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.

Serological responses among individuals in areas where both schistosomiasis and malaria are endemic: cross-reactivity between Schistosoma mansoni and Plasmodium falciparum.

We examined specific immunoglobulin G1 (IgG1) and IgG3 responses to Plasmodium falciparum schizont and Schistosoma mansoni egg and worm antigens in individuals from Kenya, Uganda, and the Sudan who had been exposed to malaria and schistosomiasis. A strong correlation between malaria- and schistosome-specific IgG3 responses was observed. This association appears to result from the presence of cross-reactive components of the 2 parasites that bind IgG3 antibodies, rather than to be mediated by immunological cross-regulation or specific regulatory mechanisms induced by either parasite. Cross-reactivity of IgG3 antibodies was confirmed in a Brazilian cohort of individuals living in an area where schistosomiasis is endemic but no malaria occurs and in a Pakistani cohort from an area where malaria is endemic but no schistosomiasis occurs. An IgG3 interaction with antigens from both parasites was observed in individuals from both cohorts, but not in uninfected European control subjects. The immunological and biological implications of this observation require further exploration.

Associations between anti-Schistosoma mansoni and anti-Plasmodium falciparum antibody responses and hepatosplenomegaly, in Kenyan schoolchildren.

Schoolchildren from 2 areas of Kenya, Kangundo and Kambu, have contrasting prevalences of hepatosplenomegaly, despite having similar prevalences and intensities of Schistosoma mansoni infection. However, in individual children, S. mansoni infection intensity is positively correlated with organomegaly. In a previous study, hepatosplenomegaly was associated with Th1-type anti-schistosome cytokine responses. Although the high-morbidity Kambu area had higher malaria transmission than did low-morbidity Kangundo, hepatosplenomegaly was not associated with clinical malaria or with patent malarial parasitemia. However, chronic exposure to malaria might be involved. Here, retrospectively, we assayed plasma from this original study, for anti-Plasmodium falciparum and anti-S. mansoni antibodies, to test whether greater exposure to Plasmodium was a cofactor for hepatosplenomegaly. We found that hepatosplenic children had significantly higher levels of anti-P. falciparum antibodies, compared with nonhepatosplenic children, a finding that strongly suggests that some experience of P. falciparum influenced the development of hepatosplenomegaly in these S. mansoni-infected children.

The relationship between age, sex, egg-count and specific antibody responses against Schistosoma mansoni antigens in a Ugandan fishing community.

In schistosomiasis endemic areas, antibody isotype responses against Schistosoma mansoni antigens vary with host age, sex and duration or intensity of infection, and are associated with susceptibility or resistance to infection. Identifying the quality and quantity of these responses is important to our understanding of the host-parasite relationship; however, the various host and parasite factors have a strong tendency to confound each other. We investigated the relationships and interactions between age, sex, faecal egg-counts and specific antibody isotype (IgA, IgG1, IgG2, IgG3, IgG4, IgE, IgM) responses to S. mansoni worm (SWA) and egg (SEA) antigens, amongst 380 individuals aged 5-59 from a fishing community from Uganda. This community was characterized by high levels of exposure, and high infection intensities, with higher infection intensities in males than in females. Multivariate anova was conducted with interaction terms between the three categorized explanatory variables. Most anti-SWA responses increased with age, whereas anti-SEA responses tended to decline with age, especially after puberty. IgG1-SWA, IgG4-SWA, IgG4-SEA, IgE-SWA responses increased with egg count, whereas IgG2-SEA decreased with egg count. IgG1-SWA, IgG4-SWA, IgE-SWA and IgG4-SEA responses were independently higher in males, whereas IgG2-SEA responses were independently higher in females. The significant effects of sex on isotype responses to adult worm antigens may be partly because of different levels of cumulative exposure. IgG4-SEA and IgG4-SWA were both strongly correlated with egg count. Patterns of IgE-SWA responses were qualitatively different to IgG4 responses, suggesting independent pathways of regulation.