Neuroinvasive West Nile Virus Infection in Kidney Transplantation: Three Case Reports.

Literature on the natural course of neuroinvasive West Nile virus (WNV) infection in solid organ transplant (SOT) recipients is sparse. In the setting of a 2021 WNV outbreak in Arizona, we reviewed our institution's experience with neuroinvasive WNV infection in patients with SOT. We retrospectively identified SOT recipients treated for neuroinvasive WNV at Mayo Clinic in Arizona from 2007 through 2021. Clinical manifestations, disease course, and outcomes were analyzed. Among 24 SOT recipients with WNV infection identified during the study period, 13 infections occurred in 2021. Most patients had gastrointestinal tract symptoms and fever at disease presentation. Five patients had cognitive impairment, and 14 initially or eventually had acute flaccid paralysis. Clinically significant deterioration occurred at a median of 4 (range, 1-11) days after hospital admission. Seventeen patients (71%) were transferred to the intensive care unit, with 15 requiring mechanical ventilation. Initial cerebrospinal fluid analysis mainly demonstrated a neutrophil-predominant pleocytosis. Almost all patients (n = 23) were treated with intravenous immunoglobulin alone or in combination with interferon alfa-2b. Sixteen patients had clinical improvement, 4 of whom recovered completely. Six patients died during hospitalization due to complications of neuroinvasive WNV infection. Two patients were discharged to hospice without clinical recovery. The overall 30-day mortality rate was 36%. Despite advances in supportive care, neuroinvasive WNV infection is associated with substantial morbidity and mortality in SOT recipients. Flaccid paralysis is an indicator of poor prognosis. This article is protected by copyright. All rights reserved.

Reduction of immunosuppression (ROI) remains the mainstay of treatment for BK virus infection (BKVI) in kidney transplantation (KT). This review explored the role of intravenous immunoglobulin (IVIG) and mammalian target of rapamycin inhibitor (mTORi) regimens as alternative therapies for KT recipients with BKVI, focusing on viral clearance and graft-related outcomes. An electronic search was conducted for articles examining IVIG or mTORi use in treating BKVI among adult and/or pediatric KT recipients. Meta-analyses of proportions were performed for relevant outcomes. Twenty-seven studies (13 evaluating IVIG and 14 evaluating mTORi) were included; all but three enrolled only adult participants. In IVIG studies, the pooled viral clearance rate was 76.4% (95% confidence interval [CI], 64.2%-85.5%), with numerically higher clearance for IVIG after ROI compared to IVIG with ROI (87.0% vs. 66.1%). Overall graft survival was 84.7% (95% CI, 70.7%-92.7%), with numerically higher survival in IVIG after ROI than in IVIG with ROI (93.6% vs. 78.4%). Pooled histological clearance and graft rejection rates were 82.8% and 14.5%, respectively. In mTORi studies, the pooled viral clearance rate was 68.0% (95% CI, 58.0%-76.7%) and overall graft survival was 89.1% (95% CI, 82.7%-93.4%), with no significant difference between patients with and without prior ROI. Histological clearance and graft rejection rates were 59.8% and 8.6%, respectively. IVIG and mTORi regimens appear to be feasible alternatives to ROI in KT recipients with BKVI, achieving viral clearance while maintaining graft survival. Future randomized controlled trials are needed to further define their role and strengthen current evidence with higher-quality data.

Persistent Neurobehavioral Signs and Symptoms Following West Nile Fever

West Nile virus, a mosquito-borne infection, is known to cause a wide spectrum of clinical manifestations ranging from asymptomatic infection to neuroinvasive disease. Advanced age is a known risk factor for developing neuroinvasive disease and also a prognostic indicator of long-term recovery. We present a case of neuroinvasive West Nile virus infection in a 78-year-old man who presented with acute flaccid paralysis and altered mental status. Positive IgM for West Nile virus in the cerebrospinal fluid confirmed the diagnosis. Individuals presenting with meningitis, encephalitis, and/or acute flaccid paralysis should be assessed for West Nile virus especially if presenting during outbreaks in the summer and fall months. Although treatment remains supportive, prompt diagnosis and reporting of the infection can identify potential outbreaks, emphasize the importance of preventative measures, and promote clinician awareness. J Med Cases. 2019;10(1):21-23 doi: https://doi.org/10.14740/jmc3212

We describe the clinical course of two cases of neuroinvasive West Nile Virus (WNV) infection in the critical care unit. The first case is a 70-year-old man who presented during summer with mental status changes. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with lymphocyte predominance. WNV serology was positive in the CSF. His condition worsened with development of left-sided weakness and deterioration of mental status requiring intensive care. The patient gradually improved and was discharged with residual left-sided weakness and near-complete improvement in his mental status. The second case is an 81-year-old man who presented with mental status changes, fever, lower extremity weakness, and difficulty in walking. CSF analysis showed pleocytosis with neutrophil predominance. WNV serology was also positive in CSF. During the hospital stay his mentation worsened, eventually requiring intubation for airway protection and critical care support. The patient gradually improved and was discharged with residual upper and lower extremity paresis. Neuroinvasive WNV infection can lead to significant morbidity, especially in the elderly. These cases should be suspected in patients with antecedent outdoor activities during summer. It is important for critical care providers to be aware of and maintain a high clinical suspicion of this disease process.

We present the clinical course, and treatment of two consecutive cases of neuroinvasive West Nile virus (WNV) infection in the Clinic of Intensive Care, an Intensive Care Unit (ICU) at the Military Medical Academy - Sofia. Clinical and epidemiological data, microbiological, laboratory, molecular methods, and imaging techniques were used. Both patients resided in Sofia, Bulgaria, and had not travelled in recent months. The first case was a 60-year-old man who have had mental status changes, fever, and progression of existing Parkinson's disease. Antibodies to WNV were present in cerebrospinal fluid (CSF). His condition worsened with the development of sepsis and respiratory failure and he ended up lethally. The second case was a 72-year-old man who had fever and lower dyspeptic syndrome for one week, mental status changes, with adynamia to inability to walk independently, and head, hand and tongue tremors. CSF analysis showed mild pleocytosis with proteinorachy. Antibodies to WNV were present in serum, and PCR for WNV in urine was positive. The patient was admitted to ICU due to worsened mental and neurological status, coma and development of acute respiratory failure, necessitating intubation and assisted pulmonary ventilation. The patient ended lethally 13 days later. Neuroinvasive WNV infection can cause substantial morbidity, particularly among older adults, and high mortality, in the presence of comorbidities. Physicians should include West Nile virus infection in the differential diagnosis of aseptic meningitis and encephalitis, should perform appropriate laboratory tests, and report immediately the cases to the public health authorities.

Parvovirus B19 infection in kidney transplant recipients: A prospective study in a teaching hospital in Shanghai, China

Asymmetric Weakness and West Nile Virus Infection

West Nile virus (WNV) is a flavivirus that is recognized as one of the common causes of arboviral neurological disease in the world. WNV infections usually manifest with constitutional symptoms such as fever, fatigue, myalgia, rash, arthralgia, and headache. Neuroinvasive WNV infections are characterized by signs and symptoms suggestive of meningitis, encephalitis, meningoencephalitis, and acute flaccid paralysis. In addition, many patients with neuroinvasive WNV infection develop a wide range of movement disorders. This article aims to comprehensively review the spectrum and natural course of the movement disorders observed in patients with neuroinvasive WNV infections. A literature search was performed in March 2019 (in PubMed and EMBASE) to identify articles for this review. Movement disorders observed in the context of WNV infections include tremor, opsoclonus-myoclonus, parkinsonism, myoclonus, ataxia, and chorea. Most often, these movement disorders resolve within a few weeks to months with an indolent course. The commonly observed tremor phenotypes include action tremor of the upper extremities (bilateral > unilateral). Tremor in patients with West Nile meningitis subsides earlier than that in patients with West Nile encephalitis/acute flaccid paralysis. Opsoclonus-myoclonus in WNV infections responds well to intravenous immunoglobulins/plasmapheresis/corticosteroids. Parkinsonism has been reported to be mild in nature and usually lasts for a few weeks to months in the majority of the patients. A wide spectrum of movement disorders is observed in neuroinvasive WNV infections. Longitudinal studies are warranted to obtain better insights into the natural course of these movement disorders.

COVID-19 in Kidney Transplantation: Outcomes, Immunosuppression Management, and Operational Challenges.

Severe neuroinvasive West Nile virus infection in a child with undiagnosed Addison's disease

West Nile Virus varies in presentation from asymptomatic to a febrile illness often associated with malaise, weakness and maculopapular rash. West Nile neuro-invasive disease often manifests as meningitis, encephalitis, and less commonly acute flaccid paralysis in a "polio-like" presentation. Acute transverse myelitis (ATM) is a rare manifestation. We present a case of neuro-invasive West Nile Virus infection with radiographic evidence of longitudinally extensive transverse myelitis (LETM), a subset of ATM. A 42-year-old male from Massachusetts presented with progressive asymmetric paralysis of 4 days duration after developing a prodrome of fever, neck stiffness and urinary retention. Physical examination demonstrated asymmetric lower extremity weakness Lumbar puncture revealed lymphocytic pleocytosis with normal protein and glucose and a positive West Nile IgM in CSF (4.89, reference <0.90), and West Nile Virus detected by PCR in CSF. His West Nile serum IgM was 3.03 (reference range <0.90) and IgG was <1.30 (reference range <1.30). MRI of the lumbar spine showed findings consistent with the diagnosis of ATM. With our patient's presentation of acute onset asymmetrical weakness following a viral illness, we ruled out differentials including demyelinating syndrome such as GBS, inflammation of the meninges through meningitis or meningoencephalitis, or traumatic/ischemic involvement of the spinal cord directly. Due to the MRI findings, his motor weakness and urinary retention, supporting CSF findings and WNV positive serologies, ATM due to WNV infection was the main suspect for his presentation. Although ATM is an uncommon manifestation of WNV, it is imperative to consider this in the differential for patients presenting with acute onset flaccid paralysis in regions where WNV is endemic.

West Nile virus (WNV) is a zoonotic arbovirus transmitted by mosquitoes between wild birds (natural hosts) and other vertebrates. Horses and humans are incidental, dead-end hosts, but can develop severe neurological disorders. Owing to the close contact of cerebrospinal fluid (CSF) with the extracellular fluid of the brain, the analysis of CSF composition can reflect central nervous system (CNS) impairments enabling the diagnosis and understanding of various neurodegenerative CNS disorders. Our objective was to compare the findings from the CSF samples of horses with neuroinvasive WNV infection with those of healthy controls. We compared findings from fifteen CSF samples of 13 horses with acute WNV encephalomyelitis with those of 20 healthy controls. Protein, particular enzymes and ions, glucose and lactate showed abnormal levels in a significant number of WNV cases. None of the six horses with elevated glucose concentrations survived. Rather neutrophilic than mononuclear pleocytosis was identified with WNV infection. Neutrophils probably play a role in the development of inflammatory response and brain damage. Although elevated glucose levels reliably predicted the outcome, they might be the consequence of increased plasma levels and reflect general stress rather than CNS pathophysiology. The CSF findings of WNV encephalomyelitis patients are non-specific and variable but facilitate the differential diagnosis.

BackgroundCentral nervous system (CNS) infections in kidney transplant recipients (KTRs) remain poorly characterized, with current evidence largely derived from isolated case reports over the past two decades. This multicenter study aims to systematically delineate the epidemiology, clinical profiles, and outcomes of CNS infections in a large KTR cohort.MethodsWe conducted a retrospective analysis of 3,602 KTRs across three transplant centers in China (May 2004–July 2024). CNS infections were defined by: 1) neurological symptoms/signs, and 2) microbiological confirmation via cerebrospinal fluid (CSF) analysis, including metagenomic next-generation sequencing (mNGS) and routine microbiologic testing (bacterial and fungal cultures).ResultsCNS infections were diagnosed in 0.53% of KTRs (19/3602), with symptom onset occurring 2–121 months post-transplantation. Etiologies included bacterial (47%, 9/19), viral (32%, 6/19), and fungal (21%, 4/19) pathogens. Notably, 79% of cases (15/19) were exclusively identified by mNGS, whereas conventional cultures failed detection. Presenting symptoms included headache (79%) and altered mental status (42%). Mortality reached 42% (8/19) within 9–22 days of diagnosis; among survivors, 73% (8/11) exhibited neurological sequelae.ConclusionsCNS infections in KTRs are rare but characterized by rapid progression and high fatality rate. While the risk of CNS infections persists throughout the post-transplant period, 1–6 months after transplantation is a higher-incidence period of CNS infections. KTRs with neurological symptoms (particularly headache and elevated CSF pressure) should undergo CSF mNGS which is critical in diagnosing such infections.

BackgroundVaricella zoster virus (VZV) infection is a well-known opportunistic infection in solid organ transplant recipients. Since the various strategies of the use of anti-herpetic drugs including ganciclovir or acyclovir have evolved, the epidemiology of VZV infection is changing. However, there are limited data on the recent incidence and risk factors of post-transplant VZV infection in popular preemptive ganciclovir era for CMV infection. We evaluated the incidence, risk factors and clinical characteristic of patients with development of post-transplant VZV infection in kidney transplant (KT) recipients after 1-month acyclovir prophylaxis in the hospital that adopted preemptive ganciclovir therapy for CMV infection.MethodsAll adult patients with seropositive CMV antibody admitted to a KT unit from January 2014 to December 2017 were retrospectively reviewed in a tertiary-care hospital in South Korea. Our hospital adopted preemptive ganciclovir therapy for CMV infection in all CMV seropositive KT recipients. We administered acyclovir prophylaxis for 1-month to CMV seropositive KT recipients. The primary endpoint was VZV infection development after KT.ResultsA total of 1295 KT recipients was followed up for 4295.8 person-years. The median follow-up period was 46.6 months (interquartile range (IQR) 34.3-59.5). Of the 1295 recipients, 100 (7.7%, 2.33 per 100 person-years, 95% confidence interval (CI) 1.89-2.83) patients developed VZV infection after KT. The median time for VZV infection development was 9.5 months (IQR 4.7-22.1). All patients had VZV-associated skin lesion, 9 postherpetic neuralgia, 2 visceral involvement and 3 disseminated infection. Of 100 patients, 16 patients need hospitalization due to VZV infection. In multivariate analysis, deceased donor KT (Hazard ratio (HR) 1.6; 95% CI 1.0-2.39, p = 0.05), mycophenolate maintenance immunosuppressive therapy (HR 0.3; 95% CI 0.14-0.75, p = 0.01) and rejection episode (HR 0.31; 95% CI 0.14-0.71, p = 0.01) were independently associated with VZV infection development after KT.ConclusionAbout one tenth of CMV seropositive KT recipients developed zoster after 1-month ACV prophylaxis during CMV preemptive strategy, especially in those who received deceased donor KT, mycophenolate therapy, and rejection episodes.DisclosuresAll Authors: No reported disclosures