Varicella morbidity in Czechoslovakia

Data are presented on varicella and herpes zoster morbidity notified in Czechoslovakia in the years 1970 to 1978. The notified varicella incidence is compared with serologically confirmed varicella incidence among the selected groups of children up to the age of 12 from the North-Moravia region. Comparative analysis revealed a considerable difference between the notified and serologically detected cases of varicella. The highest rate of notified varicella was recorded in children of 3 and 4 years of age, while the highest incidence of seropositive cases was detected among the 2-year-old children. The cumulative notified morbidity involved about 35% of 6-year-old and 45% of 12-year-old children, whereas specific antibodies against the varicella-zoster virus were found in about 60% of 6-year-old and 90% of 12-year-old children. The titres of virus-specific antibodies were determined by the method of indirect hemagglutination reaction. No serological methods are applicable for herpes zoster morbidity studies in the population.     

T lymphocyte cytotoxicity with natural varicella-zoster virus infection and after immunization with live attenuated varicella vaccine

Varicella-zoster virus (VZV) specific cytotoxicity was investigated during acute primary VZV infection, in naturally immune subjects and after vaccination with the live attenuated varicella vaccine by using T cell cultures (TCC) generated by stimulating PBMC with VZV Ag and autologous VZV-superinfected lymphoblastoid cell lines as targets. Lysis of VZV-infected lymphoblastoid cell lines was observed by TCC from acutely infected subjects, naturally immune subjects, and recipients of the varicella vaccine. VZV glycoprotein I induced cytotoxic T cells but killing was less efficient than killing by TCC stimulated with VZV Ag. The TCC were primarily CD4+ (mean 86.6%) T lymphocytes with 15.2% of the cells coexpressing Leu-19. TCC were predominantly restricted by HLA class II as demonstrated by lack of any blocking using class I mAb and blocking of 15 to 71% by L243, a mAb to class II. Unrestricted killing as measured by killing of K562 cells occurred in all TCC but was minimally greater than that observed against uninfected autologous targets. Phenotypes of PBMC during acute infection had an initial increase in CD4+ cells and an overall decrease in the percentage of circulating Leu-11+ (CD16). No enhanced K562 killing was demonstrated in PBMC from subjects with acute infection compared to subjects without infection. CD4+ CTL may function as an important primary host response in acute varicella. Immunization with live attenuated varicella vaccine induced VZV-specific, memory CTL responses comparable to those of naturally immune subjects. The demonstration of their persistence long after primary VZV infection may indicate a role for CTL in restriction of viral replication during episodes of VZV reactivation from latency.     

2008—2012年荔湾区水痘流行病学特征分析

目的了解荔湾区2008—2012年水痘疫情的流行情况,为制定水痘疫情防制措施提供科学依据。方法对2008—2012年荔湾区报告的水痘病例及水痘暴发数据,采用Excel2003软件整理后,进行描述性流行病学分析,并结合当前有关文献资料提出今后水痘防制的建议。结果 2008—2012年广州市荔湾区共报告水痘5 814例,年均发病率为129.46/10万。年发病率为83.50/10万~165.33/10万,其间2008年最高,2012年最低;全区22条街都有病例发生;全年12个月均有病例发生,呈冬春季高发态势;发病主要集中在儿童和青少年,学生占42.89%;男女比例为1.4∶1,报告病例中20岁以下者4 690例,占总数80.67%(4 690/5 814);集体单位聚集性疫情13起,其中暴发疫情4起。结论荔湾区近年水痘疫情主要发生在冬春季节,学生和托幼儿童及散居儿童是水痘的高发人群。建议加强普及防控水痘基本知识,提高水痘疫苗第1剂接种率,落实应急接种的同时,开展水痘疫苗第2剂接种程序的研讨,确保水痘疫情的有效控制,保护公众健康。     

Prevalence of hyperthyroidism after exposure during childhood or adolescence to radioiodines from the chornobyl nuclear accident: dose-response results from the Ukrainian-American Cohort Study

Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of <0.3 mIU/liter, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 ((131)I) (mean and median doses = 0.6 Gy and 0.2 Gy). We investigated the relationship between (131)I and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12-14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n = 5,767) and males (23 cases, n = 6,086) separately but found no convincing evidence of a dose-response relationship between (131)I and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR = 1.86, P = 0.06), but the statistical significance level was reduced (P = 0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose-response relationship between individual (131)I thyroid doses and prevalent hyperthyroidism.     

Complete DNA sequences of two oka strain varicella-zoster virus genomes

Varicella-zoster virus (VZV) is a herpesvirus and is the causative agent of chicken pox (varicella) and shingles (herpes zoster). Active immunization against varicella became possible with the development of live attenuated varicella vaccine. The Oka vaccine strain was isolated in Japan from a child who had typical varicella, and it was then attenuated by serial passages in cell culture. Several manufacturers have obtained this attenuated Oka strain and, following additional passages, have developed their own vaccine strains. Notably, the vaccines Varilrix and Varivax are produced by GlaxoSmithKline Biologicals and Merck & Co., Inc., respectively. Both vaccines have been well studied in terms of safety and immunogenicity. In this study, we report the complete nucleotide sequence of the Varilrix (Oka-V_GSK) and Varivax (Oka-V_Merck) vaccine strain genomes. Their genomes are composed of 124,821 and 124,815 bp, respectively. Full genome annotations covering the features of Oka-derived vaccine genomes have been established for the first time. Sequence analysis indicates 36 nucleotide differences between the two vaccine strains throughout the entire genome, among which only 14 are involved in unique amino acid substitutions. These results demonstrate that, although Oka-V_GSK and Oka-V_Merck vaccine strains are not identical, they are very similar, which supports the clinical data showing that both vaccines are well tolerated and elicit strong immune responses against varicella.     

Study of cognitive function among the Adult Health Study (AHS) population in Hiroshima and Nagasaki

Although neuropsychological dysfunction is found among A-bomb survivors exposed in utero as it is among patients who receive central nervous system radiotherapy, neuropsychological examinations have not been conducted on the survivors. Its prevalence may be increased as a result of the increased rate of strokes reported among those exposed to a high radiation dose. In this study, we examined the effects of radiation exposure on cognitive function among adult survivors in the Adult Health Study (AHS). The study subjects were men and women born prior to September 1932 who had undergone biennial examinations during the period 1992-1996 in Hiroshima or 1993-1998 in Nagasaki. We evaluated cognitive performance for 3,113 subjects with the Cognitive Abilities Screening Instrument (CASI), and we examined the relationship between cognitive performance and potentially related factors (sex, age, city where the subjects were exposed, years of education, and radiation dose). In contrast to exposure to radiotherapy, exposure to atomic bomb radiation had no apparent effect on cognitive function. Factors that did affect cognitive function were age, sex, city and years of education. Further investigation, including examination of other neurological functions, is required before a final conclusion regarding radiation-induced neurological dysfunction can be reached.     

Antibody prophylaxis of varicella in immunosuppressed patients

ZIG prophylaxis was administered to a total of 39 children immunosuppressed under antitumour therapy and presenting a negative varicella history. Varicella developed in only 2 of them. 47 children received a substitutive prophylaxis consisting of ordinary gammaglobulin NORGA. Fourteen of the children fell ill with varicella, two of the cases being complicated. With a few exceptions, the cases represented hospital contacts, because most children with anticancer therapy are in hospital. The difference between the numbers of varicella cases after ZIG and after NORGA was statistically highly significant in the group of seronegative children. On the other hand, the difference between the numbers of cases among preprophylactically seropositive children in both prophylactic groups was not substantial. Varicella was not encountered either among children with a titre of minimally 1:128 at the time of contact with the disease. In contrast, varicella developed in 20-30% of children with a titre of at most 1:64. Four children were serologically followed up for 35-49 days after the injection of ZIG. The degradation of VZV antibodies in these children under immunosuppression was far more rapide than that of known passively transferred IgG in normal individuals. In states of deep immunosuppression a quantitatively or qualitatively different mechanism of passively transferred antibody clearance is probably involved.     

Modeling the effects of varicella vaccination programs on the incidence of chickenpox and shingles

Two possible dangers of an extensive varicella vaccination program are more varicella (chickenpox) cases in adults, when the complication rates are higher, and an increase in cases of zoster (shingles). Here an age-structured epidemiologic—demographic model with vaccination is developed for varicella and zoster. Parameters are estimated from epidemiological data. This mathematical and computer simulation model is used to evaluate the effects of varicella vaccination programs. Although the age distribution of varicella cases does shift in the simulations, this does not seem to be a danger because many of the adult cases occur after vaccine-induced immunity wanes, so they are mild varicella cases with fewer complications. In the simulations, zoster incidence increases in the first three decades after initiation of a vaccination program, because people who had varicella in childhood age without boosting, but then it decreases. Thus the simulations validate the second danger of more zoster cases.     

Effect of radiation dose on the height of atomic bomb survivors: a longitudinal study

We conducted a longitudinal analysis of height after age 20 for atomic bomb survivors in the Adult Health Study (AHS) cohort. The measurements we used were made from July 1958 to June 1998 (AHS examination cycles 1-20). We analyzed only the subjects with known atomic bomb radiation doses, excluding those who were not in the city at the time of bombing (ATB) and those exposed in utero. We also excluded from the analysis measurements made after the occurrence of vertebral fracture. The total number of subjects was 11,862, and the total number of measurements was 109,770; the mean number of measurements per subject was 9.25. Assuming that stature after age 20 is approximately constant, a simple mixed-effects model was fitted to stature after age 20, and linear dose effects for young ATB subjects were modeled for both sexes. The estimated mean heights for subjects born in 1945 in Hiroshima were 166.0 cm for men and 155.4 cm for women. The sex difference in height was 10.6 cm, with men significantly taller than women (P < 0.001). The difference between the cities was not significant (P = 0.162). The birth cohort effects per decade were -1.7 cm for men (P < 0.001) and -2.1 cm for women (P < 0.001). A reduction of stature due to radiation exposure was observed for individuals of both sexes who were below 19 years of age ATB (95% confidence interval, 17-21 years), and the dose effect was larger for women than for men (P = 0.028). The estimated effects per gray for those who were age 0 ATB were -1.2 cm for men and -2.0 cm for women and for those who were age 10 ATB were-0.57 cm for men and -0.96 cm for women.     

A five-year immunological follow-up study of the institutionalized handicapped children vaccinated with live varicella vaccine or infected with natural varicella

Twenty-two institutionalized handicapped children who were susceptible to varicella were vaccinated with live varicella vaccine of the Oka strain and their immune status was followed for 5 years under conditions without exposure to natural varicella. Simultaneously, 7 children infected with natural varicella were followed. Of the 22 vaccinees, 16 showed sero-positive conversion by the fluorescent antibody to membrane antigen (FAMA) test, the other 6 remaining seronegative during 5 years of observation period. All the 16 cases showing seroconversion had detectable antibody for 5 years after vaccination, and 14 of them gave a positive reaction in the varicella skin test. All the 7 cases after natural varicella gave positive reactions in both the FAMA and skin test. These results suggest that immunity conferred by the vaccination would persist long even in the absence of exposure to natural varicella, though further follow-up studies are needed.     

IgG subclass distribution among antibodies to varicella-zoster virus in human varicella/zoster immunoglobulin preparations and the corresponding donor plasma

IgG subclasses to varicella-zoster virus (VZV) were detected in plasma from different sources used for the production of varicella/zoster immunoglobulin (VZIG). IgG1 and IgG3 were the principal virus antibodies in plasma from healthy donors as well as from convalescents after primary and reactivated disease. Anti-VZV IgG3 antibodies were predominant among varicella convalescents while IgG1 antibodies dominated among zoster convalescents. IgG4 antibodies were present in zoster convalescents and healthy donors but were rarely detected in varicella convalescents. Antiviral IgG2 antibodies were found only in a few cases. Studies of plasma samples collected from one varicella convalescent during a period of seven months following an outbreak of disease, demonstrated a rapid fall in antiviral IgG1 and IgG3, while IgG4 increased to reach a maximum six months after the onset of symptoms. The relative distribution of VZV-specific subclasses in a plasma pool was conserved during a fractionation procedure combining polyethyleneglycol 6000 precipitation with ion exchange chromatography, thus suggesting that the protective efficacy is maintained in the resulting immunoglobin preparations.     

Sister-chromatid exchanges in association with occupational exposure to ethylene oxide

Sister-chromatid exchange (SCE) frequencies in employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. Three worksites where the previous environmental control of ETO was known to have differed were chosen. Within these worksites, subjects were categorized into high potential exposed, low potential exposed and control groups. An additional community control group was obtained. Blood samples for chromosome studies of peripheral lymphocytes were drawn at several time points over a period of 24 months. The effects on SCE of age, sex, smoking habits and reader variation were considered. Worksites I, II and III, respectively, represented increasing levels of exposure. At Worksite III large differences among groups persisted over 24 months. At Worksite II, the SCEs in the high potential exposed workers were higher than those in the other groups. At no time was the low potential exposed group at Worksite II statistically significantly higher in mean SCE than the worksite controls. No consistent differences among groups were noted in Worksite I.     

Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect

Hereditary paraganglioma type 1 (PGL1) is characterized by slow-growing and vascularized tumors that often develop in the carotid body (CB) and is caused by mutations in the gene for succinate dehydrogenase D (SDHD) of mitochondrial complex II. The mechanisms of tumorigenesis and the factors affecting penetrance and expressivity are unknown. Because chronic hypoxic stimulation at high altitudes causes sporadic CB paragangliomas, it has been hypothesized that the SDHD gene product may be involved in oxygen sensing. On this background, we examined genotype-phenotype-environment relationships and tested whether higher altitudes adversely affect the phenotype in PGL1. An analysis of 58 subjects from 23 families revealed that nonsense/splicing mutation carriers developed symptoms 8.5 years earlier than missense mutation carriers (P<0.012). We also found that subjects who were diagnosed with single tumors at their first clinical evaluation lived at lower average altitudes and were exposed to lower altitude-years than those with multiple tumors (P<0.012). Pheochromocytomas developed in six subjects (approximately 10%), five of whom had nonsense mutations (P=0.052). Subjects with pheochromocytomas also lived at higher average altitudes and were exposed to higher altitude-years than those without them (P=0.026). To test whether altitude is also associated with the more frequent detection of germ-line founder mutations among sporadic cases in The Netherlands than in the USA (P=0.00033), we calculated population-weighted elevations of the two countries. We found that the population-weighted elevations were approximately 260 m for the US and 2 m for the central-western Netherlands (P~0), where three Dutch founder mutations were discovered. This finding suggests that low altitudes in The Netherlands reduce penetrance and relax the natural selection on SDHD mutations. Collectively, these data suggest that higher altitudes and nonsense/splicing mutations are associated with phenotypic severity in PGL1 and support the hypothesis that SDHD mutations impair oxygen sensing.     

Independent effects of weight change and attained body weight on prevalence of arterial hypertension in obese and non-obese men.

OBJECTIVE--To assess the relations among prevalence of arterial hypertension, history of weight change, and current body weight in the range from normal weight to severe obesity. DESIGN--Retrospective analysis of medical records of men registered with Danish military authorities from 1943 to 1977 and followed up four to 40 years later. SETTING--Draft board of Copenhagen and surrounding counties and the rest of Sjaelland and surrounding islands. SUBJECTS--964 Men who were severely obese (body mass index greater than or equal to kg/m2 at the first examination) and 1134 random controls. MAIN OUTCOME MEASURES--Blood pressure and weight. RESULTS--Hypertension was more prevalent in subjects with an unchanged body mass index as that index increased over the range studied. At any body mass index hypertension was more prevalent in subjects who had increased to this index and less common in those who had decreased to it than in those who had stayed the same weight since the first examination. Hypertension among controls was most common in those subjects who had become obese during adulthood. CONCLUSIONS--Changes in body weight have a great influence on arterial hypertension independent of the effect of attained weight, particularly in obese subjects.     

Prevention of varicella in urgent cases by passive transfer of vaccine-induced immunity

For the purpose of preventing spread of infection to high risk children whose immunities were severely impaired by intensive chemotherapy or for some other reason, when cases of varicella occurred in a children's ward or in a family, healthy adults (mothers and a doctor) were immediately given live varicella vaccine, blood was collected from these adults 5 to 7 days after vaccination and the whole blood or plasma including the buffy coat was transferred in the high risk children. Subsequently the children showed little or no clinical reaction, and follow-up studies by the neutralizing test and skin test with varicella antigen indicated that their inapparent or subclinical varicella infection occurred in them and that their immunity to varicella was lasting. Skin tests with varicella antigen showed that booster reaction occurred in adults with a previous history of varicella as early as 5 to 7 days after vaccination. The cellular immunity thus induced in the donors may have played a role in preventing a clinical reaction in the high risk children. Thus passive transfer of vaccine-induced immunity seems a convenient and effective method for preventing infection in subjects whose immune capacities are severely impaired.     

Malaria in migrants

An increasing proportion of malaria cases in Italy is observed in immigrants revisiting their country of origin, but little specific research work has been carried out in this field. All malaria cases occurring from 1990 to 1998 at the Reference Clinic for Infectious and Tropical Diseases in Brescia were prospectically evaluated to compare clinical outcome in migrant and non-immune cases. No difference was observed between parasitaemia at diagnosis and time to clearance of peripheral parasitaemia. Clinical presentation was milder in migrants than in non-immunes, with an OR for severe malaria of 0.27 (c.i. = 0.09-0.84) (p = 0.01). Fever clearance time was significantly shorter in migrants (3.0 days, SD = 1.2) than in non-immunes (4.3 days, SD = 1.7) (p < 0.001). Among immigrants, the proportion of severe cases was higher in residents since 2 years or less (12.5%) compared to residents since 2 to 5 years (3.3%) and residents since more than 5 years (0.9%) (p = 0.02). The proportion of malaria cases who had used chemoprophylaxis was significantly lower among immigrants (30/272, 11.0%) compared to non-immunes (41/74, 55.4%) (p < 0.001). In a population based malaria KAP analysis among 504 migrants from malaria endemic countries, correct knowledge of malaria risk was reported by 351 (69.5%). Of 170 subjects who reported at least one visit back to the home country, 30 (17.6%) had sought pre-travel advice, 24 (14.1%) had started chemoprophylaxis and 7 (4.1%) had completed it during the last visit. Of 140 migrants who failed to seek pre-travel advice, 73 (52%) were unaware of malaria risk, 56 (40%) did not know how to protect themselves, and 11 (8%) refused to use protective measures. Migrants account for a significant proportion of imported malaria cases in industrialised countries. Clinical presentation is milder compared to non-immune subjects. The proportion of migrants who adopt malaria protective measure while returning home is very low, due to both unawareness of risk and inappropriateness of medical advice.     

Effect and follow-up study on varicella vaccine

Attenuated liver varicella vaccine (Oka strain) was used to vaccinate 242 children and 5 adults between August 1976 and December 1982; namely emergency vaccinations were given to 163 cases, including 35 high risk children, on 17 occasions, and non-emergency vaccinations were given to 84 cases including 7 high risk ones in remission. The viral doses varied from 250 to 3,000 PFU. Vaccinations prevented subsequent infection in all cases. Emergency vaccinations were given within 100 h after contact of the subjects with cases of varicella. Humoral and/or cellular immunity was acquired in 97.6% (40/41) of the high risk group and 91.8% (179/195) of the non-high risk group. As clinical reactions, rashes and fever developed in 43.9% (18/41) and in 17.0% (7/41) of high risk patients, and 7.8% (16/204) and 1.0% (2/204) of the non-high risk patients respectively. Reactions were generally slight, but were severe or atypical in 3 immunocompromized patients. Follow-up studies were carried out every year since 1980. Among the 41 high risk patients, herpes-zoster developed in 4, and varicella in 5 patients. Among the 179 non-high risk patients, there were no cases of herpes-zoster but 21 cases (12.3%) of varicella, which were mostly extremely mild. Six patients were revaccinated because of their humoral and/or cellular immunity decreased, and as a result acquired an immune response again. Criteria for varicella vaccination and details of the results of vaccination and follow-up studies are described.     

Invasive group A streptococcal disease and association with varicella in Germany, 1996-2009

A nationwide laboratory-based surveillance study was conducted to analyse the epidemiology of varicella-associated invasive group A streptococcal (iGAS) infections in Germany. A total of 1342 iGAS samples were collected between 1 January 1996 and 22 September 2009. For 21 of these isolates, an association with varicella was observed. The median age of this subgroup was 4.2 years (mean 12.1). Most of these patients presented with sepsis (42.9%), streptococcal toxic shock syndrome (23.8%) and necrotizing fasciitis (19.0%). The most common complications among patients with underlying varicella were hypotensive shock and soft-tissue necrosis (38.1% each), disseminated intravascular coagulopathy (33.3%) and renal impairment (28.6%). The overall rate of complications was higher among the patients with underlying varicella than among those without. In the varicella-positive group, emm types 1 (38.1%), 12 (19.0%) and 4 (14.3%) were predominant, while among the varicella-negative isolates, emm types 1 (32.5%), 28 (14.0%) and 3 (8.3%) were found most often. Among the varicella-positive group, the rate of ssa-positive isolates was considerably higher than that among the varicella-negative group (28.6% vs. 12.6%), as well as the coexistence of speC and ssa (14.3% vs. 3.6%).     

Clinical course of primary HIV infection: consequences for subsequent course of infection.

OBJECTIVE--To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection. DESIGN--Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables. PATIENTS--86 Men in whom seroconversion occurred within 12 months. PRIMARY OUTCOME MEASURE--Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV. MAIN RESULTS--Median follow up was 670 (range 45-1506) days. An acute illness like glandular fever occurred in 46 (53%) subjects. Three year progression rates to Centers for Disease Control group IV was 78% at three years for those who had longlasting illnesses (duration greater than or equal to 14 days) during seroconversion as compared with 10% for those who were free of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those who had no symptoms or mild illness (75% v 42% and 55% v 14%, respectively). CONCLUSION--The course of primary infection may determine the subsequent course of the infection.