We report on 17 Australian cases of human infection or colonization with Scedosporium inflatum. The spectrum of clinical manifestations was similar to that in infection caused by Scedosporium apiospermum. The patients were classified into three groups. Four immunocompetent patients who presented with localized infections of a joint, nail bed, eye, or sphenoidal sinus made up the first group. Our first case, in a boy with posttraumatic septic arthritis, responded to surgical drainage with amphotericin B followed by treatment with itraconazole. The other three cases were cured by surgery alone. The second group consisted of five immunocompromised patients who presented with disseminated infections in a variety of sites. Four of these patients did not respond to antifungal therapy and died. The fifth apparently responded to antifungal drugs after correction of his neutropenia. The third group included eight patients with asymptomatic colonization in the external ear (five cases) or respiratory secretions (three cases). The nine isolates of S. inflatum tested by both disk and agar dilution methods were resistant to antifungal drugs. In our first case, which responded clinically to itraconazole, the MIC of this drug for the fungal isolate was 25 micrograms/mL. Thus S. inflatum can cause a broad spectrum of human infections whose severity and prognosis depend largely on the host's immune status.
Throughout the world, dermatophytosis (ringworm) is an important zoonosis [26]. This symposium attempts to highlight significant epidemiological features of these infections, to discuss mycological and laboratory aspects of the causal dermatophytes including an unusual pathogen of sheep, and to comment on current therapeutic options for the treatment of infected humans. Aetiology and public health significance of animal ringwormDermatophytes can conveniently be divided into three ecological groups depending on their natural animal or environmental hosts: (i) anthropophilic species which have humans as the normal host; (ii) zoophilic species which normally occur in other animals; and (iii) geophilic species whose natural habitat is still the soil [26]. Under appropriate conditions zoophilic and some geophilic species are transmissible to humans. The main zoophilic dermatophytes and their common hosts are listed in Table 1; only three species, Microsporum canis, Trichophyton verrucosum and Trichophyton mentagrophytes, are consistently recovered from human disease.On a geographical basis, zoophilic dermatophytes tend to be more common as human pathogens in temperate to colder areas of the world, although exceptions do occur (e.g.M. canis is uncommon in the Chicago area of the USA) [20]. Also, in some areas (e.g. Australia) where M. canis has been the dominant agent of childhood tineas, other fungi such as the anthropophilic Trichophyton tonsurans are now emerging as equally significant agents of tinea capitis [21]. Reasons for this are unclear, although it does seem that this may be associated with a decline in the incidence of cat and dog ringworm in these areas. A summary indicating the importance of M. canis, T verrucosum and the animal varieties of T. mentagrophytes (vat. mentagrophytes, var. erinacei and var. quinckeanum) in human ringworm on a worldwide basis is shown in Table 2. Although potential animal reservoirs are present in many tropical areas of the world, zoophilic tineas are uncommon in humans in such regions; reasons for this are unknown, although it seems that the degree and closeness of animal to human contact is a major factor.It is also apparent that most infected and/or significantly colonized animals appear clinically normal. In one survey in New Zealand [2], 36% of cats and 7"5% of dogs examined routinely (by a skin brushing technique) were found to be carriers of M. canis
Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonists attenuate pain and inflammation in preclinical models. This study tested whether systemic delivery of an α7 nAChR agonist attenuates neuropathic pain and associated immune-mediated pro-inflammation. Hind paw response thresholds to mechanical stimuli in male Sprague Dawley rats were assessed before and after sciatic chronic constriction injury (CCI) or sham surgery. Osmotic mini-pumps containing TC-7020, an α7 nAChR selective agonist, were implanted 10 to 14 days after surgery. TC-7020 (1, 3, and 10 mg/kg/d; s.c.) significantly attenuated CCI-induced allodynia, which lasted through 2 weeks of test compound administration. Spinal cords were collected after 2 weeks and processed for microglial and astrocyte activation markers within the ipsilateral L4-L6 dorsal horn. In addition, ipsilateral L4-5 dorsal root ganglia (DRGs) were processed for neuronal injury and satellite cell activation markers. CCI-induced central glial cell activation markers were not suppressed by TC-7020, even though TC-7020 is mildly blood-brain barrier permeable. However, TC-7020 downregulated the integrated density of activation transcription factor 3 (ATF3) but not the number of ATF positive cells. TC-7020 also downregulated phosphorylated extracellular signal kinase (p-ERK) and satellite cell activation in the CCI-affected DRGs. Therefore, systemic α7 nAChR agonist may be effective in treating neuropathic pain via reducing neuronal injury and immune cells activation occurring in the periphery. Perspective These studies demonstrated that TC-7020, an alpha7 nicotinic acetylcholine receptor agonist with partial blood-brain barrier permeability, reversed neuropathic pain in rats, likely via attenuation of inflammation in the DRG and/or the site of sciatic injury.
Four cases of peritonitis caused by the filamentous fungus Paecilomyces variotii in patients on continuous ambulatory peritoneal dialysis are reported. Removal of the Tenckhoff catheter and antifungal chemotherapy led to resolution of symptoms in all cases. Possible contaminating events are discussed, and reported infections with P. variotii are reviewed.
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