Details

Autor(en) / Beteiligte

• Stebbins, Erin
• Jumani, Rajiv S
• Klopfer, Connor
• Barlow, John
• Miller, Peter
• Campbell, Mary A
• Meyers, Marvin J
• Griggs, David W
• Huston, Christopher D
• Sinnis, Photini

Titel

Clinical and microbiologic efficacy of the piperazine-based drug lead MMV665917 in the dairy calf cryptosporidiosis model

Ist Teil von

• PLoS neglected tropical diseases, 2018-01, Vol.12 (1), p.e0006183-e0006183

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cryptosporidiosis causes life-threatening diarrhea in infants, but the best available treatment is only modestly efficacious. Rodents infected with relevant Cryptosporidium species do not develop diarrhea, which complicates drug development. Cryptosporidium parvum infection of dairy calves, however, causes an illness like that seen in infants. Here, the clinical and microbiologic anti-Cryptosporidium efficacy of the piperazine-based compound MMV665917 was demonstrated in neonatal calves. Oral administration of MMV665917 (22 mg/kg once daily) was begun two days after the onset of severe diarrhea and continued for seven days. Treatment resulted in prompt resolution of diarrhea, and reduced total fecal oocyst shedding by ~94%. MMV665917 was useful for treatment, rather than just prophylaxis, since it was safe and effective when administered well after the onset of diarrhea. Furthermore, even though all animals received intensive supportive care, there was a strong trend towards improved secondary health outcomes, including general health, appetite, and dehydration measures amongst treated animals. These data establish MMV665917 as an outstanding lead compound for Cryptosporidium drug development.