Passive immunisation as therapy for gastrointestinal infections in children
Author: Casswall, Thomas
Date: 1999-12-17
Location: Föreläsningssalen R64, Rehabgatan, plan 6, Huddinge sjukhus
Time: 9.00
Department: - / -
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.
Issue date: 1999-11-26
Publication year: 1999
ISBN: 91-628-3862-8
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