Drug treatment and novel drug target againstCryptosporidium

Abstract

Summary :Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ)'s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro-thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.

Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice

“…Nitazoxanide has broadspectrum activity against nematodes [15], trematodes [16], and protozoa, including Giardia lamblia, Cryptosporidium spp., Ascaris lumbricoides, Entamoeba histolytica, and Taenia solium [17]. In humans, nitazoxanide has been approved by the US FDA for the treatment of diarrhea caused by Cryptosporidium parvum and G. lamblia infection in children 1-11 years of age [18].…”

Validation of cell-free culture using scanning electron microscopy (SEM) and gene expression studies

“…Currently, nitazoxanide (NTZ) is approved for treatment of cryptosporidiosis in children and immunocompetent adults in the U.S.A., however treatment failures are common and NTZ is not effective without an appropriate immune response and is therefore ineffective for the treatment of immunocompromised individuals and young children (Gargala, 2008;Rossignol, 2010).…”

An evaluation of the potential use ofCryptosporidiumspecies as agents for deliberate release

“…Several therapeutic drugs have been screened for potential anti-cryptosporidial activity; however, the majority, including probiotic bacteria, were ineffective 53. Cell culture studies suggest potential synergistic effects of nitazoxanide in combination with azithromycin or rifabutin 54.…”