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Background Interleukin 4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanized anti–IL-4 monoclonal antibody) as adjunctive tuberculosis treatment. Methods Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo, and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: (1) nonrandomized 0.05 mg/kg (n = 4); (2) nonrandomized 0.5 mg/kg (n = 4); (3) randomized 2.5 mg/kg (n = 9) or placebo (n = 3); and (4) randomized 10 mg/kg (n = 9) or placebo (n = 3). Coprimary safety outcome was study-drug–related grade 4 or serious adverse event (G4/SAE) in all cohorts (1–4). Coprimary efficacy outcome was week 8 sputum culture time-to-positivity (TTP) in randomized cohorts (3–4) combined. Results Pascolizumab levels exceeded IL-4 50% neutralizing dose for 8 weeks in 78%–100% of participants in cohorts 3–4. There were no study-drug–related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (P =.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 log10 TTP/day; 95% Bayesian credible interval 0.006 to 0.015 log10 TTP/day). Conclusions There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti–IL-4 interventions for tuberculosis in larger phase 2 trials. Clinical Trials Registration NCT 01638520. [ABSTRACT FROM AUTHOR]

Background: Tuberculous pleural effusion (TPE) is paucibacillary, making its diagnosis difficult based on laboratory investigations alone. We present a case of a patient with a TPE who was initially misdiagnosed to have azathioprine-induced lung injury. The diagnosis of TPE was arrived at with the help of clinical assessment, laboratory and radiological investigations. Case presentation: A 25-year-old chronic smoker with sympathetic ophthalmia on long-term immunosuppression, latent tuberculosis infection and a significant family history of tuberculosis presented with a three-week history of productive cough, low-grade fever, night sweats and weight loss. Examination of the lungs showed reduced breath sounds at the right lower zone. Chest x-ray showed minimal right pleural effusion with a small area of right upper lobe consolidation. The pleural fluid was exudative with predominant mononuclear leukocytes. Direct smears of sputum and pleural fluid; polymerase chain reaction of pleural fluid; and sputum, pleural fluid and blood cultures were negative for M. tuberculosis (MTB) and other organisms. As he did not respond to a course of broad-spectrum antibiotics, he was then treated as a case of azathioprine-induced lung injury. However, his condition did not improve despite the cessation of azathioprine. A contrast-enhanced computed tomography of the thorax showed right upper lobe consolidation with tree-in-bud changes, bilateral lung atelectasis, subpleural nodule, mild right pleural effusion and mediastinal lymphadenopathy. Bronchoalveolar lavage was negative for malignant cells and microorganisms including, MTB. However, no pleural biopsy was done. He was empirically treated with antitubercular therapy for 9 months duration and showed complete recovery. Conclusion: A high index of suspicion for TPE is required in individuals with immunosuppression living in regions endemic to tuberculosis. Targeted investigations and sound clinical judgement allow early diagnosis and prompt treatment initiation to prevent morbidity and mortality. [ABSTRACT FROM AUTHOR]