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Schistosoma japonicum Reinfection after Praziquantel Treatment Causes Anemia Associated with Inflammation

Center for International Health Research, Lifespan Hospitals, Providence, Rhode Island,¹ Department of Pediatrics, Brown University Medical School, Providence, Rhode Island,² Department of Immunology, Research Institute for Tropical Medicine, Department of Health, Manila, The Philippines,³ Department of Pathology and Laboratory Medicine, Brown University Medical School, Providence, Rhode Island,⁴ Center for Statistical Sciences, Brown University, Providence, Rhode Island,⁵ International Health Institute, Brown University, Providence, Rhode Island⁶

Received 12 May 2006/ Returned for modification 21 June 2006/ Accepted 11 August 2006

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.

Published ahead of print on 21 August 2006.

Editor: W. A. Petri, Jr.

This article has been cited by other articles:

• King, C. H., Dangerfield-Cha, M. (2008). The unacknowledged impact of chronic schistosomiasis. Chronic Illness 4: 65-79 [Abstract]