Biomedical subjects

A M Deelder

Publications and source records attributed to A M Deelder.

At least 55 records · Page 3Linked to original sources

PubMed1997

Detection of the circulating antigens CAA and CCA in a group of Dutch travellers with acute schistosomiasis.

Detection of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine is a highly specific and sensitive alternative for the diagnosis of schistosome infections in endemic areas. However, it is not known how soon after the onset of infection these antigens can be detected in humans. Neither has there been much research on the detection of these antigens in individuals normally living in non-endemic areas. We studied the kinetics of CAA and CCA in serum and urine of a group of 28 Dutch tourists, shortly after accidental exposure to a Schistosoma infection during a visit to Mali. Twenty-seven were found to be positive for Schistosoma eggs and/or specific antibodies. From each individual, 1-4 serum samples were tested for circulating antigen level, 4-15 weeks after exposure, and urine samples were also tested from 22 subjects. CAA and CCA levels were quantified by monoclonal antibody-based ELISAs and TRIFMAs. In serum, 23 individuals (85%) were positive at least once for one or both antigens, but titres were generally very low. CAA and CCA could be detected 5 and 6 weeks after exposure, respectively. Urines were all found to be negative. Almost all cases were negative at 7 months' follow-up.

Adult↗

PubMed1997

Anti-schistosome IgG4 and IgE at 2 years after chemotherapy: infected versus uninfected individuals.

Specific IgG4 and IgE responses to adult worm antigen (AWA) and soluble egg antigen (SEA) were examined in 37 subjects from an area in which schistosomiasis is endemic, who were previously infected with Schistosoma haematobium and who became reinfected or remained free of infection 2 years after chemotherapy. The reinfected group was significantly younger (median age, 11 years) than the uninfected group (median age, 24 years). Posttreatment levels of IgG4 to egg antigens (IgG4-SEA) were significantly correlated with reinfection intensity (r = .74, P < .0001), and 13-fold lower levels of IgG4-SEA were observed in uninfected subjects compared with reinfected subjects. Although no correlation was observed between posttreatment IgE to AWA or to SEA, pretreatment IgE-AWA was inversely correlated with the level of reinfection (r = -.39, P = .02).

Adolescent↗

PubMed1997

Therapeutic evaluation of two different dose regimens of praziquantel in a recent Schistosoma mansoni focus in Northern Senegal.

A therapeutic trial, involving 130 Schistosoma mansoni-infected children, with no previous history of antischistosomal treatment, was carried out to evaluate the efficacy of two different dose regimens of praziquantel. The study was carried out because low cure rates were described in this recently established (1990) S. mansoni focus in northern Senegal, following treatment with a standard dosage of 40 mg/kg. The subjects were randomly allocated into two groups: one group (1) received 40 mg/kg in one oral dose, the other group (2) was treated with two oral doses of 30 mg/kg at a 6-hr interval. Parasitologic examination and circulating anodic antigen (CAA) detection were performed before, 10 days, three, six, and 21 weeks after chemotherapy. No significant differences in cure rates were found between the two groups. Six weeks after treatment, 34% and 44% of the individuals were found to be stool negative in group 1 and group 2, respectively. However, only 10-15% became completely negative according to the serum CAA antigen assay. Mean egg counts were reduced by 99% in both groups. Antigen detection confirmed the parasitologic results. Fewer side effects were observed in the group treated with 2 x 30 mg/kg, which may be explained by split dosage administration. Our study shows that the low cure rates observed in this area could not be improved by using a higher dosage of praziquantel.

Adolescent↗

PubMed1997

Day-to-day variation of egg output and schistosome circulating antigens in urine of Schistosoma haematobium-infected school children from Gabon and follow-up after chemotherapy.

A group of 31 school children from Gabon infected with Schistosoma haematobium was examined before praziquantel therapy and followed on days 3, 9, 14, 21, 24, 28, 31 and 35 after therapy. The day-to-day variation of schistosome circulating antigens, urinary egg output, and the reagent strip index (RSI, a pathologic marker) was studied in six consecutive pretreatment urine samples collected under standardized conditions. The geometric mean pretreatment for egg output ranged between 97 and 223 eggs per 10 ml of urine; for urine circulating anodic antigen (CAA) levels this was 44-154 pg/ml and for circulating cathodic antigen (CCA) levels this was 180-601 pg/ml. On the day of treatment, 97% of the children had viable eggs in their urine, 87% had a positive RSI; positive CAA levels were detected in 61% of the children and positive CCA levels in 77%. A significant correlation was consistently found between RSI and egg counts. Five weeks after chemotherapy egg output, levels of CAA and CCA and the severity of pathologic findings in the lower renal tract, as indicated by the RSI, had decreased significantly in all cases. Our results indicate that egg output in urine is an accurate method for diagnosis of S. haematobium, and additionally show less day-to-day variation than detection by ELISA of schistosome circulating antigens in urine.

Adolescent↗

PubMed1996

Reversibility of lower reproductive tract abnormalities in women with Schistosoma haematobium infection after treatment with praziquantel--an interim report.

Little is known whether and to what extent antiparasitic treatment cures female genital schistosomiasis (FGS). Using a standard protocol, of twenty-one women with FGS nine were re-examined at two to nine weeks after they had been treated with praziquantel at a single dose of 40 mg/kg. Symptoms related to pathology of the urinary tract and to a lesser extent of genital pathology subsided in most patients. Schistosoma haematobium ova were no longer detectable in urine of any of the patients post-treatment. Efficiency of chemotherapy against adult worms was confirmed by the disappearance of circulating anodic antigen (CAA) in serum. Sandy patches showed resolution in two of four cases after chemotherapy. Papillomata due to schistosomiasis alone improved, but persisted in mixed infection with human papilloma virus (HPV) or when HPV was the only underlying cause. In one patient ulcera could not be related with certainty to schistosomiasis at admission, but resolved after treatment with parziquantel. Leukoplakia (two cases) was not influenced by chemotherapy, or even increased during follow-up, regardless of whether ova had been detected or not. Although the follow-up period was rather short, time intervals were not standardized, and a relatively small number of patients was investigated, it could be shown that genital pathology due to sequestered S. haematobium ova is, at least partially, reversible already two to nine weeks after killing the adult worms by praziquantel. This is paralleled by a normalization of inflammatory immune responses detectable in histological sections and vaginal lavage.

Adolescent↗

PubMed1996

Schistosoma mansoni excretory circulating cathodic antigen shares Lewis-x epitopes with a human granulocyte surface antigen and evokes host antibodies mediating complement-dependent lysis of granulocytes.

Parasitic worms of the genus Schistosoma excrete relatively large amounts of immunogenic glycoproteins (circulating cathodic antigen [CCA]) that contain polysaccharide side chains with the trisaccharide Lewis-x (L(ex)) as a repeating unit. These carbohydrates evoke high titers of specific IgM antibodies that cross-react with the repeating L(ex) units on the surface of granulocytes. Consequently this might lead, in the presence of complement, to lysis of the granulocytes. In the present study, this hypothesis was investigated using anti-CCA mouse monoclonal antibodies (MoAbs) and polyclonal antibodies purified from sera of infected humans. By flow cytometry, it was demonstrated that the mouse MoAbs directed against CCA strongly recognized the granulocytes. It could also be shown that these MoAbs, as well as anti-CCA IgM antibodies purified from infected human sera, caused lysis of granulocytes in a complement-dependent cytotoxicity assay. Sera from healthy controls or from patients with other helminth infections resulted in negligible granulocytotoxicity. These in vitro observed phenomena may explain the mild to moderate neutropenia that occurs in schistosomiasis patients.

Animals↗

PubMed1996

Elevated proliferation and interleukin-4 release from CD4+ cells after chemotherapy in human Schistosoma haematobium infection.

Cellular immune responses to schistosomal antigens were examined in 110 Schistosoma haematobium-infected individuals before and 5 weeks after treatment with praziquantel. Chemotherapy resulted in significant decrease in worm load as measured by egg output and circulating antigens. The proliferative responses to adult worm antigen (AWA) increased significantly after treatment (p < 0.001) whereas purified protein derivative of tuberculin or phytohemagglutinin responsiveness was unaffected. Interleukin (IL)-4 production in response to both AWA and soluble egg antigen (SEA) increased markedly after treatment (p < 0.001), but IL-5 remained unchanged. None of the studied subjects released any measurable IL-2 and only 21% produced interferon (IFN)-gamma in response to parasite antigens. The deficiency in either IFN-gamma or IL-2 release was not restored by chemotherapy. Thus chronic infection with S. haematobium is associated with the reversible down-regulation of T cell proliferative responses and IL-4 release. Results from cell depletion experiments indicated that CD4+ T cells were the target of this down-modulation.

Adolescent↗

PubMed1996

A comparative study on specific antibodies and circulating antigen (CAA) in serum and parasitological findings for diagnosis of schistosomiasis mansoni in an endemic area in Tanzania.

A baseline study to evaluate the prevalence of Schistosoma mansoni infection as well as the diagnostic efficacy of serodiagnostic tests was performed in Kabaganga village, Kome island, Lake Victoria, Tanzania. A total of 1108 individuals were examined parasitologically and clinically. Egg excretion was demonstrated by one-sample Kato-Katz test. Specific IgG1 and IgG4 antibodies against S. mansoni adult worm (SAWA) and egg (SEA) antigens as well as circulating anodic antigen (CAA) were determined in serum samples from 250 of these subjects. As a control population 41 individuals from a non-endemic area were examined parasitologically, clinically and serologically. In the parasitologically examined Kabaganga population 45% were excreting eggs. The pattern of egg excretion was typical for an endemic area with a peak in the age group 10-14 years. Sixty-five percent of the serologically tested villagers were positive in the CAA test. A total of 80% were positive in either of the two tests, indicating an active infection. In 67-95% of these individuals the levels of isotype specific antibodies were increased. The prevalence of CAA positivity corresponded fairly well with that of Kato-Katz results in the age groups 10-29 years, but in the younger age groups a considerably greater number of individuals were positive in the CAA test than in the Kato-Katz test. The results obtained indicate that virtually all of the Kabaganga villagers, regardless of age, had an ongoing, active infection or had previously been infected with S. mansoni. This population, therefore, may be useful for evaluation of the diagnostic efficacy of various antibody tests. The highest degree of discrimination between the endemic and the non-endemic village populations was noted for anti-egg IgG4 antibodies. It is concluded that the combined determination of parasite eggs in faeces and CAA in serum provides high sensitivity as regards active infection. Increased levels of isotype-specific antibodies, particularly of the IgG4 subclass, is a sensitive indicator of past or present infection, and the prevalence of individuals with such increased levels may be a simple and reliable indicator of the frequency of schistosomiasis in a community.

Adolescent↗

PubMed1996

Schistosoma: analysis of monoclonal antibodies reactive with the circulating antigens CAA and CCA.

Using spleen cells of mice infected or immunized respectively with cercariae or antigen preparations of Schistosoma mansoni, S. haematobium or S. japonicum monoclonal antibodies (mAbs) were produced against the schistosome gut-associated antigens CAA (circulating anodic antigen) and CCA (circulating cathodic antigen). Fusions nearly exclusively produced either anti-CAA (n = 25) or anti-CCA mAbs (n = 55) with a strong isotype restriction (IgM, IgG1 and IgG3) against both antigens, the majority of anti-CAA mAbs being IgG1 and the majority of anti-CCA mAbs being IgM. The mAbs, which on the basis of their selection were reactive with multiple carbohydrate epitopes of CAA or CCA, were applied in different immunological techniques including immunofluorescence, a dot immunobinding assay and immunoelectrophoresis to study the epitope repertoire. Anti-CAA mAbs were found to be reactive with 5 different epitopes, none of which occurred as multiple epitopes on eggs. Anti-CCA mAbs, on the other hand, recognized at least 10 different epitopes, while 44% of anti-CCA mAbs recognized epitopes common to the adult worm and the egg. Both CAA- and CCA-epitopes were found to be developmentally expressed at the level of the tegument in cercariae, schistosomula and 5-day-old lung worms, but in the adult worm were primarily found in the gut. Thus, the production of panels of mAbs has not only resulted in the selection of reagents optimally performing in diagnostic immunoassays, but also allowed a more detailed study of the epitope repertoire of these important schistosome antigens.

Animals↗

PubMed1996

Immunohistochemical and ultrastructural localization of Schistosoma mansoni soluble egg antigens processed by the infected host.

The detection of egg-derived antigens in the serum and urine of Schistosoma mansoni-infected individuals and experimental animals would provide an alternative method to assess the tissue egg burden. The detected levels are, however, not only a function of the amounts of antigen produced, but also of the processing or clearance by the host. In the present study the immunolocalization pattern of antigens using 2 recently described monoclonal antibodies to repetitive carbohydrate epitopes of S. mansoni soluble egg antigen (114-5B1-A and 114-4D12-A) in various organs of the host was investigated. In the liver strong immunoreactivity could be detected around the entrapped eggs and in egg-shells, as well as in Kupffer cells accumulating both antigen and schistosomal pigment. In the spleen, immunohistochemistry revealed antigen in the plasma as well as in secondary lysosomes of macrophages. Strong labelling was found in the vesicles of the eosinophilic granulocytes: indirect evidence perhaps for the presence of antigen-antibody complexes. In conclusion, the secreted egg antigens were sequestered in the reticulo-endothelial macrophages of the liver and the spleen as already partly described for worm-derived antigens. The presence of large quantities of antigenic material in the spleen could suggest an important role of this organ in the clearance of antigen and might even provide an additional explanation for the hepatosplenomegaly mainly present in S. mansoni-infected children.

Animals↗

PubMed1996

Circulating antigen levels in serum of cattle naturally infected with Schistosoma mattheei.

Levels of 2 Schistosoma circulating antigens, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA), were determined in serum samples collected, on a monthly basis over a period of 1.5 years, from 32 farm animals of different ages and from 12 tracer calves exposed to Schistosoma mattheei infection on a Zambian farm. Faecal egg counts were monitored in all animals and worm burdens in tracers determined after perfusion. Antigen determination tests in serum, with sensitivities between 95 and 100% in heifers and adult cows, proved to be excellent tools for the diagnosis of cattle schistosomiasis. Also in young calves, some infections could be demonstrated earlier by CCA determination than by faecal egg examination. A poor correlation was seen between the data for faecal egg counts and for CAA and CCA levels. It therefore appears that circulating antigen measurements in serum are of limited value as indicators of the pathogenesis of infection in cattle. Although all tracer calves were found infected at perfusion, large variations were recorded in antigen levels. An unexpected finding was the observation in farm animals of a clear seasonal pattern in CAA levels, with significant increase between August and October during the second half of the dry season, when animals are subjected to heavy physical and nutritional stress. It therefore appears that, although circulating antigen determination may provide an indication of the worm burden in ageing infections, possible variations of antigen clearance rate with the physiological condition of the host may complicate the interpretation of the results.

Age Factors↗

PubMed1996

Antibody response patterns against Schistosoma mansoni in a recently exposed community in Senegal.

Acquired immune resistance is believed to be largely responsible for age-dependent infection and reinfection patterns in schistosomiasis. In a recently established but intense focus of Schistosoma mansoni in Senegal, the humoral immune response was studied in a random population sample of 289. Antibody levels of various isotypes to schistosome worm and egg antigens were determined by ELISA and related to egg counts (eggs per gram of feces [EPG]), age, and sex. Both IgG1 and IgG4 followed age-related patterns similar to egg counts and strongly correlated with EPG, even after allowing for age. Specific IgE levels increased slowly with age. The humoral immune response patterns in this recently infected population appeared to be largely similar to those in chronically infected communities. Thus far, the observations do not support the current hypothesis that age-related resistance to Schistosoma is determined by IgE-mediated protective immunity acquired during many years of exposure.

Adolescent↗

PubMed1996

Antischistosome IgG4 and IgE responses are affected differentially by chemotherapy in children versus adults.

Specific IgG4 and IgE responses and polyclonal cytokine profiles were studied in 110 Schistosoma haematobium-infected persons before and 5 weeks after chemotherapy. Pretreatment IgG4 responses to soluble egg antigen (SEA) correlated with intensity of infection. After chemotherapy, a significant decrease in egg output and circulating anodic antigen was associated with a substantial drop in the IgG4 response to SEA (IgG4-SEA) in adults and children, suggesting that egg laying is a major stimulus for IgG4-SEA. After chemotherapy, IgG4 and IgE to adult worm antigen and IgE to SEA increased in children but remained unchanged in adults. This indicates that the immunoregulatory mechanisms operative in S. haematobium-infected adults differ from those in infected children. The effect of treatment on cytokine profiles was determined following stimulation of whole blood with anti-CD3 antibodies. A significant decrease in interleukin-4 production after treatment indicated that reduction in helminth load may lead to a reduced number of Th2-type cells.

Adolescent↗

PubMed1996

Quantitative and morphological aspects of Unicryl versus Lowicryl K4M embedding in immunoelectron microscopic studies.

In this study we compared the recently commercialized electron microscopy embedding resin Unicryl with the well-known resin Lowicryl K4M with regard to morphological and immunohistochemical preservation properties. The standard embedding procedure recommended by the manufacturer for the use of Unicryl resulted in considerable morphological alterations of the tissue, with the appearance of large gaps in and between the cells of the examined tissue. Morphometric analysis pointed to a swelling of the extracellular matrix as the main cause of these morphological artifacts. A slight modification in the protocol to correct this artifact is proposed and tested. Immunohistochemically, tissue embedded in Unicryl resulted in a significantly stronger immunogold labeling than identical tissue embedded in Lowicryl K4M. From the results of this technical study, it can be concluded that Unicryl embedding is a valuable new tool to supplement the available techniques for immunoelectron microscopic studies.

Acrylic Resins↗

PubMed1996

Circulating anodic antigen for detection of Schistosoma mansoni infection in Egyptian patients.

We evaluated the ability of circulating anodic antigen (CAA) to identify infection with Schistosoma mansoni in a prospective cohort study of 257 Egyptian men, 147 with infection diagnosed by repeated Kato thick smears, and 110 without detectable infection. The CAA levels were obtained and the stool examinations were performed two weeks and one, two, four, and six months after praziquantel therapy for infected men. A CAA enzyme-linked immunosorbent assay was repeated twice on subjects who were otherwise negative for schistosomiasis. Circulating anodic antigen was detected in 117 cases, with an overall test sensitivity before treatment of 0.8. Sensitivity was related to the intensity of infection, ranging from 1.00 with > 400 eggs per gram (epg) of feces to 0.60 for those with < 100 epg. After praziquantel therapy, the level of the antigen was significantly reduced. Specificity was excellent before treatment (1.00, 95% confidence interval = 0.97-1.0), but it decreased to 0.98 four months after treatment. Likelihood ratios were significant for all titers > or = 4. We conclude that CAA has moderate sensitivity and excellent specificity when used to identify infection with schistosomiasis, as well as to monitor the results of therapy after at least one month after treatment.

Adult↗

PubMed1996

Fluctuation of schistosome circulating antigen levels in urine of individuals with Schistosoma mansoni infection in Burundi.

We studied the fluctuations of schistosome circulating antigens in urine as compared with fecal egg counts in 60 Burundese individuals infected with Schistosoma mansoni. Levels of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in the urine were determined by quantitative enzyme-linked immunosorbent assays. Fecal samples were simultaneously collected and examined with duplicate Kato-Katz slides. Significant correlations were consistently found between circulating antigen levels in urine and fecal egg counts. Although both antigen levels and egg output fluctuated, there was less fluctuation of CCA levels in urine than of fecal egg counts. All individuals had CCA in at least one urine sample and 82% were at least once positive for egg counts. Positive CCA levels were found in at least one urine sample in 75% of all individuals, but levels were low. Our results show that detection of CCA in urine is a sensitive, quantitative, and reliable method for noninvasive diagnosis and screening of S. mansoni infections, due to the relatively low fluctuations.

Adolescent↗

PubMed1996

Circulating anodic antigen (CAA) levels in different age groups in a Zimbabwean rural community endemic for Schistosoma haematobium determined using the magnetic beads antigen-capture enzyme-linked immunoassay.

A simplified version of the magnetic bead antigen-capture enzyme-linked immunoassay (MBAC-EIA) was used to detect circulating anodic antigen (CAA) in individuals of different age groups with Schistosoma haematobium infection only in an endemic area of Zimbabwe. An overall positive correlation between S. haematobium egg excretion and CAA levels was demonstrated. The age profile for CAA levels was generally comparable with the age profile of S. haematobium prevalence and intensity of infection. The CAA levels were higher in younger (5-14 years of age) individuals than in older (greater than 14 years of age) ones. Since the sensitivity of the MBAC-EIA in the diagnosis of S. haematobium infection was found to be 97%, CAA levels appear to be a useful indicator of worm burden in an endemic area.

Adolescent↗

PubMed1996

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↗