Biomedical subjects
Publications and source records attributed to A M Deelder.
In the present paper a brief overview will be given of the recent progress and trends in assaying diagnostic markers in schistosomiasis; only markers of the humoral immunological system and biochemical markers will be discussed, as markers for cellular immunological reactivity will be discussed by other authors. The following diagnostic markers will be reviewed: markers for infection, markers for immunity and markers for morbidity.
Serum and urine levels of two Schistosoma circulating antigens, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA), were determined by monoclonal antibody-based enzyme-linked immunosorbent assays in 56 Egyptian patients infected with S. mansoni and in 12 patients infected with both S. mansoni and S. haematobium. Both CAA and CCA could be specifically demonstrated in 82% and 88% of the serum samples and in 88% and 87% of the urine samples, respectively. While complete specificity was maintained, sensitivity was increased to a range of 91-98% by parallel use of the two circulating antigen assays, i.e., an individual with a positive titer for at least one of the assays was considered to be infected. A combination of CAA and CCA determinations in urine samples only resulted in a sensitivity of 94%. However, the highest sensitivity was achieved when the serum-CCA assay was combined with the urine-CCA assay (98%) or with the urine-CAA assay (97%). Sensitivity could not be increased further by combining more than two tests. A significant correlation was demonstrated between the level of circulating antigen and the number of parasite eggs in feces in each of the four assays. In addition, the levels of CAA and CCA in serum and urine were significantly correlated with each other. Our results indicate that diagnosis of schistosome infections by detection of circulating antigens can be significantly improved by parallel testing for multiple antigens.
Monoclonal antibody (MAb) 5H11 reacted with repeating epitopes on Schistosoma mansoni circulating cathodic antigen (CCA) and detected CCA in sera of Egyptian S. mansoni-infected patients. MAb 5H11 was both capture and biotinylated detection antibody in a sandwich ELISA of trichloroacetic acid-pretreated serum samples. Sera of patients with 7-500 eggs/g of stool were positive by MAb 5H11-CCA sandwich ELISA. Stool egg counts and CCA serum levels correlated (r = .52), and CCA levels decreased by 4 weeks after praziquantel treatment in patients with pretreatment egg counts of greater than or equal to 50/g of stool (P less than .05). Sera of Schistosoma haematobium-infected patients, uninfected individuals, and most patients with other helminths were negative in this assay. The MAb 5H11-CCA sandwich ELISA appears sensitive and specific for immunodetection of active schistosomiasis mansoni and useful for monitoring its chemotherapy.
Information regarding glomerular lesions related to Schistosoma haematobium infection in man or animal are extremely lacking and disputed. The objective of this experimental study was to investigate glomerular lesions in S. haematobium-infected golden hamsters. In this work, 53 hamsters were infected with S. haematobium cercariae and 18 animals of similar age and sex served as controls. Hamsters were infected either with 50, 200, 300, 400 or 600 cercariae and sacrified after 8, 9, 10, 14, 18, 24 or 32 weeks. Infected and control hamsters were subjected to laboratory examinations including serum creatinine, serum albumin, total protein, serum cholesterol, total urine protein as well as histopathologic evaluations. Kidney biopsies were examined by light microscopy, indirect immunofluorescence and by electron microscopy. Significant proteinuria, hypoalbuminaemia and hypercholesterolaemia were observed in all but 5 S. haematobium-infected, but in none of the control hamsters. Renal impairment was observed in 5 hamsters. Histopathologic evaluations showed IgG, circulating anodic antigen and circulating cathodic antigen deposits in the renal glomeruli. By electron-microscopic examination, these deposits were seen mainly in the subendothelial, mesangial and paramesangial areas. Amyloid deposits were also seen in the renal glomeruli, tubular basement membrane and in the interstitium. A correlation was found between the extent of amyloid deposition and the duration but not the intensity of schistosomal infection. We have concluded that S. haematobium infection can lead to glomerulopathy in golden hamsters.
We report the application of a fluorescein isothiocyanate (FITC)-anti-FITC method to localize antigens at the ultrastructural level. In the systems studied, the anti-FITC-based detection method displays high specificity and sensitivity. These observations, combined with ease of production and with availability of FITC-protein conjugates, suggest that the FITC-anti-FITC method is a good alternative to presently used methods and is widely applicable to immunochemical and immunocytochemical procedures. The same preparation and protocol can be used for light and electron microscopic studies, thereby reducing possible artifacts introduced if different procedures are used. In the present study, two systems were used to test the method. One system used an FITC-labeled monoclonal antibody (MAb) to schistosome circulating cathodic antigen. In this system, the label was detected in the gut of adult Schistosoma mansoni by an anti-FITC MAb conjugated to 10-nm gold particles. The second system used human IgM antibodies pooled from patients infected with Schistosoma mansoni. In this system detection was accomplished using an anti-human IgM-FITC conjugate followed by the anti-FITC-Au antibody conjugate.
The kinetics of circulating anodic antigen (CAA) levels in urine were studied in Egyptian male patients infected with Schistosoma mansoni or with both S. mansoni and S. haematobium, before treatment, and at one, three and six weeks after chemotherapy. A quantitative enzyme-linked immunosorbent assay (ELISA) demonstrated CAA in 82% of the serum and 89% of the urine samples from these 28 patients. To evaluate the possibility of circadian variability in urine CAA levels, samples were examined in 15 patients at four intervals during a 24-hour period. No significant differences in CAA titers were observed. Seventeen patients were subsequently treated with praziquantel and followed for six weeks. CAA titers in serum and urine decreased significantly one week after therapy. Thereafter, the profile of CAA titer in urine continued to show a parallel but delayed decline compared to that in serum. While all serum CAA titers became negative three to six weeks after treatment, urine titers were negative in 47% at three weeks and 69% at six weeks. The remaining positive patients had low titers. A significant quantitative correlation in CAA titer was found between serum and urine before and after treatment. Seventeen Egyptian control subjects with no active schistosome infection were negative for CAA in both serum and urine. Our results confirm that the CAA urine assay could be used as a sensitive and non-invasive method to diagnose the disease, and indicate that the assay can be used to monitor efficacy of schistosome chemotherapy.
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In this study, levels of circulating anodic antigen (CAA) in serum were investigated after differential treatment of 160 Sudanese patients with mixed Schistosoma haematobium and S. mansoni infections. The patients were randomly divided into four groups, which were treated with metrifonate (two doses of 10 mg/kg bodyweight), oxamniquine (60 mg/kg), praziquantel (40 mg/kg), or a multivitamin preparation, respectively. Serum, stool and urine samples were taken prior to treatment as well as one month and five months after chemotherapy. Before chemotherapy CAA levels were similar in the four groups. Antigenemia remained unchanged in the control group. In patients treated with praziquantel or oxamniquine the concentration of CAA decreased to a similar extent. However, whereas in the praziquantel group absence of CAA was already observed one month after treatment, clearing of CAA from the circulation seemed to take longer in patients treated with oxamniquine. Treatment with metrifonate did not result in a reduction of the CAA titres.
Antigens of the Schistosoma mansoni digestive tract are recognized early in the infective process. Two immunogenic components of the excretory/secretory products are proteolytic enzymes that degrade host hemoglobin in the lumen of the parasite gut. These enzymes, CP1 and CP2, belong to the class of cysteine proteinases. In this study, a preparation containing both proteinases has been used to detect proteinase antibodies in the sera of individuals living in Burundi. Of 133 individuals tested, 92% were excreting schistosome eggs. All patients with documented infections had positive anti-proteinase IgG titers (mean = 1:614), while 82% had positive IgM titers (mean = 1:267). Six weeks following praziquantel treatment, patients were assessed for egg excretion and antibody titer. Anti-proteinase IgG titers were significantly lower (mean = 1:259) than pre-treatment titers. Patients who were infected with S. japonicum or S. haematobium typically showed a cross-reactive IgG response. Patients from non-endemic regions yielded negative titers, and those with non-trematode parasites were negative (79%) or weakly positive. S. mansoni cysteine proteinases may be used for the detection of schistosome infections.
We investigated in a retrospective study the application of an enzyme-linked immunosorbent assay (ELISA) for the quantitative detection of the schistosome circulating anodic antigen (CAA) to the diagnosis of schistosomiasis in our laboratory. CAA-titres were compared with IgG-titres as determined with an ELISA using soluble egg antigen (SEA) and IgM-titres as determined in an immuno fluorescence assay (IFA) on sections of Rossman's fixed schistosomes. Pre- and post-treatment serum samples of 182 individuals, suspected for schistosomiasis, were used for this study, including 100 control samples. CAA was detected in 20.7% of all patients who were positive in either IFA or SEA-ELISA or both. CAA-titres did not correlate with either IgM-titres or IgG-titres. No significant drop in IgG level was found after specific treatment (Wilcoxon's P = 0.35). In contrast, a significant fall in both IgM-titre (P less than 0.01), and CAA-level (P less than 0.01) was observed. All CAA-titres became negative after chemotherapy.
Schistosomiasis is a very frequent import infection in the Netherlands. The serotesting for schistosomiasis in Leyden affords reasonable insight into the prevalence of this import infection among different groups of the population in the Netherlands. Out of 3032 serum samples submitted in the period from 1983 to April 1986, 40% was positive. Most people with positive serum tests were of Surinam origin. Currently, there is a shift toward more infections among Dutch travellers. Many of these patients have high IFA titres indicating a recently incurred infection. Often no ova are found in spite of positive serotest: this phenomenon was seen in 36% of the Dutch travellers and in 48% of the Surinam people.
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The presence of the schistosome circulating anodic antigen (CAA) in serum of Schistosoma intercalatum-infected patients from Gabon has been investigated using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected from 10 endemic controls, 29 patients which excreted viable S. intercalatum eggs in rectal mucosa and stool, six persons in which only non-viable eggs were found in rectal biopsy specimens and one person in which besides non-viable eggs a small number of viable eggs was found in the rectal biopsy specimen. CAA, a genus-specific antigen, could be demonstrated in 58.6% of the patients with S. intercalatum eggs in their stools. In comparison to S. mansoni infections, very light infections (0.6 eggs per gram faeces) could be detected by the ELISA. A strong correlation between parasite burden (eggs per gram faeces) and antigen-level (CAA-titer) was found (Spearman's rho = 0.65). Only one positive ELISA-results was found in the group with solely non-viable eggs in rectal tissue. As no false positive results were detected for the negative controls, the present results suggest, in accordance with results earlier obtained for schistosomiasis mansoni, that only in active S. intercalatum infections is antigen demonstrable.
In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs plus cyclosporine. The schistosomal specificity of kidney lesions was assessed by detecting the schistosomal specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. Patients who had another etiologic cause which may explain their kidney disease were not admitted to this study. After initiation of the treatment, patients were followed up every other week in the outpatient clinic for 12 months. Follow-up showed complete remission of proteinuria in two cases in group II (duration of remission was 4 and 8 months) and in one case in group III (duration of remission was 6 months) but in none in group I. Partial remission was observed in one case in group I, in three cases in group II and in one case in group III. During the observation period, improvement in kidney function was observed in two cases in group II but deterioration in kidney function was observed in one case in group I and in one other case in group III. We conclude that in patients with schistosomal nephropathy, none of the tried therapeutic regimens produce regression of the disease if given to patients with established disease.
From a panel of mouse monoclonal antibodies reactive with a repeating epitope of the schistosome circulating anodic antigen, an IgG1 monoclonal antibody was selected. This monoclonal antibody was applied in a sandwich enzyme-linked immunosorbent assay as capture antibody and as alkaline phosphatase labeled conjugate. This assay allowed a sensitive quantitation of circulating anodic antigen in serum samples of infected individuals, detecting less than 1 ng antigen/ml serum. In Schistosoma mansoni infected individuals from Zaire, the level of antigen in serum correlated with fecal egg output. The lower detection level of the immunoassay corresponded to a level of about 10 eggs/gm feces.
In serum and urine specimens collected from a group of Schistosoma mansoni infected individuals from Makundju, Zaire, the schistosome circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA) were quantitatively determined using an indirect hemagglutination reaction with sheep erythrocytes sensitized with mouse IgM monoclonal antibodies directed against these circulating antigens. Levels of CAA in serum (up to 5 ng/ml) and CCA in serum and urine (up to 50 ng/ml) were strongly correlated with egg excretion and with each other. No correlation was found between egg excretion and antibody levels against the circulating antigens. Antigen was detectable only in patients excreting greater than 500 eggs per gram of feces.
We investigated the presence of the circulating anodic antigen (CAA) in the urine of schistosomiasis patients. This genus specific antigen was hitherto demonstrated only in the serum of schistosomiasis patients. The urine of 80 patients with Schistosoma mansoni infections, 33 patients with S. haematobium infections, and 2 patients with mixed S. haematobium and S. mansoni infections were screened by a quantitative enzyme-linked immunosorbent assay (ELISA). CAA was demonstrated in 81% of those with intestinal schistosomiasis and in 97% of those with urinary schistosomiasis. CAA titers were less than 1:0.2-1:51.2. Results were compared with circulating cathodic antigen (CCA) titers in urine obtained in an indirect hemagglutination assay (IHA). CCA was generally not detectable in the urine of patients with S. haematobium infection, but was demonstrated in the urine of 85% of the patients with S. mansoni infection. Both CAA titers and CCA titers correlated positively with the number of S. mansoni eggs excreted in the feces, but CAA titers did not show a significant correlation with the number of S. haematobium eggs in urine. Both antigen titers showed a moderate correlation with the serum CAA level in schistosomiasis mansoni. The discovery of CAA in the urine of the majority of schistosomiasis patients tested suggests the use of urine samples for non-invasive immunodiagnosis of the disease.