Description | 1 Laborato´ rio de Inovac¸ões em Terapias, Ensino e Bioprodutos (LITEB), Instituto Oswaldo Cruz, Fundac¸ão Oswaldo Cruz,
Rio de Janeiro, Brazil, 2 Programa Acadeˆ mico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de
Janeiro, Rio de Janeiro, Brazil, 3 Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United
States, 4 Laborato´ rio de Micobacteriologia Molecular, Faculdade de Medicina e Complexo Hospitalar Hospital Universita´ rio
Clementino Fraga Filho—Instituto de Doenc¸as do To´ rax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil,
5 Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador,
Brazil, 6 Instituto Brasileiro para Investigac¸ão da Tuberculose, Fundac¸ão Jose´ Silveira, Salvador, Brazil, 7 Gereˆ ncia de
Micobacteriologia, Fundac¸ão de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil, 8 Laborato´ rio de Inflamac¸ão
e Biomarcadores, Instituto Gonc¸alo Moniz, Fundac¸ão Oswaldo Cruz, Salvador, Brazil, 9 Faculdade de Medicina, Universidade
Federal da Bahia, Salvador, Brazil, 10 Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of
Medicine, Nashville, TN, United States, 11 Secretaria Municipal de Sau´ de do Rio de Janeiro, Rio de Janeiro, Brazil, 12 Instituto
Nacional de Infectologia Evandro Chagas, Fundac¸ão Oswaldo Cruz, Rio de Janeiro, Brazil, 13 Curso de Medicina, Escola
Bahiana de Medicina e Sau´ de Pu´ blica, Salvador, Brazil, 14 Curso de Medicina, Universidade Salvador (UNIFACS), Salvador,
Brazil, 15 Laborato´ rio Reconhecer Biologia, Centro de Biocieˆ ncia e Biotecniologia, Universidade Estadual do Norte
Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil | pt_BR |
Sponsorship | Departamento de Ciência e Tecnologia, Ministério da Saúde,
Brazil and the National Institutes of Allergy and Infectious
Diseases, USA. The work of AK, BA, ES, GA, AC, MF, JL, SC,
VR, BD, TS, and MC-S was supported by grants from NIH
(U01AI069923, R01AI120790). BA, AK, and JL are senior
scientists from the Conselho Nacional de Desenvolvimento
Cientı́fico e Tecnológico (CNPq). MM received a scholarship
from CNPq. MA received a scholarship from Fundação de
Amparo à Pesquisa do Estado da Bahia (FAPESB). MA-P
received a research fellowship from the Coordenação de
Aperfeiçoamento de Pessoal de Nı́vel Superior (CAPES,
finance code: 001). | pt_BR |
Abstract | Background: Neutrophils 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.
Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with cultureconfirmed
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. Results: Among 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]).
Conclusion: Increased 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. | pt_BR |