Robert S Wallis

..Further research is needed to determine how best to prevent and manage their infectious complications and to determine their potential adjunctive therapeutic role in chronic infectious diseases...

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..Clinical improvement occurred only after resumption of adalimumab treatment...

..However, additional studies will be required to confirm these observations in additional patient and microbial populations that are distinct according to geography and microbial and host genetics...

..Clinical strategies for prevention and management of tuberculosis in patients treated with TNF blockers may be improved based on our evolving understanding of these differences...

..06 log) (P = 0.002). In conclusion, PNU-100480 was safe and well tolerated at all tested doses. Further studies in patients with tuberculosis are warranted. Biomarkers can accelerate early development of new tuberculosis treatments...

..We review progress in tuberculosis biomarker development and efforts being made to harness resources to meet future challenges...

..Translation of scientific progress in biomarkers and diagnostics into clinical and public health programmes is possible-with political commitment, increased funding, and engagement of all stakeholders...

..These 2 pathogenic mechanisms cannot otherwise be readily distinguished...

..IL-10 production was equally suppressed by all three drugs, excluding excess IL-10 as a regulatory mechanism. The tuberculosis risk posed by infliximab may reflect its combined effects on TNF and IFNgamma...

..Two metabolites contribute to but do not fully account for its superiority. This study examined the safety, tolerability, pharmacokinetics, and mycobactericidal activity of single ascending doses of PNU-100480...

..These studies will benefit from multidisciplinary collaborations including microbiologists, immunologists, clinicians, tuberculosis control personnel, and the pharmaceutical and biotechnology industry...

..This article focuses on recent studies that inform prevention and management of infections in this susceptible patient population...

..Prolonged treatment is presently required to prevent relapse, which is thought to arise from persisting foci of semidormant infection contained within granulomas...

..The data presented in this supplement highlight the need for further research into these key areas, and illustrate our current understanding of the mode of action of TNF blockers as only the tip of the iceberg...

..The potential role of corticosteroids as tools to examine this question will be limited by concerns regarding their toxicity; however, further studies of other agents to limit cellular activation in AIDS are warranted...

..This phase 1 study examined the safety, microbiology, immunology, and virology of TNF blockade using etanercept (soluble TNF receptor, Enbrel) during the initial treatment of HIV-associated tuberculosis...

..TNF is known to participate in the induction and maintenance of protective granulomas at multiple steps, and evidence supporting a differential inhibition of TNF bioactivity and signaling by the 2 drugs is discussed...

..The ability of infliximab to disrupt established granulomas may be distinct from its ability to neutralize soluble TNF. Further research to elucidate the mechanism of the antigranuloma activity of infliximab is warranted...

..tuberculosis. None of the drugs induced significant levels of apoptosis or necrosis, in either monocytes or T cells. CONCLUSIONS: The tuberculosis risk posed by infliximab may reflect its combined effects on TNF and IFN- gamma ...

..These experiments indicate that whole blood culture may be used to measure immunity to M. tuberculosis and that further studies of repeated BCG vaccination are warranted...