Varicella zoster virus immunity in multinational health care workers of a Saudi Arabian hospital

INTRODUCTION: The health care worker (HCW) is vulnerable to hospital-acquired varicella zoster virus (VZV) infection, and thereafter may transmit infection to coworkers and patients who are susceptible and hospitalized. Interventions to prevent varicella transmission in HCW groups of uncertain immunity prove labor intensive, costly, and disruptive. Therefore, documentation of total varicella immunity in HCWs is desirable. SETTING: The National Guard King Abdulaziz Medical City is a 600-bed tertiary care center in Riyadh, Saudi Arabia with a multinational staff. MATERIAL AND METHOD: A program to assess the VZV status of HCWs was initiated in 1999. The survey was confined to HCWs having direct patient contact. Questions elucidated previous history of varicella (chicken pox) infection, antibody testing against varicella, and varicella vaccination. HCWs with a negative or unknown history were subsequently tested for varicella antibodies (IgG). RESULTS: Seventy-six percent (2,047) of the HCWs responded to the questionnaire. Of these, 562 (28%) were physicians, 761 (37%) were nurses, 438 (21%) were medical technicians, and 286 (14%) were involved in clerical work. A total of 802 (39%) were from the Middle East including Saudi Arabia, 633 (31%) were from the Far East, 361 (18%) were from the West and from temperate areas, 138 (7%) were from South Africa, and 113 (5%) were from other nationalities. A previous history of VZV infection was reported by 1303 (64%); 262 (13%) had a history of positive test for varicella antibody, and only 44 (2%) had a history of varicella vaccination. Of the 744 (36%) HCWs who had a negative or unknown history of VZV infection, 217 (29%) underwent antibody testing. Of these, 181 (83%) proved to be immune (IgG > or = 1.10), and 36 (17%) nonimmune (IgG < 1.2). The latter group have completed varicella immunization. Staff from the West (81%), Far East (78%), and South Africa (59%) reported more histories of VZV infection compared with the employees of Middle Eastern origin (46%) (P <.001) and disclosed a history of positive antibodies in 13%, 18%, 17%, and 8%, respectively (P <.001). In relation to occupation, nurses reported history of varicella infection (75%) and a history of positive varicella antibodies (16%) more than physicians (54% and 8%, respectively) (P <.05). Conversely, serologic immunity to VZV infection proved consistent among the different nationalities and among the 4 occupational groups. CONCLUSION: Total varicella immunity of a multinational workforce can be realized through screening of HCWs and vaccination of susceptible individuals. It is preferred above repeated interventions after varicella exposure for its simplicity, cost-effectiveness, and efficiency. Knowledge of VZV infection varies between different nationalities and cannot be used as a true predictor of immunity. There is no difference in the immunity by antibody testing of staff recruited from temperate and tropical climates. Total varicella immunity should, therefore, be achieved through screening of all HCWs and vaccination of those susceptible.     

Measles, rubella, mumps, and varicella seroprevalence among health care workers in Turkey: is prevaccination screening cost-effective?

BACKGROUND: To investigate the immune status of health care workers (HCWs) against measles, rubella, mumps, and varicella zoster (MMRV) in Turkey and to define an appropriate vaccination program among HCWs. METHODS: Voluntary HCWs from a children's hospital and a general hospital were included in the study between March and May 2005. The specific IgG antibodies against MMRV viruses were screened by ELISA. RESULTS: Three hundred sixty-three HCWs participated in the study; 186 (51%) were physicians, 118 (33%) were nurses, 36 (10%) were housekeeping staff, and 23 (6%) were medical technicians. The proportion of HCWs who had antibodies against measles was 98.6%; rubella, 98.3%; mumps, 92.2%; and varicella, 98%. No association was found between the susceptibility to at least 1 of MMRV virus infections and gender, age, duration of work, profession, and department of work in analysis either among the whole study group, or each hospital. The positive predictive value for the history of varicella was 100%, whereas it was 92% for MMR. The cost of vaccination for varicella was significantly expensive without screening before vaccination. However, there was not much difference for MMR infections. CONCLUSION: A policy based on obtaining the history of varicella infection from the staff and then screening the ones with negative history and vaccination of only seronegative HCWs was found to be appropriate.     

How reliable is the history of chickenpox? Varicella serology among children up to 14 years of age.

OBJECTIVES: The aim of this study was to assess the seroprevalence of antibodies to varicella-zoster virus (VZV) in children of northern Greece and to estimate the reliability of varicella history. METHODS: A serosurvey of 632 children, aged 13 months to 14 years (median 5.2 years), was conducted between April 1999 and July 2001. Serum samples were tested by enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to VZV (IgG Genzyme Virotech GmbH). A history of varicella in these children was obtained from the parents of all these patients. Also, a check of state health cards of the patients was done. RESULTS: Two hundred and forty-eight (39%) of the children were seropositive for VZV. Two hundred and thirty (36%) of the 632 children claimed to have had previous varicella infection; 87.8% were seropositive, and 12.2% lacked antibodies to VZV. One hundred and seven of the 230 children with a history of varicella had the information about the disease confirmed, as it was reported on their state health card by a pediatrician; 10.2% were seronegative for VZV. Absence of history of varicella was reported in 402 (63.6%) of the 632 children; 88.6% of those were seronegative, and 11.4% were seropositive. The percentage of incorrect negative history ranged from 6% (13-60 months of age) to 48% (120-168 months of age). CONCLUSIONS: A large proportion of the study group (61%), mainly below 7 years of age, is susceptible to varicella. The positive predictive value of a history of varicella is 87.8%, whereas the negative predictive value of a negative history is 11.4%, which means that there is an 88.6% probability of a negative history being correct. Varicella serology may be reasonable prior to vaccination in children >10 years old with a negative chickenpox history. However, if one excludes cost considerations, it is also reasonable to vaccinate all children, irrespective of serostatus.     

Detection of varicella-zoster virus DNA in the oropharynx and blood of patients with varicella.

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.     

A seroepidemiology study of varicella among children aged 0-12 years in Taiwan

The epidemiology pattern of varicella appears to vary among regions with different climates, population densities, and degrees of development. This study investigated the age-specific varicella zoster virus (VZV) seroprevalence in children aged 0 to 12 years in Taiwan and compared these seroprevalences between free and private vaccination areas. Residual sera were collected from 13 hospitals with 1,401 valid samples. Immunoglobulin G antibodies to VZV were measured by enzyme-linked immunosorbent assay. Parents of 656 children answered questions about the varicella incidence and varicella vaccination history of their children. In the 8-12 year-olds, the seroprevance ranged between 88.0-93.8% in northern, central, and eastern, while it was only 76.1% in southern Taiwan. The seroprevalence of children 0-5 years old were significantly different between free and private vaccination areas. Seropositive children who reported no history of varicella or receiving varicella vaccine accounted for 26.1-59.3% of the total positive cases. Our findings suggest the possible effects of climate, geographical conditions, and lifestyle on the seroepidemiology of VZV in Taiwan. The efforts of implementing a varicella vaccination program in Taiwan should focus on reaching high levels of coverage.     

Immunogenicity and reactogenicity of a single dose of live attenuated varicella vaccine and a booster dose of measles-mumps-rubella vaccine given concomitantly at 12 years of age

Universal varicella-zoster virus (VZV) childhood vaccination is still debated, but adult chickenpox may be severe. It could be prevented by vaccination of seronegative adolescents. This study aimed to determine the feasibility of coadministration of a VZV vaccine and the measles-mumps-rubella (MMR) booster at 12 y of age. Guardians of 1231 12-y-old pupils where asked about the history of chickenpox in their children. 190 had no chickenpox history and 12 of 62 of them lacked VZV antibodies. Additional history-negative children were also recruited. 199 history-positive children received only MMR and 98 history-negative children received an MMR vaccine and a VZV vaccine. Serum samples were drawn before vaccination and after 8 weeks. Viral antibodies were measured by immunofluorescence (VZV) and enzyme-linked immunosorbent assays (VZV, MMR). All 184 history-positive children tested had VZV antibodies. 17/89 VZV-vaccinated and tested children (19%) lacked VZV antibodies before vaccination. 12 (71%) seroconverted after 1 dose. Cell-mediated immunity (CMI) against varicella was tested in 3/5 children who did not seroconvert after 1 dose of VZV vaccine. They seroconverted after a second dose and had measurable CMI. VZV vaccination did not affect the MMR response and there were no severe side-effects. A history of varicella infection, as reported by the guardian, is reliable, but a negative history was incorrect in 81% of the cases. This population of 12-y-old children may require 2 doses of VZV vaccine, at least when given simultaneously with the MMR vaccine.     

Seroepidemiology of varicella-zoster in Pakistan.

The availability of safe and effective vaccines has renewed interest in the epidemiology of varicella worldwide. To date published data on the epidemiology of varicella in Pakistan is very scarce. Therefore, we conducted a study to determine the age-specific seroprevalence rate of varicella-zoster virus (VZV) antibodies in Pakistan. Between December 1997 and March 1998, 1,509 healthy volunteers aged between 1 month and 30 years were recruited from the Islamabad, Karachi, Lahore and Rawalpindi areas. Demographic information, socioeconomic status and past medical history were obtained by questionnaire. Serum samples were assayed for IgG antibodies against VZV by enzyme-linked immunosorbent assay. Overall 41.8% (600/1,435) of those tested were found to be seropositive for VZV antibodies. No difference was found in results obtained from the different cities. A higher seroprevalence was observed among women (45.2%) compared to men (39.6%). Seroprevalence rates increased with age and were 28.4% in those aged 0-5 years, 41.5% in the 6-10 year age group, 42.5% in the 11-15 year age group, 46.7% in the 16-20 year age group and 53.6% in those aged 21-30 years. Socioeconomic status was not a significant risk factor for VZV seropositivity. This is the first report of the seroepidemiology of VZV in Pakistan. The results indicate that seroprevalence of VZV increases with age in the Pakistani population studied. As in other tropical countries, there is greater susceptibility to varicella among the adolescent and young adult population. The results of this study suggest that these at-risk groups should be included in vaccination programs aimed at reducing the public health impact of varicella.     

Investigation of varicella-zoster virus infection by polymerase chain reaction in the immunocompetent host with acute varicella.

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.     

Susceptibility of hospital-based health care personnel to varicella-zoster virus infections

Varicella-zoster virus (VZV) transmission poses a major infection risk for health care workers in the hospital environment. Immunologically normal adults who contract varicella have 9 to 25 times the risk of major morbidity or death from infection compared with healthy children. Moreover, varicella infection during pregnancy is associated with a high rate of complications and the risk of the congenital varicella syndrome. To evaluate susceptibility to VZV infection among hospital workers, the employee health service screened 241 personnel for VZV antibody by the indirect fluorescent antibody technique. Overall, 7 (2.9%) of 241 personnel lacked VZV antibody and were therefore presumed susceptible to infection. Susceptibility varied dramatically by age and was significantly higher among persons 35 years of age and younger (7/93 = 7.5%) than among those aged 36 years and older (0/148 = 0%, p = 0.001). Persons 35 years old or younger with a clinical history of chickenpox or herpes zoster were much less likely to lack immunity (3/71 = 4.2%) than those stating they had no history of either (4/11 = 36.4%, p = 0.005). Screening strategies for VZV immunity in hospital employees could be made more efficient by performing serologic tests only on those persons aged 35 years or younger with a negative or uncertain history of the disease. Persons who lack antibody may be considered for preexposure immunization with live attenuated varicella vaccine as an alternative to varicella-zoster immune globulin or enforced absence from patient care after exposure to a VZV-infected patient.     

Virus-specific antibodies to Epstein-Barr virus, varicellazoster virus and rubella virus in renal transplant patients with cytomegalovirus infections

Renal transplant patients with primary and recurrent cytomegalovirus (CMV) infection had higher antibody titres to Epstein-Barr virus viral capsid antigen (EBV-VCA-IgG) before and after transplantation than healthy blood donors. The geometric mean titres (GMT) of EBV-VCA-IgG were higher in renal transplant patients without CMV infection than in renal transplant patients with CMV infection. Four-fold or greater rises in EBV-VCA-IgG antibody were detected in six patients and a similar rise in antibody to EBV early antigen (EBV-EA-IgG) was detected in one other patient. IgM antibody to EBV-VCA (EBV-VCA-IgM) was detected in only three of these patients. EBV-EA-IgG was present in 39% patients and in 30% control subjects. IgG titres to varicella zoster virus (VZV-IgG) and rubella virus (rubella HI) were higher in patients without CMV infection compared to the patients with CMV infection. Raised titres were detected to VZV in five patients and to rubella virus in three patients. Reductions in antibody titre of four-fold or more were also detected in EBV-EA-IgG (one patient) and to rubella virus (one patient). Raised antibody titres to EBV, VZV, and rubella virus in renal transplant patients may indicate reactivation of these viruses without any symptoms.     

Detection of antibodies to varicella-zoster virus proteins in sera from the elderly

Sera from 40 elderly individuals ranging in age from 60 to 94 years were tested for the presence of antibodies to varicella-zoster virus (VZV)-specific proteins. Sodium dodecylsulfate polyacrylamide gel electrophoresis analysis of lysates of VZV-infected BSC-1 cells labeled with either [35S]methionine or [3H]mannose and immunoprecipitated with human sera revealed the variable presence of VZV-specific antibodies to four VZV glycoproteins (gpI, gpII, gpIII, and gpIV), and three nonglycosylated proteins (155, 140, 32 kilodaltons, kDa). The predominant antibody response in the sera from the elderly was to VZV gpII and the 155-kDa species. In addition, some sera from elderly individuals without an identifiable history of varicella or zoster contained antibodies to VZV proteins, suggesting a possible subclinical infection in these patients. Finally a history of zoster in the elderly was significantly correlated (p = 0.02) with the presence of antibody to gpIV.     

Absence of circulating natural killer and primed CD8+ cells in life-threatening varicella

Five pediatric patients with no history of immunodeficiency had a life-threatening course of varicella. Strikingly, natural killer (NK) cells were absent from the circulation in all children, and, despite active viral infection, up to 98% of the CD8(+) cells were naive. Primary immunodeficiencies were excluded--NK cells and primed CD8(+) cells reappeared in the circulation, granzymes were detectable in plasma early during infection, and no abnormalities could be detected in interleukin-15 receptor function. Our data indicate that varicella-zoster virus (VZV) has a unique capability to seclude primed CD8(+) cells and NK cells from the circulating lymphocyte pool. This may be the consequence of an overwhelming immune response to VZV that is influenced by factors such as infectious dose, age, and the presence of maternal antibodies during infancy. Because both homozygous twin sisters in the study had a severe course of varicella, particular genetic factors may contribute to severe varicella.     

Susceptibility to varicella-zoster virus in Thai children and young adults

During 1982-1983, susceptibility to varicella-zoster virus (VZV) in 224 Thai subjects at high risk for varicella infection was studied. The immune adherence hemagglutination (IAHA) and VZ skin test were carried out to determine VZV immunity in immunocompromised children and young adults. The history of varicella and herpes zoster from each subject was recorded. The mean +/- SD age in children and young adults were 7.3 +/- 2.8 and 19.6 +/- 1.2. Negative IAHA test was found in 74.2% of 62 children and 35.2% of 162 young adults. The increase in immune individuals was demonstrated with advancing age. Response to VZ skin test showed positive results in 79 of 162 (48.8%) young adults. The seronegativity was related to the negative VZ skin test (p less than 0.001, X2 test). Regardless of antibody detection or VZ skin test, 47 of 162 (29%) young adults were susceptible. According to the positive history of varicella and of herpes zoster obtained from 95 young adults, 80% had developed varicella during 1 to 10 years of age and 8.8% had positive history of herpes zoster. The findings suggest that the IAHA and VZ skin test should be used together for assessing VZ immunity. Varicella vaccination is highly recommended for susceptible persons who may develop severe illness.     

The safety profile of varicella vaccine: a 10-year review

Varivax (varicella virus vaccine live [Oka/Merck]; Merck), a live attenuated varicella vaccine, is indicated for vaccination against varicella in appropriate individuals > or =12 months of age. The 10-year safety profile for Varivax is described using data submitted to Merck from routine global postmarketing surveillance, combined with information from a Varicella Zoster Virus Identification Program, which uses polymerase chain reaction (PCR) analysis to identify the presence and strain of VZV in selected specimens. There were 16,683 reports worldwide voluntarily submitted to Merck, for an overall reporting rate of 3.4 reports/10,000 doses of vaccine distributed. PCR analysis of vesicular rashes that occurred within the first 2 weeks after vaccination was more likely to identify wild-type varicella-zoster virus (VZV), whereas the presence of Oka VZV was generally associated with vesicular rashes that occurred 15-42 days after vaccination. Reports of breakthrough varicella that occurred >42 days after vaccination were associated with wild-type VZV. Among 697 herpes zoster reports, PCR analysis identified Oka VZV in 57 reports and wild-type VZV in 38 reports. There were no primary neurologic adverse events associated with Oka VZV. Secondary transmission of Oka VZV from vaccine recipients with postvaccination vesicular rashes was identified in 3 susceptible household contacts. Disseminated Oka VZV was identified in 6 immunocompromised patients and 1 patient with Down syndrome. This review has shown that the vaccine is generally safe and well tolerated.     

Distribution of varicella-zoster virus DNA and gene products in tissues of a first-trimester varicella-infected fetus

Precise information about varicella-zoster virus (VZV) infection in first-trimester fetuses remains sketchy. After varicella infection was diagnosed in a woman, her 12-week-old fetus was aborted and was investigated, by histological examination, virus culturing, polymerase chain reaction, in situ hybridization (ISH), and immunohistochemistry (IHC), for the presence of VZV infection. Only the results of the histological examination suggested the presence of alpha -herpesvirus infection, in the gastrointestinal tract and liver; results of ISH were positive for VZV, and results of IHC staining were positive for intermediate early protein 63 (IE63) but negative for glycoprotein E (gE), in the dorsal root ganglia (DRG), meninges, gastrointestinal tract, pancreas, smooth muscle, liver, and placental trophoblast, indicating the presence of a nonproductive, latency-like VZV infection. Only the gastrointestinal tract and liver exhibited simultaneous staining for IE63 and gE, a result suggesting that active replication of VZV was present. In conclusion, widespread nonproductive VZV infection in the absence of histological clues is an early event in VZV infection in fetuses. The observed gene-expression pattern in most tissues resembles that of latent VZV infection in DRG. Latency-like infection in nonneural cell types may potentially reactivate, leading to multifocal necrosis, fibrosis, and dystrophic calcifications, as observed in advanced congenital varicella syndrome.     

Seroprevalence of varicella zoster virus in Colombo district,Sri Lanka

Objective: To determine the seroprevalence of varicella zoster virus(VZV) antibodies among the population residing in the Colombo district of Sri Lanka. Methods: A cross-sectional population-based study was conducted which included 1 258 participants. Blood samples were collected and questionnaires administered to obtain sociodemographic information and history of varicella and/or herpes zoster. Serum samples were assayed for VZV IgG antibodies using a commercial enzyme-linked immunosorbent assay kit. Results: Overall, the seroprevalence was 54.2%(95% CI= 51.5% 57.0%). Children below 1 year of age were seronegative, and only about 20.0% of children between 1 and 10 years of age were seropositive. Seropositivitiy increased with age and by the age of 40 years 74.3% were seropositive. Among women of childbearing age, the overall seroprevalence was about 62.0%(95% CI = 57.7%-66.1%) but was low 37.0% in the 15-19 age group. Conclusion: In this population, 45.8% lacked natural immunity against varicella. Of women of childbearing age, 39.9% lacked immunity and in the subgroup of women 15-19 years of age, 63.0% women lacked immunity. In light of the country's success with the control and high coverage of other vaccine preventable diseases and that the vaccine is available in the private sector, the inclusion of varicella vaccine in the national immunization program may be considered.     

Persistence of varicella zoster virus DNA in saliva after herpes zoster

Analysis of saliva samples from individuals aged ≥ 60 years who had a history of zoster (group 1), zoster and postherpetic neuralgia (PHN; group 2), or no history of zoster (group 3) revealed varicella zoster virus (VZV) DNA in saliva samples from 11 of 17 individuals in group 1, 10 of 15 individuals in group 2, and 2 of 17 individuals in group 3. The frequency of VZV DNA detection was significantly higher (P = .001) in saliva of subjects with a history of zoster, with or without PHN (21 [67%] of 32 subjects in groups 1 and 2), than in saliva of age-matched subjects with no zoster history (2 [12%] of 17 subjects in group 3). Thus, persistence of VZV DNA in saliva is the outcome of zoster, independent of PHN. Because VZV infection can produce neurological and ocular disease without zoster rash, future studies are needed to establish whether VZV DNA can be detected in the saliva of such patients.     

Seroprevalence survey of measles,rubella, varicella,and mumps antibodies in health care workers and evaluation of a vaccination program in a tertiary care hospital in Japan

Vaccine-preventable viral infections in health care workers (HCWs) have been on the rise for the past 10 years in Japan. To reduce the viral infections and the burden of exposure follow-up surveys at a tertiary care hospital in Osaka, Japan, a seroprevalence survey was conducted, and free vaccinations for measles, rubella, varicella, and mumps were offered to newly hired HCWs (199 physicians and 72 nurses and nursing assistants) who had negative serologic results for antibodies against these viruses. Negative antibody titers were obtained from 7.4% of the newly hired HCWs for measles, 12.5% for rubella, 4.1% for varicella, and 15.9% for mumps. The vaccination program for HCWs improved the vaccine-preventable infection rates and resulted in fewer exposure follow-up surveys, fewer lost work days, and fewer HCWs requiring hospitalization for these viral infections compared with those counted for the previous year. These data indicate that all HCWs should be strongly recommended to be vaccinated against (or have documented immunity to) these viruses in Japan, as is the case in the United States.     

Prevalence of IgG varicella zoster virus antibodies in the Kuikuro and Kaiabi indigenous communities in Xingu National Park, Brazil, before varicella vaccination

The purpose of the study was to estimate the prevalence of IgG antibodies against varicella zoster virus (VZV) in the two most populated indigenous ethnic groups from Xingu Indigenous National Park, in Brazil, prior to the introduction of vaccination against the disease, and to determine the positive and the negative predictive values of a history of varicella infection. In 2001, 589 inhabitants of two Kuikuro villages and three Kaiabi villages were evaluated and provided information concerning previous varicella infection. An indirect immunosorbent assay (ELISA) to detect IgG anti-VZV antibodies was performed in 224 blood samples--volunteer selection had no interference of anamnesis. IgG prevalence was 80.8% (95% Confidence Interval: 76%-86%). The seroepidemiology of varicella in Xingu National Park prior to varicella vaccine introduction was comparable to the Brazilian national seroprevalence described in the literature, and so were the positive (98%) and the negative predictive value (41%) of the referred history.     

Varicella zoster virus deoxythymidine kinase is present in serum before the onset of varicella

A sensitive enzyme assay with 125I-iododeoxyuridine as substrate and cytidine triphosphate as phosphate donor was used for the direct detection of varicella zoster virus (VZV) deoxythymidine kinase (TK) in human serum. Sera sampled during the incubation period of varicella from 2 patients, a 42-year-old man and his 11-year-old son, have been analysed for TK activity. A simultaneous increase in cellular and VZV TK activity, starting 5 to 3 days before the onset of clinical varicella, was observed.