Eight patients have previously been reported to have central nervous system infections caused by Sporothrix schenckii. In those patients the fungus proved quite difficult to culture, delaying correct diagnosis and treatment. We describe seven additional patients with sporotrichosis meningitis, all of whom had antibody to this fungus in cerebrospinal fluid and serum. The antibody in the cerebrospinal fluid was most likely produced locally, as evidenced by its oligoclonality and the relatively high ratio of immunoglobulin to albumin in the cerebrospinal fluid as compared with the serum. Only one of these seven patients, who had active sporotrichosis of the knee joint, had obvious extrameningeal infection. None of 130 patients with meningitis known to be caused by other agents and none of 170 patients with other neurologic disorders had antibody to S. schenckii in their cerebrospinal fluid. We suggest that cerebrospinal fluid should be tested for S. schenckii antibody (in addition to other fungal agents) in any patient with chronic meningitis for which no cause is discovered by the usual diagnostic tests.
Background and aims:The development of a prophylactic hepatitis C virus (HCV) vaccine has been hindered by viral genomic variability. A phase-I human clinical trial demonstrated that a viral vector T-cell vaccine encoding a subtype-1b HCV immunogen (non-structural proteins 3 to 5) induces HCV-specific T-cell responses targeting dominant epitopes that are highly variable and have reduced crossrecognition of variants at the population level. Therefore, we generated simian adenovirus vaccines encoding an immunogen with genetic sequence that is conserved between HCV genotypes with genetic adjuvant, truncated class-II shark invariant chain, sIi(tr) aa47-72. Methods: Combined conserved segments formed novel immunogens for HCV genotypes 1 and 3, and 1 to 6. Putative artificial epitopes in junction regions were abrogated. In silico analysis enabled exclusion of potential cross-reactive human selfpeptides and identified HCV T-cell epitopes. Simian adenoviral vaccine vectors encoding the HCV immunogen (ChAdOx1-gt1-6) were constructed with and without sIi(tr). Immunogenicity was evaluated in inbred and outbred mice at 10 7-8 IU intramuscular dose, using both genotype-specific and conserved sequence peptide pools in ex vivo IFN-ϒ ELISpot assays and intracellular staining. A genotype-1b
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