A 14-year follow-up of ultrasound-detected urinary tract pathology associated with urogenital schistosomiasis in women living in the Msambweni region of coastal Kenya.

BACKGROUND: Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. METHODS: Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. RESULTS: Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. CONCLUSIONS: Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.

Evaluation of morbidity in Schistosoma mansoni-positive primary and secondary school children after four years of mass drug administration of praziquantel in western Kenya.

BACKGROUND: World Health Organization guidelines recommend preventive chemotherapy with praziquantel to control morbidity due to schistosomiasis. The primary aim of this cross-sectional study was to determine if 4 years of annual mass drug administration (MDA) in primary and secondary schools lowered potential markers of morbidity in infected children 1 year after the final MDA compared to infected children prior to initial MDA intervention. METHODS: Between 2012 and 2016 all students in two primary and three secondary schools within three kilometers of Lake Victoria in western Kenya received annual mass praziquantel administration. To evaluate potential changes in morbidity we measured height, weight, mid-upper arm circumference, hemoglobin levels, abdominal ultrasound, and quality of life in children in these schools. This study compared two cross-sectional samples of Schistosoma mansoni egg-positive children: one at baseline and one at year five, 1 year after the fourth annual MDA. Data were analyzed for all ages (6-18 years old) and stratified by primary (6-12 years old) and secondary (12-18 years old) school groups. RESULTS: The prevalence of multiple potential morbidity markers did not differ significantly between the egg-positive participants at baseline and those at 5 years by Mann Whitney nonparametric analysis and Fisher's exact test for continuous and categorical data, respectively. There was a small but significantly higher score in school-related quality of life assessment by year five compared to baseline by Mann Whitney analysis (P = 0.048) in 13-18 year olds where malaria-negative. However, anemia was not positively impacted by four annual rounds of MDA, but registered a significant negative outcome. CONCLUSIONS: We did not detect differences in morbidity markers measured in a population of those infected or re-infected after multiple MDA. This could have been due to their relative insensitivity or a failure of MDA to prevent morbidity among those who remain infected. High malaria transmission in this area and/or a lack of suitable methods to measure the more subtle functional morbidities caused by schistosomiasis could be a factor. Further research is needed to identify and develop well-defined, easily quantifiable S. mansoni morbidity markers for this age group.

Case-Control Study of Posttreatment Regression of Urinary Tract Morbidity Among Adults in Schistosoma haematobium-Endemic Communities in Kwale County, Kenya.

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 impact of single versus mixed Schistosoma haematobium and S. mansoni infections on morbidity profiles amongst school-children in Taveta, Kenya.

Two schistosome species--Schistosoma haematobium and S. mansoni--with two very different pathological profiles (urogenital versus intestinal), are responsible for the majority of human schistosomiasis infections across sub-Saharan Africa. The aim of this study was to determine whether coinfections have an impact on species-specific morbidity measures when compared to single species infections. Children from two neighbouring schools in Taveta, Kenya were grouped by infection status, i.e. uninfected, single species infections or coinfected. Clinical examination of the liver and spleen by palpation was performed and urinary albumin levels were recorded at baseline and at 12 months after praziquantel administration. Additional ultrasonographic profiles of the children's liver, spleen and bladder were incorporated at follow-up. It was found that S. haematobium-associated urogenital morbidity was lower in the coinfected group relative to single S. haematobium infections, even when infection intensities were taken into account. We also observed an association between S. haematobium infection and liver (intestinal-associated) morbidity regardless of coinfections. The findings reported here suggest that further research should be performed on the impact of S. haematobium infections on liver morbidity as well as to determine the impact of mixed schistosome species infections on human morbidity outcomes across different endemic settings.

Schistosoma mansoni morbidity among school-aged children: a SCORE project in Kenya.

Schistosomiasis control programs aim to reduce morbidity but are evaluated by infection prevalence and intensity reduction. We present baseline cross-sectional data from a nested cohort study comparing indicators of morbidity for measuring program impact. Eight hundred twenty-two schoolchildren 7-8 years of age from Nyanza Province, Kenya, contributed stool for diagnosis of Schistosoma mansoni and soil-transmitted helminths (STH) and blood smears for malaria, and were evaluated for anemia, quality of life, exercise tolerance, anthropometry, and ultrasound abnormalities. Schistosoma mansoni, STH, and malaria infection prevalence were 69%, 25%, and 8%, respectively. Only anemia and S. mansoni infection (adjusted odds ratio [aOR] = 1.70; confidence interval [CI] = 1.03-2.80), and hepatomegaly and heavy S. mansoni infection (aOR = 2.21; CI = 1.19-4.11) were associated. Though anemia and hepatomegaly appeared most useful at baseline, additional morbidity indicators may be sensitive longitudinal measures to evaluate schistosomiasis program health impact.

Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni.

Hepatosplenomegaly among school-aged children in sub-Saharan Africa is highly prevalent. Two of the more common aetiological agents of hepatosplenomegaly, namely chronic exposure to malaria and Schistosoma mansoni infection, can result in similar clinical presentation, with the liver and spleen being chronically enlarged and of a firm consistency. Where co-endemic, the two parasites are thought to synergistically exacerbate hepatosplenomegaly. Here, two potential health consequences, i.e. dilation of the portal vein (indicative of increased portal pressure) and stunting of growth, were investigated in a study area where children were chronically exposed to malaria throughout while S. mansoni transmission was geographically restricted. Hepatosplenomegaly was associated with increased portal vein diameters, with enlargement of the spleen rather than the liver being more closely associated with dilation. Dilation of the portal vein was exacerbated by S. mansoni infection in an intensity-dependent manner. The prevalence of growth stunting was not associated with either relative exposure rates to malarial infection or with S. mansoni infection status but was significantly associated with hepatosplenomegaly. Children who presented with hepatosplenomegaly had the lowest height-for-age Z-scores. This study shows that hepatosplenomegaly associated with chronic exposure to malaria and schistosomiasis is not a benign symptom amongst school-aged children but has potential long-term health consequences.

Hepatosplenomegaly in Kenyan schoolchildren: exacerbation by concurrent chronic exposure to malaria and Schistosoma mansoni infection.

OBJECTIVES: Chronic exposure to malaria exacerbates Schistosoma mansoni-associated hepatosplenomegaly in school-aged children. However, residual hepatosplenomegaly after treatment of S. mansoni with concurrent mollusciciding suggests malaria could be an underlying cause of hepatosplenomegaly. We investigated the role of chronic malaria in childhood hepatosplenomegaly in the presence and absence of concurrent S. mansoni infection. METHODS: Cross-sectional study of children in an study area where transmission of S. mansoni, but not malaria, is restricted to the eastern end. Clinical and ultrasound examinations were conducted, and parasitological and serological tests used to determine S. mansoni infection intensities and comparative exposure levels to malaria. RESULTS: Chronic exposure to malaria, as determined by Pfs-IgG3 levels, was associated with hepatosplenomegaly even in the absence of S. mansoni infection. Children infected with S. mansoni mostly had light to moderate infection intensities but greater enlargement of the liver and spleen than children who did not have schistosomiasis, and for the left liver lobe this was S. mansoni infection intensity dependent. CONCLUSIONS: Children chronically exposed to malaria but without S. mansoni infection can have hepatosplenomegaly, which even light S. mansoni infections can exacerbate in an intensity-dependent manner. Thus, concurrent chronic exposure to S. mansoni and Plasmodium falciparum can have an additive or synergistic effect on childhood morbidity.

The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic Protein (ECP) correlates with the natural course of Schistosoma mansoni infection.

Schistosomiasis is a chronic parasitic infection with over 200 million people infected worldwide. In Schistosoma mansoni infections, parasite-derived eggs get trapped in the liver, causing the formation of granulomas, which may develop into periportal fibrosis and portal hypertension, and thus severe morbidity. Eosinophil cationic protein (ECP) is a secretory protein of eosinophil granulocytes that efficiently kills the larval stage of S. mansoni, but also affects fibroblast functions. We have investigated the prevalence of the ECP gene polymorphism 434(G>C) in two African populations, from an S. mansoni endemic area in Uganda (n=297) and from a non-endemic area in Sudan (n=78), and also compared these with a Swedish population (n=209). The genotype frequencies in the Ugandan population differed significantly from both the Sudanese and Swedish populations (P<0.001). In the Ugandan population there was a significant association between genotype and prevalence of infection (P=0.03), with lower prevalence in subjects with the GG genotype compared with GC (P=0.02) and CC (P=0.03). There was also a trend towards an association with periportal fibrosis (P=0.08) in the Ugandan population. This suggested association was confirmed when the predominant tribe (n=212) was analysed separately (P=0.004). Our results suggest that ECP may be an important protein, both in the immune response against S. mansoni and in the development of periportal fibrosis. The results also suggest genetic selection towards the ECP 434CC genotype in populations living in S. mansoni endemic areas.

Late benefits 10-18 years after drug therapy for infection with Schistosoma haematobium in Kwale District, Coast Province, Kenya.

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.

Regression of hepatosplenomegaly in Kenyan school-aged children after praziquantel treatment and three years of greatly reduced exposure to Schistosoma mansoni.

Evaluating regression of morbidity associated with parasitic infections is an important component of community-based control programmes. We performed an intervention against Schistosoma mansoni infection, focusing on hepatosplenomegaly in the absence of periportal fibrosis, in a cohort of 67 Kenyan children aged 7-18 years from Makueni District, selected on the basis of hepatosplenomegaly detected by ultrasonography. Clinical and ultrasound examinations were conducted annually for three years after treatment, and the source of infection (a river) was regularly treated with molluscicide, thereby severely reducing exposure to schistosomiasis. Malaria transmission was uninterrupted. The prevalence of hard spleens, and the magnitude of clinically assessed splenomegaly along the mid-axillary and mid-clavicular lines decreased monotonically over time, independently of age, whereas clinically measured hepatomegaly along the mid-sternal line and the prevalence of firm livers decreased in an age-specific manner, being more pronounced amongst children aged 14 years or older at enrolment. Ultrasound data were less informative, and did not concur with clinical observations. These results demonstrate that praziquantel treatment reduces hepatosplenomegaly in the absence of exposure to S. mansoni, even with continuing exposure to malaria. The lack of complete resolution of hepatosplenomegaly in most children suggests, among other things, a residual organomegaly attributable to malaria.

High prevalence of ectopic kidney in Coast Province, Kenya.

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.

Micro-geographical variation in exposure to Schistosoma mansoni and malaria, and exacerbation of splenomegaly in Kenyan school-aged children.

BACKGROUND: Schistosoma mansoni and Plasmodium falciparum are common infections of school aged children in Kenya. They both cause enlargement of the spleen, but their relative contribution to the condition of splenomegaly remains unknown in areas where both infections are endemic. Here, we have investigated whether relatively high exposure to both infections has a clinically measurable effect on this condition. METHODS: 96 children aged 6-16 years living along a ten kilometre stretch and within 4 km south of a river that is a source of both S. mansoni and malaria infections were examined clinically for splenomegaly along the mid clavicular line (MCL) and mid axillary line (MAL). The survey was conducted outside the malaria transmission season. The consistency of the organ was recorded as soft, firm or hard. Mapping of the locations of houses and the course of the river was undertaken. Egg counts were mapped at the household level, as were IgG3 responses to Plasmodium falciparum schizont antigen (anti-Pfs IgG3), in order to identify areas with relatively high exposure to both infections, either infection or neither infection. ANOVA was used to test for differences in egg counts, IgG3 levels and the magnitude of spleen enlargement between these areas. RESULTS: 4 contiguous sectors were identified, one where anti-Pfs IgG3 responses and S. mansoni egg counts were both high, one where only anti-Pfs IgG3 responses were high, one where only egg counts were high, and one where both anti-Pfs IgG3 responses and egg counts were low. Spleen MAL and MCL values were significantly higher amongst children from the sector with highest IgG3 levels and highest egg counts but similar amongst children from elsewhere. Both egg counts and anti-Pfs IgG3 responses were significantly higher in children with MAL values > or =4 cm. Hardening of spleens was associated with proximity of domicile to the river. CONCLUSIONS: Micro-geographical variation in exposure to S. mansoni and malaria infections can be exploited to investigate the chronic impact of these two infections. These results provide firm evidence that relatively high exposure to both infections exacerbates splenomegaly even outside the malaria transmission season. Major implications include assessing the burden of infection in school age-children.

Detailed clinical and ultrasound examination of children and adolescents in a Schistosoma mansoni endemic area in Kenya: hepatosplenic disease in the absence of portal fibrosis.

Hepatosplenic schistosomiasis involving organomegaly, portal fibrosis and portal hypertension has been observed in autopsy studies. Here, we have tested the hypothesis that hepatosplenic disease including organomegaly and markers of increased portal pressure can occur in school aged children in the absence of fibrosis. A case-only study of 96 children aged 7-20 years defined by ultrasound detectable hepatomegaly was undertaken in Makueni district, Kenya. A novel method of clinical examination that involved a consensus scoring by three or four examiners was used to classify children as presenting with severe or moderate hepatosplenic disease after palpation of livers and spleens. Ultrasound examination of livers and spleens was based on the Niamey protocol. Clinical measurements included spleen enlargement along the mid-clavicular and mid-axillary lines, liver enlargement along the mid-sternal (MSL) and mid-clavicular lines, as well as organ consistency. The clinical examination indicated that 9% and 60% of the children had severe or moderate hepatosplenomegaly, respectively. Amongst egg-positive children, all clinical measurements, except MSL liver enlargement, correlated with egg count, as did portal vein diameter, spleen length and liver length measured by ultrasound. Peri-portal fibrosis was not observed in any child, whereas 28% of the children were classified as having increased portal pressure according to World Health Organization criteria. There was no effect of malaria parasitaemia or hepatitis seropositvity on any of the observed parameters. These results indicate that hepatosplenic disease in school-aged children attributable to S. mansoni infection, involving hepatosplenomegaly and increased portal vein diameter, can occur in the absence of peri-portal fibrosis.

Low heritable component of risk for infection intensity and infection-associated disease in urinary schistosomiasis among Wadigo village populations in Coast Province, Kenya.

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.

Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender.

Schistosoma mansoni infection is highly endemic in parts of Uganda, and periportal fibrosis is common in communities along the shore of Lake Albert. In this study, we have identified cellular immune responses associated with fibrosis. A cohort of 199 individuals aged 6-50, resident in the village for at least 10 years or since birth, were examined for evidence of periportal fibrosis by ultrasound using the Niamey protocol. Whole-blood samples were assayed for levels of nine cellular immune molecules (IL-3, IL-4, IL-5, IL-10, IL-13, TNF-alpha, IFN-gamma, IL-1beta, and RANTES) in the absence of in vitro Ag stimulation, and after stimulation with egg and worm Ags. A lack of Ag specificity allowed the number of variables in the analysis to be reduced by factor analysis. The resulting factor scores were then entered into a risk analysis using a classification tree algorithm. Children, adult males, and adult females had different factors associated with fibrosis. Most cases of fibrosis in children (eight of nine) were associated with low (<47th percentile) IL-10 factor scores. Adult females at lowest risk had relatively high IFN-gamma factor scores (>83rd percentile), whereas those at highest risk had a combination of intermediate (32nd to 83rd percentile) IFN-gamma and relatively high (>60th percentile) TNF-alpha factor scores. Adult males at lowest risk of fibrosis had moderate TNF-alpha factor scores (55th to 82nd percentile), and a high risk was associated with either high TNF-alpha factor scores (>82nd percentile), or intermediate TNF-alpha combined with low RANTES factor scores (<58th percentile). These results demonstrate that periportal fibrosis is associated with cytokine production profiles that vary with both age and gender.

Prevalence of hepatocellular carcinoma, liver cirhosis and HBV carriers in liver disease patients referred to Clinical Research Centre, Kemri.

The prevalence of HBsAg positivity, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) is studied in 139 patients at the Clinical Research Centre of KEMRI. The prevalences were found to be 15.1%, 9.3 % and 10 % respectively. 14% of the HBsAg positives were also E antigen positive. The positivity of HBsAg in HCC was 42.9% only 15.4% in LC and 57.1% HCC had AFP compared to only 15.4% in LC. It is suggested that the findings support an association of Hepatitis B virus with LC and HCC.

Serological studies and ultrasonographic diagnosis of chronic liver disease in Kenya.

Blood samples were obtained from blood donors and patients with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) from provincial hospitals and Kenyatta National Hospital (KNH). Patients with chronic liver disease (CH, LC and HCC) underwent abdominal ultrasound screening as well. The blood samples were screened for Hepatitis B surface antigen (HBsAg), anti hepatitis C virus (Hep CV) antibodies and alpha fetoprotein (AFP). A total of 44665 blood samples from blood donors were screened for HBsAg between July 1991 and January 1993. Of these 4.1% were found to be HBsAg positive. A total of 983 samples were taken from chronic liver disease patients out of which 22.2% were found to be HBsAg positive. Sixty-three patients were found to have liver cirrhosis and 53 patients had HCC on ultrasound screening. Anti Hep CV antibodies were found in 4.3% (5/116) of patients with LC and HCC. AFP levels were found to be significantly higher in HCC patients than in LC patients, levels of above 200 ng/ml being diagnostic of HCC. Follow up of high risk patients, i.e. those with HBsAg positive, chronic liver disease, by ultrasound screening and AFP detection may be useful in the early detection of HCC.