Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation

Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V‐GCV), a valine ester pro‐drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella‐like illness. First‐line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V‐GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox‐like illness treated successfully with V‐GCV.     

Disseminated herpes simplex virus and varicella zoster virus coinfection in a patient taking thalidomide for relapsed multiple myeloma

Disseminated herpes simplex virus (HSV) and varicella zoster virus (VZV) have been reported individually in immunosuppressed adults. We present a case of coinfection with disseminated HSV and VZV infection in a patient taking thalidomide for relapsed multiple myeloma. This is the first report of opportunistic infection associated with thalidomide.     

Rapid diagnosis of varicella-zoster virus infection with a monoclonal antibody based direct immunofluorescence technique

Diagnosis of varicella-zoster virus (VZV) infection in immunocompromised patients is difficult because of the frequent atypical appearance. Accurate and early diagnosis is important to allow rapid commencement of antiviral chemotherapy, with consequent improvement in antiviral efficacy. A monoclonal based direct immunofluorescence antibody technique (VZV IFA) was assessed in parallel with viral culture in 56 patients with suspected VZV infection. A subgroup of 17 patients from this group with classical dermatomal herpes zoster all had positive VZV IFA tests. Only 6 patients (35%) were positive on viral culture. None of the 15 patients with proven herpes simplex virus infection had a positive VZV IFA, nor did any patient with positive VZV viral culture have a negative VZV IFA. The VZV IFA test is a rapid and sensitive technique for detecting infection with VZV.     

Meningoencephalomyelitis with vasculitis due to varicella zoster virus: a case report and review of the literature

Varicella zoster virus (VZV) encephalitis is associated with large or small vessel vasculopathy. We report the case of a 67-year-old woman with a history of non-Hodgkin's lymphoma and cancers of the breast and colon, who presented with a zosteriform rash and Brown-Sequard syndrome. Despite 10 days therapy with intravenous acyclovir, meningoencephalitis developed and the patient died 15 days after onset of neurological symptoms. Autopsy showed meningoencephalomyelitis with necrotising vasculitis of leptomeningeal vessels, which is a rare complication of VZV, and we review the literature of the nine similar published cases. Polymerase chain reaction of cerebrospinal fluid for VZV was negative 6 days after onset of neurological symptoms, but became positive by day 10. Only one multinucleated giant cell with intranuclear Cowdry type A inclusions was seen within an endothelial cell in a leptomeningeal vessel involved by vasculitis.     

Gastropericardial Fistula as a Complication in a Refractory Gastric Ulcer after Esophagogastrostomy with Gastric Pull-Up

A gastropericardial fistula, defined as penetration of a gastric lesion into the pericardium, is a rare occurrence. Such a fistula is usually associated with a huge ulcer in the gastric fundus, an ulcer within a hiatus hernia, a history of esophagogastric surgery, the concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs), or Zollinger-Ellison syndrome. The patient in this case presented with shoulder pain and melena, caused by a gastropericardial fistula that had occurred as a late complication of postoperative esophagogastrostomy and a refractory gastric ulcer. Despite the severity of the condition, the patient showed great improvement after medical treatment and the fistula was cured at the end.     

Transsynaptic spread of varicella zoster virus through the visual system: a mechanism of viral dissemination in the central nervous system

We report a patient with pathologic evidence of anterograde spread of varicella zoster virus (VZV) through the visual system. A 29-year-old homosexual man developed the acquired immunodeficiency syndrome (AIDS) 2 months before the onset of left herpes zoster ophthalmicus. During the next 11 months, the zoster infection progressed to involve the left eye, with resultant keratitis, iritis, retinitis, and eventual blindness. Later, the patient developed bilateral blindness, left hemiparesis, and fatal pneumonia. At autopsy, the brain revealed destruction of the visual system and adjacent structures, with sparing of the remainder of the brain. Glial cells near the areas of necrosis showed Cowdry type A intranuclear inclusions. In situ hybridization with probes to VZV nucleic acid sequences were positive in the necrotic brain and retinal areas. Hybridization with probes to cytomegalovirus, herpes simplex virus type II, human immunodeficiency virus, and Epstein-Barr virus were negative. Electron microscopy revealed characteristic herpes group nucleocapsids. This case provides insight into the mechanisms of virus dissemination and the production of encephalitis.     

Meningoradiculoneuritis due to acyclovir-resistant varicella zoster virus in an acquired immune deficiency syndrome patient

Varicella zoster virus (VZV) is recognized as one of the major viral pathogens reactivated in patients with the acquired immune deficiency syndrome (AIDS). We report the case of meningora-diculoneuritis in an AIDS patient, associated with the isolation in the cerebrospinal fluid (CSF) of a thymidine kinase (TK)-deficient, acyclovir (ACV)-resistant strain of VZV. Although the virus was sensitive in vitro to phosphonoformate (PFA), the patient did not improve during PFA therapy and finally died. Several VZV strains isolated from this patient (including two isolates from the patient's CSF) were analyzed for their TK activity and subsequently the viral TK gene was sequenced showing a major deletion leading to a truncated protein. Their susceptibility to several antiviral agents including ACV, PFA, (E)-5-(2-bro-movinyl)-2′-deoxyuridine (BVDU), 9-β-D-ara-binofuranosyladenine (vidarabine), (S)-1-(3-hy-droxy - 2 - phosphonylmethoxypropyl) cytosine (HPMPC), and (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine (HPMPA) was evaluated. All the virus strains isolated from this patient remained sensitive to HPMPA and HPMPC, pointing to the potential usefulness of these acyclic nucleoside phosphonates for the treatment of ACV-resistant VZV infections in immunocom-promised patients. © 1994 Wiley-Liss, Inc.     

Immunoelectron microscopy for rapid diagnosis of varicella-zoster virus in a complicated case of human T-cell lymphotropic virus type 1 infection.

Rapid techniques for the detection of herpes simplex virus (HSV) and varicella-zoster virus (VZV) are needed for optimal therapeutic management. VZV infection poses a serious threat, especially to seriously ill patients, for instance, immunocompromised patients. We report a case of human T-cell lymphotropic virus type 1-positive leukemia complicated by atypical multidermatomal herpes zoster. Viral culture and standard serological tests failed to prove VZV infection. Herpesvirus infection was confirmed by cytodiagnosis (Tzanck test). The final diagnosis of VZV was made by immunoelectron microscopy (IEM), which can differentiate between HSV and VZV. Immunoglobulin M antibodies in serum directed against VZV were detected by IEM but not by immunofluorescence. Because IEM was able to identify virus and analyze sera in only 2 h, it is considered a valuable additional tool for the rapid diagnosis of HSV and VZV infections.     

Oesophagitis—a complication of inhaled steroid therapy

The hazards of steroid therapy, both inhaled and oral, in the asthmatic patient are well recognized. The following case report presents an unusual complication of steroid therapy, namely, that of a concomitant Candida and Herpes simplex oesophagitis occurring in a steroid-dependent 15-year-old asthmatic who had been maintained on inhaled beclomethasone for approximately 15 months. Oesophagoscopy revealed a ‘cottage cheese’ appearance of the distal oesophagus. Cultures of the biopsy specimens obtained during oesophagoscopy grew Candida and Herpes simplex virus. Lymphocyte stimulation studies were consistent with a primary cellular response, although the neutralizing antibody titres to the Herpes simplex virus were intially high and remained stable throughout the illness and convalescent period. The patient responded well to oral nystatin therapy and developed no evidence of disseminated herpes. Eleven months after the initial episode, the patient's oropharynx cultured Herpes simplex virus but not Candida. Doctors who care for asthmatic patients need to be aware of the possibility of a herpetic as well as a candidal oesophagitis as a significant complication of inhaled steroid therapy.     

Diagnosing herpesvirus infections by real-time amplification and rapid culture

Procedures using real-time technique were developed to demonstrate the presence of herpes simplex virus type 1 (HSV-1) and HSV-2, varicella zoster virus (VZV), and cytomegalovirus (CMV) in miscellaneous clinical specimens. The assays were compared to rapid culture using centrifugation followed by detection with monoclonal antibodies. A total of 711 consecutive samples were collected from different patient groups. Throat swabs were obtained from transplant patients; dermal or oral specimens were collected from patients suspected for VZV or HSV infection. Genital specimens were taken from patients who attended the Clinic for Sexually Transmitted Diseases at the Dijkzigt Hospital Rotterdam presenting with symptoms of a primary genital ulcer. Nucleic acid extraction was carried out using a MagnaPure LC instrument. The amplification steps were performed on the ABI Prism 7700 sequence detection system. To monitor the process of extraction and amplification, a universal control consisting of seal herpesvirus type 1 (PhHV-1) was added to the clinical specimens. By culture 127 of 668 (19%) samples were positive for HSV-1, 72 of 668 (10.8%) specimens were positive for HSV-2, and 17 of 366 (4.6%) were positive for VZV. Using real-time amplification the numbers of positive specimens were 143 of 668 (21.4%), 97 of 668 (14.5%), and 27 of 366 (7.4%), respectively. Eighty-six specimens were tested for CMV, 12 (14.0%) were positive by culture, and 17 (19.8%) were positive by real-time PCR. The clinical data of the patients with discrepant results were reviewed thoroughly. In all cases the patients with only real-time PCR-positive results could be considered as truly infected. We concluded that the real-time amplification technique is suitable for the detection of human herpesvirus infection. It offers a semiquantitative and reliable assay with a quick result that is more sensitive than rapid culture, especially for the diagnosis of HSV-2 and VZV infections.     

A novel mutation of varicella-zoster virus associated to fatal hepatitis.

BACKGROUND: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unknown. The discovery of glycoprotein E (gE) mutants showing attributes consistent with increased virulence in vitro and in animal models, provided a possible molecular mechanism underlying a more aggressive virus infection. However, these mutants have never been associated with unusually severe clinical cases. OBJECTIVES: To varicella-zoster virus (VZV) mutations that correlate with increased virulence. RESULTS: We report a case of fatal hepatitis caused by a VZV bearing a novel mutation on the 3B3 monoclonal antibody epitope of gE in an immunocompetent host. CONCLUSIONS: This report describes a mutant VZV responsible for an aggressive clinical course in an immunocompetent host. Linking these severe clinical presentations of VZV infection to virus mutations might provide insights into the underlying pathogenic mechanisms.     

Comparative restriction endonuclease analysis of varicella-zoster virus clinical isolates

The DNAs of 67 isolates of varicella-zoster virus (VZV) obtained from 31 individuals were compared by restriction endonuclease analysis using BamHI, EcoRI, PstI and SmaI. All of the epidemiologically unrelated 26 isolates could be differentiated using SmaI and another one or two enzymes. However, the DNA cleavage profiles of multiple VZV isolates from the same patient and the isolates from a group of patients who were infected with VZV from the same source were found to be identical to each other, as reported previously. No patients were found who were simultaneously infected with different VZV strains. Moreover, VZV showed no change in DNA fragment profiles after serial passages not only through human embryonic lung cells but also through patients.     

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.     

Challenges in designing a Taqman-based multiplex assay for the simultaneous detection of herpes simplex virus types 1 and 2 and Varicella-zoster virus

To optimise molecular detection of herpesviruses an internally controlled multiplex Taqman-PCR for the detection of Herpes simplex virus 1 (HSV1), Herpes simplex virus 2 (HSV2) and Varicella-zoster virus (VZV) was developed. The selection of the dye combination working on the ABI 7700 cycler for this multiplex PCR revealed crosstalk phenomena between several combinations of reference dyes and reporter dyes. A final dye combination with CY5 as reference dye and FAM/JOE/TXR as reporter dyes was selected. The influence of the concentration of the internal positive control (IPC) concentration on the quantitative results of HSV1, HSV2 and VZV positive patient samples was analysed. The results indicate that high IPC concentrations are detrimental for the sensitivity of the multiplex assay and that the presence of the IPC molecule narrows the dynamic range of the duplex PCRs between any of the virus PCRs and the IPC-PCR. The optimised multiplex assay detecting HSV1, HSV2 and VZV using 10(3) IPC molecules showed a performance and sensitivity comparable to that of the individual assays.     

Varicella zoster gastritis in a bone marrow transplant recipient.

A case is reported of a patient who had previously undergone autologous bone marrow transplantation for recurrent Hodgkin's disease. The patient developed a generalised vesicular skin eruption. The clinical diagnosis was of disseminated shingles. Herpes viral particles were identified within the vesicular fluid by electron microscopy and using a specific monoclonal antibody to varicella zoster virus (VZV), positive immunofluorescence was detected in scrapings from the base of a vesicle. Gastroscopy and biopsy were performed because of severe abdominal pain and vomiting. The histological features were of non-specific active inflammation. Despite the histological absence of viral inclusions electron microscopy of the gastric biopsy revealed the presence of intranuclear herpes viral particles with a diameter of 90-100 nm. VZV specific DNA was detected by the polymerase chain reaction in the gastric biopsy extract. The patient was treated with acyclovir and made a full recovery.     

Serological studies on the antigenic relationship between herpes simplex virus and varicella-zoster virus.

If crossreacting antibodies between varicella-zoster virus (VZV) and herpes simplex virus (HSV) exist, one would expect more positive reactions with VZV in a group of HSV positive patients than in a group of HSV negative patients. This statement can only apply to a group of individuals where positive and negative reactions with respect to HSV and VZV are evenly distributed. Such a distribution can only be found among children. Therefore, the relationship between HSV-1 and VZV was the only one which was considered in this investigation, since the incidence of HSV-2 antibodies in children is very rare. The sera from 197 children were examined using the neutralization test (NT), the complement fixation test (CFT) and the indirect immunofluorescent assay (IFT) and could be classified as either HSV positive (80) or HSV negative (117). The children's ages were similar in both groups. Approximately the same proportion of VZV positive sera was found in both groups when examined using IFT (53% in the HSV positive and 47% in the HSV negative group). However, when the CFT was applied the proportion of VZV positive sera in the two groups differed markedly (22% of the HSV positive sera and 38% of the HSV negative sera). These findings suggest that crossreactivity observed between HSV and VZV in acute HSV and VZV infections is evidently not dependent on crossreacting antibodies but is apparently confined to the cellular level of the immune response.     

Concurrent reactivation of varicella zoster virus and herpes simplex virus in an immunocompetent child

Latency within the nervous system is a characteristic feature of herpesviridae infection. It is reactivated by triggering factors such as UV exposure, stress, and trauma. Simultaneous reactivation of herpes simplex and herpes zoster is uncommon, however, an observation provably explained by differences in the triggering mechanism. Concurrent reactivation of herpes simplex virus (HSV) and varicella zoster virus (VZV) is occasionally encountered in immunosuppressed patients; on the other hand, it is rarely reported in immunocompetent individuals. We present the case of an immunocompetent 8-yr-old female patient with concurrent reactivation of HSV on the face and VZV on the right L2 dermatome.     

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.     

The First Case of Monkeypox in the Republic of Korea

A rapid outbreak of monkeypox is ongoing in non-endemic countries since May 2022. We report the first case of monkeypox in the Republic of Korea. This occurred in a 34-year-old male patient who traveled to Europe in June 2022. On the day of his return to the Republic of Korea (June 21, 2022), the patient presented with a genital lesion. The results of the monkeypox real-time polymerase chain reaction tests were positive in the penile ulcer, oropharyngeal and nasopharyngeal specimens. The patient subsequently developed fever and skin rash after hospital admission. Careful history taking along physical examination should be conducted in the patients who have epidemiologic risk factors for monkeypox. Moreover, appropriate specimens should be obtained from lesions and tested for the monkeypox virus.     

Determination of specific IGA antibodies to varicella zoster virus by immunoperoxidase assay.

An indirect peroxidase technique was developed for determination of IgA antibodies to varicella zoster virus (VZV). The antigen consisted of acetone-fixed trypsinised VZV-infected cells. Rabbit antihuman IgA peroxidase conjugate was used to detect human IgA antibodies bound to viral antigen. In parallel IgG antibodies to VZV were determined by an immunoperoxidase antibody to membrane antigen (IPAMA) technique. Varicella zoster virus IgA antibodies were detected in all five varicella and seven zoster patients. No VZV IgA antibodies (less than 2) were detected in 45 healthy control sera. Neither were they found in paired sera of five patients with herpes simplex infection, five patients with human cytomegalovirus infection and two patients with Epstein-Barr virus infection. Application of immunoperoxidase IgA technique in serodiagnosis of primary and reactivated VZV infections is discussed.