Blood Neutrophil Counts in HIV-Infected Patients with Pulmonary Tuberculosis: Association with Sputum Mycobacterial Load

Andrew D Kerkhoff,Robin Wood,Monica Vogt,David M Lowe,Stephen D Lawn,Pere-Joan Cardona

doi:10.1371/journal.pone.0067956

Abstract

BackgroundIncreasing evidence suggests that neutrophils play a role in the host response to Mycobacterium tuberculosis. We determined whether neutrophil counts in peripheral blood are associated with tuberculosis (TB) and with mycobacterial load in sputum in HIV-infected patients.Methodology/Principal FindingsAdults enrolling in an antiretroviral treatment (ART) clinic in a Cape Town township were screened for TB regardless of symptoms. Paired sputum samples were examined using liquid culture, fluorescence microscopy, and the Xpert MTB/RIF assay. Absolute neutrophil counts (ANC) were measured in blood samples. Of 602 HIV-infected patients screened, 523 produced one or more sputum samples and had complete results available for analysis. Among these 523 patients, the median CD4 count was 169×109/L (IQR, 96–232) and median ANC was 2.6×109/L (IQR, 1.9–3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients. Patients with TB had a median ANC of 3.4×109/L (IQR, 2.4–5.1) compared to 2.5×109/L (IQR, 1.8–3.4) among those who were culture negative (p<0.0001). In multivariable analyses, having pulmonary TB was associated with an adjusted risk ratio (aRR) of 2.6 (95%CI, 1.5–4.5) for having an ANC level that exceeded the median value (ANC ≥2.6×109/L; p = 0.0006) and an aRR of 6.8 (95%CI, 2.3–20.4) for having neutrophilia defined by a neutrophil count exceeding the upper limit of the normal range (ANC >7.5×109/L; p = 0.0005). Patients were then classified into four mutually exclusive groups with increasing sputum mycobacterial load as defined by the results of culture, Xpert MTB/RIF and sputum smear microscopy. Multivariable analyses demonstrated that increasing sputum mycobacterial load was positively associated with blood ANC ≥2.6×109/L and with neutrophilia.Conclusions/SignificanceIncreased blood neutrophil counts were independently associated with pulmonary TB and sputum mycobacterial burden in this HIV-infected patient group. This observation supports the growing body of literature regarding the potential role for neutrophils in the host response to TB.

Highlights

The host response to Mycobacterium tuberculosis (MTB) is complex and incompletely understood. While this response is thought to be predominantly mediated by mononuclear leukocytes, evidence has emerged in recent years suggesting that neutrophils may play a role [1]
Some evidence suggests that neutrophils play a role in both early TB infection and late TB disease the specific roles in host responses and TB pathology remain incompletely defined
We found that pulmonary TB disease was independently associated with increased blood neutrophil counts and that these parameters were positively associated with sputum mycobacterial load

Summary

Introduction

The host response to Mycobacterium tuberculosis (MTB) is complex and incompletely understood While this response is thought to be predominantly mediated by mononuclear leukocytes, evidence has emerged in recent years suggesting that neutrophils may play a role [1]. Neutrophils appear to have a phagocytic role, but they produce antimicrobial peptides such as cathelicidin LL-37, which has immunomodulatory functions as well as direct activity against MTB [3,4]. These findings suggest that neutrophils may play an important role as part of the innate host response to mycobacteria and contribute to the early control of MTB infection. We determined whether neutrophil counts in peripheral blood are associated with tuberculosis (TB) and with mycobacterial load in sputum in HIV-infected patients

Methods

Results

Conclusion