Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis

The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear. Here, immune responses induced by combinations of the bacterium Salmonella Typhimurium (STm) and the helminth Nippostrongylus brasiliensis (Nb), which causes a murine hookworm infection and an experimental porin protein vaccine against STm, were examined. Mice infected with both STm and Nb induced similar numbers of Th1 and Th2 lymphocytes compared with singly infected mice, as determined by flow cytometry, although lower levels of secreted Th2, but not Th1 cytokines were detected by ELISA after re-stimulation of splenocytes. Furthermore, the density of FoxP3+ T cells in the T zone of co-infected mice was lower compared to mice that only received Nb, but was greater than those that received STm. This reflected the intermediate levels of IL-10 detected from splenocytes. Co-infection compromised clearance of both pathogens, with worms still detectable in mice weeks after they were cleared in the control group. Despite altered control of bacterial and helminth colonization in co-infected mice, robust extrafollicular Th1 and Th2-reflecting immunoglobulin-switching profiles were detected, with IgG2a, IgG1 and IgE plasma cells all detected in parallel. Whilst extrafollicular antibody responses were maintained in the first weeks after co-infection, the GC response was less than that in mice infected with Nb only. Nb infection resulted in some abrogation of the longer-term development of anti-STm IgG responses. This suggested that prior Nb infection may modulate the induction of protective antibody responses to vaccination. To assess this we immunized mice with porins, which confer protection in an antibody-dependent manner, before challenging with STm. Mice that had resolved a Nb infection prior to immunization induced less anti-porin IgG and had compromised protection against infection. These findings demonstrate that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization

Survey of Anticoagulation Practices with the Impella Percutaneous Ventricular Assist Device at High-Volume Centers

Objectives. To characterize anticoagulation practices with the Impella percutaneous ventricular assist device (pVAD). Background. Managing anticoagulation in patients being supported by the Impella pVAD is made challenging by several unique features of the device. These include the release of a dextrose-based purge solution containing unfractionated heparin (UFH), the need to concurrently administer systemic anticoagulation with intravenous UFH, and the lack of an alternative strategy in patients with contraindications to UFH. Methods. To characterize anticoagulation practices with the Impella pVAD, we conducted a survey of centers in the United States performing a high volume of Impella cases, which we defined as > 1 per month. Centers were contacted via email or phone and individuals who agreed to participate were provided with a link to complete the survey online. The primary measures of interest were variations in practice across centers and variations from the manufacturer’s recommendations. Results. Practices varied considerably among respondents (65 of 182 centers, or 35.7%) and often diverged from manufacturer recommendations. Approximately half of centers (52.4%) reported using a UFH concentration of 50 units/mL in the purge solution, whereas most of the remaining centers (41.3%) reported using lower concentrations. Strategies for the initiation and adjustment of systemic therapy also varied, as did practices for routinely monitoring for hemolysis. Nearly one-fifth of centers (16.7%) had not developed an alternative strategy for the purge solution in patients with contraindications to UFH. Most centers (58.4%) reported using argatroban or bivalirudin in this scenario, a strategy that diverges from the manufacturer’s recommendations. Conclusions. Given these findings, studies to determine a systematic approach to anticoagulation with the Impella device are warranted