The effect of halofuginone lactate on experimental Cryptosporidium parvum infections in calves

Abstract

The chemoprophylactic effects of halofuginone lactate were tested against calf experimental cryptosporidiosis. Twenty 2-day-old calves, divided into four groups, were orally inoculated with 1 x 10(6) oocysts of Cryptosporidium parvum. The infected control group was unmedicated whereas the three other groups were medicated with the drug at 30, 60 and 120 micrograms kg-1 day-1, respectively, for 7 days, from Day (D) 2 to D8 post-inoculation (D 0 was inoculation day). The calves were weighed twice weekly and disease development and drug efficacy were assessed daily from D0 to D30 from consistency of feces, shedding of oocysts and mortality. Experimental C. parvum infection caused a severe clinical disease with profuse watery diarrhea, high oocyst shedding and mortality (3 out of 5) in the unmedicated group. The results clearly demonstrated the efficacy of halofuginone lactate in reducing the severity of clinical cryptosporidiosis. This efficacy was dose-dependent. The lowest dose (30 micrograms kg-1 day-1) was not able to prevent clinical disease and mortality (3 out of 5). No clinical signs were observed with the 60 and 120 micrograms kg-1 day-1 doses, but the animals shed oocysts after drug withdrawal. This shedding was more delayed the higher the dose of drug administered, but the delayed shedding had no effect on the growth of the animals.

Cryptosporidiosis in People: It's Not Just About the Cows

“…Halofuginone, a quinazoline, is registered for prevention and treatment of cryptosporidiosis in newborn calves in some European countries but its mechanism of action is unknown 27 . At a dose rate of 0.06–0.12 mg/kg bodyweight daily PO, halofuginone improved the clinical status and decreased case fatality and fecal oocyst excretion in a dose‐dependent manner in calves with experimentally induced cryptosporidial infection 28 . In another study, halofuginone at an oral dose rate of 0.1 mg/kg bodyweight daily to calves ranging from 7 to 14 days of life was efficacious in decreasing oocyst shedding, but had no effect on prevalence of diarrhea, fecal water percentage, or severity of dehydration in naturally infected calves in Quebec, compared with untreated controls 29 .…”

Anticoccidial effect of halofuginone hydrobromide against Eimeria tenella with associated histology

“…Halofuginone hydrobromide {[7-bromo-6-chloro-3-[3-(3-hydroxy-2-piperidinyl)-2-oxopropyl]-4 (3H)-quinazolinone]} (Stenorol, Hoechst-Roussel, Somerville, NJ, USA) is one of 11 coccidiostats licensed by the European Union. It is also used as a feed additive for broiler chickens and in turkey coccidiosis control, as approved by the US Food and Drug Administration (Naciri et al 1993;Villacorta et al 1991). Halofuginone hydrobromide is a synthesized analog of febrifugine, which is extracted from the leaf and root of traditional Chinese herbal Dichroa febrifuga Lour.…”

Liquid chromatography-electrospray tandem mass spectrometric assay suitable for quantitation of halofuginone in plasma

“…1) is a quinazolinone alkaloid that is approved to prevent coccidiosis in poultry [1,2] and to treat cryptosporidiosis [3][4][5] and theileriosis in cattle [6,7]. The ability of halofuginone to inhibit both Type 1 collagen synthesis [8][9][10][11][12][13][14] and matrix metalloprotease gene expression [15,16] is potentially useful in reducing tumor growth, because angiogenesis in a growing tumor utilizes Type 1 collagen [15,17], and matrix metalloproteinases are associated with the ability of a tumor to metastasize [15,16,18,19].…”