Chemotherapy-based control of schistosomiasis haematobia. 3. Snail studies monitoring the effect of chemotherapy on transmission in the Msambweni area, Kenya.

Regular snail sampling was performed at 40 sites, representing the principal snail habitats, during a 4 year chemotherapy programme targetted at school-children in the Msambweni area of the coastal plain of Kenya. Populations of Bulinus africanus group snails, primarily from pools, showed seasonal variations, dropping when sites dried out and rising when they were refilled by the rains. Transmission, judged by the recovery of snails shedding typical fucocercous cercariae, continued throughout the treatment period at very low levels (less than 1% of the snails collected were infected) with peaks in October/November and in January/February after seasonal rains. Spatially, most infected snails were recovered from 2 large pools near the sea, close to the school that responded least well to the initial chemotherapy programme. Later, infected snails were found sporadically in inland pools, rice fields and temporary streams near another school where there was evidence of substantial reinfection as the study progressed. The snail findings are consistent with a reduction but not elimination of transmission associated with the chemotherapy programme.

Effects of borehole wells on water utilization in Schistosoma haematobium endemic communities in Coast Province, Kenya.

To determine the impact of the introduction of borehole wells on water use patterns and the consequent risk of transmission of Schistosoma haematobium in 3 endemic villages in Kenya, we performed a survey (a 1:6 sample of affected households) to identify sources of water and types of water utilization before and after well introduction. Water usage was also determined in 2 unaffected neighboring villages not given borehole wells, but having continuous access to piped water from communal taps. Prior to borehole well construction, significantly more high-risk water use occurred in the borehole villages vs. comparison villages in terms of water gathered for cooking, drinking, dish washing, and bathing; residents of both types of villages preferred high-risk sources (marshes and ponds) for clothes washing. Following well introduction, there were significant declines in the use of high-risk water for drinking, cooking, and dish washing, but not for bathing or clothes washing. A higher proportion of individuals from the 3 borehole villages reported some type of continued contact with high-risk water sources. Despite well introduction and a 3 year chemotherapy program among school-aged children, a 21-28% incidence of infection persisted among children in the villages, suggesting minimal impact on transmission. Regular monitoring for S. haematobium infected snail sites showed no decline in the number or proportion of infected snails. Borehole well introduction can significantly alter some forms of water usage, but social and water quality factors may limit the ability of communal wells to reduce S. haematobium transmission.

Identification of snails infected with schistosomes by ELISA employing monoclonal antibodies: Schistosoma mansoni in laboratory snails (Biomphalaria glabrata) and in field snails (Biomphalaria pfeifferi) from Kenya.

An enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibodies was used for detecting Schistosoma mansoni antigens in hemolymph of laboratory snails (Biomphalaria glabrata) in Kenya. Infected laboratory snails shedding cercariae were differentially identified by ELISA from uninfected snails with 100% sensitivity and specificity. Prepatent infections were detected by ELISA from 2 weeks after exposure to miracidia. Thus, ELISA revealed infection 3 weeks before maximal patency was reached (5-6 weeks post-exposure). Infected field snails (B. pfeifferi) shedding cercariae were differentially identified by ELISA, with 100% sensitivity and specificity, from uninfected field snails and from snails naturally infected with other trematodes (echinostomes and strigeids). Prepatent infections with S. mansoni were readily identified by ELISA in field snails. A case is demonstrated where infection rate, as determined by shedding test alone, was 9.8%, whereas the combined figure of prepatent and patent infection rates was 22.9%

Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya.

To assess the efficacy of low dose praziquantel regimens in comparison with standard 40 mg/kg dosing in the treatment of urinary schistosomiasis, a random allocation dose-finding trial was performed in children and adults from a Schistosoma haematobium endemic region in Coast Province, Kenya. Following an initial screening, 280 individuals with greater than or equal to 50 eggs/10 ml urine were randomly assigned to receive either 10, 20, 30, or 40 mg/kg of the drug in a single oral dose. Two to three months later, cure rates of 26%, 68%, 78%, and 84% were found for the 10, 20, 30, and 40 mg/kg doses, respectively. The results of 10 mg/kg oral dosing were significantly worse than for all other doses in terms of cure rate and of post-treatment prevalence of morbidity. The 40 mg/kg dosing resulted in a significantly higher cure rate than the 20 mg/kg doses; nevertheless, there was no significant difference between 20 mg/kg and 40 mg/kg doses in terms of mean post-treatment intensity of infection or post-treatment prevalence of hematuria or proteinuria. For large-scale control programs, oral 20 mg/kg praziquantel therapy for urinary schistosomiasis may prove as effective as the standard oral 40 mg/kg dosing for control of infection-associated morbidity and reduction of parasite transmission.

Urinary tract morbidity in schistosomiasis haematobia: associations with age and intensity of infection in an endemic area of Coast Province, Kenya.

To gain better understanding of the natural history of Schistosoma haematobium associated disease, age- and intensity-related urinary tract morbidity were assessed in a cross-sectional study of Kilole (population 719) in Coast Province, Kenya. Overall prevalence of infection was 65% (39% light, 16% moderate, 9% heavy). Infection prevalence and mean intensity of infection were highest in the 5-14-year-old bracket for both sexes. Although significant intensity-associated increases in hematuria prevalence were noted for both children and adults in all infection categories, hematuria was more common in those less than 15 years of age. Children had a significant increase in the prevalence of dysuria at higher levels of infection, whereas adults did not. Radiographic study of a 1:9 random sample, stratified for age, revealed a greater prevalence of urinary tract granulomas in those less than 15 years. Subjects greater than 15 years of age had a greater frequency of hydronephrosis. Hydronephrosis, hydroureter, and bladder calcification were not associated with higher infection intensity. Among individuals with bladder calcification, a potential marker of cumulative inflammation, 87% had hydronephrosis or hydroureter, compared to a 40% prevalence among individuals without bladder calcification. These findings suggest that certain structural forms of urinary tract disease, such as hydronephrosis, progress during the course of untreated schistosomiasis haematobia despite age-related reductions in egg burden, whereas other forms of morbidity, such as hematuria, remain sensitive to the level of urinary egg excretion at the time of diagnosis.

Predisposition of humans to infection with Schistosoma mansoni: evidence from the reinfection of individuals following chemotherapy.

In a study of faecal egg counts of Schistosoma mansoni from 359 people of all ages from a rural Kenyan community, a positive association was demonstrated between infection intensity in individuals before treatment and reinfection intensity in the same individuals 9 months after treatment in certain age groups of the sampled population. Consequences and possible causes of these observations are discussed in terms of the epidemiology and control of schistosomiasis.

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.

Chronic splenomegaly in Nairobi, Kenya. II. Portal hypertension.

Eighty-five patients with chronic splenomegaly and proven oesophageal varices were studied at Kenyatta National Hospital, Nairobi. The major defined groups were hepatosplenic schistosomiasis (24%), cirrhosis (20%) and portal vein occlusion (11%). Hyper-reactive malarial splenomegaly (tropical splenomegaly syndrome) was considered as the cause of oesophageal varices in only one patient. In 26% of cases liver biopsy was non-diagnostic and the extrahepatic portal vein was demonstrated radiologically to be patent. Such patients were thought to be suffering from idiopathic portal hypertension, not previously described elsewhere in Africa. Hepatitis B surface antigen was detected in 12% of controls and in 58% of patients with cirrhosis (p less than 0.001). Some serological marker of previous hepatitis B virus infection was present in 92% of patients with cirrhosis and in 79% of controls. Kamba patients from Machakos and Kitui Districts were significantly more prevalent than expected among these 85 cases of portal hypertension.

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 quantitative and qualitative antibody responses to tegumental membrane antigens prepared from adult worms.

Quantitative antibody responses of individual Kenyan children to a tegument membrane preparation from adult schistosomes have been studied by enzyme-linked immunosorbent assay. Qualitative differences between patients were examined by electrophoretic fractionation of the membrane preparation followed by Western blotting analysis. All individuals had antibodies to the preparation, the level increasing twofold shortly after chemotherapy and declining to pre-treatment levels by 6 months. Susceptible children had significantly higher levels of antibody than resistant individuals at 12 and 18 months after chemotherapy. Antibody levels were positively associated with patient age (particularly over the range 8-12 years at the first bleed after chemotherapy) and the logarithm of pre-treatment egg excretion. The strongest association was observed between initial antibody level and subsequent levels. A total of 47 distinct antigens was detected in the membrane preparation. The major antigens were detected equally strongly by sera from both susceptible and resistant groups of children. At the outset the resistant group responded more strongly to 35%, and more weakly to 15%, of the antigens than the susceptible group. At the end of the study the figures were reversed, being 21% and 38% respectively, probably reflecting the reflecting the reinfection of the susceptible group. 3 antigens of molecular mass 100, 50 and 27 kDa were exceptions to the trend, being detected more strongly by the resistant than the susceptible group at one or more later times. It was concluded that the differences in total antibody level to the tegument membrane preparation were insufficient to account for the resistant or susceptible status of the children.

Chronic splenomegaly in Nairobi, Kenya. I. Epidemiology, malarial antibody and immunoglobulin levels.

Chronic splenomegaly in 131 Kenyan patients was investigated at Kenyatta National Hospital, Nairobi. Patients were allocated to diagnostic groups on the basis of clinical, haematological, parasitological, histological, radiological and endoscopic data. The major diagnostic groups were hyper-reactive malarial splenomegaly, our preferred name for tropical splenomegaly syndrome, (31%), hepatosplenic schistosomiasis (18%), visceral leishmaniasis (5%) and "indeterminate splenomegaly", where no diagnosis could be reached (12%). Another 20% of patients were suffering from various non-schistosomal forms of portal hypertension. A number of specific and rarer causes accounted for the rest of the cases. The tribal and geographical distribution of patients with chronic splenomegaly was compared with the pattern of general medical admissions. Splenomegaly was more frequent than expected in Kamba and Luo patients. Hyper-reactive malarial splenomegaly and hepatosplenic schistosomiasis were common in both groups, whereas visceral leishmaniasis was almost restricted to the Kamba and indeterminate splenomegaly was especially prevalent in the Luo. Malarial antibody and immunoglobulin levels differed significantly between the various diagnostic categories of patients and controls. Malarial serology can be diagnostically useful for chronic splenomegaly, provided results are interpreted in their geographical context.

Immunoglobin M and malarial antibody levels in hyper-reactive malarial splenomegaly.

In a study of chronic splenomegaly in Kenya, hyper-reactive malarial splenomegaly, our preferred name for tropical splenomegaly syndrome, was diagnosed in 38 patients. This diagnosis was based on exclusion of other conditions and observations of hepatic sinusoidal lymphocytosis on liver biopsy. To assess the previously recommended diagnostic criterion of elevation of serum IgM, to two standard deviations (s.d.) above the local mean, serum IgM levels were measured in patients and in 90 geographically matched controls. Patients with IgM levels 2 s.d. above the local mean were compared with those with lower levels. No differences were found other than higher malarial antibody titres in the group with higher IgM levels. Agreement is required concerning diagnostic criteria for hyper-reactive malarial splenomegaly; other features of the syndrome may occur in the absence of marked IgM elevation.

Hepatosplenic schistosomiasis in Kenya: an assessment of the enzyme-linked immunosorbent assay (ELISA).

Sera from 124 adult Kenyan patients with chronic splenomegaly and from 93 geographically matched controls without splenomegaly were tested for evidence of Schistosoma mansoni infection by enzyme-linked immunosorbent assay (ELISA). Ova of S. mansoni were detected on stool or rectal snip examination in 23.4% of all patients, whereas 57.3% had a positive ELISA. All patients with parasitological or histological evidence of schistosomal infection had a positive ELISA, and a negative test reliably excluded schistosomiasis. On the basis of liver histology, 23 patients (18.5%) were considered to have hepatosplenic schistosomiasis, of whom 17 (73.9%) had a positive stool or snip. The ELISA was positive in 47.5% of cases of non-schistosomal splenomegaly, and in 52.7% of apparently normal controls. This high seropositive rate in the latter two groups emphasizes that schistosomal infection does not signify disease, and limits the diagnostic value of the test in individual cases of splenomegaly. Marked tribal and, therefore geographical, differences were noted in the prevalence of infection.

The effect of repeated targeted mass treatment on the prevalence of schistosomiasis mansoni and the intensity of infection in Machakos, Kenya.

In a valley in Machakos District, Kenya, the entire population was surveyed in 1976 for the presence and number of eggs of Schistosoma mansoni in their faeces. All persons with 300 or more eggs g-1 faeces were then treated with a single dose of hycanthone, 1.5 mg kg-1 body-weight. A re-survey was carried out in 1977, followed by the treatment of all persons with 200 or more eggs g-1 faeces. After another re-survey in 1978, all persons with 100 or more eggs g-1 were treated. The final survey was carried out in 1981. It was found that the treatment of persons with a high egg output had a pronounced effect on the intensity of infection in the total population, but that, after a first considerable drop in the prevalence rate, further decreases were much smaller. Continuing moderate prevalence rates in very young children were an indication of continuing transmission.

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.