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The impact of Schistosoma haematobium hybridization on molecular diagnosis of schistosomiasis: A review with emphasis on female genital schistosomiasis.

Female genital schistosomiasis (FGS) is a gynecological manifestation of urinary schistosomiasis in female genitals. FGS is a neglected tropical disease; not only are most patients unaware of the condition, but healthcare workers and policymakers have inadequate knowledge about it. The treatment and control of FGS relies on current guidelines for controlling and eliminating schistosomiasis without rigorous focus on clinical evidence of the presence of FGS. Neglect of FGS has led to the misconception that the disease is sexually transmitted. Diagnosing FGS remains challenging as there is no widely accepted reference assay. Urine examination, which is the gold standard in urogenital schistosomiasis has some limitations in diagnosing FGS as the demonstration of Schistosoma haematobium and/or eggs alone does not necessarily indicate FGS. In order to overcome challenges with the biopsy and colposcopy approach, some studies have evaluated the potential of PCR-based assays and isothermal amplification of Schistosoma DNA. Recent studies have reported hybridization between S. haematobium and other livestock schistosomes, but little is known about the impact of hybridization on schistosomiasis diagnosis. These hybrids not only affect livestock and humans but also have their genomes modified, and in some cases, abnormal egg morphology due to Schistosoma hybridization might affect the actual prevalence estimation. Herein, we highlight the potential impacts of S. haematobium hybridization on molecular diagnosis of schistosomiasis, with an emphasis on FGS.

Humans

Epidemiology and control of schistosomiasis: present situation and priorities for further research. Scientific Working Group on Schistosomiasis.

The article highlights specific aspects of the epidemiology of schistosomiasis where insufficient data are available on which to base appropriate control strategies. Emphasis is placed on the part that immunological techniques might play in improving the baseline epidemiological data. A study of acquired resistance to the disease is also important in relation to epidemiology and control. The clinical manifestations of the disease vary in different areas and further study of the relation between the clinical and pathological manifestations are therefore required. In relation to the intermediate host, the main priority for research concerns the definition of the location and time-patterns of transmission foci within any particular area: variations in transmission are of particular importance in relation to man-made water resources. Although chemotherapy will play an increasing role in control, its importance will depend on local conditions: coordinated and standardized trials are required of chemotherapeutic agents in different regions and in various defined groups of subjects. The effects of chemotherapy on immunity to reinfection and on immunopathology also require study. With all types of snail control-chemical, ecological, and biological-cost-effectiveness aspects are important. With chemicals, it is important to bear in mind other possible effects on the environment. In the field of water supplies and sanitation, several aspects are important in relation to schistosomiasis transmission and community involvement should be encouraged.

Ecology

[Criteria of identification of schistosomiasis caused by Schistosoma hamatobium and S. mansoni (486 patients: 275 case of schistosomiasis)].

Out of a total of 486 patients who originated from French Equatorial Africa, from the West Indies or from the Indian Ocean, the authors identified 275 cases of schistosomiasis of which 230 were due to S. Hematobium and 45 to S. Mansoni. The diagnostic methods were biopsy of the rectal mucosa, immunofluorescence, in the West Indians, examination of the stools, in the Africans examination of the urine, intravenous urography and less often cystoscopy. The value of these investigations was studied in each case, then by comparison with one another and with data in the literature. The most valuable investigation was biopsy of the rectum, better in Africans than examination of the urine, immunofluorescence and better than cystoscopy when this was possible.

Adolescent

Schistosomiasis: assessment of the sensitivity, specificity and reproducibility of serological methods for the diagnosis of schistosomiasis in Nigeria.

Three groups of sera were tested by indirect fluorescent antibody (IFA), complement fixation (CF) and counter-current immunoelectrophoresis (CCIE) techniques; 56 (10.1%) of 554 sera from Nigerians were anticomplementary and so could not be tested by the CF. Crude antigen extract of adult Schistosoma mansoni was used in the CF and CCIE tests and cercarial antigen in the IFA test. IFA was the most sensitive test and CF the most specific. The reproducibility of both these tests was good. The CCIE was the least sensitive and specific, and its reproducibility was poor. The IFA test was the most suitable for Nigerian conditions. Cross-reactions to S. haematobium antibodies were consistently present in all three tests and it was not possible to differentiate serologically S. mansoni from S. haemotobium. The interpretations of the results presented some difficulties because of the frequency of cross-reactions and false-positives, but the data fell within the infection prevalence rate of 50% reported earlier from south-western Nigeria. The IFA test was more specific and is considered ideal for serodiagnosis.

Adolescent

Prevalence of HBs-Ag in schistosomiasis: B-frequency in various stages of schistosomiasis.

The study included 916 schistosomal patients and 97 controls. The prevalence of HBs-Ag and anti-HBs was significantly higher in the bilharzial patients compared to controls. Their frequency was higher in the ascitic than the hepatosplenic group, and the difference between each and the simple group was highly significant. Cases with current jaundice showed highly significant frequency of both HBs-Ag and anti-HBs compared to those with no history or manifest jaundice at the time of study. In addition, cases with raised bilirubin, SGPT and SGOT showed significantly higher frequency of HBs-Ag and anti-HBs compared to cases having normal levels. On the other hand, the frequency was not affected by the level of serum alkaline phosphatases. As regards liver pathology, cases with mixed pathologic picture showed significantly higher frequency of both HBs-Ag an anti-HBs compared with those having pure schistosomal lesions.

Alanine Transaminase

Primary liver cancer coincident with Schistosomiasis japonica. A study of 24 necropsies.

The etiologic relationship of parasitic liver disease to primary liver cancer has long been debated. For this reason, a review of 4611 necropsies was carried out to determine the frequency with which hepatocellular carcinoma occurred in association with schistosomiasis. Of 227 cases of hepatocellular carcinoma, 24 (10.6%) were associated with schistosomiasis japonica. This was significantly higher than the incidence of this carcinoma without schistosomiasis (2.78%). The majority of the 24 cases exhibited the features of a mixed macronodular and micronodular cirrhosis (Gall's posthepatitic cirrhosis); this was super-imposed upon and caused a masking of schistosomiasis fibrosis. By radioimmunoassay hepatitis B antigen was positive in 27% of these cases. A review of the literature indicated that chronic schistosomiasis, on its own, is unlikely to be the cause of primary liver cell carcinoma. Histologic features resembling post-hepatitic cirrhosis combined with a high frequency of hepatitis B antigen suggest that viral hepatitis rather than S. japonicum is the more likely etiologic factor involved, or has a synergistic effect on carcinogenesis.

Adult

Control of schistosomiasis: report of a workshop.

Nineteen scientists, field workers, and representatives of funding agencies active in schistosomiasis research and control met in Bellagio, Italy in October 1977 to attempt to evaluate the effectiveness of current control methods and what might be accomplished with available technology. The deliberations included summaries of knowledge on the biology, transmission, and control of schistosomiasis and assessment of major control programs and methodologies. The groups concluded that in the major endemic areas considerable gains in control of schistosomiasis could be made with current technology. However, maintenance of control in most countries, and establishment of serious control programs in countries in which schistosomiasis is a less severe public health problem, would require development of less expensive modalities which would need little monitoring and possibly have benefits extending beyond schistosomiasis control.

Agriculture

Liver collagen synthesis in schistosomiasis mansoni.

We determined collagen synthetic rates and utilization of key amino acid precursors of collagen in slices of wedge liver biopsy specimens obtained at required surgery from 9 patients with hepatosplenic schistosomiasis and from 4 control patients. The liver specimens from the patients with schistosomiasis showed advanced fibrosis, with histologic evidence of schistosomiasis alone in four, and both schistosomiasis and chronic active hepatitis in five cases. Liver slices were incubated with radioactive proline, arginine and glutamine, using quantitative assay conditions validated earlier for murine schistosomiasis. Collagen peptide synthesis in slices from all nine fibrotic liver specimens was 4- to 25-fold greater than normal and correlated positively with liver collagen content, which was 2- to 5-fold greater than normal. Free proline, an amino acid that may contribute to regulation of collagen peptide synthesis, was increased in six of the nine fibrotic liver specimens, and proline was actively formed from arginine in liver slices from all specimens. These measurements of the initial steps of collagen biosynthesis in fibrotic human liver are quantitatively similar to those previously made of the same processes in experimental animals.

Adolescent

Perigenital cutaneous schistosomiasis.

Perigenital cutaneous schistosomiasis was diagnosed in a patient who had no previous genitourinary or gastrointestinal symptoms suggesting schistosomiasis; his only symptom was a pruritic papular rash in the perineum. Late cutaneous schistosomiasis due to deposition of ova in the dermis is rare but can affect the genital and periumbilical areas. This report highlights the difficulty in diagnosing cutaneous schistosomiasis and the need for biopsy of itchy cutaneous lesions in patients from localities where the infection is endemic.

Child

Ovaries and adrenals in murine Schistosomiasis mansoni. I. Histopathological changes of the ovaries in acute and chronic infection.

Acute and chronic infections with schistosomiasis mansoni in mice were found to cause a reduction of the ovarian weight and atrophy of the corpus luteum cells, followed by lymphocytic and stroma cell infiltration. Finally, the corpora lutea disappeared completely. Acute schistosomiasis caused arrested development of the corpora lutea. Both acute and chronic schistosomiasis led to the formation of "wheel cells" in the interstitial tissue of the ovaries. A threshold level of intensity of disease was found to be necessary for these pathological changes. With less severe schistosomiasis, the morphology of the corpora lutea remained normal. The more intensive and long-lasting the infection, the greater became the atrophy of corpora lutea. The various factors which could have caused these pathological alterations are discussed in the light of available literature, and it is suggested that a pituitary hypofunction, and particularly a lack of luteinizing hormone effect, may play a role in the pathological transformation of the ovarian tissue.

Acute Disease

Prospects of schistosomiasis at the Kidatu dam project in Tanzania.

A schistosomiasis survey was carried out to determine the present and future potential for transmission of schistosomiasis at the site of the Great Ruaha Power Project at Kidatu. Although a few cases of the disease in the human population were recorded at the dam-site and in the future reservoir lake areas, they were probably contracted outside as both areas were considered unlikely habitats for the snail transmitters of schistosomiasis. Higher prevalence rates were registered in the neighbouring areas Kidodi, Kilombero and Kidatu, where snail vectors of urinary schistosomiasis, Bulinus (Physopsis) nasutus and B(P) africanus/globosus (?) were found.

Adult

Renal amyloidosis and schistosomiasis.

A retrospective study of 60 renal biopsies obtained from nephrotic subjects with schistosomiasis showed amyloid deposits in 10 cases. Distribution was usually segmental, mainly mesangial and overlapped with the conventional mesangio-proliferative lesions of schistosomiasis. The invariable clinical presentation was proteinuria with generalized oedema of insidious onset and a slowly progressive or intermittent course. Differences from conventional schistosomal nephropathy are described. Response to anti-schistosomal treatment was very poor. Repeat renal biopsies showed no regression of the lesions. The possible links between schistosomiasis and amyloidosis are discussed and causes of amyloid deposition suggested.

Adolescent

Changing pattern of schistosomiasis in Egypt 1935--79.

A village in the Nile surveyed for schistosomiasis by J. A. Scott in 1935 was surveyed again in 1979. The same number of people as in the 1935 survey were randomly selected for investigation by the same parasitological techniques as those used by Scott. The prevalence of Schistosoma mansoni infection had increased from 3.2% to 73%, whereas S. haematobium infection, which had been very common in 1935 (74%), had almost disappeared (2.2%). In the local district hospital since 1972 the percentage of urine specimens found to contain S. haematobium ova has dropped from 30 to 9%, while the percentage of stool specimens containing S. mansoni ova has increased from 2 to 22%. In the local irrigation canals snail intermediate hosts for S. mansoni have outnumbered those for S. haematobium by a factor of 5--40 in the past 7 years. Changes in the proportions of snail vectors appear to be related to construction of the Aswan High Dam and to changes in the water-flow patterns of the Nile. The change in the relative frequencies of the two infections had important public-health implications, since the hepatosplenic schistosomiasis caused by S. mansoni is more difficult to treat and is associated with more morbidity and mortality than the urinary schistosomiasis caused by S. haematobium.

Animals

Preliminary screening of urinary host protein biomarkers for Schistosomiasis haematobium: A proteome profiling study identifying candidate diagnostic targets in school-aged children.

Schistosomiasis is a major public health challenge and a globally neglected tropical disease. Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is endemic in African countries; with school-aged children ages 7-15 years being the most vulnerable population. Current diagnostic methods rely on microscopy to identify parasite eggs in urine; which is labor-intensive, requires specialized skills, and often lacks sensitivity, especially in mild infections. To address these limitations, we explored host disease-related biomarkers as a promising avenue for advancing diagnosis and detection. We recruited 135 children ages 7-15 years from Zanzibar, a known transmission hotspot, and used data-independent acquisition (DIA) proteomics combined with machine learning to identify potential host protein biomarkers in urine samples from individuals infected with Schistosoma haematobium. Proteomic analysis identified 823 common host proteins in urine samples from the infected group. Machine learning algorithms highlighted candidate discriminative proteins; which were validated using enzyme-linked immunosorbent assays (ELISA). Machine learning emphasized SYNPO2, CD276, α2M, LCAT, and hnRNPM as the most discriminating biomarkers for Schistosoma haematobium infection. ELISA validation confirmed the differential expression trends of these proteins, while machine learning further validated LCAT and α2M, underscoring their diagnostic potential. Our study focused on host-derived proteins and identified key urinary protein biomarkers associated with Schistosoma haematobium infection, and offers new insights into host-parasite interactions and potential tools for non-invasive diagnostics. While validated in African pediatric populations from transmission hotspots, this host-protein approach inherently overcomes geographic limitations of parasite-based diagnostics; which is a critical advantage for surveillance in non-endemic regions where imported cases threaten gains toward elimination. These findings lay the groundwork for developing novel diagnostic approaches that could significantly improve the detection and surveillance of schistosomiasis, particularly in high-risk populations.

Humans

Elution of renal antischistosome antibodies in human schistosomiasis mansoni.

Elution of complexed immunoglobulins was carried out in renal tissue obtained at autopsy from schistosomiasis mansoni and control cases. Substantial amounts of IgG were found in acid eluates of 2 of 5 schistosomiasis cases and 2 of 3 controls. The IgG from schistosomiasis cases produced specific indirect immunofluorescence reactions in gut and tegument of sections of adult Schistosoma mansoni; no reactivity was present against egg granulomas, cercariae, or mouse liver tissue. Control case eluates produced no fluorescence with S. mansoni antigens.

Antibodies, Anti-Idiotypic

Bacteriuria in urinary schistosomiasis in Egypt a prevalence survey.

An epidemiologic survey to assess the prevalence of bacteriuria in urinary schistosomiasis was carried out in a region endemic for urinary schistosomiasis in Egypt. Twenty of 390 (5.1%) school boys aged 5--16 years were bacteriuric. This prevalence rate is more than 10 times greater than that found in comparable surveys in areas non-endemic for urinary schistosomiasis. In this endemic population bacteriuria was found in 6.5% of active egg excreters and 2.3% of non-egg excreters.

Adolescent

Host-parasite relationship in schistosomiasis mansoni in the mutation diabetic mouse (db/db).

Impairment of cell-mediated immunity has been described in chemically-induced as well as mutation diabetes in the mouse. The present report examines the host-parasite relationship during the acute phase of schistosomiasis mansoni in the mutation diabetic mouse (db/db). Cercarial penetration and maturation and egg output by adult worms were similar in the db/db mice and their littermate controls (db/+). In contrast, the pathological consequences of schistosomiasis were much less in the db/db mice. The mean liver weight computed as a percentage of body weight in db/db mice was 4.6 +/- 0.2 and following 8 weeks of infection it was 5.7 +/- 0.3 (difference is not statistically significant), whereas in infected db/+ mice it was 7.2 +/- 0.5. Infection in db/+ mice increased their mean portal pressure by 124% in contrast to an increase of only 12% in db/db animals. The most striking difference was noted in the mean granuloma diameter in the liver: 402 +/- 35 micrometer in db/+ in comparison to 147 +/- 10 micrometer in db/db mice (P less than 0.001). This study demonstrates the crucial role of the host granulomatous response in the causation of disease due to Schistosoma mansoni. Furthermore, it underlines the decreased pathological consequences when the host granulomatous response is suppressed, which can be compared to the response of modulated animals with chronic schistosomiasis.

Animals