A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils.

IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils. Up-regulation of intracellular IL-13 in eosinophils was also associated with eosinophil expression of ST2L, the IL-33 receptor. IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure.

Hepatosplenomegaly associated with chronic malaria exposure: evidence for a pro-inflammatory mechanism exacerbated by schistosomiasis.

In sub-Saharan Africa, chronic hepatosplenomegaly, with palpable firm/hard organ consistency, is common, particularly among school-aged children. This morbidity can be caused by long-term exposure to malaria, or by Schistosoma mansoni, and it is exacerbated when these two occur together. Although immunological mechanisms probably underlie the pathogenic process, these mechanisms have not been identified, nor is it known whether the two parasites augment the same mechanisms or induce unrelated processes that nonetheless have additive or synergistic effects. Kenyan primary schoolchildren, living in a malaria/schistosomiasis co-transmission area, participated in cross-sectional parasitological and clinical studies in which circulating immune modulator levels were also measured. Plasma IL-12p70, sTNF-RII, IL-10 and IL-13 levels correlated with relative exposure to malaria, and with hepatosplenomegaly. Soluble-TNF-RII and IL-10 were higher in children infected with S. mansoni. Hepatosplenomegaly caused by chronic exposure to malaria was clearly associated with increased circulating levels of pro-inflammatory mediators, with higher levels of regulatory modulators, and with tissue repair cytokines, perhaps being required to control the inflammatory response. The higher levels of regulatory modulators amongst S. mansoni infected children, compared to those without detectable S. mansoni and malarial infections, but exposed to malaria, suggest that S. mansoni infection may augment the underlying inflammatory reaction.

Intestinal polyparasitism in a rural Kenyan community.

BACKGROUND: Polyparasitism seems to be a common feature in human populations in sub-Saharan Africa. However, very little is known about its epidemiological significance, its long term impact on human health or the types of interactions that occur between the different parasite species involved. OBJECTIVES: To determine the prevalence and co-occurrence of intestinal parasites in a rural community in the Kibwezi, Makueni district, Kenya. DESIGN: A cross sectional study. SETTING: Kiteng'ei village, Kibwezi, Makueni district, between May and September 2006. SUBJECTS: One thousand and forty five who comprised of 263 adult males, 271 adult females > 15 years of age and 232 boys, and 279 girls <15 years of age. INTERVENTIONS: All infected members of the community were offered Praziquantel (at dosages of 40 mg/kg body weight) for Schistosomiasis and Albendazole (600 mg) for soil transmitted helminths. RESULTS: A total of ten intestinal parasite species (five protozoan and five helminth parasite species) were present in this community and polyparasitsm was common in individuals 5-24 years of age with no gendar related differences. Most of the infections were mild. The protozoan parasites of public health significance present were Entamoeba histolytica and Giardia lamblia with prevalence of 12.6% and 4.2%, respectively. The helminth parasites of public health significance in the locality were Schistosoma mansoni with a prevalence of 28%, and hookworms prevalence of 10%. About 53% of the study population harboured intestinal parasite infections, with 31% of the infected population carrying single parasite species infections, and 22% harbouring two or more intestinal parasite species per individual. Significant positive associations (p values <0.05) were observed between S. mansoni and hookworms, hookworms and Hymenolepis. nana and Entamoeba histolytica and Entamoeba coli. CONCLUSION: Intestinal polyparasitism was common in the Kiteng'ei community, particularly in individuals aged of 5-24 years old. An integrated control programme of approach would be recommended for the control of S. mansoni, hookworms and Entamoeba histolytica for this community.

Hepatosplenic morbidity in two neighbouring communities in Uganda with high levels of Schistosoma mansoni infection but very different durations of residence.

Peri-portal fibrosis can be a serious sequelae of Schistosoma mansoni infection. Age or duration of exposure have been identified as important risk factors, but their relative importance cannot be easily separated. Here, we have compared two cohorts, aged 6-50 years and resident for ten years or since birth, from two neighbouring villages (Booma and Bugoigo) on the eastern shore of Lake Albert, Uganda. Parasitological measurements were similar, whereas the prevalence of peri-portal fibrosis was 5-fold higher in Booma. Data from the cohorts were pooled to assess the relative contribution of age and duration of residency on the risk of disease. Amongst adults, duration of residency was the critical risk factor--individuals aged 17-31 years resident for more 22 years had an almost 12-fold increased risk of fibrosis than those resident for less than 15 years. Height-standardised Splenic Vein Diameter (SVD), Portal Vein Diameter (PVD), Para-sternal Liver Length (PLL) and Spleen Length (SL) values were all higher in Booma, and each organometric parameter except PLL increased with the severity of fibrosis. Our results clearly demonstrate that duration of exposure is a critical risk factor for the development of peri-portal fibrosis and its sequelae in adults. This parameter should therefore be a routine measurement during epidemiological surveys of S. mansoni.

High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni.

In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.