In a cross-sectional study of 641 Schistosoma japonicum-infected individuals in Leyte, Philippines, who were 7-30 years old, we determined the grade of hepatic fibrosis (HF) by ultrasound and used anthropometric measurements and hemoglobin levels to assess nutritional status. Serum levels of interleukin (IL)-1, IL-6, and IL-10; tumor-necrosis factor (TNF)-alpha; soluble TNF- alpha receptor I; and C-reactive protein (CRP) were measured to examine the association between these markers of inflammation and HF grade. HF was present in 8.9% of the cohort; the majority of cases were mild (grade I), and severe (grade II or grade III) cases occurred only in male individuals. Compared with individuals without HF, those with severe HF--and, to a lesser degree, those with mild HF--had a significantly lower body-mass index (BMI) and BMI z-score, a higher prevalence of anemia, and a higher level of CRP and were more likely to produce IL-6; furthermore, those with severe HF had a significantly higher level of IL-1, compared with those either without HF or with mild HF. These findings suggest that even mild HF is associated with nutritional morbidity and underscore the importance of early recognition and treatment. In addition, our data are consistent with the hypothesis that, by systemically increasing the levels of the proinflammatory cytokines IL-1 and IL-6, HF causes undernutrition and anemia.

There is a relationship between schistosomiasis and anemia, although the magnitude and exact mechanisms involved are unclear. In a cohort of 580 Schistosoma japonicum-infected 7-to 30-year-old patients from Leyte, The Philippines, we evaluated the impact of reinfection with S. japonicum after treatment with praziquantel on the mean hemoglobin level, iron-deficiency (IDA) and non-iron-deficiency anemia (NIDA), and inflammatory markers. All participants were treated at baseline and followed up every 3 months for a total of 18 months. At each follow-up, participants provided stools to quantify reinfection and venous blood samples for hemograms and measures of iron status and inflammation. After 18 months, reinfection with S. japonicum was associated with a lower mean hemoglobin level (؊0.39 g/dl; 95% confidence interval [95% CI], ؊0.63 to ؊0.16) and 1.70 (95% CI, 1.10 to 2.61) times higher odds of all-cause anemia than those without reinfection. Reinfection was associated with IDA for high reinfection intensities only. Conversely, reinfection was associated with NIDA for all infection intensities. Reinfection was associated with serum interleukin-6 responses (P < 0.01), and these responses were associated with NIDA (P ‫؍‬ 0.019) but not with IDA (P ‫؍‬ 0.29). Our results provide strong evidence for the causal relationship between S. japonicum infection and anemia. Rapidly reinfected individuals did not have the positive treatment effect on hemoglobin seen in nonreinfected individuals. The principle mechanism involved in S. japonicum-associated anemia is that of proinflammatory cytokine-mediated anemia, with iron deficiency playing a role in high-intensity infections. Based on the proposed mechanism, anemia is unlikely to be ameliorated by iron therapy alone.

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.

Aims-To determine frequency, type, determinants, and outcome of malignancies in children with end stage renal failure. Methods-All Dutch patients, aged less than 15 years, who started chronic renal replacement therapy between 1972 and 1992 and who were at least 18 years old on 1 January 1997, were retrospectively studied. Results-Mean follow up from first renal replacement therapy was 15.5 years. Twenty two malignancies were found in 21 of 249 patients. Skin cancer accounted for 59% and non-Hodgkin lymphoma for 23% of malignancies. At 25 years after first renal replacement therapy, the probability of developing a malignancy was 17% (95% CI: 9 to 24%). Compared to the general population the incidence rate for overall cancer was tenfold higher. For nonmelanoma skin cancer and non-Hodgkin lymphoma, standardised risks were 222 and 46 respectively. The use of more than 20 mg/kg cyclophosphamide showed an association with increased risk of malignancy. Six patients died as a result of their malignancy, accounting for 9.5% of overall mortality. Whereas four out of five patients with non-Hodgkin lymphoma died, the most frequent malignancy, skin cancer, did not contribute to mortality. Conclusion-The long term risk of certain malignancies is significantly increased in children who have undergone renal replacement therapy. As an important contributor to overall mortality, awareness of this risk of malignancy in these patients is necessary, especially after treatment with cyclophosphamide. (Arch Dis Child 2001;85:478-483) Keywords: renal replacement therapy; malignancy; follow up The incidence of de novo malignancies in adult recipients of renal transplants is between six and seven times higher than in the general population.1 2 This is thought to be related to the use of immunosuppressive drugs for prevention of graft rejection. Mechanisms through which malignancies can arise include impaired immune surveillance, increased susceptibility to oncogenic viruses, and direct mutagenic eVects of the drugs themselves. [1][2][3] An increased risk of malignancy has also been described in adult dialysis patients: Inamoto et al found this group to have a 1.4-fold increased risk. 4 In adult kidney recipients, post-transplant malignancy is known to be an important cause of morbidity and mortality, with cumulative incidences in long term follow up studies varying from 2.6% to 19.4%.1 2 5-9 Non-melanoma skin cancer is the most frequent malignancy in this group. 1 2 5 6 8 10 11In young adults with renal insuYciency since childhood, malignancy seems to be much less of a problem, with cumulative incidences varying from 0.8% to 3.9% [12][13][14][15] ; lymphoma is the most frequent malignancy.14-16 However, current studies are either based on incomplete data registry or follow up time is relatively short. The long term risk of malignancy in young adults with renal insuYciency since childhood has not been evaluated suYciently.We present data from a Dutch national cohort study on Late EVects of Renal InsuYciency in Children (LERIC). ...