Worms and Human Disease

mice. Granulomas can be induced in the
lungs of mice by intravenous injection of
eggs, and this process is prevented by
immunosuppressive treatments that interfere
with cellular responses. The degree of
response to eggs and the pathology that
results, following infection in mice, are
strongly influenced by genetic factors, and
this also reflects different degrees of
immune responsiveness. It has recently
been shown in humans that at least some
of the variation in pathology seen in
infected populations is due to the activity
of particular major genes, which are associated
with T-cell function (e.g. a codominant
major gene, SM1, on chromosome 5).
The immunology of granuloma formation
is complex and involves the activity of
both major subsets of CD4+ T-helper (Th)
cells. SEA is a powerful inducer of Th2
responses, but Th1 cells also play a role.
The cellular response is initiated and controlled
by the cytokines released and in
mice the phenomenon of immunomodulation
occurs – i.e. early granulomas tend to
be much larger than those formed later in
infection.
Antigen–antibody complexes have been
shown by fluorescent antibody studies to
be the cause of the Splendore–Hoeppli
phenomenon that occurs in sensitized
hosts. Glomerulonephritis has been
reported as an immune-complex disease in
schistosomiasis mansoni.
IMMUNOLOGY OF SCHISTOSOMES
Although it has been established for many
years that laboratory animals, including primates,
develop immunologically mediated
resistance to experimental infections, definite
proof that acquired immunity to schistosome
infections occurs in humans has been
very difficult to demonstrate. It is clear that
intensity of infection and prevalence with S.
haematobium and S. mansoni is greatest in
10–14-year-olds and declines in older agegroups,
but this could be explained by a
decrease in water contact. However, longitudinal
studies and detailed monitoring of
reinfection after elimination of an existing
infection by chemotherapy have demonstrated
that age-dependent resistance does
occur against these species (Wilkins et al.,
1984, 1987; Butterworth, 1998; Kabatereine
et al., 1999), and studies in Brazil link resistance
to particular genetic characteristics
(Abel and Dessein, 1997). Infections with S.
japonicum do not show this picture,
although there appears to be an age-related
reduction in pathology (Ross et al., 2000).
The slow acquisition of immunity against S.
haematobium and S. mansoni correlates
with a change in the balance between
antiparasite immunoglobulin E (IgE) and
IgG4, the former promoting protective
responses against incoming larvae, perhaps
by antibody-dependent cellular cytotoxic
(ADCC) mechanisms directed against antigens
expressed on the surface tegument. As
shown by work carried out in the 1960s,
adult schistosomes are largely unaffected by
immunity and continue to survive in hosts
immune to larval stages (concomitant immunity).
One way in which this is achieved is
by the adult schistosomes masking the foreign
nature of their surface antigens by
incorporating host-derived molecules into
the tegument and by rapid replacement of
the tegument (antigenic disguise).
Schistosomes, like many other helminths,
exert profound effects on the host’s immune
response. Not only do these parasites tend to
polarize the T-cell response selectively
towards Th2 activity, but they may also
modulate other components in ways that
result in a more general suppression of
immune and inflammatory responses.
Immunomodulation can influence the
ability of the host to respond successfully
to other infections, and there is recent evidence
that schistosomes and soil-transmitted
nematodes may increase susceptibility
to both AIDS and tuberculosis (Bundy et
al., 2000).
DIAGNOSIS
The Trematodes 23
Parasitological. The presence of eggs in the
faeces or urine is still the most widely used
method of diagnosis. This usually poses no
problems in heavy infections but diagnosis
may not be so easy in light infections, as
occur in the majority of cases, particularly
in tourists, who have probably been infected