Boletín epidemiológico semana 37: sarampión y rubéola / Epidemiological bulletin week 37: measles and rubella

A nivel mundial, con corte al mes de agosto de 2024, se han confirmado 237 572 casos de sarampión en las regiones de la Organización Mundial de la Salud (OMS). La región de Europa lidera en número de casos, con un 35,8 % del total, equivalente a 84 932 casos; le sigue la región del Mediterráneo Oriental con un 26,6 %, representando 63 252 casos, y la región Africana con un 24,6 % del total de casos confirmados. El síndrome de rubéola congénita (SRC) es una infección viral consistente en múltiples anomalías congénitas debida a una infección primaria materna. El feto presenta riesgo máximo de anomalías del desarrollo si la infección se da durante las primeras 16 semanas de gestación (1). Según la Organización Mundial de la Salud, cada año nacen en el mundo 100 000 niños con esta enfermedad (2). Entre el 85-90 % de los fetos afectados por esta infección antes de las 12 semanas de gestación, presentan la tétrada de Gregg, consistente en cardiopatía, microcefalia, cataratas y sordera, así como otros trastornos incluidos autismo, diabetes y disfunción tiroidea (3). El virus de la rubéola invade las vías respiratorias superiores, con la consiguiente diseminación del virus, incluida la placenta (3). La infección puede causar restricción del crecimiento intrauterino, alteraciones graves del desarrollo, aborto e incluso muerte del feto (2). El esquema de vacunación contra la enfermedad ha reducido la incidencia de la rubéola congénita. Sin embargo, la vacuna está contraindicada en el embarazo por el riesgo potencial para el feto.

Globally, as of August 2024, 237,572 cases of measles have been confirmed in the World Health Organization (WHO) regions. The European region leads in number of cases, with 35.8% of the total, equivalent to 84,932 cases; followed by the Eastern Mediterranean region with 26.6%, representing 63,252 cases, and the African region with 24.6% of the total confirmed cases. Congenital rubella syndrome (CRS) is a viral infection consisting of multiple congenital abnormalities due to a primary maternal infection. The fetus is at maximum risk of developmental abnormalities if the infection occurs during the first 16 weeks of gestation (1). According to the World Health Organization, 100,000 children are born with this disease every year in the world (2). Between 85-90% of fetuses affected by this infection before 12 weeks of gestation present Gregg's tetrad, consisting of heart disease, microcephaly, cataracts and deafness, as well as other disorders including autism, diabetes and thyroid dysfunction (3). The rubella virus invades the upper respiratory tract, with subsequent dissemination of the virus, including the placenta (3). The infection can cause intrauterine growth restriction, severe developmental disorders, abortion and even fetal death (2). The vaccination schedule against the disease has reduced the incidence of congenital rubella. However, the vaccine is contraindicated in pregnancy due to the potential risk to the fetus.

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.

Catarata congênita nas infecções intrauterinas mais comuns (STORCH): revisão de literatura / Congenital cataract in the most common intrauterine infections (STORCH): a review of the literature

RESUMO Objetivo: O objetivo deste estudo foi revisar os aspectos clínicos e patológicos da catarata congênita secundária às infecções por sífilis, toxoplasmose, rubéola, citomegalovírus e herpes simples. Métodos: Trata-se de uma revisão de literatura, na qual foram incluídos artigos de periódicos indexados às bases de dados PubMed®, Cochrane, Lilacs, Embase e SciELO de 2010 a 2023. Resultados: Foram encontrados 45 artigos, e, após seleção, restaram 9 artigos. Além disso, foram adicionados artigos para enriquecer a discussão. A infecção por sífilis está relacionada a alterações corneanas. O citomegalovírus e a toxoplasmose estão relacionados com a coriorretinite e/ou microftalmia. A rubéola é responsável por causar catarata, glaucoma, microftalmia e retinite em sal e pimenta. Conclusão: Foram abordadas as principais etiologias infecciosas e seu quadro clínico na CC. O melhor tratamento para CC é cirúrgico associado a acompanhamento clínico, mas a prevenção é a maneira mais eficaz de combater a CC de etiologia infecciosa. O diagnóstico precoce e o tratamento efetivo previnem alterações e sequelas visuais irreversíveis. Nesse contexto, mostram-se importantes as ações de políticas públicas para o melhor desfecho clínico e melhor qualidade de vida.

ABSTRACT Objective: To review the clinical and pathological aspects of CC secondary to infections by syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex. Methods: This is a literature review. Articles from journals indexed to PubMed, COCHRANE, LILACS, EMBASE and SCIELO from 2010 to 2023 were included. Results: A total of 45 articles were found, which, after selection, remained in 9 articles. Some articles were included to enrich the discussion in this topic. The infection caused by syphilis is related to corneal changes. Cytomegalovirus and Toxoplasmosis due to chorioretinitis and/or microphthalmia. Rubella is responsible for causing cataracts, glaucoma, microphthalmia, and salt and pepper retinitis. Conclusion: The main infectious etiologies and their clinical status in CC were addressed. The best treatment for CC is surgery associated with clinical follow-up, but prevention is the most effective way to combat CC of infectious etiology. Early diagnosis and effective treatment prevent irreversible visual changes and sequelae. In this context, public policy actions are important for the best clinical outcome and better quality of life.

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.

Measles and Rubella Seroprevalence Among Children and Adolescents of Córdoba, Argentina: A Cross-Section Study in the Context of the Elimination Program.

We determined anti-rubella and anti-measles immunoglobulin G (IgG) in 7- to 19-year-old children and adolescents with vaccine only-induced immunity of Córdoba, Argentina, during a 6-month period over 2021-2022. Of the 180 individuals studied, 92.2% and 88.3% were positive for anti-measles and anti-rubella IgG, respectively. No significant differences were found comparing anti-rubella IgG concentrations (p = 0.144) and anti-measles IgG concentrations (p = 0.105) of individuals classified by age, but anti-measles IgG and anti-rubella IgG levels were significantly higher among female individuals compared with males (p = 0.031 and p = 0.036, respectively). Female subjects in the younger age group had higher concentrations of anti-rubella IgG as well (p = 0.020), even when anti-measles IgG concentrations did not differ among female age-subgroups (p = 0.187). In contrast, age subgroups of male individuals did not have significantly different IgG concentrations for rubella (p = 0.745) or measles (p = 0.124). Among samples with discordant results (22/180, 12.6%), 9.1% were negative for rubella but positive for measles; 13.6% were equivocal for rubella and positive for measles; 22.7% were equivocal for rubella and negative for measles, while 54.5% were positive for rubella but negative for measles. The findings indicate a seroprevalence below recommended for preventing measles in the population studied, while they evidence the need for standardization of serological tests for rubella IgG.

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.

A Biotechnological Review on Patents Applied to Rubella Diagnosis.

BACKGROUND: Rubella, caused by the Rubella virus (RV), is considered a mild self-limited illness. However, RV has teratogenic potential. Laboratory investigation plays an important role in both diagnosis and surveillance of the disease. The main methods for diagnosing Rubella are serological assays for the detection of specific IgM and molecular assays for detecting viral RNA. However, some laboratories perform IgG avidity testing, virus isolation and analysis of genetic sequence as tools to help Rubella eradication. The importance of the diagnosis of Rubella involves the appropriate treatment of the disease, because the Rubella clinical symptoms may be similar to those of other diseases, and the population monitoring to avoid new emergent cases. This study addresses different methods of diagnosing Rubella and contributes as a source of knowledge to assist health systems in controlling the disease. OBJECTIVE: The main objective of this study was to review the available patents regarding Rubella diagnosis published in intellectual property databases, and provides an overview of the technologies available for the diagnosis of Rubella. METHOD: The search strategy was based on the keywords searched separately or together using a Boolean operator either in the patent title or abstract the time interval was restricted to patents filed or granted from January 2009 until February 2022. The database used was Google Patents. RESULTS: This study analyzed 24 patent documents regarding strategies for the diagnosis of Rubella. Of these, 15 patents disclose strategies for detecting Rubella antibodies, 7 patents the detection of Rubella virus nucleic acid, and 2 patents the production of antibodies applied in Rubella diagnosis. CONCLUSION: Rubella is still a public health problem in some countries, mainly those in development, especially due to congenital Rubella syndrome, which can cause malformation or fetal death. However, its diagnosis is challenging, due to similarity of symptoms with other diseases, and for this reason, laboratory diagnosis is essential. Studies like this encourage researchers and governments to invest in research to continue the development of new products, using different areas of biotechnology, to solve society's problems, especially diseases that have an impact on global health, such as Rubella.

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.

Perfil epidemiológico dos casos suspeitos de sarampo e rubéola notificados no SINAN, Brasil, 2007 a 2016 / Epidemiological profile of suspected cases of measles and rubella notified on SINAN, Brazil, 2007 to 2016

Descrever os casos suspeitos de sarampo e rubéola notificados no Sistema de Informação de Agravos de Notificação (Sinan), Brasil, 2007 a 2016. Métodos: Os dados foram extraídos do Sinan, referentes aos anos de 2007 a 2016. As variáveis utilizadas foram os números de notificações de casos de sarampo e rubéola por regiões e ano, idade, sexo, hospitalização, estado gestacional, histórico vacinal, realização de bloqueio vacinal, coletas sorológicas (S1 e S2), sinais e sintomas, investigação adequada, critério de confirmação ou descarte e classificação final do caso. Resultados: Entre 2007 e 2016 houve 127.802 casos suspeitos de sarampo e rubéola notificados. Aproximadamente 92% dos casos foram investigados, a maioria em menores de cinco anos. Os sintomas mais frequentes foram tosse (40%) e coriza (38%). Como instrumento de vigilância foi coletado sangue para confirmação laboratorial em 87% das notificações. A maioria dos casos de sarampo ocorreu entre os anos de 2011 e 2015, relacionados a casos importados, totalizando 1.443 casos; para rubéola, 10.125 casos foram confirmados. Foram descartados 1,3% (1.698/127.802) e 5,1% (6.555/127.802) das notificações de sarampo e rubéola, respectivamente. Foram ignorados 9% (11.523/127.802) para sarampo e 49% (62.978/127.802) para rubéola. Conclusão: A vigilância dos casos de doenças exantemáticas permitiu demonstrar a situação dos casos de doenças exantemáticas circulantes no país como importante ferramenta de saúde pública. O grande número de casos descartados classificados como ignorados merece atenção, no sentido de melhorar o encerramento dos casos suspeitos notificados

To describe the suspected cases of measles and rubella notified in the Notifiable Diseases Information System (Sinan), Brazil, from 2007 to 2016. Methods: Data were extracted from Sinan referring to the years 2007 to 2016. The variables used were the number of notifications of measles and rubella cases by region and year, age, gender, hospitalization, gestational status, vaccination history, vaccination blockade, serological collections (S1 and S2), signs and symptoms, adequate investigation, confirmation criteria or disposal and final case classification. Results: Between 2007 and 2016, there were 127,802 suspected cases of measles and rubella reported. Approximately 92% of cases were investigated, mostly in children under five years of age. The most frequent symptoms were cough (40%) and runny nose (38%). As a surveillance tool, blood was collected for laboratory confirmation in 87% of notifications. Most Measles cases occurred between 2011 and 2015, related to imported cases, totaling 1,443 cases; for Rubella 10,125 cases were confirmed. 1.3% (1,698/127,802) and 5.1% (6,555/127,802) of measles and rubella notifications, respectively, were discarded. 9% (11,523/127,802) for measles and 49% (62,978/127,802) for rubella were ignored. Conclusion: Surveillance of cases of exanthematous diseases allowed demonstrating the situation of cases of exanthematous diseases circulating in the country as an important public health tool. The large number of discarded cases classified as ignored deserves attention, in order to improve the closing of notified suspected cases

Análise das Doenças Exantemáticas de Notificação Compulsória no Estado de Santa Catarina Entre 2009 e 2019 / Analysis of Exanthematous Diseases of Compulsory Notification in the State of Santa Catarina from 2009 to 2019

Introdução: Doenças exantemáticas (DE) são patologias infecciosas agudas, que têm como característica principal a manifestação dermatológica. Entre elas, sarampo e rubéola são de notificação compulsória. A permanência da circulação destes vírus no mundo tem causado surtos em diversas regiões, como em SC, embora sejam doenças evitáveis por meio da imunização. Métodos: Trata-se de um estudo de delineamento ecológico, constituído de casos notificados por DE em SC no período de 2009 a 2019. Os dados foram coletados no Sistema Nacional de Agravos e Notificações (SINAN/DATASUS). Resultados: Foram notificados 190 casos de DE, 41,57% na faixa etária de 20 a 29 anos, 55,91% masculinos, 88,70% brancos e 2,15% gestantes. Houve confirmação laboratorial em 85,16%, e 72,72% foram causados pelo vírus sarampo selvagem. Exantema predominou em novembro em 46,77%, e febre em outubro, em 41,93%. Tosse esteve presente em 89,24%, coriza em 67,20% e conjuntivite em 50,53%. A macrorregião com maior média de cobertura vacinal foi a Grande Oeste, com 86,85%, e a menor, a Grande Florianópolis, com 72,07%. A maior incidência de sarampo ocorreu em 2019 no Nordeste e Planalto Norte com 11,34, e a de rubéola 0,13 no Grande Oeste no mesmo ano. Foi realizado bloqueio vacinal em 95,34% dos casos, e 64,28% foram autóctones. Conclusão: Observou-se que as DE acometem indistintamente ambos os sexos, etnias e idades, sendo a vacinação a forma mais eficaz de prevenir surtos. A reemergência ocorrida no estado foi consequência das baixas taxas de cobertura vacinal, apontando para a necessidade de melhorias nas ações de imunização.

Introduction: Exanthematous diseases (ED) are acute infectious pathologies that present mainly dermatological manifestations. Among them, measles and rubella demand compulsory notification. The continued circulation of these viruses has caused outbreaks in several regions, such as Santa Catarina, although they are preventable diseases through immunization. Methods: This is a study of ecological design consisting of cases notified of ED in SC from 2009 to 2019. Data collection from the National System of Diseases and Notifications (SINAN/DATASUS). Results: 190 cases of ED were notified, 41.57% in the age group 20 to 29 years, 55.91% male, 88.70% white, and 2.15% pregnant women. Laboratory confirmation occurred in 85.16%, and the wild measles virus was the cause in 72.72%. Exanthema predominated in November with 46.77% and fever in October with 41.93%. Cough was present in 89.24%, coryza in 67.20%, and conjunctivitis in 50.53%. The macro-region with the highest average vaccination coverage was the great west, 86.85%, and the lowest was greater Florianópolis, 72.07%. The highest incidence of measles occurred in 2019. Northeast and North Plateau scored 11.34, and rubella at 0.13 in the Great West in the same year. Vaccine block occurred in 95.34% of cases, and 64.28% were autochthonous. Conclusions: The study observed that EDs affect both sexes, ethnicities, and ages indistinctly, and vaccination is the most effective way to prevent outbreaks. The re-emergence that occurred in the state was a consequence of low rates of vaccination coverage, pointing to the need for improvements in immunization activities

Congenital Rubella Syndrome as a possible cause for persistent thrombocytopenia in early infancy: The Forgotten Culprit.

We present a case of a late preterm intrauterine growth-restricted neonate with isolated and persistent severe thrombocytopenia. At birth, the neonate did not have a complete clinical spectrum of congenital rubella syndrome (CRS) but later developed peculiar findings that helped clinch the diagnosis. The neonate also had interstitial pneumonia and died secondary to superimposed acute viral infection leading to acute respiratory distress syndrome. The serology was positive for IgM antibodies against the rubella virus. The constellation of clinical manifestations of congenital rubella in the presence of positive IgM antibody against rubella and consistent histopathology confirmed the diagnosis of CRS.

Rubella antibodies in vertically and horizontally HIV-infected young adults vaccinated early in life and response to a booster dose in those with seronegative results.

BACKGROUND: Very limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life. METHODS: Prospective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards. RESULTS: Time since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm3; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels. CONCLUSION: As vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose.

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.

Vaccine-Associated Rubella Caused by the RA 27/3 Strain.

Vaccine-associated rubella is a very rare adverse effect after rubella vaccination; we report the characteristics of a young women who, after a vaccination campaign where she received three different vaccines against influenza, tetanus/diphtheria, and measles/rubella, developed a fever and rash consistent with rubella disease that was confirmed by sequencing of the virus. The evolution was favorable. The woman had two close contacts who did not develop the disease. Follow-up of the patient and her contacts was important to detect complications and for epidemiology surveillance.

Rational Design and Evaluation of the Recombinant Multiepitope Protein for Serodiagnosis of Rubella.

BACKGROUND: Rubella is an infection caused by rubella virus (RV) and is generally regarded as a mild childhood disease. The disease continues to be of public health importance mainly because when the infection is acquired during early pregnancy, it often results in fetal abnormalities, which are classified as congenital rubella syndrome (CRS). An accurate diagnosis of rubella is thus of pivotal importance for proper treatment. OBJECTIVES: The aim of the study was to produce a recombinant multiepitope protein (rMERUB) for the diagnosis of rubella, based on conserved immunodominant epitopes of glycoprotein E1 and E2. METHODS: A synthetic gene was designed and cloned into vector pET21a with a 6xHis tag at the Cterminal for affinity purification and overexpressed in Escherichia coli cells. Biophysical analysis of rMERUB was performed by circular dichroism. Biological activity was assessed using an in-house ELISA assay. RESULTS: Expression in Escherichia coli showed a ~22 kDa protein that was purified and used to perform structural assays and an IgG ELISA. Structural analyses reveal that rMERUB has a ß leaf pattern that promotes the exposure of epitopes, thus allowing antibody recognition. Evaluation of 33 samples (22=positive; 11=negative) was performed using in-house ELISA and this was compared with a commercial kit. The sensitivity was 100% (95% CI: 85-100) and specificity 90.91% (95% CI: 62-99). Excellent agreement (Kappa index = 0.9) was obtained between ELISA assays. CONCLUSION: The careful choice of epitopes and the high epitope density, coupled with simple-step purification, pinpoints rMERUB as a promising alternative for rubella diagnosis, with potential for the development of a diagnostic kit.

Congenital Rubella Syndrome as a possible cause for persistent thrombocytopenia in early infancy: The Forgotten Culprit

Abstract We present a case of a late preterm intrauterine growth-restricted neonate with isolated and persistent severe thrombocytopenia. At birth, the neonate did not have a complete clinical spectrum of congenital rubella syndrome (CRS) but later developed peculiar findings that helped clinch the diagnosis. The neonate also had interstitial pneumonia and died secondary to superimposed acute viral infection leading to acute respiratory distress syndrome. The serology was positive for IgM antibodies against the rubella virus. The constellation of clinical manifestations of congenital rubella in the presence of positive IgM antibody against rubella and consistent histopathology confirmed the diagnosis of CRS.

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)