Spatial patterns of human water contact and Schistosoma mansoni transmission and infection in four rural areas in Machakos District, Kenya.

This paper presents the results of microgeographical studies of human water contact behavior and Schistosoma mansoni transmission levels and intensity of infection in four rural areas in Machakos District, Kenya. The relationship between intensity of infection (geometric mean egg counts) in 3502 persons aggregated in 120 household clusters and eight independent variables was investigated using straight and stepwise linear regression and mapping techniques. Results indicate that the two water contact variables, mean frequency per person and mean duration per person, as well as mean number of sites used per person, a transmission index and mean distance to the most frequently used site were the strongest predictors of geometric mean egg counts. All three distance variables were usually negatively associated with infection although intensity of infection and water contact declined relatively slowly with distance from the streams. This pattern appears to be owing to a combination of the relatively short distances, a general lack of safe alternative water sources and the use of more distant water contact sites both inside and outside the study area during periods of drought. The study of snail-to-man transmission identified number of infected snails as the major transmission variable and number of contacts as the major predictor variable. Mapping of total egg counts at the household cluster level and total number of infected snails revealed spatial association with transmission sites. All results varied considerably between study areas, owing to differences in exposure levels, transmission patterns and environmental factors. Findings are discussed in relation to the epidemiology and control of schistosomiasis and suggestions are made for further spatial studies.

Immunity in human schistosomiasis mansoni: prevention by blocking antibodies of the expression of immunity in young children.

A total of 129 children were treated for Schistosoma mansoni infections, and followed for intensity of reinfection at 3-monthly intervals over a 21-month period. Blood samples were taken before treatment and at 5 weeks and 6, 12 and 18 months after treatment. This paper presents a statistical analysis of the relationship between various immune responses and subsequent reinfection. Responses analysed were: blood eosinophil levels; IgE antibodies against schistosomulum antigens; IgG antibodies mediating eosinophil-dependent killing of schistosomula; antibodies inhibiting the binding to schistosomulum antigens of two rat monoclonal antibodies that also recognize egg antigens; the levels of anti-adult worm and of anti-egg (total, IgM and IgG) antibodies; and IgM anti-schistosomulum antibodies. Results for each assay were well correlated for each of the five separate blood samples. None of the assays were predictive of resistance to reinfection, but susceptibility to reinfection was strongly correlated with results in the preceding blood samples for total anti-egg antibodies and the inhibition of binding of one of the two monoclonal antibodies. Further analysis also revealed a correlation between reinfection intensities and both IgM anti-schistosomulum antibodies and IgM and IgG anti-egg antibodies. These results are consistent with the hypothesis that early infections elicit the development, in response to egg antigens, of antibodies that block immune mechanisms directed against schistosomula. Blocking antibodies may be IgM, but might also be of an ineffective IgG isotype. The existence of such antibodies in young children would explain the slow development of immunity in the face of a range of detectable, potentially protective immune responses.

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment.

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.

Evidence for predisposition of individual patients to reinfection with Schistosoma mansoni after treatment.

Statistical analysis of the relationship between intensities of infection before treatment and during reinfection after treatment in a sample of 119 Kenyan schoolchildren demonstrated a positive association, indicating that the individuals differed consistently in their tendency to become infected. This association was stronger in young children but the trend was detectable in older individuals. Possible reasons for this variation and for its apparently greater influence in younger age groups are discussed.

Immunity after treatment of human schistosomiasis mansoni. II. Identification of resistant individuals, and analysis of their immune responses.

Intensities of re-infection were monitored at three-monthly intervals after treatment of Schistosoma mansoni infections in a group of 119 Kenyan schoolchildren, whose levels of water contact were also observed. 22 children showed high reinfection intensities (greater than 100 eggs per gram of faeces) by 12 months after treatment, and were considered to be susceptible. Out of 70 children who showed low reinfection intensities during the same period (less than 30 eggs per gram), 35 showed high levels both of total water contact and of contact with sites containing infected snails. In these children, the relative lack of reinfection could not be attributed to a lack of exposure, and they were classified as resistant to reinfection. Comparison of the two groups, resistant and susceptible, revealed no difference in pretreatment intensities of infection. However, there was a marked difference in age, the mean age of the resistant group being two years greater than that of the susceptible group, within a restricted starting age range. These findings indicated that resistance was an acquired and age-dependent phenomenon, not obviously related to previous egg-induced pathology. Studies of immune responses revealed no clearcut correlate of resistance, but there were interesting differences between the two groups. Whereas anti-egg antigen responses declined after treatment to a greater extent in the resistant than in the susceptible group, antibodies mediating eosinophil-dependent killing of schistosomula rose markedly in both groups, strongly suggesting that the resistant children were being exposed to cercariae. Anti-adult worm antibodies rose sharply in both groups immediately after treatment, and thereafter declined to pretreatment levels. Although some individual children showed high levels of IgE anti-schistosomulum antibodies, there were no significant differences between the two groups. Since all children showed detectable levels of antibodies mediating eosinophil-dependent killing of schistosomula, the possibility was considered that such antibodies might be a necessary, but not a limiting, factor in immunity. Instead, the functional state of the effector cells mediating antibody-dependent killing might be limiting. Eosinophil levels, measured as an indirect estimate of eosinophil functional activity, did not differ between the two groups. There were, however, marked differences between different individuals in their capacity to produce eosinophil-stimulating monocyte mediators, and although this cannot yet be related to resistance, this aspect is worth further study.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunity after treatment of human schistosomiasis mansoni. I. Study design, pretreatment observations and the results of treatment.

This paper describes the design of a study on immunity to reinfection after treatment of children with Schistosoma mansoni infections, the initial observations on transmission that led to the selection of the study population, the effects of treatment, and the results of immunological tests carried out before and at five weeks after treatment. Iietune village in Machakos District, Kenya, was selected on the basis of high prevalence and intensities of infection in a small preliminary survey, a stable population living in a small area amenable to detailed study, and a lack of previous intervention in the area. Subsequent observations over a pretreatment period of one year confirmed that prevalence and intensities of infection among children attending the local primary school were high. This was associated with extensive contact of members of the community with water-bodies shown to contain large numbers of infected snails. Analysis of pretreatment intensities of infection and water contact patterns in the schoolchildren allowed the selection of 129 children showing a broad scatter between: (a) high intensity, low water contact, and predicted to be non-immune, and (b) low intensity, high water contact, and predicted to be immune. These children were treated with oxamniquine, 30 mg/kg in divided doses. Five weeks after treatment, 70% of children showed apparent complete cure, and the over-all reduction in geometric mean egg output was 98.9%. Since these children represented only a small proportion of the whole community, there was no obvious reduction in transmission, as reflected by snail infection rates, during the following five-month period. Thus, we are in a position to determine whether successfully treated children do or do not become reinfected in a high transmission environment in which it will be possible to make direct estimates of exposure. Immunological tests carried out immediately before treatment were consistent with a pattern of high exposure leading to the early expression of immune responses in most infected children. Eosinophil levels were elevated in 61% of the children, all of whom showed detectable levels of antibodies against adult worm and egg antigens, as measured by ELISA. In addition, all patients showed antibodies capable of mediating eosinophil-dependent killing of schistosomula. At five weeks after treatment, eosinophil counts and anti-adult worm antibody levels had risen, whereas anti-egg antibodies remained grossly unchanged. The wide variation in the levels of responses shown by different individuals will allow us to test whether such responses are associated with resistance to reinfection during the follow-up period.

Water-contact patterns in relation to Schistosoma haematobium infection.

Water-contact observations were carried out on a population exposed to Schistosoma haematobium in a village situated on a man-made lake, Lake Volta, Ghana.The observations were made over a period of 12 months prior to the introduction of control measures. A multiple regression analysis was performed on the results of observations on 132 individuals, with egg output as the dependent variable and various types of water-contact activity, as well as age and sex, as independent variables. In the analysis, specific activities, notably water-contact for domestic purposes and activities associated with fishermen's canoes, were found to be significantly related to schistosomiasis. Age was less important than degree of exposure as a contributory factor to variations in infection rates: the reduced intensity of infection of S. haematobium in the older age groups could be mainly due to a lower level of exposure to the cercarial population.

A socioecological approach to the control of Schistosoma mansoni in St Lucia.

Systematic observations of man/water contact in a valley endemic for S. mansoni in St Lucia were carried out prior to the introduction of a household water supply. The observations indicated that exposure of the population to cercaria-infested rivers and streams could be broken down into different types related to distinct and measurable domestic and economic activities. The number and duration of daily contacts with water played an important role in determining the relative risk of infection and correlated significantly with the number of infected persons by age in a survey conducted immediately following the observations. Consideration should be given to measuring and assessing the relative importance of different activities involving contact with water in relation to transmission and the formulation of control strategies.