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Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma haematobium and Schistosoma mansoni infected patients.

The present study presents, for the first time, the amounts of nitrate, nitrite and volatile N-nitroso compounds in saliva and urine samples of Schistosoma haematobium and Schistosoma mansoni infected patients. Mid-morning saliva and 24 h urine samples were collected from male patients infected with S.haematobium (n = 129 saliva and 79 urine samples) and S.mansoni (n = 64 saliva and 65 urine samples) and in a comparative control group of healthy individuals (n = 27) from the Nile Delta region of Egypt. Saliva samples were analyzed for the presence of nitrate and nitrite; while urine samples were analyzed for the presence of nitrate, nitrite and volatile N-nitroso compounds. In the control group, N-nitroso-dimethylamine (NDMA) was detected at concentrations (mean +/- SD) of 0.27 +/- 0.47 microgram/day. N-Nitrosopiperidine (NPIP; 0.6 microgram/day) and N-nitrosopyrrolidine (NPYR; 0.4 microgram/day) were also present in one sample. S.mansoni infected subjects showed significantly (P < 0.001) higher levels of 2.9 +/- 2.9 micrograms/day NDMA and a higher frequency of NPIP (in 40/65 samples; 0.4 +/- 0.3 microgram/day) and NPYR occurrence (in 59/65 samples; 0.9 +/- 0.9 microgram/day). Significant further increases in the excretion of volatile N-nitroso compounds were found in S.haematobium-infected patients with mean daily excretion of 19.2 +/- 21 micrograms/day NDMA (in all samples; P < 0.001), 1.6 +/- 2.3 micrograms/day NPIP (in 56/79 samples; P < 0.001) and 1.3 +/- 1.9 micrograms/day NPYR (in 58/79 samples; P < 0.1). The differences either in salivary nitrite/nitrate or in urinary nitrite between the three distinct groups were not significant. However, the urinary excretion of nitrate was elevated from 139 +/- 82 mg/day in the control group to 249 +/- 126 mg/day in S.mansoni infected patients (P < 0.001) and to 174 +/- 176 mg/day in S.haematobium infected subjects (P < 0.005 in comparison to S.mansoni infected group). These results suggest a possible role of N-nitroso compounds in the etiology of schistosome-associated bladder cancer and imply a partial participation of S.mansoni in the multistage process of urinary schistosomiasis-associated bladder carcinogenesis.

Adult↗

[Ultrasonoic diagnosis of morbidity related to schistosomiasis due to Schistosoma mansoni and Schistosoma haematobium: epidemiological and individual value].

By allowing study of large population samples, ultrasonography has revolutionized assessment of schistosomiasis-related morbidity. Previous clinical or parasitological parameters provided poor documentation of the public health impact of schistosomiasis. Thanks to a WHO-coordinated drive to standardize examination protocols and severity scores, comparison of data from different regions is now much easier. The latest "Niamey" methodology has eliminated the major shortcomings of earlier methods. Detection of periportal fibrosis is the cardinal diagnostic feature for Schistosoma mansoni. Ultrasonographic evidence has been validated by correlation with hepatic biopsy findings from hospitalized patients with severe disease. The specificity of ultrasonography is poor in low- or moderate-grade disease for which different methodologies give discordant results. Ultrasonography is highly sensitive for assessment of morbidity related to Schistosoma haematobium infection, which is associated with typical bladder lesions. Lesions involving the upper urinary tract are also well visualized but do not constitute a specific finding. The best applications for which ultrasonographic investigation of schistomsomiasis is now considered as mandatory are community-based studies and post-therapeutic follow-up of populations. In contrast ultrasonography is not well suited to individual diagnosis. In endemic areas, ultrasonography may be used for individual diagnosis if more effective methods are unavailable. However the poor specificity of some images is a major limitation for use in zones of low transmission.

Aftercare↗

A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum.

The benzodiazepine derivative (Ro 11-3128) which has central nervous effects similar to other benzodiazepines, and praziquantel (PZ), are two new antischistosomal drugs. At low concentrations these drugs will produce a marked spastic paralysis of male Schistosoma mansoni musculature. An analysis of the action of these drugs on the parasite's musculature shows that Ro 11-3128 and PZ produced a rapid rise in the tension of the musculature of male schistosomes. Various compounds known to interact with the schistosome's neuroreceptive sites did not block of potentiate the action of these drugs. Removal of Ca2+ or addition of Mg2+ to the incubation medium blocked the action of these drugs on the schistosome's musculature. Uptake studies of inorganic cations by male schistosome's indicate that Ro 11-3128 and PZ decrease the influx of K+ but stimulate the influx of Ca2+ and Na+ into the male schistosome. It is suggested that this interference with inorganic ion transport mechanisms causes the contraction of the schistosome musculature.

Animals↗

Comparative analysis of the Schistosoma mansoni and Schistosoma bovis cercarial production under the influence of praziquantel.

Snails infected with Schistosoma mansoni and S. bovis and fed with a food-Praziquantel mixture stop shedding cercariae for several days. The cercarial production restarts at different levels after stopping treatment: for some Biomphalaria glabrata, the restarting phase of production reaches a high level whereas for other B. glabrata and all of the P. metidjensis, the level of production remains low. Histological studies revealed that at the exact moment of this treatment, there is a total destruction of many nearly mature cercariae whereas the young cercarial embryos and the tegument of the sporocyst remain unharmed. When treatment stops, there is a pronounced proliferation of third-generation sporocysts (Sp III) which invade the available space of the snails' digestive gland.

Animals↗

Tricarboxylic acid cycle enzyme activities in adult Schistosoma mansoni and Schistosoma japonicum.

Reduced tricarboxylic acid cycle enzyme activities were found in paired adult Schistosoma mansoni and S. japonicum in comparison to those reported for S. mansoni cercariae (Coles, 1973). Succinate dehydrogenase activity, which has not been previously reported for either adult blood fluke, is more than twice as great in paired adult S. japonicum as in paired adult S. mansoni, but the activity is low in both species of adult worms. The similar low levels of tricarboxylic acid cycle enzyme activities which occur in adult S. mansoni and S. japonicum further substantiate the fact that anaerobic glycolysis is the major energy source in adults of both species.

Animals↗

Comparison of the cloned genes of the 26- and 28-kilodalton glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni.

Both Schistosoma japonicum and S. mansoni contain 28- and 26-kDa glutathione S-transferases (GSTs). Despite their immunological cross-reactivity using rabbit antisera, the S. japonicum 28-kDa GST (Sj28) is weakly immunogenic relative to the S. mansoni protein (Sm28) in mouse immunization experiments using GSTs purified from adult worms. The difference in immunogenicity is also observed during schistosome infection in mice. Using surface-labeled living S. japonicum worms, evidence was obtained for a surface location of Sj28 comparable to that reported for the S. mansoni molecule. The nucleotide and deduced amino acid sequences of cDNA clones corresponding to Sj28 and Sm28 were compared. Despite obvious homology (77% identity), differences were found in regions known to contain T epitopes in the S. mansoni protein which may be an explanation for the striking differences in immunogenicity in regard to antibody production in mice. The 26-kDa GSTs of these two parasites (Sj26 and Sm26) are also closely related on the basis of nucleotide and deduced amino acid sequences, there being 82% identity in the putative coding regions. When the amino acid sequences of Sj28 and Sm28 were compared with those of Sj26 and Sm26, the overall sequence identity was approximately 20%. However, a relatively conserved region was identified in otherwise structurally different molecules which may participate in common properties of these enzymes.

Amino Acid Sequence↗

Simple school questionnaires can map both Schistosoma mansoni and Schistosoma haematobium in the Democratic Republic of Congo.

The use of self-administered questionnaires has been shown in different African countries to be inexpensive and reliable for the rapid identification of communities at highest risk of urinary schistosomiasis. For intestinal schistosomiasis due to Schistosoma mansoni there is a clear need for a similar approach. We report the results from a large-scale study undertaken in the western part of the Democratic Republic of Congo (DRC, formerly Zaire). Within 4 weeks questionnaires were correctly completed in 136 out of 160 schools (85%). In 57 of these schools children were screened for infections with schistosomes and geohelminths. The prevalence of 'schistosomiasis' as reported in the questionnaires showed the best correlation with the prevalence of S. mansoni infections (r = 0.77, P < 0.0001). Calculations of the diagnostic performance of reported 'schistosomiasis' to detect schools with a high risk of intestinal schistosomiasis gave positive predictive values of 87 and 62%, and negative predictive values of 74 and 87% for moderate and high infection thresholds, respectively. Reported 'blood in stool' was another useful indicator for intestinal schistosomiasis. Reported 'blood in urine' showed the best correlation with urinary schistosomiasis (r = 0.75, P < 0.001) and the positive predictive values were 81 and 50%, and the negative predictive values were 89 and 95% for moderate and high infection thresholds, respectively. We conclude that school children in DRC have a distinct perception of intestinal and urinary schistosomiasis and that questionnaires could be useful to identify high-risk schools for both parasites.

Adolescent↗

Interactions between Schistosoma haematobium and Schistosoma mansoni in humans in north Cameroon.

OBJECTIVES: To analyse the relationships between the frequency of ectopic localizations of Schistosoma haematobium and S. mansoni eggs. METHODS: Studies were conducted in 11 villages in north Cameroon, around Bessoum, a village where an epidemic of bloody diarrhoea caused by S. mansoni occurred in 1997. RESULTS: The results revealed infection prevalence rates of 70.5% for S. haematobium and 30.8% for S. mansoni. Interestingly, S. mansoni eggs were found in 14.5% of the urine samples and S. haematobium eggs in 3% of the stool samples. These ectopic eliminations of schistosome eggs resulted from sexual interactions between the two species of schistosomes, and from a spill-over of high infection loads. The clinical study showed that the morbidity was lower in individuals with mixed infections and high loads of S. haematobium than in those with S. mansoni infections only, suggesting a possible lowering effect of S. haematobium infection on S. mansoni morbidity. DISCUSSION: The results obtained in human populations are discussed in relation to the known schistosome interspecific interactions in animal models.

Adolescent↗

A field trial using praziquantel (BiltricideR) to treat Schistosoma mansoni and Schistosoma haematobium infection in Gezira, Sudan.

A field trial was conducted in the Gezira, Sudan, to evaluate the acceptability and efficacy of praziquantel, a new schistosomicide. In one Arab village 350 patients with Schistosoma mansoni were randomly assigned to two treatment groups and given 1 X 40 mg kg-1 (Group A) or 2 X 20 mg kg-1 given four to six hours apart (Group B). In two small settlements (camps) 2 km distant from the Arab village 38 patients with S. mansoni and 43 with concurrent S. mansoni and S. haematobium infections were given 1 X 40 mg kg-1. Side effects were mild and limited to the first 24 hours after treatment. The main complaints were abdominal pain, diarrhoea, urticaria and/or vomiting and were most common in the camp residents (79%) with 60% of Group A and 45% of Group B having one or more side effects. One month after treatment 'cure' rates were: Camps 63%, Group A 84% and Group B 96%, and the reduction in egg output was over 95%. After 12 months re-infection was greater in the camps. As there was no significant difference in the egg output reduction between the two treatment regimes, praziquantel is recommended for mass chemotherapy in Gezira at the logistically simpler regimen of 1 X 40 mg kg-1.

Adolescent↗

Molecular and serological characteristics of the glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni.

When aqueous extracts of Schistosoma japonicum and S. mansoni adult worms are passed over columns of glutathione-conjugated agarose, two molecular species of Mr 26,000 and Mr 28,000 are detected in eluates as analysed by SDS-PAGE, these eluates having glutathione S-transferase (GST) activity. The molecules, termed Sj26 and Sj28 from S. japonicum and Sm26 and Sm28 from S. mansoni, can be immunogenic in rabbits or mice and appear not to be linked together as subunits of GST heterodimers. The elution profile of SjGST (Sj26+Sj28) from glutathione columns resembles that of SmGST (Sm26+Sm28) and, by peptide mapping, radioiodinated Sj26 and Sm26 are related as are the two Mr 28,000 molecules. Similarities between radioiodinated Sj28 and Sm28 are also obvious on two-dimensional gel electrophoresis with some differences being observed between Sj26 and Sm26. The Mr 28,000 molecules are more prominent than the Mr 26,000 molecules and, although Sj28 and Sm28 is a poor immunogen in mice, immunological cross-reactivity between Sj28 and Sm28 is generally more readily detected than that between Sj26 and Sm26. Whether experimental vaccination against schistosomiasis japonica and schistosomiasis mansoni reported with cloned GSTs can be improved by incorporation of both Mr 28,000 and Mr 26,000 species into the vaccine remains to be determined. On this point, the present data suggest that vaccination of mice with Sj26 plus Sm28 should be a useful means of increasing antibody responses to the GSTs of S. japonicum.

Animals↗

The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium.

The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection.

Adolescent↗

Regression of hepatic lesions after treatment of Schistosoma mansoni or Schistosoma japonicum infection in mice: a comparative study.

Experimental infections with Schistosoma mansoni and S. japonicum differ in several aspects and post-treatment resorption of fibrosis might be one of them. To investigate this point, mice infected with each of these schistosome species were treated with praziquantel and the evolution of hepatic lesions was sequentially followed for five months. Parasitologic data showing destruction of worms and eggs and biochemical findings of progressively decreased collagen concentration after cure indicated that the lesions caused by S. mansoni and S. japonicum involuted in a similar fashion following chemotherapy. The time sequence of the histologic changes indicative of decreasing inflammation and progressive matrix degradation and resorption was also similar in both cases.

Animals↗

Age-dependent reduction of schistosome fecundity in Schistosoma haematobium but not Schistosoma mansoni infections in humans.

Understanding the dynamics of schistosome infections is problematic because direct measurements of worm burden are not possible. Hitherto, the relative intensity of infection has been estimated by the number of parasite eggs excreted. Egg excretion is assumed to have a consistent relationship with worm burden with duration of infection. We have tested this assumption in Schistosoma mansoni- and S. haematobium-infected populations by looking at the relationships between a circulating parasite antigen, egg excretion level, host age, and parasite density. The study was carried out in two populations because experimental models suggested that S. haematobium but not S. mansoni suffers immune-mediated reduction of fecundity. The results were consistent with this observation, showing that S. mansoni egg output remains stable irrespective of host age or infection intensity while S. haematobium has a substantially reduced egg production with host age. This information is fundamental to understanding the immunology and epidemiology of human schistosomiasis and thus practical approaches to disease control.

Adolescent↗

Oogram pattern, egg load and hatchability of eggs in mixed infection of Schistosoma mansoni and Schistosoma haematobium in hamster.

In mixed infection with Schistosoma mansoni and S. haematobium in hamsters, either simultaneously or after the full maturation of an initial infection with either schistosome species, a high level of acquired resistance was observed. The degree of immunity was magnified by the significant reduction in the number of eggs per gram tissue and hatchability of mature eggs. Some disturbance was also observed in the oogram pattern.

Animals↗

Schistosoma-specific helper T cell clones from subjects resistant to infection by Schistosoma mansoni are Th0/2.

Although T helper cells play a critical role in human immunity against schistosomes, the properties of the T lymphocytes that govern resistance and pathogenesis in human schistosomiasis are still poorly defined. This work addresses the question as to whether human resistance to Schistosoma mansoni is associated with a particular T helper subset. Twenty-eight CD3+, CD4+, CD8- parasite-specific T cell clones were isolated from three adults with high degree of resistance to infection by S. mansoni. The lymphokine secretion profiles of these clones were determined and compared to those of 21 CD3+, CD4+, CD8- clones with unknown specificity, established from these same subjects in the same cloning experiment. Almost all parasite-specific clones produced interleukin (IL)-4 and interferon (IFN)-gamma in large amounts. However, they generally produced more IL-4 than IFN-gamma; variations in IL-4/IFN-gamma ratios were accounted for by differences in IFN-gamma production since IL-4 levels were comparable for the clones from the three subjects. T cell clones of unknown specificity produced significantly less IL-4 and more IFN-gamma than parasite-specific T cell clones. Most clones produced IL-2, and IL-2 production did not differ between the two types of clones. Parasite-specific T cell clones from the resistant subjects were compared to specific T cell clones from a sensitized adult from a nonendemic area: T cell clones from this latter subject were the highest IFN-gamma and the lowest IL-4 producers, compared to those of resistant subjects. Thus, parasite-specific T cell clones isolated from adults resistant to S. mansoni belong to the Th0 subset and produced more IL-4 than IFN-gamma (Th0/2), whereas clones of a sensitized adult from a nonendemic area are also Th0, but produce more IFN-gamma than IL-4 (Th0/1). These results support previous conclusions on the role of IgE in protection against schistosomes in humans, and may indicate that IFN-gamma is required for full protection.

Adult↗

Studies on the relationship between Schistosoma and their intermediate hosts. V. The genus Bulinus and Schistosoma bovis from Iringa, Tanzania.

The relationship between an isolate of Schistosoma bovis from Iringa, Tanzania, and various species of the host snail genus Bulinus from East Africa was studied using the total cercarial production per 100 exposed snails over a period of 4 weeks following patency as an index of the compatibility. All populations of Bulinus forskalii and B. africanus tested exhibited a high level of susceptibility while the populations of B. truncatus and B. globosus tested were either refractory or of low to moderately low susceptibility. All populations of B. abyssinicus, B. canescens, B. nasutus and B. tropicus tested were refractory. It is suggested that B. africanus is the most important host snail for S. bovis in East Africa, that B. forskalii at least locally may contribute significantly to the transmission and that B. truncatus and B. globosus only play a limited role in the transmission.

Animals↗

Vaccination against Schistosoma mansoni infection using 74 kDa Schistosoma protein antigen.

An IgG2a anti-Schistosoma mansoni mouse monoclonal antibody was shown to passively protect Swiss mice. The 74 kDa target antigen was isolated from antigenic extracts of S. mansoni adult worms. Swiss and C57 BL/6J mice were immunized with 30, 50, 100 and 200 microg antigen/mouse doses with and without Freund's adjuvant. Sera of immunized mice showed high reactivity against 74 kDa antigen. The highest protection level (76.6% in Swiss mice and 50.1% in C57 BL/6J mice) was obtained using the 50 microg antigen dose with and without Freund's adjuvant. A marked reduction in granuloma number and intensity of collagen and reticular granuloma fibers was observed. The 74 kDa antigen has the ability to protect mice of different strains and to modulate the host immune system.

Adjuvants, Immunologic↗

Studies of the relationships between Schistosoma and their intermediate hosts. II. The genus Bulinus and Schistosoma haematobium from Sudan, Zaire and Zambia.

The relationship between Schistosoma haematobium from Sudan, Zaire and Zambia and various species and strains of Bulinus, has been investigated. The main emphasis was placed on evaluating the total cercarial production per 100 exposed snails as an index of the compatibility between snail and schistosome. The observations confirmed the results of previous compatibility studies which showed that there were two groups of S. haematobium, truncatus-borne from Sudan and Zaire, and africanus-borne, from Zambia. They also revealed that this division was not absolute, as some overlapping occurred. However, if the cercarial production was taken as an indication of compatibility, instead of the infection rate, there was a more definite division between the two groups. The observation that there is a truncatus-borne strain of S. haematobium present in Zaire extends the area where there is a mixture of truncatus- and africanus-borne strains farther southwards.

Adult↗