Alpha-hemolysin of Staphylococcus aureus impairs thrombus formation

Toxins are key virulence determinants of pathogens and can impair the function of host immune cells including platelets. Insights into pathogen toxin interference with platelets will be pivotal to improve treatment of patients with bacterial bloodstream infections. In this study, we deciphered the effects of Staphylococcus aureus toxins alpha-hemolysin, LukAB, LukDE and LukSF on human platelets and compared the effects with the pore forming toxin pneumolysin of Streptococcus pneumoniae. In contrast to pneumolysin, alpha-hemolysin initially activates platelets as indicated by CD62P and alphaIIbeta3 integrin expression, but the resulting pores also induce alterations in the phenotype of platelets and induce apoptosis of platelets. The presence of small amounts of alpha-hemolysin (0.2 microgram/mL) in whole blood abrogates thrombus formation indicating that in systemic infections with S. aureus the stability of formed thrombi is impaired. This might be of high clinical relevance for S. aureus induced endocarditis of the aortic valves. Stabilizing the thrombi by inhibiting alpha-hemolysin induced impairment of platelets likely reduces the risk for septic (micro-)embolization. However, in contrast to pneumolysin, alpha-hemolysin induced platelets damage could not be neutralized by intravenous immune globulins. In contrast to alpha-hemolysin, S. aureus bi-component pore forming leukocidins LukAB, LukED and LukSF do not bind to platelets and had no significant effect on platelet activation and viability.

Delayed rabies post-exposure prophylaxis treatment among Dutch travelers during their stay abroad: a comprehensive analysis

Background After an animal-associated injury (AAI) in rabies-endemic regions, post-exposure prophylaxis (PEP) is needed to prevent infection.1,3 PEP consist of rabies vaccinations (RV) and in some cases also additional rabies immune globulins (RIG). Not always PEP medication, and RIG in particular, is accessible. Along with an increased number of exposure notifications among Dutch travelers, this might lead to treatment delay, and thus to increased health risks. Until now, research mainly focused on factors associated with exposition, but none on which factors are associated with PEP delay. This study aimed to identify which general sample characteristics are associated with PEP delay while being abroad. Methods A quantitative retrospective observational study was conducted. The study population consisted of insured Dutch international travelers who actively contacted their medical assistance company (2015-2019) because of an animal-associated injury (AAI) (N = 691). The association between general sample characteristics and delay of different PEP treatments was studied using survival analysis. Results Travelers without PrEP had an increased hazard, and therefore a shorter delay, for receiving their first RV as compared to travelers with PrEP (HR:1.11, 95%CI:1.01-1.22). The travelers needing both RV and RIG had a decreased hazard, and therefore a longer delay, as compared to travelers only needing RV (HR:0.81, 95%CI:0.67-0.96). General sample characteristic associated with RIG administration delay was travel destination. Travelers to Central and South America, East Mediterranean and Europe had a decreased hazard, and therefore a longer delay, for receiving RIG treatments relative to travelers to South East Asia (HR:0.31, 95%CI:0.13-0.70; HR:0.34, 95%CI:0.19-0.61; HR:0.46, 95%CI:0.24-0.89; HR:0.48, 95%CI:0.12-0.81 respectively). Conclusions Our results suggest that the advice for PrEP should be given based travel destination, as these was found to be the main factor for PEP delay, among travelers going to rabies endemic countries.

Immunotropic effects of therapeutic factors

Data on the immunotropic effects of traditional drugs - antibiotics, antihistamines, anti-inflammatory, and metabolic agents-are summarized. The profile properties of cytostatics, immune globulins, cytokines, vaccines, interferons and their ability to develop General organizational effects are analyzed. Data on the types, blocks, principles of immunotherapy administration, and ways to prevent complications are highlighted. For students and teachers, as well as employees of medical universities.

Presence and strength of binding of IgM, IgG and IgA antibodies against SARS-CoV-2 during CoViD-19 infection

Surface Plasmon Resonance imaging (SPRi) was used to determine the presence and strength of binding of IgG, IgM and IgA against the Receptor Binding Domain (RBD) of SARS-CoV-2 in sera of 119 CoViD-19 patients. The high-throughput assay enables to follow the specific immune response of ultimate 384 individuals for these four parameters in one run. The measured IgG, IgM and IgA levels correlated with ELISA (Euroimmun: Anti-SARS-CoV-2, IgG assay, r-0.95, ECLIA: Anti-SARS-CoV-2 Ig electrochemiluminescence r=0.73). During the course of the disease, the IgG levels and strength of binding increased while generally the IgM and IgA levels went down. Recovered patients all show high strength of binding of the IgG type to the RBD protein. The anti-RBD immune globulins SPRi assay provides additional insights in the immune status of patients recovering from CoViD-19 and can be applied for the assessment of the immune reaction of healthy individuals in vaccination programmes.

Immunology, Treatment and Public Health Aspects of Subarachnoid Hemorrhage

Background: We aimed to explore the treatment and safety of subarachnoid hemorrhage. Methods: A retrospective analysis was applied on 137 patients with subarachnoid hemorrhage treated in Binzhou Central Hospital, Bingzhou, China from March 2015 to October 2018. Seventy cases with interventional embolization of intracranial aneurysms were divided as the observation group, and 67 cases with craniotomy for aneurysm clipping were divided as the control group. The changes of immune globulins before and after surgery, CD4+, CD8+, NIHSS scores, BI scores, the total effective rate of subarachnoid hemorrhage, the total length of postoperative hospital stay and conditions of postoperative complications as well as 30-day survival were compared between the two groups. Results: The levels of Ig G, Ig M, Ig A, and CD4+ after surgery in the observation group were significantly lower than those before surgery (P<0.05), but significantly higher than those in the control group (P<0.05); the total time of postoperative hospitalization in the observation group was shorter than that in the control group (P<0.05). The incidence of intracranial infection and cerebral vasospasm in the observation group was significantly lower than that in the control group (P<0.05). The NIHSS score of the observation group was significantly lower than that of the control group (P<0.05), and the BI score was significantly higher than that of the control group (P<0.05). Conclusion: Patients with subarachnoid hemorrhage undergoing interventional embolization of aneurysms can reduce the impact on immune function, decrease the adverse reactions caused by treatments, shorten the length of hospital stay and fully improve the efficacy.

A Case of Acute Motor Sensory Axonal Neuropathy: A Variant of Guillain-Barré Syndrome, with Possible Syndrome of Irreversible Lithium-Effectuated Neurotoxicity

Acute Motor Sensory Axonal Neuropathy (AMSAN) is a rare and severe variant of Guillain-Barré syndrome (GBS) that has a prolonged recovery course. GBS is often suspected due to ascending muscle weakness, sensation difficulties, respiratory compromise, and antecedent diarrhea. The diagnosis of GBS is supported by cerebrospinal fluid analysis showing albuminocytologic dissociation. Electromyogram and nerve conduction study confirm the diagnosis and allow for further classification by variant. Treatment involves either IV immune globulins or plasmapheresis, and patients typically recover. However, depending on the variant and severity, patients may ultimately require prolonged mechanical ventilation with tracheostomy. In these cases, they may continue to have persistent muscle and sensation abnormalities requiring long-term care. We present a unique case of a 38-year-old female patient with decade-long use of lithium for bipolar disorder that presented with acute lithium toxicity. Though she was ultimately diagnosed with AMSAN, the Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) may have also contributed to her persistent neurological sequelae.

Case 60: Small Fiber Neuropathy, Seronegative, Treated with Immune Globulins

Small fiber neuropathy, mixed, length-dependent can be autoimmune even if no antineuronal antibodies can be found. Yet the seronegative small fiber neuropathy may still respond to therapy with immune globulins.

Case 11: Postural Tachycardia Syndrome with Positive Antibodies Against the P/Q-type of Calcium Channel

Orthostatic symptoms in postural tachycardia syndrome (POTS) (shortness of breath, lightheadedness, fatigue, and others) are due cerebral hypoperfusion associated with reduced cerebral blood flow velocity (CBFv), which is induced by hyperventilation. Immunomodulatory therapy using immune globulins may be effective in small fiber neuropathy with a positive antibody against the P/Q-type calcium channel.