Systemic efficacy on Cryptosporidium parvum infection of aminoxanide (RM-5061), a new amino-acid ester thiazolide prodrug of tizoxanide.

Cryptosporidiosis is a gastrointestinal illness with profuse diarrhoea. Although there are no other Food and Drug Administration (FDA)-approved alternatives for the treatment of cryptosporidiosis, nitazoxanide (NTZ) can be qualified as partially effective. In immunosuppressed conditions, severe and/or disseminated cryptosporidiosis may occur and patients should be treated parenterally. To achieve the goal of developing parenteral treatment for cryptosporidiosis, the current study was undertaken to investigate the in vitro and in vivo anticryptosporidial activity of aminoxanide. This new l-tert-leucyl thiazolide is a soluble prodrug of tizoxanide (TIZ), the main metabolite of NTZ. Confirming the good efficacy of aminoxanide in Cryptosporidium parvum-infected HCT-8 cells with a 50% inhibitory concentration of 1.55 µm (±0.21), in immunosuppressed C. parvum-infected Mongolian gerbils (Meriones unguiculatus), a 5-day treatment with a daily intramuscular dose of 100 mg kg−1 aminoxanide resulted in a 72.5% oocyst excretion inhibition, statistically equivalent to 75.5% in gerbils treated with a 4-fold lower oral dose of NTZ. Cryptosporidium parvum-induced intestinal pathology and inflammation were improved. Aminoxanide provides an injectable form of TIZ that NTZ was unable to do and is a promising drug for which optimization of the formulation should be further explored. These results represent a first promising step towards the goal of developing a parenteral treatment for cryptosporidiosis.

Common occurrence of Cryptosporidium hominis in asymptomatic and symptomatic calves in France.

BACKGROUND: Cryptosporidium spp. infections are the most frequent parasitic cause of diarrhea in humans and cattle. However, asymptomatic cases are less often documented than symptomatic cases or cases with experimentally infected animals. Cryptosporidium (C.) hominis infection accounts for the majority of pediatric cases in several countries, while C. parvum is a major cause of diarrhea in neonatal calves. In cattle Cryptosporidium spp. infection can be caused by C. parvum, C. bovis, C.andersoni and C. ryanae, and recently, reports of cattle cases of C. hominis cryptosporidiosis cases suggest that the presence of C. hominis in calves was previously underestimated. METHODOLOGY/PRINCIPAL FINDINGS: From February to November 2015, Cryptosporidium spp. infected calves were detected in 29/44 randomly included farms from 5 geographic regions of France. C. hominis and C. parvum were found in 12/44 and 26/44 farms, respectively with higher C. hominis prevalence in the western region. In 9 farms, both C. parvum and C. hominis were detected. Eighty-six of 412 (73/342 asymptomatic and 13/70 symptomatic) one to nine-week-old calves shed C. hominis or C. parvum oocysts (15 and 71 calves, respectively), with no mixed infection detected. The predominant C. hominis IbA9G3 genotype was present in all regions, and more frequent in the western region. An incompletely characterized Ib, and the IbA13G3, IbA9G2 and IbA14G2 genotypes were present only in the western region. For C. parvum, the most frequent genotype was IIaA16G3R1 with no geographic clustering. Most C. hominis infected calves were asymptomatic, with some exceptions of IbA9G2 and IbA9G3 isolates, while C. parvum IIaA16G3R1 was associated with symptoms. CONCLUSIONS/SIGNIFICANCE: Present results indicate for the first time that in several geographic regions of France, C. hominis was present in about one fifth of both asymptomatic and symptomatic infected calves, with isolated genotypes likely associated with human infection. Further investigations are aimed at documenting direct or indirect transmissions between livestock and humans.