Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αβT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p < 0.05) and 27 healthy controls (2.7-7.6-fold, p < 0.001), but higher neutrophils and classical monocytes (2.3-3.0-fold, p < 0.001). CSF leukocyte activation was higher than in blood (1.8-9-fold). CSF of TBM patients showed a predominance of αβT and NK cells, associated with better survival. Cytokine production after ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p < 0.001). Among TBM patients, high ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p < 0.05). TBM patients show a strong myeloid blood response, with a broad variation in immune function. This may influence the response to adjuvant treatment and should be considered in future trials of host-directed therapy.
The pharmacokinetic (PK) and clinical implications of combining metformin with rifampicin are relevant to increasing numbers of patients with diabetic tuberculosis (TB) across the world and are yet unclear. We assessed the impact of rifampicin on metformin PKs and its glucose-lowering effect in patients with diabetic TB by measuring plasma metformin and blood glucose during and after TB treatment. Rifampicin increased metformin exposure: plasma area under the plasma concentration-time curve from time point 0 to the end of the dosing interval (AUC ) and peak plasma concentration (C ) geometric mean ratio (GMR; during vs. after TB treatment) were 1.28 (90% confidence interval (CI) 1.13-1.44) and 1.19 (90% CI 1.02-1.38; n = 22). The metformin glucose-lowering efficacy did not change (Δglucose - C ; P = 0.890; n = 18). Thus, we conclude that additional glucose monitoring in this population is not warranted. Finally, 57% of patients on metformin and rifampicin, and 38% of patients on metformin alone experienced gastrointestinal adverse effects. Considering this observation, we advise patients to take metformin and rifampicin with food and preferably separated in time. Clinicians could consider metoclopramide if gastrointestinal adverse effects occur.
BACKGROUND: Neutrophils and lymphocytes play a significant role in inflammation and a high ratio of neutrophils over lymphocytes (NLR) has been used as an inflammatory marker to predict the severity of various diseases. Here we compared the NLR among pulmonary tuberculosis and TB/HIV co-infection.METHODS: A retrospective cross-sectional study was conducted, included patients with pulmonary TB without cavitation TB (n=50), with cavitation TB (n=50) and HIV co-infection (n=27). Complete blood count was examined, including neutrophils and lymphocyte. NLR was calculated and compared between groups. RESULTS: Neutrophils were significantly higher (p=0.004) in TB with cavitation compared to those with no cavitation (8.27±1.45 x103/μL vs. 6.61±1.4 x103/μL, respectively); whereas the lymphocytes were similar in both groups, resulting in a significantly higher NLR (p=0.009) in pulmonary TB with cavitation compared to pulmonary TB with no cavitation (5.98±1.85 vs. 4.42±1.86, respectively). On the contrary, both neutrophils as well as lymphocyte were significantly lower in TB/HIV compared to pulmonary TB, which for neutrophil were 5.14±2.19 x103/μL vs. 7.4±1.45 x103/μL, respectively (p=0.003) and for lymphocyte (1.02 ±0.57 x103/μL vs. 1.57±0.64 x103/μL, respectively (p=0.001), resulting in a significantly higher (p=0.041) NLR value in TB/HIV (6.05±2.67) compared to pulmonary TB (5.16±1.88).CONCLUSION: High NLR in pulmonary TB with cavitation as well as in TB with HIV co-infection may be of great interest for biomarker in TB severity. Further study confirming NLR as potential marker is imperative.KEYWORDS: lymphocyte, neutrophil, NLR, tuberculosis, TB/HIV
Low Birth Weight (LBW) newborns face a risk of iron deficiency. Iron deficiency hinders growth, and motoric, and cognitive development. Newborns with LBW sometimes suffer from inflammation, which affects the commonly used iron measurements. Reticulocyte hemoglobin equivalent (Ret-He) is considered a potential tool to measure iron profile because it measures functional iron, and it is not affected by inflammation. This study compared the Ret-He in LBW and normal birth weight newborns. This cross-sectional study was done retrospectively by observing and comparing the hematology data of newborns from November to December 2019. The difference in Ret-He level was assessed using a non-parametric test. Out of 70 newborns, 26 were normal and 44 were LBW. The proportion of LBW newborns with anemia was higher than the proportion of normal ones (29.6% vs 7.7%, p=0.03). The median value of Ret-He in LBW was lower compared to normal birth weight (32.6 vs 33.3 pg, p=0.09), however, the values were still within the normal limits. Five from 70 of these newborns' Ret-He levels were under the reference range (7.14%). There was found that CRP levels were higher in LBW newborns than normal ones (5.6% vs 5%, p=0.98). There was a positive correlation between Ret-He and the birth weight of the newborns (r= 0.34, p =<0.01). There was no significant difference in Ret-He levels of LBW compared to normal babies. Further research is needed with a larger sample size to better assess the association of Ret-He and iron profiles in newborns.
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