H.A. Wilkins

Resistance to reinfection after treatment of urinary schistosomiasis

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.

Dynamics of Schistosoma haematobium infection in a Gambian community. III. Acquisition and loss of infection

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.

Resistance to reinfection with Schistosoma haematobium in Gambian children: analysis of their immune responses

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 individuals 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.

Dynamics of Schistosoma haematobium infection in a Gambian community. I. The pattern of human infection in the study area

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.

Dynamics of Schistosoma haematobium infection in a Gambian community. II. The effect on transmission of the control of Bulinus senegalensis by the use of niclosamide

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 pound 0.50 (US

Schistosoma haematobium infection and haemoglobin concentrations in a Gambian community.

0.89).

Variation in urinary creatinine concentration and Schistosoma haematobium egg count

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.

Antibody to schistosomulum surface carbohydrate epitopes in subjects infected with Schistosoma haematobium

Variation in urinary creatinine concentration was studied in a Gambian community. Whilst there was appreciable day to day variation there were also differences between subjects and between different times of year. Day to day changes in creatinine concentration correlated with changes in egg count, which were, in proportion, smaller. While there are difficulties in the use of creatinine as a reference index, it is suggested that knowledge of creatinine concentrations may eliminate some of the ambiguities arising in the interpretation of Schistosoma haematobium egg counts in random, untimed urine specimens. The relation between the two variables and the extent of seasonal changes in creatinine concentration suggest that changes in the mean egg count of a group of subjects due to changes in urine flow are usually small and seldom of the magnitude which some have assumed.

Single dose use of metrifonate

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.