[Vaccinations for the immunologic memory-Repeatedly or once only?] / Impfungen für das Immungedächtnis ­ immer wieder oder einmalig?

Due to the effectiveness of vaccines some particularly threatening infectious diseases have become rare; however, vaccines are meanwhile the victims of their own success. Due to insufficient compliance and inadequate vaccination rates, there is a danger that the effectiveness of vaccination as a preventive measure will continuously disappear. In 2019 the World Health Organization classified doubts on the effectiveness of vaccines as 1 of the 10 greatest dangers to health worldwide. This article discusses important questions on vaccinations and vaccines as well as their effects in the interplay with the immune system. The following topics are covered: comparison of naturally acquired immunity and that acquired by vaccination, factors that necessitate a refresher vaccination, the role of herd immunity, prerequisites for successful eradication of a disease, influence of various T cells on the effect of vaccination, the role of immunologic memory, factors that influence protection by vaccination, vaccinations in cases of immunodeficiency, the potential and areas of implementation of passive immunization. In view of the corona pandemic and the running vaccination campaign, it must be hoped that this triggers a general renaissance of vaccinations against infectious diseases.

[Combination of COVID-19 vaccines and their efficacy: a theoretical proposalCombinação de vacinas contra a COVID-19 e sua eficácia: uma proposta teórica]. / Combinación de vacunas contra la COVID-19 y su eficacia: una propuesta teórica.

In the face of the coronavirus disease 2019 (COVID-19) pandemic, the entire world is concerned with achieving desired herd immunity to overcome the current health crisis. Estimating the efficacy that could be attained in a population by combining vaccines of different brands or technologies would be a valuable asset for public health decision-makers in the present pandemic and in similar future scenarios. This article provides a mathematical formula to estimate probable efficacy against COVID-19 when administering two vaccines in a specific population. These vaccines, given in a series, could be of different technologies and brands.

A pandemia da doença causada pelo coronavírus 2019 (COVID-19) criou a preocupação em toda a humanidade em alcançar a tão desejada imunidade coletiva para superar esta crise sanitária que o mundo está vivendo. Estimar a possível eficácia a ser obtida em uma população ao combinar vacinas de diferentes marcas ou tecnologias seria um recurso inestimável às autoridades de saúde pública na pandemia atual e em situações semelhantes futuras. O presente artigo apresenta uma fórmula matemática para estimar a provável eficácia contra a COVID-19 da vacinação em série com duas vacinas de diferentes marcas e tecnologias em uma determinada população.

Combinación de vacunas contra la COVID-19 y su eficacia: una propuesta teórica / Combination of COVID-19 vaccines and their efficacy: a theoretical proposal / Combinação de vacinas contra a COVID-19 e sua eficácia: uma proposta teórica

RESUMEN Ante la pandemia de la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés), la preocupación de toda la humanidad es alcanzar la anhelada inmunidad colectiva que permita superar esta crisis sanitaria en la que se vive. Estimar la eficacia que se podría alcanzar en una población al combinar vacunas de distintas marcas o tecnologías sería un elemento valioso para los tomadores de decisiones en el ámbito de la salud pública en la presente pandemia y en futuros escenarios similares. El presente artículo busca brindar una fórmula matemática que permita estimar la probable eficacia contra la COVID-19 al administrar dos vacunas en una población específica. Estas vacunas, aplicadas en serie, podrían ser de tecnologías y marcas distintas.

ABSTRACT In the face of the coronavirus disease 2019 (COVID-19) pandemic, the entire world is concerned with achieving desired herd immunity to overcome the current health crisis. Estimating the efficacy that could be attained in a population by combining vaccines of different brands or technologies would be a valuable asset for public health decision-makers in the present pandemic and in similar future scenarios. This article provides a mathematical formula to estimate probable efficacy against COVID-19 when administering two vaccines in a specific population. These vaccines, given in a series, could be of different technologies and brands.

RESUMO A pandemia da doença causada pelo coronavírus 2019 (COVID-19) criou a preocupação em toda a humanidade em alcançar a tão desejada imunidade coletiva para superar esta crise sanitária que o mundo está vivendo. Estimar a possível eficácia a ser obtida em uma população ao combinar vacinas de diferentes marcas ou tecnologias seria um recurso inestimável às autoridades de saúde pública na pandemia atual e em situações semelhantes futuras. O presente artigo apresenta uma fórmula matemática para estimar a provável eficácia contra a COVID-19 da vacinação em série com duas vacinas de diferentes marcas e tecnologias em uma determinada população.

Global control of COVID-19: good vaccines may not suffice.

The COVID-19 pandemic has unveiled health and socioeconomic inequities around the globe. Effective epidemic control requires the achievement of herd immunity, where susceptible individuals are conferred indirect protection by being surrounded by immunized individuals. The proportion of people that need to be vaccinated to obtain herd immunity is determined through the herd immunity threshold. However, the number of susceptible individuals and the opportunities for contact between infectious and susceptible individuals influence the progress of an epidemic. Thus, in addition to vaccination, control of a pandemic may be difficult or impossible to achieve without other public health measures, including wearing face masks and social distancing. This article discusses the factors that may contribute to herd immunity and control of COVID-19 through the availability of effective vaccines and describes how vaccine effectiveness in the community may be lower than that expected. It also discusses how pandemic control in some countries and populations may face vaccine accessibility barriers if market forces strongly regulate the new technologies available, according to the inverse care law.

La pandemia de COVID-19 ha puesto al descubierto inequidades socioeconómicas y de salud en todo el mundo. Un control epidémico eficaz requiere el logro de la inmunidad colectiva, mediante la cual se confiere a las personas vulnerables una protección indirecta al estar rodeadas de personas inmunizadas. El umbral de inmunidad colectiva determina la proporción de personas que deben vacunarse para llegar a la inmunidad colectiva. Sin embargo, el número de personas vulnerables y las oportunidades de contacto entre las personas infecciosas y las personas vulnerables influyen en el progreso de una epidemia. Por lo tanto, además de la vacunación, el control de una pandemia puede ser difícil o imposible de lograr sin otras medidas de salud pública, como las mascarillas y el distanciamiento social. Este artículo trata sobre los factores que pueden contribuir al logro de la inmunidad colectiva y el control de la COVID-19 mediante la disponibilidad de vacunas efectivas y describe cómo la efectividad de las vacunas en la comunidad puede ser inferior a la prevista. También aborda cómo el control pandémico en algunos países y grupos poblacionales puede enfrentarse a obstáculos que dificultan la accesibilidad de las vacunas si las fuerzas del mercado son el principal factor que regula las nuevas tecnologías disponibles, como se indica en la ley de atención inversa.

A pandemia de COVID-19 revelou iniquidades socioeconômicas e de saúde no mundo todo. Um controle epidêmico eficaz requer a obtenção da imunidade coletiva, em que indivíduos suscetíveis recebem proteção indireta por estarem rodeados de indivíduos imunizados. A proporção de pessoas que precisam ser vacinadas para se alcançar a imunidade coletiva é definida pelo limiar da imunidade coletiva. Porém, o número de indivíduos suscetíveis e as oportunidades de contato entre indivíduos infecciosos e suscetíveis influenciam o progresso de uma epidemia. Portanto, além da vacinação, o controle de uma pandemia pode ser difícil ou impossível de ser alcançado sem outras medidas de saúde pública, incluindo o uso de máscaras e o distanciamento social. Este artigo discute os fatores que podem contribuir para a imunidade coletiva e para o controle da COVID-19 por meio da disponibilidade de vacinas eficazes, e descreve como a eficácia das vacinas na comunidade pode ser menor do que o esperado. Também discute como o controle da pandemia em alguns países e populações pode enfrentar barreiras de acessibilidade às vacinas se as forças de mercado regularem fortemente as novas tecnologias disponíveis, conforme a lei dos cuidados inversos.

Population-level seropositivity trend for SARS-Cov-2 in Rio Grande do Sul, Brazil

ABSTRACT OBJECTIVE To describe the evolution of seropositivity in the State of Rio Grande do Sul, Brazil, through 10 consecutive surveys conducted between April 2020 and April 2021. METHODS Nine cities covering all regions of the State were studied, 500 households in each city. One resident in each household was randomly selected for testing. In survey rounds 1-8 we used the rapid WONDFO SARS-CoV-2 Antibody Test (Wondfo Biotech Co., Guangzhou, China). In rounds 9-10, we used a direct ELISA test that identifies IgG to the viral S protein (S-UFRJ). In terms of social distancing, individuals were asked three questions, from which we generated an exposure score using principal components analysis. RESULTS Antibody prevalence in early April 2020 was 0.07%, increasing to 10.0% in February 2021, and to 18.2% in April 2021. In round 10, self-reported whites showed the lowest seroprevalence (17.3%), while indigenous individuals presented the highest (44.4%). Seropositivity increased by 40% when comparing the most with the least exposed. CONCLUSIONS The proportion of the population already infected by SARS-Cov-2 in the state is still far from any perspective of herd immunity and the infection affects population groups in very different levels.

Population-based seroprevalence of SARS-CoV-2 and the herd immunity threshold in Maranhão

ABSTRACT OBJECTIVE: To estimate the seroprevalence of SARS-CoV-2 in the state of Maranhão, Brazil. METHODS: A population-based household survey was performed, from July 27, 2020 to August 8, 2020. The estimates considered clustering, stratification and non-response. Qualitative detection of IgM and IgG antibodies was performed in a fully-automated Elecsys® Anti-SARS-CoV-2 electrochemiluminescence immunoassay on the Cobas® e601 analyzer (Roche Diagnostics). RESULTS: In total, 3,156 individuals were interviewed. Seroprevalence of total antibodies against SARS-CoV-2 was 40.4% (95%CI 35.6-45.3). Population adherence to non-pharmaceutical interventions was higher at the beginning of the pandemic than in the last month. SARS-CoV-2 infection rates were significantly lower among mask wearers and among those who maintained social and physical distancing in the last month compared to their counterparts. Among the infected, 26.0% were asymptomatic. The infection fatality rate (IFR) was 0.14%, higher for men and older adults. The IFR based on excess deaths was 0.28%. The ratio of estimated infections to reported cases was 22.2. CONCLUSIONS: To the best of our knowledge, the seroprevalence of SARS-CoV-2 estimated in this population-based survey is one of the highest reported. The local herd immunity threshold may have been reached or might be reached soon.

Serosurveillance for vaccine-preventable diseases: A look inside the pertussis experience / Serovigilancia de enfermedades prevenibles por vacunación: una mirada desde la experiencia con la tosferina

Abstract Introduction: Serological surveillance (serosurveillance) provides the most direct measure of herd immunity of vaccine-preventable diseases. Little is known about the opportunities and challenges of serosurveillance experiences, particularly pertussis. Objective: To describe the process of serosurveillance for vaccine-preventable diseases with an emphasis on the experience of pertussis in the metropolitan area of Antioquia (Valle de Aburrá) in 2015 and 2016 and analyze the contributions and challenges for its sustainability. Materials and methods: We described the planning and conduction of serosurveillance of pertussis antibodies of mothers and in the umbilical cord at the time of delivery in eight hospitals based on random sampling and their capacity to advance the serosurveillance periodically. We compared the contributions and the challenges of this experience with other probabilistic and non-probabilistic programs. Results: We achieved the participation of hospitals and mothers respecting the delivery care process. We established a serum bank following ethical and technical guidelines. This program based on the random selection of hospitals and mothers has enabled the estimation of antibodies prevalence in mothers and in the umbilical cord, which has been possible given the high coverage of hospital care during childbirth at a lower cost and fewer risks than a population-based survey in conflictive areas. The main challenges for the sustainability of this program are the creation of stable jobs and access to funding and legal and methodological long-term frameworks. Conclusions: Hospital serosurveillance as described is an option to monitor the impact of vaccination on the population. Our experience could be reproduced in other regions under similar conditions if the above-mentioned challenges are solved.

Resumen Introducción. La vigilancia serológica es la forma más directa de medir la inmunidad de rebaño frente a las enfermedades prevenibles por vacunación. Poco se sabe acerca de las oportunidades y los desafíos de las experiencias de serovigilancia, en general y, específicamente, la de la tosferina. Objetivo. Describir el proceso de serovigilancia de enfermedades prevenibles por vacunación con énfasis en la experiencia en el caso de la tosferina en el área metropolitana de Antioquia (Valle de Aburrá) en el 2015 y el 2016 y analizar lo que dicha experiencia ha aportado y los desafíos que persisten para su sostenibilidad. Materiales y métodos. Se describió el proceso de planeación y el desarrollo de la serovigilancia de tosferina en el momento del parto en ocho hospitales seleccionados al azar, así como la capacidad para adelantar el programa de manera periódica. Se compararon los aportes y los desafíos en el curso de esta experiencia con los de otros programas poblacionales probabilistas e institucionales no probabilistas. Resultados. Se logró la participación de los hospitales y de las madres con pleno respeto del proceso de atención del parto, y se conformó un banco de sueros siguiendo lineamientos éticos y técnicos. El programa permitió estimar la prevalencia de anticuerpos en la madre y en el cordón umbilical, lo que se facilitó por la alta cobertura de atención hospitalaria del parto, a un menor costo y menos riesgos que los programas poblacionales en zonas conflictivas. Los principales desafíos para la sostenibilidad del programa son la estabilidad laboral del personal de salud, así como normas y una financiación de largo plazo. Conclusiones. La serovigilancia hospitalaria es una opción para monitorizar el impacto poblacional de la vacunación. Esta experiencia se podría extender a otras regiones en condiciones similares si se resuelven los retos mencionados.

Direct, indirect, total, and overall effectiveness of the rotavirus vaccines for the prevention of gastroenteritis hospitalizations in privately insured US children, 2007-2010.

We demonstrate how direct, indirect, total, and overall effectiveness estimates and absolute benefits of rotavirus vaccines vary through the years following vaccine introduction. Privately insured US children in a large claims database were followed from age 8 months until they 1) experienced a hospitalization for rotavirus or acute gastroenteritis; 2) lost continuous health plan enrollment; 3) turned 20 months of age; or 4) reached the end of the study period. Vaccine effectiveness estimates in preventing rotavirus and acute gastroenteritis hospitalizations were estimated using Cox proportional hazards regression, stratified by calendar year and adjusted for birth month. Incidence rate differences were estimated to determine the absolute number of gastroenteritis hospitalizations prevented in the cohort. Among 905,718 children, 51%, 66%, 80%, and 86% received 1 or more doses of rotavirus vaccine in each year from 2007 to 2010. The direct vaccine effectiveness of 1 or more doses of rotavirus vaccine in preventing rotavirus gastroenteritis hospitalizations ranged from 87% to 92% each year. Accounting for indirect protection increased estimates of vaccine effectiveness by an additional 3%-8% among those vaccinated. Failing to account for population-level vaccine benefits in 2010, when circulation of rotavirus was low, could underestimate the sustained impact of the vaccine program.

Seroprevalence of antibody to influenza A(H1N1)pdm09 attributed to vaccination or infection, before and after the second (2010) pandemic wave in Australia.

OBJECTIVES: Historical records of influenza pandemics demonstrate variability in incidence and severity between waves. The influenza A(H1N1)pdm09 pandemic was the first in which many countries implemented strain-specific vaccination to mitigate subsequent seasons. Serosurveys provide opportunity to examine the constraining influence of antibody on population disease experience. DESIGN: Changes in the proportion of adults seropositive to influenza A(H1N1)pdm09over the 2009/10 (summer) interepidemic period and 2010 (winter) influenza season were measured to determine whether there was a temporal relationship with vaccine distribution and influenza activity, respectively. SETTING: Australia. SAMPLE: Plasma samples were collected from healthy blood donors from seven cities at the end of the first wave (November 2009), and before (March/April 2010) and after (November 2010) the subsequent influenza season. MAIN OUTCOME MEASURES: Haemagglutination inhibition (HI) assays were performed to assess reactivity of plasma against A(H1N1)pdm09, and the proportion seropositive (HI titre ≥ 40) compared over time, by age group and location. RESULTS: Between the 2009 and 2010 influenza seasons, the seropositive proportion rose from 22% to 43%, an increase observed across all ages and sites. Brisbane alone recorded a significant rise in seropositivity over the 2010 influenza season - from a baseline of 35% to 53%. The seropositive proportion elsewhere was ≥40% pre-season, and did not rise over winter. CONCLUSIONS: A vaccine-associated increase in seropositive proportion preceding the influenza season correlated with low levels of disease activity in winter 2010. These observations support the role of immunisation in mitigating the 'second wave' of A(H1N1)pdm09, with timing critical to ensure sustained herd protection.

Changing pattern of hepatitis a virus epidemiology in an area of high endemicity.

BACKGROUND: Continuous assessment of hepatitis A virus (HAV) seroepidemiology is a useful tool to control the risk of infection. OBJECTIVES: This study aimed to evaluate the changing patterns of anti-HAV seroprevalence in a population,which isgenerally considered to be anarea ofhigh endemicity. PATIENTS AND METHODS: Overall, the results of 3349 sera collected during the period 2005-2008 from patients attending the University Hospital of Cagliari, Italy were studied; their mean age was 52.7 years, (s + 16.22). Patients with liver disease were excluded from the study. Age specific seroprevalence results were compared with those observed in similar previous studies carried out in the same area. RESULTS: The overall prevalence of anti-HAV was 74.6% with consistently lower values in subjects younger than 40 years (17.5%; P < 0.0001) particularly in those under 30 years of age (8.9%, CI 5.8-11.9). A significant declining trend in age specific seroprevalence has been foundin people under 30 years;61% in 1988, 33% in 1995 and 8.9% in 2005-2008. CONCLUSIONS: Our findings show that a significant decline inherd immunity has occurred in the last 20 years as a consequence of lower HAV circulation due to improvementsin socio-economical and hygienic conditions. Adolescents and young adults are becoming increasingly susceptible to HAV infections, as recent outbreaks of acute HAV hepatitis have occurred. Persistent environmental monitoring and the implementation of prevention measures must be considered in order to contain the risk related to this epidemiological shift.

Inmunidad colectiva contra la rubéola según una encuesta poblacional en Medellín, Colombia / Herd immunity against rubella according to a survey of the population in Medellin, Colombia

Objetivo. Calcular la proporción crítica (Pc) para el logro de la inmunidad colectiva a partir de un estudio poblacional realizado en el 2009 en Medellín, Colombia, por edad, en forma global y desagregada por sexo, zona de procedencia y estrato socioeconómico. Métodos. Se realizó una encuesta de seroprevalencia poblacional, con una muestra aleatoria de 2 124 individuos de 6 a 64 años, representativa por edad, sexo y zona. Se estimó el número básico de reproducción utilizando una regresión cuadrática de los títulos promedio de IgG contra la rubéola por edad en los individuos no vacunados con títulos mayores o iguales a 15 UI/ml. Se calculó el número efectivo de reproducción (Re ) con los datos de la proporción ponderada de protección por edad, sexo, zona y estrato socioeconómico. Resultados. En forma global, la Pc fue de 90,0% (IC95% 88,6­95,2) y el Re de 0,95 (IC95% 0,8­1,8), para una proporción ponderada de protección de 89,4% (IC95% 86,8­91,6). La protección fue menor que la Pc esperada en ambos sexos, en los estratos socioeconómicos alto y bajo, y en la zona rural. En la zona urbana la protección fue mayor que la Pc (89,4%, IC95% 86,6­91,7 en comparación con 87,4%, IC95% 85,2­87,8). Conclusiones. En la zona urbana se ha avanzado hacia la inmunidad colectiva, pero se requiere aumentar la proporción de protección en forma global, en las mujeres, en la zona rural y en los individuos de estrato socioeconómico alto. El número efectivo puede tener un valor mayor de uno, lo que indica el potencial de propagación de la enfermedad.

Objective. Calculate the critical proportion (Pc ) for achieving herd immunity based on a 2009 population study conducted in Medellin, Colombia, by age, globally and disaggregated by sex, location, and socioeconomic stratum. Methods. A survey of seroprevalence in the population was conducted by means of a random sample of 2 124 individuals aged 6 to 64 that was representative of age, sex, and location. The basic reproduction number was estimated using a quadratic regression of the average IgG titers for rubella by age in unvaccinated individuals with titers greater than or equal to 15 IU/ml. The effective reproduction number (Re) was calculated with the data on the weighted proportion of protection by age, sex, location, and socioeconomic stratum. Results. Overall, the Pc was 90.0% (95% CI, 88.6­95.2%) and the Re was 0.95 (95% CI, 0.8­1.8), for a weighted proportion of protection of 89.4% (95% CI, 86.8­ 91.6%). Protection was lower than the expected Pc in both sexes, in high and low socioeconomic strata, and in the rural area. In the urban area, protection was greater than the Pc (89.4%, with a 95% CI, 86.6­91.7%, compared to 87.4% and a 95% CI, 85.2­87.8%). Conclusions. The urban area has made progress toward herd immunity, but the overall proportion of protection in women, the rural area, and the high socioeconomic strata must be increased. The effective number may be greater than one, indicating the potential for the spread of the disease.

Uso de modelos de análise de decisão nos programas de vacinação contra a varicela / Use of decision analysis models in the programs of vaccination against varicella

INTRODUÇÃO: A escolha entre diferentes modelos de análise de decisão introduz variabilidade nos resultados das avaliações econômicas. Modelos estáticos não captam os efeitos indiretos da vacinação comprometendo a avaliação geral dos benefícios da vacinação. Neste trabalho foram desenvolvidos um modelo dinâmico e um modelo estático para a análise de custo-efetividade (ACE) da vacina contra varicela e foram comparados os resultados obtidos com os dois modelos. MÉTODOS: Avaliação econômica completa do tipo ACE usando modelagem. As análises compararam duas estratégias: 1) introdução da vacinação infantil de rotina aos 12 meses de vida; versus 2) situação existente (vacinação após os surtos em creches e vacinação de imunodeprimidos). As análises foram conduzidas no horizonte temporal de 30 anos. RESULTADOS: O modelo dinâmico estimou que na ausência do programa de vacinação ocorreriam 2 915 294 casos de varicela por ano no Brasil, resultando em 879 095 casos ambulatoriais, 4 507 hospitalizações, 119 mortes e 4 casos de sequela. O custo total anual da varicela foi estimado em R$27 378 957 para a sociedade e em R$14 412 610 para o sistema de saúde. A razão de custo-efetividade incremental (RCEI) por ano de vida salvo foi R$14 749 na perspectiva da sociedade e R$16 582 na perspectiva do sistema de saúde. O modelo estático estimou que na ausência do programa de vacinação ocorreriam 1 656 547 casos de varicela por ano no Brasil, resultando em 629 488 casos ambulatoriais, 5 120 hospitalizações, 82 mortes e 1 caso de sequela. O custo total anual da varicela foi estimado em R$17 311 412 para a sociedade e em R$9 570 551 para o sistema de saúde. A RCEI por ano de vida salvo foi R$35 254 na perspectiva da sociedade e R$36 599 na perspectiva do sistema de saúde. Aplicando o limiar de custo efetividade da Organização Mundial de Saúde (OMS) aos resultados obtidos com o modelo dinâmico a vacinação foi considerada uma estratégia custo-efetiva o mesmo não aconteceu...

BACKGROUND: The choice between different decision analysis models introduces variability in the results of economic evaluations. Static models do not take into account the indirect effects of vaccination, thus compromising the overall assessment of vaccination benefits. This work developed two models one dynamic and another static to conduct cost-effectiveness analyses (CEA) of varicella vaccine, comparing the results of the two. METHODS: Comprehensive economic evaluation CEA using modeling. The analysis compared two strategies: 1) introduction of routine vaccination for children under 12 months, versus 2) current situation (vaccination after outbreaks in nurseries and vaccination of immunocompromised). The time horizon of the analysis was 30 years. RESULTS: The dynamic model estimated that in the absence of the vaccination program, 2 915 294 cases of varicella occurred every year in Brazil, resulting in 879,095 outpatient cases, 4,507 hospitalizations, 119 deaths and 4 sequela cases. The total annual cost of varicella was estimated at R$ 27,378,957 for the society and at R$ 14,412,610 for the health care system. From the perspective of society, the incremental cost-effectiveness ratio (ICER) was R$ 14,749 per life-year saved, while from the perspective of the health care system, it amounted to R$ 16,582. The model estimated that, in the absence of a vaccination program, there would be 1,656,547 cases of varicella every year in Brazil, resulting in 629,488 outpatient cases, 5,120 hospitalizations, 82 deaths and 1 case of sequela. The total annual cost of varicella was estimated at R$ 17,311,412 for the society, and at R$ 9,570,551 for the health care system. The ICER was R$ 35,254 and R$ 36,599 from the perspective of society and the health care system, respectively. When applying the World Health Organization (WHO)'s cost-effectiveness threshold to the dynamic model results, vaccination was considered a cost-effective strategy; this was nevertheless...