Iron metabolism disorders of patients with chronic paracoccidioidomycosis

Abstract

Paracoccidioidomycosis (PCM) is caused by Paracoccidioides spp.; during infection, some host mechanisms limit the availability of iron, thereby reducing its reproduction. However, Paracoccidioides spp. can evade the immune defense and, even under limited iron conditions, use this mineral for growth and dissemination. This study evaluated the iron metabolism of 39 patients who were diagnosed with chronic PCM from 2013 to 2021. The forms of iron before treatment and at the time of clinical cure were evaluated based on the following: serum ferritin levels (storage iron); total iron-binding capacity (TIBC) and transferrin saturation (TSAT) level (transport iron); red blood cell (RBC), hemoglobin (Hb), hematocrit (HCT), and soluble transferrin receptor (sTfR) levels; and sTfR/log ferritin ratio (functional iron). The mean age of the patients was 54.5 years (±6.7 years). Most patients were men (97.4%), rural workers (92.1%), and smokers (84.6%); furthermore, most had moderate disease severity (66.7%). After achieving clinical cure, we observed that serum ferritin levels decreased, and parameters of functional iron increased. The extent of alteration in these parameters were more pronounced in severe cases than in to mild or moderate cases. Furthermore, moderate correlations were observed between C-reactive protein and the Hb (r = -0.500; p = 0.002), RBC (r = -0.461; p = 0.005), HCT (r = -0.514; p = 0.001), and iron levels (r = -0.491; p = 0.002). However, it is possible to infer that PCM interferes with functional and storage iron because improvements in these parameters after treatment as well as associations with disease severity were observed. PCM can lead to anemia of inflammation, which can be differentiated from iron deficiency anemia by a careful investigation of the iron form parameters.

Fig 1. Flowchart of the selection of participants with chronic paracoccidioidomycosis (PCM) from 2013 to 2021.

HIV, human immunodeficiency virus.

Fig 2. Comparison of median serum ferritin values before treatment (BT) and at the time of clinical cure (CC) of patients with chronic paracoccidioidomycosis.

Q1, first quartile; Q3, third quartile. Wilcoxon signed rank test.

Fig 3. Boxplot of the inflammatory process evaluation involving CRP during different stages of PCM.

Q1, first quartile; Q3, third quartile; BT, before treatment; CC, clinical cure. Wilcoxon signed rank test.

Fig 4. Pearson’s correlations of C-reactive protein (CRP) with variables used to evaluate the iron forms of patients with chronic paracoccidioidomycosis before treatment (n = 36 patients).

(a) Correlation of CRP with the total iron-binding capacity (TIBC). (b) Correlation of CRP with hemoglobin (Hb). (c) Correlation of CRP with red blood cells (RBCs; total erythrocyte count). (d) Correlation of CRP with hematocrit (HCT).