Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiving rituximab

Kapadia, Ronak K.; Gill, Christine M.; Baca, Christine B.; McMenamin, Constance; Kannappan, A.; Niehaus, William; Tyler, Kenneth L.; Pastula, Daniel M.; Piquet, Amanda L.

doi:10.1016/j.jneuroim.2021.577639

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…This study is the first to demonstrate potential efficacy of fluoxetine against enteroviruses in vivo through serial (CSF) viral load measurements in a humoral deficient patient with chronic E13 meningoencephalitis and viraemia. Although previous case reports are suggestive of an in vivo effect, the efficacy of fluoxetine could not be proved since it was associated with IVIg treatment and viral load was not measured serially [7–9]. In our patient, IVIg was halted after 6 months for lack of efficacy.…”

Section: Discussionmentioning

confidence: 70%

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Antiviral treatment with fluoxetine for rituximab‐associated chronic echovirus 13 meningoencephalitis and myofasciitis

Vermeersch

Laenen

Lens

et al. 2022

Euro J of Neurology

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Background and purpose Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. Methods Viral clearance was investigated in a patient with rituximab‐induced B‐cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi‐quantitative E13 viral load measurements by real‐time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. Results Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. Conclusion In this report of a patient with rituximab‐associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.

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Section: Discussionmentioning

confidence: 70%

“…(S)-fluoxetine binding locks 2C in a defined hexameric state thus inhibiting ATPase activity and viral replication [6]. With three published case reports all describing combination treatment with IVIg [7][8][9], the efficacy of fluoxetine remains debated.…”

Section: Introductionmentioning

confidence: 99%

Antiviral treatment with fluoxetine for rituximab‐associated chronic echovirus 13 meningoencephalitis and myofasciitis

Vermeersch

Laenen

Lens

et al. 2022

Euro J of Neurology

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“…To what extent the CNS localized antibodies participate in suppressing persistent infections is difficult to assess due to sampling logistics. Nevertheless, the potency of B cells to minimize local virus reactivation or virus CNS invasion from the periphery is clearly evident by studies of patients receiving anti‐CD20 monoclonal antibody (trade name Rituximab) B cell depletion therapy to treat rheumatoid arthritis, MS or some cancers 24‐31 . While extremely rare, prolonged treatment with Rituximab is associated with progressive multifocal leukoencephalopathy (PML), an often‐lethal opportunistic infection resulting from replication of JC virus in the CNS.…”

Section: Clinical Relevance Of B Cells During Viral Encephalitismentioning

confidence: 99%

“…PML survival has been associated with the presence of high neutralizing antibody titers in both the plasma and CSF and JC virus‐neutralizing monoclonal antibodies isolated from patients who recovered from PML appear to block virus cell entry 32‐34 . Other CNS infections reported to be linked to anti‐CD20 antibody treatment are enteroviruses and, in isolated cases, HSV and deer tick virus encephalitis 28‐31 . This highlights the need to understand how B cells contribute to suppressing latent and persistent viral infections from entering the CNS or already within the CNS.…”

Section: Clinical Relevance Of B Cells During Viral Encephalitismentioning

confidence: 99%

B cells going viral in the CNS: Dynamics, complexities, and functions of B cells responding to viral encephalitis

Cardani‐Boulton

Boylan

Stetsenko

et al. 2022

Immunological Reviews

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Summary A diverse number of DNA and RNA viruses have the potential to invade the central nervous system (CNS), causing inflammation and injury to cells that have a limited capacity for repair and regeneration. While rare, viral encephalitis in humans is often fatal and survivors commonly suffer from permanent neurological sequelae including seizures. Established treatment options are extremely limited, predominantly relying on vaccines, antivirals, or supportive care. Many viral CNS infections are characterized by the presence of antiviral antibodies in the cerebral spinal fluid (CSF), indicating local maintenance of protective antibody secreting cells. However, the mechanisms maintaining these humoral responses are poorly characterized. Furthermore, while both viral and autoimmune encephalitis are associated with the recruitment of diverse B cell subsets to the CNS, their protective and pathogenic roles aside from antibody production are just beginning to be understood. This review will focus on the relevance of B cell responses to viral CNS infections, with an emphasis on the importance of intrathecal immunity and the potential contribution to autoimmunity. Specifically, it will summarize the newest data characterizing B cell activation, differentiation, migration, and localization in clinical samples as well as experimental models of acute and persistent viral encephalitis.

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“…Enterovirus A 71 (EVA71) is the primary causative agent of hand, foot and mouth disease (HFMD), a generally mild, self-limiting condition affecting young children. In severe cases the disease can present with neurological complications reminiscent of poliomyelitis [1–4]. The financial and humanitarian cost associated with HFMD has encouraged the development of a number of vaccines against EVA71.…”

Section: Introductionmentioning

confidence: 99%

Thermal stabilization of enterovirus A 71 and production of antigenically stabilized empty capsids

Kingston

Shegdar

Snowden

et al. 2022

Journal of General Virology

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Enterovirus A71 (EVA71) infection can result in paralysis and may be fatal. In common with other picornaviruses, empty capsids are produced alongside infectious virions during the viral lifecycle. These empty capsids are antigenically indistinguishable from infectious virus, but at moderate temperatures they are converted to an expanded conformation. In the closely related poliovirus, native and expanded antigenic forms of particle have different long-term protective efficacies when used as vaccines. The native form provides long-lived protective immunity, while expanded capsids fail to generate immunological protection. Whether this is true for EVA71 remains to be determined. Here, we selected an antigenically stable EVA71 virus population using successive rounds of heating and passage and characterized the antigenic conversion of both virions and empty capsids. The mutations identified within the heated passaged virus were dispersed across the capsid, including at key sites associated with particle expansion. The data presented here indicate that the mutant sequence may be a useful resource to address the importance of antigenic conformation in EVA71 vaccines.

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Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiving rituximab

Cited by 11 publications

References 31 publications

Antiviral treatment with fluoxetine for rituximab‐associated chronic echovirus 13 meningoencephalitis and myofasciitis

Antiviral treatment with fluoxetine for rituximab‐associated chronic echovirus 13 meningoencephalitis and myofasciitis

B cells going viral in the CNS: Dynamics, complexities, and functions of B cells responding to viral encephalitis

Thermal stabilization of enterovirus A 71 and production of antigenically stabilized empty capsids

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