Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant

Vaheri, Antti; Strandin, Tomas; Jääskeläinen, Anne J.; Vapalahti, Olli; Jarva, Hanna; Lokki, Marja-Liisa; Antonen, Jaakko; Leppänen, Ilona; Mäkelä, Satu; Meri, Seppo; Mustonen, Jukka

doi:10.1016/j.antiviral.2014.08.007

Cited by 34 publications

(30 citation statements)

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“…In contrast, PUUV disease exhibits a low CFR of less than 1% [31]. However, diseases caused by DOBV-Sochi and PUUV infection may also differ individually and cases of severe hantavirus disease due to PUUV infection were reported [14, 32, 33]. We compared two severe hantavirus infections caused by these two different virus species, PUUV and DOBV-Sochi.…”

Section: Discussionmentioning

confidence: 99%

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

et al. 2016

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BackgroundHantavirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and virus-specific factors are considered.Case presentationWe analyzed severe cases of hantavirus disease in two young women. The first case was caused by Puumala virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection.ConclusionsSevere hantavirus disease caused by different hantavirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

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Section: Discussionmentioning

confidence: 99%

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

et al. 2016

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“…• Vascular leakage is described for virtually all forms of Hantavirus infection, and while the mechanism remains unknown, it is believed to involve inflammatory immune responses. • Presently, treatment options for NE as well as other Hantavirus-associated pathologies are limited [46,47]. For these reasons, future studies into the inflammatory mechanism of hantavirus infection will lead to greater understanding of disease pathogenesis and, in turn, may lead to improved treatment strategies and options for healthcare practitioners.…”

Section: Conclusion and Future Perspectivementioning

confidence: 97%

Inflammatory cytokines kinetics define the severity and phase of nephropathia epidemica

et al. 2014

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“…Recently it is reported that icadibant may be effective in infections caused by PUUV and many other hantavirus subtypes by preventing the binding of bradykinin [25] . Favipiravir (T-705, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been shown to be highly active against many Bunyaviruses via inhibiting viral replication and cytopathic effect [26,27] .…”

Section: Treatment Antiviral Drugsmentioning

confidence: 99%

Hantavirus Infections in Light of Current Knowledge

Kaya¹

2018

mjima

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Hantavirus is an enveloped virus with an RNA genome comprised of three negative-sense, single-stranded segments and belongs to the genus Hantavirus in family Bunyaviridae. Human infections are seen in two different clinical presentations: "Hemorrhagic fever with renal syndrome" and "Hantavirus cardiopulmonary syndrome". However, the main pathogenic mechanism is vascular endothelial dysfunction; viral properties and host immunogenetic factors both play a role in pathogenesis. Early diagnosis and supportive treatment are crucial to prevent mortality. Fluid/ electrolyte and oxygen therapy, renal replacement, regulation of blood pressure, and blood or blood products replacement are the main components of supportive treatment. Although ribavirin is controversial in the specific treatment, some studies have suggested that it may be beneficial, especially during the oliguric phase. Favipiravir and icatibant are other effective drugs in the treatment, and the use of αvβ3 integrin inhibitors is also suggested. In recent years, monoclonal antibodies have been proposed for treatment as well as prophylaxis. DNA vaccines prepared with new technologies have good efficacy, enhancing the neutralizing antibody response. The next major breakthrough in Hantavirus immunization will be a vaccine that is effective against all viral subtypes.

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Pathophysiology of a severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant

Cited by 34 publications

References 16 publications

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

Inflammatory cytokines kinetics define the severity and phase of nephropathia epidemica

Hantavirus Infections in Light of Current Knowledge

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