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A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium.

Mother-to-child infection with HIV-2 is thought to be rare, and there have been few previous reports of transmission by this route. Reports of morbidity associated with HIV-2 infection in children are also rare. We describe eight children born to mothers who were infected with HIV-2; five developed AIDS, and three were still seropositive at 17-49 months of age. The only apparent route of HIV-2 transmission was from mother to child, except for one child who had been transfused. Three of the children with AIDS died, all having decreased CD4+ lymphocytes and mitogen responses. Further studies are needed to determine the prevalence and natural history of mother-to-child transmission of HIV-2.Eight cases of mother-to-child transmission of HIV-2 were documented by ELISA and Western blot in Gambia between January 1988-September 1989 from a hospital-based screening of 205 malnourished children, 864 subjects in a malaria study, 34 patients with probable immunodeficiency and 24 children of 17 HIV-2 seropositive mothers. AIDS was diagnosed by WHO clinical definition. Diagnosis of HIV-2 was made if sera were positive by ELISA and Western blot (LAV Blot2, Diagnostics Pasteur, Marnes-La-Coquette, France) and negative by Wellcozyme I competitive ELISA to HIV-a (Wellcome Diagnostics, Dartford, UK). The children ranged in age from 17 months-5 years, and in ponderal index from 50-90%. 6 had CD4 percentages or counts below the normal range. 7 of the 8 could only have been infected pre- or perinatally, while 1 had been transfused from her mother. The clinical features included 5 with diarrhea 1 month; 3 with Cryptosporidium, 3 with Candida, a pneumonia, an interstitial pneumonia by x-ray, a streptococcus abscess, a staphylococcus abscess, 1 infant with failure to thrive and 1 4-year old who was asymptomatic. This group of patients was more severely affected than a series reported from Guinea Bissau: their mothers also had advanced AIDS in comparison to asymptomatic mothers in the other series. While mother-to-child transmission of HIV-1 occurs in approximately 33% of children of HIV-1 seropositive mothers, these data cannot estimate the actual rate of transmission of HIV-2.

We have measured the levels of infection with Schistosoma haematobium in children resident in an endemic area of The Gambia before and 3 months after successful chemotherapy and following reinfection. An exposure index was calculated from data collected on water contact, cercarial densities and infected snail densities at water contact sites. Peripheral blood eosinophil levels were recorded and the ability of serum (heat inactivated) from the children to allow killing of schistosomula of S. haematobium was examined. Of 50 children with a post-treatment egg count of less than 1 ovum/10 ml urine, 26 were classified as reinfected, acquiring greater than 1 ovum/10 ml urine over the transmission season. Twenty-four were classified as not reinfected, acquiring less than 1 ovum/10 ml of urine over the same period. These two groups did not differ with respect to their estimated age, weight or pretreatment egg counts. Children who were reinfected had significantly higher levels of exposure and significantly lower peripheral blood eosinophil counts than children who were not reinfected. At all levels of exposure children with high eosinophil counts were less likely to be reinfected than those with lower counts. But antibody-dependent, complement-independent killing of schistosomula of S. haematobium by eosinophils was barely detectable and did not differ between reinfected and non reinfected groups. These observations suggest that subjects with elevated counts are less susceptible to reinfection but the mechanisms involved are not apparent.

Statistical analysis has been used to find the best relationship between mean transit time calculated from corrected (blood-background subtracted) renograms and empirical indices measured directly from the standard renogram. The best formula of those compared for estimating mean transit time when both time-to-peak and % maximum activity at 15 min are known is Y=0.17+0.49X1+0.003X2, where Y is a dependent variable and X1 and X2 are predictor variables.

Today, chemotherapy has a central role in the control of schistosome infections. Although the costs involved may be high in relation to local expenditures on health, externally funded mass treatment programmes can lead to large reductions in the prevalence and intensity of schistosome infections. But the benefits of treatment to a community that has been involved in a mass chemotherapy programme, or to an individual patient seen in a health centre, will be limited if reinfection after treatment is rapid and intense. Despite the efficacy of the available drugs few, if any, control programmes based on mass chemotherapy have interrupted transmission and come anywhere near to eradicating schistosome infection.

Specimens of urine and blood were collected from as many members as possible of a community living in an area of urinary schistosomiasis in The Gambia. The light infections found in many of the subjects appeared to have little or no effect of haemoglobin levels, but some of the intense infections were associated with reduced haemoglobin levels. Significant differences in haemoglobin levels between ova-positive and ova-negative subjects were apparent only in males aged from 15 to 44 years, and significant differences in the prevalence of anaemia between groups with different egg counts were apparent only in children aged from five to seven years and from eight to 14 years.

The relationship between reinfection with Schistosoma haematobium and immunological parameters was studied in a group of Gambian children aged from 8 to 13 years. Each individual's exposure to infection was assessed from observations of water contact, cercarial densities and infected snail densities at water contact sites. Eosinophil counts were made and responses to egg antigen (SEA) and adult worm antigen (WWH) measured by ELISA. Low levels of reinfection were associated with a high eosinophil count, high levels of antibodies against WWH and SEA, increased age and low exposure. In a multiple regression analysis of the association of reinfection with eosinophil count, antibody levels, exposure, age and sex, the effects of eosinophil count and exposure were still very significant after allowing for all the other variables. The effects of the antibody levels were close to significance after allowance for exposure and eosinophil count (for WWH: P = 0 · 09; for SEA: P = 0 · 07), although the evidence was less clear after additional allowance was made for age and sex. The ability of sera from the children to recognize different parasite antigens was also examined by immunoprecipitation of labelled schistosomulum surface, WWH, SEA and S. haematobium adult worm mRNA in vitro translation products. Schistosomulum surface antigens were recognized by all the sera and there was little variation in this response. There was more variation in their responses to SEA and WWH and a marked heterogeneity in the response to in vitro translation products. However, the pattern of antigen recognition appeared unrelated to susceptibility to reinfection.

During a three-year period of effective control of Schistosoma haematobium transmission by molluscicide application the mean number of S. haematobium ova passed by subjects in the treated area fell in an exponential manner which suggested that the mean life span of the worm was 3·4 years. Parallel observations were made in a similar but untreated area. A comparison of the observations in these two areas suggested that in the untreated area subjects of all ages acquired infection during the course of the study. At the end of the study over 50% of the egg output in most age groups in the untreated area appeared to come from worms acquired during the preceding three years. There were substantial differences between age groups in the amount of infection acquired. Children, aged between eight and ten years at the end of the study, appeared to be passing perhaps a thousand times more ova from worms acquired during the preceding three years than were middle-aged subjects. Preliminary observations suggest that age- and sex-related differences in the pattern of water contact may not fully account for age- and sex-related differences in the rate of acquisition of infection and its prevalence. The probable significance of protective immunity in the epidemiology of schistosome infections is discussed.

The roles of some of the factors thought to be responsible for the characteristic relationship between age and the intensity and prevalence of Schistosoma haematobium infection have been investigated. In this initial report a study population in an area of intense infection is described, as are the methods used. Subsequent papers report the effect of interrupting transmission with molluscicide in part of the area and compare changes in egg count in this treated area with changes in an area where no intervention took place. These allow a consideration of age-specific rates of loss and acquisition of infection to be made. The intensity and prevalence of infection varied between villages both in the treated and untreated areas, but the relation of age to the pattern of infection was regardless of the level of infection in the villages. Over-all, the number of subjects and their pattern of infection was similar in both areas. The prevalence of infection tended to be higher in adult males than females but preliminary water contact observations suggest males are less exposed to infection. Observations over the three-year study period emphasize the extent of population movement in the study area and point to its importance in the planning of control measures.

A questionnaire administered to subjects seen during a serological survey in The Gambia revealed that knowledge of AIDS and HIV infection was limited. Males, those with a secondary education and people who lived in urban areas had a better understanding but only 17% of women seen in rural areas had any knowledge of the condition. Only 8% of the subjects seen had used condoms in the preceding 12 months; during this time half of them had done so on less than five occasions. Subjects with a secondary education were more likely to have used condoms. A counsellor met 31 asymptomatic seropositive subjects identified during this survey on two occasions. In the majority, the information given caused anxiety rather than modification of behaviour and, at the time of the second interview, only one subject had discussed the situation with the partner and begun using condoms. Some of the cultural factors which may affect the outcome of counselling in an African society are discussed in the light of these findings.Questionnaires given to people from rural and urban populations seen during a serological survey in The Gambia revealed knowledge about AIDS and HIV infection to be limited. Data was received on 1,898 subjects aged at least 15 years. While only 17% of women in rural areas were aware of the existence of AIDS, males, those with secondary education, and those in urban areas demonstrated better understanding of the disease. 8%, however had used condoms over the past 12 months, with 1/2 doing so on less than 5 occasions. Secondary education generally signaled greater likelihood of condom use among respondents. A counsellor met with 31 asymptomatic, HIV-positive subjects in their homes on 2 occasions during the survey. Failing to generate behavior modifications, information provided by the counsellor largely produced anxiety. By the 2nd interview, only 1 subject had discussed AIDS and HIV infection with the partner and began using condoms. Health education programs targeted to underserved rural areas, women, and those without secondary education are severely needed. Radio, used as the key mode of message dissemination, is challenged on the basis of its audience being potentially limited due to gender and/or socioeconomic factors. Limited education, limited knowledge of AIDS in the community as a whole, sociocultural and attitudinal factors fostering social rejection of the seropositive individual, and gaining acceptability for the condom are potential obstacles to effective counselling for improved education and behavioral change. Joint sessions with partners, group sessions, and repeated exposure to a counsellor are suggested approaches. Research is suggested for alternative approaches.

Surface antigens ofSchistosoma haematobiumwere identified by125I-surface labelling of schistosomula followed by immunoprecipitation of the solubilized, labelled surfaces. The major antigens, after electrophoresis, formed a continuous smear corresponding to a molecular weight in the range 35–24000; in addition, a 17000 antigen was also identified. These surface antigens, in contrast to somatic antigens, were species-specific, as judged by immunoprecipitation with human anti-S. mansoniserum and serum from mice vaccinated with highly irradiatedS. mansonicercariae.S. haematobiumsurface antigens, however, were recognized to some extent by serum from mice chronically infected withS. mansoni. It is suggested that this cross-reactivity may reflect the heterologous immunity demonstrated experimentally between these two species, whilst the species-specificity of vaccine sera to surface antigens may mirror the highly specific immunity induced by vaccination.

The binding of immunoglobulin to carbohydrate epitopes on the surface of Schistosoma mansoni schistosomula was measured with 125I-labelled protein A in sera from 67 Gambian subjects living in a focus of intense S. haematobium transmission. The levels of such antibody differed considerably between subjects and there was significant variation between age groups. The highest mean level, in subjects aged between 8 and 14 years, was significantly greater than that in older subjects. Previous studies have shown that resistance to post-treatment reinfection with S. haematobium is related to age in this focus, and is greatest in those aged 15 or more years. These differing relationships with age suggest that antibodies directed against carbohydrate epitopes on the surface of the schistosomulum do not have a major protective role in man.

The process of reinfection after treatment was studied in a cohort of subjects in a focus of intense Schistosoma haematobium infection. Detailed observations were made at water contact sites of cercarial densities and of water contact by members of the cohort. Individual values of a cumulative index of exposure to infection were calculated using these observations and assumptions which were made about the effect of different water contact activities on the entry of cercariae into the skin. Among groups of subjects with an apparently similar intensity of exposure to infection, reinfection tended to be much heavier in children under 10 years of age than in 10 to 14-year-olds, while only light infections were found in the few adults who became reinfected. This trend for reinfection to decrease with increasing age, after an allowance for variation in exposure, was highly significant (p less than 0.001). These observations suggest that subjects in this area slowly acquire an increasing degree of immunity to the acquisition of S. haematobium infection which is effective in the absence of a mature egg laying infection.

A study of Schistosoma haematobium egg counts was made in a community near Alexandria. This showed that the intensity of infection was similar to that which has been reported in some of the comparable surveys which have been made in sub-Saharan Africa. This finding highlights the need for further studies in defined communities of the pathogenicity of the infection. The egg counts of subjects who recalled treatment with tartar emetic within the last two years were similar to those who said they had never been treated. This suggests that the cost effectiveness of chemotherapeutic methods needs further evaluation.

Niclosamide was used to interrupt transmission of Schistosoma haematobium by Bulinus senegalensis in seasonal rainwater pools for a period of three years. Snail populations were progressively reduced to approximately 1% of the numbers in untreated pools. There was little or no evidence of acquisition of new infection by children in the area during the period of intervention. The intensity of infection in a cohort of children initially under 10 years old followed for three years fell by more than 50%, while there was a ten-fold increase in a similar group in a nearby untreated area. The mean annual cost 1982 of control per head of the population protected was £0·50 (US$0·89).

A transportable apparatus for isotope renography, which allowed deconvolution analysis, was used to study the prevalence and prognosis of abnormalities associated with urinary schistosomiasis. Before carrying out studies in a heavily infected community, observations were made in a non-endemic area to allow derivation of criteria for abnormality. Comparison of the findings in the two areas showed that changes suggesting urinary tract obstruction were more common in the endemic area in subjects between nine and 45 years but not in older subjects. Measurements of effective renal plasma flow showed renal function was impaired in the endemic area in subjects older than 17 years but not in younger subjects. In the endemic area the results of renography were unrelated to the urinary egg count of the subjects examined, but there was an improvement in the abnormal renograms in a group of subjects aged between nine and 20 years who were re-examined a year after treatment with metrifonate. Follow-up data about 316 subjects was obtained two years after renography. Nine subjects had died, including four of the five subjects with abnormalities suggesting both obstruction and over-all loss of renal function. These findings, which are comparable to the results of similar studies using radiological techniques, suggest urinary schistosomiasis may be a significant cause of mortality in adults in intensely infected communities.

SUMMARYOf the surface antigens identified by radio-iodination, two-dimensional gel analyses showed no similarities between those ofSchistosoma haematobiumandSchistosoma mansoni, thus providing a basis for the species specificity of these antigens described previously (Simpson, Knight, Hagan, Hodgson, Wilkins & Smithers (1985)Parasitology90, 499–508). The surface antigens ofS. haematobiumwere glycosylated and comprised an acidic polypeptide ofMr17000 as well as a complex set of polypeptides of approximate pI 6–7, which resolved in theMrrange 20000–30000. At least one of the lowerMrforms of this complex is also present in the adult worm. Limited cross-reaction was observed withS. mansoniinfection sera and this may be due to a shared carbohydrate epitope. In contrast, extensive cross-reaction was observed using sera from mice immunized withS. bovis.This pattern parallels the species-specificity of vaccine-induced immunity. Extensive cross-reaction was also observed within cell-free translation products of m-RNA from adult worms ofS. haematobiumandS. mansoniby use of heterologous human infection sera. The few antigens which were species-specific may represent surface antigens.

Individual changes in egg counts of a group of Gambian children were observed over a four-year period by obtaining replicate specimens on several successive days. In a focus where transmission begins in late July and increases in intensity until it stops in October or November, the egg counts of children less than 10 years old rose between November/December and March/April, and fell during subsequent months. These apparent annual cycles of superinfection were less obvious in older children. Some children of all ages showed large changes in counts in a few months and 7% of observations over a 12-month period were of falls by over 90%. Despite these fluctuations there was a significant degree of relative stability in subjects' counts when compared with those of other members of the group. The observations suggest that the worm burdens of some children are in a dynamic but steady state. Among the factors regulating this may be the acquisition of a degree of immunity to superinfection. The results also prompt speculation whether man's immune response may, in some circumstances, affect the egg-laying worms of the established infection. The role of protective immunity in the epidemiology of the infection appears complex and needs further study. While the findings are compatible with the hypothesis that concomitant immunity occurs in man, they suggest that it is unlikely to be solely responsible for the lower prevalence and intensity of infection in adults.

The intensity and prevalence of proteinuria and haematuria were studied with urinanalysis reagent strips in a Gambian community in which the intensity of infection with Schistosoma haematobium was high. The level of proteinuria present was shown to be related to the intensity of infection. Follow-up for 12 months showed that infected subjects with heavy proteinuria had a good prognosis. These findings suggest that the urinary protein in such subjects is likely to originate from lesions in the bladder and ureters and that advanced glomerular pathology is probably rare. The relationship of the levels of proteinuria and haematuria to the egg count suggests they may be parameters which could have value as indications for chemotherapy. Detailed study showed that the effect of treating all the subjects who had both 30 mg/100 ml or more of protein and at least a trace of haematuria would have been very similar to treating all those with an egg count of 200 ova/10 ml or more. Since urinanalysis with reagent strips is very simple and rapid it could have a role in mass chemotherapy campaigns, particularly those aimed at the identification and treatment of heavily infected subjects.

Summary Schistosomula of S. haematobium have been shown to be susceptible to in vitro killing by eosinophils in the presence of serum from an infected individual. The highest level of killing was found after 48 h in culture. Killing was related to the eosinophil to schistosomula ratio, being highest at 5000:1. Killing was also related to serum concentration, being highest at a 1/10 final dilution, falling to background levels at a 1/120 final dilution. At a cell: target ratio of 2000:1 and at a serum dilution of 1/10 eosinophils from subjects with high peripheral blood eosinophil counts were, cell for cell, more active in killing S. haematobium schistosomula than were eosinophils from subjects with lower counts. Sera taken from adults resident in an endemic area gave higher levels of killing in the presence of eosinophils than did sera taken from adults with no history of exposure.