Malaria Exacerbates Inflammation-induced Bias in Ferritin and Soluble Transferrin Receptor Values

Barffour, Maxwell A.; Schulze, Kerry; Palmer, Amanda; Chileshe, Justin; Kalungwana, Ng’andwe; Wu, Lee; Coles, Christian; Arguello, Margia; Moss, William J.; Keith,

doi:10.9734/ejnfs/2015/21266

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“…The primary exposure of interest was iron status, as defined by ferritin assessed in the low malaria season (September 2012). We previously showed in this population that ferritin concentrations are elevated in inflammation, especially in the context of concurrent malaria (17), regardless of underlying iron status. It is therefore recommended to adjust ferritin concentrations by using indicators of inflammation or infection, to control for potential bias.…”

Section: Subject and Data Collectionmentioning

confidence: 76%

“…In this study, inflammation was defined by using AGP (<1 g/L). Because recent evidence suggests that malaria exacerbates changes in inflammation (17), additional adjustment procedures were implemented to control for the potential effects of baseline malaria on baseline ferritin values. Hence, in our analyses, baseline ferritin concentrations, either corrected or uncorrected for inflammation and malaria, were separately used to define iron status.…”

Section: Subject and Data Collectionmentioning

confidence: 99%

“…To evaluate the potential effect modification by sTfR, we generated a 5-group iron status strata as follows: deficient or reference (as defined above using ferritin), moderate ferritin with high sTfR (>8.3 mg/L), moderate ferritin with normal sTfR (#8.3 mg/L), high ferritin with high sTfR, and high ferritin with normal sTfR. As in the case of ferritin, sTfR was corrected for inflammation and malaria, based on prior evidence from this population (17).…”

Section: Subject and Data Collectionmentioning

confidence: 99%

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High Iron Stores in the Low Malaria Season Increase Malaria Risk in the High Transmission Season in a Prospective Cohort of Rural Zambian Children

Barffour

Schulze

Coles

et al. 2017

The Journal of Nutrition

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Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk. We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation. Data for this prospective study were collected from children aged 4-8 y ( = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 μg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 μg/L, excluding deficient), or high (≥75 μg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline). We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37). Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148.

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Section: Subject and Data Collectionmentioning

confidence: 76%

Section: Subject and Data Collectionmentioning

confidence: 99%

Section: Subject and Data Collectionmentioning

confidence: 99%

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