Efficacy of a bovine colostrum and egg-based intervention in acute childhood diarrhoea in Guatemala: a randomised, double-blind, placebo-controlled trial

Abstract

BackgroundTreatments for paediatric diarrhoeal disease are limited. We assessed the impact of a bovine colostrum and egg-based treatment designed to reduce diarrhoea duration through non-specific and pathogen-directed mechanisms in children.MethodsRandomised, double-blind, placebo-controlled trial of PTM202, derived from bovine colostrum and hyperimmune hen’s egg on the duration of acute diarrhoeal disease in Guatemalan children. PTM202 contains specific immunoglobulins that target rotavirus, enterotoxigenic Escherichia coli, Shiga toxin-producing E. coli and Salmonella. Children aged 6–35 months presenting to three sites (one rural and two urban) with acute non-bloody diarrhoea were computer randomised to receive three daily doses of PTM202 or placebo. The primary outcome was the post-treatment duration of diarrhoea assessed in the per protocol population. Diarrhoeal pathogens were identified in stool by multiplex PCR (FilmArray Gastrointestinal-Panel, BioFire, Salt Lake City, Utah, USA). Key secondary outcomes included postdiarrhoeal weight gain and impact on diarrhoeal duration stratified by study site and presence of PTM202-targeted organisms in stool at enrolment. Safety was assessed in all participants.ResultsFrom 9 March 2015 to 25 January 2016, 325 children were enrolled, and 301 (154 intervention and 147 placebo) were analysed for the primary outcome. No difference in diarrhoea duration was observed between intervention and placebo in the total population, but a significant reduction was observed in the treatment group among children with at least one targeted pathogen in stool (HR=1.46, P=0.02), an effect most pronounced in urban subjects (HR 2.20, P=0.007) who had fewer stool pathogens and better nutritional status. No impact on 2-week or 4-week weight gain was noted. No adverse events attributed to PTM202 occurred.ConclusionResults demonstrate the potential to target specific pathogens occurring in children with acute non-bloody diarrhoea and shorten illness duration using a novel, safe, nutrition-based intervention. PTM202 may represent a new tool to ameliorate the effects of acute diarrhoeal disease in low/middle-income populations.Trial registration numberNCT02385773; Results.

Oral bovine colostrum supplementation does not increase circulating insulin-like growth factor-1 concentration in healthy adults: results from short- and long-term administration studies

“…These trials suggest that colostrum has clinical value for NSAID-induced gut injury [9], chemotherapy induced mucositis [17] and inflammatory bowel disease [18]. In addition, colostrum may have value for reducing symptoms of infective diarrhea [19], possibly acting through its specific (antibodies) and general antimicrobial constituents such as lactoferrin. Colostrum may also have value as a sports nutritional supplement to reduce the incidence of upper respiratory tract infections during training [15] and to reduce the increased gut permeability that occurs during heavy exercise [20].…”

Effects of Bovine Colostrum with or without Egg on In Vitro Bacterial-Induced Intestinal Damage with Relevance for SIBO and Infectious Diarrhea

“…The bacteria tested in the current series of experiments covered the most common aerobic organisms cultured from patients with SIBO. In addition, we included two more toxic bacteria associated with episodic diarrhea, i.e., EPEC and Salmonella , to determine if common protective mechanisms were present across bacteria with differing toxicity and because a BC and egg combination had been reported to reduce diarrhea caused by these organisms [ 18 ]. The addition of BC, egg, or the combination did not inhibit growth of the bacteria in vitro, which were results in keeping with previous findings that hyperimmune IgY antibodies raised against 078:K80 E coli .…”

“…We had previously shown that 1 mg/mL was the optimal concentration for BC or egg for inducing proliferation and migration in a variety of gut cell lines including Caco-2 cells, without causing any toxic effects [ 17 ]. Similarly, the 60:40 BC/egg ratio was used as it had been shown to reduce duration of diarrhea in patients with infectious diarrhea [ 18 ] and we previously showed synergistic responses when used in this ratio for reducing DSS-induced colitis and NSAID-induced small intestinal injury [ 17 ].…”

“…Synergistic responses were seen when the egg and BC were used in combination in the DSS and NSAID models and in in vitro models of proliferation and migration [ 17 ]. Further evidence for the value of a BC and egg combination comes from a study performed in Guatemala that showed this combination reduced duration of diarrhea in patients with infectious diarrhea, although interpretation is limited because the study did not examine the individual components (BC and egg) in isolation [ 18 ].…”

Immunoglobulin Y for Potential Diagnostic and Therapeutic Applications in Infectious Diseases

“…A randomized, double-blind, placebo-controlled trial evaluated 301 Guatemalan children (154 intervention and 147 placebo) with acute non-bloody diarrhea who received PTM202 (combined IgY specifically targets rotavirus, enterotoxigenic E. coli , Shiga toxin-positive E. coli , and salmonella) or placebo for 3 days ( 237 ). PTM202 led to a reduction in duration of diarrhea among children whose diarrheal stool at enrollment contained one or more PTM202-targeted organisms.…”