Varicella vaccine meningoencephalitis in a child receiving autologous bone marrow transplantation.

BACKGROUND: Varicella vaccine, a live-attenuated Oka-strain of varicella zoster virus (VZV), is a recommended childhood vaccine by many countries. As with wild varicella strain, after primary infection, the live-attenuated virus can establish latency in sensory ganglia and reactivate causing vaccine-strain illnesses: herpes zoster (HZ), visceral or peripheral and central nervous system dissemination. We report a case of early reactivation of live-attenuated virus-HZ and meningoencephalitis-in an immunocompromised child. METHODS: This is a retrospective descriptive report of a case, in a tertiary pediatric hospital, CHU Sainte-Justine (Montréal, Canada). RESULTS: An 18 month-year old girl diagnosed with a primitive neuro-ectodermal tumor (PNET) received the day prior to diagnosis, a first varicella vaccine (MMRV). She received chemotherapy 20 days post MMRV vaccine and autologous bone marrow transplantation 3 months post vaccination. She was considered not eligible, to acyclovir prophylaxis prior transplantation (positive for VZV IgG and negative for herpes simplex virus IgG by ELISA). At day 1 post transplantation, she developed dermatomal HZ and meningoencephalitis. Oka-strain varicella was isolated, she was treated with acyclovir and foscarnet. Neurologic status improved in 5 days. Control of VZV viral load in cerebrospinal fluid showed a slow decrease to from 5.24 log 10 copies/mL to 2.14 log 10 copies/mL in 6 weeks. No relapse was observed. She recovered without neurological sequelae. CONCLUSIONS: Our experience highlights the importance of conducting a thorough medical history regarding vaccination and serological status of newly immunocompromised patients. Intensive chemotherapy succeeding live vaccine administration <4 weeks could have influenced early and severe viral reactivation. Early initiation of prophylactic antiviral treatment is questioned in such circumstances.

Cobertura y barreras de la vacunación contra la varicela en niños que consultaron a la Fundación Salud Bosque / Coverage of and Barriers to Varicella Vaccination in Children at Fundación Salud Bosque / Cobertura e barreiras à vacinação contra varicela em crianças que consultaram a Fundação Salud Bosque

Introducción. Desde la introducción de la vacuna contra la varicela a Colombia no se ha logrado una cobertura mayor al 90%. El objetivo de este trabajo es identificar las barreras de vacunación contra varicela en niños. Metodología. Estudio descriptivo realizado en la Fundación Salud Bosque; se estudiaron 27 pacientes, 18 hombres (67%) y 9 mujeres (33%), incluyendo menores de 18 años con varicela, y excluyendo pacientes con enfermedades ampollosas distintas a varicela y quemaduras. Se hizo una caracterización demográfica. Para las variables cuantitativas se emplearon promedios y desviación estándar, y para las cualitativas la razón de proporción con Stata V12®. Resultados. La incidencia de varicela fue del 0.2%, solo 9 pacientes (33%) habían recibido la primera dosis de la vacuna, ninguno la segunda dosis. El 92.5% requirió incapacidad; el 89% analgésicos; el 63% antihistamínicos y el 26% antibióticos. Discusión. El estudio realizado demuestra una incidencia significativamente menor en contraste con otras cohortes internacionales. En Colombia no se ha alcanzado la cobertura de la vacunación contra la varicela lograda en Uruguay, Costa Rica, Estados Unidos, Australia, Europa y Taiwán dadas las mismas barreras en su aplicación, mientras que en África no se ha introducido la vacuna contra la varicela porque existen otras prioridades como la desnutrición, la malaria y la infección por Virus de la Inmunodeficiencia Humana. Conclusiones. La cobertura de la vacunación no se ha logrado por barreras modificables que incrementan la incidencia y carga de la enfermedad por costos debido a incapacidad, manejo farmacológico y ausentismo escolar. Palabras clave: Cobertura de Vacunación; Incidencia; Niño; Vacuna contra la Varicela; Varicela.

Introduction. Ever since the introduction of the varicella vaccine in Colombia, coverage has not surpassed 90%. The objective of this work is to identify the barriers to varicella vaccination in children. Methodology. A descriptive study conducted at Fundación Salud Bosque. 27 patients were studied - 18 males (67%) and 9 females (33%) - including children under 18 years of age with varicella, and excluding patients with blistering diseases other than varicella and burns. A demographic characterization was conducted. Averages and standard deviations were used for quantitative variables, and the proportion ratio was used for qualitative variables with Stata V12®. Results. The incidence of varicella was 0.2%. Only 9 patients (33%) had received the first dose of the vaccine, and none had received the second dose. 92.5% required sick leave, 89% required painkillers, 63% required antihistamines, and 26% required antibiotics. Discussion. The conducted study shows a significantly lower incidence compared to other international cohorts. Colombia has not achieved the varicella vaccination coverage of Uruguay, Costa Rica, the United States, Australia, Europe and Taiwan due to the barriers to applying it. Meanwhile, the varicella vaccine has not been introduced in Africa because there are other priorities, such as malnutrition, malaria and the Human Immunodeficiency Virus infection. Conclusions. Vaccination coverage has not been achieved because of modifiable barriers that increase the incidence and burden of the disease due to costs of sick leave, pharmacological treatment and school absenteeism. Keywords: Vaccination Coverage; Incidence; Child; Chickenpox Vaccine; Chikenpox.

Introdução. Desde a introdução da vacina contra varicela na Colômbia, não foi alcançada uma cobertura superior a 90%. O objetivo deste trabalho é identificar as barreiras à vacinação contra varicela em crianças. Metodologia. Estudo descritivo realizado na Fundação Salud Bosque. Foram estudados 27 pacientes, 18 homens (67%) e 9 mulheres (33%), incluindo crianças menores de 18 anos com varicela e excluindo pacientes com outras doenças bolhosas que não varicela e queimaduras. Foi feita uma caracterização demográfica. Média e desvio padrão foram utilizados para as variáveis quantitativas e, para variáveis qualitativas, a razão de proporção com Stata V12®. Resultados. A incidência de varicela foi de 0.2%, apenas 9 pacientes (33%) receberam a primeira dose da vacina, nenhum a segunda dose. 92,5% requeriam atestado; 89% analgésicos; 63% anti-histamínicos e 26% antibióticos. Discussão. O estudo realizado mostra uma incidência significativamente menor em comparação com outras coortes internacionais. A Colômbia não tem atingido a cobertura vacinal contra a varicela alcançada no Uruguai, Costa Rica, Estados Unidos, Austrália, Europa e Taiwan, dadas as mesmas barreiras em sua aplicação, enquanto na África a vacina contra a varicela não foi introduzida porque existem outras prioridades como a desnutrição, a malária e a infecção pelo Vírus da Imunodeficiência Humana. Conclusões. A cobertura vacinal não foi alcançada dadas as barreiras modificáveis que aumentam a incidência e carga da doença devido aos custos por atestados, manejo farmacológico e absenteísmo escolar. Palavras-chave: Cobertura Vacinal; Incidência; Criança; Vacina contra Varicela; Varicela

Disseminated vaccine-induced varicella infection in a kidney transplant recipient.

A 33-year-old kidney transplant (KT) recipient presented with a disseminated pruritic, painful, vesicular rash and hepatitis 3 weeks after receiving a varicella vaccine (VAR). A skin lesion biopsy sent to the Centers for Disease Control and Prevention for genotyping confirmed vaccine-strain varicella-zoster virus (VZV) (Oka strain; vOka). The patient was successfully treated with intravenous acyclovir during a prolonged hospital stay. This case supports the contraindication of VAR in adult KT recipients and highlights the potential for severe illness when used in this population. Optimally, VZV-seronegative KT candidates should receive VAR before starting immunosuppressive medications. If this opportunity is missed, the recombinant varicella-zoster vaccine might be considered following transplantation as it is already recommended to prevent herpes zoster in VZV-seropositive immunocompromised adults. Further study is needed as data are limited on the safety and efficacy of recombinant varicella-zoster vaccine for primary varicella prevention in VZV-seronegative immunocompromised adults.

Reações de hipersensibilidade a vacinas / Hypersensitivity reactions to vaccines

O desenvolvimento e a ampliação do uso das vacinas durante décadas contribuíram para o controle e erradicação de doenças infecciosas, causando um grande impacto na saúde pública no mundo. A análise de segurança das vacinas percorre criteriosos processos e fases dos estudos clínicos, um dos pilares essenciais para aprovação regulatória e utilização do produto na população. O evento supostamente atribuído à vacinação e imunização (ESAVI), terminologia atual, é definido como qualquer ocorrência médica indesejada após a vacinação que possui, ou não, uma relação causal com o uso de uma vacina ou outro imunobiológico. Cabe ressaltar que eventos adversos mais raros ou inesperados, incluindo os eventos de hipersensibilidade, poderão ocorrer na fase pós-comercialização, quando as vacinas são aplicadas em milhões de pessoas. Neste artigo, serão discutidos os principais aspectos relacionados aos eventos adversos de hipersensibilidade pós-vacinais de interesse do especialista, e os desafios frente ao reconhecimento do agente causal e conduta a ser adotada. Além disso, serão revisados os potenciais alérgenos presentes nas vacinas de uso rotineiro para auxiliar o profissional de saúde na identificação de pacientes com potencial de risco de ESAVI por tais componentes. A atualização do conhecimento acerca da segurança e dos benefícios das vacinas pelos profissionais de saúde, sobretudo em populações especiais, contribui para condutas em imunização mais apropriadas, reduzindo o risco de exposição a um possível alérgeno em pessoas comprovadamente alérgicas às vacinas ou a alguns dos seus componentes, além de evitar contraindicações desnecessárias em eventos coincidentes ou não graves.

The expansion of vaccine use and development in recent decades has contributed to the control and eradication of infectious diseases, causing a major impact on public health worldwide. Vaccine safety analysis, which involves careful processes and clinical study, is one of the essential pillars of regulatory approval and use in the population. In current terminology, events supposedly attributable to vaccination and immunization (ESAVI) are defined as any unwanted medical occurrence after vaccination that may or may not have a causal relationship with vaccines or other immunobiologicals. It is noteworthy that rare or unexpected adverse events, including hypersensitivity, can occur during the post-marketing phase, when vaccines are administered to millions of people. In this article, we will discuss the main aspects of post-vaccine hypersensitivity events of interest to specialists and challenges to recognizing the causal agent and appropriate clinical practice. Potential allergens in routine vaccines will also be reviewed to help health professionals identify patients with a potential risk of ESAVI due to such components. Updating health professionals' knowledge about the safety and benefits of vaccines, particularly in special populations, can contribute to more appropriate clinical practice regarding immunization, reducing the risk of exposure to possible allergens in people with allergies to vaccines or their components, avoiding unnecessary contraindications in coincidental or non-serious events.

Parental acceptance of and preferences for administration of routine varicella vaccination in the UK: A study to inform policy.

OBJECTIVES: To explore acceptability of and preferences for the introduction of varicella vaccination to the UK childhood immunisation schedule. DESIGN: We conducted an online cross-sectional survey exploring parental attitudes towards vaccines in general, and varicella vaccine specifically, and their preferences for how the vaccine should be administered. PARTICIPANTS: 596 parents (76.3% female, 23.3% male, 0.4% other; mean age 33.4 years) whose youngest child was aged 0-5 years. MAIN OUTCOME MEASURES: Willingness to accept the vaccine for their child and preferences for how the vaccine should be administered (in combination with the MMR vaccine [MMRV], on the same day as the MMR vaccine but as a separate injection [MMR + V], on a separate additional visit). RESULTS: 74.0% of parents (95% CI 70.2% to 77.5%) were extremely/somewhat likely to accept a varicella vaccine for their child if one became available, 18.3% (95% CI 15.3% to 21.8%) were extremely/somewhat unlikely to accept it and 7.7% (95% CI 5.7% to 10.2%) were neither likely nor unlikely. Reasons provided by parents likely to accept the vaccine included protection from complications of chickenpox, trust in the vaccine/healthcare professionals, and wanting their child to avoid their personal experience of chickenpox. Reasons provided by parents who were unlikely included chickenpox not being a serious illness, concern about side effects, and believing it is preferable to catch chickenpox as a child rather than as an adult. A combined MMRV vaccination or additional visit to the surgery were preferred over an additional injection at the same visit. CONCLUSIONS: Most parents would accept a varicella vaccination. These findings highlight parents' preferences for varicella vaccine administration, information needed to inform vaccine policy and practice and development of a communication strategy.

Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: a cohort study from OpenSAFELY.

BACKGROUND: While the vaccines against COVID-19 are highly effective, COVID-19 vaccine breakthrough is possible despite being fully vaccinated. With SARS-CoV-2 variants still circulating, describing the characteristics of individuals who have experienced COVID-19 vaccine breakthroughs could be hugely important in helping to determine who may be at greatest risk. METHODS: With the approval of NHS England, we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY-TPP database of fully vaccinated individuals, linked to secondary care and death registry data and described the characteristics of those experiencing COVID-19 vaccine breakthroughs. RESULTS: As of 1st November 2021, a total of 15,501,550 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: ​107-179). From within this population, a total of 579,780 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate (IR) was 98.06 (95% CI 97.93-98.19). There were 28,580 COVID-19-related hospital admissions, 1980 COVID-19-related critical care admissions and 6435 COVID-19-related deaths; corresponding IRs 4.77 (95% CI 4.74-4.80), 0.33 (95% CI 0.32-0.34) and 1.07 (95% CI 1.06-1.09), respectively. The highest rates of breakthrough COVID-19 were seen in those in care homes and in patients with chronic kidney disease, dialysis, transplant, haematological malignancy or who were immunocompromised. CONCLUSIONS: While the majority of COVID-19 vaccine breakthrough cases in England were mild, some differences in rates of breakthrough cases have been identified in several clinical groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the number of positive SARS-CoV-2 tests still occurring is concerning and as numbers of fully vaccinated (and boosted) individuals increases and as follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, to assess vaccine waning and rates of breakthrough COVID-19 between different variants, aimed at identifying individuals at higher risk, are needed.

Situação vacinatória da tríplice e da tetra viral em crianças matriculadas na Educação Infantil / The vaccination situation of triple and tetra viral in children enrolled in Early Childhood Education

Objetivo Descrever a situação vacinal de crianças matriculadas nos Centros Municipais de Educação Infantil da Zona Sul do município de Natal, Rio Grande do Norte com relação às vacinas de tríplice e tetra viral. Método Trata-se de um estudo epidemiológico, descritivo e retrospectivo, realizado a partir da análise de cartões de vacina de crianças matriculadas em 15 instituições, nas quais foi possível reunir 773 cartões que foram analisados a partir do calendário básico de vacinação do ano 2015. Os cartões foram classificados em: esquema vacinal completo, incompleto e/ou não vacinado. Resultados Observou-se que 576 (75,51%) crianças estavam com o esquema vacinal completo, sendo o esquema considerado finalizado com a segunda dose da tríplice ou com a tetra viral. A melhor situação vacinal foi atingida nas crianças de dois a quatro anos, com uma cobertura de 84,31%, sendo que 83,3% das crianças dessa faixa etária estavam com o esquema completo e 12,79% das crianças estavam com o esquema vacinal incompleto. Um total de 67 crianças (8,66%) não apresentaram registros de vacina. Com relação à tetra viral, 226 crianças (29,73%) apresentaram esquema vacinal completo. Conclusão Os resultados obtidos no presente estudo revelam uma situação vacinal abaixo da meta estabelecida pelo Programa Nacional de Imunização.

Objective To describe a vaccination situation of children up to 8 years old from the Municipal Centers of Early Childhood Education in the South Zone of the city of Natal, Rio Grande do Norte for vaccines of triple and tetra viral. Method This is an epidemiological, descriptive and retrospective study, carried out based on the analysis of vaccination cards for children from 15 institutions, where it was possible to gather 773 cards, a course based on the basic calendar of the year 2015. They were classified in: complete, incomplete and/or unvaccinated vaccination schedule. Results It is observed that 576 (75.51%) of the children have a complete vaccination schedule, the schedule being completed with a second dose of triple or tetra viral. The best vaccination status was achieved in children aged 2 to 4 years with a coverage of 84.31% and 83.3% children with the complete regimen. We have 12.79% of children with an incomplete vaccination schedule. A total of 67 children (8.66%) who did not have any vaccine records. Regarding Tetra Viral, 226 children (29.73%) had a complete vaccination schedule. Conclusion The results obtained in this study reveal a vaccination situation below the target established by the National Immunization Program.

Caracterización clínica y de costos de la hospitalización asociada a varicela en niños de la Región Metropolitana y de Valparaíso, Chile / Clinical and cost characterization of hospitalization associated with varicella in children from the Metropolitan Region and Valparaíso, Chile

INTRODUCCIÓN: La varicela es una infección relevante en la salud pública de Chile, pudiendo causar en algunas ocasiones complicaciones graves e incluso la muerte, lo que se asocia a un significativo gasto en salud. En Chile sólo se realiza vigilancia centinela a nivel ambulatorio, sin conocerse el impacto de la varicela en casos más graves que determinan hospitalización. OBJETIVOS: Realizar una descripción clínica y de los costos asociados a la atención de niños hospitalizados con diagnóstico de varicela, en años previos a la introducción de la vacuna en el Programa Nacional de Inmunización en Chile. MATERIALES Y MÉTODOS: Estudio multicéntrico, observacional y retrospectivo, en todos los casos de niños hospitalizados (0-15 años) con diagnóstico de varicela, entre enero de 2011 y diciembre de 2015 en cinco hospitales de Chile. Se realizó revisión de fichas para evaluar características clínicas de la enfermedad y los costos asociados a la hospitalización por varicela. RESULTADOS: Un total de 685 hospitalizaciones por varicela fueron incluidas en el estudio. La mediana de edad fue de 3 años (RIC:1-5), siendo la mayoría de los niños con edades comprendidas entre los 1 y 4 años (52% del total de casos). El 56% fueron hombres y sólo 7 niño s (1%) tuvieron antecedente de vacuna varicela. La mediana de días de hospitalización fue de 3 días en cada episodio (RIC: 2-5). El 13% de los casos requirió hospitalización en unidades de mayor complejidad, 7% de los niños ingresó a Unidad de Tratamiento Intensivo y 6% ingresó a Intermedio, ambos con una mediana de 3 días de hospitalización. Las principales complicaciones fueron: infección de piel y tejidos blandos (42%), alteraciones neurológicas (8%) y shock séptico/tóxico (4%). La letalidad fue de 0,4%. El costo de un caso de varicela considerando los costos directos fue de US$417, el costo indirecto fue de US$224 y los costos proporcionales de una muerte de US$3.575. Se estima que el costo total de un caso de varicela hospitalizado en Chile, considerando todos los factores anteriores, fue de US$4.216. CONCLUSIONES: La varicela es una enfermedad inmunoprevenible frecuente. Se observaron casos con una mediana de 3 días de hospitalización por complicaciones, con 13% de los casos requiriendo hospitalización en unidades de mayor complejidad, con un alto costo asociado, que se estima podría disminuir significativamente con la reciente incorporación de la vacuna al Programa Nacional de Inmunizaciones.

BACKGROUND: Varicella is a relevant infection in Chile and may cause serious complications and death, which could be associated with significant health care resource utilization and associated costs. In Chile, sentinel surveillance is carried out only on an outpatient basis, without knowing the impact of varicella in serious cases who need to be hospitalized. AIM: To describe the clinical characteristics and the costs associated with hospitalized children with diagnosis of varicella prior to the vaccine introduction in the National Immunization Program in Chile. PATIENTS AND METHODS: A multicenter, observational, and retrospective study in hospitalized children (0-15 years) with a diagnosis of varicella, were conducted in five hospitals in Chile between January 2011 and December 2015. A review of the clinical records was performed to evaluate the clinical characteristics of the disease and costs associated with hospitalization episodes for varicella. RESULTS: A total of 685 hospitalized children for varicella were included in this study. The median age was 3 years (IQR: 1-5), most children were between 1 and 4 years of age (52% of total cases). 56% were male, and only 7 patients (1%) had a history of previous varicella vaccination. The median lenght of days of hospitalization was 3 days (IQR: 2-5). 13% of the cases required hospitalization in a more complex care unit, 6% in the intermediate unit and 7% in the pediatric intensive treatment unit, both with a median stay of 3 days. The main complications were: skin and soft tissue infections (42%), neurologic (8%) and septic or toxic shock (4%). There were 3 cases of death (0.4%). The direct cost of a varicella case was US $ 417, the indirect cost was US $ 224 and the proportional cost of a case of death was US $ 3,575. It is estimated that the total cost of a hospitalized varicella case in Chile was US $ 4,216. CONCLUSIONS: Varicella is associated with a significant burden of disease in Chile. The median hospital stay was three days with 13% of cases requiring medical care in a complex unit, with high associated costs which could be significantly reduced with the recently incorporation of the varicella vaccine into the National Immunization Program.

Live Attenuated Varicella Vaccine: Prevention of Varicella and of Zoster.

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate.

Number of cases of varicella and hospitalization in a pediatric reference hospital in brazil after introducing the vaccine / Avaliação do número de casos e do perfil de internações por varicela em hospital pediátrico após a introdução da vacina

ABSTRACT Objective: To assess the number of cases and the profile of hospitalizations from varicella after the introduction of the measles, mumps, rubella and varicella combination vaccine in the public health system. Methods: Retrospective study in an infectious diseases pediatric hospital of reference in Southeast Brazil. The cases with a clinical diagnosis of varicella, from January 2011 to June 2016, were assessed from pediatricians' medical records. The hospitalizations were classified into a pre-vaccine group and post-vaccine group, based on the date the vaccine was introduced (September 2013). Both groups were compared by age, sex, time of hospitalization, reason for hospitalization, hospital complications, duration of intensive care, and clinical outcome. Results: A total of 830 hospitalizations were recorded; 543 in the pre-vaccine period and 287 in the post-vaccine period, a reduction of 47.1% (p<0.001). In both periods, a similar profile in the hospitalizations was noticed: majority male; aged between one to five years old; most complications due to secondary causes (mainly skin infections); main outcome was clinical improvement and discharge from the hospital. In the pre-vaccine period, six deaths were recorded and two were recorded in the post-vaccine period. Conclusions: The profile of the hospitalizations was expected to stay the same since this study did not compare vaccinated with unvaccinated children, but hospitalizations before and after the vaccine was introduced. In accordance with the medical literature, we found a significant fall in the number of hospitalizations from varicella.

RESUMO Objetivo: Avaliar o número de casos e o perfil das internações por varicela após a introdução da vacina quádrupla viral na rede pública. Métodos: Estudo retrospectivo conduzido em hospital pediátrico referência em doenças infectocontagiosas na Região Sudeste do Brasil. Foram avaliados os casos com diagnóstico clínico de varicela, registrados em prontuário por médico pediatra, de janeiro de 2011 até junho de 2016. As internações foram classificadas em grupo pré-vacinal e grupo pós-vacinal, com base na data de introdução da vacina (setembro de 2013). Os grupos foram comparados em relação a: faixa etária, sexo, tempo de hospitalização, causas da internação, complicações hospitalares, tempo da internação em terapia intensiva e desfecho clínico. Resultados: Foram documentadas 830 internações, 543 no período pré-vacinal e 287 no pós-vacinal, ocorrendo redução de 47,1% nas internações (p<0,001). Em ambos os períodos, notou-se um perfil similar das internações, predominantemente: sexo masculino; faixa etária de um a cinco anos; por causas secundárias (principalmente infecções de pele); evoluindo com melhora clínica e alta hospitalar. Em relação ao número de óbitos, ocorreram seis no período pré-vacinal e dois no pós-vacinal. Conclusões: A manutenção do perfil das internações era esperada, visto que o trabalho não comparou crianças vacinadas com não vacinadas, e sim internações pré e pós-vacinais. Observou-se, em concordância com a literatura, queda substancial no número de internações por varicela.

Incorporación de segunda dosis de la vacuna de la varicela al Calendario Nacional de Vacunación de Argentina / Incorporation of the second dose of the varicella vaccine to the national vaccination schedule of Argentina

A partir de 2022, a la dosis de vacuna contra la varicela contemplada a los 15 meses de edad en el Calendario Nacional de Vacunación de Argentina, se suma una segunda dosis al ingreso escolar. En este artículo se repasan los aspectos clave para la implementación de esta práctica de inmunización universal, gratuita y obligatoria. (AU)

Starting in 2022, a second dose of the varicella vaccine will be added to the 15-month-old dose included in Argentina's National Vaccination Schedule at school entry. This article reviews the key aspects for the implementation of this universal, free and mandatory immunization practice. (AU)

Varicella-zoster virus: molecular controls of cell fusion-dependent pathogenesis.

Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) and shingles (zoster). Although considered benign diseases, both varicella and zoster can cause complications. Zoster is painful and can lead to post herpetic neuralgia. VZV has also been linked to stroke, related to giant cell arteritis in some cases. Vaccines are available but the attenuated vaccine is not recommended in immunocompromised individuals and the efficacy of the glycoprotein E (gE) based subunit vaccine has not been evaluated for the prevention of varicella. A hallmark of VZV pathology is the formation of multinucleated cells termed polykaryocytes in skin lesions. This cell-cell fusion (abbreviated as cell fusion) is mediated by the VZV glycoproteins gB, gH and gL, which constitute the fusion complex of VZV, also needed for virion entry. Expression of gB, gH and gL during VZV infection and trafficking to the cell surface enables cell fusion. Recent evidence supports the concept that cellular processes are required for regulating cell fusion induced by gB/gH-gL. Mutations within the carboxyl domains of either gB or gH have profound effects on fusion regulation and dramatically restrict the ability of VZV to replicate in human skin. This loss of regulation modifies the transcriptome of VZV infected cells. Furthermore, cellular proteins have significant effects on the regulation of gB/gH-gL-mediated cell fusion and the replication of VZV, exemplified by the cellular phosphatase, calcineurin. This review provides the current state-of-the-art knowledge about the molecular controls of cell fusion-dependent pathogenesis caused by VZV.

Impact of the tetra viral vaccine introduction on varicella morbidity and mortality in the Brazilian macro regions / Impacto da introdução da vacina tetra viral na morbimortalidade por varicela nas macrorregiões brasileiras

Abstract Objective: To describe the impact of the introduction of the viral tetra vaccine in the National Immunization Program in 2013 for 15-month-old children in mortality rates and hospitalization associated with varicella in Brazil. Methods: Mortality rates and hospitalizations rates associated with varicella were evaluated between 2010 and 2016 and described according to Brazilian macro regions and age. The population was stratified into age groups: < 1 year, 1-4 years, and 5-14 years. Data were collected from the Informatics Department of the Unified Health System. A percentage difference was calculated between rates of hospitalizations and mortality in the pre (2010-2012) and post-vaccination periods (2014-2016) to estimate the approximate effectiveness of the vaccine. Data synthesis: At the national level, vaccination significantly reduced the mortality rates and hospitalizations rates in all age groups analyzed. Among those under 5 years of age, mortality rates and hospitalizations rates decreased 57-49% and 40-47%, respectively. There was a national decrease of up to 57% in the mortality rates due to the disease, with smaller decreases seen in the North and Northeast regions and the largest in the South and Southeast regions. The hospitalizations rates for varicella reached a maximum national decline of 47%. In children aged 1-4 years, with higher vaccination coverage, the highest reduction was observed in both mortality rates and hospitalizations rates, which decreased from 2.6 to 0.4/100,000/year. Conclusions: The tetra vaccine proved to be effective in reducing both mortality and hospitalizations of children and adolescents up to 15 years of age in the 2014-2016 triennium.

Resumo Objetivo: Descrever o impacto da introdução da vacina tetra viral no Programa Nacional de Imunização em 2013 para crianças de 15 meses nas taxas de mortalidade e de internação hospitalar associadas à varicela no Brasil. Métodos: As taxas de mortalidade e de internação hospitalar associadas à varicela foram avaliadas entre 2010 e 2016 e descritas conforme macrorregiões brasileiras e idade. A população foi estratificada em grupos etários: < 1 ano; 1-4 e 5-14 anos. Os dados foram coletados do Departamento de Informática do Sistema Unificado de Saúde. Foi realizado um cálculo de diferença percentual entre taxas de internações e mortalidade nos períodos pré (2010-2012) e pós-vacinal (2014-2016) para estimativa de impacto da vacina. Resultados: No nível nacional, a vacinação reduziu significativamente as taxas de mortalidade e de internação hospitalar em todas faixas etárias analisadas. Entre os menores de 5 anos, a taxas de mortalidade e de internação hospitalar diminuíram 57-49% e 40-47%, respectivamente. Houve uma queda nacional de até 57% nos índices de mortalidade pela doença, com menores quedas vistas nas regiões Norte e Nordeste e as maiores nas regiões Sul e Sudeste. As taxas de internação hospitalar por varicela atingiram queda nacional máxima de 47%. Em crianças de 1-4 anos, com maior cobertura vacinal, foi observada a maior redução tanto na taxa de internação hospitalar como na taxa de mortalidade, a qual passou de 2,6 para 0,4/100.000/ano. Conclusões: A vacinação se mostrou efetiva em reduzir tanto mortalidade quanto hospitalizações das crianças e adolescentes de até 15 anos no triênio 2014-2016.

Routine Childhood Vaccines Given From 1 through 18 Years of Age.

In addition to the vaccines due in the first year of life, the US Advisory Committee on Immunization Practices recommends that children continue to receive vaccines regularly against a variety of infectious diseases. Starting at 12 to 15 months of life, these include the two-dose measles-mumps-rubella vaccine series and the two-dose varicella vaccine series. Also in the second year of life, infants should begin the two-dose hepatitis A vaccine series and complete the Haemophilus influenzae type B vaccine series as well as the pneumococcal conjugate vaccine series. Before 19 months of life, infants should receive the third dose of the poliovirus vaccine and the fourth dose of diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The final doses of poliovirus and tetanus-diphtheria-acellular pertussis vaccines are both due at 4 to 6 years of life. Before each influenza season, every child should receive the influenza vaccine. Those less than 9 years of age who previously received less than two doses need two doses a month apart. At 11 to 12 years of life, all should get two doses of the human papillomavirus vaccine, the adolescent/adult version of the tetanus-diphtheria-acellular pertussis vaccine, and begin a two-dose series of meningococcal ACWY vaccine. Each of these vaccines is due when the vaccine works to protect against both an immediate risk as well as to provide long-term protection. Each vaccine-preventable disease varies in terms of the nature of exposure, the form of the morbidity, the risk of mortality, and potential to prevent or ameliorate its harm.

Efectividad preventiva de la vacuna varicela en pacientes sanos no expuestos / Preventive effectiveness of varicella vaccine in healthy unexposed patients

INTRODUCCIÓN: La varicela es una enfermedad infectocontagiosa producida por el virus varicela-zóster. Para su prevención, convencionalmente se utiliza la vacuna varicela, cuya administración busca disminuir la aparición de enfermedad y sus complicaciones. Sin embargo, aún existe controversia sobre la efectividad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Se identificaron dos revisiones sistemáticas que en conjunto incluyeron 16 estudios primarios, de los cuales, tres corresponden a ensayos aleatorizados. Concluimos que la vacunación contra la varicela disminuye el riesgo de contraer la enfermedad a largo plazo en pacientes sanos sin exposición previa y que probablemente disminuye el riesgo de contraer la enfermedad a corto plazo. Sin embargo, aumenta la reacción local 48 horas posterior a su administración y probablemente aumenta la aparición de fiebre y varicela-like rash.

INTRODUCTION: Chickenpox is an infectious disease caused by varicella-zoster virus. Varicella vaccine is conventionally used for its prevention, and its administration seeks to reduce the onset of the disease and complications associated. However, there is still controversy about its effectiveness. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews including 16 studies overall, of which three were randomized trials. We concluded that the varicella vaccine decreases the risk of contracting the disease in the long term and probably reduces the risk of developing the disease in the short term in healthy unexposed patients. Nevertheless, the vaccination increases the occurrence of local reactions 48 hours after its administration and probably increases the presence of fever and chickenpox-like rash.

Vaccination With Live Attenuated Vaccines in Four Children With Chronic Myeloid Leukemia While on Imatinib Treatment.

Chronic myeloid leukemia (CML) in childhood and adolescence is a rare malignancy that can successfully be treated with the tyrosine kinase inhibitor (TKI) imatinib. According to the current experience, treatment is necessary for years and, in the majority of cases, a lifelong approach is required to control the malignant disease. To what extent imatinib causes immunosuppression in different age cohorts is a controversial discussion. According to general medical recommendations, live vaccines are contraindicated in individuals treated with imatinib. However, a recent increase in the number of globally reported cases of measles has been observed and continues to rise. Due to the high contagiousness of the virus, near-perfect vaccination coverage (herd immunity of 93 to 95%) is required to effectively protect against measles resurgence-a scenario that is not realistic in many countries. When four teenagers with CML (median age 13 years, range 12-15) who were enrolled into pediatric trial CML-paed II while on imatinib treatment (median treatment duration 36 months, range 11-84) were identified without protective measles and/or varicella titers, we carefully balanced the risks of a live vaccination under immunosuppressive TKI medication against the benefit of being protected. The patients underwent live vaccination with the live attenuated vaccines M-M-RVAX Pro® and Varivax® simultaneously (Patient #1), Priorix® and Varilix® consecutively (Patient #2), and Priorix® (Patients #3 and #4). While the first three patients were vaccinated while receiving TKI therapy, treatment with imatinib was interrupted in patient #4 for 1 week prior and 2 weeks after vaccination. Patients #1 and #3 reacted with stable long-term seroconversion. In Patient #2, serum titer conversion against measles and varicella could not be demonstrated and thus revaccination with Priorix® and Varilix® was performed 3 years later. However, protective titers did not develop or were lost again. Patient #4 also lost protective titers against measles when assessed 10 months after vaccination, but revaccination resulted in stable seroprotective titers over 12 months after the last vaccination during ongoing imatinib treatment. We conclude that in all patients, the safety of live vaccines could be documented, as no acute or late adverse events were observed. However, in line with observations that memory B-cells are lost under exposure to imatinib, revaccination may become necessary (two out of four patients in this small series lost their seroprotection). Considering that the number of cases is very small, we also suggest some criteria for decision-making regarding live vaccinations of CML patients treated with imatinib.

Vaccines for measles, mumps, rubella, and varicella in children.

BACKGROUND: Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012. OBJECTIVES: To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE. MAIN RESULTS: We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.