Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study

Abstract

BackgroundNeutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.MethodsWe prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes.ResultsAmong 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]).ConclusionIncreased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.

Immune evasion and provocation by Mycobacterium tuberculosis

“…M. tuberculosis -specific CD4 + T cells that express PD1 define a population of T cells that have seen antigen and correlate with mycobacterial load 199 . Similarly, circulating natural killer cell counts decrease during active infection and can be used to track treatment response 200 , whereas a high blood neutrophil count correlates with a negative treatment outcome 201 . Thus, exploiting our understanding of host–pathogen interactions has the potential to yield novel TB diagnostics and biomarkers, but paucibacillary disease and the heterogeneity of the host response remain challenges.…”

Anemia and anti-tuberculosis treatment outcome in persons with pulmonary tuberculosis: A multi-center prospective cohort study

“…In addition, a prospective case-control study which enrolled pulmonary TB patients admitted to the emergency department of a referral TB hospital also found that severe anemia composed a prediction score to infer early mortality, which was defined as death within one week of hospital admission [ 24 ]. In a previous study of our group, we demonstrated that increased neutrophil count prior to ATT initiation was associated with unfavorable treatment outcomes [ 25 ]. Herein, neutrophil count and Hb levels had a negative correlation.…”

Type I IFN signaling in the absence of IRGM1 promotesM. tuberculosisreplication in immune cells by suppressing T cell responses

“…2H, I). Excessive neutrophil recruitment and infection is associated with Mtb replication, tissue damage, and progression of Mtb disease in mice and humans 16,[41][42][43][44][45][46][47] . If the critical role for TH1 responses that is lost in Irgm1 -/mice during Mtb infection is control of Mtb infection and replication in neutrophils, then depletion of neutrophils might prolong survival of Mtb-infected Irgm1 -/mice.…”