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No
disease entity can be studies in detail unless there is
an experimental model available for the same. There is as
yet no experimental model for amoebic liver abscess which
can mimic the human disease in all its details and which
is easily reproducible with out loss of many animals.
The three aspects to be taken into consideration are the
host (animal), the agent (amoebae) and the various
methods and modifications for producing the lesion.
The Host or
the susceptible animal
Experiments were carried out with various animals,
eg. dogs, kittens, rats, guinea pigs and golden hamsters.
Dogs are found to be unsuitable because the picture was
not always unform.1 Kittens were useful only for the
initial screening. In rats and guinea pigs, an abscess
does form but even as early as on the fourth day, it is
surrounded by a fibrous band1,2 and the infection is
self-limiting. Hence these animals were not considered
ideal to work with.
In golden hamsters the abscess which is formed in the
liver resembles the lesion found in the human beings. The
amoebae can be easily recovered from the abscess upto a
period of four days. There is no limiting wall to contain
the infection and therefore it spreads, sometimes to
occupy the whole lobe. Hence golden hamsters were
considered ideal animals for creating an experimental
model of amoebic liver abscess.3,4
An experiment carried out by Jarumilinta et al4 showed that these animals
(golden hamsters) could develop an abscess in the liver
even after injecting amoebae in the caecum. This method
has the closest resemblance of the pathogenesis of human
disease.
Feeding of steroids, specially progesterone was found to
increase the susceptibility of the animals to amoebic
infection.5 Others have found
hyper-cholesterolaemic animals to be more susceptible to
amoebic infection.6,7
The Agent
(Amoeba)
All the strains of amoebae are not capable of
producing an abscess in experimental animals.8 The organisms which are
received from patients suffering from amoebic liver
abscess are the most virulent.8 Those amoebae which are
isolated from patients with intestinal lesions are also
virulent.9,10 However, if organisms are
collected from carriers, no abscess or intestinal lesion
can be produced in experimental animals.9,10
Even an originally virulent strain becomes
avirulent after multiple subcultures.8,11 Still if these are passed
through guinea pig or hamster liver, the property of
virulence is restored.8,12 Nevertheless, an originally
avirulent strain cannot be changed to a virulent one even
by this method.12
The intensity of amoebic infection differs from
patient to patient. Surprisingly the amoebae from these
different groups have varying intensity of virulence.
Neat et al12 found that
amoebae from patients of amoebiasis who were asymptomatic
and whose serology tests were weakly positive were less
virulent as compared to those from symptomatic patients
with serological tests positive in high dilutions.
Some workers believe that the presence of certain
bacteria increase the virulence of amoebae. Others feel
that the presence or absence of bacteria does not change
the virulence of the amoebae.8 However, the invading
capacity as well as the capacity of particle phagocytosis
is found to be increased in the amoebae incubated with
viruses.14
The virulent strains of amoebae have different
surface properties as compared to avirulent ones.15
However, exact details of explanation for differences in
virulence are not known. Future work on the latest
discovery of the position of the enzyme bands would be of
help.16
The methods used
Different routes have been tried for introducing
amoebae in the experimental animals.
Simple production of colitis is not followed by
spontaneous appearance of amoebic liver abscess. However,
a small number of golden hamsters do develop an amoebic
liver abscess spontaneously secondary to production of an
intestinal infection.4
Amoebic liver abscesses have been produced in rates
and guinea pigs by injecting amoebae either in the
mesenteric17 or portal venin.18,19 The portal injection gave
better results.18 The success rate was higher
in those animals who had chronic intestinal infection.20
Direct inoculation of the liver21 is the most preferred
method. The amoebae are either injected into the
substance of liver or left on the surface (Fig.10).
The process of abscess
formation
When the amoebae are injected in the veins, they form
infarcts by probably obstructing the lumen of the
vessels. Scattered lesions appear within a few hours. The
major changes are seen at the portal triad. After ten
hours the lesions can be seen with the naked eye as well.
Within twenty-four hours greyish yellow abscesses appear.
The amoebae can be seen and even cultured from these
lesions.17
Some special problems
Axenic culture of E. Histolytica. Till very recently
it was not possible to culture amoebae axenically. Hence,
while introducing amoebae in the experimental animals
some bacteria were also introduced. Thus, there was
always some doubt regarding the actual capacity of the
amoebae to form an abscess.
Some workers produced amoebic liver abscesses by
injecting bacteria and compared them with those produced
by introducing both amoebae and the bacteria. The
abscesses produced by injecting only bacteria were solid.
Others inoculated the animals with bacteria with the idea
of developing immunity against them.2,3 When the mixture of amoebae
and bacteria was later injected for producing an amoebic
liver abscess the number of bacteria in the abscess was
much less. Still others gave appropriate antibiotics or
passed the culture through seitz filters18 without much effect.17
Immunity of the animals
When an attempt was made to produce amoebic liver
abscesses in animals who were on prednisolone and
azathioprine, it was found that the rate of success was
better and fewer amoebae were required.22
Other methods for suppressing the immunological
response of the animals have also been employed. e.g.
irradiation.
Maegraith observed that it was easier to produce amoebic
liver abscesses in animals who had chronic
intestinal lesions indicating that prior sensitization of
the animals by amoebic antigen was desirable.20
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