Varicella Zoster Virus IgM Antibodies Research Articles

Association between Serum Varicella-Zoster Virus IgM and IgG and Prognosis of Ramsay Hunt Syndrome.

Ramsay Hunt syndrome (RHS) has a poor prognosis because of varicella-zoster virus (VZV) infection. This is most closely related to severe inflammation in the geniculate ganglion of the facial nerve due to VZV infection or reactivation. This study investigated whether there were differences in the prognosis and accompanying symptoms of facial paralysis based on the presence or absence of VZV IgM and IgG antibodies. This study was conducted as a retrospective chart analysis of 105 patients with RHS who were admitted to our hospital between 2015 and 2021. The House-Brackmann (HB) grade and electroneurography (ENoG) was used to evaluate the degree of facial paralysis. Patients' subjective symptoms were evaluated by dividing them into dizziness, tinnitus, hyperacusis, and hearing loss. No difference was observed in the initial HB grade with or without IgM; however, the final HB grade was significantly higher in IgM-positive patients than in IgM-negative patients (p < 0.05). Further, when IgM was positive, the value of the orbicularis oculi muscle in the ENoG test results was significantly higher (p < 0.05), and symptoms of tinnitus and hyperacusis occurred more frequently (p < 0.05). The initial and final HB grades were significantly higher in IgG-positive patients than in IgG-negative patients (p < 0.05). When IgG was positive, the values of nasalis and oris muscles in the ENoG test results were significantly higher (p < 0.05), and symptoms of dizziness occurred more frequently (p < 0.05). This study confirmed that the more active the immunological action of the VZV in the body, the greater the damage to the facial and vestibulocochlear nerves, which are associated with the degree of facial paralysis and the accompanying otologic symptoms.

Metagenomic Next-Generation Sequencing vs. Traditional Microbiological Tests for Diagnosing Varicella-Zoster Virus Central Nervous System Infection.

BackgroundUnbiased metagenomic next-generation sequencing (mNGS) detects pathogens in a target-independent manner. It is not well-understood whether mNGS has comparable sensitivity to target-dependent nucleic acid test for pathogen identification.MethodsThis study included 31 patients with chickenpox and neurological symptoms for screening of possible varicella-zoster virus (VZV) central nervous system (CNS) infection. Microbiological diagnosing of VZV cerebrospinal fluid (CSF) infection was performed on stored CSF samples using mNGS, quantitative and qualitative VZV-specific PCR assays, and VZV IgM antibodies test.ResultsThe median age was 30.0 [interquartile range (IQR), 24.3–33.3] years. 51.6% of the patients were men. About 80.6% of the patients had normal CSF white blood cell counts (≤ 5 × 106/L). VZV IgM antibodies presented in 16.1% of the CSF samples, and nucleic acids were detectable in 16.1 and 9.7% using two different VZV-specific real-time PCR protocols. Intriguingly, maximal identification of VZV elements was achieved by CSF mNGS (p = 0.001 and p = 007; compared with qualitative PCR and VZV IgM antibody test, respectively), with sequence reads of VZV being reported in 51.6% (16/31) of the CSF samples. All VZV PCR positive samples were positive when analyzed by mNGS. Of note, human betaherpesvirus 6A with clinical significance was unexpectedly detected in one CSF sample.ConclusionsOur study suggests that CSF mNGS may have higher sensitivity for VZV detection than CSF VZV PCR and antibody tests, and has the advantage of identifying unexpected pathogens.

Assessment for varicella zoster virus in patients newly suspected of having giant cell arteritis.

There is uncertainty if varicella zoster virus (VZV) triggers GCA. This is based on discordant reports of VZV detection in GCA temporal artery biopsies. We conducted a multimodal evaluation for VZV in the inception Giant Cell Arteritis and PET Scan (GAPS) cohort. Consecutive patients who underwent temporal artery biopsy for suspected GCA were clinically reviewed for active and past VZV infection and followed for 6 months. Serum was tested for VZV IgM and IgG. Temporal artery biopsy (TAB) sections were stained for VZV antigen using the VZV Mouse Cocktail Antibody (Cell Marque, Rocklin, CA, USA). A selection of GCA and control tissues were stained with the VZV gE antibody (Santa Cruz Biotechnology, Dallas, TX, USA), which was used in previous studies. A total of 58 patients met inclusion criteria, 12 (21%) had biopsy-positive GCA and 20 had clinically positive GCA. None had herpes zoster at enrolment and only one patient developed a VZV clinical syndrome (zoster ophthalmicus) on follow-up. There was no difference in VZV exposure between GCA and non-GCA patients. None of the 53 patients who had VZV serology collected had positive VZV IgM antibodies. VZV antigen was not convincingly demonstrated in any of the TAB specimens; 57 TABs stained negative and 1 stained equivocally positive. The Santa Cruz Biotechnology VZV antibody exhibited positive staining in a range of negative control tissues, questioning its specificity for VZV antigen. The absence of active infection markers argues against VZV reactivation being the trigger for GCA. Non-specific immunohistochemistry staining may account for positive findings in previous studies.

1654. Chickenpox Outbreak in a Tribal District Rayagada, Odisha, India: Warrants Need for Vaccination

BackgroundChickenpox or varicella is caused by Varicella zoster virus. In India chickenpox outbreak is not uncommon as the vaccination against varicella is not included in the program. We report, chickenpox outbreak in a tribal district Rayagada, Odisha state of India a South Asian country. The outbreak investigation was undertaken to assess the characteristics and determinants of the outbreak and make appropriate recommendations for control and prevention of further transmission.MethodsA door to door survey was made for case finding and line listing with detailed travel, exposure and vaccination history. Qualitative research tools including key informant’s interview and focus group discussion were undertaken to understand community behavior and practice. Intravenous blood samples were collected for serological test to detect antibody to varicella-zoster virus.ResultsA total of 59 individuals out of 767 residents were affected with chickenpox in this outbreak with an attack rate of 8.73 per 100 populations. Age distribution indicated 69.5% belonged to the age group less than 14 years. No severe complication was reported. Blood sample of 33 case-patients was tested for Varicella zoster virus IgM antibodies and 24 (72.7%) found seropositive. The primary case was an 11-year-old girl who contracted infection in her residential school. None of the community members had received vaccination against chickenpox. Qualitative research indicated traditional beliefs and remedies prevailing in the communities that prevented case isolation and the modern treatment.ConclusionThe study highlights the need for regular training of peripheral health workers for an effective awareness campaign to change beliefs and traditional practice and vaccination against Varicella zoster virus for prevention of such outbreaks.Disclosures All authors: No reported disclosures.

Investigation of an Outbreak of Varicella in Chandigarh, North India, Using a Real-time Polymerase Chain Reaction Approach

Outbreaks of varicella are reported when susceptible population accumulates. This study reports a chickenpox outbreak in Burail in August 2014, wherein 20 laboratory-confirmed cases were identified by the detection of varicella zoster virus (VZV) DNA and VZV IgM antibodies. The viral load between vesicular swabs and serum samples from 8 patients with active lesions was found to have good correlation and further also related with disease severity. Real-time polymerase chain reaction can be useful for early diagnosis of an outbreak and vesicular swab can be used as a less invasive sample for assessing the disease severity.

Evaluation of three different sample populations on a new multiplex BioPlex®2200 assay for the detection of measles, Mumps, and Varicella-Zoster virus IgM antibodies

Evaluation of three different sample populations on a new multiplex BioPlex®2200 assay for the detection of measles, Mumps, and Varicella-Zoster virus IgM antibodies

The positive duration of varicella zoster immunoglobulin M antibody test in herpes zoster.

Laboratory tests for herpes zoster (HZ) are required to confirm varicella zoster virus (VZV) infection, especially when a skin lesion is not typical or apparent. The serological test for VZV IgM antibody is simple and cost-effective; however, the change in the VZV IgM-positive rate over the time course of the disease has not been investigated. Therefore, we conducted an observational study to evaluate the positive rate of VZV IgM results during the time course of HZ and estimate the VZV IgM-positive period.After obtaining serum from patients with typical HZ, the VZV IgM titer was examined using enzyme-linked immunosorbent assay methods. After logarithmic transformation of the VZV IgM titer and the period after the onset of HZ, regression analysis was performed with the 2 transformed variables.A total of 62 patients were included in this study, and VZV IgM antibody was positive only in 23 patients (37%). The estimated antibody-positive period after HZ onset was 3.5 weeks (95% confidence interval 2.8–4.6 weeks).These findings suggest that the serological diagnosis of VZV IgM to confirm HZ is only useful within 3.5 weeks after the onset of symptoms.

Outbreak of chickenpox in a Union Territory of North India

Purpose: Primary infection with a varicella-zoster virus (VZV) leads to chickenpox. Though the incidence of the disease has decreased in many developed countries due to the introduction of the varicella vaccine, outbreaks continue to occur in developing countries. Materials and Methods: The present study reports an outbreak of varicella in an urbanised village in the vicinity of Chandigarh City in North India in November 2013. The outbreak was confirmed by the detection of VZV IgM antibodies in serum samples of clinically suspected patients. Vesicular fluid samples were collected from 8 patients with active lesions and tested for VZV DNA by polymerase chain reaction. Blood samples were also collected from 17 healthy controls residing in the same locality and tested for the presence of VZV IgM and IgG antibodies. Results: A total of 18 cases occurred, and the majority of them (67%) were <15 years of age. Of 17 samples collected from patients with the clinically suspected disease, 13 (76.5%) showed the presence of VZV IgM antibodies. Of the healthy controls, 6 were VZV IgM positive and 4 of them developed symptomatic disease on follow-up. VZV DNA was positive in 5/8 (62.5%) of the patients. In one patient, VZV DNA was detected in the absence of an IgM antibody response. Conclusion: The introduction of varicella vaccine in the universal immunisation programme of India may help to prevent these outbreaks; however, the cost-benefit analysis needs to be carried out before making such policies.

Comparison of a new multiplex BioPlex® 2200 assay for the detection of measles, mumps, and varicella-zoster virus IgM antibodies in human specimens

Comparison of a new multiplex BioPlex® 2200 assay for the detection of measles, mumps, and varicella-zoster virus IgM antibodies in human specimens

The association of Varicella zoster virus reactivation with Bell's palsy in children

ObjectivesBell's palsy is considered the most common cause of facial nerve paralysis in children. Although different theories have been postulated for its diagnosis, reactivation of the Varicella zoster virus (VZV) has been implicated as one of the causes of Bell's palsy. The aim of the study was to evaluate the association of Varicella-zoster virus infection with Bell's palsy and its outcome in children. MethodsA total of 30 children with Bell's palsy were recruited and were assayed for evidence of VZV infection. The severity of facial nerve dysfunction and the recovery rate were evaluated according to House–Brackmann Facial Nerve Grading Scale (HB FGS). Paired whole blood samples from all patients were obtained at their initial visit and 3 weeks later, and serum samples were analyzed for VZV IgG and IgM antibodies using ELISA. ResultsA significantly higher percentage of Bell's palsy patients were seropositive for VZV IgM antibodies than controls (36.6% of patients vs 10% of controls) while for VZV IgG antibodies the difference was statistically nonsignificant. HB FGS in Bell's palsy patients with serologic evidence of VZV recent infection or reactivation showed a statistiacally significant less cure rate than other patients. ConclusionsVZV reactivation may be an important cause of acute peripheral facial paralysis in children. The appropriate diagnosis of VZV reactivation should be done to improve the outcome and the cure rate by the early use of antiviral treatment.

Immunity to varicella-zoster virus in Croatian women of reproductive age targeted for serology testing

The aim of this study was to determine the immunity to varicella-zoster virus (VZV) in Croatian pregnant and non-pregnant women of reproductive age. During 2007-2011, a total of 638 women aged 16-45 years were tested for the presence of VZV IgM and IgG antibodies using commercial enzyme-linked immunosorbent assay. Samples positive for IgG antibodies with positive or equivocal IgM antibodies were tested for IgG avidity. The overall IgG seroprevalence was 84.3 %. There was a significant increase in IgG seropositivity with age (OR = 1.04 for 1-year increase in age; 95 % CI 1.01-1.08). The lowest seroprevalence rate was reported in the 16-20 age groups (78.6 %), and the highest was in the 41-45 age groups (94.3 %). There was no significant difference in seroprevalence among women residing in urban and rural areas (83.6 vs. 87.0 %, OR 0.76, 95 % CI 0.43-1.34). The results of this study have shown that a high proportion of Croatian childbearing-aged women (15.7 %) who were referred to the laboratory for VZV serology testing are susceptible to VZV and, thus, at risk for contracting varicella during pregnancy. Serology testing of adolescent girls and adult women who do not have a documented history of varicella is encouraged with the aim of vaccinating seronegative girls and women against VZV before pregnancy. In addition, testing of pregnant women is advised to identify susceptible women and vaccinate them after delivery.

Epidemiologic lessons: Chickenpox outbreak investigation in a rural community around Chandigarh, North India

Primary infection with Varicella Zoster virus (VZV) leads to Varicella or chickenpox. The epidemiology of Varicella has changed dramatically since the introduction of the Varicella vaccine in 1995. The routine childhood immunization in a few countries in the western world like Germany and the United States has reduced the incidence of the disease, associated complications, hospital admissions and deaths related to its complications. However, chickenpox outbreaks are common in naive unvaccinated communities in India. We report an outbreak of chickenpox that occurred in a village situated on the outskirts of Chandigarh city in North India in the winter of 2007. The outbreak was confirmed by the detection of VZV IgM by enzyme-linked immunosorbent assay (ELISA) on serum samples from the patients. In patients showing active lesions, Giemsa and indirect immunofluorescence was carried out on scrapings from vesicular lesions. A total of 162 cases occurred in the present outbreak. The serum samples were collected from 20 patients, and all of them showed positive serology for VZV IgM antibodies while 19 showed a positive VZV IgG result by ELISA. The scrapings were collected from two patients showing active lesions, and both were positive by the Tzanck smear examination, and VZV antigen could be demonstrated by immunofluorescence. There is an urgent need to identify naive communities and unvaccinated individuals at risk. Also, there is a need for regular training programmes of health workers posted in peripheral centers so that highly contagious communicable diseases can be picked up in time and such outbreaks can be prevented.

Serology and serum DNA detection in shingles.

To investigate the sensitivity of various laboratory approaches in the diagnosis of herpes zoster from patient serum. Paired sera from 53 consecutive adult patients with acute herpes zoster were tested for the presence of varicella-zoster virus (VZV) antibodies. All acute sera were tested subsequently by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. In addition, convalescent sera of patients who tested initially positive for VZV DNA underwent PCR analysis. VZV IgM antibodies were found by enzyme immunoassay (EIA) in 5 acute (9%) and 20 convalescent (38%) zoster sera. VZV DNA was detected by PCR in 21 (40%) acute zoster sera and was no longer detectable in the convalescent samples. A seroconversion or a fourfold or greater titre increase was found by complement fixation (CF) test in 41 (77%), by IgG indirect fluorescent antibody assay (IgG IFA) in 43 (81%) and by CF and IgG IFA combined in 45 of 53 (85%) paired zoster sera. The combination of all serological methods detected 51 (96%) and PCR combined with serology identified 52 (98%) of 53 patients. Optimal laboratory sensitivity in the diagnosis of herpes zoster from serum can be achieved by the combination of PCR and serology of paired serum samples. Serological methods alone are of limited value for early diagnosis of zoster when therapy can be initiated, because CF and IgG IFA need convalescent serum and IgM test sensitivity is insufficient. Early diagnosis of VZV reactivation is possible from serum by PCR in the first days of illness and test sensitivity needs further improvement. The findings highlight the need for future studies into the usefulness of PCR and serology in atypical cases of VZV reactivation.

Serology and serum DNA detection in shingles.

To investigate the sensitivity of various laboratory approaches in the diagnosis of herpes zoster from patient serum. Paired sera from 53 consecutive adult patients with acute herpes zoster were tested for the presence of varicella-zoster virus (VZV) antibodies. All acute sera were tested subsequently by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. In addition, convalescent sera of patients who tested initially positive for VZV DNA underwent PCR analysis. VZV IgM antibodies were found by enzyme immunoassay (EIA) in 5 acute (9%) and 20 convalescent (38%) zoster sera. VZV DNA was detected by PCR in 21 (40%) acute zoster sera and was no longer detectable in the convalescent samples. A seroconversion or a fourfold or greater titre increase was found by complement fixation (CF) test in 41 (77%), by IgG indirect fluorescent antibody assay (IgG IFA) in 43 (81%) and by CF and IgG IFA combined in 45 of 53 (85%) paired zoster sera. The combination of all serological methods detected 51 (96%) and PCR combined with serology identified 52 (98%) of 53 patients. Optimal laboratory sensitivity in the diagnosis of herpes zoster from serum can be achieved by the combination of PCR and serology of paired serum samples. Serological methods alone are of limited value for early diagnosis of zoster when therapy can be initiated, because CF and IgG IFA need convalescent serum and IgM test sensitivity is insufficient. Early diagnosis of VZV reactivation is possible from serum by PCR in the first days of illness and test sensitivity needs further improvement. The findings highlight the need for future studies into the usefulness of PCR and serology in atypical cases of VZV reactivation.

Herpes zoster laryngitis: case report and serological profile

Compared to herpes zoster oticus, varicella zoster virus (VZV) reactivations in immunocompetent patients are rare in laryngeal region. Usually, associated vocal cord paralyses are reported. Herein is a case report of a patient with laryngeal zoster without any associated motor disorders. An attempt is made to assign the distribution of mucosal eruptions to the appropriate neuroanatomical structures. A description of the serological course of VZV IgM and IgG are provided. Vesicles were found on the left sensory distribution areas of the superior laryngeal nerve. VZV IgM and IgG antibodies reached their peak 1 month after initial symptoms. Attentive follow-up and no antiviral therapy were advocated because of the absence of any immune deficiency or endoscopic suspicion of malignancy. In this case of VZV reactivation in the sensitive area of the superior laryngeal nerve, serological profiles of VZV IgM and IgG were profoundly modified up to the fourth month.

The seroprevalence of varicella zoster antibodies in Behçet's and other skin diseases.

The purpose of this study was to investigate the association of the varicella zoster virus (VZV) IgG, and IgM antibodies with Behçet's and other skin diseases (group 1: recurrent aphthos stomatitis, fungal infections, psoriasis; group 2: vitiligo, lichen planus). Twenty eight patients with Behçet's disease (BD), and 117 patients with dermatological disorders other than BD were evaluated for specific VZV IgG and IgM antibodies by using a third generation enzyme-linked immunosorbent assay (ELISA). The Mantel Heizshel chi2 method was used to adjust the confounding of age and sex of the patients. The serological positivity for VZV IgG and IgM antibodies in BD was not statistically different from other skin diseases. When we considered the age of the patients, chi2 = 2.64, CI (0.27-1.65), odds ratio (1, 1.25, 2.21) (p = 0.10) and when we considered the sex of the patients, chi2 = 0.31, CI (0.81-1.28), odds ratio (1, 1.45, 1.41), (p = 0.57).

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.

Investigation of varicella-zoster virus-infected cell proteins that elicit antibody production during primary varicella using the immune transfer method.

The varicella-zoster virus-infected cell proteins (VZV-ICPs) against which IgG, IgM and IgA antibodies were made in the course of primary varicella-zoster virus (VZV) infection were analysed by the immune transfer method. IgG antibodies were made against one or more of 18 VZV-ICPs by patients with varicella. IgM antibodies were produced which reacted with 21 VZV-ICPs. The spectrum of IgG antibody production during the first week after the onset of infection was limited to an average of three VZV-ICPs while IgM antibodies which reacted with an average of seven VZV-ICPs were detectable in the acute phase of varicella. Equivalent VZV IgG or IgM antibody titres by radioimmunoassay did not correlate with a similar pattern of antibody specificity for VZV-ICPs by immune transfer. A detectable immune response to all VZV-ICPs was not required for the recovery of individual patients from primary VZV infection.

Frequency and specificity of varicella zoster virus IgM response

A direct ELISA was developed for determination of IgM antibody to varicella zoster virus (VZV). With this sensitive method VZV IgM antibodies were detected in all patients with a varicella and in 84% with a herpes zoster infection. All but one of 28 renal allograft recipients had previously had varicella. A primary infection was seen in the last patient, and reactivated infections in 11 of the others. The VZV IgM response seems to be specific since patients with a herpes simplex virus (HSV) infection and a heterotypic VZV IgG titer rise did not have detectable VZV IgM. An indirect enzymelinked immunosorbent assay (ELISA) for detection of IgG antibodies has been used for serodiagnosis of VZV infections and to determine the immune status. After injection of zoster immune globulin, it was possible to measure passively transferred antibodies.

Detection of specific IgA antibodies in serum of patients with varicella and zoster infections.

A sensitive solid-phase, enzyme-linked immunosorbent assay (ELISA) was developed for detection of serum IgA antibodies to varicella-zoster virus (VZV). The antigen consisted of a sonically disrupted extract of VZV-infected human embryo cells. Rabbit antihuman IgA peroxidase conjugate was used to detect human IgA bound to viral antigens. In parallel, IgM and IgG antibodies to VZV were studied by ELISA and by an immunoperoxidase antibody to membrane antigen technique, respectively. VZV IgA antibodies were detected in high titers in all 5 varicella and 8 zoster patients. Specific VZV IgM antibodies were detected in all 5 varicella patients, but only in 2 of 8 zoster patients. No VZV IgA antibodies (less than 40) were detected in 50 healthy control sera. Neither were they found in paired sera of 5 patients with herpes simplex infections, 2 patients with Epstein-Barr virus infections, and 5 patients with human cytomegalovirus infections. The potential application of ELISA IgA techniques in serodiagnosis of both primary and reactivated VZV infections is discussed.