Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.     

Abnormal Coronary Anatomy in Patients with Transposition of the Great Arteries and Atrial Switch: A Predictor of Serious Cardiac Adverse Events?

Sudden cardiac death and heart failure are well known long-term complications after atrial switch for D-transposition of the great arteries (D-TGA). Right systemic ventricular dysfunction is common and myocardial ischemia has been implicated as a putative mechanism for sudden death, with coronary anomalies prevalent in 30% of cases. We sought to assess an association between adverse events and coronary anomalies in patients with D-TGA and atrial switch surgery. An observational study was conducted in 3 tertiary centers (Montreal Heart Institute, Canada, Nationwide Children’s hospital, Chicago, USA and Hopital cardiologique Louis Pradel de Lyon, France). Adults with D-TGA and atrial switch surgery qualified for inclusion if they had a major adverse cardiovascular event (MACE), i.e., ventricular arrhythmia, sudden cardiac death, heart failure, cardiac transplantation, or cardiovascular death. The prevalence of coronary anomalies was compared to historical controls. Forty-five patients were included. Twenty-one (46.7%) patients experienced a ventricular arrhythmia and 35 (77.8%) suffered from symptomatic heart failure and/or severe right ventricular dysfunction. Twelve patients (26.7%) had congenitally abnormal coronary arteries. There was no difference in the prevalence of coronary anomalies between the cohort with a MACE and a pooled population of 647 historical controls with D-TGA (28.7%, p = 0.89). In conclusion, the prevalence of congenital coronary anomalies is not higher in patients with D-TGA and atrial switch surgery who had adverse cardiovascular events. It could be hypothesized that ischemic complications in this patient population are more likely to be related to a supply-demand mismatch of the distal microvasculature rather than proximal coronary anomalies.     

In Vitro and In Ovo Host Restriction of Aquatic Bird Bornavirus 1 in Different Avian Hosts

Aquatic bird bornavirus 1 (ABBV-1) is associated with chronic meningoencephalitis and ganglioneuritis. Although waterfowl species act as the natural host of ABBV-1, the virus has been sporadically isolated from other avian species, showing the potential for a broad host range. To evaluate the host restriction of ABBV-1, and its potential to infect commercial poultry species, we assessed the ability of ABBV-1 to replicate in cells and embryos of different avian species. ABBV-1 replication was measured using multi- and single-step growth curves in primary embryo fibroblasts of chicken, duck, and goose. Embryonated chicken and duck eggs were infected through either the yolk sac or chorioallantoic cavity, and virus replication was assessed by immunohistochemistry and RT-qPCR in embryonic tissues harvested at two time points after infection. Multi-step growth curves showed that ABBV-1 replicated and spread in goose and duck embryo fibroblasts, establishing a population of persistently infected cells, while it was unable to do so in chicken fibroblasts. Single-step growth curves showed that cells from all three species could be infected; however, persistence was only established in goose and duck fibroblasts. In ovo inoculation yielded no detectable viral replication or lesion in tissues. Data indicate that although chicken, duck, and goose embryo fibroblasts can be infected with ABBV-1, a persistent infection is more easily established in duck and goose cells. Therefore, ABBV-1 may be able to infect chickens in vivo, albeit inefficiently. Additionally, our data indicate that an in ovo model is inadequate to investigating ABBV-1 host restriction and pathogenesis.     

Emergence of Q Fever Arthritis in France

Osteoarticular infection is an uncommon presentation of Q fever. Positron emission tomography (PET) scanning is a valuable tool for the diagnosis of Coxiella burnetii graft prosthesis infection and endocarditis. Our objective was to test a series of culture-negative osteoarticular samples using molecular assays for Coxiella burnetii. We tested for C. burnetii by molecular assays targeting the IS1111 and the IS30A spacer regions, using culture-negative osteoarticular samples obtained in our laboratory between January 2011and December 2012. We examine a total of 1,410 osteoarticular samples, and we observed two cases of arthritis and subacromial bursitis caused by C. burnetii. The infections were localized using PET scanning, and the diagnosis was confirmed through serology. For one, a C. burnetii strain with a multispacer sequence type 8 genotype was isolated from synovial fluid culture. Q fever articular infections could be undiagnosed because of the long evolution of articular attack, and patients with high antibody titers against C. burnetii should be tested using PET scanning to localize the site of infection.     

Synthesis of Amphiphilic Polymers Based on Fatty Acids and Glycerol‐Derived Monomers – A Study of Their Self‐Assembly in Water

Amphiphilic polymers are synthesized from various biobased compounds involving telomerization of glycerin‐derived acrylate monomers with mercaptan‐modified fatty acids. The effects of the chemical structure of the saturated or unsaturated hydrophobic block are investigated. Dynamic and static light scattering measurements, transmission electronic microscopy, and atomic force microscopy observations show that these copolymers are capable of self‐assembling into nanosized spherical particles in aqueous solution, made from compound micelles. The critical micellar concentration of these polymers is in the range of 10–60 mg L^?1 determined by fluorescence. These biobased polymers could have applications in various industrial fields, such as cosmetics and agrochemicals.