Photorhabdus asymbiotica is an emerging bacterial pathogen that causes locally invasive soft tissue and disseminated bacteremic infections in the United States and Australia. Although the source of infection was previously unknown, we report that the bacterium is found in a symbiotic association with an insect-pathogenic soil nematode of the genus Heterorhabditis.
We describe a 27-year-old man with X-linked (Bruton's) hypogammaglobulinemia who presented during a 10-month period with recurrent fevers and multifocal lower-limb cellulitis associated with bacteremia due to Helicobacter-like organisms ("Flexispira rappini" and Helicobacter canis). Susceptible individuals may acquire infection of this type as a result of exposure to young dogs.
BackgroundThe continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria.MethodsIn this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 107 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A.ResultsWe demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected.ConclusionsThis is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans.Trial registrationTrial registration: ACTRN12614000228684. Registered 4 March 2014.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1173-9) contains supplementary material, which is available to authorized users.
Objectives: To identify patient populations at risk of Pneumocystis carinii pneumonia (PCP) and assess the potential role of chemoprophylaxis.
Methods: Review of cases of PCP among patients admitted to a tertiary referral hospital in Sydney between January 1990 and April 1993. Cases were identified by indirect immunofluorescent antibody microscopy performed on respiratory tract specimens.
Results: Ninety‐two episodes of PCP were diagnosed in 64 HIV‐positive patients and 28 others. All HIV‐negative patients had received corticosteroids combined with other immunosuppressive agents before the onset of PCP symptoms, which occurred within six months of immunosuppression. The group included nine of 150 kidney transplant recipients (6%), six of 138 liver transplant recipients (4.3%) and three of 25 patients with Wegener's granulomatosis (12%). Mortality associated with PCP in HIV‐negative patients was significantly higher than in those who were HIV‐positive (32% v. 8%, P < 0.005).
Conclusion: Solid organ transplant recipients and individuals receiving treatment for Wegener's granulomatosis have a significant risk of developing PCP. Given the high mortality associated with this disease in HIV‐negative patients, primary PCP chemoprophylaxis should be considered during the first six months of immunosuppression.
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