The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis

ABSTRACT The global reemergence of measles in 2018-2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

Efeitos da campanha de vacinação nas internações e mortalidade relacionados ao sarampo no Brasil na última década / Effects of the vaccination campaign on hospitalization and mortality linked to measles in Brazil in the last decade

Resumo O sarampo é uma das principais causas de morbidade e mortalidade na população pediátrica e pode ser prevenido com 100% de eficácia pela vacinação. No entanto, a doença permanece ativa no território brasileiro. O objetivo do artigo é avaliar a adesão da população à vacinação e a possível relação com hospitalização e mortalidade em relação ao sarampo no Brasil. Trata-se de um estudo ecológico realizado a partir de dados secundários de mortalidade e internações acerca do sarampo e da cobertura vacinal contra a doença no Brasil nos anos de 2013 a 2022. O ápice de adesão ao calendário vacinal contra o sarampo se deu nos três anos que precederam a erradicação da doença no país, ocorrida em 2016. Nesse intervalo, tem-se as menores taxas de internação, com a mortalidade zerada de 2014 a 2017. Em contrapartida, verifica-se, desde então, queda na taxas de vacinação, acentuadas a partir de 2019, quando a doença reaparece no Brasil. Concomitantemente, as taxas de internação e mortalidade atingem os valores mais altos registrados. A adesão populacional ao calendário vacinal completo contra o sarampo, essencial ao controle da doença e dos óbitos relacionados, está insuficiente, o que se reflete nas taxas de internações e mortalidade.

Abstract Measles is one of the main causes of morbidity and mortality in the pediatric population and it can be prevented with 100% effectiveness by vaccination. However, the disease remains active in throughout Brazil. The scope of this article is to evaluate the population's adherence to vaccination and the potential connection with hospitalizations and mortality in relation to measles in Brazil. This is an ecological study based on secondary data on mortality and hospitalizations due to measles and vaccination coverage against the disease in Brazil from 2013 to 2022. The peak of adherence to the measles vaccination schedule occurred in the 3 years that preceded the eradication of the disease in the country, which occurred in 2016. In this interval, there are the lowest hospitalization rates, with zero mortality from 2014 to 2017. On the other hand, there has been a marked drop in vaccination rates since 2019, when the disease resurfaced in Brazil. Concomitantly, hospitalization and mortality rates reach the highest recorded values. Population adherence to the complete measles vaccination schedule, which is essential to control the disease and related deaths, is insufficient, which is reflected in hospitalization and mortality rates.

Use of live viral vaccines after HCT: Still a lot to learn.

Revaccination program after HCT is necessary due to the loss of lifelong immunity acquired by previous vaccination or infections. The program is complex and even in a favourable scenario, it takes more than 2 years to be completed. As the complexity of HCT increases (alternative donors, diversity of monoclonal antibodies), studies evaluating the response to vaccination in this population are welcome, especially those that evaluate live attenuated vaccines given their scarcity. Furthermore, measles, mumps, rubella and even yellow fever, and poliomyelitis outbreaks have perplexed infectious diseases clinicians and epidemiologists globally, most of them due to the decline in vaccination coverage rates in children and adults, because of the growth of antivaccine movements around the world. The study of Lin et al. adds important information about measles, mumps and rubella vaccination after HCT.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Factors associated with incomplete vaccination and negative antibody test results for measles, mumps, and hepatitis A among children followed in the MINA-BRAZIL cohort

ABSTRACT Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

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.

Evaluación neuroepidemiológica a partir de anticuerpos antivirales de memoria generados por la vacuna triple viral / Neuro-Epidemiological Evaluation From Memory Antiviral Antibodies Generated By The MMR Vaccine

Introducción: La vacuna contra sarampión-parotiditis-rubéola es administrada en Cuba con un 99 por ciento de cobertura vacunal. Actualmente se plantea la baja inmunogenicidad de la cepa de parotiditis con que se fabrica por lo que resulta importante velar por la eficacia de las vacunas y su respuesta inmune protectora. Objetivos: Evaluar el comportamiento de los índices de anticuerpo antirubéola, antiparotiditis y antisarampión de acuerdo con la edad, y analizar la variación de la respuesta de anticuerpos antiparotiditis con respecto a estudios anteriores. Materiales y métodos: Se estudiaron muestras de suero y líquido cefalorraquídeo de 42 pacientes pediátricos con procesos neuroinflamatorios y se les cuantificó IgG total y albúmina y anticuerpos específicos contra los tres virus a partir de ensayos innmunoenzimáticos tipo ELISA. Se realizaron los reibergramas correspondientes e índices de anticuerpos específicos. Resultados: Se observó un incremento sostenido de anticuerpos contra los tres inmunógenos de forma general, sin diferencias significativas por razones de edad ni cambios notables posrevacunación. Existió un decrecimiento del índice de anticuerpos a medida que se alejaba de la fecha de revacunación por lo que se debe mantener una vigilancia en esos grupos de edades. La velocidad de producción de anticuerpos antiparotiditis fue mayor que frente a los otros virus, aunque no de forma significativa. Conclusiones: Esta vacuna garantiza protección por la uniformidad de la respuesta inmune de memoria inducida en todos los grupos de edades. Se demostró un aumento de protección de la población estudiada frente a la parotiditis con respecto a estudios previos(AU)

Introduction: The measles-mumps-rubella vaccine is administered in Cuba with 99 percent vaccination coverage. Currently, the low immunogenicity of the strain of mumps with which it is manufactured is raised, so it is important to ensure the effectiveness of vaccines and their protective immune response. Objectives: Evaluate the behavior of the anti-rubella, anti-mumps and anti-measles antibody indices according to age, and to analyze the variation of the anti-mumps antibody response with respect to previous studies. Materials and methods: Serum and cerebro-spinal fluid samples from 42 pediatric patients with neuro-inflammatory processes were studied and total IgG and albumin and specific antibodies against the three viruses were quantified from immunoenzymatic assays ELISA type. Corresponding reibergrams and specific antibody indices were performed. Results: A sustained increase in antibodies against the ethree immunogens was observed in general, without significant differences due to age or notable post-vaccination changes. There was a decrease in the antibody index as it moved away from the date of revaccination, so surveillance should be maintained in these age groups. The rate of production of anti-mumps antibodies was higher than against the other viruses, although not significantly. Conclusions: This vaccine guarantees protection by the uniformity of the memory induced immune response in all age groups. An increase in the protection of the studied population against mumps was demonstrated with respect to previous studies(AU)

Number of doses of Measles-Mumps-Rubella vaccine applied in Brazil before and during the COVID-19 pandemic.

BACKGROUND: Due to the social isolation measures adopted in an attempt to mitigate the risk of transmission of SARS-CoV-2, there has been a reduction in vaccination coverage of children and adolescents in several countries and regions of the world. OBJECTIVE: Analyze the number of doses of vaccine against Measles-Mumps-Rubella (MMR) applied before and after the beginning of mitigation measures due to COVID-19 pandemic in Brazil. METHODS: The data collected refer to the number of doses of the MMR vaccine applied monthly to the target population residing in Brazil: cahildren, aged 12 months (first dose) and children, aged 9 years (second dose), from April 2019 to December 2020. Differences in MMR vaccine doses from April 2019 to March 2020 (before the start of mitigation measures) and April 2020 to September 2020 (after the start of the mitigation measures) were evaluated. Spatial analysis identified clusters with a high percentage of reduction in the median of applied doses no Brazil. RESULTS: There was a reduction in the median of doses applied in the Regions North (- 33.03%), Northeast (- 43.49%) and South (- 39.01%) e nos Estados Acre (- 48.46%), Amazonas (- 28.96%), Roraima (- 61.91%), Paraíba (- 41.58%), Sergipe (- 47.52%), Rio de Janeiro (-59.31%) and Santa Catarina (- 49.32) (p < 0.05). High-high type spatial clusters (reduction between 34.00 and 90.00%) were formed in the five regions of Brazil (Moran's I = 0.055; p = 0.01). CONCLUSION: A reduction in the number of MMR vaccine doses was evidenced as a possible effect by the restrictive actions of COVID-19 in Brazil.

Identificación de desórdenes autoinmunes e inmunodeficiencias a través de la evaluación neuroepidemiológica del índice de anticuerpos antiparotiditis, antirubéola y antisarampión / Identification of autoimmune disorders and immunodeficiencies by neuroepidemiological evaluation of the measles, mumps and rubella antibody index

Introducción: El esquema nacional de vacunación cubano presenta coberturas superiores al 99 por ciento que incluye la vacuna contra parotiditis, rubéola y sarampión. Así, cuando existe un proceso neuroinflamatorio se produce una amplia síntesis intratecal de anticuerpos antiparotiditis, antirubéola y antisarampión, que permite realizar evaluaciones neuroepidemiológicas de las campañas de vacunación y el sesgo de casos extremos, desde el punto de vista inmunológico. Objetivos: Correlacionar el índice de anticuerpos antirubéola, antiparotiditis y antisarampión con procesos autoinmunes asociados y en la identificación de posibles pacientes con inmunodeficiencias en la muestra estudiada. Métodos: Se realizó un estudio aplicado y descriptivo de corte transversal en 42 niños evaluados en los servicios de cuerpo de guardia de los hospitales pediátricos de La Habana del 2015 al 2018. La muestra fue dividida según los tres intervalos del índice de anticuerpos (menor o igual a 0,6; de 0,6 a 1,5 y mayor o igual a 1,5). Se procedió a detectar en los segmentos extremos pacientes con posible autoinmunidad (mayor o igual a 1,5) e inmunodeficiencia (se tomó el intervalo inferior a una desviación estándar). Resultados: En el grupo con índice de anticuerpos mayor o igual a 1,5, el 75 por ciento fue positivo a la reacción MRZ, indicativo de una enfermedad autoinmune activa. En el grupo con índice de anticuerpos menor o igual a 0,6 preponderó una clínica con prevalencia de enfermedades tumorales e infecciosas asociadas a un alto índice de hospitalización, test de inmunodeficiencia positivo y bajos niveles de IgG en suero. Conclusiones: Es posible identificar pacientes pediátricos con desórdenes autoinmunes y sospecha de inmunodeficiencias, a partir de la estrategia de la evaluación neuroepidemiológica de los índices de anticuerpos antiparotiditis, antirubéola y antisarampión(AU)

Introduction: The Cuban national vaccination scheme has a coverage of more than 99 percent of the population, and includes the measles-mumps-rubella vaccine. Therefore, in the presence of a neuroinflammatory process, a broad intrathecal synthesis of measles, mumps and rubella antibodies takes place which makes it possible to conduct neuroepidemiological evaluations of the vaccination campaigns and the bias of extreme cases, from an immunological perspective. Objectives: Correlate the measles, mumps and rubella antibody index with associated autoimmune processes and in the identification of patients with possible immunodeficiencies in the study sample. Methods: An applied cross-sectional descriptive study was conducted of 42 children attending the emergency services of Havana children's hospitals in the period 2015-2018. The sample was divided according to the three antibody index intervals: smaller than or equal to 0.6, from 0.6 to 1.5, and greater than or equal to 1.5. Extreme segments were examined to detect patients with possible autoimmunity (greater than or equal to 1.5) and immunodeficiency (the interval below a standard deviation was taken as reference). Results: 75 percent of the group with an antibody index greater than or equal to 1.5 was positive to the MRZ reaction, indicative of an active autoimmune disease. In the group with an antibody index lower than or equal to 0.6, the prevailing clinical status showed a prevalence of tumoral and infectious diseases associated to a high hospitalization index, a positive immunodeficiency test and low serum IgG levels. Conclusions: It is possible to identify pediatric patients with autoimmune disorders and suspicion of immunodeficiencies applying the strategy of neuroepidemiological evaluation of the measles, mumps and rubella antibody indices(AU)

Parotiditis recurrente benigna de la infancia: experiencia en el diagnóstico en un hospital de alta complejidad en Latinoamérica

Objetivo: la parotiditis recurrente benigna de la infancia (PRBI) es una enfermedad de importancia clínica. Sin embargo, su diagnóstico puede no realizarse correctamente debido al desconocimiento de esta entidad. El propósito de este estudio es describir los aspectos clínicos fundamentales de esta condición y proponer un enfoque terapéutico simple. Materiales y métodos: se realizó un análisis descriptivo de pacientes pediátricos con diagnóstico de parotiditis viral y PRBI entre los años 2008 y 2018, en el Hospital Universitario San Ignacio de Bogotá, Colombia. Resultados: se encontraron 41 pacientes con diagnóstico de PRBI; de estos, el 51,2 % fueron de sexo femenino, con una edad media de 7,1 años. A 32 pacientes (78 %) con diagnóstico de PRBI se les realizaron imágenes diagnósticas, a pesar de que la tasa de complicaciones fue baja (19,5 %). El diagnóstico fue hecho por los servicios de pediatría y otorrinolaringología en el 80 % de los casos. Conclusiones: hasta donde sabemos, este es el estudio con mayor número de pacientes con diagnóstico de PRBI en Latinoamérica. Es indispensable conocer esta enfermedad y tener en cuenta su curso benigno y pocas complicaciones, con el fin de destinar menos recursos en el uso de imágenes innecesarias y evitar el sobrediagnóstico de parotiditis por paramixovirus.

SUMMARY Objectives: Benign recurrent parotitis of childhood (BRPC) is a clinically relevant disease in childhood. Its diagnosis, however, is usually not made due to the lack of knowledge regarding such a condition. The aim of this study is to describe the most relevant aspects of this condition and propose a simple therapeutic approach. Materials and Methods: We did a descriptive analysis of pediatric patients diagnosed with viral parotitis and BRPC between 2008 and 2018, at the Hospital Universitario San Ignacio in Bogotá, Colombia. Results: 41 patients with BRPC where included; 51.2% were female, with a mean age of 7.1 years. Thirty-two patients (78%) with diagnosis of BRPC underwent diagnostic imaging, despite the low rate of complications (19,5%). The diagnosis was made by otolaryngologists or pediatricians in 80% of the cases. Conclusions: To our knowledge, this is the study with the largest number of BRPC cases in Latin America. It is essential to know about this disease and take into account its benign course and few complication rates, in order to avoid both wasting of resources in the use of unnecessary imaging and the overdiagnosis of mumps.

Pediatricians' Knowledge and Practices Related to Mumps Diagnosis and Prevention.

OBJECTIVES: To assess pediatricians' mumps knowledge and testing practices, to identify physician and practice characteristics associated with mumps testing practices, and to assess reporting and outbreak response knowledge and practices. STUDY DESIGN: Between January and April 2020, we surveyed a nationally representative network of pediatricians. Descriptive statistics were generated for all items. The χ2 test, t tests, and Poisson regression were used to compare physician and practice characteristics between respondents who would rarely or never versus sometimes or often/always test for mumps in a vaccinated 17-year-old with parotitis in a non-outbreak setting. RESULTS: The response rate was 67% (297 of 444). For knowledge, more than one-half of the pediatricians responded incorrectly or "don't know" for 6 of the 9 true/false statements about mumps epidemiology, diagnosis, and prevention, and more than one-half reported needing additional guidance on mumps buccal swab testing. For testing practices, 59% of respondents reported they would sometimes (35%) or often/always (24%) test for mumps in a vaccinated 17-year-old with parotitis in a non-outbreak setting; older physicians, rural physicians, and physicians from the Northeast or Midwest were more likely to test for mumps. Thirty-six percent of the pediatricians reported they would often/always report a patient with suspected mumps to public health authorities. CONCLUSIONS: Pediatricians report mumps knowledge gaps and practices that do not align with public health recommendations. These gaps may lead to underdiagnosis and underreporting of mumps cases, delaying public health response measures and contributing to ongoing disease transmission.

Vaccination coverage for measles, mumps, and rubella in a tertiary hospital of Porto Alegre, state of Rio Grande do Sul.

INTRODUCTION: Measles, mumps, and rubella are viral contagious diseases preventable by the MMR vaccine. MMR is a part of the immunization schedule of the Brazilian Ministry of Health, which recommends 2 doses of the vaccine for professionals working in health care facilities. OBJECTIVES: To determine the vaccination coverage for measles, mumps, and rubella among active professionals of a tertiary hospital in the city of Porto Alegre, state of Rio Grande do Sul; to analyze the importance of vaccinating professionals that work at health care facilities; to detect and highlight high-risk services for contagious diseases according to patient profiles - children, pregnant and puerperal women, immunocompromised individuals. METHODS: This is a descriptive transversal study that analyzed the database of the Occupational Medicine Service of Hospital de Clínicas de Porto Alegre considering active professionals in January 2019. RESULTS: We evaluated the vaccination records of 7802 active professionals of this hospital; 52% of them had taken at least 1 dose of the MMR vaccine (1 or 2 doses) and 47% had not been vaccinated. Among high-risk services, 56.4% of the professionals had had at least 1 MMR dose, while 43.4% had not been vaccinated. CONCLUSIONS: This study revealed that the vaccination coverage for measles, mumps, and rubella at the analyzed health care facility was still far from the ideal; however, the Occupational Medicine Service has been making efforts to gradually broaden this coverage.

Caracterização imunológica da formulação vacinal baseada em VLP (Virus Like Particle) da Proteína Circumsporozoíta de Plasmodium vivax / Immunological characterization of the VLP (Virus Like Particle) vaccine formulation fused to Circumsporozoite Protein of Plasmodium vivax

O Plasmodium vivax é a espécie mais comum de parasita causador da malária humana encontrada fora da África, com maior endemicidade na Ásia, América Central e do Sul e Oceania. Embora o Plasmodium falciparum cause a maioria do número de mortes, o P. vivax pode levar à malária grave e resultar em morbimortalidade significativa. O desenvolvimento de uma vacina protetora será um passo importante para a eliminação da malária. Recentemente, uma formulação contendo as três variantes alélicas da proteína circumsporozoíta de P. vivax (PvCSP - All epitopes) induziu proteção parcial em camundongos após desafio com esporozoíto híbrido Plasmodium berghei (Pb), no qual as repetições centrais do PbCSP foram substituídas por repetições PvCSP-VK210 (esporozoítos Pb/Pv). No presente estudo, a proteína quimérica PvCSP contendo as variantes alélicas (VK210, VK247 e P. vivax-like) fusionadas com a proteína de nucleocapsídeo do vírus da caxumba (formando partículas semelhantes a nucleocapsídeos ou do inglês, NLP - Núcleo Like Particles) na ausência (NLP-CSPR) ou na presença do domínio C-terminal (CT) conservado da PvCSP (NLP-CSPCT). Para a realização do estudo selecionamos os adjuvantes Poly (I:C), um RNA sintético de dupla fita, agonista do receptor Toll do tipo 3 (TLR3) ou o adjuvante Montanide ISA 720, uma emulação óleo em agua. Para obter uma forte resposta imune, a levedura Pichia pastoris foi usada para expressar as proteínas recombinantes na forma de NLPs. Camundongos foram imunizados com cada uma das proteínas recombinantes em combinação com os adjuvantes citados. Embora ambas as NLPs tenham sido capazes de gerar uma forte resposta imune, com altos níveis de títulos e longevidade, apenas a formulação contendo a proteína NLP-CSPCT na presença do adjuvante Poly (I:C) foi selecionada para ser explorada em experimentos futuros. Esta proteína em combinação com o adjuvante Poly (I:C) induziu alta frequência de células secretoras de anticorpos específicas para o antígeno homólogo nos dias 5 e 30, no baço e na medula óssea, respectivamente. Altos títulos de IgG contra as 3 variantes de PvCSP foram detectados nos soros. Posteriormente camundongos imunizados com NLP-CSPCT foram desafiados com esporozoítos Pb/Pv e a parasitemia no 5º dia demonstrou proteção estéril em 30% dos camundongos desafiados. Portanto, a formulação vacinal gerada neste estudo tem potencial para ser explorada no desenvolvimento de uma vacina universal contra a malária causada por P. vivax

Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the P. vivax circumsporozoite protein (PvCSP--All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and P. vivax-like) were fused with the mumps virus nucleocapsid protein (assembling into nucleo like particles - NLP) in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To carry out the study, we selected the adjuvants Poly (I:C), a synthetic double-stranded RNA, Toll-like receptor 3 (TLR3) agonist or Montanide ISA 720 adjuvant, an oil-water emulation. To elicit stronger immune response, Pichia pastoris yeast was used to produce the NLPs. Mice were immunized with each recombinant protein in combination with above. Although both NLPs were able to generate stronger immune response, with high antibodies titer levels and longevity, formulation containing NLP-CSPCT in the presence of Poly (I:C) was selected to be explored in future experiments. NLP-CSPCT with Poly (I:C) adjuvant presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, immunized mice with NLP-CSPCT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against P. vivax malaria.

Meningitis aséptica por virus parotídeo asociada a la vacuna

Resumen Comunicamos el caso de un lactante mayor previamente sano, que luego de tres semanas de recibir la vacuna SPR (sarampión, parotiditis, rubeola) presentó fiebre, aumento de volumen parotídeo y compromiso de conciencia. Se diagnosticó una meningitis aséptica, con pleocitosis en el LCR de predominio mononuclear, detectándose virus parotídeo en LCR por biología molecular. En el Instituto de Salud Pública de Chile se realizó serología (IgM e IgG) que resultó positiva. La muestra de saliva confirmó la etiología por virus parotídeo con genotipo N. La evolución fue favorable, sin secuelas al seguimiento a seis meses. Ante esta situación clínica, se revisó la información respecto a la asociación y causalidad de esta entidad clínica y vacuna SPR, focalizado en diferentes cepas del virus parotiditis.

Abstract We report the case of an older infant with no prior morbidity that approximately 3 weeks after receiving MMR vaccination (measles, mumps, rubella) was hospitalized for feverish symptoms, increased parotid volume and compromised consciousness. Aseptic meningitis was diagnosed, detecting pleocytosis in the CSF, predominantly mononuclear, and confirming by molecular biology, presence of parotid virus in CSF. A study was carried out by the Institute of Public Health of Chile, where serology (IgM and IgG) was positive. Saliva sample confirmed the etiology of parotid virus with genotype N. The evolution was favorable and at 6-month follow-up, there were no sequelae. Given this clinical situation, information regarding the association and causality of this clinical entity and the MMR vaccine, focused on different strains of the mumps virus, was reviewed.

Sialoadenitis aguda secundaria al medio de contraste yodado

Resumen La sialoadenitis es una inflamación o infección de las glándulas salivares que puede afectar a las glándulas parótidas, submandibulares y/o a las glándulas salivares menores. La sialoadenitis aguda tras la inyección de contraste yodado es una reacción adversa tardía rara, se caracteriza por un aumento de tamaño de las glándulas salivares, más frecuentemente las submandibulares. El número de estudios de tomografía computarizada ha aumentado exponencialmente en los últimos años por lo que es de esperar que cada vez se den más casos de esta entidad. El 98% del yodo inyectado por vía intravenosa es eliminado por los riñones y el 2% por otros órganos como glándulas salivales, lacrimales y sudoríparas. En los pacientes con insuficiencia renal el retraso de la eliminación renal conlleva un mayor acúmulo de yodo en la saliva que produce, a su vez, mayor inflamación de la mucosa de los conductos glandulares. Por ello, la insuficiencia renal se considera un factor de riesgo para sialoadenitis por yodo y se ha de sospechar especialmente en estos pacientes si presentan clínica sugestiva. Presentamos el caso de un paciente que tras la realización de una tomografía computarizada con contraste yodado desarrolló una sialoadenitis aguda como reacción adversa al mismo.

Abstract Sialadenitis is an inflammation or infection of the salivary glands that may affect the pa- rotid, submandibular and/or small salivary glands. Acute sialadenitis after injection of io- dinated contrast is a rare late adverse reaction. It is characterized by an enlargement of the salivary glands, most frequently the submandibular ones. The number of studies of compu- ted tomography has increased exponentially in recent years, so it is expected that there will be more and more cases of this entity. About 98% of the iodine contrast injected intrave- nously is eliminated by the kidneys and 2% by other organs such as salivary, lacrimal and sweat glands. In patients with renal failure, delayed renal elimination leads to a greater accumulation of iodine in saliva, which produces greater inflammation of the mucosa of the glandular ducts. Therefore, kidney failure is considered a risk factor for iodine sialadenitis and it should be especially suspected in these patients if they present suggestive symptoms. We present a case of a patient who after performing a computed tomography study with intravenous iodinated contrast, developed acute sialadenitis as an adverse reaction to this contrast.

Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein.

Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the P. vivax circumsporozoite protein (PvCSP-All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and P. vivax-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To elicit stronger humoral and cellular responses, Pichia pastoris yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSPCT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against P. vivax malaria.

Brotes epidémicos de parotiditis, revisión de la literatura / Mumps outbreaks, literature review

La parotiditis es un infección viral producida por el virus parotídeo. Clínicamente se caracteriza por aumento de volumen de la glándula parótida generalmente bilateral. La estrategia que ha mostrado ser más eficaz para la prevención de esta infección ha sido la implementación de la vacuna tres vírica en los programas de inmunización. En países con población altamente inmunizada como Chile, se logró una importante disminución de la incidencia de esta enfermedad. Sin embargo, a pesar de la efectividad de la vacuna se siguen reportando brotes en todo el mundo, evidenciándose un cambio epidemiológico, trasladándose la edad de presentación clínica desde la niñez y adolescencia hacia los adultos jóvenes. Este aumento en el número de casos ha sido estudiado, determinando que el efecto protector inmunitario de la vacuna decaería con el transcurso del tiempo, contribuyendo a la propagación de los brotes. Con respecto a posibles estrategias para el manejo de los brotes la aplicación de una dosis adicional de la vacunas tres vírica en población expuesta sería una medida que mejoraría el control de los brotes.

Mumps is a viral infection caused by mumps virus. Clinically, it is characterized by increased parotid volume. The most effective strategy for preventing this infection, has been the implementation of measles-mumps-rubella (MMR) vaccine in the national immunization program. Among countries with a highly immunized population, like Chile, there has been an important reduction in the incidence of this disease. Nevertheless, despite the effectivity of the MMR, there are reports of outbreaks worldwide, with an epidemiological change, from clinical presentation in childhood, to adolescents and adults. This outbreaks have been studied, and it has been determined that they are due to the waning of vaccine-derived immunity. Regarding strategies for the management of new outbreaks, the administration of an additional dose of MMR, would be an alternative.

Estrutura e localização dos serviços de vacinação influenciam a disponibilidade da tríplice viral no Brasil / La estructura y ubicación de los servicios de vacunación influyen en la disponibilidad de la vacuna triple viral en Brasil / Structure and location of vaccination services influence the availability of the triple viral in Brazil

RESUMO OBJETIVO: analisar a associação de fatores estruturais e diferenças geográficas na disponibilidade da vacina tríplice viral nos serviços de atenção básica no Brasil. MÉTODOS: estudo transversal, com dados secundários do segundo ciclo das avaliações externas do Programa de Melhoria da Qualidade da Atenção Básica (PMAQ-AB) coletados em 19.752 serviços de vacinação de todo o país entre os anos de 2013 e 2014. Razões de prevalência (RP) ajustadas e seus respectivos intervalos de confiança de 95% (IC 95%) foram estimados com a técnica de regressão multivariada de Poisson com variâncias robustas. RESULTADOS: a vacina tríplice viral estava sempre disponível em 93% dos serviços estudados, mas com diferenças regionais, sendo a menor frequência observada na região Norte (87,4%; p<0,001). Os seguintes fatores estruturais dos serviços associaramse positivamente à maior frequência de vacina tríplice viral sempre disponível: possuir sala de vacinação (RP: 1,05; IC 95%: 1,01-1,09), sala de vacinação exclusiva para imunização (RP: 1,04; IC 95% 1,02-1,05), geladeira exclusiva para vacinas (RP: 1,13; IC 95%: 1,10-1,16); cartões de vacinação impressos sempre disponíveis (RP: 1,12 IC 95%: 1,09-1,16) e caixas térmicas para vacinas sempre disponíveis (RP: 1,18 IC 95%: 1,14-1,21). CONCLUSÃO: a localização e a estrutura dos serviços de atenção básica influenciaram na disponibilidade da vacina tríplice viral no Brasil. Serviços da região Norte e com estrutura deficiente para as ações de imunização apresentaram menor frequência da disponibilidade da vacina.

RESUMEN OBJETIVO: analizar la asociación entre los factores estructurales y las diferencias geográficas en la disponibilidad de la vacuna triple viral en los servicios de atención primaria de Brasil. MÉTODO: estudio transversal con datos secundarios del segundo ciclo de evaluaciones externas del Programa de mejora de la calidad de la atención primaria recogidos en 19.752 servicios de vacunación de todo el país entre 2013 y 2014.Las razones de prevalencia ajustadas (PR) y sus respectivos intervalos de confianza del 95% (IC del 95%) se estimaron utilizando la técnica de regresión multivariante de Poisson con varianzas robustas. RESULTADOS: la vacuna triple viral siempre estuvo disponible en el 93% de los servicios estudiados, pero con diferencias regionales, con la menor frecuencia observada en el norte (87,4%; p <0,001). Los siguientes factores estructurales de los servicios se asociaron positivamente con la mayor frecuencia de vacuna triple viral siempre disponible: tener una sala de vacunación (RP: 1.05; IC 95%: 1.01-1.09), sala de vacunación exclusiva para inmunización (RP: 1,04; IC del 95%: 1,02-1,05), refrigerador exclusivamente para vacunas (RP: 1,13; IC del 95%: 1,10-1,16); tarjetas de vacunación impresas siempre disponibles (RP: 1,12 IC 95%: 1,09-1,16) y cajas térmicas para vacunas siempre disponibles (RP: 1,18 IC 95%: 1,14-1,21). CONCLUSIÓN: la ubicación y estructura de los servicios de atención primaria influyó en la disponibilidad de la vacuna triple viral en Brasil. Los servicios de la región norte con estructura deficiente para las acciones de inmunización mostraron menor frecuencia de disponibilidad de vacunas.

ABSTRACT OBJECTIVE: to analyze the association of structural factors and geographical differences in the availability of the measle, mumps, and rubella vaccine in primary care services in Brazil. METHODS: this is a cross-sectional study, with secondary data from the second cycle of external evaluations of the Primary Care Quality Improvement Program (Programa de Melhoria da Qualidade da Atenção Básica - PMAQ-AB) collected from 19,752 vaccination services across the country between 2013 and 2014. We estimated the prevalence ratio (PR) and their respective 95% confidence intervals (CI 95%) using the Poisson multivariate regression technique with robust variances. RESULTS: the MMR vaccine was always available in 93% of the services studied, but with regional differences, with the lowest frequency observed in the North (87.4%; p <0.001). The following structural factors of the services were positively associated with the higher frequency of MMR vaccine always available: having a vaccination room (PR: 1.05; 95% CI: 1.01-1.09), exclusive vaccination room for immunization (PR: 1.04; 95% CI 1.02-1.05), refrigerator exclusively for vaccines (PR: 1.13; 95% CI: 1.10-1.16); printed vaccination cards always available (PR: 1.12 95% CI: 1.09-1.16) and coolers for vaccines always available (PR: 1.18 95% CI: 1.14-1.21). CONCLUSION: the location and structure of primary care services influenced the availability of the MMR vaccine in Brazil. Services in the North region and with a poor structure for immunization actions showed less frequency of vaccine availability.

Measles-containing vaccines in Brazil: Coverage, homogeneity of coverage and associations with contextual factors at municipal level.

We aimed to (i) describe both the coverage and the homogeneity of coverage of the first and second doses of measles-containing vaccines (MCV) in Brazil in 2017, and (ii) to investigate the potential influence of contextual factors at municipal level. All 5570 Brazilian municipalities were included. The North and Center-West regions presented the lowest coverages of the first and second doses of MCV, respectively. We found significant associations of both first and second doses of MCV with population size, coverage of Family Health Strategy (FHS) and other indicators of living conditions and inequalities. Monitoring the homogeneity of MCV coverage at national, regional and state levels is essential, as it allows identifying areas at higher risk of measles spread that should be targeted for vaccination. Targeting large cities i.e. 100,000 or more inhabitants, especially poor neighborhoods and areas with low FHS coverage, could lead to improvements in coverage homogeneity.