Herpes zóster en lactantes. Presentación de tres casos / Herpes zoster in infants. Three cases report

RESUMEN El herpes zóster es una afección infrecuente en lactantes, con una incidencia de 0,74/1 000 habitantes. Se produce por la reactivación del virus de la varicela zóster, tras una primoinfección por varicela. Puede ocurrir intraútero, por lo que resulta relevante conocer los antecedentes maternos. El diagnóstico es clínico y si se realiza de forma adecuada reduce el riesgo de complicaciones. El tratamiento en los niños es sintomático, porque su evolución es más favorable que en los adultos. Debido a la rareza de esta entidad, se presentan tres casos de herpes zóster en lactantes de 4, 6 y 11 meses de edad, que acudieron con lesiones y evolución típica de esta enfermedad al Hospital Pediátrico Provincial Docente Eliseo Noel Caamaño, de Matanzas, entre septiembre y octubre de 2017 (AU).

ABSTRACT Herpes zoster is an uncommon affection in infants, with an incidence of 0.74/1 000 inhabitants. It is produced by the reactivation of the varicella-zoster virus, after a primary infection by varicella. This can occur inside the uterus, making it relevant to know maternal antecedents. The diagnosis is clinical, and if it is made in an appropriate way, reduces complication risk. The treatment in children is symptomatic because its evolution is more favorable than in adults. Due to the rareness of this entity, we present three cases of herpes zoster in nurslings aged 4, 6 and 11 moths who assisted the Teaching Pediatric Hospital Eliseo Noel Caamaño, of Matanzas, with lesions and typical evolution of this disease in the period September-October 2017 (AU).

Cost-effectiveness of varicella and herpes zoster vaccination in Sweden: An economic evaluation using a dynamic transmission model.

OBJECTIVES: Comprehensive cost-effectiveness analyses of introducing varicella and/or herpes zoster vaccination in the Swedish national vaccination programme. DESIGN: Cost-effectiveness analyses based on epidemiological results from a specifically developed transmission model. SETTING: National vaccination programme in Sweden, over an 85- or 20-year time horizon depending on the vaccination strategy. PARTICIPANTS: Hypothetical cohorts of people aged 12 months and 65-years at baseline. INTERVENTIONS: Four alternative vaccination strategies; 1, not to vaccinate; 2, varicella vaccination with one dose of the live attenuated vaccine at age 12 months and a second dose at age 18 months; 3, herpes zoster vaccination with one dose of the live attenuated vaccine at 65 years of age; and 4, both vaccine against varicella and herpes zoster with the before-mentioned strategies. MAIN OUTCOME MEASURES: Accumulated cost and quality-adjusted life years (QALY) for each strategy, and incremental cost-effectiveness ratios (ICER). RESULTS: It would be cost-effective to vaccinate against varicella (dominant), but not to vaccinate against herpes zoster (ICER of EUR 200,000), assuming a cost-effectiveness threshold of EUR 50,000 per QALY. The incremental analysis between varicella vaccination only and the combined programme results in a cost per gained QALY of almost EUR 1.6 million. CONCLUSIONS: The results from this study are central components for policy-relevant decision-making, and suggest that it was cost-effective to introduce varicella vaccination in Sweden, whereas herpes zoster vaccination with the live attenuated vaccine for the elderly was not cost-effective-the health effects of the latter vaccination cannot be considered reasonable in relation to its costs. Future observational and surveillance studies are needed to make reasonable predictions on how boosting affects the herpes zoster incidence in the population, and thus the cost-effectiveness of a vaccination programme against varicella. Also, the link between herpes zoster and sequelae need to be studied in more detail to include it suitably in health economic evaluations.

Exploring the Seasonal Drivers of Varicella Zoster Virus Transmission and Reactivation.

Varicella zoster virus (VZV) is a herpesvirus that causes chickenpox and shingles. The biological mechanisms underpinning the multidecadal latency of VZV in the body and subsequent viral reactivation-which occurs in approximately 30% of individuals-are largely unknown. Because chickenpox and shingles are endemic worldwide, understanding the relationship between VZV transmission and reactivation is important for informing disease treatment and control. While chickenpox is a vaccine-preventable childhood disease with a rich legacy of research, shingles is not a notifiable disease in most countries. To date, population-level studies of shingles have had to rely on small-scale hospital or community-level data sets. Here, we examined chickenpox and shingles notifications from Thailand and found strong seasonal incidence in both diseases, with a 3-month lag between peak chickenpox transmission season and peak shingles reactivation. We tested and fitted 14 mathematical models examining the biological drivers of chickenpox and shingles over an 8-year period to estimate rates of VZV transmission, reactivation, and immunity-boosting, wherein reexposure to VZV boosts VZV-specific immunity to reinforce protection against shingles. The models suggested that the seasonal cycles of chickenpox and shingles have different underlying mechanisms, with ambient levels of ultraviolet radiation being correlated with shingles reactivation.

Pox Parties for Grannies? Chickenpox, Exogenous Boosting, and Harmful Injustices.

Some societies tolerate or encourage high levels of chickenpox infection among children to reduce rates of shingles among older adults. This tradeoff is unethical. The varicella zoster virus (VZV) causes both chickenpox and shingles. After people recover from chickenpox, VZV remains in their nerve cells. If their immune systems become unable to suppress the virus, they develop shingles. According to the Exogenous Boosting Hypothesis (EBH), a person's ability to keep VZV suppressed can be 'boosted' through exposure to active chickenpox infections. We argue that even if this hypothesis were true, immunization policies that discourage routine childhood varicella vaccination in order to prevent shingles for other people are unethical. Such policies harm children and treat them as mere means for the benefit of others, and are inconsistent with how parents should treat their children and physicians should treat their patients. These policies also seem incompatible with institutional transparency.

[Revised multidisciplinary guidelines 'Varicella'; broader indication for post-exposure prophylaxis]. / Herziene multidisciplinaire richtlijn 'Varicella'.

Post-exposure prophylaxis (PEP) with varicella zoster immunoglobulins (VZIG) should be administered as soon as possible after exposure to the virus, but always within ten days; in the previous guidelines this was within 96 hours. In cases of perinatal exposure, PEP with VZIG should be administered to neonates if the mother develops clinical chickenpox between seven days before delivery and seven days after delivery; in the previous guidelines this was between five days before delivery and two days after delivery. A new chapter on the treatment of chickenpox has been added to the guidelines.

Mother-to-Child Transfer of Reactivated Varicella-Zoster Virus DNA and Varicella-Zoster IgG in Pregnancy.

Stress-induced subclinical reactivation of varicella-zoster virus (VZV) has been studied previously. However, subclinical reactivation of VZV induced by the stress of pregnancy has not been investigated. The objective was to study varicella DNA and varicella antibody levels in mothers and their newborn babies. VZV immunoglobulin G (IgG) levels in 350 mother-newborn dyads were studied using indirect enzyme-linked immunosorbent assay testing. A subset of 73 dyads was selected, DNA was isolated from the serum samples, and quantitative polymerase chain reaction (qPCR) was performed. Nearly 15% (14.6%) mothers tested were positive for varicella antibodies (>100 mIU/dL) and 16% were borderline (<100 and >50 mIU/dL). Approximately 16.9% of the babies were positive, and 18% were in borderline. Among those tested for VZV-DNA, 70% of mothers with low VZ-IgG (<100 mIU/dL) and 11.32% of those with high VZ-IgG (>100 mIU/dL) were positive for DNA. Among the newborns, 60% of those with low VZ-IgG and 15% of those with high VZ-IgG were positive for DNA. Mothers who have had VZV infection in the past can transmit VZV DNA to their babies.

Cost-effectiveness analysis of universal varicella vaccination in Turkey using a dynamic transmission model.

BACKGROUND: In 2013, Turkey introduced one-dose universal varicella vaccination (UVV) at 12 months of age. Inclusion of a second dose is being considered. METHODS: We developed a dynamic transmission model to evaluate three vaccination strategies: single dose at 12 months (1D) or second dose at either 18 months (2D-short) or 6 years of age (2D-long). Costs and utilization were age-stratified and separated into inpatient and outpatient costs for varicella and herpes zoster (HZ). We ran the model including and excluding HZ-related costs and impact of exogenous boosting. RESULTS: Five years post-introduction of UVV (1D), the projected varicella incidence rate decreases from 1,674 cases pre-vaccine to 80 cases/100,000 person-years. By 25 years, varicella incidence equilibrates at 39, 12, and 16 cases/100,000 person-years for 1D, 2D-short, and 2D-long strategies, respectively, using a highly effective vaccine. With or without including exogenous boosting impact and/or HZ-related costs and health benefits, the 1D strategy is least costly, but 2-dose strategies are cost-effective considering a willingness-to-pay threshold equivalent to the gross domestic product. The model predicted a modest increase in HZ burden during the first 20-30 years, after which time HZ incidence equilibrates at a lower rate than pre-vaccine. CONCLUSIONS: Our findings support adding a second varicella vaccine dose in Turkey, as doing so is highly cost-effective across a wide range of assumptions regarding the burden associated with varicella and HZ disease.

Models for optimally controlling varicella and herpes zoster by varicella vaccination: a comparative study.

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries mainly because of the "fear" of a subsequent boom in natural herpes zoster (HZ) incidence in the first decades after the initiation of vaccination, caused by the expected decline in the protective effect of natural immunity boosting due to reduced virus circulation. Optimal control theory has proven to be a successful tool in understanding ways to curtail the spread of infectious diseases by devising the optimal disease intervention strategies. In this paper, we describe how a reduced 'toy' model can extract the essentials of the dynamics of the VZV transmission and reactivation in case of the study of optimal paths of varicella immunization programs. Results obtained using different optimization approaches are compared with the ones of a more realistic age-structured model. The reduced model shows some unreliable predictions in regards of model time scales about herpes zoster dynamic; nevertheless, it is able to reproduce the main qualitative dynamic of the more realistic model to the different optimization problems, while requiring a minimal number of parameters to be identified. Graphical abstract ᅟ.

Descriptive epidemiology of varicella based on national surveillance data before and after the introduction of routine varicella vaccination with two doses in Japan, 2000-2017.

Routine childhood immunization using two doses of the varicella vaccine was introduced in Japan in October 2014. In this study, we analyzed the data extracted from national varicella surveillance, including pediatric sentinel surveillance from 2000 to 2017 and hospitalized varicella surveillance from the 38th week of 2014 to the 37th week of 2017. Compared with the 2000-2011 baseline data, the number of varicella cases per sentinel decreased substantially by 76.6% overall and by 88.2% among children aged 1-4 years in 2017. Of 997 hospitalized patients, we found a decreasing trend in the number of cases among children aged <5 years. We also found a decreasing trend in the number of cases with complications among children aged 1-4 years. Data on the self-reported transmission sites in 35.5% (354/997) of the hospitalized varicella patients showed that transmission of varicella zoster virus (VZV) occurred frequently in household, at school for young children, in the workplace for adults, and at hospital for all age groups. Data from 29.0% (289/997) of the hospitalized patients with a self-reported source of infection showed that transmission of VZV occurred from a patient with herpes zoster (HZ) in 30.4% (88/289) of cases. Our data demonstrate a substantial decrease in the number of varicella cases in young children following introduction of routine childhood vaccination program with two-dose varicella vaccination in Japan. These data highlight the unique aspects of transmission sites across age groups and the important role of HZ cases in disease circulation.

Administrative Data to Explore the Role of Family History as a Risk Factor for Herpes Zoster.

We used administrative data to study the impact of family history on the risk of herpes zoster (HZ). Our HZ cases and our HZ family history were both ascertained on the basis of medically attended diagnoses, without reliance on self-report or recall bias. Family history was associated with HZ risk among both siblings and parents. The strength of the association differed when the index child was latently infected with vaccine-strain vs wild-type varicella zoster virus.

Apparent seronegative maternal shingles with post-natal mother-to-baby transmission of varicella zoster virus.

We present an unusual case of varicella zoster (VZ) virus IgG negative, yet clinically apparent, maternal shingles, which prompted the administration of VZ immunoglobulin to the newborn. The mother had no previous VZ vaccination. Eleven days later the baby developed a primary VZ infection, with only mild disease, likely as a result of the VZ immunoglobulin. The variable sensitivity of VZV IgG-specific assays is well-recognized. Thus, the ability of this particular VZV IgG assay to detect both maternal and infant VZV IgG, post-natally, suggests that the earlier VZV IgG negative results were due to lower circulating levels of maternal antibody.

Herpes zoster in hospitalized adults: Practice gaps, new evidence, and remaining questions.

Herpes zoster can present many uncertainties for consulting dermatologists. We review the current guidelines and recent literature on important issues that arise in the care of hospitalized patients with herpes zoster, including infection control isolation practices, treatment courses for zoster and acute zoster-associated pain, and indications for long-term prophylaxis. We present the findings of an inpatient zoster management practices survey of the membership of the Society of Dermatology Hospitalists, an expert resource group of the American Academy of Dermatology, and discuss directions for future investigation and potential opportunities for management improvements in light of these collective data.

Projections of zoster incidence in Australia based on demographic and transmission models of varicella-zoster virus infection.

Re-exposure to varicella infection is believed to delay the occurrence of herpes zoster (HZ), which has led to predictions of increased HZ following introduction of varicella vaccination programs. However, there is evidence of rising HZ rates before vaccination was introduced. Here, we explore a potential explanation for this effect through demographic change leading to reductions in varicella exposure and boosting in the context of Australia over the 20th century. To study this hypothesis, we integrated observed changes in Australian birth and age-specific death rates with a varicella transmission model. The model was then calibrated to age-specific pre-vaccination seroprevalence (1997-9) and hospitalization data (1993-2009). Model simulations predicted that declining birth rates led to a 50% reduction in varicella incidence over the 20th century. When combined with the impacts of an aging population, the simulations further suggested that HZ incidence should have increased by 50% over the 20th century. However, we found that after age-standardization, the residual increase in HZ due to reduced boosting was only about 8% over the 20th century. Results were also sensitive to the assumed duration of immunity to HZ and whether multiple HZ episodes were possible. Despite a strong predicted effect of demographic change on varicella incidence, our findings suggest that improved survival is the main contributor to any rise in HZ rates prior to vaccination in Australia. Removing survival effects through age-standardization is recommended when considering epidemiologic or model-based analysis of past trends in HZ.

The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster.

We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.

Viral Genome Sequencing Proves Nosocomial Transmission of Fatal Varicella.

We report the first use of whole viral genome sequencing to identify nosocomial transmission of varicella-zoster virus with fatal outcome. The index case patient, nursed in source isolation, developed disseminated zoster with rash present for 1 day before being transferred to the intensive care unit (ICU). Two patients who had received renal transplants while inpatients in an adjacent ward developed chickenpox and 1 died; neither patient had direct contact with the index patient.