Detection of varicella-zoster virus DNA in peripheral mononuclear cells from patients with Ramsay Hunt syndrome or zoster sine herpete

On the basis of alterations in varicella-zoster virus (VZV) antibody titers, it appears that Bell's palsy in some patients could be associated with VZV reactivation, that is, zoster sine herpete. To obtain stronger evidence of this association, polymerase chain reaction (PCR) was used to detect VZV DNA in auricular lesions or peripheral blood mononuclear cells (PBMCs) from Bell's palsy or Ramsay Hunt syndrome patients. VZV DNA was detected in the auricular lesions of Ramsay Hunt syndrome, in PBMCs from 2 Ramsay Hunt syndrome patients, and in 4 of 17 samples from 16 Bell's palsy patients. Three of these four positive patients were thought to have zoster sine herpete because of hearing difficulty, vertigo, and pain. VZV IgM antibodies were positive in 1 of the 2 patients with Ramsay Hunt syndrome, and in 2 of the 17 samples from the Bell's palsy patients. VZV IgG antibody titers during the acute phase were significantly higher in the patients positive for the PCR or VZV IgM antibody than in those negative for them. These findings provide evidence that Bell's palsy in some patients could be associated with VZV reactivation. J. Med. Virol. 56:359–363, 1998 . © 1998 Wiley-Liss, Inc.     

Variable patterns of varicella-zoster virus reactivation in Ramsay Hunt syndrome

The mechanism by which reactivation of varicella-zoster virus (VZV) causes facial paralysis in Ramsay Hunt syndrome remains unclear. The relationship between VZV load and the onset of facial paralysis was analyzed in 42 patients with Ramsay Hunt syndrome. The patients were divided into three groups according to the times of appearance of zoster and of facial paralysis; group I (zoster preceding, n = 13), group II (simultaneous, n = 22), group III (paralysis preceding, n = 7). A real-time quantitative PCR assay was used to measure VZV DNA copy number in saliva, and paired sera were assayed for anti-VZV IgG and IgM antibodies. In group I, the VZV DNA-positive rate was low and virus load decreased gradually after the initial hospital visit around the time of onset of paralysis. The level of anti-VZV antibodies had in most cases already increased at that time. In group III, viral load tended to increase after the onset of paralysis and peaked around the time of appearance of zoster. The level of anti-VZV antibodies was low at the onset of paralysis but showed a significant increase when paired sera were tested. In group II, virus load and changes in level of anti-VZV antibodies either resembled group I or group III behavior. These results indicate that facial paralysis in Ramsay Hunt syndrome can occur at various times between the early and the regression phase of VZV reactivation, suggesting that there are variable patterns of development of facial nerve dysfunction caused by VZV reactivation and the progression of neuritis.     

Detection of varicella-zoster virus DNA in patients with acute peripheral facial palsy by the polymerase chain reaction,and its use for early diagnosis of zoster sine herpete

Varicella-zoster virus (VZV) reactivation without cutaneous vesicles (zoster sine herpete) has been demonstrated in 8 to 25% of patients with acute peripheral facial palsy (APFP) by serological methods. To make an early diagnosis of zoster sine herpete, VZV DNA in oropharyngeal swabs from patients with APFP was examined by the polymerase chain reaction (PCR). VZV DNA was detected in oropharyngeal swabs from 6 of 36 (17%) patients with APFP by PCR. VZV DNA was detected in the oropharyngeal swabs from the six patients at their initial visit (2 to 4 days after the onset of APFP), while the anti-VZV IgM and IgG antibody titers were not increased significantly. In contrast, VZV DNA was undetectable in the oropharyngeal swabs at the time when the VZV specific antibody response appeared. These results indicate that detection of VZV DNA in oropharyngeal swabs by PCR is more useful than currently available serological assays for the early diagnosis of zoster sine herpete in patients with APFP. J. Med. Virol. 52:316–319, 1997. © 1997 Wiley-Liss, Inc.     

Acute pain and postherpetic neuralgia related to Varicella zoster virus reactivation: Comparison between typical herpes zoster and zoster sine herpete

Herpes zoster (HZ) is typically characterized by pain involving the area of vesicular eruption. Several patients, however, complain of unilateral radicular pain without rash (zoster sine herpete [ZSH]). To evaluate whether the severity and duration of pain and the use of analgesics are greater in ZSH patients than in typical HZ with rash, 16 consecutive patients with acute unilateral pain, without vesicular eruption (ZSH), were compared with 16 controls suffering from typical HZ eruption. Only patients with laboratory evidence of varicella-zoster virus (VZV) reactivation were selected. Serum samples were obtained from all patients at their initial visit and 1 and 2 months later. Monthly, the administered therapies and the average pain score (visual analog scale [VAS] score) were recorded. VZV DNA persisted statistically higher in ZSH sera than HZ sera 1 month after onset (P = 0.0007). ZSH patients averaged greater pain than HZ patients, scoring VAS 76.88 and 66.88 ( P = 0.0012), respectively. ZSH patients used significantly more opioid therapy than HZ patients ( P = 0.0449; OR, 9.00). This is the first study comparing pain in ZSH and HZ patients: greater severity and duration of pain and more opioid use was detected in patients with ZSH.     

Persistence of varicella-zoster virus viraemia in patients with herpes zoster

BackgroundHerpes zoster is caused by the reactivation of varicella-zoster virus from sensory neurons. The commonest complication following zoster is chronic pain termed post herpetic neuralgia.ObjectivesTo investigate the dynamics of VZV viraemia and viral load following the resolution of zoster and its relationship to PHN development.Study designBlood samples were collected at baseline, 1 month, 3 months and 6 month from a prospective study of 63 patients with active zoster. Quantification of VZV DNA in whole blood was performed using a real-time PCR assay.ResultsDuring acute zoster, all patients had detectable VZV DNA in their blood. VZV DNA remained detectable in the blood of 91% of patients at 6 months although levels declined significantly (p < 0.0001). A history of prodromal symptoms (p = 0.005) and severity of pain at baseline (p = 0.038) as well as taking antivirals (p = 0.046) and being immunocompromised (p = 0.043) were associated, with longer time to recovery from PHN. Viral DNA loads were consistently higher in patients with risk factors for PHN and higher viral DNA loads over time were associated with longer time to recovery (p = 0.058 overall and 0.038 in immunocompetent).ConclusionsBased on these observations we hypothesise that VZV replication persists following acute shingles and that higher viral DNA loads contribute to the risk factors for PHN.     

Persistence of varicella-zoster virus DNA in blood mononuclear cells of patients with varicella or zoster

Varicella-zoster virus (VZV) DNA was detectable by in-situ hybridization in blood mononuclear cells (MNCs) of patients with varicella or zoster for 2–56 days after the onset of a rash. VZV DNA was present in many MNCs from one acute varicella patient 2 days after the onset of the rash and was rarely found in MNCs during acute zoster, convalescent zoster, and convalescent varicella. The morphology of MNCs containing VZV was heterogenous, although most viral-DNA-containing MNCs were large monocytoid cells. Serial examination of blood MNCs from one adult with varicella revealed VZV DNA up until 8 weeks, but not 16 weeks, after the appearance of the rash; parallel studies in four zoster patients showed VZV DNA up until 3 weeks, but not later than 7 weeks after the appearance of the rash. These results indicate that MNCs become infected with VZV during the primary encounter with VZV (varicella) and during reactivation (zoster) and that infection continues for weeks after the onset of the skin rash. Furthermore, the detection of VZV DNA in blood MNCs of uncomplicated zoster patients coincides with the period during which these patients experience pain.     

Detection of varicella-zoster virus DNA in throat swabs of patients with herpes zoster and on air purifier filters

Zoster patients are considered to be less contagious than those with varicella because their infectious lesions are localized. However, it is not known when the spread of varicella-zoster virus (VZV) from zoster patients begins, how long it continues, and how far the virus spreads from the zoster patients. Twelve cases of hospitalized zoster patients were studied. The polymerase chain reaction (PCR) was used to detect VZV DNA in samples taken from the surface of their eruptions, throats, and the air purifier filters in their rooms. In all patients, VZV DNA was detected in the samples from eruptions. VZV DNA was detected in 8 of 12 patients from the throats. VZV DNA was detected for 9 of 12 patients from the filter samples. This study shows the possibility of a wide distribution of VZV DNA to the environment from infected patients. VZV may be excreted from cutaneous eruptions or from the throats of patients.     

Rapid contamination of the environments with varicella-zoster virus DNA from a patient with herpes zoster

Patients with zoster are considered to be less contagious than varicella patients because their infection is localised. It is not known, however, when and for how long a spread of varicella-zoster virus (VZV) from a zoster patient begins and continues and the extent of virus spread from the patient. The polymerase chain reaction (PCR) was used to detect VZV DNA in samples obtained from the hands and throat of a patient with zoster and from her room environments including surfaces of the back of a chair, the door handle, the table and the air conditioner filter. VZV DNA was detected on the surfaces of the back of the seat and the table and in peripheral blood mononuclear cells (PBMCs) and serum on Day 4 of the illness. VZV DNAemia persisted for 4 days until Day 7 of the illness. It was also detected in samples collected from throat and the air conditioner filter on Days 6 and 7 of the illness respectively. All of the surfaces, that were examined in her home environment, were contaminated with VZV DNA by Day 7 of the illness. The present study showed rapid and wide spread of VZV DNA in the environment even from a patient with zoster.     

Different genotype pattern of varicella-zoster virus obtained from patients with varicella and zoster in Germany

The general use of the varicella vaccine requires the surveillance of varicella-zoster virus (VZV) strains in patients infected with VZV. This paper reports the data achieved from a prospective study of genotyping VZV in Germany, analyzing the restriction fragment length polymorphism (RFLP) of the open reading frames (ORF) 38, 54, and 62 as well as the polymorphism of the R5 repeat region. The study included 177 patients with varicella. Seventy-eight patients with zoster served as controls. Results revealed that 78% of VZV strains in patients with varicella had the genetic profile of the dominant wild-genotype occurring in Europe and 22% had the markers of African or Asian strains. Varicella patients with the profile of African or Asian strains were significantly younger than patients with varicella caused by the dominant genotype. By contrast, all zoster patients exhibited strains representing the majority of wild-type strains in Europe. In conclusion, VZV strains from patients with varicella have a significantly higher genetic variability than viral strains from zoster patients. Since variants with the markers of African or Asian strains could only be found in young children with chickenpox, the results suggest a changing scene of VZV genotypes in Germany. As reasons, the spread of viruses, which may be imported originally by persons immigrating from warmer climates, or the recombination between wild-and vaccine-type viruses have to be considered.     

Correlation between MRI and operative findings in Bell's palsy and Ramsay Hunt syndrome

PURPOSE: To investigate the correlation between gadolinium enhanced magnetic resonance image (MRI) results and surgical findings of facial nerves in Bell's palsy and Ramsay Hunt syndrome. MATERIALS AND METHODS: From 1995 to 2004, MRI was performed on 13 patients with Bell's palsy or Ramsay Hunt syndrome, who were offered with surgical decompression of the facial nerve through the middle cranial fossa approach. Gadolinium enhanced MRI was performed on all patients and the enhancement of the facial nerve was evaluated by radiology specialists. Operative findings including the degree of the facial nerve segment swelling were examined. Furthermore, the time interval from the onset of palsy to surgery was evaluated. RESULTS: Swelling of facial nerve segments was found in patients with enhanced facial nerves from MRI. The swelling of the facial nerve in the labyrinthine segment in particular was identified in all patients with enhanced labyrinthine segments in MRI. The intraoperative swelling of geniculate ganglion of facial nerve was found in 78% of patients with enhanced facial segment in MRI (p=0.01). The intraoperative swelling of tympanic segment was observed from fourth to ninth weeks after the onset of palsy. CONCLUSION: MRI enhancement of facial nerves in Bell's palsy and Ramsay Hunt syndrome is associated with the extent of intratemporal lesions of facial nerves, especially in the labyrinthine segment.     

Quantitation of varicella-zoster virus DNA in whole blood, plasma, and serum by PCR and electrochemiluminescence

We describe a highly sensitive assay for quantitation of varicella-zoster virus (VZV) DNA in blood, involving PCR amplification, solution hybridization with Tris-(2, 2'-bipyridine)-ruthenium(II) chelate-labeled probes, and measurement by electrochemiluminescence (ECL). Extraction and amplification efficiencies were monitored by the inclusion of internal control (IC) DNA, mimicking the VZV target, in the DNA extraction. Viral DNA load was calculated from the ratio of VZV and IC ECL signals. The lower limit of sensitivity was 20 VZV DNA copies/ml of plasma or serum and 80 copies/ml of whole blood. In reconstruction experiments, expected and calculated VZV DNA loads were in excellent accordance. Blood specimens from 42 VZV-infected patients were tested for the presence of VZV DNA and showed detection rates of 86% in patients with varicella and 81% in patients with herpes zoster. In specimens obtained during the first week after onset of the rash, detection rates were 100 and 89%, respectively. Viral DNA was detected in all immunocompromised patients with herpes zoster, emphasizing the risk of disseminated disease in this patient group. VZV DNA load was similar in patients with varicella and multidermatomal herpes zoster and lower in patients with unidermatomal zoster. Despite the cell-associated nature of the virus, VZV DNA was detected in serum and plasma at high copy numbers, and at similar frequencies compared to whole-blood specimens. Quantitation of VZV DNA in blood is of potential importance for diagnosis and clinical management of VZV-infected patients. Plasma and serum provide convenient matrices for this purpose.     

Simian varicella virus DNA shares homology with human varicella-zoster virus DNA

Delta herpesvirus (DHV) and Medical Lake Macaque (MLM) virus are cell-associated simian herpesviruses that cause varicella-like disease in nonhuman primates, and are antigenically related to human varicella-zoster virus (VZV). The results of studies designed to determine if homology exists between the DNA of DHV and MLM and the DNA of VZV are reported here. Southern blot hybridizations conducted at Tm-20 degrees did not detect DNA homology between the VZV and simian varicella virus genomes. However, under conditions of lower stringency (Tm-36 degrees and Tm-43 degrees), VZV DNA probes hybridized to specific HindIII fragments within DNA isolated from simian varicella virus-infected cells. Under similar hybridization conditions, DNA homology was not detected between VZV DNA and herpes simplex virus DNA. Further studies using cloned VZV DNA HindIII fragments as probes suggested that the homology between VZV DNA and DHV DNA is distributed across the viral genomes. These results demonstrate that the genomes of VZV and simian varicella virus share regions of conserved nucleotide sequences, and indicate a close evolutionary relationship between VZV and simian varicella viruses. In addition, the studies show that the DHV and MLM strains of simian varicella virus are more closely related to each other than to human VZV.     

Association between quantitative varicella-zoster virus antibody levels and zoster reactivation in HIV-infected persons

Background

Varicella-zoster virus (VZV) reactivation is common but difficult to predict in HIV-infected persons.

Objective

Since qualitative VZV antibodies can determine past VZV disease or vaccination, we evaluated whether quantitative VZV antibody levels over time can predict future zoster.

Study design

US Military HIV Natural History (NHS) participants with a zoster diagnosis at least 5 years after HIV diagnosis (n?=?100) were included. Zoster-negative controls (n?=?200) were matched by age, race, gender, and CD4 count at HIV diagnosis. Repository plasma specimens collected at baseline and prior to zoster diagnosis were evaluated using a quantitative anti-VZV ELISA assay. Differences in quantitative VZV levels were analyzed by Wilcoxon Mann–Whitney and Fisher’s exact tests.

Results

Median CD4 count at HIV diagnosis was similar for cases and controls (535 [IQR 384–666] vs. 523 [IQR 377–690] cells/μL; p?=?0.940), but lower for cases at zoster diagnosis (436 [IQR 277–631] vs. 527 [IQR 367–744] cells/μL; p?=?0.007). Antiretroviral therapy (ART) use prior to zoster diagnosis was lower for cases (52.0%) compared to controls (64.5%; p?=?0.025). Cases had similar mean VZV antibody levels prior to zoster diagnosis compared to controls [2.25?±?0.85 vs. 2.44?±?0.96 index value/optical density (OD) ratio; p?=?0.151] with no difference in the change in antibody levels over time (0.08?±?0.71 vs. 0.01?±?0.94 index value/OD per year; p?=?0.276).

Conclusion

Quantitative VZV antibody levels are stable in HIV-infected persons and do not predict zoster reactivation. Low CD4 count and lack of ART use appear to be better predictors of future zoster diagnosis.

     

Quantitation of antibodies to varicella-zoster virus by immune adherence hemagglutination.

Immune adherence hemagglutination was compared with the complement fixation test as a means of measuring antibodies to varicella-zoster virus. Analysis of acute- and convalescent-phase sera from patients infected with varicella-zoster or with herpes simplex virus showed the immune adherence hemagglutination test to be more sensitive than the complement fixation test, and greater cross-reactivity between the two viruses appeared to be associated with the increased sensitivity. The two assay methods were used to measure antibodies to varicella-zoster virus in 265 sera obtained from patients of different ages as well as sera from 26 patients with leukemia. There were 35 cases where antibodies were detected by immune adherence hemagglutination but not by complement fixation, whereas in five cases the converse was found. Our findings support the contention that immune adherence hemagglutination is the method of choice for detecting antibodies to varicella-zoster virus.     

Detection of varicella-zoster virus DNA in blood of children with varicella

The nested polymerase chain reaction was used to detect varicella zoster virus (VZV) DNA in 67 samples of peripheral blood mononuclear cells (PBMC) from 39 otherwise healthy children with varicella. Eleven were during the incubation period and 56 were after appearance of rash. VZV DNA was detected in two of eight (25%) PBMC at the early phase of the incubation period (day –14 to –11). The rate of the detection increased to 67% in –5 to –1 days prior to the onset of the rash and 46% in 0–4 days after the onset. It declined gradually with time and was undetectable in patients after 15 days from the clinical onset. The serum antibody determined with the fluorescent antibody to membrane antigen was first detected in the samples on day 2 and subsequently increased to 100% rapidly. In conclusion, VZV DNA cannot be detected usually in PBMC of healthy children except in varicella. © 1994 Wiley-Liss, Inc.     

Detection of varicella-zoster virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients suffering from neurological complications associated with chicken pox or herpes zoster.

The polymerase chain reaction (PCR) was used to detect varicella-zoster virus (VZV) DNA in the cerebrospinal fluid of patients with VZV infection associated with neurological symptoms. Positive results were obtained in three of five children with post-chicken pox cerebellitis and in seven of seven herpes zoster patients with neurological symptoms. The PCR thus provides a useful tool for the early diagnosis of VZV-associated neurological disease.     

Management of Ramsay Hunt Syndrome in an Acute Palliative Care Setting

Introduction:

The Ramsay Hunt syndrome is characterized by combination of herpes infection and lower motor neuron type of facial nerve palsy. The disease is caused by a reactivation of Varicella Zoster virus and can be unrepresentative since the herpetic lesions may not be always be present (zoster sine herpete) and might mimic other severe neurological illnesses.

Case Report:

A 63-year-old man known case of carcinoma of gall bladder with liver metastases, post surgery and chemotherapy with no scope for further disease modifying treatment, was referred to palliative care unit for best supportive care. He was on regular analgesics and other supportive treatment. He presented to Palliative Medicine outpatient with 3 days history of ipsilateral facial pain of neuropathic character, otalgia, diffuse vesciculo-papular rash over ophthalmic and maxillary divisions of left trigeminal nerve distribution of face and ear, and was associated with secondary bacterial infection and unilateral facial edema. He was clinically diagnosed to have Herpes Zoster with superadded bacterial infection. He was treated with tablet Valacyclovir 500 mg four times a day, Acyclovir cream for local application, Acyclovir eye ointment for prophylactic treatment of Herpetic Keratitis, low dose of Prednisolone, oral Amoxicillin and Clindamycin for 7 days, and Pregabalin 150 mg per day. After 7 days of treatment, the rash and vesicles had completely resolved and good improvement of pain and other symptoms were noted.

Conclusion:

Management of acute infections and its associated complications in an acute palliative care setting improves both quality and length of life.     

Increased prevalence of varicella zoster virus DNA in cerebrospinal fluid from patients with multiple sclerosis

In order to investigate the possible involvement of viruses in Multiple Sclerosis (MS), the study evaluated the presence of viral genomic sequences in cerebrospinal fluid (CSF), as markers of viral replication within the central nervous system (CNS). A total of 85 CSF samples were collected from 38 MS patients, 28 patients with other neurological diseases and 19 subjects without neurological diseases. Using nested-PCR, the investigation focused on the presence of human herpes virus DNA, including herpes simplex virus 1 (HSV-1) and 2 (HSV-2), the Epstein-Barr virus (EBV), varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus 6 (HHV-6) and JC virus (JCV). All the CSF samples from the individuals without neurological diseases were negative for viral DNA. Genomic sequences of HSV-1, HCMV, EBV, HHV6, and JCV were found in patients with MS and other neurological diseases without significant differences between the two groups. VZV DNA was detected more frequently (P < 0.05) in the MS group (31.6%), particularly among the relapsing-remitting MS patients (43.5%), compared with patients with other neurological diseases (10.7%). In addition, the results indicated that JCV and HHV-6 were replicating actively in the CNS of a small, but significant number of patients with MS and other neurological diseases. Most importantly, the study revealed a high frequency of VZV DNA in the CSF of patients with MS, suggesting a possible role of this virus in the pathogenesis of MS.