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.
Highlights
Cryptosporidiosis is a leading cause of moderate-tosevere diarrhea in low- and middle-income countries, responsible for high mortality in children younger than two years of age, and it is strongly associated with childhood malnutrition and growth stunting
Cryptosporidium spp. are a leading cause of pediatric diarrhea in low- and middle-income countries (LMICs) and represents one of the leading causes of diarrheal deaths in young children aged 0−24 months.[5−8] Cryptosporidiosis is estimated to be responsible for 48 000−202 000 deaths annually in children younger than two years of age in South Asia and Sub-Saharan Africa and ∼7.6 million diarrhea cases annually are attributable to Cryptosporidium infection in these regions.[5,9]
Evidence suggests that repeated Cryptosporidium infections in children are associated with long-term effects and debilitating growth-stunting.[10,11]
Summary
Following a standard phase 1 with NCE in healthy adults, the Global Health, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States ‡Cynthia L. Cryptosporidium CHIM would be a stepping stone to pediatric Complete contact information is available at: trials. NCEs in healthy adults before advancing to the vulnerable pediatric population; derisking investment in juvenile toxicology studies; and providing PK/PD data to inform dose. The safety experience from several published CHIM studies.[43,44,46−48] And C. parvum infection in healthy adults causes a self-limiting illness and an effective rescue medication is available. The recent accomplishments in early drug discovery and availability of a Cryptosporidium controlled human infection model offer a compelling vision toward enabling a much-
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