Varicella-zoster virus infection in adult patients after unrelated cord blood transplantation: a single institute experience in Japan

Varicella-zoster virus (VZV) infection was studied in 40 adult patients who underwent cord blood transplantation (CBT) from unrelated donors. Twenty-five patients developed VZV reactivation at a median of 5 months after CBT (range 1.7-26 months). The cumulative incidence of VZV reactivation after CBT was 80% at 30 months. Twenty-two patients developed localized herpes zoster. The remaining three patients developed atypical non-localized herpes zoster, which was associated with visceral dissemination in one patient. All the patients responded well to antiviral therapy. Unexpectedly, the absence of grade II-IV acute graft-versus-host disease (GVHD) was associated with a higher rate of VZV reactivation after CBT (100% versus 55%, P=0.01). These results suggest that recovery of VZV-specific immune responses after CBT is delayed even in patients without severe acute GVHD.     

High prevalence of varicella-zoster virus reactivation in herpes simplex virus-seronegative patients with acute peripheral facial palsy.

Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are considered to be the major causes of acute peripheral facial palsy (APFP). One hundred and forty-two patients with APFP were analyzed by serological assays and polymerase chain reaction analysis. Ramsay Hunt syndrome was diagnosed in 21 patients. Of the remaining 121 patients clinically diagnosed with Bell's palsy, VZV reactivation without zoster (zoster sine herpete) was detected in 35 patients (29%). The prevalence of antibodies to HSV among patients with Bell's palsy was significantly higher than the prevalence among those with VZV reactivation (Ramsay Hunt syndrome or zoster sine herpete). In contrast, a high incidence (88%) of VZV reactivation among HSV-seronegative patients with APFP was observed. Our data indicate that VZV is one of the major etiologic agents of clinically diagnosed Bell's palsy and that VZV reactivation causes APFP in most patients who lack antibodies to HSV.     

Serum antibody levels as risk factors in the dissemination of herpes zoster.

Serum antibody levels against varicella-zoster virus (VZV) were examined by immune adherence hemagglutination assay (IAHA), indirect fluorescent antibody (IFA) assay, and complement fixation techniques in 67 immunocompromised patients with localized and disseminated herpes zoster. In the serum obtained initially, undetectable IAHA titers were found in 56.5% of the patients with disseminated zoster compared with 18.2% of those with localized zoster. When serum obtained within the first seven days of illness was analyzed, undetectable IAHA titers and IFA titers of less than 32 were noted in 77.8% of those with disseminated zoster but in only 18.5% of those with localized disease. Peak serum antibody titers in patients with disseminated zoster were eventually equal to or greater than those in localized zoster. The patient groups were comparable in age, underlying disease, and therapy, although Hodgkin's disease was more frequent in patients with disseminated zoster. Thus, the absent IAHA or low IFA levels of circulating antibody early in illness were highly significant risk factors in dissemination of virus in herpes zoster.     

Seroprevalence of Varicella-Zoster Virus in Children from Shiraz-Iran

Background: Varicella–zoster virus (VZV) causes herpes zoster and varicella (Chicken-pox), usually a mild disease which is diagnosed clinically with few complications. However, in neonates and healthy adults it can have a severe presentation. Herpes zoster results from VZV reactivation later in life. Objective: To determine the seroprevalence of VZV in elementary school children aged 6-10 years in Shiraz, Iran. Methods: A cross-sectional seroprevalence survey was conducted on 270 healthy subjects. All serum samples were investigated for immunoglobulin G (IgG) antibody against VZV using a commercial enzyme linked immunosorbent assay (ELISA). Results: Among the studied population, 175 (64.8%) had no detectable antibody levels. The overall seroprevalence rate was 35.2%. A breakdown of seropositivity to VZV according to age was as follows; 10 years old, 50%, 9 years old, 48.2%, 8 years old, 27.3%, 7 years old, 32.1%, and 6 years old, 13.2%. Conclusion: As VZV susceptibility in the studied age groups was higher than the expected rate, therefore childhood VZV vaccination is recommended in our region.     

Postoperative fulminant varicella zoster virus hepatitis with fatal outcome: a case report

INTRODUCTION: Fulminant hepatitis due to varicella zoster virus (VZV) infection has a poor prognosis although an effective treatment is available. CASE REPORT: We present a case of fulminant hepatic failure (FHF) as a result of disseminated VZV infection in a long-term alcoholic patient who underwent laryngectomy and radical neck dissection due to squamous cell carcinoma of the larynx. Post-mortem examination revealed the diagnosis of fulminant hepatitis and infection with VZV. Viral inclusion bodies were found in the hypopharyngeal mucosa as well as in the liver tissue. In these tissues VZV was detected by PCR. The clinical presentation is suggestive for a reactivation of VZV without cutaneous signs of herpes zoster during a state of immunosuppression. DISCUSSION: Differential diagnosis comprises hepatitis by other Herpes group viruses and toxic hepatic injury.     

Neurological complications of varicella-zoster virus infection in adults with human immunodeficiency virus infection

This multicentre retrospective study describes the clinical features and prognostic significance of Varicella-zoster virus (VZV)-associated neurological complications. The study was performed in patients with human immunodeficiency virus (HIV) infection, hospitalized for VZV neurological complications, confirmed in every case by positive VZV polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Between 1990 and 1995, 34 HIV-infected patients were included in the study. At diagnosis, 59% had AIDS, with a median CD4 count of 11 x 10(9)/l. A past history of zoster was noted in 35% of cases. A concomitant herpes zoster rash and/or acute retinal necrosis were noted in 71% and 12% of patients, respectively. The predominant neurological manifestations were encephalitis (13), myelitis (8), radiculitis (7) and meningitis (6). The mean CSF white blood cell count was 126/mm3 and the mean CSF protein concentration was 2.3 g/l. Interferon-alpha level was increased in 36% of patients. VZV was isolated from CSF cultures in 2/6 cases. Magnetic resonance imaging was abnormal, demonstrating encephalitis lesions. After intravenous antiviral therapy, complete recovery was obtained in 18 cases (53%), serious sequelae were observed in 10 cases (29%) and 6 patients died (18%). Severe symptoms and a low CD4 cell count appeared to be associated with death or sequelae. In conclusion, VZV should be considered as a possible cause of encephalitis, myelitis, radiculitis or meningitis in HIV-infected patients, especially in patients with a history of or concomitant herpes zoster or acute retinal necrosis. VZV-PCR in the CSF may allow rapid diagnosis and early specific antiviral treatment.     

Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation.

Bone marrow transplant (BMT) recipients were evaluated for subclinical varicella-zoster virus (VZV) viremia and symptoms of herpes zoster after transplantation. Viremia was demonstrated by testing peripheral blood mononuclear cells using polymerase chain reaction and was documented in 19% of 37 patients. When reactivation was defined as herpes zoster and/or subclinical VZV viremia, 41% of VZV-seropositive BMT recipients experienced VZV reactivation. None of 12 patients tested before VZV reactivation had T lymphocyte proliferation to VZV antigen (mean stimulation index, 1.0 +/- 0.42 [SD] at less than 100 days; 12.0 +/- 6.03 at greater than 100 days [P = .003]). Among patients tested at greater than 100 days, 5 (63%) of 8 with detectable T cell proliferation had subclinical or clinical VZV reactivation compared with none of 6 who lacked VZV T cell responses. Recovery of VZV-specific cytotoxic T lymphocyte function was observed in 50% of BMT patients, but BMT recipients had significantly fewer circulating cytotoxic T lymphocytes that recognized VZV immediate early protein (P = .03) or glycoprotein I (P = .004) than did healthy VZV immune subjects. In vivo reexposure to VZV antigens due to subclinical VZV viremia or symptomatic VZV reactivation may explain the recovery of virus-specific T cell immunity after BMT.     

Diagnosis of varicella-zoster virus (VZV) infection by using FITC-labeled monoclonal antibodies

Anti-varicella zoster virus (VZV) mouse monoclonal antibodies conjugated with fluorescein isothiocyanate were evaluated for their usefulness as a practical diagnostic tool in the clinical field by examining cells infected with isolated herpes viruses and 431 clinical samples. The kit stained clearly the cells infected with 14 isolated VZV strains without cross reaction to 15 isolated herpes simplex virus type-1 strains (HSV-1) and 14 type-2 (HSV-2) strains. In clinical specimens, viral antigens of VZV were detected in 92/105 (87.6%) cases of varicella and in 176/190 (92.6%) cases of herpes zoster. Specific fluorescence of VZV was also observed in 5 out of 96 cases diagnosed as HSV infections, although these samples had no specific reaction to HSV when tested by the commercially available diagnostic kit. In 24 cases which could not be clinically diagnosed as herpes zoster or herpes simplex, the VZV antigen was demonstrated in 9 cases. All 109 VZV-positive cases in virus isolation by culture were also judged VZV-antigen positive by the kit, while all 69 HSV-positive cases in virus isolation were VZV-antigen negative. Furthermore, the VZV antigen was detected by the kit in 53/60 clinical diagnoses of varicella or herpes zoster without successful virus isolation. These results clearly indicate the usefulness of the kit as a practical VZV diagnostic reagent, especially in terms of specific sensitivity and easy technical manipulation.     

Is VZV reactivation a common cause of unexplained unilateral pain? Results of a prospective study of 57 patients

OBJECTIVE: Pain is a common reason for patients to present to a doctor. Many patients with zoster have seen their doctor with pain during the days before the rash and zoster sine herpete is well described. If early varicella zoster virus (VZV) reactivation could be identified confidently, it could provide an opportunity for early antiviral intervention. This prospective study was performed to assess how often patients presenting to their general practitioner with unilateral pain of no obvious clinical cause proved to have evidence of VZV reactivation. METHODS: Fifty-seven patients were recruited and followed for 28 days; laboratory testing included VZV polymerase chain reaction (PCR) from peripheral blood mononuclear cells, VZV IgG, IgA and IgM. The control group consisted of 81 blood donors. RESULTS: Only two study patients developed the rash of zoster. There was no significant difference in PCR or serological responses between the study group and control group. Clinical characteristics did not enable identification of patients presenting to their doctor with unilateral pain who had prodromal zoster. CONCLUSION: There was no evidence on clinical or laboratory tests used in this study to support the view that reactivation of VZV is a common cause of unexplained unilateral pain.     

Clinical evaluation of commercial serological test for Bartonella infection

We evaluated the usefulness of a serological diagnostic kit (Bartonella IFA IgG, IgM; MRL Diagnostics) for Bartonella henselae infection. Of the 110 healthy individuals, 107 (97.3%) were with titers being less than 1:64 for IgG antibody to B. henselae, 2 were with titers being 1:64 and 1 with 1:128, IgM antibody to B. henselae was negative in all individuals. Serological diagnosis of cat scratch disease (CSD) using indirect fluorescence antibody (IFA) methods (in-house and diagnostic kit) was made in either elevated titers of IgM (> or = 1:20) or IgG (> or = 1:256) antibodies, or a four-fold rise in IgG titer between acute and convalescent sera. Of the 18 individuals with serological diagnosis of CSD by in-house IFA method in 26 CSD clinical diagnosed patients, 15 (83%) were compatible with the results of the diagnostic kit, whereas 3 (17%) were not compatible. Of the 8 without serological diagnosis, 1 (13%) was serologically diagnosed as CSD, and the others were negative. Overall, the serological diagnosis was made in 16 of 26 (62%). The specificity and sensitivity of this kit were 100% and 62%, respectively. The cross-reaction between B. henselae and Bartonella quintana was observed in sera from controls and patients. Our results show that the diagnostic kit as well as in-house method is an useful tool for the serological diagnosis of cat scratch disease.     

IgM and IgG responses to varicella-zoster virus p32/p36 complex after chickenpox and zoster, congenital and subclinical infections, and vaccination

Varicella-zoster virus (VZV) directs the synthesis of a nonglycosylated polypeptide complex with two prominent species with relative molecular masses of 32,000 and 36,000; the p32/p36 complex is present in both the viral nucleocapsid and the nuclear matrix of the infected cell. We have now further characterized the humoral immune response of VZV-infected humans to this complex and established that it is a major viral antigen. Antibodies to VZV p32/p36 were detected in sera from patients with both primary VZV infection (chickenpox) and VZV reactivation (zoster); the response after zoster was more pronounced. When the IgM and IgG components of the immune response were distinguished, IgM to the viral nucleoproteins was observed following chickenpox and zoster and, to a lesser extent, in recipients of VZV vaccine. An IgM response to VZV p32 also was detected during intrauterine VZV infection and subclinical VZV infection.     

Incidence of herpes zoster and seroprevalence of varicella-zoster virus in young adults of South Korea.

OBJECTIVES: This study was performed to determine the incidence of herpes zoster and seroprevalence of varicella-zoster virus (VZV) in young adults of South Korea, where VZV seroprevalence remains relatively high. METHODS: In South Korea, military service is compulsory for all healthy young men and hence those in military service might provide a reflection of the general population. The computerized database of the Armed Forces Medical Command was examined to identify the number of reported herpes zoster cases. In order to evaluate VZV seroprevalence, serum samples were obtained from randomly selected subjects among those who had been admitted to the Armed Forces Capital Hospital. RESULTS: A total of 705 cases of herpes zoster were reported between June 2004 and May 2005. The annual incidence rate of herpes zoster was 141 (95% CI 131.0-151.8) per 100000 population. A total of 192 subjects were enrolled for the analysis of VZV seroprevalence. All subjects were male and their median age was 21 (range 19-24) years. The overall anti-VZV IgG seropositivity prevalence was 92.7% (178/192, 95% CI 88.0-95.7%). CONCLUSION: We have described a population-based study of the epidemiology of VZV infections in the military personnel of South Korea.     

Bilateral brachial neuritis secondary to varicella reactivation in an HIV-positive man

We present the case of a 48-year-old HIV-positive man, who developed acute onset of pain in both upper limbs associated with proximal weakness and distal paraesthesia. Eight weeks prior to this presentation he had had varicella zoster affecting his right S1 dermatome. CD4 count was 355 cells/mm(3) and he was antiretroviral therapy (ART) naive. Power was 0/5 proximally and 4/5 distally in the upper limbs. Reflexes were absent and there was sensory loss in the C5, C6 and T1 dermatomes. Cerebrospinal fluid (CSF) examination showed a lymphocytosis with low glucose; however, CSF Mycobacterium tuberculosis (TB), and herpes simplex virus polymerase chain reaction (HSV PCR) were negative as was syphilis serology. Electromyography showed marked motor axonal loss. Magnetic resonance imaging (MRI) did not show any cervical spinal lesion. Varicella zoster virus (VZV) PCR was positive in the CSF. He was treated with high-dose intravenous aciclovir with good resolution of his syndrome over time and was commenced on ART. We believe this to be the first case report of varicella reactivation causing bilateral neuralgic amyotrophy in an HIV-positive patient.     

Herpes zoster and its cardiovascular complications in the elderly--another look at a dormant virus

Herpes zoster (shingles) is a reactivation of latent Varicella-zoster virus (VZV). We present a case of pleuropericarditis simulating acute myocardial infarction and another with complete heart block in the setting of acute/recent VZV reactivation. These cases are consistent with a modified concept: (1) the VZV dormancy is comprised of multiple foci of infections in the sensory and autonomic ganglia, and (2) the VZV reactivation could involve co-incident activations of two or more loci. Recognition of this possibility of cardiovascular complications of VZV should be helpful in the clinical management of the elderly, in the differential diagnosis of chest pain, ST elevation, and heart block etiology in the setting of acute or recent VZV reactivation.     

Herpes zoster and recurrent herpes simplex.

87 patients with the clinical diagnosis of herpes zoster were seen during a one-year period in 8 general practices in Glasgow, the rate per 1 000 practice population being approximately 2.4. Of these, 78 (90%) had serological evidence of active infection with herpes zoster. A history of recurrent herpes simplex was obtained in 25 (32%) of the 78 patients with confirmed herpes zoster; 63 (81%) of these 78 had complement-fixing (CF) antibodies to herpes simplex. Thus, latent herpes simplex infection did not prevent herpes zoster nor modify the severity of herpes zoster. In most of the patients CF antibodt to varicella-zoster was not detected within 5 days from appearance of the rash. After the acute phase of the illness CF antibody titres fell fairly rapidly, the geometric mean titre being 189 at 2-4 weeks after the rash, 27 from 3-6 months, and 8 from 12-18 months. The rapid rise and decline in CF antibody after herpes zoster infection compared with the unchanging CF titres associated with recurrent herpes simplex infection suggest that varicella-zoster and herpes simplex virus differ in their mechanism of latency.     

A Prospective Evaluation of Real-Time PCR Assays for the Detection of Orientia tsutsugamushi and Rickettsia spp. for Early Diagnosis of Rickettsial Infections during the Acute Phase of Undifferentiated Febrile Illness

One hundred and eighty febrile patients were analyzed in a prospective evaluation of Orientia tsutsugamushi and Rickettsia spp. real-time polymerase chain reaction (PCR) assays for early diagnosis of rickettsial infections. By paired serology, 3.9% (7 of 180) and 6.1% (11 of 180) of patients were confirmed to have acute scrub or murine typhus, respectively. The PCR assays for the detection of O. tsutsugamushi and Rickettsia spp. had high specificity (99.4% [95% confidence interval (CI): 96.8–100] and 100% [95% CI: 97.8–100], respectively). The PCR results were also compared with immunoglobulin M (IgM) immunofluorescence assay (IFA) on acute sera. For O. tsutsugamushi, PCR sensitivity was twice that of acute specimen IgM IFA (28.6% versus 14.3%; McNemar''s P = 0.3). For Rickettsia spp., PCR was four times as sensitive as acute specimen IgM IFA (36.4% versus 9.1%; P = 0.08), although this was not statistically significant. Whole blood and buffy coat, but not serum, were acceptable specimens for these PCRs. Further evaluation of these assays in a larger prospective study is warranted.     

The detection of VZV DNA in the smear cells of the patients of herpes zoster by in situ hybridization using biotinylated DNA probe

We performed the in situ hybridization (ISH) study of the smear cells taken from the patients of herpes zoster. We used the biotinylated EcoRI-B, H fragment of varicella-zoster-virus (VZV) DNA as the probe. In the control study of ISH VZV-infected cells showed strong staining, but no staining was observed in the infected cells by other herpes virus. We examined the smear cells of 19 patients of herpes zoster and 2 patients of herpes simplex by ISH. 30 of the 35 specimens of herpes zoster was positive by ISH. We detected VZV DNA in the smear cells of all cases of the bullous stage, but the sensitivity was about 75% in the later stage. Smear cells of herpes simplex was not stained by ISH. We also performed virus isolation of 13 cases of herpes zoster. But the sensitivity of ISH was higher than that of virus isolation in the other stages of herpes zoster. This method is very simple and can be completed in about 1 hour. It also has high specificity and sensitivity. So this method is very useful for the rapid diagnosis of VZV infection.     

Differentiation of Herpes simplex virus types 1 and 2 in sera of patients with HSV central nervous system infections by type-specific enzyme-linked immunosorbent assay.

OBJECTIVE: To differentiate by enzyme-linked immunosorbent assay (ELISA) using type-specific glycoprotein G herpes simplex virus (HSV) type 1 and type 2 in serum collected from patients with HSV central nervous system (CNS)infections. METHODS: HSV 1 and 2 typing in convalescent sera of 17 patients with HSV acute encephalitis, myelitis, or meningitis was determined by the type-specific IgG ELISA kit (Gull Laboratory, Inc.). HSV CNS infections were diagnosed by polymerase chain reaction (PCR) or conventional serologic tests from acute to convalescent stages. RESULTS: In 13 of 17 patients, HSV type 1 and HSV type 2 antibodies were positive; 11 patients with HSV type 1 and 2 patients with HSV type 2 were found. All 10 patients with encephalitis showed equivocal or positive results for HSVtype 1. In two of three cases of myelitis, HSV type 1 was demonstrated. Each case of myelitis and meningitis reacted to both types 1 and 2. CONCLUSION: These data suggest that the kit is useful for type differentiation of HSV CNS infections from convalescent sera, and can play a supplementary role in HSV typing by PCR or previous serologic tests.     

Varicella zoster virus meningitis complicating sodium stibogluconate treatment for cutaneous leishmaniasis

Sodium stibogluconate (Pentostam(R); GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with sodium stibogluconate.