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Background Plasma chemokines are biomarkers of greater disease severity, higher bacterial burden, and delayed sputum culture conversion in pulmonary tuberculosis (PTB). Whether plasma chemokines could also serve as biomarkers of unfavorable treatment outcomes in PTB is not known. Methods A cohort of newly diagnosed, sputum smear- and culture-positive adults with drug-sensitive PTB were recruited under the Effect of Diabetes on Tuberculosis Severity study in Chennai, India. Plasma chemokine levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 136 control individuals who had recurrence-free cure. A second validation cohort comprising newly diagnosed, culture-positive adults with drug-sensitive TB was used to measure plasma chemokine levels in 20 cases and 40 controls. Results Six chemokines (CCL2, CCL3, CCL4, CXCL8, CXCL10, and CX3CL1) were associated with increased risk, while CXCL1 was associated with decreased risk of unfavorable outcomes in unadjusted and adjusted analyses in the test cohort. Similarly, CCL3, CXCL8, and CXCL10 were associated with increased risk of unfavorable treatment outcomes in the validation cohort. Receiver operating characteristic analysis revealed that combinations of CCL3, CXCL8, and CXCL10 exhibited very high sensitivity and specificity in differentiating cases vs controls. Conclusions Our study reveals a plasma chemokine signature that can be used as a novel biomarker for predicting adverse treatment outcomes in PTB. [ABSTRACT FROM AUTHOR]

Abstract: The non-response to hepatitis B vaccine in health care workers (HCWs) is reported to vary between 5 and 40%. The underlying cellular and molecular events for unresponsiveness to HBV vaccine have not yet been characterized at any great extent. In the current study, we examined the CD150 surface expression levels and its association with polyclonally activated and HBV specific stimulated cellular proliferations in responders and non-responders. CD150 was identified as upregulated expression marker with suppressive regulatory cell function on all activated T cells by gene chip analysis. We found the overall weak cellular proliferation in response to specific and non-specific agents in non-responders. This is significantly associated with enhanced surface expression of CD150 in the non-responders. A strong expression of CD150 with weak cellular proliferation could be used as a predictive marker for non-responsiveness. [Copyright &y& Elsevier]

Background: Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features., Objective: To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma)., Design: Retrospective descriptive study., Methods: Children less than 12 years presenting with neurological signs and symptoms were assessed for a therapeutic TBM trial eligibility. The results of their clinical, laboratory, neuroimaging, cerebrospinal fluid evaluations were analysed for TBM diagnosis., Results: Of 600 children evaluated, 61(10%) had CNS tuberculosis; TBM 47, tuberculoma 14. 20(33%) had definite TBM. Mean age of children with TBM was 5 ± 3.4 years. Of 47, 13(28%), 21(45%) and 13(28%) had grade I, II, and III disease respectively. Abnormalities suggestive of TBM in MRI and computed tomography brain were observed in 76% (26/34) and 77% (24/31) respectively. Abnormal cerebrospinal fluid white blood cell count, protein and glucose were observed in 56% (24/43), 49% (22/45), 47% (21/45) respectively. Among 41 patients with TBM followed up until discharge, five died., Conclusion: Younger children with TBM have severe forms. Confirmatory results may not be available in all. A holistic approach to care including addressing complications of hydrocephalus and strokes is needed., (© The Author(s), 2024.)

Background: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen., Methods: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment., Results: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups)., Conclusions: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.)., (Copyright © 2022 Massachusetts Medical Society.)

Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about a half million people die every year. India represents the second largest pool of chronic HBV infection worldwide with an estimated 40 million infected people. The prevalence of chronic HBV infection in pregnant women is shown to be 0.82 per cent with the risk of mother-to-child vertical transmission. Hepatitis B e antigen (HBeAg) positivity indicates replicative form of HBV which may play a role in immunotolerance in utero by crossing the placenta. In case of HBeAg positivity and high viral load of mother, HBV immunoglobulin is preferably given along with HBV vaccination. Antiviral therapy is recommended for use in the third trimester of pregnancy to reduce the perinatal transmission of HBV, however, use of antiviral therapy should be individualized during pregnancy. Chronic HBV infection in neonates is linked with strong presence of Tregs (T regulatory cells) and defective CD8 T cells pool to produce interferon (IFN)-γ. T cell receptor (TCRζ) chain defects were also associated with decreased CD8 T cell dysfunction. Decreased TCRζ expression could be due to persistent intrauterine exposure of the viral antigens early in embryonic development leading to immune tolerance to HBV antigens in the newborns positive for hepatitis B surface antigen (HBsAg+ve). Therefore, due to HBV infection, T cell tolerance to HBV-antigen may probably leave the newborn as a chronic carrier. However, HBV vaccination may have benefits in restoring acquired immunity and better production of HBV specific antibodies.

Background: Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efficacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment., Methods: Twenty patients with CHB proven by liver biopsy, with ALT levels >1.5 X ULN, HBV DNA levels>141,500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5 microg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was defined as normalization of ALT and DNA response as HBV DNA<141,500 copies/ml. Secondary efficacy measures included HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive patients)., Results: Twenty patients were treated, of whom 16 were HBeAg positive. At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg-), HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients. At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed, with normal ALT only in 2 (10%) (1 of 16 HBeAg+ and 1 of 4 HBeAg-), and all 5 patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg-positive patients. None of the patients lost HBsAg., Conclusions: The combination of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB patients with a failed treatment. New treatment strategies need to be developed.