RESUMO Objetivo o diagnóstico da tuberculose pleural (TBpl) é um desafio devido à sua natureza paucibacilar e à necessidade de procedimentos invasivos. Este estudo visou identificar variáveis facilmente disponíveis, bem como construir um modelo preditivo para o diagnóstico da TBpl que possa permitir a utilização de uma estratégia alternativa precoce e acessível em unidades de cuidados básicos de saúde. Métodos um estudo transversal observacional comparou pacientes com TB e não TB seguidos em um hospital terciário brasileiro entre 2010 e 2018. Foi realizada uma análise de regressão logística incondicional que foi validado e aplicado em um modelo de classificação de árvore de decisão (CAD) em pacientes com diagnóstico empírico de TB. Foram calculados precisão (Prec), sensibilidade (Se), especificidade (Esp), assim como os valores preditivos positivos e negativos. Resultados de 1.135 pacientes com diagnóstico de TB, 160 foram considerados para análise (111 com TBpl confirmada e 49 com TBpl não confirmada. 58 pacientes não TB foram considerados como controles. Hiporexia [odds ratio ajustado (ORa) 27,39 (95% IC 6,26-119,89)] e características celulares/bioquímicas do líquido pleural (LP) (polimorfonuclear em duas categorias: 3%-14% ORa 26,22, 95% IC 7,11-96,68; e < 3% ORa 28,67, 95% IC 5,51-149,25; e proteína ≥ 5g/dL ORa 7,24, 95% IC 3,07-17,11) foram associadas a um risco mais elevado de tuberculose. O diagnóstico de CAD construído ao empregar essas variáveis mostrou valores de Prec = 87,6%, Se = 89,2%, Esp = 84,5% para o diagnóstico de TB e foi aplicado com sucesso em doentes com TB não confirmada. Conclusão o modelo CAD mostrou um excelente desempenho para o diagnóstico de TB e pode ser considerado como estratégia alternativa de diagnóstico, utilizando padrões clínicos em associação com características celulares/bioquímicas do LP, que são acessíveis e facilmente realizados em unidades de cuidados básicos de saúde.

ABSTRACT Objectives Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units. Methods An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated. Results From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 – 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 – 96.68 and < 3% aOR 28.67, 95% CI 5.51 – 149.25; and protein ≥ 5g/dL aOR 7.24, 95% CI 3.07 – 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients. Conclusion The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.

RESUMO Objetivo: Avaliar o desempenho diagnóstico do teste Xpert MTB/RIF - teste molecular rápido para tuberculose, comparando-o com o da pesquisa de BAAR e da cultura, em amostras de LBA de pacientes com suspeita clínica de tuberculose pulmonar (TBP) que apresentam baciloscopia de escarro negativa ou produzem amostras com quantidade insuficiente de escarro. Métodos: Estudo retrospectivo de 140 casos suspeitos de TBP em pacientes que apresentaram baciloscopia negativa ou produziram amostras de escarro insuficientes e foram avaliados em um hospital-escola terciário na cidade do Rio de Janeiro (RJ). Todos os pacientes foram submetidos à fibrobroncoscopia com LBA. Os espécimes de LBA foram avaliados por meio da realização de pesquisa de BAAR, cultura para micobactérias e teste Xpert MTB/RIF. Resultados: Entre os 140 pacientes, resultados de todos os três exames microbiológicos estavam disponíveis para 73 (52,1%), dos quais 22 apresentaram cultura positiva, 17, pesquisa de BAAR positiva, e 20, teste Xpert MTB/RIF positivo. A sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e precisão global da pesquisa de BAAR foram de 68,1%, 96,1%, 88,2%, 87,5% e 87,6%, respectivamente, contra 81,8%, 96,1%, 90,0%, 92,4% e 91,8%, respectivamente, do teste Xpert MTB/RIF. A concordância entre a pesquisa de BAAR e a cultura foi de 82,3% (kappa = 0,46; p < 0,0001), enquanto a concordância entre o teste Xpert MTB/RIF e a cultura foi de 91,8% (kappa = 0,8; p < 0,0001). Conclusões: Em amostras de LBA, o teste Xpert MTB/RIF tem melhor desempenho do que os métodos tradicionais, fornecendo uma alternativa confiável à análise do escarro em casos suspeitos de TBP. No entanto, a taxa de resultados discordantes merece uma reflexão cuidadosa.

ABSTRACT Objective: To assess the diagnostic performance of the Xpert MTB/RIF assay, a rapid molecular test for tuberculosis, comparing it with that of AFB staining and culture, in BAL fluid (BALF) samples from patients with clinically suspected pulmonary tuberculosis (PTB) who are sputum smear-negative or produce sputum samples of insufficient quantity. Methods: This was a retrospective study of 140 cases of suspected PTB in patients who were smear-negative or produced insufficient sputum samples and were evaluated at a tertiary teaching hospital in the city of Rio de Janeiro, Brazil. All of the patients underwent fiberoptic bronchoscopy with BAL. The BALF specimens were evaluated by AFB staining, mycobacterial culture, and the Xpert MTB/RIF assay. Results: Among the 140 patients, results for all three microbiological examinations were available for 73 (52.1%), of whom 22 tested positive on culture, 17 tested positive on AFB staining, and 20 tested positive on the Xpert MTB/RIF assay. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for AFB staining were 68.1%, 96.1%, 88.2%, 87.5%, and 87.6%, respectively, compared with 81.8%, 96.1%, 90.0%, 92.4%, and 91.8%, respectively, for the Xpert MTB/RIF assay. The agreement between AFB staining and culture was 82.3% (kappa = 0.46; p < 0.0001), whereas that between the Xpert MTB/RIF assay and culture was 91.8% (kappa = 0.8; p < 0.0001). Conclusions: In BALF samples, the Xpert MTB/RIF assay performs better than do traditional methods, providing a reliable alternative to sputum analysis in suspected cases of PTB. However, the rate of discordant results merits careful consideration.

BACKGROUND Although Mycobacterium leprae (ML) is well characterised as the causative agent of leprosy, the pathophysiological mechanisms underlying peripheral nerve damage still need further understanding. In vitro and in vivo studies have yielded insights into molecular mechanisms of ML interaction with Schwann cells (SC), indicating the regulation of genes and proteins crucial to neural plasticity. OBJECTIVES We aimed to investigate the effect of ML on neurotrophins expression in human SC (hSC) and mice sciatic nerves to better understand their role in leprosy neuropathy, and aiming to contribute to future therapeutic approaches. METHODS We evaluated mRNA and protein expression of BDNF, NGF, NT-3, NT-4 in hSC from amputation nerve fragments, as well as in athymic nude mice, infected by ML for eight months. FINDINGS and MAIN CONCLUSIONS Our in vitro results showed a trend to decline in NGF and BDNF mRNA in ML-treated hSC, compared to controls. The immunodetection of BDNF and NT-4 was significantly downregulated in ML-treated hSC. Conversely, ML-infected mice demonstrated upregulation of NT-3, compared to non-infected animals. Our findings indicate that ML may be involved in neurotrophins regulation, suggesting that a pathogen-related imbalance of these growth factors may have a role in the neural impairment of leprosy.

BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.