Reduced effectiveness of repeat influenza vaccination: distinguishing among within-season waning, recent clinical infection, and subclinical infection.

Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness (VE) Network (2011-2012 to 2018-2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by one week. After accounting for waning VE, repeat vaccinees were still more likely to test positive for A(H3N2) (OR=1.11, 95%CI:1.02-1.21) but not for influenza B or A(H1N1). We found that clinical infection influenced individuals' decision to vaccinate in the following season while protecting against clinical infection of the same (sub)type. However, adjusting for recent clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on VE.

Anti-SARS-CoV-2 Antibody Levels Associated With COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu Vaccine Effectiveness Network, October 2021-June 2022.

BACKGROUND: We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study. METHODS: From October 2021 to June 2022, study sites in 7 states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 - adjusted odds ratio of COVID-19) × 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. RESULTS: Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories. CONCLUSIONS: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.

Influenza Vaccine Effectiveness Against Influenza A-Associated Emergency Department, Urgent Care, and Hospitalization Encounters Among US Adults, 2022-2023.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A-associated ED/UC encounters was 44% (95% confidence interval [CI], 40%-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza A-associated hospitalizations was 35% (95% CI, 27%-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period.

BACKGROUND: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. METHODS: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. RESULTS: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. CONCLUSION: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.

US Public Health Preparedness and Response to Highly Pathogenic Avian Influenza A(H5N1) Viruses.

US public health preparedness and response to highly pathogenic avian influenza A(H5N1) viruses are assessed in this survey study conducted by the CDC.

Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults.

The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.

Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines.

Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018-19 (N = 723) and 2019-20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.

Antibody Response to Symptomatic Infection With SARS-CoV-2 Omicron Variant Viruses, December 2021-June 2022.

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection.

Late-Season Influenza Vaccine Effectiveness Against Medically Attended Outpatient Illness, United States, December 2022-April 2023.

BACKGROUND: The 2022-23 US influenza season peaked early in fall 2022. METHODS: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design. RESULTS: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups. CONCLUSIONS: 2022-23 late-season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.

Hospital-based surveillance of intussusception among infants / Vigilância hospitalar de intussuscepção entre neonatos

Abstract Objective: Intussusception surveillance was initiated after the nationwide introduction of live attenuated monovalent rotavirus vaccine (RV1). The objective is to assess the epidemiology of intussusception and compare the number of cases before and after the introduction of rotavirus vaccine. Methods: Cases of intussusception occurring between March 2006 and January 2008 were identified through a prospective enhanced passive surveillance system established in sentinel state hospitals. Retrospective review of medical records was used to identify cases, which occurred in sentinel hospitals between January 2001 and February 2006. Results: From 2001 to 2008, 331 intussusception cases were identified, 59.5% were male, with peak incidence among those 18–24 weeks of age. Overall <10% of cases were among infants 6–14 weeks of age (when the first dose of RV1 is administered). The most frequently observed signs or symptoms of intussusception included vomiting (89.4%), bloody stool (75.5%), and abdominal distention (71.8%). A majority (92.1%) of the case-patients required surgery for treatment; 31.8% of those who underwent surgery required bowel resection, and 13 (3.9%) died. Among the 21 hospitals that reported cases throughout the entire surveillance period (2001–2008), the number of intussusception events during 2007 (n = 26) and 2008 (n = 19) was not greater than the average annual number (n = 31, range 24–42) during baseline years 2001–2005. Conclusions: Although this analysis did not identify an increase in intussusception cases during the two years after RV1 introduction, these results support the need for special epidemiologic methods to assess the potential link between rotavirus vaccine and this very rare adverse event.

Resumo Objetivo: A vigilância da intussuscepção foi iniciada após a introdução da vacina monovalente viva atenuada contra rotavírus (RV1) em todo o país. O objetivo é avaliar a epidemiologia da intussuscepção e comparar a quantidade de casos antes e depois da introdução da vacina contra rotavírus. Métodos: Os casos de intussuscepção entre março de 2006 e janeiro de 2008 foram identificados por meio de um sistema de vigilância passivo prospectivo aprimorado estabelecido em hospitais-sentinela estaduais. A análise retrospectiva de prontuários médicos foi usada para identificar os casos que ocorreram em hospitais-sentinela entre janeiro de 2001 e fevereiro de 2006. Resultados: De 2001-2008, identificamos 331 casos de intussuscepção, 59,5% dos quais ocorreram em pacientes do sexo masculino, com pico de incidência entre aqueles com 18-24 semanas de idade. Em geral, < 10% dos casos ocorreram entre neonatos com 6-14 semanas de idade (quando a 1a dose de RV1 é administrada). Os sinais ou sintomas de intussuscepção observados com mais frequência incluíam vômito (89,4%), fezes com sangue (75,5%) e distensão abdominal (71,8%). A maioria (92,1%) dos pacientes precisou de cirurgia para o tratamento; 31,8% dos que se submeteram à cirurgia precisaram de ressecção intestinal e 13 (3,9%) vieram a óbito. Entre os 21 hospitais que relataram casos durante todo o período de vigilância (2001-2008), a quantidade de casos de intussuscepção em 2007 (n = 26) e 2008 (n = 19) não foi maior do que a quantidade média anual (31, faixa de 24-42) durante os anos-base de 2001-2005. Conclusões: Embora esta análise não tenha identificado um aumento nos casos de intussuscepção nos dois anos após a introdução da RV1, esses resultados justificam a necessidade de métodos epidemiológicos especiais para avaliar a possível associação entre a vacina contra rotavírus e esse evento adverso muito raro.

Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil / Impacto de la vacuna neumocócica conjugada 10-valente en la meningitis neumocócica en niños de hasta dos años de edad en Brasil / Impacto da vacina pneumocócica conjugada 10-valente na meningite pneumocócica em crianças com até dois anos de idade no Brasil

The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009) and post-vaccination (2011-2012) periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.

El objetivo de este estudio fue analizar el impacto de la vacunación contra el Streptococcus pneumoniae en la morbilidad y mortalidad de la meningitis neumocócica en niños ≤ 2 años en Brasil, 2007-2012. Se trata de un estudio descriptivo ecológico que analiza los datos del Sistema de Información Enfermedades de Notificación Obligatoria en Brasil. El período previo (2007-2009) y posterior a la vacunación (2011-2012) fueron examinados para comparar las tasas de incidencia y mortalidad. 1.311 casos de meningitis neumocócica con 430 muertes se registraron durante el período de estudio. Hubo una disminución de la incidencia de 3,70 casos por 100.000 habitantes en 2007, a 1,84/100.000 en 2012, mientras que la tasa de mortalidad cayó 1,30 a 0,40 óbitos/100.000, se produjeron reducciones del 50% y 69%, respectivamente, con mayores impactos identificados entre los niños de 6-11 meses de edad. Los resultados indican una reducción en la morbilidad y mortalidad por meningitis neumocócica dos años después de la introducción de la vacuna conjugada antineumocócica 10-valente, lo que sugiere su eficacia.

O objetivo deste trabalho foi analisar o impacto da vacinação contra o Streptococcus pneumoniae na morbidade e mortalidade por meningite pneumocócica em crianças ≤ 2 anos, no Brasil, entre 2007-2012. Este é um estudo descritivo com análise ecológica, utilizando dados do Sistema de Informação de Agravos de Notificação. Foram definidos os períodos pré-vacinal (2007-2009) e pós-vacinal (2011-2012) para comparar as taxas de incidência e mortalidade. Foram identificados 1.311 casos e 430 óbitos no período do estudo. A taxa de incidência diminuiu de 3,70/100.000 no ano de 2007 para 1,84/100.000 em 2012, e a mortalidade reduziu de 1,30/100.000 para 0,40/100.000, o que significa uma redução de 50% e 69%, respectivamente, com maior impacto identificado na faixa etária de 6 a 11 meses. Os resultados indicam uma diminuição nos indicadores de morbidade e mortalidade de meningite pneumocócica, observados dois anos após a introdução da vacina pneumocócica conjugada 10-valente, sugerindo sua efetividade.

Survey of rubella knowledge and acceptability of rubella vaccination among Brazilian adults prior to mass vaccination / Encuesta sobre el conocimiento de la rubéola y la aceptabilidad de la vacunación antirrubeólica en los adultos brasileños antes de una campaña de vacunación masiva

OBJECTIVE: Evaluate knowledge of rubella and acceptability of vaccination and identify sources of health information among brazilian adults to inform communication strategies for a national vaccination campaign to eliminate rubella and congenital rubella syndrome (CRS). METHODS: From 5-8 July 2008 a qualitative telephone survey was conducted among a nonprobabilistic sample of brazilian adults 18 to 65 years of age (n = 1 023) from all five geographic regions of Brazil to measure knowledge of rubella and willingness to receive the vaccine and to identify sources of health information. Frequencies of responses were stratified by respondents' sex, age, education, and income. RESULTS: Although 69.9 percent of respondents said they knew what rubella was, actual knowledge of the disease was limited, with only 29.9 percent answering affirmatively when asked if they would recognize symptoms of rubella infection. Self-reported knowledge increased with increasing age, education, and income, and was higher among women than men. A total of 94.5 percent of the respondents expressed willingness to be vaccinated for rubella elimination. The most frequently mentioned sources of health information were television and doctors. CONCLUSIONS: Despite limited knowledge of rubella, brazilian adults expressed willingness to be vaccinated for disease elimination.

OBJETIVO: Evaluar el conocimiento de la rubéola y la aceptabilidad de la vacunación antirrubeólica, y determinar las fuentes de información sanitaria en los adultos brasileños, con objeto de fundamentar las estrategias de comunicación de una campaña nacional de vacunación dirigida a eliminar la rubéola y el síndrome de rubéola congénita (SRC). MÉTODOS: Del 5 al 8 de julio del 2008 se llevó a cabo una encuesta telefónica cualitativa en una muestra no probabilística de adultos brasileños de 18 a 65 años de edad (n = 1 023) de las cinco regiones geográficas del Brasil, con objeto de evaluar el conocimiento de la rubéola y la disposición a recibir la vacuna antirrubeólica, y determinar las fuentes de información sanitaria. Las frecuencias de las respuestas se estratificaron según el sexo, la edad, el nivel educativo y los ingresos de los entrevistados RESULTADOS: Aunque 69,9 por ciento de los entrevistados dijeron que sabían lo que era la rubéola, el conocimiento real de la enfermedad era limitado, ya que solo 29,9 por ciento respondieron afirmativamente cuando se les preguntó si reconocerían los síntomas de esta infección. El grado de conocimiento notificado por los propios entrevistados aumentó con la edad, el nivel educativo y los ingresos, y fue mayor en las mujeres que en los hombres. El 94,5 por ciento de los entrevistados expresaron su disposición a vacunarse con objeto de eliminar la rubéola. Las fuentes de información sanitaria mencionadas con mayor frecuencia fueron la televisión y los médicos. CONCLUSIONES: A pesar de tener un conocimiento limitado de la rubéola, los adultos brasileños expresaron su disposición a vacunarse con objeto de eliminar la enfermedad.

Evolução histórica da vigilância epidemiológica e do controle da febre amarela no Brasil / Historical development and evolution of epidemiological surveillance and control of yellow fever in Brazil

A febre amarela representou, no passado, um grande flagelo para a população brasileira, como um dos mais dramáticos problemas de saúde pública registrados no país. O Brasil investiu e alcançou um grande desenvolvimento técnico e científico que eliminou a transmissão urbana em nosso país em 1942 e influenciou a campanha de erradicação do Aedes aegypti das Américas, em 1958. A impossibilidade de erradicação da febre amarela silvestre, por se tratar de uma zoonose de animais silvestres, acrescida da ampla dispersão do Aedes aegypti no Brasil após a descontinuidade do programa continental por sua eliminação, torna presente a ameaça de sua re-emergência nos espaços urbanos. Embora os avanços da medicina não tenham impactado de maneira específica a terapêutica da doença, o advento da vacina antiamarílica permitiu controlar e levar para níveis reduzidos a transmissão da forma silvestre para humanos, o que, aliado ao combate do vetor urbano, tem impedido a circulação deste vírus nas populações humanas urbanas nas Américas. Neste trabalho, lança-se um olhar sobre as diversas formas de enfrentamento deste relevante problema de saúde pública desde o seu aparecimento no território brasileiro, sobre as bases técnicas e científicas que fundamentaram as ações em diferentes momentos do passado, sobre o momento atual e, também, sobre as perspectivas do seu controle; sobretudo, busca-se revisar a evolução do sistema de vigilância da febre amarela no Brasil.

In the past, yellow fever was a major scourge for the Brazilian population, one of the most dramatic public health problems in the country. Brazilian government has invested and achieved a major technical and scientific development, which finally led to the eradication of the urban transmission of the disease in Brazil, in 1 942, and influenced the campaign to eliminate Aedes aegypti in the Americas, in 1 958. The eradication of sylvaticyellow fever is impossible because it is a zoonosis of wild animals and Aedes aegypti has become widely spread in Brazil since the discontinuation of the continental elimination program; therefore its re-emergence in urban areas is a current threat. Although advances in medical sciences have not impacted on the disease's therapeutics in a specific manner, the development of the yellow fever vaccine has allowed its control, and has reduced the transmission levels of its sylvatic type to humans. This reduction and the combat against its urban vector have prevented the circulation of this virus in urban human populations in the Americas. This article casts a glance at the different ways this important public health problem has been confronted since its introduction to the Brazilian territory. It also covers the technical and scientific bases that underlie the actions at different moments of the past, the current status and the prospects for its control. Finally, it aims to analyze the evolution of the surveillance network of yellow fever in Brazil.

Brazilian experience with rapid monitoring of vaccination coverage during a national rubella elimination campaign / Monitoreo rápido de la cobertura de vacunación durante una campaña nacional de eliminación de la rubéola en el Brasil

OBJECTIVE: To describe an adapted version of the Pan American Health Organization (PAHO) methodology for rapid monitoring of vaccination coverage and its use as a supervisory tool to guide decision-making and strategies for end-stage vaccination activities ("mopup" operations) following a six-week national rubella elimination campaign in Brazil. METHODS: Vaccination coverage assessments modeled on a variation of PAHO's rapid house-to-house coverage monitoring methodology were conducted by Brazilian municipalities following mass immunization of adults and adolescents from August to December 2008. Results of monitoring assessments conducted in 3 658 (65.7 percent) of 5 564 municipalities were reported to Brazil's National Immunization Program. RESULTS: Information on vaccination against rubella was obtained from more than 1.5 million Brazilians (2.1 percent of the 70.1 million people targeted for immunization) during vaccination coverage monitoring. According to the assessment data, vaccination targets of 95 percent coverage were reached in 2 175 (59.5 percent) of the 3 658 municipalities that reported results. The percentage of municipalities that reached coverage targets was lower than administrative coverage estimates (number of vaccine doses administered divided by the immunization target population). These results informed targeted "mop-up" campaigns to reach unvaccinated populations. CONCLUSIONS: Rapid coverage monitoring implemented at the local level proved useful for deciding when to conclude vaccination activities and where to focus additional efforts to achieve desired coverage.

Describir una versión adaptada de la metodología de la Organización Panamericana de la Salud (OPS) para el monitoreo rápido de la cobertura de vacunación. Exponer su uso como herramienta de supervisión para guiar la toma de decisiones y las estrategias para las actividades de vacunación finales (campañas "de barrido") después de una campaña nacional de eliminación de la rubéola de 6 semanas de duración en el Brasil. MÉTODOS: Los municipios brasileños llevaron a cabo una evaluación de la cobertura de vacunación basada en una variante de la metodología de monitoreo rápido "casa por casa" de la OPS, después de una campaña masiva de vacunación de adultos y adolescentes efectuada entre agosto y diciembre del 2008. Los resultados de las evaluaciones de seguimiento realizadas en 3 658 (65,7 por ciento) de 5 564 municipios se comunicaron al Programa Nacional de Vacunación del Brasil. RESULTADOS: Mediante el monitoreo de la cobertura de vacunación se obtuvo información sobre la vacunación antirrubeólica de más de 1,5 millones de brasileños (2,1 por ciento de los 70,1 millones de destinatarios de la inmunización). Según estos datos, se alcanzó la meta de vacunación (cobertura del 95 por ciento) en 2 175 (59,5 por ciento) de los 3 658 municipios que presentaron resultados. El porcentaje de municipios que alcanzaron la meta de cobertura fue menor que las estimaciones de cobertura administrativa (cantidad de dosis de vacuna administradas dividida por la población destinataria de la inmunización). Estos resultados se usaron para las campañas de vacunación "de barrido" a fin de alcanzar a las poblaciones no vacunadas. CONCLUSIONES: El monitoreo rápido de la cobertura de vacunación en el nivel local resultó útil para decidir cuándo concluir las actividades de vacunación y en qué aspectos se debían concentrar los esfuerzos posteriores para lograr la cobertura deseada.

Outbreak of rubella after mass vaccination of children and adult women: challenges for rubella elimination strategies / Brote epidémico de rubéola tras la vacunación masiva de niños y mujeres adultas: un reto para las estrategias de eliminación de la rubéola

OBJECTIVE: To describe rubella outbreaks and control strategies in the Brazilian state of Rio Grande do Sul before rubella elimination. METHODS: We analyzed rubella and congenital rubella syndrome surveillance data for the state of Rio Grande do Sul and calculated age- and gender-specific incidence of confirmed rubella cases in 2007. We obtained data on measles-rubella doses administered during the outbreak from the state immunization program and reviewed the timing of suspect case notification and implementation of control measures. RESULTS: Of 2 842 confirmed rubella cases reported to the state health department in 2007, 2 145 (75.5 percent) were in males (39.5 cases per 100 000 population) and 697 (24.5 percent) were in females (12.3 per 100 000 population). Incidence among 15- to 39-year-olds was 1.8 to 5.5 times higher in males than in females. Rubella genotype 2B was detected in nasopharyngeal specimens from 13 patients from multiple chains of transmission. Eight children were born with congenital rubella syndrome (5.9 cases per 100 000 births in 2008). Delayed notification of initial cases hampered early control efforts, resulting in outbreak spread throughout the state. Rubella transmission was interrupted after mass vaccination of adult men and women as part of a national vaccination campaign. CONCLUSIONS: Routine vaccination strategies and mass vaccination of adolescents and adults for accelerated rubella control and elimination should target men and women.

OBJETIVO: Describir los brotes de rubéola y las estrategias para el control de la enfermedad anteriores a la eliminación de la rubéola en el estado brasileño de Rio Grande do Sul. MÉTODOS: Se analizaron los datos de vigilancia epidemiológica sobre la rubéola y el síndrome de rubéola congénita del estado de Rio Grande do Sul y se calculó la incidencia específica por edad y sexo de los casos confirmados de rubéola en el 2007. A partir del programa de vacunación estatal se obtuvieron datos sobre las dosis de vacunación antisarampionosa y antirrubeólica administradas durante el brote y se analizaron el momento de notificación de los casos sospechosos y la puesta en práctica de medidas de control. RESULTADOS: De los 2842 casos confirmados de rubéola notificados al departamento de salud estatal en el 2007, 2 145 (75,5 por ciento) correspondieron a hombres (39,5 casos por 100000 habitantes) y 697 (24,5 por ciento) a mujeres (12,3 por 100000 habitantes). La incidencia en las personas de 15 a 39 años de edad fue de 1,8 a 5,5 veces mayor en los varones que en las mujeres. En 13 pacientes provenientes de distintas cadenas de transmisión se detectó el genotipo 2B del virus de la rubéola en muestras obtenidas de la nasofaringe. Nacieron 8 niños con síndrome de rubéola congénita (5,9 casos por 100000 nacimientos en el 2008). La demora en la notificación de los casos iniciales obstaculizó la adopción temprana de medidas de control, lo que hizo que el brote se propagara a todo el estado. La transmisión de la rubéola se interrumpió después de la vacunación masiva de varones y mujeres adultos como parte de una campaña nacional de vacunación. CONCLUSIONES: Las estrategias de vacunación sistemática y la vacunación masiva de adolescentes y adultos tendientes a acelerar el control y la eliminación de la rubéola deben dirigirse tanto a varones como a mujeres.

Participação em dias nacionais de vacinação contra poliomielite: resultados de inquérito de cobertura vacinal em crianças nas 27 capitais brasileiras / Participation in national polio immunization days: results of a vaccine coverage survey among children in 27 Brazilian cities

No Brasil, os Dias Nacionais de Vacinação (DNV) são realizados duas vezes ao ano para manter a eliminação da poliomielite e prover a vacinação de rotina para crianças menores de cinco anos. Poucos estudos examinam fatores associados à participação das crianças brasileiras nos Dias Nacionais de Vacinação ou a contribuição desses dias de vacinação para a cobertura com as vacinas recomendadas. MÉTODOS: Inquérito domiciliar com amostragem por conglomerados realizado nas 26 capitais e no Distrito Federal. Foram estudadas as datas de aplicação das vacinas, verificando-se a participação das crianças entre 19 e 35 meses de idade no DNV mais recente, ou o motivo alegado para não fazê-lo. Os dados obtidos foram cotejados com dados administrativos. RESULTADOS: Das 17.749 crianças incluídas no inquérito, 16.213 (91 por cento) participaram no último DNV. Crianças que receberam vacinas no setor privado tiveram menor participação (84 por cento) no DNV. Em 13 capitais, as estimativas de cobertura baseadas no número de doses aplicadas foram superiores às do inquérito. Entre as crianças que não participaram no último DNV, os principais motivos de não participação foram decisão dos pais, orientação médica, a criança estar doente e fatores associados com a organização do DNV. No total, 15 por cento das crianças incluídas receberam pelo menos uma dose de vacina além da vacina oral contra poliomielite no último DNV, incluindo vacinas contra febre amarela, hepatite B, tríplice viral (sarampo-rubéola-caxumba) e difteria-tétano-pertussis-Haemophilus influenzae tipo b. CONCLUSÕES: Nas capitais brasileiras, os dias nacionais de vacinação continuam tendo altos níveis de participação da população e oferecem oportunidades para recuperação da cobertura vacinal. Os motivos para não comparecer aos DNV evidenciam a necessidade de se estudar estratégias diferenciadas de comunicação para incorporação destas crianças.

Investigation of measles IgM-seropositive cases of febrile rash illnesses in the absence of documented measles virus transmission, State of São Paulo, Brazil, 2000-2004 / Investigação dos casos de doenças febris exantemáticas com IgM reagente contra o sarampo na ausência de transmissão documentada do vírus do sarampo, Estado de São Paulo, 2000-2004

INTRODUCTION: To review measles IgM-positive cases of febrile rash illnesses in the State of São Paulo, Brazil, over the five-year period following interruption of measles virus transmission. METHODS: We reviewed 463 measles IgM-positive cases of febrile rash illness in the State of São Paulo, from 2000 to 2004. Individuals vaccinated against measles < 56 days prior to specimen collection were considered to be exposed to the vaccine. Serum from the acute and convalescent phases was tested for evidence of measles, rubella, parvovirus B19 and human herpes virus-6 infection. In the absence of seroconversion to measles immunoglobulin-G, measles IgM-positive cases were considered false positives in individuals with evidence of other viral infections. RESULTS: Among the 463 individuals with febrile rash illness who tested positive for measles IgM antibodies during the period, 297 (64 percent) were classified as exposed to the vaccine. Among the 166 cases that were not exposed to the vaccine, 109 (66 percent) were considered false positives based on the absence of seroconversion, among which 21 (13 percent) had evidence of rubella virus infection, 49 (30 percent) parvovirus B19 and 28 (17 percent) human herpes virus-6 infection. CONCLUSIONS: Following the interruption of measles virus transmission, thorough investigation of measles IgM-positive cases is required, especially among cases not exposed to the vaccine. Laboratory testing for etiologies of febrile rash illness aids interpretation of these cases.

INTRODUÇÃO: Revisar os casos de doenças febris exantemáticas com IgM reagente contra o sarampo, no Estado de São Paulo, Brasil, durante os cinco anos seguidos a interrupção da transmissão do vírus do sarampo. MÉTODOS: Nós revisamos 463 casos de doenças febris exantemáticas com IgM reagente contra o sarampo, no Estado de São Paulo, Brasil, de 2000 a 2004. Indivíduos vacinados contra o sarampo 56 dias antes da coleta de amostra foram considerados expostos à vacina. Soros da fase aguda e de convalescença foram testados para a evidência de infecção de sarampo, rubéola, parvovírus B19 e herpes vírus 6. Na ausência de soroconversão para imunoglobulina G contra o sarampo, casos com IgM reagente contra o sarampo foram considerados falsos positivos em pessoas com evidência de outras infecções virais. RESULTADOS: Entre as 463 pessoas com doenças febris exantemáticas que testaram positivo para anticorpos IgM contra o sarampo durante o período, 297 (64 por cento) pessoas foram classificadas como expostas à vacina. Entre os 166 casos não expostos à vacina, 109 (66 por cento) foram considerados falsos positivos baseado na ausência de soroconversão, dos quais 21 (13 por cento) tiveram evidência de infecção por vírus da rubéola, 49 (30 por cento) parvovírus B19 e 28 (17 por cento) infecção por herpes vírus humano 6. CONCLUSÕES: Após a interrupção da transmissão do vírus do sarampo é necessária exaustiva investigação dos casos com IgM reagente contra o sarampo, especialmente dos casos não expostos à vacina. Testes laboratoriais para etiologias das doenças febris exantemáticas ajudam na interpretação destes casos.

The burden of pneumococcal disease among Latin American and Caribbean children: review of the evidence / La carga de enfermedad neumocócica en niños de América Latina y el Caribe: revisión de la información científica

OBJECTIVE: To conduct a comprehensive review of data on pneumococcal disease incidence in Latin America and the Caribbean and project the annual number of pneumococcal disease episodes and deaths among children < 5 years of age in the region. METHODS: We carried out a systematic review (1990 to 2006) on the burden of pneumococcal disease in children < 5 years of age in the region. We summarized annual incidence rates and case fatality ratios using medians and interquartile ranges for invasive pneumococcal disease (IPD) (including all-IPD and separately abstracting pneumococcal meningitis, pneumonia, bacteremia, and sepsis data), pneumonia (all cause and radiologically confirmed), and acute otitis media by age group: < 1 year, < 2 years, and < 5 years. We modeled age-specific cumulative incidence of disease obtained from standard Kaplan-Meier analysis and projected data to obtain regional estimates of disease burden. We adjusted burden estimates by serotype coverage, vaccination coverage, and vaccine efficacy to estimate the number of cases and deaths averted. RESULTS: Of 5 998 citations identified, 26 papers from 10 countries were included. The estimated annual burden of pneumonia, meningitis, and acute otitis media caused by pneumococcus in children < 5 years of age ranged from 980 000 to 1 500 000, 2 600 to 6 800, and 980 000 to 1 500 000, respectively. An estimated 12 000 to 28 000 deaths due to pneumococcal disease occur in the region annually. Pneumococcal conjugate vaccine could save 1 life per 1 100 and prevent 1 case per 13 children vaccinated. CONCLUSION: A substantial burden of pneumococcal disease in the region is potentially preventable with pneumococcal conjugate vaccines and should be considered in regional vaccine decision making. Results are limited by the very few studies, conducted in selected settings, included in this review.

OBJETIVO: Realizar una revisión amplia de los datos sobre la incidencia de la enfermedad neumocócica en América Latina y el Caribe y proyectar el número anual de episodios de la enfermedad y de defunciones entre niños menores de 5 años de edad en la región. MÉTODOS: Se llevó a cabo una revisión sistemática (1990-2006) sobre la carga de la enfermedad neumocócica en niños < 5 años en la región. Las incidencias anuales y las tasas de letalidad se compendiaron mediante las medianas y los rangos intercuartiles de la enfermedad neumocócica invasiva (en su conjunto y por separado para meningitis, neumonía, bacteremia y sepsis neumocócicas), la neumonía (todos los casos confirmados mediante radiología) y la otitis media aguda, por grupos de edad: < 1 año, < 2 años y < 5 años. Se modeló la incidencia acumulada de la enfermedad específica para la edad mediante el análisis estándar de Kaplan-Meier y se proyectaron los datos para obtener estimados regionales de la carga de la enfermedad. Para estimar el número de casos y muertes evitados se ajustaron los estimados de la carga según la cobertura de los serotipos bacterianos, la cobertura de la vacunación y la eficacia de la vacuna. RESULTADOS: De las 5 998 referencias identificadas se seleccionaron 26 artículos de 10 países. La carga anual estimada de neumonía, meningitis y otitis media aguda causadas por neumococos en niños < 5 años varió entre 980 000 y 1 500 000, 2 600 y 6 800, y 980 000 y 1 500 000, respectivamente. Se estimó que en la región podrían morir anualmente entre 12 000 y 28 000 niños debido a la enfermedad neumocócica. La vacuna antineumocócica conjugada podría salvar una vida por cada 1 100 niños vacunados y evitar un caso de enfermedad por cada 13. CONCLUSIONES: Se podría evitar una parte substancial de la carga de enfermedad neumocócica en la región mediante la aplicación de vacunas antineumocócicas conjugadas y esto se debe tener en cuenta al tomar decisiones sobre la vacunación...

Impact of Haemophilus influenzae type b conjugate vaccine on bacterial meningitis in the Dominican Republic

OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib) vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children < 5 years of age were identified from admission records of the main pediatric hospital in Santo Domingo during 1998 - 2004. Laboratory criteria were used to classify meningitis cases with probable bacterial etiology; confirmed cases had positive bacterial culture or antigen detection in cerebrospinal fluid. Cumulative incidence rates of confirmed and probable bacterial meningitis were calculated for children living in the National District. Confirmed cases of Hib meningitis were enrolled in a case control study with age- and neighborhood-matched control children to calculate vaccine effectiveness. RESULTS: Before vaccine introduction, annual rates of meningitis with probable bacterial etiology were 49 cases per 100000 children < 5 years old; Hib accounted for 60 percent of confirmed bacterial cases. During 2002 - 2004, after vaccine introduction, annual rates of probable bacterial meningitis were 65 percent lower at 16 cases per 100000, and Hib accounted for 26 percent of confirmed cases. Rates of Hib meningitis and probable bacterial meningitis with no determined etiology declined by 13 and 17 cases per 100000, respectively. CONCLUSIONS: Introduction of Hib vaccine substantially reduced the incidence of confirmed and probable bacterial meningitis in the Dominican Republic. The estimated impact of Hib vaccination was twice as great when non-culture-confirmed disease was included