K. Polman

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.

Evaluation of the patterns of Schistosoma mansoni infection and re-infection in Senegal, from faecal egg counts and serum concentrations of circulating anodic antigen

Abstract Infection and re-infection patterns were evaluated in a recent Schistosoma mansoni focus in northern Senegal, by determining concentrations of serum circulating anodic antigen (CAA), as a measure of worm burden, and counting eggs in faeces before, 6 or 12 weeks and 1 year after praziquantel treatment in two subsequent cohorts (cohort A and B). No differences in egg counts and CAA concentrations or their relationship were found between the cohorts, which were examined 2 years apart. Within both cohorts, CAA concentrations showed the same, typical, age-related patterns as egg counts, with a peak in children and a strong decline in adults. These trends were apparent both before and 1 year after treatment. The results indicate that an age-related resistance to infection and to re-infection has been firmly established, at a steady level, in the recent S. mansoni focus investigated, with no indication of a gradual development of immunity or anti-fecundity immunity over a period of 2 years. Both shortly and 1 year after treatment, the decrease in egg counts was stronger than that in CAA concentrations, indicating that that there had been a reduction in worm fecundity after treatment. The possibility that praziquantel may induce anti-fecundity immunity has important implications for the use and interpretation of the results of (egg-count-based) re-infection studies designed to follow the development of naturally acquired immunity.

Evaluation of density-dependent fecundity in human Schistosoma mansoni infections by relating egg counts to circulating antigens through Deming regression.

Regression analysis of the relationship of serum circulating anodic and cathodic antigens (CAA and CCA), as a possible direct measure of worm burden, and fecal egg counts allows the study of phenomena like density-dependent fecundity in human Schistosoma mansoni infections. For a reliable analysis, variations in egg count measurements as well as in circulating antigen levels have to be taken into account, and an accurate estimation of these variations (represented by parameter lambda in the so-called Deming regression) is of great importance. From a new, extensive data set of repeated measurements of fecal egg counts and CAA and CCA concentrations we determined the respective values for parameter lambda, and (re)analysed the relationship between circulating antigens and egg counts in 3 data sets from Burundi, Senegal and Zaire by Deming regression. For comparison, ordinary linear regression was performed as well, which considerably biased the regression lines for CCA, but not for CAA. The analyses resulted in a clearly non-proportional relationship between egg counts and CAA, and, to a lesser extent, CCA. Assuming that egg counts and antigen measurements directly reflect egg production and worm burdens, respectively, our findings reinforce the indication of density-dependent fecundity in schistosomiasis mansoni, as suggested by others.

Dynamics of egg counts and circulating antigen levels in a recent Schistosoma mansoni focus in northern Senegal

Serum circulating anodic antigen (CAA) levels were compared with faecal egg counts in four subsequent population samples, randomly selected at 8‐month intervals, in a recent Schistosoma mansoni focus in northern Senegal. In all four samples, antigen levels showed the same age‐intensity profiles as egg counts, with a strong decline in adults. Also across population samples, a consistent relationship was found between egg counts and antigen levels. Assuming the level of CAA to be a direct reflection of worm burden, these findings support the idea that the observed egg count patterns and levels indeed reflect dynamics of worm burdens, and not of egg excretion or worm fecundity. Remarkably similar levels of both egg counts and CAA were observed in the first and last sample, collected in the same season (August–September), but 2 years apart. This suggests that a steady state of S. mansoni infection had already been reached shortly after the onset of the epidemic in this focus (3 years). Significantly lower infection levels were found in the intermediate population samples collected in January and April. The differences in infection levels across the four population samples may be because of seasonal transmission patterns. They would indicate a substantial turnover of worm populations, with an estimated average life span of only 7 months, probably less, in this recently emerged, intense S. mansoni focus.

Immuno-epidemiology of Schistosoma mansoni infections in a recently exposed community in Senegal.

Schistosoma mansoni was introduced in the Senegal basin around 1988, due to man-made ecological changes. Since 1991, we investigate a recent but very intense focus, Ndombo, a village near the city of Richard Toll where the outbreak was first described. Four cohorts, each a random sample (+/- 400 subjects each) from this community, were examined and followed up after treatment, starting at 8 month intervals over a 2-year period. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; followed up 6-10 weeks, one and two years after treatment; and monitored for water contact patterns and local snail densities. In the first cohort, the prevalence was 91%, with a mean egg count of 663 epg. Prevalences are near 100% in all age groups, but egg counts decline strongly in adults. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens, not e.g. of worm fecundity. This is surprising, as in this focus acquired immunity in adults should not have yet developed according to current hypothesis. The antigen detection assays (CAA/CCA) showed high sensitivity and quantitative power, and promising perspectives as a research tool and possibly as a method for non-invasive diagnosis and screening in urine. Epidemiological in subsequent cohorts were highly similar, although seasonal variations were observed possibly due to transmission fluctuations. Anti-AWA and anti-SEA IgE levels increased with age, while IgG4 peaked in the age-group 10 years and correlated well with egg counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating anodic antigen levels in two areas endemic for schistosomiasis mansoni indicate differences in worm fecundity

Serum levels of the adult schistosome circulating anodic antigen (CAA) were compared in 2 populations, both living in an area with extremely high transmission levels of Schistosoma mansoni. In one focus (Maniema, eastern Zaire) transmission has been established for several decades, while in the other focus (Ndombo, northern Senegal) transmission started only recently. While parasite egg counts in the 2 populations were virtually similar, including analogous age-related distributions, serum levels of CAA were approximately 5 times higher in the chronically exposed community. This difference in antigen level was most pronounced in adolescents and adults. As the level of CAA is assumed to be a direct reflection of worm burden, these findings suggest higher parasite fecundity in the recently exposed community. It is not very likely that these observations could be explained solely by differences in clearance mechanisms caused by a variation in experience of infection. The relationship between circulating antigen levels and egg counts was consistent for all age groups in the Maniema population, while in the Ndombo population only children showed a pattern similar to that in the chronically exposed community.

Serum circulating egg antigen levels in two areas endemic for Schistosoma mansoni

A monoclonal antibody-based enzyme-linked immunosorbent assay detecting Schistosoma mansoni circulating soluble egg antigen (CSEA) was applied in epidemiological studies. The serum CSEA levels were determined for 2 populations with a high prevalence (> 95%) and high intensity of infection as determined by faecal egg counts. In one population (Maniema, Zaire) transmission had been occurring for several decades, while in the other population (Ndombo, Senegal) transmission had started only recently. CSEA could be detected in 88% and 70% of the serum samples from Maniema and Ndombo, respectively. The sensitivity of the CSEA assay increased with rising egg count. The age-related CSEA profiles of the Maniema population followed a pattern similar to that of egg counts and of the adult worm antigen CAA (circulating anodic antigen). However, the recently infected Ndombo population showed a clearly different profile: while the CSEA prevalence reached a peak in children and adolescents, the mean CSEA levels did not vary significantly in the different age groups. CSEA levels were significantly lower in Ndombo than in Maniema. As egg antigens in serum are thought to be in part, or even primarily, derived from eggs in the tissues, these findings indicate a relatively smaller tissue egg load in Ndombo than in Maniema.

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.

Rapid screening and diagnostic tests for human schistosomiasis in endemic areas

This is the protocol for a review and there is no abstract. The objectives are as follows: To obtain summary estimates of the diagnostic accuracy of urine reagent strip tests for haematuria/ protenuria/ leukocyturia in detecting active S. haematobium infection, using microscopy as the reference standard. To obtain summary estimates of the diagnostic accuracy of a POC urine CCA test (urine CCA dipstick) for the detection of an active Schistosoma infection in geographical regions endemic for S. mansoni or S. haematobium, or both, using microscopy of stool or urine, or both, as the reference standard. To obtain summary estimates of the diagnostic accuracy of ELISA for CCA or CAA in serum or urine for the detection of active Schistosoma infection in geographical regions endemic for S. mansoni or S. haematobium, or both. We will investigate whether age and sex of participants, prevalence of infection, stage of infection, intensity of infection, mixed infections, effect of treatment with praziquantel and number of urine or stool samples used can explain the expected heterogeneity in test accuracy estimates. 1 Rapid screening and diagnostic tests for human schistosomiasis in endemic areas (Protocol) Copyright