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Histocompatibilty-linked susceptibility for hepatospleenomegaly in human schistosomiasis mansoni.

In schistosomiasis mansoni, the pathogenesis of hepatosplenic disease has been shown to be due primarily to immune mechanisms. The present study was designed to examine the relationship between the development of schistosomal hepatosplenomegaly in Egyptian school children and the HLA antigens. Two groups of schistosome-infected children with similar fecal egg counts were examined: one group (23 children) had no clinically demonstrable hepatosplenomegaly whereas all the children (28) in the second group suffered from liver enlargement. Furthermore, 13 of the 28 individuals in the latter group had splenomegaly as well. Our results show that hepatosplenomegaly was related to the presence of two HLA antigens: HLA AI and B5. The average relative risk of developing hepatomegaly is 29 for HLA AI and 18.9 for 55.6. Furthermore, the severity of hepatomegaly was correlated with the presence of these two HLA antigens. These findings represent a step toward elucidating the factors controlling the pathogenic mechanisms in human schistosomiasis mansoni.

Child

Factors in the pathogenesis of acute schistosomiasis mansoni.

Acute schistosomiasis mansoni was studied in 26 Puerto Rican patients whose clinical presentations differed widely in severity. Severity of illness was found to be positively correlated (r = 0.79) with the intensity of infection as measured by the concentration of eggs of Schistosoma mansoni in stool specimens. However, some patients had severe illness but relatively light infections. The disappearnace of symptoms and return toward normal of laboratory measures of disease activity were not associated with any diminution in the fecal egg count. Elevations of IgG, IgM, IgE, and of titers of anibody in serum indicated that the illness is associated with intense immune activity. The magnitude of the IgG and IgE responses was related to intensity of infection. The fact that incubation periods were shorter than the time needed for schistosomes to reach adulthood and lay eggs suggests that the syndrome can be initiated by parasite stages present before oviposition. No marked changes in complement (C3, C3p, C4, and CH50) and no signs of renal disease were noted in any of these patients.

Acute Disease

Intestinal parameters in acute murine schistosomiasis mansoni.

Intestinal involvement is very important in acute murine schistosomiasis mansoni. Nevertheless intestinal parameters have not previously been used in assessing the severity of intestinal disease. The present observations demonstrate that in Schistosoma mansoni-infected mice, the mean total egg count of the small intestine and the mean number of eggs per g in the small and the large intestine were higher than the corresponding egg counts in the liver. The increase in weight of the small intestines of infected compared with uninfected mice was greater than the increase in weight of the corresponding livers. The small intestines from infected mice were considerably shorter than those from uninfected mice. These findings argue for the small intestine as a valuable organ for pathophysiological studies in acute murine schistosomiasis mansoni and simple parameters such as total egg count of the small intestine, the number of eggs per g tissue in small and large intestine and the weight and length of the small intestine, are recommended.

Acute Disease

Hemostasis in schistosomiasis mansoni.

Hemostasis was studied in 18 patients with the hepato-intestinal form of Schistosomiasis mansoni and in 23 with the hepato-splenic form. Both groups are compared referring to alterations found. The relations between plasmatic coagulation factors and hepatocytic function tests are studied. In 6 patients the explorations were repeated after administration of hycanthone. In the patients with the hepato-splenic form, the presence of chronic consumptive coagulophathy was found. The coagulopathy disappeared either by treatment with heparine or by splenectomy. This observation points out the importance of splenomegaly in the development of chronic consumptive coagulopathy, and may be an important factor in indicating splenectomy in a patient with portal hypertension due to Schistosomiasis mansoni.

Adult

Experimental chemotherapy of schistosomiasis mansoni. XIII. Activity of praziquantel, an isoquinoline-pyrazino derivative, on mice, hamsters and Cebus monkeys.

In mice experimentally infected with Schistosoma mansoni, praziquantel (2-cyclohexylcarbonyl-1,3,4,6,7,11b-hexahydro-2H-pyrazino[2,1-a]isoquinoline-4-one), administered orally at the levels of 100 and 50 mg/kg, for 5 consecutive days, produces oogram changes in all animals and a pronounced hepatic shift of schistosomes (97.1 and 89.1, respectively). At lowest levels (12.5 and 6.3 mg/kg), alterations in the oogram could still be detected, although hepatic shift of schistosomes was no more evident. After a single intramuscular injection, the results obtained paralleled those observed with a single-dose oral treatment. The hepatic shift was only moderate at 200 and 100 mg/kg and the percentages of worms retained in the liver, after perfusion, were particularly low. When nasal route in a 1-day regimen was used, the results obtained were slightly less evident as compared with those observed by oral route (5-day schedule). Considering the percentage of oogram changes, the degree of hepatic shift of schistosomes and the percentage of worms fixed in the liver, the antischistosomal activity of praziquantel was greater in hamsters than in mice. Actually, a daily dose as low as 12.5 mg/kg, administered for 5 consecutive days, was sufficient to shift 60.4% of the worms towards the liver and to produce alterations of the oogram in 60% of the animals. In Cebus monkeys orally treated with 10 and 20 mg/kg of praziquantel, given 3 times within a single day (total doses of 30 and 60 mg/kg, respectively), a remarkable reduction in worm burden was observed. A single oral or intramuscular dose of 100 mg/kg was found to be curative. One Cebus doses with 100 mg/kg, by nasal spray, was found to harbor only female worms at autopsy performed 69 days after treatment.

Animals

Streptozotocin-induced diabetes mellitus and the host-parasite relation in murine schistosomiasis mansoni.

The effect of streptozotocin-induced diabetes mellitus on both the host and the parasite was studied in mice infected with Schistosoma mansoni. Neither the drug nor the marked rise in concentration of blood glucose had any effect on penetration of the skin by the cercariae, their subsequent maturation into adult worms, or their output of eggs. During the acute stages of the infection (at eight weeks), the diabetic animals showed marked suppression of the host granulomatous reaction to schistosome eggs trapped in the liver, accompanied by an alleviation of hepatosplenic disease. During the chronic stages of infection (at 16 weeks), there was a pronounced megalocytosis of the hepatocytes only in the infected animals with streptozotocin-induced diabetes; these animals also had an exacerbation of hepatosplenic disease.

Animals

Mother-child relationship in human schistosomiasis mansoni. I. Parasitic antigens and antibodies in milk.

Immunoglobulins, anti-Schistosoma mansoni antibodies, complement components and schistosome antigens were investigated in milk from mothers infected with S. mansoni. No significant differences of immunoglobulins or complement component levels were observed between infected and control mothers. Anti-S. mansoni antibodies were detected in the milk of 8 out of 25 infected mothers. A significant relationship was observed between serum and "4", were demonstrated in milk from infected patients by the double diffusion micromethod. The function of these immunologically active substances transmitted by milk from mother to child is discussed.

Antibodies

Schistosomiasis mansoni in the hamster: cellular and humoral immune responses to soluble egg antigens (SEA).

Cellular and humoral immune responses to soluble egg antigens (SEA) were studied in the course of Schistosoma mansoni infection in the hamster. No immune response to SEA could be detected before the parasite had started oviposition. The liver granuloma size reached a maximum 6 weeks after infection and decreased rapidly thereafter. The in vitro cell-mediated immune response to SEA (lymphocyte blast transformation) showed a maximum reaction 12 to 16 weeks after infection (depending on the infection rate) and also declined later. Parallel to the lowered reactivity of the lymphocytes to SEA in vitro, responsiveness to the nonspecific T-cell mitogen, phytohemagglutinin M, was also reduced in chronic infections. Humoral anti-SEA antibodies could be detected in increasing amounts up to 10 weeks after exposure.

Animals

Failure of plasma from human schistosomiasis mansoni patients to protect mice from Schistosoma mansoni cercarial challenge.

Plasma samples obtained from patients with well defined Schistosoma mansoni infections, or control subjects, were passively transferred to CF1 mice. Three, 12, or 24 hours after passive transfer, the recipient and control mice were challenged with either 200 or 600 live cercariae, and the adult worm burdens or schistosomula lung recoveries, respectively, were determined 7 weeks or 6 days after challenge. None of the human plasmas afforded the recipient mice protection against the development of schistosomes. Worm and larval yields were equivalent in all cases, even though many of the patient plasmas were shown, as assessed by an in vitro eosinophil-dependent cytotoxic antibody assay, to contain high levels of antischistosomular antibody.

Animals