Infecção por sars-cov-2 em pacientes submetidos à transplante cardíaco: uma revisão integrativa sobre o novo desafio para a cardiologia

Introdução: O SARS-CoV-2 é um vírus de alta disseminação cujo principal alvo de infecção é o sistema respiratório, porém, ao desencadear uma resposta imunológica exacerbada, sinalizada pela tempestade de citocinas, pode provocar lesões em múltiplos órgãos. Diante disso, este estudo busca reunir evidências que avaliem a vulnerabilidade de pacientes transplantados às manifestações clínicas do COVID-19, considerando o manejo do regime de imunossupressão e os efeitos das interações medicamentosas, na tentativa de promover estratégias adequadas de gerenciamento terapêutico. Desenvolvimento: Trata-se de uma revisão integrativa da literatura, realizada em março de 2023, na qual foram selecionados 6  artigos. Pacientes submetidos a transplantes cardíacos, devido ao quadro de imunossupressão, apresentam maior tendência em apresentar doenças cardiovasculares. A contaminação por SARS-CoV-2 aumenta significativamente o risco de complicações, e estabelece um desafio: equilibrar o regime de imunossupressores com a terapia antiviral, tendo em vista as interações medicamentosas. Considerações finais: O uso de imunossupressores parece ser responsável por um curso mais brando da COVID-19 em pacientes submetidos a transplante cardíaco, pela atenuação da tempestade de citocinas. Apesar disso, ainda há risco de gravidade da COVID-19, sendo necessário priorizar o manejo com terapias antivirais que melhor se adaptem às medicações imunossupressoras.Introduction: SARS-CoV-2 is a highly disseminated virus whose main target of infection is the respiratory system, however, by triggering an exacerbated immune response, signaled by the cytokine storm, it can cause damage to multiple organs. Therefore, this study seeks to gather evidence to assess the vulnerability of transplanted patients to the clinical manifestations of COVID-19, considering the management of the immunosuppression regimen and the effects of drug interactions in an attempt to promote adequate therapeutic management strategies. Development: This is an integrative literature review, carried out in March 2023, in which 6 articles were selected. Patients submitted to heart transplants, due to immunosuppression, are more likely to have cardiovascular diseases. The contamination by SARS-CoV-2 significantly increases the risk of complications, and sets a challenge: balancing the immunosuppressant regimen with antiviral therapy, in view of drug interactions. Final considerations: The use of immunosuppressants seems to be responsible for a milder course of COVID-19 in patients undergoing heart transplantation, by attenuating the cytokine storm. Nevertheless, there is still a serious risk of severity to COVID-19, and it is necessary to prioritize management with antiviral therapies that best adapt to immunosuppressive medications

Os fatores sociodemográficos interferem na adesão aos anti-hipertensivos na Atenção Primária? Revisão integrativa

This study aimed to gather scientific evidence on the role of sociodemographic factors in adherence to antihypertensive drugs in Primary Care in Brazil. This is an integrative review with studies published between 2015 and 2019 in national journals. Original studies developed with hypertensive Primary Care users in Brazil were included, and articles published outside the range between 2015 and 2019 were excluded, as well as literature reviews, and those that did not focus on the elements of interest in this review. Five studies that investigated sociodemographic variables in the context of adherence to antihypertensive drugs in Primary Care were selected. Although some studies have found a possible interference of some sociodemographic variables in adherence to antihypertensive drugs in Primary Care, there are, for each of these variables, divergent results, showing that the sociodemographic dimension may or may not interfere with medication adherence in a given population group. In this sense, there are also results suggestive that, with effective provision of assistance to users, such variables seem to lose their interference in adherence to antihypertensive drugs, in line with the hypothesis that organizational characteristics of health services have a much greater impact on adherence than sociodemographic differences

Efficacy of an Immunotherapy Combining Immunogenic Chimeric Protein Plus Adjuvant and Amphotericin B against Murine Visceral Leishmaniasis

Visceral leishmaniasis (VL) in the Americas is a chronic systemic disease caused by infection with Leishmania infantum parasites. The toxicity of antileishmanial drugs, long treatment course and limited efficacy are significant concerns that hamper adequate treatment against the disease. Studies have shown the promise of an immunotherapeutics approach, combining antileishmanial drugs to reduce the parasitism and vaccine immunogens to activate the host immune system. In the current study, we developed an immunotherapy using a recombinant T cell epitope-based chimeric protein, ChimT, previously shown to be protective against Leishmania infantum, with the adjuvant monophosphoryl lipid A (MPLA) and amphotericin B (AmpB) as the antileishmanial drug. BALB/c mice were infected with L. infantum stationary promastigotes and later they received saline or were treated with AmpB, MPLA, ChimT/Amp, ChimT/MPLA or ChimT/MPLA/AmpB. The combination of ChimT/MPLA/AmpB significantly reduced the parasite load in mouse organs (p p Leishmania parasites and to produce Th1-type cytokines into the culture supernatants. To conclude, our data suggest that the combination of ChimT/MPLA/AmpB could be considered for further studies as an immunotherapy for L. infantum infection

Immunization with recombinant LiHyp1 protein plus adjuvant is protective against tegumentary leishmaniasis

Tegumentary leishmaniasis (TL) is the main clinical manifestation of leishmaniasis, and it can cause the infected hosts to self-healing cutaneous lesions until mutilating scars in mucosal membranes, particularly in the nose and throat. The treatment against disease presents problems, and the diagnosis is hampered by variable sensitivity and/or specificity of the tests. In this context, the development of prophylactic vaccines could be considered as a strategy to control the disease. Previously, we showed that the recombinant LiHyp1 protein plus adjuvant protected mice from infection with Leishmania infantum, which causes visceral leishmaniasis. In the present study, we tested whether rLiHyp1 could induce protection against infection with L. amazonensis, a parasite species able to cause TL. We immunized BALB/c mice with rLiHyp1 plus saponin (rLiHyp1/S) or incorporated in micelles (rLiHyp1/M) as adjuvants and performed parasitological and immunological evaluations before and after infection. Results showed that after in vitro stimulation from spleen cell cultures using rLiHyp1 or a Leishmania antigenic extract (SLA), rLiHyp1/S and rLiHyp1/M groups developed a Th1-type immune response, which was characterized by high levels of IFN-γ, IL-2, TNF-α and IL-12 cytokines, nitrite, and IgG2a isotype antibodies when compared to values found in the control (saline, saponin, micelles alone) groups, which showed higher levels of anti-SLA IL-4, IL-10, and IgG1 antibodies before and after challenge. In addition, mice receiving rLiHyp1/S or rLiHyp1/M presented significant reductions in the lesion average diameter and parasite load in the infected tissue and internal organs. Blood samples were collected from healthy subjects and TL patients to obtain PBMC cultures, which were in vitro stimulated with rLiHyp1 or SLA, and results showed higher lymphoproliferation and IFN-γ production after stimulus using rLiHyp1, as compared to values found using SLA. These results suggest that rLiHyp1 plus adjuvant was protective against experimental TL and could also be considered for future studies as a vaccine candidate against human disease

Canine visceral leishmaniasis biomarkers and their employment in vaccines.

The natural history of canine visceral leishmaniasis (CVL) has been well described, particularly with respect to the parasite load in different tissues and immunopathological changes according to the progression of clinical forms. The biomarkers evaluated in these studies provide support for the improvement of the tools used in developing vaccines against CVL. Thus, we describe the major studies using the dog model that supplies the rationale for including different biomarkers (tissue parasitism, histopathology, hematological changes, leucocytes immunophenotyping, cytokines patterns, and in vitro co-culture systems using purified T-cells subsets and macrophages infected with L. infantum) for immunogenicity and protection evaluations in phases I and II applied to pre-clinical and clinical vaccine trials against CVL. The search for biomarkers related to resistance or susceptibility has revealed a mixed cytokine profile with a prominent proinflammatory immune response as relevant for Leishmania replication at low levels as observed in asymptomatic dogs (highlighted by high levels of IFN-? and TNF-? and decreased levels in IL-4, TGF-? and IL-10). Furthermore, increased levels in CD4+ and CD8+ T-cell subsets, presenting intracytoplasmic proinflammatory cytokine balance, have been associated with a resistance profile against CVL. In contrast, a polyclonal B-cell expansion towards plasma cell differentiation contributes to high antibody production, which is the hallmark of symptomatic dogs associated with high susceptibility in CVL. Finally, the different studies used to analyze biomarkers have been incorporated into vaccine immunogenicity and protection evaluations. Those biomarkers identified as resistance or susceptibility markers in CVL have been used to evaluate the vaccine performance against L. infantum in a kennel trial conducted before the field trial in an area known to be endemic for visceral leishmaniasis. This rationale has been a guiding force in the testing and selection of the best vaccine candidates against CVL and provides a way for the veterinary industry to register commercial immunobiological products