Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin A or toxin B in cell-based in vitro neutralization assays. Three anti-toxin A HuMAbs (3H2, CDA1, and 1B11) could all inhibit the enterotoxicity of toxin A in mouse intestinal loops and the in vivo toxicity in a systemic mouse model. Four anti-toxin B HuMAbs (MDX-1388, 103-174, 1G10, and 2A11) could neutralize cytotoxicity in vitro, although systemic toxicity in the mouse could not be neutralized. Anti-toxin A HuMAb CDA1 and anti-toxin B HuMAb MDX-1388 were tested in the well-established hamster model of C. difficile disease. CDA1 alone resulted in a statistically significant reduction of mortality in hamsters; however, the combination treatment offered enhanced protection. Compared to controls, combination therapy reduced mortality from 100% to 45% (P < 0.0001) in the primary disease hamster model and from 78% to 32% (P < 0.0001) in the less stringent relapse model.
West African musicians such as Baaba Maal and Youssou N'Dour of Senegal, Oumou Sangaré and Ali Farka Touré of Mali, have become known for their commitment to their constituencies back home, as well as for their appeal to non‐African audiences. Fully embracing a post‐colonial and post‐modern sensibility, their layered musical compositions include rap, reggae, blues, and jazz at the same time as they draw on traditional instruments, rhythms, themes, and melodies. They may choose between the traditional format of praise songs of the griots and more modern messages. Cultural interpreters at home and in Europe, these ethnographers write in sound, choosing carefully their subject, rhythm, delivery, and style, depending on their audience. Equally layered, however, is the complex response to these artists in France. This paper draws on field work in Paris and in eastern France to discuss the appeal of West African music for a French audience vis a vis the mixed understanding of the purveyors of that music. West African music may open France's door to immigrants, only to shut out the musicians as they negotiate its daily life. Immigrants' individual experiences are discussed in regard to their ambivalently received personhood, on one hand, and their positively received, yet frequently exoticized, music on the other.
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