Diarrheal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of pediatric diarrhea with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor effective treatment. We establish a drug discovery process built on scalable phenotypic assays and mouse models that takes advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity we identified pyrazolopyridines as inhibitors of Cryptosporidium parvum and C. hominis. Oral treatment with the pyrazolopyridine KDU731 results in potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest the Cryptosporidium lipid kinase PI(4)K as a target for pyrazolopyridines and warrant further preclinical evaluation of KDU731 as a drug candidate for the treatment of cryptosporidiosis.

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Aeromonas hydrophila was identified by culture technique in diarrhoeal stools and ascites in a patient of 57 years of age who suffered from known alcoholic cirrhosis and additional acute gastroenteritis. No other pathogens that would produce acute diarrhoea were found. The isolated Aeromonas hydrophila strain was characterised by the pathogenic properties known to date as pertaining to this species (formation of haemolysin and enterotoxins). Hence it is evident that Aeromonas hydrophila occurs in Germany also as an autochthonous pathogen of acute infectious enteritis.