Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease

Gnann, John W.; Agrawal, Amy Guillet; Hart, John; Buitrago, Martha; Carson, Paul J.; Hanfelt-Goade, Diane; Tyler, Ken; Spotkov, Jared; Freifeld, Alison G.; Moore, Thomas W.; Reyno, Jorge; Masur, Henry; Jester, Penelope; Dale, Ilet; Li, Yufeng; Aban, Inmaculada; Lakeman, Fred D.; Whitley, Richard J.

doi:10.3201/eid2511.190537

Cited by 36 publications

(39 citation statements)

References 33 publications

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“…Several authors report successful application of these preparations in human patients. [65][66][67] While their use seems intuitively convincing, data as to their efficiency is controversial: a recently published trial of 62 hospitalized WNV encephalitis patients randomized to receive Omr-IgG-am ® (an IVIG containing antibodies specific for WNV), standard IVIG, or normal saline showed no significant differences between groups receiving Omr-IgGam compared with IVIG or saline for either the safety or efficacy endpoints [26]. Reasons may have included a small study population (the trial was terminated prematurely), delayed enrolment of participants (mean time from admission to infusion of study drug 2.7 days), and dosage (only a single infusion of the trial drug).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

Wagner¹,

Leibetseder²,

Troescher³

et al. 2021

J Neurol

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Background For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. Methods We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. Results We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033–0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. Conclusion Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

Wagner¹,

Leibetseder²,

Troescher³

et al. 2021

J Neurol

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“…Subsequent clinical trials have shown limited efficacy for IVIG in treatment of WNv encephalitis [ 16 ]. In the first trial, 242 patients were screened, but only 64 (26%) met the entry criteria; therefore, their data were not tabulated.…”

Section: Discussionmentioning

confidence: 99%

Unusual Movement Disorders and Atypical Magnetic Resonance Imaging (MRI) Findings in Patients with West Nile Encephalitis: Case Reports of 2 Patients with Evidence of Clinical and Imaging Resolution with IVIG

2021

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Case series Patients: Male, 34-year-old • Female, 57-year-old Final Diagnosis: West Nile virus myeloradiculitis • West Nile virus opsoclonus myoclonus ataxia syndrome Symptoms: Confusion • lower extremity weakness • opsoclonus-myoclonus-ataxia Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases • Neurology Objective: Unusual clinical course Background: West Nile virus (WNv) is the leading cause of epidemic arbovirus encephalitis in the continental United States. Movement disorders (MDs) have been reported in 20% to 40% of patients with WNv and about 37% of patients with WNv encephalitis have changes on magnetic resonance imaging (MRI). We report 2 unusual cases of neuroinvasive WNv in patients with unusual MDs and unreported MRI findings. Case Reports: In the first case, a 34-year-old man presented with a 1-week history of disinhibition, agitation, opsoclonus-myoclonus and ataxia syndrome (OMAS), tremor, and facial agnosia. Evaluation of his cerebrospinal fluid (CSF) revealed elevated immunoglobulin (Ig)M against WNv, a high level of protein (98 mg/dL), and an elevated white blood cell (WBC) count (134, 37% lymphocytes). An MRI of the brain showed an area of diffusion restriction in the splenium of the corpus callosum . The patient’s MRI findings and OMA improved significantly after 2 treatments with i.v. IG (IVIG). In the second case, a 57-year-old woman presented with fever, headaches, psychosis, and ataxia; she was subsequently intubated for airway protection. Analysis of her CSF showed elevated IgM against WNv, a high level of protein (79 mg/dL), and elevated WBC count (106, 90% lymphocytes). One week after the onset of symptoms, the patient experienced facial dyskinesia. Later, she developed proximal bilateral lower extremity weakness. An MRI of her lumbar spine showed evidence of myeloradiculitis with contrast enhancement of the conus medullaris and ventral nerve roots. After a single treatment with IVIG, she had partial improvement in weakness. Conclusions: MDs and changes on MRI have been reported in patients with neuroinvasive WNv disease. Our patient with OMAS also had transient splenial diffusion restriction on imaging, which, to the best of our knowledge, has not been previously reported with WNv infection. In both patients, treatment with IVIG resulted in improvement in symptoms.

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“…No significant difference was noted between the treatment, active placebo, or passive placebo groups regarding adverse effects or 90-day outcome. Unfortunately, this trial experienced multiple challenges enrolling participants and obtaining both the study drug and the active placebo, so it was ended before target enrollment was reached, and the higher dose treatment arm was abandoned [ 78 ].…”

Section: Geographic Emergencementioning

confidence: 99%

“…This precludes the enrollment of any acute cases that present at a hospital or clinic which is not already approved. These authors argue that having one centralized IRB would have facilitated the timely enrollment of participants from a wide variety of clinical sites [ 78 ]. Additionally, the sporadic occurrence of many WNND cases can make it difficult to reach necessary target enrollment.…”

Section: Geographic Emergencementioning

confidence: 99%

A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease?

2021

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After the unexpected arrival of West Nile virus (WNV) in the United States in 1999, the mosquito-borne virus quickly spread throughout North America. Over the past 20 years, WNV has become endemic, with sporadic epizootics. Concerns about the economic impact of infection in horses lead to the licensure of an equine vaccine as early as 2005, but few advances regarding human vaccines or treatments have since been made. There is a high level of virus transmission in hot/humid, subtropical climates, and high morbidity that may disproportionately affect vulnerable populations including the homeless, elderly, and those with underlying health conditions. Although WNV continues to cause significant morbidity and mortality at great cost, funding and research have declined in recent years. These factors, combined with neglect by policy makers and amenability of control measures, indicate that WNV has become a neglected tropical disease.

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Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease

Abstract: Immunoglobulin administered to adults with neuroinvasive disease appeared to be safe but was not demonstrated to improve clinical outcomes.

Cited by 36 publications

References 33 publications

Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review

Unusual Movement Disorders and Atypical Magnetic Resonance Imaging (MRI) Findings in Patients with West Nile Encephalitis: Case Reports of 2 Patients with Evidence of Clinical and Imaging Resolution with IVIG

A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease?

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