Opportunities and Challenges in Developing a Controlled Human Infection Model for Testing Antiparasitic Agents
AuthorJumani, Rajiv S
Chen, Wilbur H
Chappell, Cynthia L
Diagana, Thierry T
Manjunatha, Ujjini H
JournalACS Infectious Diseases
PublisherAmerican Chemical Society
MetadataShow full item record
AbstractCryptosporidiosis 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.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15645
- A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis.
- Authors: Love MS, Beasley FC, Jumani RS, Wright TM, Chatterjee AK, Huston CD, Schultz PG, McNamara CW
- Issue date: 2017 Feb
- Cryptosporidiosis Drug Discovery: Opportunities and Challenges.
- Authors: Manjunatha UH, Chao AT, Leong FJ, Diagana TT
- Issue date: 2016 Aug 12
- Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial.
- Authors: Nachipo P, Hermann D, Quinnan G, Gordon MA, Van Voorhis WC, Iroh Tam PY
- Issue date: 2018 Aug 23
- Phenotypic screening techniques for <i>Cryptosporidium</i> drug discovery.
- Authors: Love MS, McNamara CW
- Issue date: 2021 Jan
- Metal-captured inhibition of pre-mRNA processing activity by CPSF3 controls <i>Cryptosporidium</i> infection.
- Authors: Swale C, Bougdour A, Gnahoui-David A, Tottey J, Georgeault S, Laurent F, Palencia A, Hakimi MA
- Issue date: 2019 Nov 6