Elevated Ferritin and Malaria: Cause or Effect?: Table 1

Abstract

To the Editor In the article by Kabyemela et al. [1], the authors demonstrate that patients with higher serum ferritin are more likely to have placental malaria. They conclude that iron deficiency is protective, while being iron replete is a relative risk factor for both the presence and severity of placental malaria. Although this conclusion correlates with the findings of many other studies and may well be correct, we do not feel that it can be extrapolated from the presented data. Elevation of serum ferritin concentration is of course associated with malaria, because it is an acute-phase protein [2-4]. The authors attempt to control for the presence of concomitant inflammation by using differential cutoffs in serum ferritin concentration, depending on C-reactive protein (CRP) level. They derive these values from an article by Leenstra et al. [5]. Notwithstanding the fact that in this referenced article the ferritin concentration cut off of 70 ng/mL in those with elevated CRP levels is purely arbitrary, the authors use these same values solely to define iron deficiency. Although it may be valid to conclude that ferritin levels below certain thresholds represent iron deficiency, to conclude that levels above these thresholds should be equated with an iron-replete state is not valid in the context of either systemic inflammation (from any cause) or malaria parasitemia even in the absence of systemic inflammation (there is ample evidence that asymptomatic malaria increases serum ferritin concentration [2] but does not necessarily increase CRP level [6]). Furthermore, ferritin concentration may be raised in the presence of HIV infection or other chronic diseases, regardless of CRP level [7]. Some data suggest that ferritin concentration may not be affected in patients with malaria parasitemia levels of < 1000 parasites//mL (0.02%) [8], but the patients dis ussed here had far higher median parasitemia levels of 0.4%-1.7% (again, the h gher parasitemia level was found in the group with higher ferritin levels, ex ctly as would be expected in fact, Odunukwe et al. found a strong positive correlation between ferritin level and parasitemia level [2]). If we thus consider the groups as presented in Kabyemela et al. [ 1 ] , we can assess whether the ferritin level is a reliable