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Tuberculous meningitis causes substantial mortality and morbidity in children and adults. More research is urgently needed to better understand the pathogenesis of disease and to improve its clinical management and outcome. A major stumbling block is the absence of standardised diagnostic criteria. The different case definitions used in various studies makes comparison of research findings difficult, prevents the best use of existing data, and limits the management of disease. To address this problem, a 3-day tuberculous meningitis workshop took place in Cape Town, South Africa, and was attended by 41 international participants experienced in the research or management of tuberculous meningitis. During the meeting, diagnostic criteria were assessed and discussed, after which a writing committee was appointed to finalise a consensus case definition for tuberculous meningitis for use in future clinical research. We present the consensus case definition together with the rationale behind the recommendations. This case definition is applicable irrespective of the patient's age, HIV infection status, or the resources available in the research setting. Consistent use of the proposed case definition will aid comparison of studies, improve scientific communication, and ultimately improve care., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

HIV-associated tuberculous meningitis (TBM) poses significant diagnostic and therapeutic challenges and carries a dismal prognosis. In this review, we present the clinical features and management of HIV-associated TBM, and compare this to disease in HIV-uninfected individuals. Although the clinical presentation, laboratory findings and radiological features of TBM are similar in HIV-infected and HIV-uninfected patients, some important differences exist. HIV-infected patients present more frequently with extra-meningeal tuberculosis and systemic features of HIV infection. In HIV-associated TBM, clinical course and outcome are influenced by profound immunosuppression at presentation, emphasising the need for earlier diagnosis of HIV infection and initiation of antiretroviral treatment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Patients with serious infections requiring parenteral antimicrobial therapy are usually hospitalized for treatment. For certain conditions, however, administration of parenteral antibiotics outside the hospital setting may be safe, efficacious, convenient for patients and cost-beneficial. Outpatient parenteral antimicrobial therapy (OPAT) was developed in the US initially and its use has expanded globally during the past three decades. A wide variety of infections are amenable to treatment by OPAT. Once-daily agents such as ceftriaxone or teicoplanin and, more recently, antimicrobials such as ertapenem or daptomycin have been used for OPAT. The use of higher doses and less-frequent dosing of existing agents is being explored, and exciting new developments include the emergence of agents with broader-spectrum activity against drug-resistant organisms and the use of antifungal agents in the OPAT setting. Future prospects in OPAT include the use of more recently launched drugs such as telavancin, as well as drugs in development, including dalbavancin (Durata Therapeutics Inc) and omadacycline (PTK-0796; Novartis AG/PARATEK Pharmaceuticals Inc). This review outlines recent developments in, and future prospects for, the antimicrobial agents used in OPAT.

Tuberculous meningitis (TBM) remains difficult to diagnose. We prospectively evaluated a diagnostic algorithm for TBM in 205 HIV-negative patients with meningitis and a low CSF glucose. Patients were classified as having TBM or bacterial meningitis (BM) by two diagnostic methods: logistic regression method (LRM) and classification and regression tree (CART). We performed analyses of TBM versus BM and TBM versus non-TBM in all patients and in patients with microbiologically confirmed diagnoses. Diagnostic sensitivities for TBM were 99% (LRM) and 87% (CART). For BM, diagnostic sensitivities were 81.5% (LRM) and 86.5% (CART) in the primary analysis and 86.5% (LRM) and 74% (CART) in the secondary analysis. In microbiologically confirmed cases, similar rates were achieved. These figures are superior to microbiological confirmation rates in routine laboratories and support the use of this algorithm in high-prevalence TB settings with limited diagnostic facilities. Validation in an HIV-endemic setting is required.

Background: Chronic infection with the hepatitis C virus has been reported to cause a wide variety of ophthalmic lesions. The incidence and significance of these lesions in an unselected population has not been assessed., Methods: We studied a group of unselected patients with chronic hepatitis C and performed a full ophthalmic examination on each. As a control group we studied patients with chronic hepatitis B infection., Results: In 25 patients with chronic hepatitis C we found no increase in the prevalence of significant ocular disease when compared with a cohort of patients with chronic hepatitis B., Conclusion: Chronic heptatitis C does not cause any marked increase in the incidence of ocular disease.

The known mechanisms of hepatitis C virus (HCV) clearance and their failure in persistent infection are discussed. Interferon-alpha is the main treatment in chronic HCV but has shown poor sustained virological response rates when used as a monotherapy. The effects of interferon-a may include inhibition of HCV virion production by an effect on viral RNA and protein synthesis, enhancement of immune lysis of HCV infected cells, inhibition of hepatic fibrosis by an effect on TGFbeta, and an effect on HCV induced carcinogenesis. Mathematical modelling studies have provided insights into the mechanisms of action of interferon-alpha in chronic HCV. The two-phase plasma HCV RNA disappearance curve may reflect the presence of an interferon-resistant second site of HCV replication either within or outside the liver. Clinical observations and cerebral magnetic resonance scans provide evidence of functional cerebral impairment in HCV infected patients, raising the issue of the central nervous system (CNS) as a site for HCV replication. Recent studies using ribavirin in combination with interferon suggest that this approach doubles the sustained response rates obtained without having a major effect on the initial rate of HCV clearance (see Zeuzem paper). The potential mechanisms of action of ribavirin, although not yet fully understood, include inhibition of synthesis of GTP by an effect on inosine monophosphate dehydrogenase thereby limiting viral RNA synthesis, and enhancement of TH1 responses, which may assist viral clearance. There is no significant effect on HCV RNA polymerase activity. It is possible that ribavirin may have activity at extrahepatic sites of HCV infection, thus explaining the marked reduction in relapse rates with combination therapy, without an appreciable effect on initial antiviral response.