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The Global Enteric Multicenter Study (GEMS), a study of infectious diarrhea involving over 20,000 children at seven sites in sub-Saharan Africa and South Asia, recently reported that the little-studied protozoan parasite Cryptosporidium ranks second to rotavirus as a cause of life-threatening diarrhea in infants and was also associated with growth stunting and excess mortality [1]. Cryptosporidium species, predominantly Cryptosporidium hominis and Cryptosporidium parvum, were previously well known for causing chronic diarrhea in AIDS patients, as well as for their chlorine resistance and their association with waterborne outbreaks in the developed world [2–4]. Numerous smaller studies had also demonstrated the importance of cryptosporidiosis in young children and its association with malnutrition (reviewed in [5]) [5–19], but Cryptosporidium had not previously garnered significant attention from the pharmaceutical industry or major funding organizations such as the Bill and Melinda Gates Foundation. The GEMS put cryptosporidiosis into context amongst more studied diarrheal pathogens and brought it to the attention of these organizations. No vaccine for cryptosporidiosis exists, and the available treatments for those most at risk are inadequate. The only licensed drug, nitazoxanide, is unreliable in severely malnourished children (~56% improvement in diarrhea at 7 days versus 26% in controls [20]), and shows no benefit relative to placebo in HIV-infected patients [20–22]. More reliable, efficacious, and faster-acting treatments are needed for these populations.  Interest in Cryptosporidium drug development has correspondingly increased, and despite a limited experimental system, several new molecules with in vitro and, in some cases, validated in vivo activity against Cryptosporidium have been reported [23–35]. However, data regarding these compounds are difficult to compare due to use of differing in vitro and in vivo models and lack of assay standardization (see [36] for a thorough review of this and other barriers). A major current challenge then is to develop a common framework to help Cryptosporidium researchers and funding agencies to prioritize screening hits and leads for further development and to define essential developmental milestones. In this article, we propose a target product profile (TPP) (Table 1) and testing cascade (Fig 1) that can be used to guide this process. This TPP will undoubtedly require revision as progress is made, but can provide clear initial goals and a framework for go/no-go decision making in order to facilitate the appropriate distribution of effort and limited resources.    Fig 1  Proposed development scheme and anticipated costs for Cryptosporidium drug development.      Table 1  Proposed target product profile for treatments for diarrhea due to cryptosporidiosis.

A Proposed Target Product Profile and Developmental Cascade for New Cryptosporidiosis Treatments