الفهرس 
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Abstract
Liver disease is one of the main disorders in Egypt. In addition to schistosomal hepatic fibrosis, human fascioliasis is becoming a problem of increasing importance. The disease is more common than was hithero believed. Recent outbreaks are reported in the vicinity of Alexandria and Behira Governorates.
As the signs and symptoms of early fascioliasis are not pathognomonic it should be taken in consideration that all suspected cases with fever and eosinophilia should be serologically confirmed.
Bithionol is the drug of choice for human fascioliasis because of its therapeutic activity, easy route of administration and capability of enhancement or cooperation with the immune response against Fasciola worms.
The aim of this work was to study the immune response in human fascioliasis before and after bithionol therapy. *
The study was carried out on fourty subjects, 15-30 years old,
they were divided into: r
Group 1: ten patients with incubating fascioliasis. /
i
Group 2: ten patients with established fascioliasis. I Group 3: ten patients with established fascioliasis treated with bithionol. Group 4: ten healthy normal corresponding control.
All individuals under study were subjected to the following: Ar
1. Thorough clinical assessment.
2. Laboratory investigation:
a- Hematological study: complete blood picture including absolute eosinophilic count and blood indices to know type of anaemia.
b- Liver function tests: serum bilirubin and alkaline phosphatase, serum alanine transferase (GOT) and serum aspertate transferase (GPT).
c- Parasitological studies: urine and stool examination by simple sedimentation to exclude schistosomiasis infection. Egg count by kato technique to determine parasite load.
3. Immunological studies:
a- Indirect haemagglutination technique was applied to assess the antifasciola antibody titre.
b- Cellular immunity study:
i. T-cell count by the rosette formation technique, ii. T-cell function by the blast transformation technique, iii. T-cell subsets (Th-Ts) both in the peripheral blood using the indirect immunofluorescent technique and in the liver tissue by
immunoalkaline phosphatase technique. OKT4 and OKT8 monoclonal antibodies were used for the detection Th and Ts.
4. Histopathological study of H and E stained liver tissue specimens of established Fasciola patients.
Results: < | Clinical findings:
- The presenting clinical manifestations:
In incubating fascioliasis the clinical picture was fever, right
abdominal pain, urticaria and bowel disorders.
I i
In established Fasciola patients, there were right abdominal colic, easy fatiguabflity and bowel disorders.
- The haematological findings:
Early fascioliasis was shown to be characterized with eosinophilia that may be attributed to stimulation of T- lymphocytes (Th2) by larval antigens leading to release of lymphokins (IL-5) and consequently enhancement of eosinophil proliferation.
On the other hand, in established Fasciola patients, the eosinophilic counts were reduced and retained the normal range after bithionol treatment. Such reduction in the eosinophilic count may
indicate that the larval antigens are more immunogenic rather than that of the adult worm.
In the established Fasciola patients, normocytic normochromic anaemia was observed. After bithionol therapy the haemoglobin levels were improved indicating a parasite factor may be a cause for anaemia in fascioliasis. Blood loss in the biliary tree (haemobilia) may be another contributing factor.
As regards the liver function tests, serum bilirubin was within the normal range in all Fasciola patients under study. A mild increase in SGOT and SGPT was detected in patients with incubating fascioliasis. On the other hand in the established fascioliasis there were a mild increase in SGPT and significant increase in the alkaline phosphatase enzyme level. After treatment, all the liver function tests regained the normal levels.
The increase in SGOT and SGPT may be attributed to liver damage associating early fascioliasis. The increase of alkaline phosphatase level could be due to accumulation of the en2yme as a result of relative narrowing of the biliary passages during the chronic phase of the disease. There was a significant correlation between eosinophilic count and SGOT and SGPT.
In the present work, a low intensity of infection was observed. The few egg number may be due to the low worm load as a sequence of poor adaptation of the worm in man who is not the suitable host for Fasciola infection.
There was no correlation between the egg count and either eosinophilic count or the serum transferases (GOT-GPT). Such finding may be due to the fact that Fasciola eggs do not share in the pathology as in schistosomiasis.
As regards the humoral immune response in fascioliasis, it
takes the upper hand in the incubating patients as the highest titre
values (1/640-1/2560) were observed in such patients. In established
infection, a significant reduction in the antibody titre was
encountered.The reduction in the Ab titre may be due to the lower
antigenicity of the adult worms which are located in the bile ducts away from the immune system. The correlation between the antibody titre and both eosinophilic count and the serum transferases (GOT, GPT) may support that view.
In the present study, a reduced T-cell count was observed in both incubating and established Fasciola patients The reduction may be a true one as a sort of immunosuppression produced by the disease or a false reduction. Masking of T- cell receptors by circulating immune complexes may be the cause of false reduction.
Although the T-cell count was reduced in incubating patients, yet T-celi function was more or less similar to that of normal control. Such finding may be due to strong stimulation of T-cells by the larval antigens. The high antibody level, allergic manifestation in early fascioliasis and T-cell stimulation could support the view of the strong immunogenicity of larval antigens which may act like cytokines activating the host immune cells.
In established fascioliasis, T-cell function was reduced either due to the reduced T-cell count and/or to a lower immunogenicity of the adult worm.
The present study revealed in incubating as well as established Fasciola patients both Th and Ts cell counts were significantly reduced that may be due to the immunosuppression associating fascioliasis.
Inspite of the reduced Th count in both incubating and established patients’ groups, yet a high antibody level was observed in the first group and a reduced level in the second. Such observation may be attributed to variation in Th cell subtypes according to the stage of the disease, namely Th2 in the acute phase (recognisable for eosinophilia and Ig production) and Thl in the chronic stage (responsible for delayed hypersensitivity).
The correlation between Th cell count and either eosinophilic count or the antibody titre may support the view of the important role played by the helper T-cells in incubating fascioliasis.
In established fascioliasis, the manifestations of delayed hypersensitivity were shown in the histopathological picture of liver biopsies. There were granulomatous reactions, fibrovascular tracks and foci of degeneration and necrosis around the portal tract and in the granulomas. Multifocal aggregates of lymphocytic infiltration and ductular hyperplasia were observed.
The widespread lymphocytic infiltration was shown to be made of more T8 (suppressor/cytotoxic) cells and few T4 (helper) cells. The greater detection of T8 (suppressor/cytotoxic) cells is in accord with the hypothesis of immunosuppression in facsioliasis.
After bithionol treatment, T-cell count and function were improved to approach the normal level. The liver had nearly regained the normal archeticture with regression of the lymphocytic infiltration. Few T8 (suppressor/cytotoxic) cells and absent T4 (helper) cells were shown. Such finding may indicate that the mode of action of the drug may be through accentuation of the immunoregulatory mechanisms mediated by T8 (suppressor/cytotoxic) cells.