Monocyte fluorescence as a potential biomarker of tuberculosis in a HIV-prevalent setting: a hospital-based study in South Africa

Abstract

Introduction: South Africa (SA) has a high burden of tuberculosis (TB) with human immunodeficiency virus (HIV) coinfection. These patients have higher rates of sputum smear negativity, and TB diagnostics display lower sensitivity. Thus, an inexpensive, non-sputum-based TB biomarker is needed. Monocyte-derived macrophages are critical in the immune response to TB, resulting in characteristic changes in the frequency of various monocyte subsets. Sysmex haematology analysers (Sysmex, Kobe, Japan) measure monocyte activation via monocyte fluorescence (MO-Y). We evaluated MO-Y as a biomarker of TB infection in people living with HIV (PLWH). Other Sysmex extended differential parameters (EDP) and full blood count (FBC) values were assessed as secondary objectives.
Methods: The MO-Y, EDPs, and FBC values were compared among HIV seropositive and seronegative patients tested for TB in a large South African hospital.
Results: There were 120 patients (57 with TB, 63 controls) with an 84% HIV seropositivity rate. MO-Y did not differ significantly between these groups. PLWH with a CD4 count < 100 cells/?l showed significantly higher MO-Y levels, irrespective of TB status. Neutrophil surface fluorescence (NE-SFL, a marker of neutrophil activation) was considerably higher in PLWH with TB than in their HIV-negative counterparts. Possible contributing factors include more pronounced immune activation, worse illness, or concomitant bacterial infection in PLWH with TB. Among the PLWH, those with TB had significantly lower haemoglobin (Hb) levels, CD4 counts, lymphocyte counts, and mean cell volume (MCV) values. The MCV (87.4 fl cut-off value) displayed the strongest utility for discriminating between PLWH with and without TB (area under the curve [AUC] 0.78).
Conclusion: MO-Y is not an effective biomarker for TB. The MCV showed good discriminatory power between PLWH with and without TB at an 87.4 fl cut-off value.