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Infect. Immun. doi:10.1128/IAI.00757-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Schistosoma japonicum reinfection after praziquantel treatment causes anemia of inflammation

Center for International Health Research, Lifespan Hospitals, Providence, RI, USA (TL, HMC, GCL, JDK, JFF); Department of Pediatrics, Brown University Medical School, Providence, RI, USA (TL, JFF); Department of Immunology, Research Institute for Tropical Medicine, Department of Health, Manila, The Philippines (LPA, DLM, RMO); Department of Pathology and Laboratory Medicine, Brown University Medical School, Providence, RI, USA (JDK); Center for Statistical Sciences, Brown University, Providence, RI, USA (LS); International Health Institute, Brown University, Providence, RI, USA (HMC, STM)

^* To whom correspondence should be addressed. Email: Tjalling_Leenstra{at}Brown.edu,

	Abstract

There is a relationship between schistosomiasis and anemia, though the magnitude and exact mechanisms involved are unclear. In a cohort of 580 Schistosoma japonicum infected 7-30 year-olds from Leyte the Philippines we evaluate the impact of reinfection with S. japonicum after treatment with praziquantel on mean hemoglobin, 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 -0.39 g/dL (95% CI: -0.63, -0.16) lower mean hemoglobin and 1.70 (95% CI: 1.10, 2.61) times higher odds of all-cause anemia, compared to no reinfection. Reinfection was associated with IDA in the high reinfection intensities only. Conversely, reinfection was associated with NIDA in all infection intensities. Reinfection was associated with serum IL-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 non-reinfected individuals. The principle mechanisms involved in S. japonicum-associated anemia is that of pro-inflammatory 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.

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