Schistosoma japonicum Reinfection after Praziquantel Treatment Causes Anemia Associated with Inflammation

Abstract

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.

Anemia Among Children Exposed to Polyparasitism in Coastal Kenya

“…Successful treatment of anemia in this setting should rely on strategies based on this and other evidence of infectionrelated AI frequency. Our findings, combined with those of other recent studies, 6,25,28,29 suggest that both chronic infection and iron deficiency need to be addressed as part of integrated management of childhood anemia.…”

“…What has become more evident over the last decade is that chronic inflammation caused by long-lasting parasitic infections appears to strongly reduce the body's ability to absorb dietary iron (via gut ferroportin) and to use existing body iron stores for erythropoiesis. 6,25 Infection-related AI has been strongly linked to the presence of subclinical infection, both for children with subclinical malaria in Cote d'Ivoire, 6 and for Philippine children having persistent or recurrent low-level Schistosoma japonicum infection after praziquantel therapy. 25,26 Our current study of the mechanisms of anemia associated with prevalence parasitic infections suggests that AI combined with true iron deficiency is the primary source of childhood anemia in this area of coastal Kenya.…”

Reduction in Hookworm Infection after Praziquantel Treatment among Children and Young Adults in Leyte, the Philippines

“…Given the rapid increase after treatment without provision of iron in most studies, much of that improvement is likely caused by amelioration of S. japonicum -related anemia of inflammation. 16,25 It is possible, however, that some of the sustained improvement in hemoglobin found in other studies may be caused by reduction in hookworm burden. Interestingly, a previous study conducted in Leyte, The Philippines, showed that coinfection with S. japonicum and hookworm had a Hookworm: low = 1-1,999 eggs per gram of stool (epg), moderate = 2,000-3,999 epg, high ≥ 4,000 epg.…”

Awareness of Iron Deficiency Anemia among Women of Reproductive Age in Hubei Province, China

“…There is increased awareness due to the media as well. 9 "The burden of iron deficiency can be reduced by taking a more holistic approach that would include promotion of healthy weaning practices and use of appropriate complementary foods, together with improving the nutritional value of such foods. There is an increasing body of peer-reviewed literature to support the contention that "micronutrient Sprinkles" is an effective strategy to improve the nutritional value of home-prepared complementary foods and thus to reduce the burden of iron deficiency among children".…”