Immunolocalization of macrophage adhesion molecule-1 and macrophage inflammatory protein-1 in schistosomal soluble egg antigen-induced granulomatous hyporesponsiveness.

This work studied the histopathological changes and the changes in the expression of macrophage adhesion molecule-1 (Mac-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) in a murine model of soluble egg antigen (SEA) - induced granulomatous hyporesponsiveness. Histopathological results of hepatic sections in an SEA group showed early acceleration of ova destruction and markedly diminished granuloma cellularity with eosinophils and macrophages still being the predominant cells. Later, giant cells and pigmented macrophages that were scattered among granuloma cells and in intimate contact with the deposited eggs were more predominant in the SEA group than in the infected control group. Concurrently, the counts of Mac-1 positive cells were significantly increased in liver sections of the SEA group than the infected control group during the course of infection. MIP-1alpha showed early higher counts followed by lower counts in the later stages of infection on granuloma cells in the SEA group than the infected control group. During the course of infection, similar distribution of Mac-1 and MIP-1alpha was present in both groups. This study suggests that sensitization with SEA probably leads to enhancement of phagocytic activity of macrophages via increasing expression of Mac-1 and hence engulfment of ic3b coated schistosomal products such as ova. It leads to rapid destruction of ova and hence decreases the host inflammatory response to infection and amelioration of hepatic pathology which would be a promising approach in reduction of host morbidity and mortality.

Identification of surface tegumental antigens of normal and irradiated schistosomula.

Sodium dodecyl sulphate- poly acrylamide gel electronphoresis (SDS-PAGE) fractionation of tegumental surface antigens (STEG-Ags.) of 7-day cultured normal and irradiated schistosomula showed no obvious qualitative differences. The observed polypeptide bands of both normal irradiated STEG-Ags. were almost identical and have similar corresponding molecular weights. The immunoblotting assay, using different types of mouse sera, revealed similarity between the bands of both normal and irradiated STEG-Ags. recognized by each type of mouse serum. No qualitative rather than quantitative differences have been observed. The quantitative differences were reflected in intensively staining of some bands from normal STEG-Ag. rather than their corresponding bands of the same molecular weights from irradiated STEG-Ag.

Immunoregulatory potential of exogenous Schistosoma mansoni soluble egg antigen in a model of experimental schistosomiasis--I. Regulation of granuloma formation in vivo.

This study was undertaken to assess the optimum conditions required to reduce the vigorous host granulomatous reaction around Schistosoma mansoni eggs. Soluble schistosomal egg antigen (SEA) at a concentration of 10 or 100 micrograms protein was administered i.p. or i.v. into unprimed C57BL/6 mice. SEA was injected either alone or in combination with cyclophosphamide (CY) 100 or 50 mg/kg via i.p. route. Seven or 14 days later viable eggs of S. mansoni were injected via the tail vein into treated groups and untreated normal controls. Mice were sacrificed 8, 16 and 24 days after the injection of eggs. The lungs were removed for histopathological study, measurement of granuloma diameter and phenotypic analysis of granuloma intralesional T-cell subsets. Compared to untreated controls, the lower concentration of SEA (10 micrograms) administered by the i.v. route 7 days before egg injection, induced a significant reduction in granuloma diameter 16 days after egg injection than that by the i.p. route or at a higher SEA concentration (100 micrograms). Compared to untreated controls, the higher dose of CY (100 mg/kg), given i.p. alone or in combination with 10 micrograms SEA by the i.v. or i.p. route, induced a significant reduction in granuloma diameter, while 50 mg/kg CY did not cause any reduction. The reduction in granuloma diameter by i.v. administration of low SEA concentration alone or in combination with CY IP, was associated with a decrease in the granuloma intralesional L3T4+/Lyt2+ ratio. The decrease in the ratio was due to an increase in Lyt2+ cells. The results suggest that the use of low dose SEA by the i.v. route alone or combined with an immunosuppressive drug ameliorates pathological changes concurrent with S. mansoni infection.

Immunological response to diphtheria/tetanus vaccine in Schistosomiasis mansoni patients.

The cellular and humoral immune responses of patients with S. mansoni infection were evaluated before and one month after each of two intramuscular doses of diphtheria/tetanus toxoid vaccine. Patients were divided into "responder" and "non-responder" groups based on anti-tetanus toxoid (anti-TT) IgG levels after vaccination. The specific anti-TT IgG1 response of the responder group was predominantly in the IgG, subclass. The lymphoproliferative response to PHA was also significantly higher in the responder group; this elevation was detectable before and after each vaccination. The responses to PWM and SPL were comparable in the two groups before vaccination, although the responder group had a higher response to SPL after vaccination. IgG antibodies for schistosome adult worm and egg antigens were significantly lower in the responder group prior to vaccination but not thereafter. Anti-diphtheria IgG antibodies were comparable in the two groups after vaccination at all times. Clinically, the non-responder patients had a higher incidence of splenomegaly (84.6% vs 44.8%) and were significantly older than the responder patients (mean 34.1 yrs vs 18.7 yrs). The cause for the reduced anti-tetanus IgG response in schistosomiasis patients is believed to be multifactorial. T cell or antigen presenting cell dysfunction, high levels of IgG antibodies specific for schistosome antigens, splenomegaly and age are factors that might lead to reduced anti-TT IgG response.

Are tuberculosis wards a risk factor for HIV in Africa?

A twenty-year-old female prostitute had an indeterminant HIV western blot in Djibouti during June 1988. She was hospitalised at the tuberculosis hospital in October and was re-tested for HIV in November. Her western blot result was still indeterminant, despite a progressive profile, and she therefore escaped to the hospital's HIV surveillance system. There were strong indications that while in-hospital, the patient resumed the activities of her previous profession. We conclude that active tuberculosis may develop in African HIV patients prior to the development of a confirmatory HIV western blot profile. Thorough precautionary measures are indicated for preventing HIV from spreading to health care personnel and amongst hospitalised patients in Africa.

T lymphocyte subset modulation of hepatic fibroblast function in murine schistosomiasis.

We have previously shown that co-culture of T cell enriched spleen lymphocytes can reduce collagen synthesis and stimulate proliferative activity by liver fibroblasts from S. mansoni infected mice. The present study examines which subset of T cells is responsible for this modulation. Co-culture of fibroblasts with the total T cell population lead to significant stimulation in fibroblast proliferative activity and a significant decrease in the incorporation of 14C-proline into collagenase-sensitive protein. There was virtually no effect on total incorporation of 14C-proline in non-collagen proteins. An additional significant increase in fibroblast proliferative activity and another significant decrease in collagen synthesis accompanied by a 2-fold increase in non-collagen protein production was noted when fibroblasts were co-cultured with Lyt-1+ cells. Co-culture of fibroblasts with Lyt-2+ cells did not differ significantly from co-culture with total T cells. Mitomycin treatment of the lymphocytes blunted their specific effects, suggesting that proliferation of T cells is required for maximal exertion of their regulatory activity. These results suggest that the T cells which mediate these effects belong to the Lyt-1+ helper class and are distinct from the Lyt-2+ suppressor cells.

Maternal-infant transmission of hepatitis B in Egypt.

In order to determine whether maternal-infant (vertical) transmission of hepatitis B is a common route of infection leading to chronic antigenemia in Egypt, 901 asymptomatic women in labor were evaluated. Forty-three women (4.8 percent) were positive for HBsAg, but only one woman was positive for HBeAg. From one year of observation of children born to 13 of the HBsAg-positive mothers, vertical transmission of hepatitis B was estimated to have occurred in approximately 1.7% of births, with chronic antigenemia resulting from 0.6% of births. It was also possible to observe 29 children born to women negative for HBsAg. Horizontal transmission of hepatitis B occurred in 17.2 percent of these children during the first year of life. Maternal-infant transmission of hepatitis B at birth does not appear to be the predominant mechanism of hepatitis B transmission or a common cause of chronic antigenemia in Egypt. The first year after birth appears to be a more important period of hepatitis B transmission. Therefore, vaccination of all children at birth with hepatitis B vaccine could be an effective vaccine strategy despite a low incidence of vertical hepatitis B transmission.

Immunogenicity of hepatitis B vaccine in patients infected with Schistosoma mansoni.

Because dual infection with Schistosoma mansoni and hepatitis B may lead to severe liver disease, populations living in schistosomiasis-endemic areas might benefit if effectively immunized against hepatitis B. To determine whether a plasma-derived hepatitis B vaccine is immunogenic in patients with schistosomiasis, 32 individuals infected with S. mansoni were given three 20-micrograms doses of Heptavax-B vaccine and treated with praziquantel. Antibody to hepatitis B surface antigen developed in 90.6% of the study subjects after three doses of vaccine. Five patients (15.6%) had a weak response to the vaccine, and three patients (9.4%) failed to develop antibody. A weak or failed response to the vaccine was significantly associated with the presence of hepatosplenomegaly. A plasma-derived vaccine is immunogenic for persons infected with S. mansoni; however, vaccine response is diminished in hepatosplenic schistosomiasis.

Risk of hepatitis B infection among Egyptians infected with Schistosoma mansoni.

Three hundred twenty-four individuals in a farming village located in the Nile Delta of Egypt were serially tested for hepatitis markers and Schistosoma mansoni to determine whether there is an increased risk of hepatitis B in persons infected with schistosomiasis. One-half of the subjects had stools positive for S. mansoni. Thirty-seven percent of the individuals had been infected with hepatitis B, and 3% were chronic HBsAg carriers. No statistical association was found between S. mansoni infection and hepatitis B infection, including chronic hepatitis B. Although there was no evidence of an association between these 2 pathogens, larger nonhospital based studies are needed to resolve this question.

Acute sporadic hepatitis in adults living in Cairo, Egypt.

A group of 295 adult male patients from Cairo, Egypt, with acute hepatitis were studied. Acute hepatitis A was diagnosed in 8 patients (2.7%), hepatitis B in 115 (38.9%), delta infection in 19 (6.4%) and possible Epstein-Barr virus or cytomegalovirus-mediated hepatitis in 7 patients (2.4%). The remaining 146 patients (49.5%) were considered to have hepatitis non-A non-B. The clinical presentation of the various causes of hepatitis was similar, although patients with hepatitis B and delta infection had significantly higher mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels than patients diagnosed as having hepatitis non-A non-B. Various risk factors for the acquisition of hepatitis were evaluated. A history of an injection for medical treatment and a history of anti-schistosomal therapy were significantly associated with delta infection when compared to patients with either hepatitis B or non-A non-B (P less than 0.05). Hepatitis non-A non-B is a major cause of acute hepatitis in adults living in Cairo, and an iatrogenic source of infection may be important in the epidemiology of delta infection.