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Cadernos CRIS - Fiocruz: Saúde Global e Diplomacia da Saúde - Informe 16 - Agosto/Setembro - 2021
No full textInforme 16 produzido pelo CRIS-Fiocruz, sobre a semana de 24 de agosto a 06 de setembro de 2021
Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity
No full textAbstract: The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic – obesity. Currently, several studies have documented the association between obesity and COVID-19 severity. The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are of diverse nature. Inflammation plays a central role in obesity. Metabolic alterations seen in obese patients are related to an inflammatory response, and several studies report elevated levels of circulating inflammatory cytokines in obese patients. Also, deregulated expression of adipo kines, such as leptin and resistin, increase the expression of vascular adhesion molecule 1 and intercellular adhesion molecule 1 that contribute to increased vascular leukocyte adhe siveness and additional oxidative stress. Additionally, it is now recognized that the chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including obesity, when intensified by the detrimental effects of SARS CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. In fact, vascular endothelial dysfunction may contribute to a unfavorable response of the endothe lium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity may also provide a link to the increased cardiovascular events in these patients
Synthesis, Antitrypanosomal and Antimycobacterial Activities of Coumarin N-acylhydrazonic Derivatives
No full textBackground: Near to 5-7 million people are infected with T. cruzi in the world, and about 10,000 people per year die of problems associated with this disease.
Methods: Herein, the synthesis, antitrypanosomal and antimycobacterial activities of seventeen coumarinic N-acylhydrazonic derivatives have been reported.
Results: These compounds were synthesized using methodology with reactions global yields ranging from 46%-70%. T. cruzi in vitro effects were evaluated against trypomastigote and amastigote, forming M. tuberculosis activity towards H37Rv sensitive strain and resistant strains.
Discussion: Against T. cruzi, the more active compounds revealed only moderate activity IC50/96h~20 μM for both trypomastigotes and amastigotes intracellular forms. (E)-2-oxo-N'- (3,4,5-trimethoxybenzylidene)-2H-chromene-3-carbohydrazide showed meaningful activity in INH resistant/RIP resistant strain.
Conclusion: These compound acting as multitarget could be good leads for the development of new trypanocidal and bactericidal agents
COVID-19 challenges: From SARS-CoV-2 infection to effective point-of-care diagnosis by electrochemical biosensing platforms
No full textSince January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.In January 2020, the World Health Organization (WHO) identified a new zoonotic virus, SARS-CoV-2, responsible for causing the COVID-19 (coronavirus disease 2019). Since then, there has been a collaborative trend between the scientific community and industry. Multidisciplinary research networks try to understand the whole SARS-CoV-2 pathophysiology and its relationship with the different grades of severity presented by COVID-19. The scientific community has gathered all the data in the quickly developed vaccines that offer a protective effect for all variants of the virus and promote new diagnostic alternatives able to have a high standard of efficiency, added to shorter response analysis time and portability. The industry enters in the context of accelerating the path taken by science until obtaining the final product. In this review, we show the principal diagnostic methods developed during the COVID-19 pandemic. However, when we observe the diagnostic tools section of an efficient infection outbreak containment report and the features required for such tools, we could observe a highlight of electrochemical biosensing platforms. Such devices present a high standard of analytical performance, are lowcost tools, easy to handle and interpret, and can be used in the most remote and low-resource regions. Therefore, probably, they are the ideal point-of-care diagnostic tools for pandemic scenarios
The Maze Pathway of Coevolution: A Critical Review over the Leishmania and Its Endosymbiotic History
No full textThe description of the genus Leishmania as the causative agent of leishmaniasis occurred in
the modern age. However, evolutionary studies suggest that the origin of Leishmania can be traced
back to the Mesozoic era. Subsequently, during its evolutionary process, it achieved worldwide
dispersion predating the breakup of the Gondwana supercontinent. It is assumed that this parasite
evolved from monoxenic Trypanosomatidae. Phylogenetic studies locate dixenous Leishmania in a
well-supported clade, in the recently named subfamily Leishmaniinae, which also includes monoxe nous trypanosomatids. Virus-like particles have been reported in many species of this family. To date,
several Leishmania species have been reported to be infected by Leishmania RNA virus (LRV) and
Leishbunyavirus (LBV). Since the first descriptions of LRVs decades ago, differences in their genomic
structures have been highlighted, leading to the designation of LRV1 in L. (Viannia) species and LRV2
in L. (Leishmania) species. There are strong indications that viruses that infect Leishmania spp. have
the ability to enhance parasitic survival in humans as well as in experimental infections, through
highly complex and specialized mechanisms. Phylogenetic analyses of these viruses have shown that
their genomic differences correlate with the parasite species infected, suggesting a coevolutionary
process. Herein, we will explore what has been described in the literature regarding the relationship
between Leishmania and endosymbiotic Leishmania viruses and what is known about this association
that could contribute to discussions about the worldwide dispersion of Leishmania
Low prevalence of human gammaherpesvirus 8 (HHV-8) infection among HIV-infected pregnant women in Rio de Janeiro, Brazil
No full textPregnant women coinfected with the human immunodeficiency virus (HIV) and human gammaherpesvirus
8 (HHV-8) are at higher risk of Kaposi’s sarcoma development, increased viral load,
and vertical transmission of these viruses. A total of 131 pregnant women infected with HIV
were examined for antibodies against HHV-8 latency-associated nuclear antigen (LANA) and lytic
antigens using immunofluorescence assays. The presence of HHV-8 DNA was confirmed using
real-time polymerase chain reaction (qPCR) and nested PCR. Overall, 0.8% (1/131) of the patients
contained antibodies to HHV-8 LANA and lytic antigens, and no HHV-8 DNA was detected. This
study, including a small population of HIV-infected pregnant women in Brazil, indicates a low
prevalence of HHV-8 seropositivity and absence of active infection in this group. However, a
potential role of HHV-8 in the increased transmission and pathogenic activity of HIV in pregnant
women is suggested. Attention should be given to the emergence of HHV-8 infection in this
population group in order to avoid comorbidities and transmission of HIV.202
Anti-Leishmania IgG is a marker of disseminated leishmaniasis caused by Leishmania braziliensis
No full textNational Institutes of Health grant AI 136032.In this study we determine the accuracy of anti-Leishmania IgG
and IgG subclasses to distinguish clinical forms of American tegumentary
leishmaniasis (ATL), and the relationship between antibodies levels with cytokine
production and severity of ATL.
Methods: Participants were 40 cutaneous leishmaniasis (CL), 20 mucosal
leishmaniasis (ML), 20 disseminated leishmaniasis (DL) patients and 20 subjects
with subclinical L. braziliensis infection (SC). Diagnosis was performed by DNA
of L. braziliensis or IFN-γ production in SC. IgG and subclasses of IgG to soluble
Leishmania antigen, as well cytokine levels in supernatants of mononuclear cells
were detected by ELISA.
Results: IgG were detected in 95%, 95% and 100% of CL, ML and DL patients,
respectively. Higher levels of anti-Leishmania IgG and IgG2 were seen in DL
compared to CL, ML and SC. ROC analysis confirmed the ability of IgG to
distinguish DL from the other clinical forms. A direct correlation was observed
between IgG titers and levels of IFN-γ and CXCL10 in CL and DL, and IgG2
antibodies correlated with the number of lesions in DL.
Conclusions: High Anti-Leishmania IgG and IgG2 levels are characteristic of DL,
and while IgG was correlated with pro-inflammatory cytokines, IgG2 was direct
correlated with number of lesions
Caracterização molecular dos coxsackievírus B5 associados a infecções no sistema nervoso central no Brasil
No full textOs enterovírus humanos (EV) são vírus de RNA, não envelopados, pertencentes à família Picornaviridae. Embora a maioria das infecções por EV sejam assintomáticas e autolimitadas, esses vírus podem causar um amplo espectro de apresentações clínicas, incluindo síndromes graves do sistema nervoso central (SNC). O coxsackievírus B5 (CVB5) é um dos tipos de EV mais prevalentes em humanos e epidemias causadas por esses vírus são relatadas anualmente em todo o mundo. O objetivo deste estudo foi determinar a diversidade genética dos CVB5 associados a infecções no sistema nervoso central no Brasil. Para isso, foram utilizados isolados de CVB5 obtidos a partir de amostras de líquido cefalorraquidiano e fezes de pacientes com meningite asséptica e paralisia flácida aguda, respectivamente. Foi realizada a reinoculação das amostras em linhagens celulares (HEp2C e RD). Em seguida, foi realizada a extração do RNA, síntese do cDNA e PCR para amplificação da principal proteína do capsídeo viral (VP1). Posteriormente, foi realizada a reação de sequenciamento baseada no método de Sanger e a análise filogenética das sequências obtidas. De 2005 a 2019, 58 isolados de CVB5 foram identificados no âmbito do Programa Brasileiro de Vigilância da Poliomielite. As análises das sequências de VP1 revelaram dois genogrupos CVB5, A e B, circulando no Brasil. A análise filogenética sugeriu a circulação do genogrupo A (subgenogrupo A4) a partir de 2017 no país, enquanto os isolados de CVB5 pertencentes ao genogrupo B (subgenogrupo B2) antes de 2017 A análise baseada nas sequências de aminoácidos mostrou substituições importantes em resíduos conhecidos por desempenhar papéis importantes no tropismo viral. Este trabalho fornece informações valiosas sobre a diversidade de CVB5 associada à infecção do SNC no Brasil, apontando para a importância da vigilância dos enterovírus não-pólio em doenças neurológicasHuman enteroviruses (EV) are non-enveloped RNA viruses belonging to the Picornaviridae family. Although most EV infections are asymptomatic and self-limiting, these viruses can cause a wide spectrum of clinical outcomes, including severe central nervous system (CNS) syndromes. Globally, coxsackievirus B5 (CVB5) is one of the most prevalent EV-types in humans and epidemics caused by these viruses are reported annually. The aim of this study was to determine the genetic diversity of CVB5 associated with infections in the central nervous system in Brazil. For this purpose, assays were performed with CVB5 isolates obtained from cerebrospinal fluid and stool samples of aseptic meningitis and acute flaccid paralysis patients, respectively. Specimens were inoculated in cell lines (HEp2C and RD). After cytopathic effect (CPE), RNA extraction, cDNA synthesis and PCR were performed to amplify the main viral capsid protein (VP1). Subsequently, we performed the sequencing reaction based on the Sanger method and phylogenetic analysis. From 2005 to 2019, 58 isolates of CVB5 were identified in the scope of the Brazilian Poliomyelitis Surveillance Program. VP1 sequence analyzes revealed two CVB5 genogroups, A and B, circulating in Brazil A. Phylogenetic analysis suggested the circulation of genogroup A (subgenogroup A4) from 2017 in the country, while CVB5 isolates belonging to genogroup B (subgenogroup B2) showed a circulation prior to 2017. Network analysis based on deduced amino acid sequences showed important substitutions in residues known to play critical roles in viral host tropism, cell entry and viral antigenicity. This work provides valuable information on CVB5 diversity associated with CNS infection in Brazil, pointing to the importance of surveillance of non-polio enteroviruses in neurological disease
Predisposition to severe forms of COVID-19 and adherence to preventive measures: the role of social support
No full textObjetivou-se verificar a adesão às medidas de prevenção em idosos com maior prediposição a formas graves de COVID-19 e sua associação e interação com o apoio social. Trata-se de um estudo transversal realizado em amostra de 3.477 participantes do inquérito telefônico do Estudo Longitudinal da Saúde dos Idosos Brasileiros (iniciativa ELSI-COVID-19), que informaram ter saído de casa na semana anterior à realização do inquérito. A adesão foi aferida pela frequência com que saiu de casa, necessidade de sair de casa, uso de máscara e higienização das mãos. As análises basearam-se no modelo Poisson com variância robusta. Idade ≥ 65 anos, hipertensão, diabetes e obesidade foram considerados fatores predisponentes para formas graves de COVID-19. O apoio social incluiu o arranjo domiciliar e a conexão social na pandemia. Aproximadamente 46% apresentaram melhor adesão, que foi associada positivamente ao número de fatores predisponentes para formas graves. O apoio social não foi associado à adesão e não modificou essa associação, após ajustamentos. Conclui-se que a adesão às medidas de prevenção, que deveria ser estendida a todos, está concentrada nos idosos com maior predisposição a formas graves de COVID-19, independentemente do apoio socialThis study sought to assess the adherence to preventive measures among the elderly more prone to severe forms of COVID-19, and the association and interaction with social support. It is a cross-sectional study conducted with a sample of 3,477 participants of the telephone survey of the Brazilian Longitudinal Study of Aging (ELSI-COVID-19 initiative), who reported going out of the home in the past week. The adherence was based on the frequency of leaving the house, the need to venture outside the home, use of masks, and sanitization of hands. Statistical analysis was based on the Poisson model with robust variance. Predisposing factors for severe forms of COVID-19 included age ≥65 years, hypertension, diabetes, and obesity. Social support included liv-
ing arrangements and social distancing during the pandemic. Approximately 46% of the participants showed higher adherence, which was positively associated with the number of predisposing factors for severe forms of COVID-19. Social support was not associated with adherence, nor was this association modified after adjustments. The conclusion drawn is that higher adherence is concentrated among the elderly with greater predisposition to severe forms of COVID-19, irrespective of social support, albeit preventive measures should be adopted by all