Abstract: Primary infection with varicella-zoster virus (VZV) causes the characteristic syndrome of varicella, or chickenpox. Experiments in severe combined immunodeficiency mice with human skin grafts (SCIDhu mice) indicate that VZV infection of T cells can mediate transfer of infectious virus to skin. VZV-infected T cells reached epithelial sites of replication within 24 h after entering the circulation. Memory CD4+ T cells were the predominant population recovered from skin in SCIDhu mice given uninfected or infected mononuclear cells, suggesting that immune surveillance by memory T cells may facilitate VZV transfer. The increased susceptibility of memory T cells to VZV infection may further enhance their role in VZV pathogenesis. During VZV skin infection, viral gene products down-regulated interferon-α to permit focal replication, whereas adjacent epidermal cells mounted a potent interferon-α response against cell–cell spread. Interleukin-1α, although activated in VZV-infected cells, did not trigger expression of endothelial adhesion molecules, thereby avoiding early recruitment of inflammatory cells. The prolonged varicella incubation period appears to represent the time required for VZV to overcome antiviral responses of epidermal cells and generate vesicles at the skin surface. Modulation of VZV replication by cutaneous innate immunity may avoid an incapacitating infection of the host that would limit opportunities for VZV transmission.

Abstract: Background. Since licensure in the United States, studies have shown that varicella vaccine’s overall effectiveness ranges from 44% to 100%, with substantial protection against moderate and severe varicella; however, breakthrough illness has been documented in up to 56% of vaccinated individuals. Methods. A varicella outbreak occurred in a Minnesota school with 319 students. Phone surveys were conducted with students’ parents. Information was collected on students who had recent varicella infections, including onset date, rash characteristics, duration, and underlying medical conditions. Results. Fifty-four cases occurred after a primary breakthrough case. Twenty-nine (53%) students had been vaccinated. Unvaccinated students had an increased risk of moderate varicella, compared with vaccinated students (relative risk [RR], 4.4 [95% confidence interval {CI}, 2.2–9.1]; ). The vaccine was 56% effective at P ! .001 preventing any varicella and 90% effective against moderate illness. Students vaccinated 5 years before the outbreak had a greater risk of breakthrough varicella than did those vaccinated within 4 years (RR, 2.6 [95% CI, 1.3–5.4]; ). P ! .01 Conclusions. Vaccinated students presented with milder varicella symptoms than did unvaccinated students. Individuals with breakthrough illness can be highly infectious. Time since varicella vaccination was associated with illness. Despite 29 breakthrough cases, the varicella vaccine conferred a high degree of protection against moderate illness.

Abstract: Background A possible viral cause for multiple sclerosis (MS) has long been suspected. A progressive increase in MS has been reported in Mexico during the past 20 years; a conspicuous antecedent of varicella infection during childhood has been the most relevant finding in the medical history of patients with MS. Objective To investigate the possible participation of varicella-zoster virus (VZV) in the etiopathogenesis of MS. Design, Setting, and Patients We searched, by polymerase chain reaction (PCR), for VZV DNA in peripheral mononuclear cells of 82 patients with relapsing-remitting MS. Additionally, genes gD from herpes simplex viruses 1 and 2 were sought by PCR, as well as IgG and IgM serum antibodies to VZV. Results Viral DNA from the genes open reading frame (ORF)31, ORF62 , ORF63 , and ORF67 of VZV was found in mononuclear cells from 13 (87%) of 15 patients with MS who were tested during acute relapse. All patients who were tested during remission (n = 67) were negative for the DNA, including patients who were initially positive and were tested again after 2 months of remission. All control patients with a comprehensive variety of neurologic diseases (n = 100) and healthy controls (n = 20) also tested negative. All subjects were negative for herpes simplex viruses 1 and 2 DNA, and no differences were found in serum antibodies to VZV. Conclusions The finding of genes of VZV in peripheral mononuclear cells, restricted to a brief period during clinical relapse of MS, suggests either its participation in the etiopathogenesis of MS or an epiphenomenon of viral activation simultaneous with the relapse of MS.

Abstract: Varicella zoster virus (VZV), a ubiquitous neurotropic human herpesvirus, causes chickenpox (varicella) and then remains latent for decades in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis. Virus reactivation, most often after age 60, produces shingles (zoster), characterized by pain and rash usually restricted to 1-3 dermatomes. In elderly individuals, zoster is frequently complicated by postherpetic neuralgia (PHN), pain that persists for months to years after the resolution of rash. Virus may also spread beyond ganglia to the spinal cord to cause myelitis, as well as to blood vessels of the brain, producing a unifocal or multifocal vasculopathy. The increased incidence of zoster in the elderly and immunocompromised individuals appears to be due to a VZV-specific host immunodeficiency. Recent studies indicate that PHN may be due to a chronic active VZV ganglionitis, and that VZV vasculopathy is caused by a productive virus infection in cerebral arteries. Since neurological disease produced by VZV is due to reactivation from ganglia, the physical state of viral nucleic acid and expression during latency as well as the possible mechanisms by which VZV latency is maintained and reactivates are discussed. Finally, VZV is an exclusively human herpesvirus, and experimental infection of animals with VZV does not produce disease nor does VZV reactivate from ganglia. Two varicella models in primates have proven useful: one that mimics varicella latency in humans, and one that can be used to study the efficacy of antiviral agent in driving varicella virus back to a latent state.

Abstract: Vaccination against chickenpox causes a varicella-like rash in up to 5% of healthy children and 50% of children with leukemia. The vaccine may establish latency and reactivate to cause herpes zoster, albeit more rarely than wild-type virus. All vaccine preparations are composed of a mixture of varicella-zoster virus strains that show genotypic variation at several loci. We have shown, by DNA sequencing of 40 polymorphic loci, that viruses sampled from vesicles in varicella-like and herpes zoster rashes are single clones. This finding suggests that, between the time of inoculation of the vaccine and development of rash, selection of single strains occurs. The results have general implications for the pathogenesis of varicella-zoster virus.

Abstract: : Objective: Live-attenuated varicella vaccine is effective and safe in immunocompetent children. In this study, we assess the immunogenicity and adverse events following varicella vaccination in immunosuppressed cancer children. Methods: Varicella-zoster virus (VZV)-seronegative cancer children received two doses of live-attenuated VZV vaccine (Varilrix®) in a span of 3 months. Patients with acute lymphoblastic leukaemia (ALL) were in the maintenance phase of chemotherapy, whereas those with solid tumours joined the study around 3–6 months from treatment discontinuation. VZV-specific cellular and humoral immune responses were measured before and after VZV vaccination. Results: The median (range) age of the 17 patients was 4.4 yr (2.0–14.5). Thirteen had ALL, one had myelodysplastic syndrome and three had solid tumours. Following vaccination, the VZV-specific stimulation index (SI) increased from 1.7 (0.9–2.9) to 17.9 (5.9–36.0) (P < 0.001). Similarly, SI to phytohaemagglutinin mitogen increased from 1136 (499–1930) to 1714 (848–2518) (P = 0.028). There were also significant increases in CD4+ cells and CD4 : CD8 ratio as well as a reduction in CD16/56+ cells in peripheral blood lymphocytes. Seroconversion rate to VZV was 19% after one dose and increased to 94% after the second dose of VZV vaccine. Serum VZV-specific IgG concentrations also increased significantly following two doses when compared with one dose of VZV vaccine (P = 0.0004). One subject developed possibly vaccine-related chickenpox with self-limiting hepatitis at 5 wk following vaccination. None of the patients developed herpes-zoster at a median (range) follow-up of 27.5 months (24.0–30.0). Conclusions: Non-immune cancer children can be effectively vaccinated against chickenpox at the defined period. However, the safety of chickenpox vaccine in these immunosuppressed children needs to be further studied.

Abstract: Varicella virus vaccine strain Oka (V-Oka) has in rare cases caused zoster in vaccinated people. Despite broad usage of V-Oka, little is known about varicella-zoster virus genomic sequence variation of strains in vaccine and isolates from patients with vaccine adverse events. Direct sequencing of 20 regions of V-Oka-GSK was compared to the sequences of the original V-Oka-Biken, GlaxoSmithKline Oka vaccine (V-Oka-GSK), and Oka-parental (P-Oka) strains. We analyzed single nucleotide polymorphisms (SNP) differentiating the Oka parental and Oka vaccine strains identified in open reading frames (ORFs) 6, 9A, 10, 21, 31, 39, 50, 51, 52, 54, 55, and 59 and eight base substitutions within ORF 62. Sixteen of these SNP impose an amino acid change in the corresponding gene product. The genotypic analysis revealed that (i) both V-Oka-GSK and V-Oka-Biken comprise mixtures of strains represented in variable proportion from lot to lot; (ii) V-Oka-GSK/zoster isolated from the zoster patient had six wild-type SNP in ORF 9A, 10, 21, 52, 55, and 62 (mutation 108838); (iii) none of the six revertant SNP would reliably discriminate Oka vaccine from the wild type; and (iv) the genomic variation found in V-Oka/zoster might be associated with changes in the biological behavior of the virus. Further studies will be needed to identify potential virulence factors in variant vaccine strains.

Abstract: Chickenpox infections are generally mild but due to their very high incidence among healthy children they give rise to considerable morbidity and occasional mortality. With the development of a varicella vaccine in the early 1970s and its progressive licensing in many countries, interest in the efficiency of varicella immunisation programmes grew. The objective of this review was to discuss the methodological aspects and results of published economic evaluations of varicella vaccination. From this, we attempted to make recommendations. A computerised search was carried out; 17 full economic evaluations of varicella vaccination were retrieved. The review identified the methodological divergences and similarities between the articles in four areas: study design, epidemiological data, economic data and model characteristics. We assessed to what extent the applied methods conform to general guidelines for the economic evaluation of healthcare interventions and compared the studies' results. The desirability of a universal vaccination programme depends on whose perspective is taken. Despite variability in data and model assumptions, the studies suggest that universal vaccination of infants is attractive to society because large savings occur from averted unproductive days for parents. For the healthcare payer, universal vaccination of infants does not generate savings. Vaccination of susceptible adolescents has been proposed by some authors as a viable alternative; the attractiveness of this is highly dependent on the negative predictive value of anamnestic screening. Targeted vaccination of healthcare workers and immunocompromised individuals appears relatively cost effective. Findings for other target groups are either contradictory or provide insufficient evidence for any unequivocal recommendations to be made. High sensitivity to vaccine price was reported in most studies. This review highlights that some aspects of these studies need to be further improved before final recommendations can be made. First, more transparency, completeness and compliance to general methodological guidelines are required. Second, because of the increasing severity of varicella with age, it is preferable and in some cases essential to use dynamic models for the assessment of universal vaccination strategies. Third, most studies focused on the strategy of vaccinating children only while their results depended heavily on disputable assumptions (regarding vaccine effectiveness and impact on herpes zoster). Since violation of these assumptions could have important adverse public health effects, we suggest pre-adolescent vaccination as a more secure alternative. This option deserves more attention in future analyses.

Abstract: Guidance from the Joint Committee on Vaccination and Immunisation regarding varicella vaccination of workers in healthcare settings is imminent.1 The new recommendations will advise that all those with a negative or uncertain history of chickenpox or shingles at pre-employment assessment should be tested for varicella zoster virus IgG. Vaccination with the newly licensed varicella vaccine will be advised for those with a seronegative result. A history of chickenpox has a high positive predictive value for immunity among healthcare workers in Europe, where the seroprevalence is as high as 98.5%.2 The validity of a history of chickenpox is unknown in those from tropical countries, however, where the mean age of infection is in early adulthood.3 Guy's and St Thomas' Hospital NHS Trust in inner London has some 8000 staff and 4700 healthcare students of increasingly heterogeneous origins.4 5 We conducted a questionnaire and seroprevalence study at the hospital to ascertain the relations between history of chickenpox, countries …

Abstract: Purpose of reviewVaricella zoster virus is the cause of both varicella (chickenpox) and herpes zoster (shingles). A live attenuated varicella vaccine was developed in 1974 and was approved in 1995 by the United States Food and Drug Administration for administration to both healthy children (>12 mont

Abstract: OBJECTIVE: To determine the relationship between immunity and a history of chickenpox based on a self-administered questionnaire. METHODS: We investigated immunity to varicella-zoster virus in a cohort of newly recruited employees with different job categories and different nationalities using enzyme-linked immunosorbent assay IgG. RESULTS: There were 1,058 new recruits. Of these, 890 (84%) were immune and 168 (16%) were susceptible. The susceptibility rate was 23% (n = 77) for Asian, 15% (n = 14) for South African, 13% (n = 66) for Middle Eastern, and 9% (n = 11) for Western employees. Physicians were more likely to be immune (93%) than were nurses (85%), medical technicians (75%), or administrative clerks (84%). Seropositivity was not affected by age or gender. The positive predictive value of a history of chickenpox for the seropositivity was 89% (511 of 574); the negative predictive value was 22% (105 of 484). History of chickenpox had a sensitivity of 57% (511 of 890) and a specificity of 63% (105 of 168). CONCLUSIONS: The varicella-zoster virus seroprevalence among new employees was low, posing an important risk to existing employees and patients. Positive or negative history of chickenpox was an unreliable indicator of susceptibility among healthcare workers of different nationalities. Serologic screening of all employees and vaccination of those susceptible was recommended.

Abstract: Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very low protein S levels as well as anticardiolipin antibodies. Aggressive treatment by low-molecular-weight heparin, steroids, intravenous immunoglobulins and fresh frozen plasma was able to prevent the extension of the lesions and to correct the coagulation abnormalities. No lesions required skin grafting. As in our patient, an acquired protein S deficiency is probably responsible for most cases of purpura fulminans occurring after varicella, but the concomitant presence of antiphospholipid antibodies may also play a role.

Abstract: The disease burden of chickenpox to children has been described, and a lower force of neutralising antibody to varicella-zoster virus (VZV) than against measles, either after natural infection or after vaccination, has been reported. In the case of VZV, strong cell-mediated immunity may work efficiently to prevent the spread of the virus. The lower force of humoral antibody to VZV might be related to the occurrence of "breakthrough" varicella cases in a small portion of the vaccine recipients. Safety and high effectiveness of the varicella vaccine--approximately 85% effective for all diseases and 95-100% effective for moderate-to-severe diseases--have been reported. Vaccine-induced immunity persists for 10-20 years. However, concerns have been raised that universal immunisation in children may shift the susceptibility from children to adults, whose symptoms are usually moderate-to-severe. In addition, other concerns have been expressed that, due to lack of exposure to varicella in children, the elderly may develop zoster infections more frequently than before. A clear answer is difficult to give at present, although, for several reasons, such situations may be unlikely to occur.

Abstract: Varicella (chickenpox) has traditionally been regarded as a benign, inevitable disease of childhood. In Germany information on the clinical and economic impact of varicella is limited. This study assessed the health risks and economic burden of varicella with a special focus on the relevance of complications as a cost driver. We used an age-structured, dynamic infectious disease model for the spread of infection in the German population combined with a module modeling the course of disease and medical management in the case of infection. Model input data were derived mainly from a retrospective epidemiological survey of 1,334 varicella cases in Germany. This survey included detailed information on outpatient care, complications, inpatient treatment, and sick leave. In the base case analysis the model predicted approx. 740,000 varicella cases per year. Some 40,000 experienced complications, of which 5,700 required inpatient care. Total annual costs for payers, i.e., sickness funds, was 78 million euro, the largest portion of which was due to the significant coverage of work loss costs incurred by parents caring for their sick children ("Kinderpflegekrankengeld"). For the society total annual costs were 187.5 million euro, 82% of which was indirect. Complications account for disproportionate 32% (25%) of cost from the payers' (societal) perspective. However, the vast majority of costs are due to uncomplicated cases. The burden of varicella in Germany is thus significant, not only in terms of morbidity but also from an economic viewpoint. Vaccination strategies targeting groups with high risk of complications might fail to reduce the considerable burden of varicella substantially. Routine vaccination against varicella would be a meaningful measure to reduce the burden of VZV infection in Germany.

Abstract: There is limited data on immunity against varicella-zoster virus (VZV) in adults in different parts of Argentina, and it is not known which VZV strains are circulating in Argentina. The objectives of this study were as follows: (i) to evaluate seroprevalence of varicella among adults, assessing the accuracy of clinical history and determining the sociodemographic factors associated with seropositivity; and (ii) to determine the VZV strains circulating in Argentina. A cross-sectional serological survey enrolling 2,807 women aged 15 to 49 years attending public health-care settings in four cities in Argentina (i.e., Buenos Aires, Salta, Mendoza, and Rosario) and one rural area was conducted from August to November 2002. Specimens for identification of VZV strains were obtained from vesicular lesions from 13 pediatric patients with varicella from different areas of the country. PCR amplification was used for genotyping. The overall seroprevalence of varicella antibodies was 98.5% (95% confidence interval, 98.0 to 98.9), ranging from 97.2% in central Buenos Aires to 99.3% in southern Buenos Aires and Salta. Varicella seroprevalence increased with age. Crowding and length of residence in the same place were associated with seropositivity. The positive predictive value of varicella history for immunity to varicella was 99.4%; however, the negative predictive value was 2.5%. The European genotype was identified in all viral specimens. In Argentina, seroprevalence in women more than 15 years old was high regardless of the area of residence. Negative or uncertain varicella history was not a good predictor of immunity. VZV genotype was stable in all areas of the country.

Abstract: Varicella-zoster virus (VZV), the causative agent of chickenpox and herpes zoster, can be life-threatening in prematurely born children and in children with immune defects or who are under immunosuppressive treatment. Therefore agents for passive immunization, such as VZV-specific immunoglobulin preparations (VZIG) derived from convalescent plasma, are crucial in the prophylaxis of VZV infection. This study describes the isolation of human VZV-neutralizing recombinant antibodies. A human single-chain variable fragment (scFv) phage display library was generated from RNA extracted from peripheral blood lymphocytes of a convalescent varicella patient. Specific phage antibodies were selected against VZV-infected human fibroblasts, and eight unique clones were further expressed as soluble scFv in Escherichia coli. They all showed binding characteristics to varicella antigens with affinities in the K(D) range 0.1-0.2 muM. Two of the scFv antibodies, VZV4 and VZV5, showed dose-dependent in vitro neutralization of VZV. VZV39 also showed a neutralizing effect as scFv, an effect that was increased 4000-fold by conversion into IgG and was further increased by the addition of complement. This is possibly the first time that monovalent scFv antibodies have been shown to neutralize VZV in vitro. This finding will have an impact on the production of new prophylactic antibodies, as such antibody fragments can be cost-effectively produced in E. coli. The antibodies isolated bind both complement-dependent and -independent epitopes for neutralization, thus they may prove useful tools for the study of VZV virulence mechanisms.

Abstract: Objective Our study examines risk factors for severe varicella in an outbreak among Mexican-born adults, and it compares susceptibility to infection and reliability of self-reported varicella history for these individuals with that for adults born in the United States in the outbreak locale, which may guide vaccination strategies. Methods We interviewed case patients and non-case persons in the affected apartment complex and workplace, assessed disease history and susceptibility by testing for varicella-zoster virus immunoglobulin G antibodies, and reviewed the clinical data of case patients. Results Five of 18 case patients had serious complications for which they sought medical care; 1 was hospitalized for pneumonia, and 1 was hospitalized for Guillain-Barre syndrome. Only intense exposure (e.g., sharing a bed) was marginally associated with severe disease (P=.08). In the workplace, varicella susceptibility was higher among Mexican-born workers (20%) than among workers born in the United States (3%) (adjusted prevalence odds ratio, 5.4; 95% confidence interval, 2.3-14.8). Mexican-born persons had the highest positive predictive value of self-reported disease (100%) in predicting immunity, and those born in the United States had the lowest negative predictive value of self-reported history (10%) in predicting susceptibility. Conclusions Varicella is a more serious disease among adults than among children, and Mexican-born adults living in the United States might have a higher risk of acquiring varicella than US-born adults. Varicella outbreaks involving adults should be prioritized for control efforts. Outbreaks can be prevented by vaccinating susceptible adults.

Abstract: INTRODUCTION Chickenpox (varicella) in adults can be severe with increased mortality. This study investigated the clinical presentation and outcome of 12 adult chickenpox patients requiring intensive care. MATERIALS AND METHODS A retrospective, observational study was performed in an adult medical intensive care unit of a university-affiliated hospital involving consecutive patients with varicella admitted over 4 years (1997-2000). RESULTS The 12 patients had a mean +/- SD age of 40 +/- 20 (range, 15 to 86) years. Two patients were above 65 years old (aged 73 and 86 years). All but 1 were male. None had previous varicella vaccination. Six patients had direct exposure to persons with chickenpox infection. Four patients had underlying pulmonary pathology: past pulmonary tuberculosis (2), emphysema (1) and recurrent right pleural effusion from autoimmune serositis (1). The mean APACHE II score was 14.2 (range, 6 to 26). Ten patients had varicella pneumonia (of whom 2 had acute respiratory distress syndrome and 5 had acute lung injury), 1 had chickenpox encephalitis and 1 patient presented concomitantly with diabetic ketoacidosis. The median duration of stay in the intensive care unit (ICU) was 11 days (range, less than 1 day to 76 days). Nine patients (75%) required mechanical ventilation (median duration, 14 days; range, less than 1 day to 79 days). All patients were treated with acyclovir. There were 3 deaths (25%); 2 were above 65 years old and 1 was 37 years old with acute myeloid leukaemia on chemotherapy. CONCLUSION Patients with varicella infection requiring intensive care carry significant mortality. In our series, old age appears to be associated with increased mortality (P = 0.045).

Abstract: We are reporting a previously well 5-year-old child with varicella-zoster meningitis who had a history of a previous immunization against varicella. This child also developed a transient sensorineural hearing loss. The child was treated with acyclovir and made a full recovery.

Abstract: In the eastern part of Germany, the age of primigravid women has clearly increased since 1990. This may change the protection provided by antibodies in pregnant women as well as their newborns. The objective of the present study was to assess antibodies against vaccine-preventable viral infectious diseases in pregnant women and their offspring to draw conclusions about their protection. Maternal and cord blood samples of 290 women from the eastern part of Germany with a mean age of 28 years were analyzed for antibodies against measles, mumps, rubella, poliomyelitis, and varicella. The study showed that the pregnant women had detectable levels of antibodies against measles virus in 79%, against mumps virus in 96%, against rubella virus in 87%, against polioviruses types 1-3 in 62-64%, and against varicella-zoster virus (VZV) in 97% of the cases. The seroprevalence of the antibodies in the newborns were not significantly different from those of their mothers. When antibody titers of mothers and newborns were compared, significantly higher titers to VZV could be detected in the cord blood sera of newborns. It is suggested that the prevalence of antibodies against measles and poliomyelitis is insufficient to protect the newborns efficiently. An immunity gap of 13% against rubella in mothers results in a potential risk for a congenital rubella syndrome in newborns. Despite the high seroprevalence of rubella and chickenpox, there is considerable potential for infections during pregnancy and neonatal period.

Abstract: Background: Although surveillance for varicella in the United States has documented a reduction in cases since vaccine licensure in 1995, information is lacking on varicella-related mortality since vaccine introduction. This study identifies varicella-related mortality in California before and after vaccine introduction and assesses how high risk conditions and complications contributed to varicella deaths during this period. Methods: California death records mentioning varicella as either an underlying or contributing cause of death were selected from the 1988-2000 multiple cause-of-death files. Pre- and postvaccine periods were compared to assess differences in varicella mortality before and after vaccine introduction. Differences in varicella mortality by age, race/ethnicity and gender were also examined. ICD codes were used to identify high risk conditions and varicella-related complications. Results: A total of 228 varicella-related deaths were reported between 1988 and 2000 in California. Age-adjusted varicella mortality rates showed a downward trend during this period, dropping from a high of 0.97 per million in 1990 to a low of 0.22 per million in 1999. The average age-adjusted mortality rate declined from 0.67 per million prevaccine to 0.38 per million postvaccine. Compared with the prevaccine period, the average rate of decline in varicella mortality was greater after vaccine implementation. Infants had the highest mortality rate for the period. At least one immunocompromising condition was present in 38% of varicella-related deaths. Pneumonia was the most commonly reported complication. Conclusions: Varicella-related mortality declined in California after vaccine implementation, but potentially preventable varicella-related deaths continue to occur.

Abstract: In July 2004 varicella (chickenpox) vaccination was added to the national routine vaccination schedule for all children in Germany

Abstract: We present the case of a 38-yr-old woman who required an epidural blood patch in the context of acute varicella (chickenpox). The unique risks in this case include the possible triggering of central nervous system complications after the introduction of viremic blood into the epidural or intrathecal space. However, the risk was believed to be acceptable because the patient was receiving antiviral coverage. She enjoyed complete relief of her headache but experienced transient back and leg pain. Leptomen-ingeal irritation caused by acute varicella infection may put patients at increased risk for pain after epidural blood patch.

Abstract: Background The ability to differentiate chickenpox from smallpox is important for early recognition of bioterrorism events and prevention of false alarms. The febrile prodrome is a clinical feature used to differentiate these conditions. However, the prevalence of prodromal manifestations in chickenpox has not been well established. Methods We evaluated prodrome characteristics of all chickenpox cases identified through an active varicella surveillance program over a 21-month period. The frequencies of various prodromal manifestations among vaccinated and unvaccinated case patients were assessed, and the impact of other demographic features on these manifestations was evaluated. Data were analyzed to determine what proportion met the smallpox febrile prodrome criteria as elaborated in the Centers for Disease Control and Prevention algorithm for evaluating patients suspected of having smallpox. Finally, we compared our data with historical data on smallpox prodromes. Results Data on prodrome characteristics were available for 932 chickenpox cases. Prodromal fever was present in 37% of unvaccinated chickenpox case patients and in 25% of vaccinated case patients. Among unvaccinated case patients, adults were 70% more likely than children to have fever in the prodrome period. We found that prodromes are less common and less severe in chickenpox than in smallpox. Nevertheless, 7%-17% of unvaccinated chickenpox case patients meet the smallpox febrile prodrome criteria. Conclusions Febrile prodromes occur in a significant proportion of patients with chickenpox, particularly among unvaccinated case patients and adults. Therefore, the febrile prodrome alone is not a sufficient marker of smallpox risk. All major and minor smallpox criteria should be considered together in assessing the likelihood of smallpox.