Serum Circulating Anodic Antigen Research Articles

Effects of Schistosoma mansoni and praziquantel treatment on the lower gastrointestinal mucosa: A cohort study in Tanzania

Schistosomes infect over 200 million people worldwide, but few studies have characterized the effects of Schistosoma mansoni infection and effective treatment on the lower gastrointestinal mucosa. In this prospective cohort study, we compared the clinical findings on sigmoidoscopy and laboratory measures in Tanzanian adults with and without S. mansoni infection at baseline and 6 months after praziquantel treatment. Grading of the endoscopic findings was done using the Mayo Scoring System for Assessment of Ulcerative Colitis Activity. Schistosome infection was confirmed by stool microscopy and serum circulating anodic antigen (CAA). Baseline comparisons were performed in Stata using Fisher's exact and Wilcoxon rank-sum tests, and pre- and post-treatment comparisons using Wilcoxon matched-pairs signed-rank and McNemar's tests.We investigated the clinical characteristics of 48 individuals: 32 with and 16 without S. mansoni infection. Infected individuals had greater severity of sigmoid and rectal mucosal abnormalities and higher Mayo scores and serum eosinophils (all p < 0.05) than uninfected individuals at initial evaluation. At 6 months, 28 individuals completed repeat blood tests and sigmoidoscopy. Of these, 14 cleared their baseline infection (n = 7) or experienced a greater than 7-fold decrease in serum CAA (n = 7). Follow-up sigmoidoscopies revealed some improvements in sigmoid and rectal mucosal findings, although Mayo scores were not significantly lower. Both the median erythrocyte sedimentation rates (32.5→12.5 mm/hr) and percent of eosinophils (7.1→3.1%) decreased in this group from baseline to follow-up.S. mansoni infection was associated with mild-to-moderate lower gastrointestinal mucosal abnormalities that were grossly visible during sigmoidoscopy, and these improved partially 6 months after effective treatment with praziquantel. Additional studies, of longer duration and focused on both clinical and mucosal immunologic effects of S. mansoni, could provide additional insight.

Mycobacterium fortuitum infection from needlefish impalement during diving: A diagnostic challenge

In order to evaluate the diagnostic value of schistosome circulating anodic antigen (CAA) detection, serum and urine CAA-levels were determined in a single cluster of 34 Belgian tourists at three timepoints within a period of 14 weeks following proven Schistosoma exposure in South Africa and compared with two in-house antibody assays.Samples were collected 4–5 and 7–8 weeks post-exposure and subsequently 5–6 weeks following praziquantel treatment. Schistosoma antibodies were detected by an adult worm antigen-immunofluorescence assay (AWA-IFA) and a soluble egg antigen-enzyme-linked immunosorbent assay (SEA-ELISA), while CAA concentrations were determined by the Up-Converting reporter Particle labelled Lateral Flow (UCP-LF) test.Antibodies were detected in 25/34 (73%) travellers pre-treatment and in 27/34 (79%) post-treatment, with the AWA-IFA showing better performance than the SEA-ELISA. Pre-treatment, CAA was detected in 13/34 (38%) and 33/34 (97%) of the travellers in urine and serum, respectively. Post-treatment, all except one traveller became serum CAA negative. This in contrast to the detected antibodies, as well as the previously reported diagnostic results of this cluster.The UCP-LF CAA serum assay has been demonstrated as the most sensitive method for the diagnosis of early Schistosoma infections and post-treatment monitoring in travellers.

Early diagnosis and follow-up of acute schistosomiasis in a cluster of infected Belgian travellers by detection of antibodies and circulating anodic antigen (CAA): A diagnostic evaluation study

BackgroundIn order to evaluate the diagnostic value of schistosome circulating anodic antigen (CAA) detection, serum and urine CAA-levels were determined in a single cluster of 34 Belgian tourists at three timepoints within a period of 14 weeks following proven Schistosoma exposure in South Africa and compared with two in-house antibody assays. MethodsSamples were collected 4–5 and 7–8 weeks post-exposure and subsequently 5–6 weeks following praziquantel treatment. Schistosoma antibodies were detected by an adult worm antigen-immunofluorescence assay (AWA-IFA) and a soluble egg antigen-enzyme-linked immunosorbent assay (SEA-ELISA), while CAA concentrations were determined by the Up-Converting reporter Particle labelled Lateral Flow (UCP-LF) test. ResultsAntibodies were detected in 25/34 (73%) travellers pre-treatment and in 27/34 (79%) post-treatment, with the AWA-IFA showing better performance than the SEA-ELISA. Pre-treatment, CAA was detected in 13/34 (38%) and 33/34 (97%) of the travellers in urine and serum, respectively. Post-treatment, all except one traveller became serum CAA negative. This in contrast to the detected antibodies, as well as the previously reported diagnostic results of this cluster. ConclusionsThe UCP-LF CAA serum assay has been demonstrated as the most sensitive method for the diagnosis of early Schistosoma infections and post-treatment monitoring in travellers.

Antigen-based diagnosis of Schistosoma infection in travellers: a prospective study.

BackgroundTravellers infected with Schistosoma spp. might be pauci- or even asymptomatic on first presentation. Therefore, schistosomiasis may remain undiagnosed in this population. Active infection, as evidenced by the presence of the tissue-dwelling worm, can be demonstrated via the detection of adult worm-derived circulating anodic antigen (CAA) utilising a robust well-described lateral flow-(LF) based test applying background-free up-converting reporter particles (UCP). In this prospective study, we assessed the diagnostic value of serum and urine UCP-LF CAA test in comparison with two Schistosoma-specific serological assays detecting antibodies against adult worm antigen-immuno fluorescence assay (AWA-IFA) and against soluble egg antigen–enzyme-linked immunosorbent assay (SEA-ELISA) antigens in travellers.MethodsSamples were collected from 106 Dutch travellers who reported freshwater contact in sub-Saharan Africa and who were recruited up to 2 years after return. Subjects were asked to complete a detailed questionnaire on travel history, water contact, signs and symptoms compatible with schistosomiasis.ResultsTwo travellers were positive by serum CAA and an additional one by urine CAA. A total of 22/106 (21%) samples were antibody positive by AWA-IFA and 9/106 (9%) by SEA-ELISA. At follow-up 6 weeks and 6 months after praziquantel treatment, all seropositives remained antibody positive whereas CAA was cleared. Seropositivity could not be predicted by the type of fresh water-related activity, country visited or symptoms reported.ConclusionThe low number of UCP-LF CAA positives suggests that in travellers, active infections often do not establish or have very low worm burden. Based on our high seroconversion rates, we conclude that the AWA-IFA assay is the most sensitive test to detect schistosome exposure. Given the lack of predictive symptoms or risk factors, we recommend schistosomiasis screening at least by serology in all travellers with reported freshwater contact in high-endemic areas.

Performance of an Ultra-Sensitive Assay Targeting the Circulating Anodic Antigen (CAA) for Detection of Schistosoma mansoni Infection in a Low Endemic Area in Brazil.

Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings, where the conventional parasitological methods are insensitive. We determined the accuracy of an up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay in urine and serum for Schistosoma mansoni diagnosis in low-prevalence settings in Ceará, Brazil, before and after praziquantel treatment. Clinical samples of a total of 258 individuals were investigated by UCP-LF CAA, point-of-care—circulating cathodic antigen (POC-CCA), soluble worm antigen preparation (SWAP)-ELISA and Kato-Katz (KK); a selection of 128 stools by real-time PCR technique. Three and 6-weeks after treatment, samples were collected and evaluated by detection Schistosoma circulating antigens (CAA and CCA). The UCP-LF CAA assays detected 80 positives (31%) with urine and 82 positives (31.8%) with serum. The urine POC-CCA and serum SWAP-ELISA assays detected 30 (11.6%) and 107 (40.7%) positives, respectively. The Kato-Katz technique revealed only 4 positive stool samples (1.6%). Among the 128 individuals with complete data records, 19 cases were identified by PCR (14.8%); Sensitivities and specificities of the UCP-LF CAA assays, determined versus a combined reference standard based on CCA/KK/PCR positivity, ranged from 60–68% to 68–77%, respectively. In addition only for comparative purposes, sensitivities of the different assays were determined vs. a comparative reference based on CAA/KK/PCR positivity, showing the highest sensitivity for the urine CAA assay (80%), followed by the serum CAA (70.9%), SWAP-ELISA (43.6%), PCR (34.5%), POC-CCA (29.1%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (3.6%). CAA concentrations were higher in serum than in urine and were significantly correlated. There was a significant decrease in urine and serum CAA levels 3 and 6-weeks after treatment. The UCP-LF CAA assays revealed 33 and 28 S. mansoni-infected patients at the 3- and 6-week post-treatment follow-up, respectively. The UCP-LF CAA assays show high sensitivity for the diagnosis of S. mansoni in low-endemicity settings. It detects a considerably higher number of infections than microscopy, POC-CCA or PCR. Also it shows to be very useful for evaluating cure rates after treatment. Hence, the UCP-LF CAA assay is a robust and promising diagnostic approach in low-transmission settings.

Improved diagnosis of active Schistosoma infection in travellers and migrants using the ultra-sensitive in-house lateral flow test for detection of circulating anodic antigen (CAA) in serum

Schistosomiasis is a parasitic disease affecting over 250 million people in the tropics. In non-endemic regions, imported Schistosoma infections are commonly diagnosed by serology, but based on antibody detection an active infection cannot be distinguished from a cured infection and it may take more than 8 weeks after exposure before seroconversion occurs. In endemic populations, excellent results have been described in diagnosing low-grade active Schistosoma infections by the detection of the adult worm-derived circulating anodic antigen (CAA) utilising robust lateral flow (LF) assays combined with up-converting phosphor (UCP) reporter technology. The purpose of this study is to explore the diagnostic value of the UCP-LF CAA assay in a non-endemic setting. CAA concentrations were determined in 111 serum samples originating from 81 serology-positive individuals. In nine individuals, serum could be collected before travel and an additional five provided samples before and after seroconversion occurred. Based on detectable CAA levels, an active infection was seen in 56/81 (69%) of the exposed individuals, while the 10 controls and the 9 sera collected before travel were tested negative for CAA. Positive CAA levels were observed starting 4 weeks after exposure and in four cases CAA was detected even before Schistosoma-specific antibodies became positive. Higher serum CAA levels were seen in migrants than in travellers and CAA concentrations dropped sharply when testing follow-up samples after treatment. This explorative study indicates the UCP-LF CAA serum assay to be a highly accurate test for detecting active low-grade Schistosoma infections in a non-endemic routine diagnostic setting.

Decreased Sensitivity of Schistosoma sp. Egg Microscopy in Women and HIV-Infected Individuals.

It has been postulated that impaired host immunity due to HIV infection reduces parasite egg excretion. Schistosoma/HIV interactions have also been shown to differ by sex. We hypothesized that egg excretion would vary based on both HIV status and sex. We examined data from more than 1,700 participants in eight studies conducted in northwest Tanzania between 2010 and 2016. Schistosoma infection was defined by circulating anodic antigen (CAA) serum levels ≥ 30 pg/mL and/or egg positivity in either stool by Kato Katz method or urine by filtration. We used multivariable analyses to determine the impact of confounding factors such as sex, age, previous praziquantel treatment, and worm burden as measured by serum CAA level, on the relationship between egg excretion and HIV status. HIV-infected individuals were significantly less likely to excrete schistosome eggs than HIV-uninfected individuals, even after controlling for worm burden and sex (OR = 0.6 [0.4, 0.9], P = 0.005). Furthermore, after controlling for worm burden and HIV status, women had lower odds of egg excretion than men (OR = 0.4 [0.3, 0.5], P < 0.001). Sensitivity of egg microscopy was lower in HIV-infected women than HIV-uninfected men (41% versus 61%, P < 0.001), whereas sensitivity in women remained low in both groups (33% versus 37%, P = 0.664). Our study is the first to report that women with Schistosoma infection excrete fewer eggs than men for a given worm burden, regardless of HIV the status. These findings suggest that guidelines for use of microscopy to diagnose Schistosoma infections in HIV-infected individuals and in women merit reconsideration.

Eosinophil Cationic Protein, Soluble Egg Antigen, Circulating Anodic Antigen, and Egg Excretion in Male Urogenital Schistosomiasis

Markers of male genital schistosomiasis (MGS) are needed to elucidate the consequences for reproductive health. Eosinophil cationic protein (ECP) and soluble egg antigen (SEA) in urine and semen, and circulating anodic antigen (CAA) in serum were assessed as MGS markers. Egg counts, ECP, and SEA in urine and CAA in serum, correlated positively. Seminal egg excretion exhibited marked day-to-day variations, but counts correlated positively with urinary egg counts and SEA in semen and with CAA. Positive predictive values with reference to seminal egg excretion were as follows: seminal ECP (52%), seminal SEA (83%), CAA (97%), and urinary egg excretion (82%). SEA in semen and CAA in serum constitute potential markers of MGS. However, urine egg counts as an indirect marker of MGS remains the preferred diagnostic method from a public health perspective.

Relating serum circulating anodic antigens to faecal egg counts in Schistosoma mansoni infections: a modelling approach.

Circulating anodic antigen (CAA) levels in serum and faecal egg counts are both quantitative measures of Schistosoma mansoni worm burdens. In this study, we have tested whether circulating anodic antigens can be included into an established egg count model. A data set with 3 repeated faecal egg count and serum CAA measurements of 50 individuals from a community in Burundi with moderate endemicity was used. By means of Monte Carlo simulation, both antigens and egg counts were related to an underlying worm pair distribution, taking into account the variation in repeated measurements (within individuals) and the variation in worm burdens (between individuals). Models with various assumptions (e.g. presence or absence of density-dependent egg production) were tested. Whereas observed and predicted egg counts agreed fairly well, the circulating antigen data could not be described satisfactorily. In particular, the predicted number of negative antigen concentrations was much lower than observed, while the number of light positives was overestimated. There seems to be a mechanism that causes a shift of expected (low) positive CAA concentrations towards zeros, which the proposed models do not provide for. Possible biological as well as assay-related mechanisms that may account for this shift are discussed. The assumption that serum CAA concentrations are a simple direct reflection of worm (pair) burdens could not be corroborated by this modelling exercise. Apparently, the relationship between (measured) CAA concentrations, egg counts and worm burdens in human S. mansoni infections is more complex than assumed.

Specificity of circulating antigen detection for schistosomiasis mansoni in Senegal and Burundi.

The specificity of schistosome circulating antigen detection was determined in negative individuals from two S. mansoni- endemic countries, Senegal and Burundi, and compared with results from Dutch control individuals. A nearly absolute specificity was achieved for circulating anodic antigen (CAA) detection in serum, irrespective of the target population or sample pretreatment method. Circulating cathodic antigen (CCA) detection in serum and urine resulted in a lower specificity than serum CAA detection. Apparent large differences in specificity of CCA detection between countries were mainly due to pretreatment methods. Apparently, the alkaline/heating pretreatment method is not as effective as trichloroacetic acid (TCA)-pretreatment in removing (certain) interfering components, which may vary between populations. In view of the development of the urine CCA assay into a noninvasive screening test, a slightly lower specificity may still be acceptable. For precise epidemiological analyses the highly specific serum CAA assay remains the method of choice.

Application of immunodiagnostic assays: detection of antibodies and circulating antigens in human schistosomiasis and correlation with clinical findings.

In an initial cross-sectional survey, serum, urine, and stool samples were collected from 370 participants representing about 10% of the population (n = 4,438) in Behbeet village, 50 km south of Cairo, Egypt, an area well known to be endemic solely for Schistosoma haematobium. Diagnosis was approached in two parallel ways. The first approach, which simulated actual conditions in many endemic areas in Egypt, was based on physical examination and urine and stool microscopic analysis. The second approach was based on two advanced immunodiagnostic assay systems. One system detected antibodies to species-specific microsomal antigens, the other detected circulating schistosomal antigens. Microsomal antigens from S. haematobium and S. mansoni were used to detect antibodies in the Falcon assay screening test (FAST)-ELISA and the enzyme-linked immunoelectrotransfer blot (EITB). Circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were quantified in serum and urine samples in a sandwich ELISA using monoclonal antibodies. Parasitologically, the prevalence of S. haematobium was 7.01% in females and 25.82% in males, giving an overall prevalence of 15.8%. The combination of urine CCA and serum CAA for detecting circulating antigens and the combination of the S. haematobium adult worm microsomal antigens (HAMA) FAST-ELISA and the HAMA EITB for detecting antibodies significantly improved the sensitivity of detecting S. haematobium circulating antigens and antibodies. Also, including a medical examination as an integral part of field studies and correlating immunodiagnostic results with other clinical and investigational data allowed us to calculate an accurate estimation of S. haematobium prevalence in this area of low endemicity.

Puberty and Age-intensity Profiles in Schistosome Infections: Another Hypothesis

In an excellent focus article on puberty and age-related changes in susceptibility to schistosome infection, Fulford et al.[1xFulford, A.J.C. et al. Parasitol. Today. 1998; 14: 23–26Abstract | Full Text | Full Text PDF | PubMed | Scopus (91)See all References[1]provide a new explanation for the characteristic age-intensity profile in areas where schistosomiasis is endemic. An age-dependent host factor seems to override—at least during adolescence—the variation in intensity of infection expected both from the variability of exposure with changing age and from the dynamics of acquired immunity. Fulford and colleagues put forward the hypothesis that physiological changes in the production of sex hormones could be one explanation. The authors explore how sex hormones might exert a regulatory effect on the immune system, eventually leading to an increased resistance to infection. Other modes of action by which sex hormones, particularly in females, may influence parasites are only mentioned briefly, but not commented on.Pelvic vascularization alters when girls enter puberty, resulting in multiple anastomoses between the rectal and the vesical plexus, and between the plexus of external and internal genital organs[2xSee all References, 3xSee all References]. These adaptive changes are accentuated during pregnancy. As adult worms tend to migrate, the adaptive changes in pelvic vascularization add to the chance that parasites reach the adjacent vascular beds, thereby increasing the probability of a settlement in female genital organs. In fact, at least in Schistosoma haematobium infection, involvement of external and internal genital organs is extremely common. Of women infected with this parasite species 40–80% are considered to have manifestations in the lower reproductive tract[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References, 5xKjetland, E. et al. Acta Trop. 1996; 62: 239–255Crossref | PubMed | Scopus (65)See all References, 6xLeutscher, P. et al. Acta Trop. 1997; 66: 27–34Crossref | PubMed | Scopus (27)See all References]. How many women also have worms located in the internal genital organs is unknown; post-mortem studies in female schistosomiasis patients, however, show that the ovaries, the fallopian tubes and the uterus are affected in 10–80% of cases[7xEdington, G.M. et al. Trans. R. Soc. Trop. Med. Hyg. 1971; 20: 846–849See all References, 8xGelfand, M. and Ross, W. Trans. R. Soc. Trop. Med. Hyg. 1953; 47: 218–220PubMed | Scopus (17)See all References, 9xYoussef, A.F. et al. J. Obstet. Gynaecol. Br. Commonw. 1970; 77: 847–851Crossref | PubMedSee all References].A shift of adult worms to topographic sites from which eggs cannot reach the lumen of the bladder, and thus are not excreted, obviously has an important consequence on age-intensity profiles: even if reinfection rates remain unchanged, egg excretion in urine will diminish and thus create the impression that there is an age-associated decrease of intensity of infection with onset of puberty.Two lines of evidence support this assumption. First, according to the literature, female genital schistosomiasis (FGS) occurs mainly after girls have reached sexual maturity[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References[4], ie. at an age when intensity of infection—as measured by egg excretion—decreases. Recently, these clinical observations were supported by data from a community-based study in Tanzania; the existence of FGS as measured by the presence of eggs in cervical biopsies and the prevalence/intensity of egg excretion in urine were inversely correlated during adolescence (Poggensee et al., unpublished).Second, if with the beginning of puberty a topographic shift of adult worms, rather than a diminished worm burden, is responsible for a decrease of egg excretion in urine, then the simultaneous measurement of egg excretion and circulating antigens should provide an important clue. Agnew et al.[10xAgnew, A. et al. Am. J. Trop. Med. Hyg. 1996; 55: 338–343PubMedSee all References[10]examined S. haematobium- or S. mansoni-infected populations for egg excretion as well as circulating anodic antigen (CAA). Schistosoma haematobium egg output relative to serum CAA was significantly reduced with onset of puberty. Nothing like that was observed in patients infected with S. mansoni, a parasite less commonly affecting the genital tract[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References[4]. Moreover, the effect observed by Agnew et al.[10xAgnew, A. et al. Am. J. Trop. Med. Hyg. 1996; 55: 338–343PubMedSee all References[10]was highly significant in women, but not in men, whose genitals are less frequently affected by ectopic schistosomiasis.Taken together, these circumstantial facts favour the hypothesis that in S. haematobium infection in women yet another mechanism may explain the familar age-intensity profile with the typical decline of the curve after onset of puberty. Whether vascular changes induced by sex hormones during puberty and pregnancy and subsequent anatomical compartmentalization of adult worms also have a regulatory effect on protective immune mechanisms is another intriguing question. The dynamics of schistosomiasis are probably much more complex than we still know. Why should it not be different between women and men?

Day-to-day fluctuation of schistosome circulating antigen levels in serum and urine of humans infected with Schistosoma mansoni in Burundi.

Day-to-day fluctuations of both circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were examined simultaneously in a group of Schistosoma mansoni-infected individuals from Burundi and compared with each other and with fecal egg count fluctuations. Significant correlations were found between fecal egg counts and circulating antigens (CAA and CCA) and between circulating antigen levels in serum and urine samples. The cumulative percentage of positive results after three samplings was highest for urine CCA detection, followed by fecal egg counts, serum CCA, serum CAA, and urine CAA detection, respectively. It was demonstrated that circulating antigen levels in both serum and urine showed less fluctuation than fecal egg counts, except for urine CAA levels. The serum CAA detection assay in particular, although less sensitive in this low endemic area in Burundi, gave very constant measurements over a period of one week. Our results indicate that detection of circulating antigens in a single serum or urine sample provides a quantitatively more stable diagnosis of S. mansoni infection than fecal egg counts based on a single stool examination.

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.

Epidemiologic application of circulating antigen detection in a recent Schistosoma mansoni focus in northern Senegal.

Quantitative enzyme-linked immunosorbent assays (ELISAs) for the detection of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were applied as an epidemiologic tool in a recent, intense focus of Schistosoma mansoni in Senegal. Both CAA and CCA in serum and CCA in urine were found in 94%, 83%, and 95%, respectively, of the population, of which 91% were positive on stool examination. Circulating antigens were also detectable in sera and urines of most egg-negative individuals. The sensitivities of the urine CCA and serum CAA ELISA were substantially higher than that of a single egg count, and increased with egg output. The CAA and CCA levels correlated well with egg counts and with each other. The age-related evolution of antigen levels followed a similar pattern as egg counts, providing supplementary evidence for a genuine reduction of worm burdens in adults in spite of the supposed absence of acquired immunity in this recently exposed community. The antigen:egg ratios decreased in adults, suggesting lower worm fecundity in children. This would be compatible with a density-dependent reduction of fecundity, but not with anti-fecundity immunity in adults that perhaps has not yet developed in this new focus.

Immunodiagnosis of schistosomiasis mansoni in a low endemic area in Surinam by determination of the circulating antigens CAA and CCA

We evaluated the applicability of circulating antigen detection in serum and urine for the diagnosis of Schistosoma infections in a low endemic area. In total 389 individuals from Saramacca (Surinam) participated in the survey. Stool samples were examined using the Kato method, while circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were determined by highly specific monoclonal antibody-based ELISA's. Also schistosome specific IgM antibodies were measured by the indirect immunofluorescence assay, but the diagnostic performance of this test was found to be poor in this population. S. mansoni eggs were found in 29% of the examined cases, while CAA and CCA could be demonstrated in 23% and 17% of the serum samples and in 3% and 28% of the urine samples, respectively. Forty three percent of the study population was positive in at least one of these diagnostic assays, indicating that each individual test misses a substantial part of the subjects with an active infection. In most positive cases, intensities of infection were very low. As 204 individuals participated in all screening assays, diagnostic performance of each test was evaluated in this sub-population. The highest sensitivities were achieved with the urine-CCA assay and the parasitological examination, detecting 59 and 58 out of the 107 cases with an active infection, respectively. The serum-CAA assay detected 47 positive cases. Our results demonstrate that determination of circulating antigens, especially CCA in urine and CAA in serum, provides information additional to the parasitological examination, for the assessment of prevalence and intensity of Schistosoma infection in low endemic areas.

Monitoring the efficacy of different doses of praziquantel by quantification of circulating antigens in serum and urine of schistosomiasis patients

We evaluated the quantitation of two schistosome circulating antigens in serum and urine as a tool for the assessment of the efficacy of praziquantel dosage regimens (40 versus 60 mg/kgbw). In addition we compared the efficacy of two different brands of praziquantel (Biltricide and Distocide), given at the same dosage (40 mg/kgbw). Thirty five Egyptian hospitalized schistosomiasis mansoni patients participated in this study. Thirteen patients (Group 1) received 60 mg/kgbw Biltricide, administered in 3 oral doses of 20 mg in one day; 22 individuals (Group 2) were treated with 40 mg/kgbw (12 Biltricide, 10 Distocide), given in one oral dose. Circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were quantitated by monoclonal antibody-based ELISA's before, and 1, 3 and 6 weeks after chemotherapy. Before treatment, all patients were positive for at least one of the circulating antigen assays. Three to six weeks after treatment significantly more patients were found to be negative in Group 1 compared to Group 2 (X2 = 7.13, P = 0.008, n = 35). Also the levels of CCA and CAA in serum and of CCA in urine were found to be significantly higher in Group 2 (Mann-Whitney U < 85, P < 0.05, n = 35). These results were confirmed by parasitological data. No differences were found between treatment with Biltricide or Distocide.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple technique to pretreat urine and serum samples for quantitation of schistosome circulating anodic and cathodic antigen

For the detection of the circulating schistosome antigens CAA (circulating anodic antigen) and CCA (circulating cathodic antigen) in serum and urine samples of Schistosoma infected individuals, pretreatment of samples with trichloroacetic acid (TCA) is a standard procedure. In the present study several methods were evaluated in order to develop a more simple and rapid technique than the - especially for pretreatment of urine samples - laborious TCA technique. Optimal results were obtained with a method in which serum or urine samples were pretreated by a heat-incubation step (70°C, 30 min) in an alkaline buffer (pH 9.6). In a comparison of the new technique with the TCA pretreatment, serum and urine samples of S. mansoni infected individuals from Zaire ( n=80) and of uninfected controls from The Netherlands ( n=208) were pretreated and assayed for CAA and CCA. Both pretreatment techniques showed similar sensitivities and specificities for CAA and CCA in serum, and CCA in urine. However, for the determination of CAA in urine the new technique performed significantly better, resulting in an increase of the sensitivity from 32 to 70% (titre determination).

A model system for the study of antigen secretion by adult Schistosoma mansoni in vivo.

Schistosoma mansoni (6 weeks old) were surgically transferred from donor C57BI/6 mice to the hepatic portal veins of naive recipients of the same inbred strain. Between 70% and 100% of the parasites were alive 15 days later, and egg deposition was observed after transfer of worm pairs. The physiological status of the parasites was monitored by measuring the levels of a schistosome gut antigen, circulating anodic antigen (CAA), in the serum of the recipients. When only male worms were transferred, serum CAA levels increased slowly to a peak 9 days later, which was followed by a rapid decline. When worm pairs were transferred, there was an early peak in serum CAA levels followed by a gradual decline, but these levels were always higher than those recorded after male-only transfer; in two mice the pattern was similar to that observed following receipt of male worms. More CAA and eggs were produced after transfer of paired versus separated worms. It was concluded that although worm pairs can be successfully transferred, their physiological status may be sub-optimal. In contrast, male worms survive consistently well, and their transfer to a naive recipient provides a convenient model with which to study the release of antigens by schistosomes in vivo.

Assessment of Cure in Schistosomiasis Patients after Chemotherapy with Praziquantel by Quantitation of Circulating Anodic Antigen (CAA) in Urine

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.