Melioidosis in Tsunami Survivors

Eugene Athan, Anthony M. Allworth, Catherine Engler, Ivan Bastian, and Allen C. Chen

Antimicrobial resistance in outpatient Escherichia coli urinary isolates in Dakar, Senegal.

International audienceBACKGROUND: Data regarding the evolution of antimicrobial resistance are needed to suggest appropriate empirical treatment of urinary tract infections (UTI) in developing countries. To assess the antimicrobial susceptibility of Escherichia coli, the predominant pathogen in community-acquired UTI, a prospective multicenter study was carried out in Dakar, Senegal. METHODOLOGY: From February 2004 to October 2006, 1010 non-duplicate E. coli strains were collected from four centres. Antimicrobial susceptibility testing was performed using disk diffusion method according to the recommendations of the CA-SFM (2004). RESULTS: Most of the isolates were resistant to amoxicillin (73.1%), amoxicillin-clavulanic acid (67.5%), cephalothin (55.8%), and trimethoprim/sulfamethoxazole (68.1%). Extended spectrum beta-lactamase was detected in 38 strains. The overall resistance rates to nalidixic acid, norfloxacin and ciprofloxacin were 23.9%, 16.4% and 15.5%, respectively. Most of the strains were susceptible to gentamicin, nitrofurantoin and fosfomycin (respective susceptibility rates, 93.8%, 89.9%, and 99.3%). During this period, a significant decrease in sensitivity was observed for cephalothin, fluoroquinolones and trimethoprim/sulfamethoxazole (p<0.001). CONCLUSIONS: These data suggest that trimethoprim/sulfamethoxazole may no longer be used as empirical treatment for community-acquired UTI in Dakar. In order to preserve the activity of fluoroquinolones for future years, alternatives such as fosfomycin or nitrofurantoin should be considered

Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers.: CYCLON-induced Rituximab resistance

International audienceImmuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma

Genomic history of the seventh pandemic of cholera in Africa.

The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa

Dipstick Test for Rapid Diagnosis of Shigella dysenteriae 1 in Bacterial Cultures and Its Potential Use on Stool Samples

International audienceBACKGROUND: We describe a test for rapid detection of S. dysenteriae 1 in bacterial cultures and in stools, at the bedside of patients. METHODOLOGY/PRINCIPAL FINDINGS: The test is based on the detection of S. dysenteriae 1 lipopolysaccharide (LPS) using serotype 1-specific monoclonal antibodies coupled to gold particles and displayed on a one-step immunochromatographic dipstick. A concentration as low as 15 ng/ml of LPS was detected in distilled water and in reconstituted stools in 10 minutes. In distilled water and in reconstituted stools, an unequivocal positive reaction was obtained with 1.6×10⁶ CFU/ml and 4.9×10⁶ CFU/ml of S. dysenteriae 1, respectively. Optimal conditions to read the test have been determined to limit the risk of ambiguous results due to appearance of a faint yellow test band in some negative samples. The specificity was 100% when tested with a battery of Shigella and unrelated strains in culture. When tested on 328 clinical samples in India, Vietnam, Senegal and France by laboratory technicians and in Democratic Republic of Congo by a field technician, the specificity (312/316) was 98.7% (95% CI:96.6-99.6%) and the sensitivity (11/12) was 91.7% (95% CI:59.8-99.6%). Stool cultures and the immunochromatographic test showed concordant results in 98.4 % of cases (323/328) in comparative studies. Positive and negative predictive values were 73.3% (95% CI:44.8-91.1%) and 99.7% (95% CI:98-100%). CONCLUSION: The initial findings presented here for a simple dipstick-based test to diagnose S. dysenteriae 1 demonstrates its promising potential to become a powerful tool for case management and epidemiological surveys