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Abstract Background Schistosoma mansoni and malaria infections are often endemic in the same communities in sub-Saharan Africa, and both have pathological effects on the liver and the spleen. Hepatosplenomegaly associated with S. mansoni is exacerbated in children with relatively high exposure to malaria. Treatment with praziquantel reduces the degree of hepatosplenomegaly, but the condition does not completely resolve in some cases. The present analysis focused on the possibility that exposure to malaria infection may have limited the resolution of hepatosplenomegaly in a cohort of Kenyan schoolchildren. Methods Ninety-six children aged 6–16, from one community in Makueni district, Kenya, were treated with praziquantel. At baseline, all children had hepatomegaly and most had splenomegaly. The source of S. mansoni infection, a river, was molluscicided regularly over the following three years to limit S. mansoni re-infection, whereas malaria exposure was uninterrupted. Hepatic and splenic enlargement was assessed annually outside the malaria transmission season. Results Children living in an area of relatively high exposure to both infections presented with the largest spleens before treatment and at each follow-up. Spleens of firm consistency were associated with proximity to the river. The regression of hepatomegaly was also affected by location, being minimal in an area with relatively low S. mansoni exposure but high exposure to malaria, and maximal in an area with relatively low exposure to both infections. Conclusions The outcome of treating cases of hepatosplenomegaly with praziquantel in this cohort of Kenyan children depended strongly on their level of exposure to malaria infection. Furthermore, a residual burden of hepatosplenic morbidity was observed, which was possibly attributable to the level of exposure to malaria. The results suggest that exposure to malaria infection may be a significant factor affecting the outcome of praziquantel treatment to reduce the level of hepatosplenic morbidity.

Abstract 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 >=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.

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., (Copyright 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

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.

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.

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.