Opportunities and Challenges in Developing a Controlled Human Infection Model for Testing Antiparasitic Agents
Author
Jumani, Rajiv SBlais, 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
Date
2021-04-06Journal
ACS Infectious DiseasesPublisher
American Chemical SocietyType
Article
Metadata
Show full item recordAbstract
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
CHIMCryptosporidium
antiparasitic agent
cryptosporidiosis
diarrhea
drug discovery
human-challenge model
pediatric development
Identifier to cite or link to this item
http://hdl.handle.net/10713/15645ae974a485f413a2113503eed53cd6c53
10.1021/acsinfecdis.1c00057
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