Resumo O contexto brasileiro de desigualdades sociais e barreiras no acesso aos serviços de saúde pode agravar a situação da pandemia de COVID-19, que já afeta todos os estados da federação, com a curva crescente de aumento de casos confirmados e mortes. O governo dos países e os agentes do campo científico têm buscado evidências para as melhores práticas de prevenção e controle da transmissão, e cuidado da infecção e doença, incluindo medidas de diagnóstico, tratamento e de atenção à saúde. A estratégia de testagem em larga escala, visando o diagnóstico precoce, quarentena dos casos leves identificados, bem como dos contactantes, e cuidado adequado dos casos graves, tem sido revisada e indicada como uma das medidas eficientes para o controle da pandemia em vários países do mundo. O artigo tem como objetivo discutir os desafios da testagem e do diagnóstico de COVID-19 no Brasil.

In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63_lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0–3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63_lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63_lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63_lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63_lo strain can be the basis of an improved vaccine against tuberculosis.

Introduction The key tools for mitigating the impact of COVID-19 and reducing its transmission include testing, quarantine and isolation, as well as telemonitoring. Primary healthcare (PHC) can be essential in increasing access to these tools. Therefore, the primary objective of this study is to implement and expand an intervention consisting of COVID-19 testing, isolation, quarantine and telemonitoring (TQT) strategies and other prevention measures at PHC services in highly socioeconomically vulnerable neighbourhoods of Brazil. Methods and analysis This study will implement and expand COVID-19 testing in PHC services in two large Brazilian capital cities: Salvador and Rio de Janeiro. Qualitative formative research was conducted to understand the testing context in the communities and at PCH services. The TQT strategy was structured in three subcomponents: (1) training and technical support for tailoring the work processes of health professional teams, (2) recruitment and demand creation strategies and (3) TQT. To evaluate this intervention, we will conduct an epidemiological study with two stages: (1) a cross-sectional sociobehavioural survey among individuals from these two communities covered by PHC services, presenting symptoms associated with COVID-19 or being a close contact of a patient with COVID-19, and (2) a cohort of those who tested positive, collecting clinical data. Ethics and dissemination The WHO Ethics Research Committee (ERC) (#CERC.0128A and #CERC.0128B) and each city’s local ERC approved the study protocol (Salvador, ISC/UFBA: #53844121.4.1001.5030; and Rio de Janeiro, INI/Fiocruz: #53844121.4.3001.5240, ENSP/Fiocruz: #53844121.4.3001.5240 and SMS/RJ #53844121.4.3002.5279). Findings will be published in scientific journals and presented at meetings. In addition, informative flyers and online campaigns will be developed to communicate study findings to participants, members of communities and key stakeholders.

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-β, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB.

Pioneering research in the genetic manipulation of Mycobacterium, such as performed by Jacobs Jr et al. allowed the introduction of foreign DNA into Mycobacterium smegmatis and BCG.¹¹ This opened the possibility for development of multi-vaccines based on BCG as a live vehicle to present heterologous antigens from different pathogens. Since then, several groups have had success in the development of rBCG strains, expressing antigens from virus, bacteria or parasites, or even cytokine molecules.^1,2,12 Despite several reports on the successful construction of rBCG strains, many rBCG constructs did not attain expression, revealing the importance of characterising other expression vectors construct. On the other hand, there are studies that have indicated a role for antigen expression level in the induction of immune responses. For the Mycobacterium tuberculosis (Mtb) antigen, 85B, low-level expression skewed the immune response towards a T helper 1 (Th1) immune response, and higher expression levels towards a Th2 immune response.¹³

Background: Brazil was strongly affected by the COVID-19 pandemic and the impact of the pandemic on sexual and gender minorities’ youth remains unknown. This study aimed to estimate the seroprevalence of SARS-CoV-2 antibodies and associated factors among adolescent men who have sex with men (AMSM) and transgender women (ATGW) participants of a human immunodeficiency virus (HIV) pre-exposure prophylaxis cohort study (PrEP1519). Methods: This is a cross-sectional design conducted between June and October 2020 in Salvador, Brazil. Serum samples were collected from AMSM and ATGW aged 16-21 years between June-October 2020. IgG and IgM anti-SARS-CoV-2 were detected by chemiluminescence immunoassay, and data were collected through a socio-behavioral questionnaire. Results: Among the 137 participants, the seroprevalence of anti-SARS-CoV-2 IgG and IgM was 20.4%; 16.8% of the participants were positive for IgG, and 11.7% for IgM. In the multivariable analysis, the seroprevalence was two times higher among those who never wore masks (OR= 2.22; 95% CI: 1.08-4.57) and among those who believed that they could be easily cured of the disease (OR= 2.05; 95% CI: 1.05-4.01). Conclusions: The high seroprevalence of SARS-CoV-2 antibodies among gender and sexual minority youth seems to be informed by behaviors and attitudes that contrast with public health measures and the potential severity of the disease when vaccination was still not available.