The host -parasite relationship of sheep and the
nematode Trichostrongylus colubriformis was studied in
terms of the population dynamics of the parasite in the
host and the pathological and pathophysiological outcome
of such a relationship.
Two different patterns of prolonged daily infections
which were intended to simulate two distinct epidemiological situations, and a limited number of single
infections were used. The course of the infections was
monitored by means of regular faecal egg counts,
differential post -mortem worm counts, determination of
plasma or serum protein changes and measurement of gastrointestinal plasma loss. At the completion of each of the
experiments suitable infected and worm -free lambs were
used to study the macroscopic, histological and ultra - structural changes in the mucosa of the proximal small
intestine.
It was shown that the trend in the faecal egg counts
of lambs exposed from early post -natal life to an
escalating infection with T.colubriformis followed a
characteristic pattern. Faecal egg counts increased
logarithmically during the first 12 weeks of exposure to
this pattern of infection. The egg count curve thus
reflected the pattern of infection during most of this
period. In most lambs the peak egg count which was
reached soon after the 12th week was maintained for the
rest of the experimental period. There was no evidence
of an abrupt decline in faecal egg counts.
The population of T.colubriformis in these lambs
increased steadily to a peak of about 100,000 worms by
the 16th week. This large burden remained fairly stable
for the rest of the experimental period despite repeated
daily infections or a single heavy challenge infection.
During this period exsheathed infective larvae of
T.colubriformis could be recovered from the freshly - collected faeces of the lambs especially within 24 to 48
hours after the challenge infection. It thus appears
that the early exposure of the lambs to T.colubriformis
infections did not result in the lambs tolerating
re- infection by this parasite but instead conferred strong
resistance to a heavy challenge infection which produced
clinical disease in previously uninfected worm -free
controls of similar age. There was no evidence that the
populations of T.colubriformis in these lambs were
regulated by either self -cure reactions or by a mechanism
involving continual and rapid turnover of worms.
The faecal egg count of older lambs infected daily
with 5,000 larvae of T.colubriformis was also characteristic. Egg counts rose rapidly to a peak 28 to 40 days
after first infection and then declined exponentially at
a rate which varied with the individual lamb and its age.
As in the younger lambs the infection appeared to be
cumulative during the first 4 weeks when the numbers of
worms which succeeded in establishing themselves in the
lambs far exceeded those being lost. Thereafter the
rate of increase in worm populations was reduced as the
host became increasingly more resistant tothe establishment of new infections. Prom about the 10th week
onwards most lambs were virtually totally refractory to
either the continued daily infections or to a single heavy
challenge infection. Large numbers of exsheathed
infective larvae of T.colubriformis could be recovered
from freshly- collected faeces of such lambs.
In most lambs a peak worm burden of 90,000 to 100,000
was reached by the 8th week after first infection. In
some lambs this peak burden remained fairly stable for
about 4 weeks before an apparently exponential decline
occurred. In more resistant lambs, however, this decline
commenced soon after the peak burden was reached.
Four manifestations of acauired resistance were
observed in most lambs following prolonged daily
infections with T.colubriformis, namely: -
1. Resistance to the establishment of new infections
2. Inhibition of ovulation of female worms
3. Stunting of adult worms
4. An exponential loss of worms
It is concluded that the immunological control of
T.colubriformis infections in lambs under conditions of
continual re- infection is achieved through these phenomena
which are probably separate and distinct aspects of the
host resistance mechanism.
T,colubriformis infections in lambs were often
accompanied by a marked hypoproteinaemia which was
essentially a hypoalbuminaemia, the magnitude of which
was directly related to the severity of the disease.
Radiotracer studies showed that a protein- losing
enteropathy was the most probable cause of the hypo - proteinaenia. This daily leakage of plasma into the gut
was not accompanied by the loss of red blood cells.
The intestinal plasma loss was a sensitive index of
the pathogenicity of T.colubriformis, in lambs. Furthermore a significant positive correlation was found between
the worm burden of the lambs and their terminal intestinal
plasma loss. The prolonged leakage of plasma proteins
into the gut at an excessive rate constitutes a
derangement of the host's plasma protein metabolism and
probably has important physiological and biochemical
consequences to the parasitized lamb.
Regular monitoring of the gastro- intestinal plasma
loss of Iambs during prolonged infections was made possible
by the development of a new method for the in -vivo
labelling of plasma proteins, in which ⁵¹Cr as ⁵¹CrCl₃ was
administered subcutaneously in a water -in -oil emulsion. A
simple but reliable in-vitro test system was also devised
and used to evaluate various emulsions for their rate of
release of ⁵¹Cr. Both the in-vitro and in-vivo tests
showed that the most satisfactory emulsions for use in the
measurement of gastro- intestinal plasma protein leakage in
lambs would be those with the following compositions : -
1. Arlacel A concentration of 8 to 12 percent
2. Phase volume of 35 to 50 percent and
3. Tween 80 concentration of 0 to 5 Percent
The macroscopic, histological and ultrastructural
features of the mucous membrane of the -proximal small
intestine of lambs with trichostrongylosis were
remarkably similar to those commonly seen in malabsorption
syndromes in man. The most notable feature was marked
stunting of the villi or, in severe cases, total loss of
villi. These findings support the suggestions of other
workers who have found similar chances in a variety of
aetiologically unrelated conditions in man and animals that
these changes arc a non -specific reaction of the small
intestinal mucosa to damaging agents. The significance of
these morphological changes in intestinal physiological
functions in lambs, especially digestion and absorption,
is uncertain.
No evidence was found from the ultrastructural studies
to suggest that defects in the zonulae occludentes between
adjacent epithelial cells were responsible for the
increased permeability of the parasitized mucous membrane
to plasma proteins. It is considered more probable that
the areas of epithelial erosion and ulceration which were
demonstrated histologically and ultrastructurally were the
sites of the increased plasma protein leakage into the gut.
Such mucosal damage is more likely to be caused directly
by the parasite rather than by pharmacologically active
substances. It is therefore improbable that a mechanism
which involves a local anaphylactic reaction leading to
increased gut permeability to plasma proteins is
important in the regulation of populations of
T.colubriformi s in most lambs. However the kinetics of
the worm populations in two of the experimental lambs
suggested that such a mechanism
might have been involved
in the relatively rapid expulsion of worms which occurred
in these lambs.
