Chemotherapy for Schistosomiasis in Ugandan Fishermen: Treatment Can Cause a Rapid Increase in Interleukin-5 Levels in Plasma but Decreased Levels of Eosinophilia and Worm-Specific Immunoglobulin E

Abstract

Chemotherapy for blood-dwelling schistosomes kills the worms and exposes parasite antigen to the circulation. In many people from areas of endemicity, this treatment increases parasite-specific immunoglobulin E (IgE) and other Th2 responses in the months following therapy, responses that have been associated with subsequent resistance to reinfection. Here we investigate much earlier changes in immune reactions after praziquantel therapy in Schistosoma mansoni-infected fishermen working in an area of high transmission in Uganda. The subjects gave blood before treatment and at 1 and 21 days posttreatment. Blood cultures were incubated with schistosome soluble worm antigen (SWA) or soluble egg antigen (SEA). Interleukin-4 (IL-4), IL-5, IL-10, IL-13, gamma interferon, and transforming growth factor ␤ levels were measured in the cultures and in plasma. A marked transient increase in plasma IL-5 levels was observed in 75% of the subjects (n ‫؍‬ 48) by 1 day posttreatment. This response was dependent on pretreatment intensity of infection and was accompanied by a transient decrease in eosinophil numbers. One day posttreatment, blood cultures from the 16 subjects with the greatest increase in plasma IL-5 level (>100 pg/ml) displayed reduced IL-5, IL-13, and IL-10 responses to SWA, and in contrast to the rest of the cohort, these high-IL-5 subjects displayed reduced levels of SWA-specific IgE in plasma 21 days posttreatment. Twenty months after treatment, the intensity of reinfection was positively correlated with the increase in plasma IL-5 level seen 1 day posttreatment. These studies describe the heterogeneity in early immune reactions to treatment, identifying subgroups who have different patterns of reaction and who may have different capacities to mount the responses that have been associated with resistance to reinfection.Schistosomiasis is a condition caused by parasitic helminths of the genus Schistosoma, with S. mansoni, S. haematobium, and S. japonicum accounting for most of the world's estimated 200 million cases of human schistosomiasis. The disease is contracted from waterborne larvae that penetrate the skin and enter the bloodstream, where they develop, pair, and reach sexual maturity. Adult pairs of S. mansoni reside in the mesenteric veins of the intestine, where each female lays up to 300 eggs per day.In numerous treatment studies carried out in areas of endemicity (4,6,7,11,12,16,23,45,46), the intensity of reinfection after chemotherapy has been shown to be highest in children and adolescents and then to decrease during adult life. This suggests that acquired resistance to infection may develop gradually with age. It has, however, been difficult to draw firm conclusions from these age profiles, as in most communities of endemicity adults have less contact with infected water than do children. For this reason, Kabatereine et al. (28) examined the intensity of S. mansoni reinfection in a Ugandan fishing community following treatment with praziquantel (PZQ). Due to occupational contact with water in the...

Ecology of Biomphalaria (Gastropoda: Planorbidae) in Lake Albert, Western Uganda: snail distributions, infection with schistosomes and temporal associations with environmental dynamics

“…In Uganda the distribution and extent of schistosomiasis is relatively well known (Booth et al, 2004;Fitzsimmons et al, 2004;Kabatereine et al, 2004); intestinal schistosomiasis occurs in 38 out of 56 Ugandan districts and is caused by infection with the trematode blood fluke Schistosoma mansoni while the urinary form of schistosomiasis, caused by infection with Schistosoma haematobium, is totally confined within 2 districts surrounding Lake Kwania and Kyoga (Bradley et al, 1967;Kabatereine, 2000. Many of these predominantly semi-rural communities are in daily contact with schistosome-infested water and in certain places infections can be universal within school-aged children (Stothard et al, 2005).…”

Eosinophil Activity inSchistosoma mansoniInfections In Vivo and In Vitro in Relation to Plasma Cytokine Profile Pre- and Posttreatment with Praziquantel

“…We previously reported that treatment induced significant changes in circulating eosinophil numbers in S. mansoni-infected Ugandan fishermen (24). In the present study, we examine in detail the eosinophil activity before treatment and 24 h and 3 weeks posttreatment in vivo and in vitro in a subgroup of these fishermen in relation to plasma cytokine levels and infection intensities.…”

“…Diluted blood was dispensed into 48-well plates (flatbottomed wells; Costar, United Kingdom) and stimulated with soluble worm antigen (SWA) or soluble egg antigen (SEA) (final concentration, 10 g/ml) or incubated with medium alone. Antigens were prepared as previously described (24,31). All cultures were set up in duplicate wells, and the plates were incubated at 37°C in sealed boxes after the addition of a "gas-generating kit" (Oxoid Ltd., United Kingdom), providing a 5% CO 2 atmosphere.…”

“…Interleukin-4 (IL-4), IL-5, IL-6, eotaxin, RANTES, tumor necrosis factor alpha (TNF-␣), transforming growth factor ␤ (TGF-␤), IL-10, IL-13, and gamma interferon (IFN-␥) were measured using an in-house sandwich ELISA as previously described in detail (24,31). The standard operating procedure for the IL-10 assay, however, was slightly modified compared to the previously reported standard operating procedure, as subsequent studies and retesting of plasma from the same study population indicated that heterophilic antibody activity in a small number of subjects was a source of inaccuracy in the IL-10 determinations.…”

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“…In this context, it has been previously suggested that drug-dependent killing of worms in situ might boost protective immunity against reinfection by immunizing with antigens released from dying worms (Dunne et al 1992, Webster et al 1997, Woolhouse & Hagan 1999). More recently, it was shown that the immune responses induced by chemotherapy is heterogeneous, depending on the type of antigen used and time of analysis after treatment (Fitzsimmons et al 2004). However, most of the immunological studies after schistosomiasis treatment were undertaken in chronically infected patients living in endemic areas.…”