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    Opportunities and Challenges in Developing a Controlled Human Infection Model for Testing Antiparasitic Agents

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    Author
    Jumani, Rajiv S
    Blais, Johanne
    Tillmann, Hanns-Christian
    Segal, Florencia
    Wetty, Dean
    Ostermeier, Christian
    Nuber, Natko
    Lakshman, Jay
    Aziz, Natasha
    Chandra, Richa
    Chen, Wilbur H
    Chappell, Cynthia L
    Diagana, Thierry T
    Manjunatha, Ujjini H
    Show allShow less

    Date
    2021-04-06
    Journal
    ACS Infectious Diseases
    Publisher
    American Chemical Society
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1021/acsinfecdis.1c00057
    Abstract
    Cryptosporidiosis is a leading cause of moderate-to-severe diarrhea in low- and middle-income countries, responsible for high mortality in children younger than two years of age, and it is also strongly associated with childhood malnutrition and growth stunting. There is no vaccine for cryptosporidiosis and existing therapeutic options are suboptimal to prevent morbidity and mortality in young children. Recently, novel therapeutic agents have been discovered through high-throughput phenotypic and target-based screening strategies, repurposing malaria hits, etc., and these agents have a promising preclinical in vitro and in vivo anti-Cryptosporidium efficacy. One key step in bringing safe and effective new therapies to young vulnerable children is the establishment of some prospect of direct benefit before initiating pediatric clinical studies. A Cryptosporidium controlled human infection model (CHIM) in healthy adult volunteers can be a robust clinical proof of concept model for evaluating novel therapeutics. CHIM could potentially accelerate the development path to pediatric studies by establishing the safety of a proposed pediatric dosing regimen and documenting preliminary efficacy in adults. We present, here, perspectives regarding the opportunities and perceived challenges with the Cryptosporidium human challenge model.
    Keyword
    CHIM
    Cryptosporidium
    antiparasitic agent
    cryptosporidiosis
    diarrhea
    drug discovery
    human-challenge model
    pediatric development
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15645
    ae974a485f413a2113503eed53cd6c53
    10.1021/acsinfecdis.1c00057
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