Duration of post-vaccination immunity to yellow fever in volunteers ten years after a dose-response study - A complementary study.

A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose-response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses. Clinical trial registry: NCT04416477.

Um retrato de UTI Pediátricas em um recorte transversal durante a pandemia de COVID-19: uma avaliação de estrutura das unidades / A cross-sectional Portrait of Pediatric ICUs during the COVI-19 pandemic: an assessment of the structure of the units

O interesse da presente Dissertação surgiu com o intuito de avaliar as Unidades de Terapia Intensiva Pediátricas no aspecto de estrutura do serviço. O inquérito do estudo foi colhido de 01/07/2020 a 31/10/2020 através de um questionário autopreenchido pelos 29 médicos responsáveis técnicos e pelos 1084 profissionais de saúde atuantes nas unidades. O objetivo primário da Dissertação foi avaliar a adequabilidade de aspectos estruturais de 29 Unidades de Terapia Intensiva Pediátricas de sete estados no Brasil à regulamentação normativa que já estava vigente no país antes da pandemia, e às normativas e demandas impostas durante a pandemia. Foram analisados seletos indicadores de estrutura (recursos humanos, protocolos, estrutura física, orientações e rotinas na pandemia, educação continuada e treinamento, e recursos materiais). Na análise de indicadores para verificação de adequação à normativa regulamentadora, avaliou-se que na dimensão de recursos humanos e protocolos ao menos um terço das unidades não cumpriam requisitos previstos em norma. Em recursos humanos, as menores proporções observadas foram para a categoria de técnicos de enfermagem, médicos diaristas e fisioterapeutas (65.5%, 69.1%, 82.7%). Para protocolos clínicos, há 55.2% de unidades que têm protocolos de sepse, sedação e dor instalados e vigentes. Apesar de já haver essa defasagem em questões estruturais, quando se analisou a adequação para as normativas e demandas da pandemia, verificou-se que a resposta das unidades nas diferentes dimensões de estrutura analisadas foi em geral melhor ou semelhante ao observado em estudos feitos na mesma época na América Latina. Foram entrevistados 1084 profissionais de saúde e 60% tiveram disponibilidade de Equipamentos de Proteção Individual (EPI) para assistência em procedimentos geradores de aerossol. As unidades com financiamento privado obtiveram maiores proporções de adequação em recursos humanos para algumas categorias profissionais durante a pandemia como para médicos intensivistas (44.8% x 17.2%; p<0.01). Também houve diferença significativa em recursos materiais, como para assistência em procedimentos geradores de aerossol (31.3% x 28.8%; p=0.02). A categoria profissional que teve mais inadequação à normativa para disponibilidade de EPI foi a de técnicos de enfermagem (14.4% x 11.3%; p<0.01). O que se observou, portanto, foi que nos aspectos avaliados a situação pré-pandemia era razoável, mas já com espaços para melhorias, e durante a crise sanitária houve uma resposta comparável a resultados encontrados em outros estudos na região. Porém, se tivesse havido uma gestão mais eficiente com deslocamento adequado de recursos, é provável que a reação tivesse sido melhor. (AU)

The interest of this dissertation arose to evaluate Pediatric Intensive Care Units (PICU) in terms of service structure. The study survey was collected from 07/01/2020 to 10/31/2020 through a self-completed questionnaire by the 29 technical responsible physicians and 1084 health professionals working in the unit. The primary objective was to describe and evaluate the suitability of structural aspects of 29 Pediatric Intensive Care Units from seven states in Brazil to the normative regulation that was already in course in Brazil before the pandemic, and to the norms and demands imposed during the pandemic. It is proposed to analyze structure indicators (human resources, protocols, physical structure, guidelines and routines in the pandemic, continuing education and training, and material resources). In the analysis of indicators for verification of adequacy to the regulatory norms, it was evaluated that in the dimension of human resources and protocols, at least one third of the units did not fulfill requirements foressen in the norm. In human resources, the lowest proportions observed were for the category of nursing technicians, diarist doctors and physiotherapists (65.5%, 69.1%, 82.7%). For protocols and routines, there are 55.2% of units that have sepsis sedation and pain protocols installed and current. Despite this lag, already existing, when the suitability for the pandemic's regulations and demands was analyzed, it was found that the response of the units in the different structural dimensions analyzed was generally better or similar to that observed in studies carried out at that period in Latin America. There were 1084 health professionals interviewed and 60% had personal protective Equipment (PPE) available for assistance in aerosol- generating procedures. Units with private funding had higher proportions of adequacy in human resources for some professional categories during the pandemic such as intensive care physicians (44.8% x 17.2%; p<0.01), and material resources, such as assistance in aerosol-generating procedures (31.3% x 28.8%; p=0.02). The professional category that had the most inadequacy to the regulations for the availability for of PPE (personal protective equipment) was that of nursing technicians (14.4% x 11.3%; p<0.01). What was observed, therefore, was that in the aspects evaluated, the pre-pandemic situation was reasonable, but already with room for improvement, and during the health crisis there was a response comparable to results found in other studies in the region. However, if there had been more efficient management with adequate allocation of resources, it is likely that the reaction would have been better. (AU)

Molecularly distinct memory CD4+ T cells are induced by SARS-CoV-2 infection and mRNA vaccination

Adaptive immune responses are induced by vaccination and infection, yet little is known about how CD4+ T cell memory differs between these two contexts. Notable differences in humoral and cellular immune responses to primary mRNA vaccination were observed and associated with prior COVID-19 history, including in the establishment and recall of Spike-specific CD4+ T cells. It was unclear whether CD4+ T cell memory established by infection or mRNA vaccination as the first exposure to Spike was qualitatively similar. To assess whether the mechanism of initial memory T cell priming affected subsequent responses to Spike protein, 14 people who were receiving a third mRNA vaccination, referenced here as the booster, were stratified based on whether the first exposure to Spike protein was by viral infection or immunization (infection-primed or vaccine-primed). Using multimodal scRNA-seq of activation-induced marker (AIM)-reactive Spike-specific CD4+ T cells, we identified 220 differentially expressed genes between infection- and vaccine-primed patients at the post-booster time point. Infection-primed participants had greater expression of genes related to cytotoxicity and interferon signaling. Gene set enrichment analysis (GSEA) revealed enrichment for Interferon Alpha, Interferon Gamma, and Inflammatory response gene sets in Spike-specific CD4+ T cells from infection-primed individuals, whereas Spike-specific CD4+ T cells from vaccine-primed individuals had strong enrichment for proliferative pathways by GSEA. Finally, SARS-CoV-2 breakthrough infection in vaccine-primed participants resulted in subtle changes in the transcriptional landscape of Spike-specific memory CD4+ T cells relative to pre-breakthrough samples but did not recapitulate the transcriptional profile of infection-primed Spike-specific CD4+ T cells. Together, these data suggest that CD4+ T cell memory is durably imprinted by the inflammatory context of SARS-CoV-2 infection, which has implications for personalization of vaccination based on prior infection history. One Sentence SummarySARS-CoV-2 infection and mRNA vaccination prime transcriptionally distinct CD4+ T cell memory landscapes which are sustained with subsequent doses of vaccine.

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance and high Spike-specific neutralizing antibodies

The vast spectrum of clinical features of COVID-19 keeps challenging scientists and clinicians. Control of pathogen load (host resistance) and prevention of tissue damage (disease tolerance) are essential for the outcome of infectious diseases. Both low resistance and high disease tolerance might result in long-term viral persistence, but the underlying mechanisms remain unclear. Here, we studied the immune response of immunocompetent COVID-19 patients with prolonged SARS-CoV-2 infection by immunophenotyping, cytokine and serological analysis. Despite viral loads and symptoms comparable to regular mildly-symptomatic patients, long-term carriers displayed weaker systemic IFN-I responses and fewer circulating pDCs and NK cells at disease onset. Type 1 cytokines remained low, while type-3 cytokines were in turn enhanced. Interestingly, the plasma of these patients showed a higher spike-specific neutralization capacity. The identification of very early distinct immune responses in long-term carriers adds up to our understanding on essential host protective mechanisms to ensure tissue damage control despite prolonged viral infection.

[Seroepidemiological survey of canine leishmaniasis in endemic areas of Cuiabá, State of Mato Grosso]. / Inquérito soroepidemiológico de leishmaniose canina em áreas endêmicas de Cuiabá, Estado de Mato Grosso.

Leishmaniases are zoonoses that are undergoing expansion in Brazil. Dogs are of importance regarding transmission and dispersion of the disease, especially in areas presenting visceral leishmaniasis. The aim of this study was to evaluate the seroprevalence of leishmaniasis among domestic dogs in the urban area of Cuiabá. For this investigation, four districts of Cuiabá were selected, one in each administrative region. The dog sampling was defined statistically, taking the prevalence to be 8.4%. Among the 468 dogs examined, 16 presented an indirect immunofluorescence reaction, thus resulting in an overall prevalence of 3.4%. There was no predisposition towards canine leishmaniasis occurrences in relation to breed, sex or age. The main risk factors for occurrences of canine infection identified in the city of Cuiabá were the presence of dogs living in areas surrounding homes and the proximity of homes to forests. Thus, there have been changes in leishmaniasis occurrences within the urban environment.

Inquérito soroepidemiológico de leishmaniose canina em áreas endêmicas de Cuiabá, Estado de Mato Grosso / Seroepidemiological survey of canine leishmaniasis in endemic areas of Cuiabá, State of Mato Grosso

As leishmanioses são zoonoses em expansão no Brasil, tendo o cão importância na transmissão e dispersão da doença, principalmente em áreas de leishmaniose visceral. O objetivo desta pesquisa foi avaliar a soroprevalência de leishmaniose em cães domiciliados na zona urbana de Cuiabá. Para a pesquisa foram selecionados quatro bairros de Cuiabá, sendo um em cada regional administrativa. A amostragem canina foi definida estatisticamente, considerando-se a prevalência de 8,4 por cento. Dos 468 cães analisados, 16 foram reagentes na imunofluorescência indireta, obtendo-se uma prevalência geral de 3,4 por cento. Não foi observada predisposição racial, sexual e etária para a ocorrência da leishmaniose canina. Os principais fatores de risco identificados na ocorrência da infecção canina na Cidade de Cuiabá, foram a localização dos cães no peridomicílio, bem como a proximidade das residências de matas, evidenciando mudanças na ocorrência da doença no ambiente urbano.

Leishmaniases are zoonoses that are undergoing expansion in Brazil. Dogs are of importance regarding transmission and dispersion of the disease, especially in areas presenting visceral leishmaniasis. The aim of this study was to evaluate the seroprevalence of leishmaniasis among domestic dogs in the urban area of Cuiabá. For this investigation, four districts of Cuiabá were selected, one in each administrative region. The dog sampling was defined statistically, taking the prevalence to be 8.4 percent. Among the 468 dogs examined, 16 presented an indirect immunofluorescence reaction, thus resulting in an overall prevalence of 3.4 percent. There was no predisposition towards canine leishmaniasis occurrences in relation to breed, sex or age. The main risk factors for occurrences of canine infection identified in the city of Cuiabá were the presence of dogs living in areas surrounding homes and the proximity of homes to forests. Thus, there have been changes in leishmaniasis occurrences within the urban environment.