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Background: The true incidence of SARS-CoV-2 infection in Costa Rica was likely much higher than officially reported, because infection is often associated with mild symptoms and testing was limited by official guidelines and socio-economic factors. Methods: Using serology to define natural infection, we developed a statistical model to estimate the true cumulative incidence of SARS-CoV-2 in Costa Rica early in the pandemic. We estimated seroprevalence from 2223 blood samples collected from November 2020 to October 2021 from 1976 population-based controls from the RESPIRA study. Samples were tested for antibodies against SARS-CoV-2 nucleocapsid and the receptor-binding-domain of the spike proteins. Using a generalized linear model, we estimated the ratio of true infections to officially reported cases. Applying these ratios to officially reported totals by age, sex, and geographic area, we estimated the true number of infections in the study area, where 70% of Costa Ricans reside. We adjusted the seroprevalence estimates for antibody decay over time, estimated from 1562 blood samples from 996 PCR-confirmed COVID-19 cases. Findings: The estimated total proportion infected (ETPI) was 4.0 times higher than the officially reported total proportion infected (OTPI). By December 16th, 2021, the ETPI was 47% [42-52] while the OTPI was 12%. In children and adolescents, the ETPI was 11.0 times higher than the OTPI. Interpretation: Our findings suggest that nearly half the population had been infected by the end of 2021. By the end of 2022, it is likely that a large majority of the population had been infected. Funding: This work was sponsored and funded by the National Institute of Allergy and Infectious Diseases through the National Cancer Institute, the Science, Innovation, Technology and Telecommunications Ministry of Costa Rica, and Costa Rican Biomedical Research Agency-Fundacion INCIENSA (grant N/A).
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OBJECTIVE: To evaluate the duration of protection against reinfection conferred by a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. STUDY DESIGN: We applied 2 complementary approaches: a matched test-negative, case-control design and a retrospective cohort design. A total of 458â959 unvaccinated individuals aged 5-18 years were included. The analyses focused on the period July 1, 2021, to December 13, 2021, a period of Delta variant dominance in Israel. We evaluated 3 SARS-CoV-2-related outcomes: documented polymerase chain reaction-confirmed infection or reinfection, symptomatic infection or reinfection, and SARS-CoV-2-related hospitalization or death. RESULTS: Overall, children and adolescents who were previously infected acquired durable protection against reinfection with SARS-CoV-2 for at least 18 months. Importantly, no SARS-CoV-2-related deaths were recorded in either the SARS-CoV-2-naïve group or the previously infected group. The effectiveness of naturally acquired immunity against a recurrent infection reached 89.2% (95% CI, 84.7%-92.4%) at 3-6 months after the first infection and declined slightly to 82.5% (95% CI, 79.1%-85.3%) by 9-12 months after infection, with a slight nonsignificant waning trend seen up to 18 months after infection. Additionally, children aged 5-11 years exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in those aged 12-18 years was more prominent but still mild. CONCLUSIONS: Children and adolescents who were previously infected with SARS-CoV-2 remain protected to a high degree for 18 months. Further research is needed to examine naturally acquired immunity against Omicron and newer emerging variants.
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COVID-19 , Humanos , Adolescente , Criança , Reinfecção , Estudos Retrospectivos , SARS-CoV-2 , Imunidade AdaptativaRESUMO
Introducción: La duración de la inmunidad natural generada por la COVID-19 está por definir, lo que determina la probable reinfección. Objetivo: Destacar la necesidad de mantener las medidas de prevención a propósito de un caso de reinfección en un trabajador sanitario. Presentación de caso: Paciente femenina de 48 años de edad con antecedentes de salud que, en junio, 2020 y marzo, 2021 se le diagnóstica la COVID-19, en ambos casos con el comportamiento de enfermedad sintomática leve. Después de 24 horas de comenzar con cefalea, mareos y tos seca se confirma el diagnóstico de infección por SARS CoV-2 con PCR positivo y umbral de ciclo (CT) en 24.84. Pasados 9 meses y 9 días de la infección original, y dos días posteriores a recibir la vacuna BNT162b2 (Pfizer-BioNTech), comienza con malestar general, tos seca, secreción nasal y dolor de garganta, con PCR positivo y CT de 17.61. Conclusiones: La posibilidad de la reinfección por la COVID-19 orienta la necesidad de fortalecer las acciones de prevención de la transmisión en instituciones de salud en tanto las evidencias científicas nos provean de recursos más eficaces para su control(AU)
Introduction: The duration of natural immunity generated by COVID-19 is yet to be defined, which determines the probable reinfection. Objective: To analyze issues related to natural infection and the need to maintain prevention practices regarding a case of reinfection in a health care worker. Case presentation: Forty-eight-year-old female patient without comorbidities who was diagnosed with COVID-19 in June 2020 and March 2021, in both cases as a mild symptomatic disease. Twenty-four hours after the onset with headache, dizziness, and dry cough, the diagnosis of SARS CoV-2 infection was confirmed by positive PCR and cycle threshold (CT) at 24.84. Nine months and nine days after original infection, and two days after receiving the BNT162b2 vaccine (Pfizer-BioNTech), the patient began with general malaise, dry cough, runny nose, and sore throat, with a positive PCR and CT of 17.61. Conclusions: The possibility of reinfection by COVID-19 points to the need to strengthen transmission prevention practices in healthcare facilities as long as scientific evidence provides us with more effective resources for its control(AU)
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Humanos , Feminino , Pessoa de Meia-Idade , Reinfecção , COVID-19 , Instalações de Saúde , Imunidade Inata , Reação em Cadeia da Polimerase , Síndrome Respiratória Aguda GraveRESUMO
The objective of this study was to compare the antimicrobial activity of macrophages and serum in laying hen (MM, CC, and CCc) and broiler chicken lineages (TT and LL). Macrophages were evaluated for phagocytic and antimicrobial activity. Microbicidal serum activity was evaluated by the resistance test for serum and the agar test. The results showed that phagocytic activity was higher in males of the MM strain, with 13% of macrophages presenting phagocytosis, while the other lineages studied, and even female MM, presented a rate of 6% of phagocytic cells. However, antimicrobial activity in macrophages from males of CCc lineage and females of TT lineage were higher, eliminating more than 30% of the Salmonella enterica inoculum, while in the other strains, the results were similar, with inoculum reduction below 30%. In the serum resistance assay, female laying lines presented higher antibacterial activity than female broiler lines. In the trials to evaluate the microbicide activity of the serum, females of both broiler and laying lineages presented higher performance when compared with males of the same lineage. Females of laying hen lines (MM and CC) present a greater antibacterium activity than males. These results can contribute to a better understanding of the immune response in broiler chicken and laying hen lineages, to aid development of lineages of birds more resistant to pathogens.
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Animais , Seleção Genética , Galinhas/imunologia , Soro/microbiologia , Macrófagos/microbiologia , Padrões de HerançaRESUMO
BACKGROUND: The increasing prevalence of antibiotic resistant bacteria has raised an urgent need for substitute remedies. Antimicrobial peptides (AMPs) are considered promising candidates to address infections by multidrug-resistant bacteria through new mechanisms of action that require a careful evaluation of their performance. OBJECTIVE: Identification of effective AMPs against Neisseria meningitidis, which represents a pathogen of great public health importance worldwide that is intrinsically resistant to some AMPs, such as polymyxin B. METHODS: A cationic 11-residue peptide (KLKLLLLLKLK), referred to as poly-Leu, was synthesized and its antimeningococcal activity was compared to cecropin A and poly-P (KLKPPPPPKLK) through a variety of assays. Flow cytometry was used to measure propidium iodide uptake by N. meningitidis serotype B as an indicator of the effectiveness of each peptide when added to cultures at different concentrations. RESULTS: The addition of the poly-Leu peptide led to a 90.3% uptake of the dye with an EC50 value of 7.9 µg mL-1. In contrast, uptake was <10% in cells grown in the absence of peptides or with an identical concentration of cecropin and poly-Pro peptides. Electron micrographs indicated that the integrity of the cellular wall and internal membrane was impacted in relation to peptide concentrations, which was confirmed by the detection of released alkaline phosphatase from the periplasmic space due to disruption of the external membrane. CONCLUSION: Poly-Leu peptide demonstrated definitive antimicrobial activity against N. meningitidis.
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Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Neisseria meningitidis/efeitos dos fármacos , Antibacterianos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Propídio/metabolismoRESUMO
Almost all kidney cancers are associated to immune dysfunction. Among these, renal cell carcinoma (RCC) represents approximately 2% of malignancies that affect adults and for 90–95% of all kidney cancers. Recent evidences have collaborated to elucidate the mechanisms involved in the development of this disease. In this view, dysfunctional neutrophil migration, as well as T lymphocyte-DC (dendritic cell) cross talk, DC maturation, immune cell metabolism, and reactivity and abnormal expression of cytokines and chemokines and their receptors have been highlighted in RCC and stroma cells. A rational development of novel therapies to recover antitumor activity of immune system is closely related to the understanding of the complex interactions between immune system and tumor. Some insights have been reached and immunomodulatory molecules, such as interleukin-2 (IL-2) and IFN-α, immune checkpoint inhibitors, and chemokines antagonists have shown clinical efficacy. In this chapter, we overview the essential role of innate and adaptive immune response in RCC and discuss drugs approved or in development for its treatment.
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The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using "gold-standard" methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted.
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Antídotos/uso terapêutico , Metaloendopeptidases/antagonistas & inibidores , Inibidores de Proteases/uso terapêutico , Proteínas de Répteis/antagonistas & inibidores , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Serpentes/antagonistas & inibidores , Animais , Antídotos/história , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Metaloendopeptidases/química , Metaloendopeptidases/história , Metaloendopeptidases/metabolismo , Inibidores de Proteases/história , Conformação Proteica , Proteínas de Répteis/química , Proteínas de Répteis/história , Proteínas de Répteis/metabolismo , Mordeduras de Serpentes/enzimologia , Mordeduras de Serpentes/história , Venenos de Serpentes/química , Venenos de Serpentes/enzimologia , Venenos de Serpentes/história , Relação Estrutura-AtividadeRESUMO
AIMS: The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function. MAIN METHODS: Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies. KEY FINDINGS: All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (ß -0.347; P<0.05). SIGNIFICANCE: These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function.
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Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Imunidade Inata/efeitos dos fármacos , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Feminino , Humanos , Hidroclorotiazida/farmacologia , Hipertensão/imunologia , Imunidade Inata/imunologia , Indapamida/farmacologia , Masculino , Pessoa de Meia-Idade , Perindopril/farmacologia , Método Simples-CegoRESUMO
Um papel importante foi atribuído ao receptor toll-like 4 (TLR4) no desenvolvimento da placa aterosclerótica. O TLR4 foi primeiramente descrito como um receptor para bactérias gram-negativas; posteriormente foi demonstrado que sua expressão está aumentada em placas ateroscleróticas e que pacientes que possuem um polimorfismo disfuncional do TLR4 são menos suscetíveis ao desenvolvimento dessa doença. Portanto, o objetivo desse estudo foi o de investigar, em um modelo experimental de aterosclerose, a influência da deleção do TLR4 na formação e morfologia da placa aterosclerótica, no perfil lipídico e em marcadores inflamatórios. Camundongos duplo knockout (DKO), deficientes no receptor de LDL e TLR4, foram gerados cruzando-se camundongos deficientes para o receptor de LDL (LDLrKO) com camundongos deficientes para o TLR4 (TLR4KO). Todos os grupos receberam dieta rica em gordura e colesterol por 12 semanas. As concentrações plasmáticas de colesterol e triglicérides foram medidas por ensaio colorimétrico. Cortes seriados da raiz aórtica foram corados com Oil red O e as áreas de lesão quantificadas por analisador de imagens. O colágeno foi medido por coloração de picrossirius. A formação de nitrotirosina e expressão de CD40L, MMP9 e iNOS nas placas foram feitas por imunohistoquímica. As comparações foram feitas por ANOVA com pós teste de Student Newman-Keuls. Os dados foram expressos como média ± EPM. Camundongos DKO desenvolveram placas menores que camundongos LDLrKO (117.6 ±1.4 vs 198.8 ± 3.3 104m2). Camundongos TLR4KO não formaram placa. As placas dos camundongos DKO apresentaram menor núcleo lipídico que as dos LDLrKO (76.2± 13.2 vs 161.7 ± 2.9 104m2). O colágeno ao redor do núcleo lipídico é maior nos camundongos DKO do que nos LDLrKO (24.9 ± 1.8 vs 16.5 ± 2.5 % da placa). A distribuição do colágeno nos camundongos DKO ocorre principalmente ao redor da placa, de forma mais organizada, enquanto que nos LDLrKO onde sua distribuição é mais difusa. As placas...
A crucial role has been suggested for toll-like receptor 4 (TLR4) in atherosclerotic plaque formation and development. TLR4 was described primarily, as a receptor for gram-negative bacteria lipopolisacharide; later it was showed that its expression is increased in atherosclerotic plaques and patients that carries a TLR4 dysfunctional polymorphism are less susceptible to development of this disease. Therefore, the aim of this study was to investigate, in an experimental model of atherosclerosis, the influence of TLR4 deletion in atherosclerotic plaque formation and morphology, cholesterol profile and inflammatory markers. Double knockout mice (DKO), deficient in LDL receptor and TLR4, were generated by breeding LDL receptor knockout mice (LDLrKO) with TLR4 knockout mice (TLR4KO). All three experimental groups, LDLrKO, TLR4KO and DKO were fed a high fat-cholesterol diet for 12 weeks. Plasma cholesterol and triacylglicerol concentrations were measured by colorimetric assay. Cross sections of aortic sinus were stained with Oil red O and lesion areas were quantified by an image analyzer. Collagen content was measured by picrossirius staining. We also measured nitrotyrosine formation, CD40L, MMP9 and iNOS expression by immunohistochemistry. Comparisons were made by ANOVA followed by Student-Newman-Keuls post- test. Data are mean ± SEM. DKO mice developed smaller plaques than LDLrKO mice (117.6 ±1.4 vs 198.8 ± 3.3 104m2). TLR4KO mice developed no plaque. Plaques from DKO mice have also a smaller lipid core than the ones from LDLrKO mice (76.2± 13.2 vs 161.7 ± 2.9 104m2). Collagen content around the lipid core is higher in DKO mice compared to LDLrKO mice (24.9 ± 1.8 vs 16.5 ± 2.5 % of the whole plaque). Interestingly, collagen distribution in DKO mice seems to occur mainly on the plaque periphery, in a more organized manner, while in LDLrKO mice it is fuzzier, being present also inside the plaque. Plaques from DKO present lower expression of CD40L and iNOS...
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Animais , Camundongos , Aterosclerose , Imunidade Inata , InflamaçãoRESUMO
The existence of mammals and reptilia with a natural resistance to snake venoms is known since a long time. This fact has been subjected to the study by several research workers. Our experiments showed us that in the marsupial Didelphis marsupialis, a mammal highly resistant to the venom of Bothrops jararaca, and other Bothrops venoms, has a genetically origin protein, a alpha-1, acid glycoprotein, now highly purified, with protective action in mice against the jararaca snake venom.