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Community and International Nutrition

Adjusting for the Acute Phase Response Is Essential to Interpret Iron Status Indicators among Young Zanzibari Children Prone to Chronic Malaria and Helminth Infections^1,2

³ Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853; ⁴ London School of Hygiene and Tropical Medicine, London WC1E 7HT; UK; ⁵ Public Health Laboratory-Ivo de Carneri, Chake Chake, Zanzibar, Tanzania; and ⁶ Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205

The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and -1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever. We then examined the influence of the APR on each iron status indicator using regression analysis with Hb as the outcome variable. Ferritin was inversely related to Hb in the APR-unadjusted model. Adjusting for the APR using reported recent fever alone was not sufficient to reverse the inverse Hb-ferritin relationship. However, using CRP and/or AGP resulted in the expected positive relationship. The best fit model included reported recent fever, AGP and CRP (R² = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models included reported recent fever and AGP but not CRP (R² = 0.253, 0.310, and 0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by the APR, whereas ferritin was immensely affected. Reported recent fever alone cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting if only 1 APP can be measured. However, AGP best predicted the APR in this population.

^* To whom correspondence should be addressed. E-mail: jm453{at}cornell.edu.

Manuscript received 30 January 2009. Initial review completed 16 March 2009. Revision accepted 11 August 2009.

Published online 9 September 2009.