Phase of Malaria Infection (Sharon Patray Diversity Supplement)R01AI132359 · NIAID · JOHNS HOPKINS UNIVERSITY · PI SINNIS, PHOTINI · 2017 to 2021
$2.7M
Malaria and Mosquito/Tick-borne DiseasesT32AI138953 · NIAID · JOHNS HOPKINS UNIVERSITY · PI DAVID Joseph SULLIVAN · 2019 to 2026
$2.0M
NIAID NIH HHS R01 AI095453NIAID NIH HHS R01 AI132359NIAID NIH HHS R01 AI150763NIAID NIH HHS T32 AI138953
6 · The paper itself

Abstract

Long-acting injectable medications, such as atovaquone, offer the prospect of a "chemical vaccine" for malaria, combining drug efficacy with vaccine durability. However, selection and transmission of drug-resistant parasites is of concern. Laboratory studies have indicated that atovaquone resistance disadvantages parasites in mosquitoes, but lack of data on clinically relevant Plasmodium falciparum has hampered integration of these variable findings into drug development decisions. Here we generate atovaquone-resistant parasites that differ from wild type parent by only a Y268S mutation in cytochrome b, a modification associated with atovaquone treatment failure in humans. Relative to wild type, Y268S parasites evidence multiple defects, most marked in their development in mosquitoes, whether from Southeast Asia (Anopheles stephensi) or Africa (An. gambiae). Growth of asexual Y268S P. falciparum in human red cells is impaired, but parasite loss in the mosquito is progressive, from reduced gametocyte exflagellation, to smaller number and size of oocysts, and finally to absence of sporozoites. The Y268S mutant fails to transmit from mosquitoes to mice engrafted with human liver cells and erythrocytes. The severe-to-lethal fitness cost of clinically relevant atovaquone resistance to P. falciparum in the mosquito substantially lessens the likelihood of its transmission in the field.

Indexed as

AnophelesAntimalarialsMalariaMalaria, FalciparumParasitesVaccinesAnimalsAntiparasitic AgentsAtovaquoneHumansMicePlasmodium falciparumAntimalarialsAntiparasitic AgentsAtovaquoneVaccines

Identifiers

PMID37828012
PMCPMC10570281
OpenAlexW4387568474

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.