Efficacy of halofuginone products to prevent or treat cryptosporidiosis in bovine calves: a systematic review and meta-analyses.

A prior systematic review on the efficacy of halofuginone (HFG) treatment to prevent or treat cryptosporidiosis in bovine calves was inconclusive. We undertook an updated synthesis and meta-analyses on key outcomes for the treatment of calves with HFG. Evaluated outcomes were oocyst shedding, diarrhoea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Most doses were 100-150 mcg kg-1 day-1. Results were subgrouped by study design, experiments with the lowest risk of bias and lack of industry funding. Eighteen articles were found that described 25 experiments. Most evidence came from randomized controlled trials in Europe. Significantly lower incidence of oocyst shedding, diarrhoea burden and mortality was reported when treatment started before calves were 5 days old. Most studies reported on outcomes for animals up to at least 28 days old. Publication bias was possible in all outcomes and seemed especially likely for diarrhoea outcomes. Beneficial results when HFG treatment was initiated in calves older than 5 days were also found. Prophylactic treatment to prevent cryptosporidiosis is effective in preventing multiple negative outcomes and is beneficial to calf health and will result in a reduction of environmental contamination by Cryptosporidium oocysts.

Microbiome diversity is a modifiable virulence factor for cryptosporidiosis.

Cryptosporidium spp. infection causes significant disease in immunosuppressed individuals and children under the age of 5 years. The severity of the pathological presentation of cryptosporidiosis is a function of the host and parasite genotypes, host immune status, and the enteric environment or microbiome of the host. Cryptosporidiosis often presents with abdominal pain and severe diarrhoea and is associated with intestinal dysbiosis and inflammation. Our systematic analysis of the available literature revealed that bacterial diversity is reduced during infection in larger animal models, lending support to recent studies which indicate that the use of probiotics or the presence of a naturally diverse gut microbiome can prevent or minimise pathology caused by gastrointestinal pathogens. In summary, we present evidence that the presence of a diverse gut microbiome, natural or induced, reduces both symptomatic pathology and oocyst output.