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Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load.

ABSTRACT: Increasing 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.Adults 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 169×10(9)/L (IQR, 96-232) and median ANC was 2.6×10(9)/L (IQR, 1.9-3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients. Patients with TB had a median ANC of 3.4×10(9)/L (IQR, 2.4-5.1) compared to 2.5×10(9)/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 ?2.6×10(9)/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 >7.5×10(9)/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 ?2.6×10(9)/L and with neutrophilia.Increased 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.

SUBMITTER: Kerkhoff AD

PROVIDER: S-EPMC3706476 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load.

Kerkhoff Andrew D AD Wood Robin R Lowe David M DM Vogt Monica M Lawn Stephen D SD

PloS one 20130709 7

<h4>Background</h4>Increasing 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.<h4>Methodology/principal findings</h4>Adults 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 ...[more]

PMID: 23874476

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Project description:BACKGROUNDControl of the tuberculosis (TB) pandemic remains hindered in part by a lack of simple and accurate measures of treatment efficacy, as current gold standard markers rely on sputum-based assays that are slow and challenging to implement. However, previous work identified urinary N1, N12-diacetylspermine (DiAcSpm), neopterin, hydroxykynurenine, N-acetylhexosamine, ureidopropionic acid, sialic acid, and mass-to-charge ratio (m/z) 241.0903 as potential biomarkers of active pulmonary TB (ATB). Here, we evaluated their ability to serve as biomarkers of TB treatment response and mycobacterial load.METHODSWe analyzed urine samples prospectively collected from 2 cohorts with ATB. A total of 34 study participants from African countries treated with first-line TB therapy rifampin, isoniazid, pyrazinamide, and ethambutol (HRZE) were followed for 1 year, and 35 participants from Haiti treated with either HRZE or an experimental drug were followed for 14 days. Blinded samples were analyzed by untargeted HPLC-coupled high-resolution TOF-mass spectrometry.RESULTSUrinary levels of all 7 molecules significantly decreased by week 26 of successful treatment (P = 0.01 to P < 0.0001) and positively correlated with sputum mycobacterial load (P < 0.0001). Urinary DiAcSpm levels decreased significantly in participants treated with HRZE as early as 14 days (P < 0.0001) but remained unchanged in cases of ineffective therapy (P = 0.14).CONCLUSIONUrinary DiAcSpm, neopterin, hydroxykynurenine, N-acetylhexosamine, ureidopropionic acid, sialic acid, and m/z 241.0903 reductions correlated with successful anti-TB treatment and sputum mycobacterial load. Urinary DiAcSpm levels exhibited reductions capable of differentiating treatment success from failure as early as 2 weeks after the initiation of chemotherapy, advocating its further development as a potentially simple, noninvasive biomarker for assessing treatment response and bacterial load.FUNDINGThis work was supported by the Clinical and Translational Science Center at Weill Cornell College of Medicine (NIH/NCATS 1 UL1 TR002384-02 and KL2TR000458), the Department of Defense (PR170782), the National Institute of Allergy and Infectious Disease grants (NIAID T32AI007613-16, K24 AI098627, and K23 AI131913), the NIH Fogarty International Center grants (R24 TW007988 and TW010062), NIH grant (R01 GM135926), the Abby and Howard P. Milstein Program in Chemical Biology and Translational Medicine, and the Tuberculosis Research Units Networks (TBRU-N, AI111143).

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Dataset Information

Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load.

Publications

Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load.

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