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Previous population-based studies have examined treatment impact on Schistosoma-associated urinary tract disease among children, but much less is known about longer-term treatment benefits for affected adult populations in areas where risk of recurrent infection is high. In communities in Msambweni, along the Kenya coast, we identified, using a portable ultrasound, 77 adults (aged 17-85) with moderate-to-severe obstructive uropathy or bladder disease due to Schistosoma haematobium. Treatment response was assessed by repeat ultrasound 1-2 years after praziquantel (PZQ) therapy and compared with interval changes among age- and sex-matched infected/treated control subjects who did not have urinary tract abnormalities at the time of initial examination. Of the 77 affected adults, 62 (81%) had improvement in bladder and/or kidney scores after treatment, 14 (18%) had no change, and one (1.3%) had progression of disease. Of the 77 controls, 75 (97%) remained disease free by ultrasound, while two (3%) had apparent progression with abnormal findings on follow-up examination. We conclude that PZQ therapy for S. haematobium is effective in significantly reducing urinary tract morbidity from urogenital schistosomiasis among adult age groups, and affected adults stand to benefit from inclusion in mass treatment campaigns., (© The American Society of Tropical Medicine and Hygiene.)

Late benefits of remote antischistosomal therapy were estimated among long-term residents of an area with high transmission of Schistosoma haematobium (Msambweni, Kenya) by comparing infection and disease prevalence in two local adult cohorts. We compared 132 formerly treated adults (given treatment in childhood or adolescence > or = 10 years previously) compared with 132 age- and sex-matched adults from the same villages who had not received prior treatment. The prevalence of current infection, hematuria, and ultrasound bladder abnormalities were significantly lower among the previously treated group, who were found to be free of severe bladder disease. Nevertheless, heavy infection was equally prevalent (2-3%) in both study groups, and present rates of hydronephrosis were not significantly different. Therapy given in childhood or adolescence appears to improve risk for some but not all manifestations of S. haematobium infection in later adult life. Future prospective studies of continued treatment into adulthood will better define means to obtain optimal, community-based control of S. haematobium-related disease in high-risk locations.

Objective: To establish the prevalence of congenital urinary tract abnormalities in a full population-based ultrasound survey of an area of coastal Kenya., Methods: Ultrasound examination of 3118 residents of 912 households, including all available subjects over 2 years of age, residing in five contiguous rural villages 50 km south of Mombasa., Results: Survey findings indicated simple renal ectopia in 11 of 3118 subjects (0.35%) and renal agenesis in three (0.096%). No cases of horseshoe kidney or complex urinary anomaly were detected, and no cases of multiple congenital anomaly were found. Ectopia cases were evenly distributed between men and women, and across the five study villages. None of the individuals affected by renal ectopia were closely related (i.e. <5th-degree relations)., Conclusion: There is an unusually high prevalence of ectopia among unrelated subjects in this area. In this setting, the findings suggest either a common exposure to teratogenetic factors, or a hereditary condition with variable penetrance, where more severely affected individuals are not observed because of foetal/infant mortality.

To estimate their heritable component of risk for Schistosoma haematobium infection intensity and disease, we performed a community-based family study among an endemic population in coastal Kenya. Demography and family linkages were defined by house-to-house interviews, and infection prevalence and disease severity were assessed by standard parasitologic testing and by ultrasound. The total population was 4,408 among 912 households, with 241 identified pedigree-household groups. Although age- and sex-adjusted risk for greater infection intensity was clustered within households (odds ratio = 2.7), analysis of extended pedigree-household groups indicated a relatively low heritability score for this trait (h2 = 0.199), particularly after adjustment for common household exposure effects (adjusted h2 = 0.086). Statistical evidence was slightly stronger (h2 = 0.353) for familial clustering of bladder morbidity, with an adjusted h2 = 0.142 after accounting for household exposure factors. We conclude that among long-established populations of coastal Kenya, heritable variation in host susceptibility is low, and likely plays a minimal role in determining individual risk for infection or disease.

Objective: World Health Organization consensus meetings on 'Ultrasound in Schistosomiasis' in 1996 and 1997 anticipated further challenges in the global implementation of a standardized protocol for morbidity assessment in schistosomiasis mansoni. We evaluated the performance of the qualitative and quantitative components of the new Niamey criteria., Method: Use of the Niamey protocol among 3954 subjects in two linked, cross-sectional ultrasound surveys of Schistosoma mansoni-endemic populations in Egypt and Kenya., Results: There were significant differences between Egyptian and Kenyan sites in prevalence and age distribution of S. mansoni-related hepatic fibrosis (36%vs. 3%, P < 0.001). Protocol image pattern scoring could be performed quickly and was stable to interobserver variation. However, there were unintended but systematic differences between study sites in the measurement of portal vein diameter (PVD) and wall thickness. By Niamey criteria, a high prevalence of portal dilation was scored for normal Egyptian subjects, which reduced the predictive value of image pattern for portal hypertension. Using alternative height-indexing of PVD, image pattern plus PVD findings predicted 15% of Egyptians and 2.5% of Kenyans were at risk for variceal bleeding, whereas locally derived PVD norms estimated 25% of Egyptians and 12% of Kenyans to be at possible risk., Conclusion: Niamey scoring criteria performed acceptably as a relative grading system for disease in schistosomiasis mansoni, but failed to account fully for site-to-site variation in test performance and morbidity prevalence. Consequently, standardized image pattern scoring appears to provide the most useful tool for detection and comparison of S. mansoni-associated morbidity in large-scale surveys.

At present, anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body weight is the recommended treatment for control of urinary tract morbidity caused by Schistosoma haematobium. Although this standard regimen is effective, drug cost may represent a significant barrier to implementation of large-scale schistosomiasis control programs in developing areas. Previous comparison trials have established that low-dose (20-30 mg/kg) praziquantel regimens can effectively suppress the intensity of S. haematobium infection in endemic settings. However, the efficacy of these low-dose regimens in controlling infection-related morbidity has not been determined in a randomized field trial. The present random allocation study examined the relative efficacy of a 20 mg/kg dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder and renal abnormalities associated with S. haematobium infection in an endemic area of Coast Province, Kenya. After a nine-month observation period, the results indicated an advantage to the standard 40 mg/kg praziquantel dose in terms of reduction of infection prevalence and hematuria after therapy (P < 0.01 and P < 0.005, respectively). However, the two treatment groups were equally effective in reducing structural urinary tract morbidity detected on ultrasound examination. We conclude that in certain settings, a 20 mg/kg dose of praziquantel may be sufficient in providing control of morbidity due to urinary schistosomiasis in population-based treatment programs.

Two populations with differing histories of Schistosoma mansoni and hepatitis C infection were compared directly for severity of disease and extent of comorbidity. Demographic, parasitologic, and ultrasound surveys were conducted on 2038 Egyptians and on 2120 Kenyans. Hepatitis B and C serologies and transaminase levels were obtained from a subset at each site. Despite significantly lower prevalence and intensity of infection, Egyptians had a higher prevalence of severe schistosomal fibrosis than Kenyans (36.8% vs. 4.6%). Hepatitis C infection was 3 times more prevalent among Egyptians, and evidence of hepatocellular damage was significantly greater among Egyptians. There was no interaction between S. mansoni infection or disease and the prevalence or severity of hepatitis C. For both infections, the intensity or prevalence of infection was a poor predictor of morbidity. The prevalence of disease in the Egyptian population from different pathogens suggests a generalized susceptibility to inflammatory liver disease.

Severe periportal fibrosis is not an inevitable consequence of infection with Schistosoma mansoni. Genetic predisposition may be a deciding factor in the development of disease. To assess the contribution of genetic factors in the severity of hepatic fibrosis, the degree of familial aggregation was determined in a Kenyan population. Schistosomal fibrosis was identified with hepatic ultrasound and newly proposed World Health Organization criteria, which include both qualitative and quantitative observations. These 2 aspects of the criteria correlated well with one another. The peak prevalence of ultrasound proven fibrosis trailed 5-10 years behind peak prevalence of infection and declined sharply after age 50 years. This pattern was consistent with either resolution of severe fibrosis over 10-20 years or early death of those severely affected. Genetic predisposition appears to be a weak factor in the development of severe disease in this population, since no household or familial aggregation could be identified.

Repeated selective population chemotherapy of school age children reduces infection and morbidity associated with Schistosoma haematobium infection. To examine the long-term effect of this treatment on susceptibility to re-infection and late disease, a cohort of Kenyans (n = 194) were re-examined for infection and urinary tract morbidity 7-13 years after they underwent annual ultrasonography and treatment for an average of 5 years beginning in 1984 as children. Controls were previously untreated age-matched individuals residing in the same or adjacent villages. The overall prevalence and intensity of infection were equivalent between the 2 groups. In contrast, the prevalence of bladder wall pathology was 11-fold lower in previously treated (1.5%) versus untreated subjects (17%). Severe hydronephrosis was completely reversed. These data demonstrate that treatment significantly reduced urinary tract morbidity despite re-infection, and suggest that the important risk factors for urinary tract morbidity in adulthood are cumulative intensity and duration of infection during early adolescence.

The pre- and post-treatment level of eosinophiluria, as measured indirectly by the amount of free or cell bound eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in urine from Schistosoma haematobium-infected Kenyan school children, were measured and compared with intensity of infection (eggs/10 ml of urine), albuminuria and pathological changes as detected by ultrasonography. ECP and EPX were determined by means of specific ELISA methods and levels were determined in both urine supernatants and extracted urine deposits (cells and cell debris). The level of ECP was significantly raised in urine supernatants from infected children compared to controls, whereas high amounts of EPX were found in urine supernatants from infected children as well as from controls. However, the amounts of cell bound ECP and EPX were significantly raised in infected children. In pre-treatment observations significant correlations were demonstrated between egg counts, albuminuria and eosinophiluria as measured by the amount of cell bound ECP and EPX, or ECP in urine supernatants. No such correlations were demonstrated with the amount of EPX in the urine supernatants. Comparable amounts of ECP and EPX could be extracted from the urine deposits from infected children, but due to the high amounts of EPX in urine deposit extracts from controls, extracted ECP gave the best discrimination between infected and non-infected children. While albuminuria disappeared in most children at the 6 week post-treatment follow-up, eosinophiluria persisted in a significant proportion of the treated children indicating continued eosinophil activity in the bladder wall. Detection and quantification of early acute inflammatory reactions using ECP/eosinophils in combination with detection of later stages of bladder pathology using ultrasound may allow for a dynamic evaluation of the pathological process, the morbidity development and post treatment pathological changes in S. haematobium infections.