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Irrigation for intensive sugar cultivation started in the early 1980s at Richard Toll, some 100 km from the mouth of the Senegal River. Infections with Schistosoma mansoni were first seen in late 1988. This study records quantitative snail surveys for over 3 years from 1992 at sites representing different habitats in and around the irrigation scheme. Populations of both Biomphalaria pfeifferi (the intermediate host of S. mansoni) and Bulinus spp. (mainly B. truncatus, the local host of S. boris) peaked in late 'spring' or early 'summer', depending on the habitat, and then remained low until the following spring', B. pfeifferi favoured smaller, man-made habitats with most transmission between May and August each year. The less abundant Bulinus spp. favoured larger natural and man-made habitats with most S. bovis transmission between April and July. S. mansoni infections were more, but S. bovis infections were less abundant than other trematodes in their respective snail hosts. Ecological changes in the early 1980s due to sugar irrigation pre-dated similar, more widespread changes in the late 1980s when the completion of dams across the Senegal River prevented seasonal rain fed floods and sea water intrusion. S. mansoni has since spread rapidly around Richard Toll. The incompatibility of the local S. haematobium strains with the dominant bulinid snails has so far prevented an epidemic of urinary schistosomiasis at Richard Toll, but the invasion of similar downstream habitats by susceptible B. globosus is worrying. The principal control measure, chemotherapy, given in the 'winter' would minimise the rate of reinfection. It could be reinforced by judicious mollusciciding within the sugar irrigation scheme but not elsewhere.

The reduction of Schistosoma fecundity observed after experimental vaccination with the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) antigen has been related to the inhibition of glutathione S-transferase (GST) enzymatic activity by specific antibody. The humoral immune response to the protective antigen Sm28GST and to the epitopes involved in the enzymatic site (amino acid ¿aa sequences 10-43 and 190-211) was evaluated in infected individuals before chemotherapy treatment. The capacity of the serum samples to inhibit GST enzymatic activity was assessed. Specific IgG3 response was predominant in the male population with a low intensity of infection and was associated with maximal GST inhibition. In contrast, the neutralizing activity of serum samples from women with a low intensity of infection was correlated with high specific IgA response specifically directed toward the 190-211 epitope. These results strongly support the hypothesis that GST-neutralizing IgG3 and IgA isotypes are sex dependent. The relationship of this specific acquired immune response with the level of intensity of infection is discussed.

A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).

In studies of schistosomasis mansoni-endemic communities, individuals with IgE responses to a 22 kD adult worm antigen (rSm22.6) suffered lower intensities of reinfection after treatment. It is of interest to define the factors that lead to the production of rSm22.6-specific IgE because it is a marker for resistant individuals and it may be involved in the development of resistance to reinfection. In endemic populations rSm22.6-specific IgE increases linearly with age. However, it is not possible to distinguish between age per se and 'history of infection' in endemic populations because individuals are exposed to the parasite at an early age. We have, therefore, quantified pre- and post-treatment isotype responses to rSm22.6 in a comparatively 'epidemic' Senegalese community where the patients were infected at different ages and where pre-treatment intensity of infection can be taken as a reasonable measure of antigen exposure. Post-treatment isotype responses to rSm22.6 correlated positively with pre-treatment intensities of infection but were not shown to be related to age. IgG1, IgG4 and IgE responses to rSm22.6 were significantly higher after treatment with the difference increasing with the pre-treatment level of infection. These results from a recently established focus of infection suggest that isotype responses to rSm22.6 are antigen-exposure dependent rather than dependent on age per se.

With the intention of ultrasonographically assessing hepatosplenic morbidity in Schistosoma mansoni infection and of validating the grading system applied (Cairo classification), 191 subjects in a schistosomiasis endemic village and 247 controls from a nonendemic village in northern Senegal underwent sonographic examination of the liver and spleen. Measurements of the diameters of the peripheral periportal vein branches, the main portal vein stem, liver size (left lobe and right lobe), and spleen length in the endemic village were compared with those in the nonendemic village to evaluate the much discussed influence of S. mansoni infection on those variables. To subtract this presumed influence from reference values for the named variables, they are given as measured in the nonendemic village, stratified by body weight, enabling future investigators on schistosomiasis-induced morbidity to refer to these reference values. The 95th percentile regarding peripheral periportal vein branch diameter in the control groups was exceeded in 24% of the subjects in the endemic group. It was exceeded by 6% for the main portal vein stem diameter, 13% for the left liver lobe, 12% for the right liver lobe, and 14% for the spleen length. According to the Cairo classification, 97% of the endemic population and 81% of the controls had periportal thickening of the liver, mostly grade I. We conclude that 1) hepatic morbidity in the S. mansoni endemic area was low, despite strikingly high intensities of infection; 2) the Cairo classification in its present form overestimates periportal thickening, especially in the case of mild morbidity; and 3) body height-dependent reference values, obtained from endemic controls, must be applied for organometric parameters.

An outbreak of Schistosoma mansoni in northern Senegal was observed in 1988, and chemotherapy with praziquantel in this recently established focus resulted in very low parasitologic cure rates. Among other explanations, the emergence of a praziquantel-tolerant parasite strain was feared. To study this hypothesis further, 138 persons with endemic S. mansoni infection were randomly allocated to treatment with either 20 mg/kg oxamniquine or 40 mg/kg praziquantel. Parasitologic cure rates at 6 weeks were significantly higher in the oxamniquine group (79%) compared with those in the praziquantel group (36%; P = .0043). The reduction in egg counts was generally good, but 12% less reduced in the praziquantel group. These results confirm that cure rates with praziquantel were abnormally low, whereas oxamniquine performed satisfactorily, as in other areas in which S. mansoni is endemic. The possibility of a praziquantel-tolerant S. mansoni strain must therefore be studied carefully.

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.

The fecundities and drug susceptibilities of Schistosoma mansoni isolates from Senegal, Puerto Rico, and Kenya have been examined in mice. The Senegal parasite, obtained from the field in 1993, was shown to have a longer prepatent period (eggs first recovered in the faeces on Day 46 after infection) than those of two isolates, from Puerto Rico and Kenya, that had been maintained for a long period in the laboratory (faecal eggs recovered on Days 38 and 36 after infection, respectively). A Kenyan isolate, also collected from the field in 1994, was shown to mature more slowly than the laboratory-maintained Kenyan isolate. Tissue egg counts confirmed that early in infection the fecundity of the recently collected isolates from Senegal and Kenya was significantly lower than that of the long-term laboratory-maintained Kenyan isolate. Praziquantel and oxamniquine treatment of 8-week-old infections caused a significant (P < 0.001) reduction in worm burden in all isolates tested. However, the reduction in worm burden after praziquantel treatment of infections of the Senegal isolate (50% reduction) was significantly lower than the > 90% reductions in worm burdens after praziquantel treatment of mice infected with either of the Kenyan isolates (P < 0.001). The study confirms that despite being tolerant to praziquantel, the Senegal isolate is fully susceptible to oxamniquine. The praziquantel tolerance of the Senegal parasite is not solely attributed to the state of maturation of the parasite at the time of drug administration.

Endemic schistosomiasis due to Schistosoma mansoni has been observed in Richard-Toll (The Senegal River basin) in Senegal since 1990. Because of its high prevalence, schistosomiasis is assumed to be the cause of most cases of diarrhea observed in the region. The purpose of the present study carried out within the framework of the ESPOIR program for control of bilharziasis in the Senegal River region was to confirm the exact etiology of diarrhea in the region. A total of 109 subjects presenting diarrhea including 57 children under the age of 5 years were included in the study. In all cases, stool examination using appropriate techniques was performed to detect bacterial, viral, and parasitic agents. Schistosoma mansoni was identified in 47 cases (43.1%). Stool cultures were positive in 28 cases (25.6%) for Escherichia coli (n = 9), Shigella spp. (n = 18), and Salmonella spp. (n = 1). With regard to Shigella, a predominance of the Shigella dysenteriae type I stereotype (10/18) and a high incidence of co-infection involving Shigella spp. and Schistosoma was noted. Rotavirus infection was observed in 6 cases involving subjects under the age of 5 years. The relative incidence of the different infectious agents varied widely in function of age. This study in an endemic area of bilharziasis in Senegal demonstrates that Schistosoma mansoni should not be assumed to account for all cases of diarrhea occurring in the area.

Extensive water development has taken place in the north of Senegal over the last decade, resulting in a large increase in the amount of fresh water for irrigation. The objectives of the present study were to determine the prevalence and intensity of Schistosoma mansoni and S. haematobium in the Senegal river basin (SRB), and to ascertain the distribution of the snail species acting as intermediate hosts for both species of schistosomes. The schistosomiasis survey started in January 1994 and was completed in March 1995. Compared to studies before the construction of the Diama dam, there was a significant increase in both the prevalence and intensity of urinary and intestinal schistosomiasis in the human population in parts of the SRB. From the 9014 people who were registered from 180 villages and 4 towns (10 districts), 7750 were examined. S. mansoni was found in the lower valley (lower delta-Senegal river, lower delta-Lampsar river, upper delta, and diéré) but not in the middle valley. The mean prevalence ranged from 4.4% in the lower delta-Senegal River to 71.8% in the zone of Lac de Guiers, where prevalence and intensity of infection were higher on the eastern side of the lake (81.3% with a mean number of 2088 eggs/g of faeces) compared with the western side (50.3% with a mean 1111 eggs/g). S. haematobium was recorded throughout the area of study, ranging from a mean prevalence of 0.37% in diére (lower valley) to 41.5% in the lower valley (Lampsar river), where the mean egg count was 313/10 mL of urine. Physical and chemical changes to the environment have favoured the spread and increase in the populations of freshwater snails. The only snail involved in the transmission of S. mansoni was Biomphalaria pfeifferi. Five species of bulinid snails were present--Bulinus globosus, Bu. umbilicatus, Bu. senegalensis, Bu. forskalii and Bu. truncatus--but only the first 3 species were involved in the transmission of S. haematobium in the lower and middle valleys.

Inhabitants of Ndombo (n = 614), a village in an area recently infected with Schistosoma mansoni in Northern Senegal, were examined clinically, parasitologically, and ultrasonographically to investigate the presence and degree of S. mansoni-related hepatosplenic morbidity after a few years of exposure to schistosomal infection of regional canals. Despite previous praziquantel treatment of 56% of the inhabitants prior to our investigation, the prevalence of S. mansoni infection in 1993 was 90%, and 42% of the villagers excreted more than 1,000 eggs per gram of stool. Previously untreated individuals were found to have significantly higher egg counts than treated ones. Despite the high intensities of infection, ultrasonographically detected severe periportal thickening of the liver was infrequent. Grading according to body length-dependent normal values of cross-section diameter of peripheral portal vein branches of a European control group correlated with intensities of infection. Of the total group of patients, 30% (n = 182) had more severe thickening of portal vein branch diameters above the 97th percentile and 70% of these had a splenomegaly. The highest egg counts and the most frequent development of periportal thickening were found in 11-20 year-old individuals. Periportal thickening was less frequent in praziquantel-treated adolescents than in untreated ones. This suggests that early antischistosomal medication may be useful to limit schistosomiasis-induced hepatic morbidity especially in children, even though reinfection seems inevitable.

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.

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.

Schistosoma mansoni was first reported in the area of Richard Toll (Senegal) in 1988 and spread rapidly in the community, after a series of human-engineered ecologic changes. A random population sample (n = 422) from Ndombo, a village near Richard-Toll, was studied in 1991 by stool examination (four Kato slides from two stool samples) and antigen detection in urine and blood. Stool-positive individuals were treated with 40 mg/kg of praziquantel. A house-to-house interview regarding side effects was conducted 24 hr after treatment. Two hundred ninety-eight subjects were re-examined 10 days (antigen detection) and 12 weeks (egg counts, antigen detection) after treatment. Before treatment, positive egg counts were found in 91% of the subjects, with 41% excreting more than 1,000 eggs per gram (epg) of feces. Treatment of 352 individuals caused serious but transient side effects (colic, vomiting, urticaria, and edema), the frequency of which increased with increasing egg counts. The parasitologic cure rate 12 weeks after treatment was only 18%, the frequency of egg counts with more than 1,000 epg decreased to 5%, and the mean egg count of those remaining positive was reduced by 86%. Antigen detection in serum 10 days and 12 weeks after treatment remained positive in 90% of the subjects, although titers decreased sharply. The low cure rates may be due to intense transmission and/or undeveloped immune responses in this recently exposed population. However, reduced drug susceptibility of the parasite strain has now been confirmed in one local isolate.

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)

A study of morbidity due to Schistosoma mansoni infection was carried out in Ndombo, a recently established but intense focus in northern Senegal. A random population sample (n = 422) was examined by repeated egg counts, standardized interviews, and clinical examinations. Egg counts were positive in 91%, with more than 1,000 eggs per gram of feces in 41% of the subjects. Abdominal discomfort was reported by 60% of the subjects, diarrhea by 33%; 17% of the stools were liquid upon inspection. Hepatomegaly was mostly mild and found in 7% of the subjects, mainly in males less than 20 years of age. Splenomegaly was detected in only 0.5% of the people examined. There was no significant correlation between the frequency of complaints or symptoms and egg counts. The remarkably mild morbidity in spite of the intense level of many infections may be explained by the recent nature of the focus; more severe chronic morbidity may develop in the future.

The epidemiology of Schistosoma mansoni infection was investigated in Ndombo, a village in the epicenter of a very recent outbreak of schistosomiasis in northern Senegal. Repeated fecal egg counts and antigen detection in urine and serum were carried out in a random population sample (n = 422). Eggs were found in 91% of the subjects, with 41% excreting > 1,000 eggs per gram of feces (epg) (mean egg load of 646 epg). The prevalence was almost 100% in groups greater than five years of age. In spite of the supposed absence of acquired immunity, intensities of infection decreased strongly in adults. Antigen detection confirmed the high prevalence and intensity of infection and the age-related distribution of worm loads. The emergence of this new focus is probably due to the ecologic impact of newly built dams and the extension of irrigation projects in the Senegal basin.

Three years after intestinal schistosomiasis had been reported for the first time in the delta of the Senegal River Basin, an ultrasonographic study was conducted on 358 subjects of the community of Richard-Toll with a proven Schistosoma mansoni infection and compared with the findings from 352 uninfected subjects of a nearby town. Periportal thickening was found in 119 subjects (33%) in only one of whom it was greater than 10 mm; liver parenchyma lesions were found in 40 subjects (11%), at about the same rate in all age groups. No correlation was found between hepatomegaly and schistosomiasis. Frequency of thickening of the omentum was significantly higher in Richard-Toll than in the control group. 11% of the Richard-Toll subjects had portal vein diameters significantly larger than the values in the control group; of those, 6% had no periportal fibrosis sign in the liver. Significantly more splenomegaly was found in the infected group, though malaria as an aetiological agent cannot be ruled out. Based on periportal alterations and parenchyma lesions only, 141 (39%) subjects in the Richard-Toll group had alterations, corresponding to the World Health Organization proposed criteria for stage I; one subject had alterations corresponding to stage II. As S. mansoni infection is still new in this area, the patho-anatomical pattern is likely to change significantly in the future.