Anemia Is a Strong Predictor of Wasting, Disease Severity, and Progression, in Clinical Tuberculosis (TB)

Abstract

A typical trait of chronic tuberculosis (TB) is substantial weight loss that concurs with a drop in blood hemoglobin (Hb) levels, causing anemia. In this observational study, we explored Hb levels in 345 pulmonary TB patients. They were divided into anemic or non-anemic groups which related to clinical symptoms, anthropometric measurements, and immune status. Data was obtained in a randomized controlled trial that we previously conducted using nutritional supplementation of TB patients in Ethiopia. A post hoc analysis demonstrated that anemic patients have a higher composite clinical TB score at baseline than non-anemic patients. Consequently, Hb values were significantly lower in underweight patients with moderate to severe disease and/or cavitary TB compared to normal weight patients with mild disease or non-cavitary TB. Anemia was associated with a low body mass index (BMI), low mid-upper arm circumference (MUAC), lower peripheral CD4 and CD8 T cells counts and IFN-γ levels, and a higher erythrocyte sedimentation rate (ESR). Chronic inflammation and TB disease progression appeared to be driven by elevated systemic levels of pro-inflammatory IL-6 in anemic patients. Multivariable modeling confirmed that a low Hb and a low BMI were key variables related to an unfavorable TB disease status. Although Hb levels increased with successful chemotherapy, anemic TB patients maintained a slower clinical recovery compared to non-anemic patients during the intensive phase treatment (two months). In conclusion, anemia is a strong predictor of wasting, disease severity, inflammation, and slower recovery in patients with pulmonary TB.

Keywords: IL-6; anemia; body mass index; clinical symptoms; disease severity; hemoglobin; inflammation; tuberculosis; wasting.

Figure 1

Baseline variables in TB patients with mild versus moderate-severe disease including (A) clinical TB score, (B) BMI, (C) blood Hb, (D) ESR, and (E) IFN-γ, and blood Hb levels in TB patients based on (F) chest X-ray findings, (G) BMI, or (H) MUAC. Combined blood Hb and BMI are shown in (I). Data (mean or mean ± SD) are presented in bar graphs or scatter plots and were analyzed using an unpaired t-test, p < 0.05 *, p < 0.0001 ****. Data in (I) were analyzed using a Chi-square test.

Figure 2

Correlation analyses between the clinical TB score and (A) BMI, (B) blood Hb, and (C) ESR, or blood Hb and (D) BMI, or (E) ESR. There was a strong correlation between BMI and MUAC (F). Correlation was determined using Spearman´s correlation test.

Figure 3

Baseline variables in non-anemic compared to anemic TB patients including (A) blood Hb, (B) clinical TB score, (C) BMI, (D) MUAC, (E) ESR, (F) CD4 T cell counts, (G) CD8 T cell counts, and (H) IFN-γ. Data (mean or mean ± SD) are presented in bar graphs or scatter plots and were analyzed using an unpaired t-test, p < 0.05 *, p < 0.005 **, p < 0.0005 ***, p < 0.0001 ****.

Figure 4

Longitudinal changes in non-anemic (light-grey bars) versus anemic (white bars) TB patients: (A) clinical TB score, (B) blood Hb levels, (C) the numbers of non-anemic and anemic TB patients, (D) blood Hb levels in TB patients based on their vitD₃ status at baseline, (E) plasma vitD₃ levels, and (F) the number of anemic TB patients in the placebo group (grey bars) or in the intervention group (dark-grey bars) at weeks zero (baseline), four, eight, and 16. Data (mean ± 95% CI) from placebo-treated TB patients (n = 143) are shown in bar graphs and were analyzed using a two-way ANOVA and Sidak´s multiple comparisons test, while Hb levels (mean) in TB patients (n = 345) with sufficient, insufficient, deficient, or severely deficient 25(OH)D₃ levels are shown in the dot plot graph and were analyzed using a one-way ANOVA and Holm–Sidak´s multiple comparisons test, p < 0.05 *, p < 0.01 **, p = 0.0001 ***, p < 0.0001 ****, ns = not significant.

Figure 5

Peripheral IL-6 (A–C) and IFN-γ (D–F) levels in TB patients (n = 30) and healthy controls (n = 19) and in different sub-groups of TB patients. Longitudinal changes in (G) IL-6 levels, (H) IFN-γ levels, and (I) blood Hb levels in the TB patients at weeks zero (baseline), four, eight, and 16. Correlation analyses between IL-6 and (J) the clinical TB score, (K) blood Hb, and (L) IFN-γ levels as determined using Spearman´s correlation test. Data (median) from placebo-treated TB patients (n = 30) are shown in scatter plots and were analyzed using a Mann–Whitney test, p < 0.05 *, p < 0.0001 ****, while longitudinal data (median ± IQR) are shown in bar graphs and were analyzed using a Friedmans test, p < 0.05 *, p = 0.0001 ***, p < 0.0001 ****.