Age-related worm load and worm fecundity patterns in human populations, as indicated by schistosome circulating antigens

Recently, our group determined the relationship between serum CAA levels and fecal egg counts in two foci very intense Schistosoma mansoni transmission: Maniema (Zaire), an area endemic for S. mansoni since several decades, and Ndombo (Senegal), where transmission has only been established since a few years. The objetive was to study and compare age-related worm load and worm fecundity patterns in these two different endemic settings. Here, we will summarize the most important findings and conclusions of this study.

Age-related worm load and worm fecundity patterns in human populations, as indicated by schistosome circulating antigens.

Recently, our group determined the relationship between serum CAA levels and fecal egg counts in two foci with very intense Schistosoma mansoni transmission: Maniema (Zaire), an area endemic for S. mansoni since several decades, and Ndombo (Senegal), where transmission has only been established since a few years. The objective was to study and compare age-related worm load and worm fecundity patterns in these two different endemic settings. Here, we will summarize the most important findings and conclusions of this study.

Daily fluctuation of levels of circulating cathodic antigen in urine of children infected with Schistosoma mansoni in Brazil.

The fluctuation of circulating cathodic antigen (CCA) levels in urine was studied in 69 Brazilian school-children infected with Schistosoma mansoni and compared to egg counts. Faeces and urine samples were simultaneously collected at 7 times during a period of 2 weeks. CCA was determined by enzyme-linked immunosorbent assay and could be detected in 96% of the urine samples; the individual mean CCA level ranged from 609 to 350,700 pg/mL. 90% of the faecal samples contained S. mansoni eggs and the individual mean egg output ranged from 9 to 5510 eggs/g. The Spearman rank correlation coefficient between these individual means was 0.69. Kendall's coefficient of concordance (W) was 0.88 for CCA levels and 0.80 for egg counts.

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.

Diagnostic markers in schistosomiasis.

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.

The susceptibility of adult schistosomes to immune attrition.

Mouse infection models are described that demonstrate reduction of egg production in Schistosoma haematobium infections and both worm loss and reduced fecundity in S. bovis infections. Neither phenomenon could be shown in S. mansoni infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by serum transfer of the ability to reduce a S. bovis worm burden into immunocompromised hosts. Vaccination with irradiation attenuated parasites was also shown to have consequences for the adults of a challenge infection of S. haematobium and S. bovis specifically. Prior vaccination resulted in an abrogation of the anti-fecundity and adult worm elimination that occurred in non-vaccinated similarly infected mice. These models are being used to define the targets and mechanisms involved in anti-adult attrition. A serological assay, quantitation of a circulating antigen (CAA) has been assessed for its ability to measure worm burdens of different species of schistosome in mice. This assay will be used to question whether anti-adult immunity contributes to the pattern of infection with S. mansoni and S. haematobium in man.

Diagnostic markers in schistosomiasis

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

The susceptibility of adult schistosomes to immune attrition

Mouse infection models are described that demonstrate reduction of egg production in Schistosoma haematobium infections and both worm loss and reduced fecundity in S. bovis infections. Neither phenomenum could be shown in S. mansoni infected mice. The immunological basis for these anti-adult responses was inferred by comparison with infections in T-cell deprived mice and by the serum transfer of the ability to reduce a S. bovis worm burden into immunocompromised hosts. Vaccination with irradiation attenuated parasites was also shown to have consequences for the adults of a challenge infections of S. haematobium and S. bovis specifically. Prior vaccination resulted in an abrogation of the anti-fecundity and adult worm elimination that occurred in non-vaccinated similary infected mice. hese models are being used to define the targets and mechanisms involved in anti-adult attrition. A serological assay, quantitation of a circulating antigen (CAA) has been assessed for its ability to measure worm burdens of different species of schistosome in mice. This assay will be used to question whether anti-adult immunity contributes to the pattern of infection with S. mansoni and S. haematobium in man

Levels of the schistosome circulating anodic and cathodic antigens in serum of schistosomiasis patients from Brazil.

Serum levels of 2 schistosome circulating antigens, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CAA), were determined in persons infected with Schistosoma mansoni in Brazil. Sensitive monoclonal antibody-based enzyme-linked immunosorbent assays were used to measure levels of the 2 antigens. The study group consisted of 38 individuals with intestinal schistosomiasis, and 20 persons with the hepatosplenic form of the disease. Age and intensity of infection were comparable for the 2 groups. CAA was detected in 65.5% of all patients' sera and CCA was found in the serum of 82.8% of all patients. CAA levels correlated well with the egg output, as determined by duplicate Kato-Katz smears; CCA was significantly positively correlated with egg output in patients with intestinal schistosomiasis only. Whereas no significant difference was found between CAA titre in patients with intestinal schistosomiasis and those with the hepatosplenic form, a significantly higher CCA titre was found in patients with hepatosplenomegaly compared to patients with intestinal schistosomiasis.