Search

Myocarditis is an inflammatory disease of the myocardium with either focal or diffuse involvement and usually gives rise to chest pain, dyspnea, palpitations, and fatigue. In severe cases, arrythmias, syncope, and cardiogenic shock may occur. Acute myocarditis is most commonly caused by a variety of viruses with cardiotropic properties. Rare causes of myocarditis include bacterial infections. We, herein, describe a case of acute myocarditis caused by the intracellular bacterium Francisella tularensis. A young and previously healthy male in Northern Sweden was referred to the emergency department due to intense upper-chest pain and dyspnea. ECG exhibited minimal ST-segment elevations and laboratory parameters revealed pathological levels of high-sensitivity cardiac troponin and C-reactive protein. Radiological imaging showed increased metabolism in enlarged lymph nodes in the chest and signs that could be compatible with increased metabolism in the left ventricular of the heart. The combination of acute myocarditis and enlarged lymph nodes was believed to be caused by the intracellular bacterium Francisella tularensis, endemic in the Northern Sweden, and was verified with positive serology. The patient showed full recovery after antimicrobial treatment. As this is the fifth published case of myocarditis associated with Francisella tularensis, we suggest considering tularemia in acute myocarditis in tularemia-endemic area.

BACKGROUND: Orthohantaviruses are rodent-borne emerging viruses that cause haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in America. Transmission between humans have been reported and the case-fatality rate ranges from 0.4% to 40% depending on virus strain. There is no specific and efficient treatment for patients with severe HFRS. Here, we characterised a fatal case of HFRS and sequenced the causing Puumala orthohantavirus (PUUV). METHODS: PUUV RNA and virus specific neutralising antibodies were quantified in plasma samples from the fatal case and other patients with non-fatal PUUV infection. To investigate if the causing PUUV strain was different from previously known strains, Sanger sequencing was performed directly from the patient's plasma. Biopsies obtained from autopsy were stained for immunohistochemistry. RESULTS: The patient had approximately tenfold lower levels of PUUV neutralising antibodies and twice higher viral load than was normally seen for patients with less severe PUUV infection. We could demonstrate unique mutations in the S and M segments of the virus that could have had an impact on the severity of infection. Due to the severe course of infection, the patient was treated with the bradykinin receptor inhibitor icatibant to reduce bradykinin-mediated vessel permeability and maintain vascular circulation. CONCLUSIONS: Our data suggest that bradykinin receptor inhibitor may not be highly efficient to treat patients that are at an advanced stage of HFRS. Low neutralising antibodies and high viral load at admission to the hospital were associated with the fatal outcome and may be useful for future predictions of disease outcome.

Abstract Spinal epidural hematomas (SEH) are a rare hemorrhagic event occurring after trauma, epidural anesthesia, or operative inventions. However, in 40–50% of cases, they occur spontaneously. Spontaneous spinal epidural hematomas (SSEH) are rare in occurrence with an estimated incidence of 1 case per million annually. Pregnancy is an independent risk factor. Sudden neck or back pain, often in combination with a rapid onset of neurological symptoms, is the most common presentation of SEH (1). A 36-year-old Caucasian female with rheumatoid arthritis (RA) presented to the emergency department approximately 48 h after an uncomplicated vaginal delivery. She sought medical attention due to constant headaches and neck pain that started during active labor. An MRI of the spine revealed an extensive SEH spreading from C1 to L5. The patient was without neurological symptoms or deficits and was successfully treated conservatively without any sequelae. Even though the definitive cause of this case of SEH will remain unknown, several possible synergistic mechanisms have been identified. These include female gender, full-term pregnancy, physical activity with increased intraabdominal pressure (i.e., Valsalva maneuver), systemic administration of platelet aggregation inhibitor (PAI), and iatrogenic manipulation such as spinal epidural anesthesia. Even though autoimmune and inflammatory disorders have been described in the literature to be rare sources of hemorrhage in the spinal canal, it is unclear whether the patient’s RA should be regarded as an individual risk factor. Key Facts Spinal epidural hematomas are a rare hemorrhagic event characterized by an accumulation of blood between the vertebrae and the dura of the spinal canal, and can be a clinical challenge to diagnose due to the insidious presentation, with symptoms ranging from asymptomatic to non-specific head or neck pain, or neurological deficits. The etiology of spontaneous spinal epidural hematomas remains largely unknown, although there are many predisposing factors, including vascular malformation, anticoagulation therapy, trauma, iatrogenic manipulations, and hypertension. The differential diagnosis to spinal epidural hematomas are several, e.g., meningitis, migraine, subarachnoid or intracranial hemorrhage, pituitary apoplexy, venous sinus thrombosis, and thrombosis, and radiological examination is key to diagnose and map the distribution of the hemorrhage.

International audience; Objective : Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.Methods : We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.Results : We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27−IgD− B cells and CD27−/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.Conclusion : Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infected individuals have significantly elevated levels of extracellular ATP in circulation.

Objective Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction. Methods We performed a comprehensive characterisation of longitudinal antiviral B‐cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells. Results We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27−IgD− B cells and CD27−/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection. Conclusion Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus‐infected individuals have significantly elevated levels of extracellular ATP in circulation., We show a comprehensive study to correlate two pathologies associated with haemorrhagic fever with renal syndrome (HFRS), thrombocytopenia and kidney dysfunction, with changes in the circulating B‐cell compartment (cells and antibodies). We show that thrombocytopenia is associated with mobilization of both activated and resting plasmablasts and plasma cells in circulation. However, the level of kidney dysfunction associated with longitudinal development of neutralizing antibodies in patients and associated with the reduction of surface CD27 expression on both plasmablasts and B cells in circulation. The low CD27 expression might be explained by elevated levels of ATP that could contribute to shedding of CD27 from B cells by a MMP‐8‐dependent mechanism.

Human hantavirus infections can cause hemorrhagic fever with renal syndrome (HFRS), major signs of the disease being thrombocytopenia and transient kidney dysfunction. By a comprehensive and longitudinal study of circulating B cells, we demonstrate that these two pathologies associate with distinct effects on the humoral immune system during HFRS. Low thrombocyte counts strongly associated with an abnormal frequency of plasmablasts in circulation, whereas kidney dysfunction was indicative of an accumulation of CD27−B cells and plasmablasts. Finally, we provide evidence that high levels of extracellular ATP in circulation during HFRS correlates with shedding of surface CD27 on B cells via a metallomatrix proteinase-8-mediated mechanism. Since extracellular ATP is known to regulate kidney function, our study reveals a link between kidney dysfunction and the generation of CD27−IgD−B cells, and a potential molecular target for treatment of the symptomatic phase of HFRS.

The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection - an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings.