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)

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.

Varicella zoster virus related deaths and hospitalizations before the introduction of universal vaccination with the tetraviral vaccine / Óbitos e internações relacionados ao vírus varicela-zoster antes da introdução da vacinação universal com a vacina tetravalente

Abstract Objective: To characterize varicella zoster virus-related deaths and hospitalizations in Brazil before universal vaccination with the tetravalent (measles, mumps, rubella, and varicella) vaccine, attempting to collect baseline data on varicella morbidity and mortality in order to evaluate the impact of the varicella vaccination program. Methods: Varicella-associated mortality data were evaluated between 1996 and 2011 and varicella zoster virus-associated hospitalizations between 1998 and 2013. Data were gathered from the Informatics Department of the Unified Health System, considering the International Classification of Diseases, 10th Revision, code B01. All age groups were assessed. Varicella-specific mortality rates were calculated and seasonality of varicella-zoster virus-associated hospitalizations was described. Results: There were 2334 varicella deaths between 1996 and 2011, 19.3% in infants aged less than 1 year and 36% in children from 1 to 4 years. In infants under 1 year, varicella mortality rates reached 3.2/100,000/year. In children aged 1–4 years, varicella mortality rates reach 1.64/100,000/year. Average annual mortality rates for varicella in Brazil are 0.88/100,000 in infants under 1 year and 0.40/100,000 in children aged 1–4 years. The total number of hospitalizations associated with varicella zoster virus was 62,246 from 2008 to 2013. Varicella-associated hospitalizations have a seasonal distribution in children, peaking in November. In the elderly, monthly averages of herpes zoster-associated hospitalizations present no significant seasonal variation. Conclusions: Varicella is associated, in the pre-vaccine period, to significant morbidity and mortality in Brazil. The universal vaccination program is expected to decrease the disease burden from varicella.

Resumo Objetivo: Caracterizar os óbitos e internações relacionados ao vírus varicela-zoster no Brasil antes da vacinação universal com a vacina tetravalente (sarampo, caxumba, rubéola e varicela), tentando coletar dados de referência sobre a morbidez e mortalidade por varicela, para avaliar o impacto do programa de vacinação contra a varicela. Métodos: Os dados de mortalidade associada à varicela foram avaliados entre 1996 e 2011 e as internações associadas ao vírus varicela-zoster, entre 1998 e 2013. Os dados foram coletados do Departamento de Informática do Sistema Unificado de Saúde, considerando a Classificação Internacional de Doenças, 10ª Revisão, código B01. Todas as faixas etárias foram avaliadas. Foram calculadas as taxas de mortalidade específicas por varicela e foi descrita a sazonalidade das internações associadas ao vírus varicela-zoster. Resultados: Houve 2.334 óbitos por varicela entre 1996 e 2011, 19,3% em neonatos com menos de 1 ano e 36% em crianças de 1 a 4 anos. Em neonatos com menos de 1 ano, as taxas de mortalidade por varicela atingiram 3,2/100.000/ano. Em crianças de 1–4 anos de idade, as taxas de mortalidade por varicela atingem 1,64/100.000/ano. As taxas de mortalidade anuais médias por varicela no Brasil são de 0,88/100.000 em neonatos com menos de 1 ano de idade e 0,40/100.000 em crianças de 1 a 4 anos de idade. O número total de internações associadas ao vírus varicela-zoster foi de 62.246 de 2008 a 2013. As internações relacionadas à varicela apresentaram distribuição sazonal em crianças, com pico em novembro. Em idosos, as médias mensais de internações associadas ao herpes zoster não apresentam variação sazonal significativa. Conclusões: A varicela está associada a morbidez e mortalidade significativas no período pré-vacinação no Brasil. O programa de vacinação universal deve diminuir a carga de doença da varicela.

Efectividad de la vacuna antivaricela como profilaxis post exposición en niños chilenos / Effectiveness of varicella vaccine as post exposure prophylaxis in Chilean children

Introduction: Efficacy and effectiveness of varicella vaccine (VV) as post exposure prophylaxis (PEP) strategy have shown discordant results for disease risk reduction, and more consistent results in their ability to attenuate the disease. Aim: To assess the effectiveness of VV as PEP among household contacts. Material and Methods: We followed up 33 children after household exposure to a varicella case, of which 15 received VV as PEP and 18 did not received VV. The presence and severity of the disease were clinically determined. Results: Secondary attack rate was 53% among vaccinated and 89% among non-vaccinated children. Overall effectiveness of VV as PEP was 40% (CI95% 1%-64%). The effectiveness for preventing moderate or severe disease was 63% (CI95% 8%-85%) in the entire group and 77% (CI95% 14%-94%) among children vaccinated during the first 3 days post exposure. Vaccine tolerance was acceptable, with a low number of adverse reactions, all of them mild. Conclusion: The results suggest that VV as PEP is effective among household contacts, especially for reducing the severity of the disease.

Introducción: Los estudios de eficacia y efectividad de la vacuna antivaricela (V AV) como profilaxis post exposición (PPE) han mostrado resultados disímiles en cuanto a la reducción del riesgo de enfermar, y algo más consistentes en su capacidad de atenuar la enfermedad. Objetivo: Evaluar la efectividad de la VAV como PPE utilizada en contactos domiciliarios. Material y Métodos: Se realizó el seguimiento post exposición de 33 contactos domiciliarios de casos de varicela, de los cuales 15 recibieron VAV como PPE y 18 no la recibieron. Se determinó clínicamente el desarrollo de enfermedad y la intensidad de la misma. Resultados: La tasa de ataque secundario fue 53% en vacunados y 89% en no-vacunados, siendo la efectividad global de la VAV como PEP 40% (IC95% 1%-64%). La efectividad para prevenir enfermedad moderada o intensa fue 63% (IC95% 8-85%) en el grupo completo y 77% (IC95% 14-94%) en los niños vacunados durante los primeros tres días post exposición. La tolerancia a la vacuna fue aceptable, con un bajo número de reacciones adversas, todas leves. Conclusión: Los resultados sugieren que la VAV es efectiva como PPE en contactos domiciliarios, especialmente para reducir la intensidad de la enfermedad.

Occupational and nosocomial transmission of varicella

We examined varicella transmission in a hospital specialized in cancer treatment. A cases series study was made of a case of intra-hospital transmission of varicella, based on a revision of the records of patients who had been admitted during the time the index case was in the same service. Records of interviews of employees were also reviewed. During the period that the index case was in the intensive care unit, 34 patients were admitted and 35 employees worked there. Two employees and a patient developed the illness, due to transmission directly or indirectly from the index case. Although this is a service in which most of the patients are adults who have cancer, attention needs to be directed towards diagnosis and to procedures to reduce the transmission of this illness, both to healthcare professionals, and to other patients. A standard schedule for varicella prevention already exists; however, this case reinforces the need for specific vaccination of at-risk professionals.

Economic burden of varicella in Singapore--a cost benefit estimate of implementation of a routine varicella vaccination.

Varicella is a common childhood illness that can result in significant morbidity and mortality. As early as 1995, recommendations for routine varicella vaccination have been published, but have not been universally implemented, with cost of vaccination as a major reason. Though available from 1996, the vaccine has yet to be routinely implemented in Singapore. We set out to assess the economic burden of varicella and the cost-benefit of adding a varicella vaccine to the existing immunization schedule in Singapore. In this study, using data from 1994--1995 the direct cost estimates were based on all levels of medical care; inpatient care, emergency room visits, primary health care and medication. Indirect costs were estimated from the cost of time lost by patients and their families attending to medical needs, as well as loss of productivity due to absenteeism. The cost of a vaccination program targeted at 15-month old infants receiving concomitant measles-mumps-rubella immunization was also assessed. The cost-benefit ratio was then estimated. The total cost of varicella in Singapore was estimated to be US$11.8 million per annum. The loss of productivity accounted for a large proportion of the total cost as a lot of parents took leave when their children were ill. The estimates of total cost represent approximately US$188 per varicella case per year. In comparison, the cost of a vaccination program was found to be US$3.3 million per annum. The cost per case averted was US$104. From a societal point of view, for every dollar invested in a vaccination program, we would save about US$2 dollars.

Advantage of a two-dose versus one-dose varicella vaccine in healthy non-immune teenagers and young adults.

This study was undertaken to compare the immunogenicity and reactogenicity of two vaccines based on the attenuated Oka-strain of Varicella zoster virus (VZV), in adolescents and young adults. One hundred and eighty-six subjects, aged 13 to 29 years, were randomized to one of two groups to receive a one- or a two-dose VZV vaccine. Pre- and post-vaccination blood samples were assayed for VZV-specific IgG. Solicited local and general symptoms, as well as unsolicited symptoms, were recorded post-vaccination. Seroconversion rates were 94.9% in the one-dose, and 100% in the two-dose, regimen. The two-dose vaccine elicited significantly higher geometric mean antibody titer, 392.5 vs 86.8 pfu. Transient local injection site pain was the most frequently-reported symptom per dose in both groups (one dose: 48.9%; two-dose: 32.8%). The two-dose vaccine regimen afforded the advantage of higher antibody titers and potential increased protection from disease, without significantly increased reactogenicity.

Immunogenicity and safety of a varicella vaccine, Okavax, and a trivalent measles, mumps and rubella vaccine, MMR-II, administered concomitantly in healthy Filipino children aged 12-24 months.

This trial was conducted to assess the immunogenicity and safety of the varicella vaccine, Okavax, when administered concomitantly with the measles, mumps and rubella vaccine, MMR-II, to children aged 12-24 months. A total of 299 children were randomized into three groups, those receiving Okavax only, MMR-II only, or both vaccines concomitantly. Antibody titers were determined by ELISA in blood samples taken immediately before, and 6 weeks after, vaccination. Parents recorded local and systemic reactions. Okavax elicited similar varicella seroconversion rates (> or = 93.9%) and high GMTs when given alone or with MMR-II (99.6 and 95.7 mIU/ml, respectively). The seroconversion rates (measles and rubella 100%, mumps > or = 75.0%) and high GMTs elicited by MMR-II were not affected by concomitant administration of Okavax. The incidence of adverse events was similar whether MMR-II and Okavax were administered concomitantly or separately, and the majority of local reactions were mild and transient, with fever the most frequent systemic event in all groups. In conclusion, these results show that the immune response and the reactogenicity profile of Okavax and MMR-II were similar when given together or alone. Concomitant administration of these vaccines can therefore be recommended for children in their second year of life.

Controversies in chicken-pox immunization.

Chicken-pox is one more newer vaccine in our armamentarium against infectious diseases. Due to its extremely contagious nature, varicella is experienced by almost every child or young adult in the world. Each year from 1990 to 1994, prior to availability of varicella vaccine, about 4 million cases of varicella occurred in the United States. Of these cases approximately 10,000 required hospitalization and 100 died. Although varicella is not commonly perceived as an important public health problem, the socioeconomic consequences in industrialized countries of a disease that affects practically every child and causes the carrier absence from work should not be underestimated. The varicella vaccines available in the market are safe and effective. A recent cost-benefit analysis in USA showed that routine chicken-pox vaccination is likely to save five times the investment. Even when only direct costs were considered, benefits almost balanced the costs. At present similar studies from developing countries are not available. The public health impact of varicella and zoster may be increasing in regions with high endemic rates of HIV infection. Varicella vaccine may be used either at an individual level to protect susceptible adolescents and adults, or at a population level, to cover all children as part of a national immunization programme. Vaccination of adolescents and adults will protect at-risk individuals, but will not have a significant impact on the epidemiology of the disease on a population basis. On the other hand, extensive use as a routine vaccine in children will have a significant impact on the epidemiology of the disease. If sustained high coverage can be achieved, the disease may virtually disappear. If only partial coverage can be obtained, the epidemiology may shift, leading to an increase in the number of cases in older children and adults. Hence, routine childhood varicella immunization programmes should emphasize high, sustained coverage. At present, this vaccine will have a lower priority in the National Immunization Schedule that does not have MMR and typhoid, which have a greater socioeconomic impact. Hence, at the present time WHO does not recommend the inclusion of varicella vaccination into the routine immunization programmes of developing countries.

Flexibility in the administration schedule of varicella vaccination in healthy adolescents and young adults.

A clinical trial to assess the immunogenicity and reactogenicity of two doses of varicella vaccine (live attenuated Oka-strain, GlaxoSmithKline Biologicals), when either given 8 or 4 weeks apart in healthy seronegative adolescents and young adults, was conducted in Khon Kaen and Bangkok, Thailand. Contrary to seroconversion rates generally reported for this age group, in our study all subjects were already seropositive after the first vaccine dose. After the first vaccine dose, geometric mean titers (GMTs) for anti-varicella antibodies were 78.4 (median 64) for the adolescent group and 136.5 (median 128) for the young adult group. Six weeks after administration of the second dose, anti-varicella GMTs reached 331.7 (median 256) and 636.9 (median 512) for the adolescent and young adult groups, respectively, with a 4.2-4.7-fold increase from pre-vaccination titers. The difference in GMTs between post-dose I and dose II was statistically significant for each group. The reactogenicity after the first and second doses of vaccination was low: no varicella rash was seen, in either the shorter or longer schedule. GlaxoSmithKline Biologicals varicella vaccine (Varilix) offered a high flexibility, administration possible at either 4 or 8 weeks interval, whilst eliciting good immunogenicity and good tolerability.

Reactogenicity and immunogenicity of a varicella vaccine in healthy seronegative and seropositive subjects.

The epidemiology of varicella appears to be changing: an unexplained upward age shift in varicella prevalence and a subsequent dramatic rise in morbidity and mortality among adolescents and adults have highlighted the importance of effective varicella mass vaccination programs. This age shift is being seen in temperate regions but is particularly marked in tropical and sub-tropical regions. To assess the need for serological pre-screening in mass vaccination programs, we performed an open study to compare the reactogenicity and immunogenicity of a varicella vaccine in initially seronegative and seropositive subjects to see whether there was an increase in reactogenicity among initially seropositive subjects. Two hundred and forty-six seronegative and seropositive male and female subjects, aged 9 months to 60 years, received a single dose of a live attenuated varicella virus (Oka-strain) vaccine, Varilrix (GlaxoSmithKline Biologicals, Rixensart, Belgium). Subjects were categorized according to antibody status and age group; serum antibodies were measured before and after vaccination (day 42). The study showed that there was no difference in reactogenicity in initially seropositive vaccinees compared with initially seronegative subjects. The varicella vaccine was found to be safe and well tolerated in all age groups. Ninety-eight percent of initially seropositive and 94.8% of initially seronegative subjects reported no clinical signs or symptoms during the 42-day follow-up period. The vaccine was immunogenic in both groups. The seroconversion rate after 6 weeks in initially seronegative subjects was 94.3%. In 53.0% of initially seropositive subjects of all age classes, a 4-fold rise in antibody titer was observed.

Concomitant administration of varicella vaccine with combined measles, mumps, and rubella vaccine in healthy children aged 12 to 24 months of age.

The reactogenicity and immunogenicity of three combined measles, mumps and rubella (MMR) vaccines and one administered with a varicella vaccine was studied in infants. The vaccines were Priorix (designated MeMuRu, Group 1), M-M-R II (Group 2), Triviraten (Group 3) and Priorix + a varicella vaccine, Varilrix (Group 4). Fever was greater in Group 2 (61.3%) compared to Group 1 (48.5%; p = 0.033) or Group 3 (37.1%; p = 0.009). Rash with fever was reported in Group 2 (4.8%) and Group 4 (3.3%), but not for Group 1. Anti-measles, -mumps and -rubella seroconversion was similar for Group 1 (96.1%, 96.1% and 100%, respectively), Group 4 (98% for all three), and Group 2 (91.5%, 93.6% and 97.9%) 60 days post-vaccination. GMTs for measles (3,053.7-3,412.2 mIU/ml), mumps (1,001.5-1,158.8 U/ml) and rubella (68.7-89.1 IU/ml) were similar for Groups 1, 2 and 4 at Day 60. Antibody persistence was noted 2 years post-vaccination. The MeMuRu + varicella combination showed no clinically relevant increase in reactogenicity and should facilitate introduction of a varicella vaccine into national immunization schedules.