Detection Of Varicella-zoster Virus DNA Research Articles

Treatment with Brivudine in Immunocompromised Pediatric Patients with Herpes Zoster

Introduction: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increase during immunosuppression. Especially, immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudine), one of the most potent oral inhibitors of VZV replication, is widely used in the therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudine in immunocompromised children to provide an outpatient treatment option. Methods: In this retrospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudine was administered orally at a single dose of 2 mg/kg per day. We monitored the patients’ response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred. Results: Patients received medication for 7–21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications. Crusting of lesions was reached after 3–14 days (median: 6 days). Full healing of skin lesions was ascertained within 7–21 days (median: 12 days). Overall, brivudine therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner. Conclusion: Oral brivudine was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers the potential for outpatient treatment of HZ in these patients.

Woman with dyspnea after skin rash.

Woman with dyspnea after skin rash.

A case of chickenpox with multiple bacterial complications requiring surgical treatment

Chickenpox is a controlled infection, even a single vaccination effectively prevents the development of severe forms (up to 98%).Purpose — to demonstrate a case of severe chicken pox in a child aged 3.8 years with secondary infection of the skin of the right subscapular region and subcutaneous fat (phlegmon of the trunk) of streptococcal etiology.The diagnosis of varicella was confirmed by the detection of Varicella-Zoster virus DNA by PCR from the skin. Surgical treatment was performed — opening and drainage of phlegmon, purulent-serous discharge was obtained, sowing was performed, Streptococcus pyogenes was isolated.The child received antibiotic therapy — cefepime sulbactam, amikacin, acyclovir, infusion therapy, local treatment.Conclusions. The given clinical case demonstrates the development of a severe bacterial complication of chicken pox, which required surgical treatment and substantiates the need for vaccination against chicken pox and its possible complications.

Varicella zoster-associated progressive lower cranial and upper cervical polyneuropathy: a case report

BackgroundMultiple cranial neuropathies carry a wide range of differential diagnoses, and when combined with cerebrospinal fluid monocytosis they often suggest an infective etiology. Reactivation of varicella zoster virus has been associated with a wide range of neurological complications. Among the cranial nerves, the upper cranial nerves (trigeminal and facial nerves) are more commonly affected; there have been some reports of lower cranial polyneuropathies resulting from varicella zoster virus reactivation. However, polyneuropathy involving both the cranial and cervical nerves is rarely reported.Case presentationThis report highlights the case of a 64-year-old Chinese man presenting with an acute, severe dysphagia and dysphonia secondary to herpes zoster-associated progressive polyneuropathy involving the lower cranial and upper cervical nerves, without any mucocutaneous manifestations.ConclusionsTo our knowledge, this is the first case of varicella zoster virus-associated cranial and cervical polyneuropathy in the literature. The report also highlights the poor sensitivity of varicella zoster virus DNA detection by polymerase chain reaction in the cerebrospinal fluid, and proposes that serology be routinely performed in such polymerase chain reaction-negative cases without a clear diagnosis.

Meningitis retention syndrome caused by varicella zoster virus in a patient without a rash: a case report

BackgroundMeningitis retention syndrome (MRS) is a rare condition that presents with acute urinary retention as a complication of aseptic meningitis. Cases of MRS due to varicella zoster virus (VZV) infection without a rash are rare. We report the case of a patient who had no signs of meningitis or VZV infection, including a rash.Case presentationA 58-year-old man presented with dysesthesia of the lower limbs and acute urinary retention. He had fever but no rash and no signs of meningitis. He was diagnosed to have VZV infection based on the detection of VZV DNA in the cerebrospinal fluid. He responded satisfactorily to a course of intravenous acyclovir and experienced no sequelae during a 2-year follow-up period.ConclusionMRS due to aseptic meningitis of viral origin should be considered in the differential diagnosis of acute urinary retention even in the absence of specific signs and symptoms of meningitis or a suggestive rash.

Varicella zoster virus (VZV)-specific immunity and subclinical VZV reactivation in patients with autoimmune diseases.

Background/AimsThe risk of herpes zoster (HZ) is increased in patients with autoimmune diseases (AID), probably due to immunosuppressive therapy.MethodsThis prospective cross-sectional study investigated varicella zoster virus (VZV)-specific immunity in relation to subclinical VZV reactivation in 48 AID patients and 48 healthy controls (HCs). We assessed humoral immunity (serum VZV immunoglobulin g [IgG], IgA, and IgM) and cell-mediated immunity (interferon-γ [IFNγ]-releasing assay) to VZV as well as salivary VZV DNA status. Subclinical VZV reactivation was confirmed by detecting VZV DNA in saliva or VZV IgM in serum in the absence of typical HZ symptoms.ResultsMedian IgA levels were higher in the AID group than in the HC group, while VZV IgG and IgM levels were comparable between the groups. AID patients showed fewer IFNγ spot-forming cells (SFCs) upon VZV stimulation than HCs (58.2 vs. 122.0 SFCs/106 peripheral blood mononuclear cells [PBMCs], p < 0.0001). Subclinical VZV reactivation was more frequent in AID patients than in HCs (12.5% vs. 0%, p = 0.01). AID patients with VZV reactivation received prednisolone more frequently and at a higher dose than AID patients without reactivation. VZV-specific IFNγ SFCs were significantly lower in patients with VZV reactivation among AID patients (26.3 vs. 62.6 SFCs/106 PBMCs, p < 0.0001).ConclusionsResults suggest that poor cellular response against VZV might cause clinical and subclinical reactivation of VZV in AID patients.

Varicella zoster virus infection in neurological patients in Bulgaria.

The clinical manifestations of neurological complications associated with varicella zoster virus (VZV) are non-specific and indistinguishable from those of other viral infections. Therefore, the definite diagnosis requires evidence of VZV infection in cerebrospinal fluid (CSF). The aim of this study was to determine the frequency of VZV DNA detection in CSF of patients with neurological diseases in order to obtain information concerning involvement of VZV infection in neuropathology in the country. This study is a retrospective survey of test results obtained from January 2015 to October 2019. During this period, 411 CSF specimens were tested for the presence of VZV DNA by nested PCR. Fisher's exact test was used to test for statistically significant difference in the frequency of VZV DNA positivity of CSF specimens from different groups. Of all 411 tested CSF samples, 11.2% were positive for VZV DNA. The highest VZV prevalence was detected in CFS from patients with meningitis-18.2%, followed by patients with cranial neuritis (15.4%), encephalitis (12.2%), Guillain-Barré syndrome (11.1%), myelitis (10%), and with other neurological syndromes (8.2%). The difference of VZV prevalence in CSF of patients according to the gender and age was not statistically significant. Our results indicated that VZV is a frequent causative agent of neurological diseases, suggesting an important role of VZV infection for neuropathology in the country. Therefore, efforts for wider application of VZV identification in CSF to facilitate faster onset of antiviral treatment and further strategies concerning varicella zoster virus vaccines in the country are needed.

Characteristics and Long-term Prognosis of Danish Patients With Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared With the Background Population.

Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown. We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes. Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort. Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity.

Cognitive impairment without altered levels of cerebrospinal fluid biomarkers in patients with encephalitis caused by varicella-zoster virus: a pilot study

Varicella-zoster virus (VZV) is one of the most common agents causing viral infections of the central nervous system (CNS). VZV encephalitis is associated with severe neurological sequelae, despite antiviral treatment. Cognitive impairment has been reported and VZV has been associated with dementia. Our aim was to investigate the cognitive impairment and cerebrospinal fluid biomarkers in a follow-up study of patients with VZV encephalitis. Thirteen patients with VZV encephalitis, diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF) by PCR and concomitant symptoms of encephalitis, were included. Neuropsychological assessment in parallel with a lumbar puncture to obtain CSF was performed 1.5–7 years after acute disease. The CSF biomarkers neurofilament light chain (NFL), S100B, glial fibrillary acidic protein (GFAP), amyloid-β (Aβ) 40 and Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) were analysed and compared to controls (n = 24). Cognitive impairment was shown in the domains of executive functions and speed/attention and to a minor degree in the domains of learning/memory and language, indicated by a significantly poorer performance on seven neuropsychological test variables. No convincing evidence of alterations in concentrations of biomarkers in the CSF were shown. Our results indicate that patients with VZV encephalitis suffer from cognitive impairment long time after acute disease. Importantly, these impairments do not seem to be accompanied by biomarker evidence of ongoing neuronal or astrocytic injury/activation or induction of dementia-related brain pathologies by the infection.

Encephalitis due to herpes zoster without rash in an immunocompetent 12-year-old girl: case report and review of the literature

BackgroundNeurological complications due to reactivation of varicella-zoster virus (VZV) are very uncommon in immunocompetent patients. Generally a vesicular rash is present on one or more dermatomes, preceding or following the main manifestation. Few cases are reported in the international literature, but they concern mainly adult or elderly patients.Case presentationA 12-year-old girl was referred to our hospital for persisting headache, cough and rhinitis for six days. After first examination, diagnosis of anterior sinusitis was made by nasal endoscopy. The day after, the girl developed psychotic symptoms and altered mental status. Computed tomography (CT) scan was immediately performed but was unremarkable; lumbar puncture revealed leukocytosis with lymphocytic predominance and cerebrospinal fluid polymerase chain reaction (PCR) detected varicella-zoster virus DNA. The diagnosis of acute VZV encephalitis was made. The patient was promptly treated with acyclovir infused intravenously and her clinical conditions rapidly improved. Tests made did not show any condition of immunosuppression.ConclusionsAlthough if rare, reactivation of VZV can occur in immunocompetent children and its complications can involve central nervous system. Among these complications, meningitis is more common, but cerebral parenchyma can also be involved leading to a severe medical condition that is defined meningoencephalitis. In rare cases vesicular rash may be absent; therefore high level of suspicion is required even in those patients in which suggestive clinical features are not present to guide the diagnosis. Intravenous acyclovir represents the treatment of choice to obtain a fast clinical response and to prevent the onset of late-term complications.

DISCREPANCIES IN BRONCHIAL WASH AND LAVAGE: THE DUBIOUS CASE OF VARICELLA PNEUMONIA

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Varicella pneumonia is a rare but serious infection caused by Varicella Zoster virus (VZV). Diagnosis is attained by clinical presentation, radiologic findings & is aided by detection of VZV in respiratory secretions by polymerase chain reaction (PCR). We present a diagnostic dilemma when two tests have a discrepancy. CASE PRESENTATION: A 41 year old female presented with left upper quadrant (LUQ) abdominal pain, hypotension, melena & somnolence which prompted intubation. She had medical history of end stage liver disease due to alcoholic cirrhosis, esophageal varices, refractory ascites & encephalopathy. Endoscopy showed varices & small bowel ulcer; & paracentesis ruled out bacterial peritonitis. After treatment with octreotide, nexium & prophylactic ceftriaxone; she was was successfully extubated. 3 days later, she developed a new, vesicular, dermatomal rash of shingles on LUQ. This was followed by new extensive multifocal infiltrates, crazy paving pattern & diffuse ground glass opacities on chest imaging (Figure) along with hypoxic respiratory failure which warranted re-intubation. A bronchoscopy was done which showed thick white secretions on bronchial washing (BW) & cloudy fluid on bronchoalveolar lavage (BAL) of right middle lobe & left upper-lingular segment. VZV PCR resulted positive on BW but negative on BAL. Patient was started on Varicella-Zoster immune globulin (VZIG) and acyclovir based on clinical presentation and radiologic features which led to clinical improvement. DISCUSSION: Varicella pneumonia can manifest 1-6 days after onset of the typical rash & is highly infectious with a secondary attack rate of > 90%. In the presence of clinical features of VZV infection, the diagnosis is mediated by chest imaging showing nodular or interstitial pneumonitis with ground glass opacities. Molecular diagnostic assays using PCR are often employed and have sensitivity as high as 96% for detection of VZV (1). However, it can be limited by false positive rate due to contamination and depends on the methodology (2) as well as specimen source although BAL has high sensitivity (3). Our patient developed respiratory failure with radiologic findings shortly after typical zoster rash. Despite adequate sampling, there was a discrepancy in the result obtained from BAL and BW. A comparison of these two hasn’t been studied yet in respect to VZV as well as other common pathogens. We favored to treat the patient due to detection of VZV on BW & the clinical presentation. VZIG administration within 72 hours of exposure is highly efficacious for disease prevention in immunocompromised along with intravenous acyclovir for 7-10 days and has led to overall decline in mortality. CONCLUSIONS: Although VZV DNA detection by PCR is helpful in diagnosing VZV pneumonia, there is no consensus data on its utility on BW in comparison to BAL. The paucity of VZV pneumonia is a hindrance for more extensive studies. Reference #1: Mirouse A et al. Severe varicella-zoster virus pneumonia: a multicenter cohort study. Critical Care. 2017 Dec;21(1):137 Reference #2: Schmutzhard J, Riedel HM, Wirgart BZ, Grillner L. Detection of herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus in skin lesions. Comparison of real-time PCR, nested PCR and virus isolation. Journal of clinical virology. 2004 Feb 1;29(2):120-6 Reference #3: Stránská R, Schuurman R, de Vos M, van Loon AM. Routine use of a highly automated and internally controlled real-time PCR assay for the diagnosis of herpes simplex and varicella-zoster virus infections. Journal of Clinical Virology. 2004 May 1;30(1):39-44 DISCLOSURES: No relevant relationships by Enambir Josan, source=Web Response No relevant relationships by Supriya Singh, source=Web Response No relevant relationships by Yasir Tarabichi, source=Web Response

Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series

Background: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy. Methods: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid. Results: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high β-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia. Conclusions: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.

Varicella-Zoster Virus and the Enteric Nervous System.

Varicella zoster virus (VZV) infects and becomes latent in sensory, enteric, and other autonomic neurons during the viremia of varicella. Reactivation of VZV in neurons that project to the skin causes the rash of zoster; however, reactivation of VZV in enteric neurons can cause a painful gastrointestinal disorder ("enteric zoster") without cutaneous manifestations. Detection of VZV DNA in saliva of patients with gastrointestinal symptoms may suggest enteric zoster. This diagnosis is reinforced by observing a response to antiviral therapy and can be confirmed by detecting VZV gene products in intestinal mucosal biopsies. We developed an in vivo guinea pig model that may be useful in studies of VZV latency and reactivation. VZV-infected lymphocytes are used to induce latent infection in sensory and enteric neurons; evidence suggests that exosomes and stimulator of interferon genes (STING) may, by preventing proliferation play roles in the establishment of neuronal latency.

Characteristics of patients with acute peripheral facial palsy showing Varicella zoster virus DNA in saliva.

Infection caused by Varicella zoster virus (VZV) is a common etiology of acute peripheral facial palsy (APFP). We aimed to assess the clinical significance of detecting VZV DNA from the saliva of patients with APFP. Saliva collected from 36 patients with unilateral APFP at initial visit was analyzed to detect VZV DNA by polymerase chain reaction. The House-Brackmann (HB) scale was used to evaluate FP severity on admission day, at week 2, and at weeks 10-12 after start of treatment. Among the 28 patients without rash, VZV DNA was detected in 3 patients (10.7%); 6 of 8 patients (75.0%) with rash showed VZV DNA (P = 0.001). VZV DNA-positive patients had worse hearing than VZV DNA-negative patients (P < 0.05). A significantly higher proportion of VZV DNA-negative patients (96.3%) showed complete recovery than VZV DNA-positive patients (55.6%) (P = 0.006). In conclusion, VZV DNA-positive patients had worse hearing and incomplete recovery compared to VZV DNA-negative patients, irrespective of the presence of rash. Tests for the detection of VZV DNA in saliva may be helpful for early differential diagnosis and choosing an appropriate medical treatment of APFP.

Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007-2014).

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n=9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.

Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome.

Reactivation of varicella zoster virus (VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome (RHS) or Ramsay Hunt Syndrome zoster sine herpete (RHS-ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein (NFL), S-100β protein and glial fibrillary acidic protein (GFAp) have previously been measured in cerebrospinal fluid (CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S-100β protein and GFAp in CSF from patients with RHS (n=15) and RHS-ZSH (n=13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group (n=52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House-Brackmann score. NFL and GFAp concentrations were increased compared with controls (P=0.008 and P=0.04), while S-100β levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS-ZSH (NS and P=0.028). The amount of viral DNA in CSF correlated with increased GFAp (P=0.003) and NFL (P=0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests.

Varicella-zoster virus (VZV) DNA in serum of patients with VZV central nervous system infections

Varicella-zoster virus (VZV) is a common viral agent causing central nervous system (CNS) infections, normally diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF). Our aim was to investigate trends in VZV DNAemia in VZV CNS infections, which could potentially contribute to diagnosis and secondly, correlate the amount of VZV DNA in serum to severity of disease. Seventy-two patients with VZV CNS infections diagnosed by detection of VZV DNA in CSF and concomitant neurological symptoms were included. The amount of VZV DNA was measured by real-time PCR in paired serum and CSF samples and compared to a control group of herpes zoster (n=36). An increased amount of VZV DNA was detected in serum in patients with encephalitis compared to patients with meningitis or Ramsay-Hunt syndrome, respectively (p=0.003 and p=0.024). A greater proportion of patients with VZV CNS infections and detectable VZV DNA in serum had ongoing rash compared to those without detectable VZV DNA in serum (p≤0.001). The viral load in serum of patients with neurological symptoms was lower compared to in patients with herpes zoster without neurological symptoms (p≤0.001) and only 32/72 of the patients with VZV CNS disease had VZV DNA detected in serum. Increased amount of VZV DNA in serum of patients with VZV CNS infections seems associated with encephalitis and ongoing rash. Additionally, viral DNA analysis by PCR in serum may be a helpful diagnostic tool although viral DNA analysis by PCR in CSF is the method of choice for diagnosis.

Cerebrospinal fluid biomarkers in facial nerve palsy caused by Varicella Zoster virus

No: 1680 Presentation at ESCV 2015: Poster 1 Cerebrospinal fluid biomarkers in facial nerve palsy caused by Varicella Zoster virus J. Lindstrom1,∗, A. Grahn1, H. Zetterberg2, M. Studahl1 1 Department of Infectious Diseases, Sahlgrenska University Hospital, Ostra, Goteborg, Sweden 2 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sweden Background: Reactivation of Varicella Zoster virus (VZV) can cause facial nerve palsy with neurological sequels despite treatment with aciclovir and/or corticosteroids. Associated symptoms such as vertigo and loss of hearing are frequent. Facial nerve palsy caused by VZV manifest as Ramsay Hunt syndrome when blisters are present, or as zoster sine herpete without blisters. Neurofilament light protein (NFL), glial fibrillary acidic protein (GFAp) and S-100 are cerebrospinal fluid (CSF) biomarkers that have been used to estimate severity of neuronal damage and prognosis in various CNS diseases. One previous study has been performed on VZV in the central nervous system (CNS), but patients with facial palsy have not been specifically studied. Methods: 28 patientswith VZV facial palsy, diagnosed by detection of VZV DNA in CSF by PCR, were retrospectively identified. GFAp, NFL and S-100 were measured in stored CSF samples and compared with a control group (n=52). Medical records were studied for relevant patient data such as severity of symptoms, treatment and laboratory parameters. Results: CSF concentrations of NFL and GFAp were significantly elevated compared to controls (p<0.01 and p<0.05) and S-100 concentrations were reduced. Additionally, NFL kinetics indicated slightly increasing concentrations in CSF samples drawn more than seven days after onset of neurological symptoms. Viral load (VZV DNA copies/ml) correlated with both NFL (Spearman r=0.51; p<0.01) and GFAp (Spearman r=0.54; p<0.01). No correlations were found between biomarkers and severity of symptoms, clinical outcome at follow-up, or treatment with aciclovir prior to CSF sampling in this small study. Conclusion: In this first study on biomarkers in facial palsy caused by VZV, we identified a pattern of elevated NFL, elevated GFAp and decreased S-100 compared to controls. Increased NFL levels reflect axonal damage, and elevated levels of GFAp, in combination with decreased concentrations of S-100 , indicate astrogliosis rather than damage to the astroglial cell membrane. Biomarkers of neuron and glial cell damage can be used to understand pathogenesis, and in future studies assessment of these biomarkers in relation to treatment and clinical outcome should be explored. http://dx.doi.org/10.1016/j.jcv.2015.07.137 Abstract No: 1682 Presentation at ESCV 2015: Poster 1 False negative influenza A virus subtype H3N2 in Prodesse GenProbe ProFlu+ PCR assay in season 2014–2015 N. Kirkby1,∗, T.N. Thomsen1, R. Trebbien2, K. Vorborg2, J. Ronn2, T.K. Fischer2, C.B. Christiansen1 1 Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark 2 National Influenza Center, Virological Surveillance and Research Department of Microbiological

Rapid salive test for varicella zoster virus

Varicella zoster virus (VZV) is a ubiquitous human herpesvirus typically causing childhood varicella (chickenpox) at which time a life-long latent infection is established in ganglionic neurons throughout the neuraxis. Reactivation of latent virus, typically in the elderly and immunocompetent usually causes zoster (shingles) but can also result in serious neurologic disease. In cases of vasculopathy, meningoencephalitis and myelitis where VZV is suspected, diagnosis requires detection of virus DNA or antibody in CSF. In collaboration with NASA, VZV DNA was found in saliva of health astronauts suggesting asymptomatic virus reaction due to the stress of spaceflight. This lead to a series of studies indicating virus DNA can be found in saliva of patients with VZV associated neurologic disease. With the goal of eliminating the need for lumbar puncture to diagnose VZV associated neurologic disease; we developed a rapid saliva test for the detection of VZV DNA in saliva that can be used in space as well as on Earth. Herein the test and its potential application will be present.

Neurological complications of varicella zoster virus reactivation.

Varicella zoster virus (VZV) reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis, and VZV vasculopathy. This review highlights the clinical features, laboratory abnormalities, imaging changes, and optimal treatment of each of those conditions. Because all of these neurological disorders produced by VZV reactivation can occur in the absence of rash, the virological tests proving that VZV caused disease are discussed. After primary infection, VZV becomes latent in ganglionic neurons along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity, VZV reactivates from ganglia and travels anterograde to the skin to cause zoster, which is often complicated by postherpetic neuralgia. VZV can also travel retrograde to produce meningoencephalitis, myelitis, and stroke. When these complications occur without rash, VZV-induced disease can be diagnosed by detection of VZV DNA or anti-VZV antibody in cerebrospinal fluid and treated with intravenous acyclovir. Awareness of the expanding spectrum of neurological complications caused by VZV reactivation with and without rash will improve diagnosis and treatment.