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Background: Varicella, common in childhood and most often self-limiting, may cause complications including bacterial superinfection, pneumonia and encephalitis. Universal childhood varicella vaccination has been introduced in several countries, but is controversial in Europe. In Denmark, varicella is not part of the national immunization program and there is no national surveillance of varicella. The primary aim of the study was to describe the epidemiology and clinical characteristics of children hospitalized with varicella in Denmark. The secondary aim was to validate the sensitivity and completeness of the Danish National Patient Register., Methods: Active surveillance of children hospitalized with varicella was carried out at 4 pediatric departments. In the Danish National Patient Register, we identified all children discharged with an International Classification of Diseases, 10th revision code of varicella from the 4 departments. We used a capture-recapture analysis to estimate the "true" number of hospitalized children with varicella., Results: By active surveillance, we identified 86 children eligible for clinical description. In 87% of cases, the children were 0-4 years of age. Complications were identified in 69% of patients, including 1 child with postvaricella cerebral angiopathy. In the National Patient register (NPR), we identified 125 children with a discharge diagnosis of varicella. By capture-recapture analysis, the sensitivity of the NPR was estimated to be 74%., Conclusions: Varicella can cause serious complications including cerebral angiopathy in children in Denmark. The NPR will be a useful tool for estimating hospitalization incidence, but will underestimate the true number of hospitalizations.

Eight children with post-varicella musculoskeletal complications were treated between 2001 and 2009. The complications that were observed were cellulitis (three children), pyomyositis (three children), osteomyelitis (two children) and gangrene (one child). On average, 8.8 days elapsed between primary varicella infection and complication. The most common presentation was pain. Before we started treating them, all children received antibiotics during interhospital transfers (average: 2.4). Interventions included drainage (eight), fasciatomy (one), arthrotomy (one), bone drilling (one), and amputation (one). Blood cultures were negative in all children. Two children had positive pus cultures for Staphylococcus aureus, one of them had a methicillin-resistant S. aureus infection. One of the four children who developed coagulopathy ended with significant morbidity. Varicella-related methicillin-resistant S. aureus osteomyelitis suggests a widening spectrum of these infections.

A 43-year-old lady with type 2 diabetes mellitus and bronchial asthma presented with varicella zoster infection, dyspnea, and neck fullness. An urgent computed tomography scan revealed a mediastinal abscess with superior vena cava thrombus. Blood, mediastinal pus, and swab from a vesiculopustule on the neck cultured group A beta hemolytic Streptococcus. She recovered with a combination of broad spectrum antimicrobials, antivirals, and surgical drainage. This case illustrates the rare occurrence of mediastinal abscess and acute superior vena cava obstruction caused by group A beta hemolytic Streptococcus complicating adult varicella zoster.

The report described here presents a fatal streptococcal toxic shock syndrome secondary to a necrotizing fasciitis of the face in a 3-year-old girl with varicella. Pathogenesis and treatment of streptococcal toxic shock syndrome are discussed below.

This 1-year multicentre prospective study in northern France sought to evaluate the incidence of secondary bacterial skin complications related to varicella, describe these superinfections, and analyse risk factors for their onset. The study included every child admitted to a district paediatric unit with a varicella infection. Patients with varicella infection, with and without secondary bacterial skin complication, were compared. The study included 159 children, 43 of whom had a secondary bacterial skin complication on admission, 21 of them had a severe secondary bacterial skin complication (respective incidence: 7.5 and 3.7/100,000 children younger than 16 years old). Persistence or recurrence of fever > or =38.5 degrees C for > or =3 days after the beginning of varicella infection (adjusted odds ratio (aOR)=8.1; 95% confidence interval (CI): 2.3-28.4) and the use of non-steroidal anti-inflammatory drugs (aOR=4.8; 95% CI: 1.6-14.4) were independent factors associated with severe secondary bacterial skin complication.

A 5-year-old boy presented with primary varicella zoster virus infection, group A streptococcal sepsis, toxic shock, and multisite osteonecrosis. An association between osteonecrosis and group A streptococcal sepsis has not been previously reported. Clinical recognition with supportive radiologic and pathologic findings are presented. Therapeutic guidelines are suggested.

Background: Previous studies of occult bacteremia in febrile children have excluded patients with recognizable viral syndromes (RVS). There is little information in the literature regarding the rate of bacteremia in febrile children with RVS., Objective: To determine the rate of bacteremia in children 3 to 36 months of age with fever and RVS., Methods: We performed a retrospective analysis of all patients 3 to 36 months of age with a temperature > or =39 degrees C seen during a 5 1/2-year period in the Emergency Department of a tertiary care pediatric hospital. From this group those with a discharge diagnosis of croup, varicella, bronchiolitis or stomatitis and no apparent concomitant bacterial infection were considered to have an RVS. The rate of bacteremia was determined for those subjects with RVS who had blood cultures., Results: Of 21,216 patients 3 to 36 months of age with a temperature > or =39 degrees C, 1347 (6%) were diagnosed with an RVS. Blood cultures were obtained in 876 (65%) of RVS patients. Of patients who had blood cultures, true pathogens were found in only 2 of 876 (0.2%) subjects with RVS [95% confidence interval (CI) 0.01, 0.8%]. The rate of bacteremia was 1 of 411 (0.2%) for subjects with bronchiolitis, O of 249 (0%) for subjects with croup, O of 123 (0%) for subjects with stomatitis and 1 of 93 (1.1%) for subjects with varicella., Conclusions: Highly febrile children 3 to 36 months of age with uncomplicated croup, bronchiolitis, varicella or stomatitis have a very low rate of bacteremia and need not have blood drawn for culture.

Osteomyelitis is a rare complication after varicella. It should, however, be considered in any child who develops pain in a limb during or after a varicella infection. An 18 month old boy with a five day history of varicella infection was hospitalized. Movement of his right arm made him cry intensively. Blood cultures showed growth of group A beta haemolytic streptococcus. The day after admission to hospital the bone scintigrams showed increased activity in the right humeral diaphysis consistent with osteomyelitis, and penicillin therapy was started. On radiograms of the right humerus performed on the second day, no pathological changes could be shown. Radiograms after ten days showed irregular osteolytic lesions in the upper part of the humeral diaphysis. Clinically, the boy improved rapidly and could be dismissed from hospital after 17 days. Follow-up radiograms showed slowly normalized conditions, and five months after the start of symptoms, no pathological changes should be demonstrated.

Bacterial complications of varicella in 84 patients younger than 16 years of age (48 females; median age, 2.9 years) who required hospitalization between 1985 and 1995 were retrospectively analyzed. The purpose of the study was to describe demographics, clinical manifestations, bacteriology, and factors affecting outcome. Seventy-six percent of patients were younger than 5 years of age. The eldest children in households were significantly underrepresented (P = .00025). Skin infections occurred in 61 patients (73%), and deep-seated infections and/or shock occurred in 23 (27%). The latter complications were significantly associated with thrombocytopenia (P = .011) and bacteremia (P = .014) at the time of admission, prolonged fever (P = .001), prolonged hospitalization (P < .0001), intensive care management (P < .0001), and fatal outcome (P = .019). Group A beta-hemolytic streptococcus (59% of isolates) and Staphylococcus aureus (28%) were the predominant isolates. Before and after 1990, five (31%) of 16 and 13 (62%) of 21 streptococcal complications, respectively, were invasive infections (P = .09). These data underscore the need for universal immunization against chickenpox.

To clarify the cause of herpes zoster in immunocompetent children, specific humoral and cellular immunity was determined using an ELISA and a lymphoproliferative assay, respectively, in infants < 1 year of age and children > or = 1 year of age who had chickenpox. Thirteen (59.1%) of 22 infants, 17 (81.0%) of 21 children > or = 1 year of age (P < .02), and 13 (86.7%) of 15 children > or = 2 years of age (P < .001) had positive varicella-zoster virus (VZV)-specific cellular immunity. VZV-specific antibodies in infants were significantly lower than those in children > or = 1 year old (P < .01) and > or = 2 years old (P < .001). The possibility of subclinical reactivation was demonstrated by an increase in the specific cellular or humoral immunity (or both) in all of 6 infants who had negative specific cellular immunity. The low response of specific immunity and the immunologic evidence of reactivation in infants after chickenpox provide a possible explanation for the finding that chickenpox in infancy is a risk factor for herpes zoster.

Pathological findings of an otherwise healthy 17 month old boy who was exposed to Varicella-zoster virus (VZV) in his family and unexpectedly died 3 days after onset of varicella are reported. They showed a disseminated VZV infection with involvement of skin, lung, liver, spleen, gastrointestinal tract and other organs where VZV antigen was detected by the enzyme-immunoassay with monoclonal antibodies to VZV. Since the subject was the full-term product of an uncomplicated pregnancy, who grew and developed normally, and had no symptoms or laboratory findings suggestive of immunodeficiency until his death, these findings suggest that many organs are involved as major internal sites of viral replication before or during infection of skin with VZV in the immunocompetent host.

The incidence of varicella in Singapore has been increasing since 1984. In 1991, 17,930 cases were reported in a population of about 3 million. A serological survey completed in 1990 demonstrated that only 43% of the cohort had antibodies to varicella-zoster virus (VZV), indicating inadequate herd immunity. To exclude novel VZV strains, representative VZV isolates from 9 chicken pox and 4 zoster patients were characterised by restriction endonuclease analysis. DNAs were extracted from viral isolates propagated in MRC5 human embryo lung cells and were digested separately with BglII, EcoRI, PstI, SalI, and XbaI enzymes. The cleavage profiles of these VZV strains derived from both chicken pox and zoster lesions revealed no distinct differences. This observation implies that the current upsurge of chicken pox most likely stems from closely related VZV genotypes infecting a susceptible population with insufficient herd immunity. Comparison of the restriction fragments of the Singapore and the Dumas strains revealed polymorphisms of the SalI-D, SalI-E, and XbaI-I fragment lengths, which correlated with variable regions I, II, and III of the VZV genome, thereby representing geographically distinct genotypic variants of VZV.

We have previously examined a case of varicella embryopathy (VE) occurring in a 41-week gestational age infant, showing some of the most severe lesions reported to be associated with the syndrome to date. A previous survey of the postmortem tissue with two anti-varicella zoster antibodies was negative. It was hypothesized that if varicella-zoster virus (VZV) was associated with VE, a latent viral infection might be expected, similar to that occurring in adults infected with VZV. Subsequently, an attempt was made to identify DNA encoding three separate and specific VZV genes using the highly sensitive polymerase chain reaction from formalin-fixed tissues of the central nervous system including cerebral cortex, cerebellum, and brainstem, in addition to frozen tissue of liver, adrenal, and thymus. Although amplifications utilizing primers for a normal human DNA sequence (ME491) demonstrated the ability of the samples to serve as a target for the PCR, none of the samples contained amplifiable VZV DNA. Substitution of biotin 11-dUTP in the PCR and subsequent detection of the biotinylated amplimers resulted in a large increase of the sensitivity of the PCR amplimer detection, but still failed to detect the presence of VZV DNA in the samples. The most likely explanation for these findings suggests a complete destruction of fetal tissue tropic for VZV with a subsequent inability for a latent VZV infection to be established.

The authors treated 93 adult patients (83 male, 10 female) with varicella from 1st June 1987 to 30th April 1991. 13 patients had varicella pneumonia, two patients died. Special attention has been focused upon the diagnostic and prognostic problems, including bacterial superinfection. Authors stress the importance of the early diagnosis and treatment and discuss in detail the recent therapeutical and prophylactic opportunities.

Objective: To compare Tzanck smears, viral cultures, and DNA diagnostic methods using the polymerase chain reaction (PCR) in detection of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection in clinically suspected cases., Design: A 12-month trial comparing PCR with viral cultures and Tzanck smears in patients with clinically suspected HSV or VZV infection., Setting: Both ambulatory and hospitalized patients were recruited from a tertiary referral center and the Miami (Fla) Veterans Affairs Medical Center., Patients: Convenience samples of patients clinically suspected to have HSV (n = 48) or VZV (n = 35). To be included in the final analysis patients needed to have a positive Tzanck smear, viral culture, or PCR result. Patients who were clinically suspected to have HSV but had VZV by viral culture or PCR were analyzed in the VZV group. Similarly, patients who were clinically suspected to have VZV, but had HSV by viral culture or PCR were analyzed in the HSV group. Seventy-seven patients were available for final analysis: HSV (n = 30), VZV (n = 32), and 15 control cases who did not have evidence of viral infection., Results: For HSV, PCR detected HSV DNA sequences in 73% of stained smears and 83% of unstained smears. For VZV infection, VZV DNA sequences were detected in 88% of stained smears and 97% of unstained smears. Viral DNA sequences were not detected in the 15 control cases. Viral cultures were positive in 83% and 44% of HSV and VZV cases, respectively. The Tzanck smear was positive in 60% and 75% of HSV and VZV cases, respectively., Conclusions: PCR is a reliable method for detecting HSV and VZV DNA sequences from single stained and unstained Tzanck smears. It is clearly superior to viral culture in identifying VZV infection and is equivalent to conventional culture techniques in identifying cases of HSV.

The polymerase chain reaction (PCR) was used to detect varicella-zoster virus (VZV) DNA in respiratory epithelial cells and in peripheral blood leukocytes from adults with varicella. VZV DNA was detected in oropharyngeal epithelium in 62% of patients early in the course of varicella; the amount of VZV DNA declined with time and was detectable in only 22% of patients for greater than 6 days. VZV DNA was also detected in peripheral blood leukocytes in 74% of patients early in disease and was detected in both polymorphonuclear and mononuclear leukocytes. PCR demonstrated the presence of VZV DNA in the oropharynx and blood of most patients during varicella, in contrast to the ability to detect VZV in these tissues by viral culture.

Normal human trigeminal and thoracic ganglia latently infected with varicella-zoster virus (VZV) were identified by polymerase chain reaction (PCR). Total RNA was extracted from these ganglia and treated with DNase until ganglionic RNA was free of VZV DNA as determined by PCR. Radiolabeled cDNA synthesized by priming with random oligonucleotides was hybridized to Southern blots containing recombinant clones that spanned greater than 95% of the VZV genome. The single region of the VZV genome detected was the 12.5-kb SalI C fragment located in the unique long segment of the viral genome. Two additional regions of the VZV genome, EcoRI G and SalI B, were detected in RNA from adult dorsal root ganglia and infant nervous system tissue.

The events leading to the isolation of varicella-zoster virus (VZV) are described beginning with the pioneering contributions of Ernest Tyzzer and Ernest Goodpasture and the early epidemiologic observations that indicated a relationship between varicella and zoster. Isolation, propagation, and immunologic proof of the coidentity of the viruses from the two clinical entities evolved from the introduction of human cell culture systems, a development that revolutionized virus research. Now the social significance of VZV is increasing. This reflects an aging population, increasing use of immunosuppressive therapeutic procedures, and the advent of a biologic immunosuppressive agent, the virus that causes AIDS. Currently there are unsolved problems: For unknown reasons varicella is often an adult disease in the tropics, and cell cultures fail to demonstrate VZV in throat washings from cases. These peculiarities warrant elucidation.

The clinicoepidemiologic features of varicella-zoster virus and herpes simplex virus latency are clearly distinctive. These differences indicate that each virus has evolved a unique strategy to ensure the establishment and maintenance of latency and to reactive therefrom. Indeed, current data reveal divergent pathogenetic and molecular biologic properties that may account for the clinicoepidemiologic characteristics that distinguish recurrent infections with these herpesviruses.

Varicella-zoster virus (VZV) is highly species-specific and has been demonstrated to naturally infect only humans and great apes. Simian varicella, a group of antigenically related agents distinct from VZV, infects cercopithecoids producing severe varicella-like disease but does not infect humanoids. Seroconversion following inoculation of VZV in small laboratory animals has been demonstrated in the rat, rabbit, and guinea pig; however, animal-to-animal spread, viremia, and exanthem have been demonstrated only in guinea pigs. Both humoral and cellular immune responses to VZV infection have also been examined in the guinea pig model. Ocular infection with VZV has been explored in both the guinea pig and rabbit. Animal models of VZV persistence have been elusive although persistence may be established in the rat.

This paper uses mathematical models and data analysis to examine the epidemiological implications of possible immunologically mediated links between patterns of varicella and herpes-zoster incidence in human communities. A review of previously published reports does not clarify whether or not there is a relationship between the incidence of varicella and the incidence of zoster. However, new analysis of data collected by the Royal College of General Practitioners provides indirect evidence for the hypothesis that a high intensity of varicella transmission suppresses viral reactivation. The significance of this finding for proposed varicella vaccination campaigns is explored by a review of published data on the use of the vaccine. No significant difference is shown to exist between the risk of zoster caused by the vaccine and the wild virus. A mathematical model is then developed to take into consideration the influence of the prevalence of varicella on viral reactivation and the impact of vaccination with attenuated virus, which may be able to recrudesce. Under some conditions, mass application of such vaccines may have the impact of increasing zoster incidence. The results presented here indicate that, before starting any vaccination programme against varicella, its consequences need to be assessed in much more depth.

The herpes simplex and varicella-zoster viruses are members of the subfamily alpha herpesviruses with specific properties of the virion and with the capacity to establish latent infections in humans. The genome of each of these viruses has been determined with an estimate of the number of genes and proteins encoded. The biology and molecular events of the herpes simplex virus productive and latent infection have been detailed with the use of both in vitro and in vivo model systems. The neuron is the site of latency in the ganglia with a limited transcription of genes expressed during the latent period. The specific molecular regulation of latency and reactivation are not well established. There are co-cultivation, electron microscopy, and biochemical studies that support the concept of corneal latency, although this has not been proven conclusively. Details about the varicella-zoster virus biology and molecular events are not as well advanced since animal models have been lacking. The biology of the productive infection (varicella) is different from herpes simplex virus infection since the portal of entry is the respiratory system. Data support the concept of the maintenance of latency within satellite cells in the ganglia rather than within neurons. There are multiple genes expressed during this latency. These features may explain the different clinical presentations and course of reactivation (zoster) compared with herpes simplex virus reactivation.

A 9 year old boy developed acute monoarthritis of the left knee concurrent with the appearance of a varicella zoster virus (VZV) rash. Repeated VZV DNA hybridisation of the cells within the synovial fluid and synovial membrane failed to show any evidence of intracellular virus. Virus was isolated from synovial fluid 24 hours after the start of clinical infection but not later. These findings suggest that the mechanism of the arthritis is not due to viral replication inside the swollen joint.

A simplified assay for the diagnosis of varicella-zoster virus (VZV) infections based on the polymerase chain reaction (PCR) is described. Omitting the procedures for extraction and purification of DNA, the crude vesicle fluid materials were used for PCR. Moreover, hybridization was not necessary for detection of the amplification products because they were already visible after ethidium bromide staining of the electrophoresis gel. Results could therefore be obtained within one day. In comparison to virus isolation, PCR proved much more rapid, highly sensitive, and specific. DNA extraction and a double PCR assay with nested primers were necessary for detection of latent VZV infections in trigeminal and thoracic ganglia. The data suggest that the procedures described are universally applicable to several types of specimens dependent on the calculated amount of target DNA.

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

A polymerase chain reaction (PCR) method developed to detect varicella zoster virus (VZV) in clinical samples is based on amplifying sequences of viral gene 31, the coding region for glycoprotein II. Its sensitivity was evaluated by amplification from plasmid VZV DNA containing VZV gene 31; 45 copies were detected in 1 microgram of human DNA. In testing within 24 h after the onset of varicella exanthem, 21 (75%) of 28 lesion samples were positive by VZV PCR, whereas VZV was isolated from only 21% by a standard tissue culture method. Only 1 (3.3%) of 30 samples of oropharyngeal secretions but peripheral blood mononuclear cells from 8 (67%) of 12 patients were positive. The sensitivity and specificity of the VZV PCR method indicates its usefulness for investigating the pathogenesis of VZV infection. Direct contact with cutaneous lesions rather than respiratory secretions may be the most important route of VZV transmission from healthy individuals with acute varicella.

Serological and clinical follow-up of 35 pregnancies complicated with varicella-zoster virus (VZV) infection showed insufficient antibody response in 2 children with undetectable IgG levels in ELISA and indirect haemagglutination (IHA) test. Secondary infection with VZV at the age of 4 1/2 years of the first child and inapparent infection at the age of 4 years and 3 months in the second child born with congenital varicella lead to seroconversion against VZV. None of the children in question developed acquired varicella primoinfection. We believe that a temporary specific inhibition of antibody formation was caused by transplacentar transmission of maternal antibodies into foetal circulation.

A high proportion of depilated newborn or euthymic congenitally hairless adult guinea pigs develop an erythematous papular exanthem during infection with varicella-zoster virus (VZV) previously cultivated in guinea pig cell culture. Virus has been demonstrated in tissues during varicella using polymerase chain reaction amplification and nucleic acid hybridization methods. The frequency of exanthem expression can be reduced by the prophylactic administration of VZV convalescent-phase guinea pig serum. This model should prove useful for further study of VZV pathogenesis as well as for testing putative antiviral compounds.

Eighty-one throat swabs from 18 patients infected with varicella were tested for varicella zoster virus DNA by the polymerase chain reaction. The positive rates were 26.2% (11/42) during the incubation period and 89.7% (35/39) after clinical onset. The results indicate the pharynx is a site for early replication of the virus.

Herpesviruses include seven human viruses and numerous animal viruses. The human herpesviruses, in addition to their trivial names, are named from 1 to 7. The two most recently discovered herpesviruses thus being Human herpesvirus 6 and 7. Human herpesvirus 6 is the aetiologic agent causing exanthema subitum. Human herpesvirus 7 has, as yet, not been associated with any disease. A characteristic feature of the herpesviruses is the persistence in a latent form after primary infection which may later cause reactivated infection resulting in considerable morbidity, for example, in genital herpes. The clinical spectrum of herpes infections is very broad. In general, the primary infection is more severe than the reactivated. Other important determinants of morbidity are the patients' age and immune status. Many severe herpes infections are almost exclusively seen in immunocompromised patients. This review deals with the clinical manifestations of herpetic infections in normal and immunocompromised hosts with emphasis on the clinical recognition.

A case of herpes zoster oticus in a 2 1/2 year-old girl with a history of varicella at the age of 4 months is reported. Peripheral facial palsy was the prominent clinical symptom. Following treatment with Acyclovir 15 mg/kg/day i.v. for 7 days a complete remission was noted. Course, treatment and prognosis of zoster oticus are discussed, as well as the increased incidence of herpes zoster in children who had varicella before the age of 1 year.

The purpose of the present study was to determine whether a high number of bacteria could be demonstrated in the upper small bowel during the chickenpox infection. Intestinal juice was drawn in nine malnourished children, during and two weeks after the acute period of the disease. The results of the study fail to demonstrate quantitative differences in the bacterial flora of the small bowel in both periods. Besides that, the bacterial overgrowth previously reported in malnutrition, is confirmed.

In a retrospective study of 421 patients infected with human immunodeficiency virus, 15 (3.5%) had varicella. Twelve patients had a typical varicella. Complications were as follows: profuse eruption, 6; hemorrhagic eruption, 1; hepatitis, 5; and pulmonary involvement, 1; 1 patient developed an intravascular disseminated coagulation and died of varicella. Three patients with acquired immunodeficiency syndrome, having a history of varicella, presented with an atypical form of varicella with a small number of disseminated cutaneous poxlike lesions; 1 of these patients experienced three relapses of atypical varicella. Assay of serum antibodies to varicella zoster virus showed that, while typical varicella was the primary varicella zoster virus infection, atypical varicella was a reactivation of varicella zoster virus infection. Acyclovir was given to 11 patients and vidarabine to 1 patient. The one patient who died and the one who suffered a relapse had received acyclovir. Thus, varicella in patients infected with human immunodeficiency virus may be complicated and even lethal. Atypical forms of varicella could be, as is the case with herpes zoster, a reactivation of endogenous varicella zoster virus.

The number of varicella zoster virus-infected mononuclear cells in blood samples obtained during 3 days before appearance of vesicular skin rashes could be estimated in 13 of 21 immunocompetent children with varicella and viremia (range, 1-83 per 10(7) mononuclear cells). The virus was isolated from 5% of adherent cells (1/21), 71% of nonadherent cells (12/17), 43% of T lymphocytes (9/21), and 33% of B lymphocytes (7/21). The number of vesicles on the body correlated with the maximum body temperature, duration of fever, and number of infected cells in the blood. These results indicate that varicella zoster virus infection in immunocompetent children is disseminated by circulating T and B lymphocytes and the severity of the viremia is reflected in the severity of the disease.

Study Objective: To determine whether acyclovir administered orally affects the duration and severity of varicella in otherwise normal children., Design: Randomized, placebo-controlled, double-blind trial., Setting: Patients' residence and university hospital clinic., Patients: One hundred five children between 5 and 16 years of age with laboratory-confirmed varicella entered the study. Of the 102 who were included in the final analysis, 50 received acyclovir and 52 received placebo., Intervention: Placebo or acyclovir was given orally four times daily, for 5 to 7 days. The acyclovir dose was adjusted as follows: 5 to 7 years of age, 20 mg/kg; 7 to 12 years, 15 mg/kg; and 12 to 16 years, 10 mg/kg., Measurements and Main Results: Acyclovir recipients, compared with the placebo group, defervesced sooner (median, 1 day vs 2 days; p = 0.001), experienced onset of cutaneous healing sooner, as reflected by a decrease in number of lesions (median, 3 days vs 2 days; p = 0.002), and had fewer skin lesions (median, 500 vs 336; p = 0.02). Acyclovir did not significantly change the rate of complications of varicella (10% in the acyclovir group vs 13.5% among placebo subjects). Adverse drug effects were not observed. Acyclovir recipients had lower geometric mean serum antibody titers to varicella-zoster virus than their placebo counterparts 4 weeks after the onset of illness, but antibody titers in both groups were similar 1 year later., Conclusions: These results provide evidence that acyclovir is useful and well tolerated for treatment of varicella in otherwise healthy children.

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.

The live varicella virus vaccine which was developed by Takahashi et al, in Japan in 1974 is under study in many countries. This vaccine is able to induce a high degree of immunity in the absence of acute reactions, and therefore it appears to be an effective help in the prevention of VZ infection. The capacity of VZV to become latent in neuronal cells represents a major difficulty in developing strategies for extensive vaccination. Other potential problems are summarized. More extensive studies and clinical trials are required, on the assumption that benefits will outweigh hypothetical risks, before this new immunization is started in children with or without underlying disease.

We report seven cases of seven pulmonary varicella occurring in seven adults without any previous history of known immunological deficit. In all the cases the vesicular eruption was diffuse, occurring after contact with a child presenting with benign varicella. The respiratory signs appeared five to seven days after the cutaneous signs. On admission there was significant hypoxaemia (PaO2 = 35 to 47 mmHg on air), requiring positive pressure expiration (10 to 18 cmH2O) on mechanical ventilation (4 times) or spontaneous ventilation (3 times). The pulmonary radiographs showed diffuse nodular interstitial shadowing. Treatment consisted of Acyclovir (10 mg/kg/8 h). Five patients were cured without any sequellae five to six days after ventilation. One patient died (3 months pregnant), 1 patient presented with a superinfection with staphylococcus aureus. The occurrence of respiratory signs in an adult presenting with varicella requires hospitalisation for treatment with Acyclovir and also the prevention of superinfections.