Passive immunisation as therapy for gastrointestinal infections in children

Abstract

Several prophylactic studies in animals and humans have shown potential efficacy of oral therapy with non-human antibodies against different pathogens. Passive immunisation with oral antibodies against different pathogens is an attractive way to treat different gastrointestinal infections caused by pathogens such as rotavirus or enteropathogenic and enterotoxigenic Escherichia coli (EPEC; ETEC). These pathogens give rise to high morbidity and mortality from infantile diarrhoea, especially in the developing world. In addition, Helicobacter pylori, has emerged as an important pathogen for gastrointestinal disease (i.e. ulcers and gastritis).

The aim was to study the efficacy of passive immunisation as therapy via the oral route. In four double-blind placebo-controlled trials, we evaluated bovine and chicken antibodies (IgY) in rotavirus and E. coli induced diarrhoea and Helicobacter pylori infection in 4-24 month old infants from Bangladesh. We also compared ELISA and immunoblotting (IB), 13 C-urea breath test (UBT) and IMS-PCR in stool for the detection of H pylori in the same population. In the diarrhoeal studies, male infants with acute watery diarrhoea were included. The children in the rotavirus trials received either 10g of hyperimmune bovine colostrum (HBC) or hyperimmune egg yolk concentrate (HEYC) per day for four days or a control preparation. Children in the E. coli study received 10g of anti-ETEC HBC and 10g of anti-EPEC HBC. Oral intake and stool losses were recorded in addition to stool frequency and clearance of pathogens from the stool.

In the H. pylori trials children were screened for H. pylori with ELISA, IB, UBT, and IMSPCR in stool. H. pylori UBT-positive children received either I g/day of HBC/placebo for 30 days. Eradication of H. pylori was followed with UBT. In a separate evaluation the diagnostic methods to detect H. pylori were compared.

In the HBC-rotavirus study on 80 children, there was a statistically significantly shorter duration of diarrhoea (p = 0.016), less stool output (g/kg/24h), p = 0.01, and less ORS intake (p = 0.03) in the children receiving HBC compared to placebo. The duration of rotavirus in stool was also shorter in the HBC treated group (p = 0.001). In the HEYC-rotavirus study of 85 children there was no difference in the mean duration of diarrhoea after treatment with HEYC between the groups. However, there was a statistically significant lower stool output, lesser ORS intake (p = 0.01), and lesser stool frequency (p = 0.03) on day one. Rotavirus was found less frequent in stool on day four in the HEYC treated group (p = 0.01). In the HBC-E.coli study on 63 children there were no differences between the groups regarding duration of diarrhoea, daily and total ORS intake, daily and total stool output, and stool frequency. Nor was there any difference in clearance of E. coli from the stool between the groups. In the HBC-H pylori study of 24 H. pylori infected infants, none of the children cleared the infection after one month treatment with HBC. However, measured by UBT, there seemed to be spontaneous eradication or reinfection among the children in the groups. Finally, the concordance between the three screening methods in 68 children was 62% and the prevalence adding all three methods together was 78%.

Giving bovine antibodies from hyperimmunised cows, are effective as oral therapy for rotavirus diarrhoea in children, which previously has been shown for prophylactic treatment. On the other hand, the pathogenesis of E. coli may be too complex as no effect of the treatment was found. Using chicken IgY, there seems to be a beneficial potential, although further studies with higher titres are needed. It is difficult to perform clinical studies on H. pylori in high endemic areas. Better preparations containing factors directed against specific virulence factors may be effective. There is a high prevalence of H. pylori already at an early age in high endemic countries. The screening methods of H. pylori have to be validated in areas where they are used. Presently, there are no good diagnostic methods for infants.