Epidemiology of herpes zoster. The herpes zoster patient as a source of infection with chickenpox

The authors analyse the inpatient findings accumulated from 2,179 observations on herpes zoster cases for 10 years. The clinico-epidemiological characterization of herpes zoster patients as the potential source of chickenpox infection is presented. The clinical data speak for the droplet transfer of the agent (varicella zoster virus) in this infection, which has permitted the formulation of exact practical recommendations of quarantine and isolation measures in the focus of herpes zoster.     

Epidemiology of chickenpox in England and Wales, 1967-85

Routine sources of data on chickenpox morbidity and mortality in England and Wales were reviewed for 1967-85. Only two epidemics occurred, one in 1967 and one in 1980, both of which were immediately followed by two to three years of low incidence. The age distribution of the disease appears to be changing, with more cases now being reported in children aged 0-4 years. The number of deaths in adults have, however, increased, particularly those deaths that are associated with pneumonia and immunosuppression. At present in England and Wales more deaths are attributed to chickenpox than to whooping cough and mumps.Widespread use of selective immunisation against chickenpox might be justified in England and Wales, but before routine immunisation of the child population can be considered special surveys to determine the incidence and severity of chickenpox and the effect of the vaccine on the subsequent development of herpes zoster are needed as well as cost-benefit studies of immunisation.     

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field.     

Detection of herpes simplex and varicella zoster viruses in clinical specimens using direct immunofluorescence and cell culture assays

Patients (33 in toto) with a clinical diagnosis of herpes infections (simplex, zoster or chickenpox) were investigated for the presence of herpes simplex virus (HSV) and varicella zoster virus (VZV) in skin samples, using direct immunofluorescence and cell culture assays. Five patients with nonherpetic vesiculobullous disorders were included as negative controls. Of the 33 patients, nineteen (57.6%) were positive for HSV or VZV and fourteen (42.4%) were negative. Five controls were all negative for HSV or VZV. Of the nineteen positive patients, HSV was isolated from eight (42.1%) patients, by both direct immunofluorescence and cell culture assays. VZV was isolated from eleven (57.9%) patients, eleven (100%) by direct immunofluorescence assay, and six (54.5%) by cell culture assays. HSV was isolated from one patient clinically diagnosed as chickenpox (VZV), but otherwise the positive laboratory results were concordant with the clinical diagnosis. For epidemiological studies, atypical cases and immunocompromised patients the clinical diagnosis should be confirmed in the laboratory.     

Comparison of several ELISA tests for detecting the presence of IgG and IgM against herpes simplex viruses

Four enzyme-linked immunosorbent assays designated test 1 (ETI-HSVK-G 1/2); test 2 (ETI-HSVK-M 1/2); test 3 (ETI-HSVK-G 2), and test 4 (BioElisa HSV2 IgG) were studied to evaluate different stages of herpes simplex virus (HSV) infection. Samples (50 sera and 14 cerebrospinal fluid) were included in four groups. Group 1 consisted of samples from patients with primary HSV infections; group 2 comprised samples from patients with recurrent HSV infections; group 3 were samples nonreactive to HSV; and group 4 were samples from patients with infections by other herpes viruses (4a, chickenpox; 4b, herpes zoster; and 4c, infectious mononucleosis by Epstein-Barr virus). The percentages of agreement between tests 1 and 2 were 100 and 72.1%, respectively. The total diagnostic values of tests 1 and 2 were: 100 and 50% sensitivity, respectively; and 100 and 89% specificity, respectively. Few positive results for HSV-2 infection were found, and so, tests 3 and 4 were not evaluated. The results of tests 3 and 4 for a chickenpox patient, and a herpes zoster patient were not in agreement.     

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.     

Clinically Evident,Non-terminal Infections with Herpesviruses and the Wart Virus in Immunosuppressed Renal Allograft Recipients

The clinical incidence of herpes simplex lesions, herpes zoster, cytomegalovirus infection, and warts has been determined in a group of renal allograft recipients. Herpes simplex lesions appeared to be no more common after transplantation than before in those patients subject to recurrent attacks. Among 74 patients there were seven cases of herpes zoster and seven serologically proved cases of cytomegalovirus infection with clinical manifestations. The incidence of warts increased with length of time after transplantation, 42% of patients being affected more than one year after transplantation. All of the viral infections studied behaved as in healthy adults, and serious illness, dissemination, wide-spread lesions, and complications were not seen. No factors other than immunosuppression and steroid therapy could be identified with certainty as predisposing to these infections.     

Can annual cyclicity of protozoan communities reflect water quality status in coastal ecosystems?

With many advantages, many ecological parameters of protozoan communities have been successfully used as a useful bioindicator for bioassessment of water quality in Chinese marine waters. However, as regard the response of the annual cyclicity of protozoan communities to seasonal environmental stress, a further investigation was needed. In this study, the cyclicity of annual variations in community patterns of biofilm-dwelling protozoa was studied based on an annual dataset. Samples were monthly collected, using glass slide method, at four stations, within a pollution gradient, in coastal waters of the Yellow Sea, northern China during a 1-year period. The cyclicity patterns of the microbiota represented a significant spatial variation among four stations. The low value of cyclicity coefficients occurred in heavily polluted area, while the high values were in less stressed areas. Correlation analysis showed that the cyclicity measure was significantly related to environmental variables ammonia, transparency and dissolved oxygen. Thus, it is suggested that the annual cyclicity of protozoan communities may be used as a potential bioindicator of bioassessment in marine ecosystems.     

Revisited measles and chickenpox dynamics through orthogonal transformation

The question addressed is whether or not childhood epidemics such as measles and chickenpox are characterized by low-dimensional chaos. We propose a new method for the detection and extraction of hidden periodic components embedded in an irregular cyclical series, and study the characterization of the epidemiological series in terms of the characteristic features or periodicity attributes of the extracted components. It is shown that the measles series possesses two periodic components each having a period of one year. Both the periodic components have time-varying pattern, and the process is nonlinear and deterministic; there is no evidence of strong chaoticity in the measles dynamics. The chickenpox series has one seasonal component with stable pattern, and the process is deterministic but linear, and hence non-chaotic. We also propose surrogate generators based on null hypotheses relating to the variability of the periodicity attributes to analyse the dynamics in the epidemic series. The process dynamics is also studied using seasonally forced SEIR epidemic model, and the characterization performance of the proposed schemes is assessed.     

Possibilities for the treatment of varicella-herpes zoster infections in juvenile leukemia]

Chicken pox and herpes zoster represent afraid complications in patients with malignant diseases which may take a noxious course. During the sequence of two chicken pox epidemias in 1973 in children with acute lymphoblastic leukaemias, the prevention and therapeutic possibilities were checked again. Chicken pox or herpes zoster convalescent sera being compatible for blood groups and zoster-immunoglobulin were not available. At the time of the epidemia the first reports on the effect of cytarabine (Alexan) were published. Moreover, we received an information on the therapeutic application of small pox vaccine inactivated with formaldehyde (vaccinia antigen) in adults with herpes zoster and herpes labialis. From 10 children with leukaemias, who were affected with chicken pox or herpes zoster, 7 received up to 1.0 ml of inactivated small pox vaccine intramuscularly on the first day of manifestation. In 6 of the patients there were no new efflorescences on the third day. A third child died. First of all it seems probable that this influence may be due to an induction of interferon formation. Further studies will have to elucidate to what extent this mechanism will also be efficient in severe cases of immunosuppression.     

Mandibular herpes zoster; with report on the use of cortisone in a case with geniculate ganglion symptoms

Herpes zoster, an acute specific viral infection, occurs more commonly than is generally supposed. It should be differentiated from other diseases involving the ear and skin; it must be considered as a possible etiologic agent in some palsies of the facial, glossopharyngeal or vagal nerves. The type of cephalic herpes zoster should be carefully differentiated; cases involving the "geniculate zone" may be other than "Ramsay Hunt's syndrome." This syndrome is now defined as a herpes zoster eruption of the external ear at the "geniculate zone" with involvement of the seventh or seventh and eighth nerves. The "topognostic" method is the best for determining the level at which the facial nerve has been affected. It is questioned whether there is a single outstanding therapeutic agent for this disease. Cortisone had no apparent therapeutic effect in a case reported herein.     

Thirty one years of herpes zoster in a rural practice.

The principal finding in this study of 151 cases of herpes zoster in a rural practice was the predominance of patients who had a lesion on the right side. This supports the proposition that the site of occurrence may be determined by repeated trauma. The decline in the frequency of attacks in older men was significant. Studying these cases and published reports has elucidated some of the problems of the occurrence and distribution of herpes zoster in the body, which still await definition. Others may be encouraged to carry these studies further.     

Genome-Wide Analysis of T Cell Responses during Acute and Latent Simian Varicella Virus Infections in Rhesus Macaques

Varicella zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (HZ [shingles]). Clinical observations suggest that VZV-specific T cell immunity plays a more critical role than humoral immunity in the prevention of VZV reactivation and development of herpes zoster. Although numerous studies have characterized T cell responses directed against select VZV open reading frames (ORFs), a comprehensive analysis of the T cell response to the entire VZV genome has not yet been conducted. We have recently shown that intrabronchial inoculation of young rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we characterized the specificity of T cell responses during acute and latent SVV infection. Animals generated a robust and broad T cell response directed against both structural and nonstructural viral proteins during acute infection in bronchoalveolar lavage (BAL) fluid and peripheral blood. During latency, T cell responses were detected only in the BAL fluid and were lower and more restricted than those observed during acute infection. Interestingly, we identified a small set of ORFs that were immunogenic during both acute and latent infection in the BAL fluid. Given the close genome relatedness of SVV and VZV, our studies highlight immunogenic ORFs that may be further investigated as potential components of novel VZV vaccines that specifically boost T cell immunity.     

No Increased Risk of Herpes Zoster Found in Cirrhotic Patients: A Nationwide Population-Based Study in Taiwan

Background

The association between liver cirrhosis (LC) and herpes zoster has rarely been studied. We investigated the hypothesis that LC, known as an immunodeficiency disease, may increase the risk of herpes zoster using a national health insurance database in Taiwan.

Materials and Methods

The study cohort included cirrhotic patients between 1998 and 2005 (n = 4667), and a ratio of 1∶5 randomly sampled age- and gender-matched control patients (n = 23,335). All subjects were followed up for 5 years from the date of cohort entry to identify whether or not they had developed herpes zoster. Cox proportional-hazard regressions were performed to evaluate 5-year herpes zoster-free survival rates.

Results

Of all patients, 523 patients developed herpes zoster during the 5-year follow-up period, among whom 82 were LC patients and 441 were in the comparison cohort. The adjusted hazard ratio (AHR) of herpes zoster in patients with LC was not higher (AHR: 0.77, 95% confidence interval: 0.59–1.01, p = 0.06) than that of the controls during the 5-year follow-up. No increased risk of herpes zoster was found in LC patients after stratification by age, gender, urbanization level, income, geographic region, and all comorbidities.

Conclusions

This large nationwide population-based cohort study suggests that there is no increased risk for herpes zoster among people who have LC compared to a matching population.     

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.     

National Lupus Hospitalization Trends Reveal Rising Rates of Herpes Zoster and Declines in Pneumocystis Pneumonia

Objective

Infection is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Therapeutic practices have evolved over the past 15 years, but effects on infectious complications of SLE are unknown. We evaluated trends in hospitalizations for severe and opportunistic infections in a population-based SLE study.

Methods

Data derive from the 2000 to 2011 United States National Inpatient Sample, including individuals who met a validated administrative definition of SLE. Primary outcomes were diagnoses of bacteremia, pneumonia, opportunistic fungal infection, herpes zoster, cytomegalovirus, or pneumocystis pneumonia (PCP). We used Poisson regression to determine whether infection rates were changing in SLE hospitalizations and used predictive marginals to generate annual adjusted rates of specific infections.

Results

We identified 361,337 SLE hospitalizations from 2000 to 2011 meeting study inclusion criteria. Compared to non-SLE hospitalizations, SLE patients were younger (51 vs. 62 years), predominantly female (89% vs. 54%), and more likely to be racial/ethnic minorities. SLE diagnosis was significantly associated with all measured severe and opportunistic infections. From 2000 to 2011, adjusted SLE hospitalization rates for herpes zoster increased more than non-SLE rates: 54 to 79 per 10,000 SLE hospitalizations compared with 24 to 29 per 10,000 non-SLE hospitalizations. Conversely, SLE hospitalizations for PCP disproportionately decreased: 5.1 to 2.5 per 10,000 SLE hospitalizations compared with 0.9 to 1.3 per 10,000 non-SLE hospitalizations.

Conclusions

Among patients with SLE, herpes zoster hospitalizations are rising while PCP hospitalizations are declining. These trends likely reflect evolving SLE treatment strategies. Further research is needed to identify patients at greatest risk for infectious complications.     

Simian Varicella in Old World Monkeys

Simian varicella virus (SVV) causes a natural erythematous disease in Old World monkeys and is responsible for simian varicella epizootics that occur sporadically in facilities housing nonhuman primates. This review summarizes the biology of SVV and simian varicella as a veterinary disease of nonhuman primates. SVV is closely related to varicella–zoster virus, the causative agent of human varicella and herpes zoster. Clinical signs of simian varicella include fever, vesicular skin rash, and hepatitis. Simian varicella may range from a mild infection to a severe and life-threatening disease, and epizootics may have high morbidity and mortality rates. SVV establishes a lifelong latent infection in neural ganglia of animals in which the primary disease resolves, and the virus may reactivate later in life to cause a secondary disease corresponding to herpes zoster. Prompt diagnosis is important for control and prevention of epizootics. Antiviral treatment for simian varicella may be effective if administered early in the course of infection.Abbreviations: FEAU, 1-(2′-deoxy-2′-flouro-β-D-arabinofuranosyl)-5-iodouracil, IE, immediate early, ORF, open reading frame, PBL, peripheral blood lymphocyte, SVV, simian varicella virus, VZV, varicella–zoster virusSimian varicella is a natural erythematous disease of Old World primates (Superfamily Cercopithecoidea, Subfamily Cercopithecinae), involving particularly patas (Erythrocebus patas), African green or vervet (Chlorocebus aethiops), and various species of macaque (Macaca spp.) monkeys. Epizootics of simian varicella occur sporadically in facilities housing nonhuman primates. These outbreaks are sometimes associated with high morbidity and mortality and the loss of valuable research animals. Simian varicella virus (SVV; Cercopithecine herpesvirus 9), a primate herpesvirus, is the etiologic agent of the disease. SVV is antigenically and genetically related to varicella–zoster virus (VZV; Human herpesvirus 3), the cause of human varicella (chickenpox) and herpes zoster (shingles). The clinical similarities between simian and human varicella and the relatedness of SVV and VZV, indicate that SVV infection of nonhuman primates is a useful model for study of varicella pathogenesis and development of antiviral therapies. A previous comprehensive review emphasized simian varicella as an experimental model for VZV infections.²² This review focuses on simian varicella as a veterinary disease of nonhuman primates. Simian varicella outbreaks and their epidemiology are considered, and the etiologic agent, clinical manifestations, pathogenesis, diagnosis, treatment, and control of the disease are discussed.     

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.     

Risk of cancer among patients with herpes zoster infection: a population-based study

Background:

Whether the risk of cancer is increased among patients with herpes zoster is unclear. We investigated the risk of cancer among patients with herpes zoster using a nationwide health registry in Taiwan.

Methods:

We identified 35 871 patients with newly diagnosed herpes zoster during 2000–2008 from the National Health Insurance Research Database in Taiwan. We analyzed the standardized incidence ratios for various types of cancer.

Results:

Among patients with herpes zoster, 895 cases of cancer were reported. Patients with herpes zoster were not at increased risk of cancer (standardized incidence ratio 0.99, 95% confidence interval 0.93–1.06). Among the subgroups stratified by sex, age and years of follow-up, there was also no increased risk of overall cancer.

Interpretation:

Herpes zoster is not associated with increased risk of cancer in the general population. These findings do not support extensive investigations for occult cancer or enhanced surveillance for cancer in patients with herpes zoster.Herpes zoster, or shingles, is caused by reactivation of the varicella–zoster virus, a member of the Herpesviridae family. Established risk factors for herpes zoster include older age, chronic kidney disease, malignant disease and immunocompromised conditions (e.g., those experienced by patients with AIDS, transplant recipients, and those taking immunosuppressive medication because of autoimmune diseases).^1–5 Herpes zoster occurs more frequently among patients with cancer than among those without cancer;^6,7 however the relation between herpes zoster and risk of subsequent cancer is not well established.In 1955, Wyburn-Mason and colleagues reported several cases of skin cancer that arose from the healed lesions of herpes zoster.⁸ In 1972, a retrospective cohort study and a case series reported a higher prevalence of herpes zoster among patients with cancer, especially hematological cancer;^6,7 however, they did not investigate whether herpes zoster was a risk factor for cancer. In 1982, Ragozzino and colleagues found no increased incidence of cancer (including hematologic malignancy) among patients with herpes zoster.⁹ There have been reports of significantly increased risk of some subtypes of cancer among patients aged more than 65 years with herpes zoster¹⁰ and among those admitted to hospital because of herpes zoster.¹¹ Although these studies have suggested an association between herpes zoster and subsequent cancer, their results might not be generalizable because of differences in the severity of herpes zoster in the enrolled patients.Whether the risk of cancer is increased after herpes zoster remains controversial. The published studies^8–11 were nearly all conducted in western countries, and data focusing on Asian populations are lacking.¹² The results from western countries may not be directly generalizable to other ethnic groups because of differences in cancer types and profiles. Recently, a study reported that herpes zoster ophthalmicus may be a marker of increased risk of cancer in the following year.¹³ In the present study, we investigated the incidence rate ratio of cancer, including specific types of cancer, after diagnosis of herpes zoster.     

Dynamics of typhoid-paratyphoid infection morbidity in Chimkent Province

The study of the time course of typhoid-paratyphoid infections in the Chimkent region for the period of 1944-1979 has revealed the periodicity of their rises (falls) repeating every 2-4 years. Since 1964 the tendency towards the decrease of morbidity has been observed. The annual rate of this decrease is 4.9%. Periodic changes in the annual level of typhoid-paratyphoid infections do not depend on the temperature of the air and the seasonal number of winged flies. There is a pronounced direct correlation between the annual morbidity level and the frequency of summer precipitations, this correlation being more pronounced during the first 2 summer months.