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  1. Article: Global gene expression of human malaria parasite liver stages throughout intrahepatocytic development.

    Zanghi, Gigliola / Patel, Hardik / Camargo, Nelly / Smith, Jenny L / Bae, Yeji / Flannery, Erika L / Chuenchob, Vorada / Fishbaugher, Matthew E / Mikolajczak, Sebastian A / Roobsoong, Wanlapa / Sattabongkot, Jetsumon / Hayes, Kiera / Vaughan, Ashley M / Kappe, Stefan H I

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Plasmodium ... ...

    Abstract Plasmodium falciparum
    Language English
    Publishing date 2023-01-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.05.522945
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  2. Article ; Online: Plasmodium vivax.

    Flannery, Erika L / Markus, Miles B / Vaughan, Ashley M

    Trends in parasitology

    2019  Volume 35, Issue 7, Page(s) 583–584

    MeSH term(s) Animals ; Asia, Southeastern ; Culicidae/parasitology ; Life Cycle Stages ; Malaria, Vivax/parasitology ; Malaria, Vivax/prevention & control ; Malaria, Vivax/transmission ; Mosquito Vectors/parasitology ; Plasmodium vivax/physiology ; South America
    Language English
    Publishing date 2019-06-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2019.04.005
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  3. Article ; Online: Correlative light-electron microscopy methods to characterize the ultrastructural features of the replicative and dormant liver stages of Plasmodium parasites.

    Mitchell, Gabriel / Torres, Laura / Fishbaugher, Matthew E / Lam, Melanie / Chuenchob, Vorada / Zalpuri, Reena / Ramasubban, Shreya / Baxter, Caitlin N / Flannery, Erika L / Harupa, Anke / Mikolajczak, Sebastian A / Jorgens, Danielle M

    Malaria journal

    2024  Volume 23, Issue 1, Page(s) 53

    Abstract: Background: The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing ...

    Abstract Background: The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy. A deeper understanding of hypnozoite biology could prove essential in the development of radical cure therapeutics against malaria.
    Results: The liver stages of the rodent parasite Plasmodium berghei, causing non-relapsing malaria, and the simian parasite Plasmodium cynomolgi, causing relapsing malaria, were characterized in human Huh7 cells or primary non-human primate hepatocytes using Correlative Light-Electron Microscopy (CLEM). Specifically, CLEM approaches that rely on GFP-expressing parasites (GFP-CLEM) or on an immunofluorescence assay (IFA-CLEM) were used for imaging liver stages. The results from P. berghei showed that host and parasite organelles can be identified and imaged at high resolution using both CLEM approaches. While IFA-CLEM was associated with more pronounced extraction of cellular content, samples' features were generally well preserved. Using IFA-CLEM, a collection of micrographs was acquired for P. cynomolgi liver stage schizonts and hypnozoites, demonstrating the potential of this approach for characterizing the liver stages of Plasmodium species causing relapsing malaria.
    Conclusions: A CLEM approach that does not rely on parasites expressing genetically encoded tags was developed, therefore suitable for imaging the liver stages of Plasmodium species that lack established protocols to perform genetic engineering. This study also provides a dataset that characterizes the ultrastructural features of liver stage schizonts and hypnozoites from the simian parasite species P. cynomolgi.
    MeSH term(s) Animals ; Humans ; Parasites ; Liver/parasitology ; Malaria/parasitology ; Plasmodium berghei ; Microscopy, Electron
    Language English
    Publishing date 2024-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091229-8
    ISSN 1475-2875 ; 1475-2875
    ISSN (online) 1475-2875
    ISSN 1475-2875
    DOI 10.1186/s12936-024-04862-w
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  4. Article ; Online: Antimalarial drug discovery - approaches and progress towards new medicines.

    Flannery, Erika L / Chatterjee, Arnab K / Winzeler, Elizabeth A

    Nature reviews. Microbiology

    2017  Volume 15, Issue 9, Page(s) 572

    Language English
    Publishing date 2017-07-24
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/nrmicro.2017.88
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  5. Article: Plasmodium vivax

    Flannery, Erika L / Kangwanrangsan, Niwat / Chuenchob, Vorada / Roobsoong, Wanlapa / Fishbaugher, Matthew / Zhou, Kevin / Billman, Zachary P / Martinson, Thomas / Olsen, Tayla M / Schäfer, Carola / Campo, Brice / Murphy, Sean C / Mikolajczak, Sebastian A / Kappe, Stefan H I / Sattabongkot, Jetsumon

    Molecular therapy. Methods & clinical development

    2022  Volume 26, Page(s) 427–440

    Abstract: Plasmodium ... ...

    Abstract Plasmodium vivax
    Language English
    Publishing date 2022-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2022.07.016
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  6. Article ; Online: Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi.

    Mitchell, Gabriel / Roma, Guglielmo / Voorberg-van der Wel, Annemarie / Beibel, Martin / Zeeman, Anne-Marie / Schuierer, Sven / Torres, Laura / Flannery, Erika L / Kocken, Clemens H M / Mikolajczak, Sebastian A / Diagana, Thierry T

    Malaria journal

    2022  Volume 21, Issue 1, Page(s) 393

    Abstract: Background: The zoonotic simian parasite Plasmodium cynomolgi develops into replicating schizonts and dormant hypnozoites during the infection of hepatocytes and is used as a model organism to study relapsing malaria. The transcriptional profiling of P. ...

    Abstract Background: The zoonotic simian parasite Plasmodium cynomolgi develops into replicating schizonts and dormant hypnozoites during the infection of hepatocytes and is used as a model organism to study relapsing malaria. The transcriptional profiling of P. cynomolgi liver stages was previously reported and revealed many important biological features of the parasite but left out the host response to malaria infection.
    Methods: Previously published RNA sequencing data were used to quantify the expression of host genes in rhesus macaque hepatocytes infected with P. cynomolgi in comparison to either cells from uninfected samples or uninfected bystander cells.
    Results: Although the dataset could not be used to resolve the transcriptional profile of hypnozoite-infected hepatocytes, it provided a snapshot of the host response to liver stage schizonts at 9-10 day post-infection and identified specific host pathways that are modulated during the exo-erythrocytic stage of P. cynomolgi.
    Conclusions: This study constitutes a valuable resource characterizing the hepatocyte response to P. cynomolgi infection and provides a framework to build on future research that aims at understanding hepatocyte-parasite interactions during relapsing malaria infection.
    Language English
    Publishing date 2022-12-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2091229-8
    ISSN 1475-2875 ; 1475-2875
    ISSN (online) 1475-2875
    ISSN 1475-2875
    DOI 10.1186/s12936-022-04411-3
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  7. Article ; Online: Burden of medically attended influenza infection and cases averted by vaccination - United States, 2016/17 through 2018/19 influenza seasons.

    Jackson, Michael L / Phillips, C Hallie / Wellwood, Stacie / Kiniry, Erika / Jackson, Lisa A / Martin, Emily T / Monto, Arnold S / McLean, Huong Q / Belongia, Edward A / Gaglani, Manjusha / Dunnigan, Kayan / Raiyani, Chandni / Murthy, Kempapura / Flannery, Brendan / Chung, Jessie R

    Vaccine

    2022  Volume 40, Issue 52, Page(s) 7703–7708

    Abstract: Background: Epidemics of seasonal influenza vary in intensity annually, and influenza vaccine effectiveness (VE) fluctuates based in part on antigenic match to circulating viruses. We estimated the incidence of influenza and influenza cases averted by ... ...

    Abstract Background: Epidemics of seasonal influenza vary in intensity annually, and influenza vaccine effectiveness (VE) fluctuates based in part on antigenic match to circulating viruses. We estimated the incidence of influenza and influenza cases averted by vaccination in four ambulatory care sites in the United States, during seasons when overall influenza VE ranged from 29% to 40%.
    Methods: We conducted active surveillance for influenza at ambulatory care settings at four sites within the United States Influenza Vaccine Effectiveness Network. We extrapolated the total number of influenza cases in the source populations served by these organizations based on incidence of medically attended acute respiratory illness in the source population and influenza test results in those actively tested for influenza. We estimated the number of medically attended influenza cases averted based on incidence, vaccine coverage, and VE.
    Results: From 2016/17 through 2018/19, incidence of ambulatory visits for laboratory-confirmed influenza ranged from 31 to 51 per 1,000 population. Incidence was highest in children aged 9-17 years (range, 56 to 81 per 1,000) and lowest in adults aged 18-49 years (range, 23-32 per 1,000). Medically attended cases averted by vaccination ranged from a high of 46.6 (95 % CI, 12.1- 91.9) per 1,000 vaccinees in children aged 6 months to 8 years, to a low of 6.9 (95 % CI, -5.1- 27.3) per 1,000 vaccinees in adults aged ≥ 65 years.
    Discussion: Even in seasons with low vaccine effectiveness for a particular virus subtype, influenza vaccines can still lead to clinically meaningful reductions in ambulatory care visits for influenza.
    MeSH term(s) Adult ; Child ; Humans ; Infant ; Influenza Vaccines ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Population Surveillance ; Seasons ; United States/epidemiology ; Vaccination
    Chemical Substances Influenza Vaccines
    Language English
    Publishing date 2022-11-12
    Publishing country Netherlands
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2022.11.011
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  8. Article ; Online: Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses.

    Schäfer, Carola / Dambrauskas, Nicholas / Reynolds, Laura M / Trakhimets, Olesya / Raappana, Andrew / Flannery, Erika L / Roobsoong, Wanlapa / Sattabongkot, Jetsumon / Mikolajczak, Sebastian A / Kappe, Stefan H I / Sather, D Noah

    Cell host & microbe

    2021  Volume 29, Issue 5, Page(s) 752–756.e4

    Abstract: Latent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on ... ...

    Abstract Latent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P. vivax sporozoites. Although this regimen did not completely prevent primary infection, antibody-treated mice experienced 62% fewer relapses. The data constitute unprecedented direct experimental evidence that suboptimal efficacy of infection-blocking antibodies, while not completely preventing primary infection, has a pronounced benefit in reducing the number of relapses. These findings suggest that a partially efficacious pre-erythrocytic Plasmodium vivax vaccine can have a disproportionately high impact in positive public health outcomes.
    MeSH term(s) Animals ; Blood/parasitology ; Disease Models, Animal ; Female ; Humans ; Liver/parasitology ; Malaria, Vivax/blood ; Malaria, Vivax/parasitology ; Mice ; Plasmodium vivax/genetics ; Plasmodium vivax/growth & development ; Recurrence
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2021.03.011
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  9. Article ; Online: Antimalarial drug discovery - approaches and progress towards new medicines.

    Flannery, Erika L / Chatterjee, Arnab K / Winzeler, Elizabeth A

    Nature reviews. Microbiology

    2013  Volume 11, Issue 12, Page(s) 849–862

    Abstract: Malaria elimination has recently been reinstated as a global health priority but current therapies seem to be insufficient for the task. Elimination efforts require new drug classes that alleviate symptoms, prevent transmission and provide a radical cure. ...

    Abstract Malaria elimination has recently been reinstated as a global health priority but current therapies seem to be insufficient for the task. Elimination efforts require new drug classes that alleviate symptoms, prevent transmission and provide a radical cure. To develop these next-generation medicines, public-private partnerships are funding innovative approaches to identify compounds that target multiple parasite species at multiple stages of the parasite life cycle. In this Review, we discuss the cell-, chemistry- and target-based approaches used to discover new drug candidates that are currently in clinical trials or undergoing preclinical testing.
    MeSH term(s) Antimalarials/isolation & purification ; Antimalarials/pharmacology ; Clinical Trials as Topic ; Drug Discovery/methods ; Drug Discovery/trends ; Drug Evaluation, Preclinical ; Humans
    Chemical Substances Antimalarials
    Language English
    Publishing date 2013-11-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/nrmicro3138
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  10. Article ; Online: Understanding Treatment Tolerability in Older Adults With Cancer.

    Flannery, Marie A / Culakova, Eva / Canin, Beverly E / Peppone, Luke / Ramsdale, Erika / Mohile, Supriya G

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2021  Volume 39, Issue 19, Page(s) 2150–2163

    MeSH term(s) Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Geriatric Assessment/methods ; Humans ; Neoplasms/therapy ; Patient Reported Outcome Measures ; Randomized Controlled Trials as Topic
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2021-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.21.00195
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