Viral strain identification in varicella vaccinees with disseminated rashes

BACKGROUND: Approximately 15% of recipients of live attenuated varicella vaccine may develop mild breakthrough varicella months to years after immunization. Although some vaccinees will develop zoster, it is less common in recipients of vaccine than in those who have had natural varicella. OBJECTIVE: To determine the varicella-zoster virus (VZV) strain responsible for breakthrough varicella and zoster in recipients of varicella vaccine. METHODS: A PCR assay capable of distinguishing wild-type from vaccine strain VZV was performed on samples from skin lesions from vaccinees with breakthrough varicella and zoster. RESULTS: All of 57 vaccinees with breakthrough varicella, clinically diagnosed on the basis of a generalized maculopapular or vesicular rash, in which there was amplifiable DNA [corrected], had wild-type VZV infection based on analysis of viral DNA. The Oka vaccine strain of VZV was not identified in any of these cases. In contrast, in 32 patients with zosteriform rashes, the vaccine strain was identified in 22 samples, and the wild-type strain was identified in 10 samples. CONCLUSIONS: Wild-type virus was identified in all generalized rashes occurring after the immediate 6-week postvaccination period. When reactivation of vaccine strain occurred, it presented as typical zoster. We find no evidence that reactivation of vaccine virus occurs with the clinical picture of generalized rash.     

Streptococcus pulmonary empyema after varicella infection in a serologically immunocompetent boy

Varicella zoster virus (VZV) is the etiologic agent of varicella, and it remains common among children in Japan due to low vaccination rates. It can cause a variety of serious and life‐threatening complications. Generally, the most frequent complication of varicella in healthy children is bacterial superinfection, but empyema after VZV infection is a rare condition. This case report describes a previously healthy 21‐month‐old boy who attended nursery school with a recent varicella and group A β‐hemolytic streptococcus (GABHS) pharyngitis outbreak and who presented with a 7 day history of vesicular rash along with progressive fever. Due to continued mild cough and prolonged fever, however, chest radiography was done, which showed a right pleural effusion. Further computed tomography showed a right pulmonary empyema, and purulent material was drained and eventually grew GABHS. This report hereby describes the development of pleural empyema caused by GABHS after VZV infection in a serologically immunocompetent patient.     

Herpes zoster by reactivated vaccine varicella zoster virus in a healthy child

Varicella can be prevented by vaccination using the live-attenuated Oka vaccine strain of varicella zoster virus (VZV). Only mild breakthrough disease has been reported in seronegative vaccinees when exposed to the wild-type virus. The latent varicella vaccine virus has rarely caused herpes zoster in childhood and adolescence. We report a healthy 2-year-old girl who developed an impressive herpes zoster infection 16 months after vaccination, localised in three cervical dermatoma. As causative virus, VZV vaccine strain was identified by polymerase chain reaction and analysis of restriction fragment length polymorphisms of the amplified products. CONCLUSION: vaccine varicella zoster virus can occasionally reactivate in healthy children and present as herpes zoster. Virus characterisation is necessary to identify the strain and provide information on the incidence of occurrence.     

Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation

Because of the severe complications that may result from varicella zoster virus (VZV) infection following renal transplantation (Tx), transplanted varicella-susceptible children exposed to varicella are typically given varicella zoster immunoglobulin (VZIG) as prophylaxis or are admitted and treated with parenteral acyclovir if VZIG prophylaxis fails. As both VZIG and hospitalization are costly, prevention of varicella infection by vaccination could potentially result in significant cost savings in addition to decreasing morbidity and mortality. To test this hypothesis, we developed a decision-analysis model to evaluate the cost-effectiveness of vaccinating patients with chronic renal failure (CRF) against varicella prior to renal transplant. Under baseline assumptions, vaccination for varicella pretransplant was a cost-effective strategy, with a cost of $211 per patient vaccinated compared with $1,828 per patient not vaccinated. The magnitude of cost savings from vaccination was sensitive to variations in the cost of varicella vaccine, the percentage of patients hospitalized for treatment with acyclovir, and the percentage of patients exposed to varicella infection. One- and two-way sensitivity analyses confirmed that vaccination was the dominant cost-effective strategy under all conditions examined. We conclude that vaccination for varicella pretransplant is cost-effective for patients with CRF, and that the magnitude of cost savings is sensitive to the cost of hospitalization, the percentage of patients exposed to varicella, and the cost of varicella vaccination. Pending results of ongoing studies of the safety and efficacy of VZV vaccine in children with CRF, we recommend that VZV vaccine be given to all children with CRF.     

Increased incidence of herpes zoster in normal children infected with varicella zoster virus during infancy: community-based follow-up study

We surveyed outbreaks of varicella zoster virus (VZV) and herpes zoster virus, involving 31 outbreaks of chicken pox, in a semiclosed institution in Osaka Japan during the 34 years between 1949 and 1984. Eight hundred forty-nine infants and children who had had clinical varicella during the first 4 years of life and those who had resided in the institution at least 12 to 144 months after the onset of varicella were included in the study. Nine cases of zoster were observed among children who had acquired varicella during the first year of life, but there was no case of zoster in those who had acquired varicella after 1 year of age. In 61,800 person-months of observation, the overall incidence rate of zoster was calculated as 0.15 per 1000 person-months for the population at risk. The incidence rate in children infected with VZV when younger than 2 months was 1.0 per 1000 person-months during the first decade of life. This rate was significantly (P less than 0.005) greater than that (0.19 per 1000 person-months) in children who had varicella when they were 2 to 11 months of age. These observations suggest that zoster occurs at a significantly shorter interval if VZV infection is acquired during infancy. More than 85% of subjects with prior infection were intimately reexposed to epidemic varicella during their residency in the institution, before having zoster. Epidemic reexposure to varicella during follow-up resulted in enhancement of preexisting immunologic reactivity, but did not prevent subsequent zoster in the population studied.     

The impact of varicella vaccination in the United States

The addition of varicella vaccine to the universal childhood immunization schedule in the United States in 1995 can be seen as a bold step. Shown to be safe and efficacious against varicella in extensive prelicensure studies, it is nonetheless the first vaccine against a herpesvirus and, furthermore, it is a live, attenuated vaccine. Both wild-type and vaccine strain varicella zoster virus (VZV) are noteworthy for their ability to establish latent infection within the host, with the subsequent possibility of reactivation. Therefore, at the population level, a successful vaccination program could result in the eventual displacement of wild-type VZV by the attenuated vaccine virus. The immediate objective of universal vaccination, however, was to reduce the significant morbidity and mortality associated with primary VZV infection. Data now accumulating suggest that the varicella vaccine as used in the United States has so far been highly effective. The challenge for the future is to predict how the resulting substantial reduction in circulation of VZV will affect immunity among both vaccinees and the unvaccinated. Vaccination strategies likely will need to be adjusted as the epidemiology of VZV in the United States continues to evolve.     

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??Objective To discuss the diagnosis, high risk factors, prevention and treatment of disseminated varicella zoster virus??VZV?? infection after allogeneic hematopoietic stem cell transplantation??allo-HSCT?? in children with aplastic anemia??AA??. Methods A retrospective analysis was made about the clinical data of 3 children with disseminated VZV infection after allo-HSCT for AA. Results Three children, aged 10??13 years old??who didn’t present graft-versus host disease??GVHD?? after transplantation, were given single drug as anti-viral prophylaxis of VZV. During the period of prophylaxis, none of them developed VZV reactivation but they showed symptoms of disseminated VZV infection after discontinuation of anti-viral prophylaxis. All of them were treated with intravenous ganciclovir, oral valaciclovir combined with external application of penciclovir and with gamma globulin until the rush crusted, and eventually all of them recovered well. Conclusion Patients with allo-HSCT for aplastic anemia are at high risk of developing disseminated VZV infection and they have high incidence of mortality and poor prognosis. We recommend anti-viral prophylaxis after allo-HSCT for prevention?? and reduced dose of immunosuppressive drugs and combination use of ganciclovir, valaciclovir and gamma globulin when patients present symptoms of VZV infection.     

Zona in children]

Herpes zoster is the clinical consequence of a late reactivation of the varicella zoster virus (VZV). It infects mainly the elderly, but pediatric cases are not uncommon. It occurs mostly in immunocompromised children, or in infancy after reactivation of latent VZV infection acquired transplacentally during intrauterine life. Rarely, herpes zoster occurs in otherwise normal children, especially following varicella during the first year of life. Clinical presentation of herpes zoster in children is identical to that of adult, with usually a benign course. The impairment of cellular and non specific immunity (Natural Killer cells) appears to have a particular role in the occurrence of herpes zoster. Treatment of the usual form comprises antiseptic measures and prevention of pruritus. In immunocompromised children, the infection is generally severe and disseminated, and can result in high rates of morbidity and mortality, thus requiring specific intravenous antiviral therapy with antiviral drugs such as acyclovir without delay. There is no single approach towards VZV infection prevention in immunocompromised hosts. Vaccination with live attenuated varicella vaccine, has proved to be efficient and safe in immunocompromised children.     

Atypical varicella zoster infection associated with hemophagocytic lymphohistiocytosis

Two adolescents, on immunosuppressive therapy for graft‐versus‐host disease, developed hemophagocytic lymphohistiocytosis (HLH) after varicella zoster virus (VZV) reactivation. In the absence of dermatome restricted characteristic skin lesions, VZV reactivation was not immediately recognized and treatment with acyclovir was delayed. The first patient developed optical neuritis and died 2 months after the VZV episode due to massive intracranial hemorrhage. The second patient presented with severe abdominal pain and pancreatitis, followed by atypical skin eruptions, which prompted a faster diagnosis. Both patients recovered from their HLH, the first patient being successfully treated with immunosuppressive agents and the second with VZV treatment only. These two cases demonstrate the difficulties in recognizing VZV reactivation, and in order to start adequate and timely treatment, the need to consider VZV as a possible cause of HLH in severely immunocompromised patients. Pediatr Blood Cancer 2009;53:226–228. © 2009 Wiley‐Liss, Inc.     

Pre-eruptive varicella encephalitis: case report and review of the literature

Varicella-related neurological complications usually appear after the rash. Pre-eruptive neurological complications of primary varicella zoster virus infections have been rarely described. We report on a 5.5-year-old boy who developed encephalitis 4 days before the onset of a mild vesicular skin rash and 5 days after known exposure. Primary varicella zoster virus infection was confirmed serologically. Cranial magnetic resonance imaging revealed temporary inflammatory oedema in the right cerebellar peduncle. Conclusion Neurological complications of varicella may appear up to 2.5 weeks before the onset of the exanthema. Physicians treating patients with ataxia or encephalitis should inquire about exposure to varicella zoster virus. Received: 15 January 1998 / Accepted: 27 March 1998     

Clinical and serologic testing of a live varicella vaccine and two-year follow-up for immunity of the vaccinated children.

A live varicella vaccine derived from the Oka strain was given on 181 children who had no history of varicella and were seronegative by complement fixation (CF) and neutralization (NT) tests; 125 children were hospitalized and 54 were receiving steroid therapy. Overall, seroconversion was achieved in 85.1% of the children by the CF test and in 97.8% by the NT test. Clinical reaction consisting of mild fever and rash appeared in only two children. One hundred seventy-nine of the vaccinated children were followed up by questionnaire and 51 were followed up serologically approximately two years later, at which time 10 of 51 (19.6%) were seropositive by the CF test and 50 of 51 (98.0%) by the NT test. Only one out of 80 children who had postvaccinal contact with varicella contracted mild varicella 16 months after vaccination. None of the vaccinees developed herpes zoster. These results suggest that this live varicella vaccine may safely and effectively be used for children with or without underlying diseases, including those receiving steroid therapy, and that immunity of at least two years' duration is conferred upon the vaccinated subjects.     

A case of meningitis due to varicella zoster virus reactivation in an immunocompetent child

Background

The development of neurological complications due to varicella zoster virus (VZV) reactivation is relatively uncommon, particularly in the case of immunocompetent patients. Only a few cases have been described in the literature, most of which involved adult or elderly patients.

Clinical presentation

Two days after his pediatrician had diagnosed herpes zoster and prescribed oral acyclovir 400 mg three times a day, a 14-year-old boy was admitted to our hospital because of mild fever, severe headache, slowness, drowsiness and vomiting. A cerebrospinal fluid examination was performed and showed an increased protein concentration (95 mg/dL), normal glucose level (48 mg/dL; blood glucose level, 76 mg/dL) and lymphocytic pleocytosis (1,400 lymphocytes/μL), and VZV DNA was detected by means of polymerase chain reaction (1,250 copies/mL). The results of immunological screening for HIV, lymphocyte subpopulation counts, serum immunoglobulin and complement (C3 and C4) levels, vaccine responsiveness and lymphocytes stimulation tests were unremarkable. Acyclovir was administered intravenously at a dose of 10 mg/kg three times a day and continued for 10 days. The therapy was highly effective and the patient’s clinical condition rapidly improved: fever disappeared after two days, and all of the signs and symptoms of neurological involvement after four days. The skin lesions resolved in about one week, and no pain or dysesthesia was ever reported. Given the favourable evolution of the illness, the child was discharged without further therapy after the 10-day treatment. The findings of a magnetic resonance examination immediately after the discontinuation of the antiviral therapy were normal, and a control examination carried out about four weeks later did not find any sign or symptom of disease.

Conclusion

VZV reactivation can also lead to various neurological complications in immunocompetent children. Prompt therapy with acyclovir and the integrity of the immune system are important in conditioning outcome, but other currently unknown factors probably also play a role.

     

Congenital Langerhans-cell histiocytosis presenting as a varicella infection

We report on a preterm infant (33rd gestational week) with a varicella-like congenital rash, which initially appeared to respond to therapy with acyclovir. At the age of 3 weeks, lesions were in different stages of evolution and still resembled a varicella zoster virus (VZV) infection. However, since proof of VZV infection was lacking and new lesions erupted at the age of 4 weeks, a skin biopsy was performed which revealed a diagnosis of Langerhans cells histiocytosis. Therapy with prednisone resulted in prompt healing of the lesions. DISCUSSION: Congenital Langerhans cell histiocytosis is rare and symptoms may vary substantially from case to case. Like in our observation it may be confused with congenital varicella. In case of congenital skin lesions of uncertain etiology a skin biopsy should be performed.     

Immunologic and epidemiologic aspects of varicella infection acquired during infancy and early childhood

The development of varicella zoster infection was studied in a population of infants under one year of age during three outbreaks of varicella in a semi-closed domiciliary institution for infants in Japan. Over a period of four years, many residents ranging in age from 27 days to 32 months were tested for cutaneous reactivity to VZV antigen, and VZV-specific antibody activity before, during, and after each outbreak of varicella. Of these, 85 subjects developed clinical varicella, with an overall attack rate of 100% for all susceptible subjects. All the infants under 2 months of age were infected following such exposure, despite the presence of pre-existing maternal antibody. The degree of cutaneous involvement appeared to be milder (less than 20 vesicles) in infants less than 2 months of age, and severe cutaneous disease (with over 300 eruptions or confluent rash) occurred more frequently in subjects 2 to 11 months of age. Pre-existing antibody did not prevent development of illness, or alter the degree of antibody or cellular immune response to subsequent infection. However, the peak cutaneous reactivity to VZV antigen after infection was found to be significantly lower in infants under 2 months of age.     

Varicella vaccine trials in healthy children. A summary of comparative and follow-up studies

Beginning in 1979, OKA and KMcC strains of varicella zoster virus (VZV) vaccine were administered to 369 healthy seronegative children in a sequence of ten comparative clinical trials. Postimmunization clinical reactivity was minimal with the OKA vaccines but was unacceptably high (32%) with the KMcC passage-40 vaccine. Ninety-three percent to 100% immunogenicity was noted by fluorescent antibody assay and in vitro lymphocyte proliferation to VZV antigens. Follow-up studies demonstrated persistence of antibody and in vitro lymphocyte proliferation responses and protection or modification of infection nine to 48 months after immunization. Only five episodes of mild varicella occurred in children in whom seroconversion had occurred. These episodes were noted after at least 281 known varicella exposures. Vaccine virus reactivation as zoster had not occurred in any child.     

Specific autologous cytotoxic T lymphocytes for chronic varicella in a liver transplanted child

Infections by herpesviruses may have severe complications in liver transplant patients. Although prophylactic varicella zoster virus vaccination is strongly recommended and widely applied, severe infection may still occur. We report the case of systemic chronic varicella, which developed in a liver allograft recipient, unresponsive to antiviral drug treatment, successfully treated by varicella zooster-specific CTL. Graft failure ensued, likely, because of massive cytolysis of infected hepatocytes. The patient, who was re-transplanted in the absence of signs of varicella zooster reactivation, is now well and disease free 3 yr after second liver transplant.     

儿童再生障碍性贫血造血干细胞移植后并发播散型带状疱疹3例报告并文献复习

目的 探讨儿童再生障碍性贫血（AA）造血干细胞移植（HSCT）后并发播散型带状疱疹的诊断、高危因素、预防及治疗措施。方法 回顾性分析2014年12月至2015年9月中山大学孙逸仙纪念医院儿科收治的3例AA患儿接受全相合非血缘相关供者HSCT后予免疫抑制剂治疗期间出现播散型带状疱疹的临床资料。结果 3例患儿年龄分别为13、12和10岁,移植后未出现移植物抗宿主病,予抗病毒药物单药预防水痘-带状疱疹病毒（VZV）期间均未出现VZV再激活,在HSCT后4.0、5.5和8.0个月停用抗病毒药物,分别在停用抗病毒药物后13.0、10.5和3.0个月出现皮肤播散型带状疱疹,予静脉更昔洛韦联合口服伐昔洛韦及外用喷昔洛韦抗病毒治疗至皮疹结痂,并予丙种球蛋白治疗,均完全治愈。结论 接受HSCT的AA患者是播散型带状疱疹的高发人群,其发病率高、病情严重且病死率高。移植后予预防性抗病毒处理,出现播散型带状疱疹时减少免疫抑制剂量,联合更昔洛韦、伐昔洛韦及丙种球蛋白治疗,可明显改善疗效。     

Herpes zoster in a normal child after varicella vaccination

A healthy 5 year old girl developed herpes zoster in the dermatome supplied by the ophthalmic branch of the fifth cranial nerve 40 months after varicella vaccination. She was admitted to our hospital because of high fever and painful vesicular lesions over the left side of her forehead. She was treated successfully with systemic and topical acyclovir without developing herpetic keratoconjunctivitis. Our acute and convalescent phase evaluations showed that non-specific cellular and humoral immunity was normal. This is the fourth case of herpes zoster developing in an immunocompetent child following vaccination. Unlike the previously reported cases, our patient required hospitalization mainly to prevent ocular involvement. The issue concerning whether the universal introduction of varicella vaccination of normal children will reduce the incidence of the subsequent occurrence of herpes zoster must await further studies involving longer follow-up periods.     

Oral BVDU treatment of varicella and zoster in children with cancer

In the period June 1980–April 1983, 21 children with malignant discase were admitted because of an intercurrent varicella or zoster infection. They were treated with the new antiviral drug BVDU [(E)-5-(2-bromovinyl)-2-deoxyuridine]. The drug was administered orally at a dose of 15 mg/kg per day for 5 days. All our patients responded promptly to BVDU treatment and recovered completely from their varicella or zoster infections without complications. No toxic side-effects due to the drug were observed.Abbreviations BVDU bromovinyldeoxyuridine - HSV-1 herpes simplex virus type 1 - VZV varicella-zoster virus - SGPT glutamic-pyruvic transaminase - SGOT glutamicoxaloacetic transaminase     

Arthritis and vasculitis during the incubation period of varicella

Messaritakis J, Psychou F, Dracou C, Nicolaidou P, Kakourou T. Arthritis and vasculitis during the incubation period of varicella. Acta Prediatr 1994;83:681–3. Stockholm. ISSN 0803–5253
Arthritis and vasculitis are very rare complications of varicella occurring almost exclusively after the eruption of the characteristic rash. We report two children, aged three and seven years, who developed vasculitis and polyarthritis (patient No. 1) and arthritis (patient No. 2) 13 and 9 days, respectively, before the onset of their typical varicella. Arthritis and vasculitis so early in the incubation period of varicella have not been described previously. In all previously reported cases the arthritis occurred after or together with the onset of varicella and only in one instance preceded the exanthem by 2 days. Although this may have been an unfortunate coincidence, an association between varicella zoster virus and these manifestations should be seriously considered. Clinicians confronted with such cases must be cautious and search for varicella infection, especially in times of epidemics.