Association of baseline white blood cell counts with tuberculosis treatment outcome: a prospective multicentered cohort study

Abstract

Objectives: Tuberculosis (TB) is the leading infectious cause of death in the world. Cheaper and more accessible TB treatment monitoring methods are needed. Here, we evaluated white blood cell (WBC) absolute counts, lymphocyte, and monocyte proportions during TB treatment, and characterized their association with treatment failure. Methods: This multicentered prospective cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included and followed up after two months of treatment and at the end of therapy. Blood counts were compared to treatment outcome using descriptive statistics, logistic regression, and Receiver Operating Characteristic (ROC) analyses. Results: Between December 2017 and August 2020, 198 participants were enrolled, and 152 completed treatment, including 28 (18.5%) drug-resistant patients. The rate of cure at the end of treatment was 90.8% (138/152). WBC absolute counts decreased, and lymphocyte proportions increased throughout treatment. In multivariate analyses, baseline high WBC counts and low lymphocyte proportions were associated with positive sputum culture results at the end of treatment (WBC > 11,450 cells/mm 3 : p = 0.048; lymphocytes <16.0%: p = 0.039; WBC > 11,450 cells/mm 3 and lymphocytes <16.0%: p = 0.024). Conclusion: High WBC counts and low lymphocyte proportions at baseline are significantly associated with the risk of TB treatment failure.

Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study

“…In downstream analyses, patients under immunocompromising treatment, patients with negative cultures at inclusion, and patients who were lost-to-follow-up were excluded. Detailed procedures for microbiological diagnosis, drug sensitivity testing, and therapeutic regimen composition were described previously ( 29 ).…”

“…At every follow-up visit, 10 ml of whole blood were drawn: 4 ml was used for other downstream analyses, 1 ml was collected in EDTA tubes and used to measure whole blood cell counts by standardized automated systems available in the study sites as listed previously ( 29 ), and 5 ml was used for in vitro blood stimulation. For the QFT-P assay, 1 ml of whole blood was seeded directly into each of four QuantiFERON-TB Gold Plus (QFT-P, Qiagen) tubes as per the manufacturer’s instructions.…”

“…Standardized clinical report and data collection forms were implemented to ensure dataset homogeneity as described previously ( 29 ). Data were entered into the CASTOR database system (Version 1.4, Netherlands) ( 36 ), and cleaned and analyzed in R (version 3.6.2).…”

“…The overall QFT-P test was considered positive if either TB1 or TB2 was above their respective thresholds. ROC analyses and logistic regression were performed as described previously ( 29 ). In particular, multivariate logistic regression analyses were adjusted with the combination of variables that minimized the Akaike Information Criterion (AIC) for most tested predictors, while including important adjustment variables (age, sex, drug sensitivity, country).…”

“…The primary objective of this prospective multicentered cohort study was to monitor the plasma IFN- γ response to rmsHBHA and QFT-P antigens during anti-TB treatment. Moreover, recent data collected in the same cohort highlighted an association between baseline circulating white blood cells (WBC) and TB treatment outcome ( 29 ); hence, a secondary objective was to describe rmsHBHA and QFT-P IFN- γ values in subsets of patients stratified according to demographics, immune cell counts, and culture conversion during treatment. For that purpose, we conducted a cohort study in five countries with low- or middle income status and high- or middle TB incidence rates ( 30 ) (Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay), focusing on adult, HIV-uninfected, culture confirmed drug-susceptible or drug-resistant pulmonary TB patients.…”