Recombinant viruses as tools to induce protective cellular immunity against infectious diseases

Infections by intracellular pathogens such as viruses, some bacteria and many parasites, are cleared in most cases after activation of specific T cellular immune responses that recognize foreign antigens and eliminate infected cells. Vaccines against those infectious organisms have been traditionally developed by administration of whole live attenuated or inactivated microorganisms. Nowadays, research is focused on the development of subunit vaccines, containing the most immunogenic antigens from the particular pathogen. However, when purified subunit vaccines are administered using traditional immunization protocols, the levels of cellular immunity induced are mostly low and not capable of eliciting complete protection against diseases caused by intracellular microbes. In this review, we present a promising alternative to those traditional protocols, which is the use of recombinant viruses encoding subunit vaccines as immunization tools. Recombinant viruses have several interesting features that make them extremely efficient at inducing immune responses mediated by T-lymphocytes. This cellular immunity has recently been demonstrated to be of key importance for protection against malaria and AIDS, both of which are major targets of the World Health Organization for vaccine development. Thus, this review will focus in particular on the development of new vaccination protocols against these diseases. [Int Microbiol 2004; 7(2):83–94

Living on the Edge: Physiological and Kinetic Trade-Offs Shape Thermal Tolerance in Intertidal Crabs From Tropical to Sub-Antarctic South America

Temperature is an important abiotic factor that drives the evolution of ectotherms owing to its pervasive effects at all levels of organization. Although a species’ thermal tolerance is environmentally driven within a spatial cline, it may be constrained over time due to differential phylogenetic inheritance. At the limits of thermal tolerance, hemolymph oxygen is reduced and lactate formation is increased due to mismatch between oxygen supply and demand; imbalance between enzyme flexibility/stability also impairs the ability to generate energy. Here, we characterized the effects of lower (LL50) and upper (UL50) critical thermal limits on selected descriptors of aerobic and anaerobic metabolism in 12 intertidal crab species distributed from northern Brazil (≈7.8°S) to southern Patagonia (≈53.2°S), considering their phylogeny. We tested for (i) functional trade-offs regarding aerobic and anaerobic metabolism and LDH kinetics in shaping thermal tolerance; (ii) influence of shared ancestry and thermal province on metabolic evolution; and (iii) presence of evolutionary convergences and adaptive peaks in the crab phylogeny. The tropical and subtropical species showed similar systemic and kinetic responses, both differing from the sub-Antarctic crabs. The lower UL50’s of the sub-Antarctic crabs may reflect mismatch between the evolution of aerobic and anaerobic metabolism since these crabs exhibit lower oxygen consumption but higher lactate formation than tropical and subtropical species also at their respective UL50’s. LDH activity increased with temperature increase, while KmPyr remained fairly constant; catalytic coefficient correlated negatively with thermal niche. Thermal tolerance may rely on a putative evolutionary trade-off between aerobic and anaerobic metabolism regarding energy supply, while temperature compensation of kinetic performance is driven by thermal habitat as revealed by the LDH affinity/efficiency equilibrium. The overall physiological evolution revealed two homoplastic adaptive peaks in the sub-Antarctic crabs with a further shift in the tropical/subtropical clade. The physiological traits at UL50 have evolved in a phylogenetic manner while all others were more plastic. Thus, shared inheritance and thermal environment have driven the crabs’ thermal tolerance and metabolic evolution, revealing physiological transformations that have arisen in both colder and warmer climes, especially at higher levels of biological organization and phylogenetic diversity.Fil: Coelho Faria, Samuel. Universidade de Sao Paulo; BrasilFil: Bianchini, Adalto. Universidade Federal Do Rio Grande.; BrasilFil: Machado Lauer, Mariana. Universidade Federal Do Rio Grande.; BrasilFil: Ribeiro Latorre Zimbardi, Ana Lúcia. Universidade de Sao Paulo; BrasilFil: Tapella, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Romero, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Campbell McNamara, John. Universidade de Sao Paulo; Brasi

Evaluación de la calidad seminal de conejos alimentados con dietas que contienen diferentes niveles de inclusión de semillas de linaza (Linum usitatissimum)

The aim of this study was to evaluate the effect of flaxseed (Linum usitatissimum) on the physical and morphological quality of fresh and refrigerated rabbit semen. Twenty New Zealand males were used, and distributed in four groups according to the level of inclusion of flaxseed in the total diet for 100 days: 0 %, 3 %, 6 %, and 9 %. Fifteen days after starting the supply of the diet, seminal collections were made once a week with an artificial vagina and a female as a dummy. For the physical and morphological evaluations, the semen was diluted in Tris-Egg Yolk medium and cooling at 5 °C; progressive sperm motility, and spermatic vigor and morphology were assessed at 0, 2, 12, 24, 48, and 72 post-cooling hours. This information was analyzed through analyses of variance and regression at 5 % significance. For the morphology, volume, color, and seminal appearance of fresh semen (p > 0.05), there was no difference. For volume, turbidity, motility, vigor, and concentration, average values of 0.92 ± 0.24 mL; 0.86 ± 0.35; 76.58 ± 7.13 %; 3.37 ± 0.28, and 205.75 ± 20.77 x 106 sptz were recorded, respectively. There were differences for motility and vigor at 0, 2, 12, 24, 48, and 72 post-cooling hours (p > 0.005). In conclusion, the inclusion of up to 9 % flaxseed in the rabbit diet did not alter the physical and microscopic parameters evaluated in this study in fresh and refrigerated rabbit semen.El objetivo de este trabajo fue evaluar el efecto de la semilla de linaza (Linum usitatissimum) en la calidad física y morfológica del semen fresco y refrigerado de conejos. Se emplearon 20 machos Nueva Zelandia distribuidos en grupos según niveles de inclusión de semilla en su dieta durante 100 días: 0 %, 3 %, 6 % y 9 %. 15 días después de iniciar el suministro de la dieta se realizaron colectas seminales una vez por semana con vagina artificial y una hembra como maniquí. Para la evaluación física y morfológica se diluyó en medio Tris-yema y refrigerado a 5 °C; se valoró la motilidad espermática progresiva, el vigor espermático y la morfología espermática a las 0, 2, 12, 24, 48 y 72 horas post-refrigeración. La información fue analizada mediante análisis de varianza y de regresión al 5 % de significancia. Para la morfología, volumen, color y aspecto seminal del semen fresco (p > 0,05) no hubo diferencia. Para volumen, turbidez, motilidad, vigor y concentración, hubo valores medios de 0,92 ± 0,24 mL; 0,86 ± 0,35; 76,58 ± 7,13 %; 3,37 ± 0,28 y 205,75 ± 20,77 × 106 sptz, respectivamente. Hubo diferencia para motilidad y vigor espermático a las 0, 2, 12, 24, 48 y 72 horas post-refrigeración (p < 0,005). Se concluyó que la inclusión de hasta 9 % de semilla de linaza en la dieta de conejos no alteró los parámetros físicos y microscópicos evaluados en este estudio en semen fresco y refrigerado de conejo

Perfil metabólico de conejos suplementados con niveles de semilla de linaza (Linum usitatissimum) en la dieta

Many oilseeds are a source of essentials fatty acids that are necessary for the coverage of the basic functions in the organism. The study aimed to evaluate the effect of flaxseed (Linum usitatissimum) inclusion in the diet of rabbits through the metabolic profile. Twenty males of the New Zealand breed of 8 months were used. Divided in four groups, they received flaxseed (L. usitatissimum) levels in the total diet: 0 %, 3 %, 6 % y 9 %, for a period of 88 days. The animals were subjected to a blood collection every 22 days to determine glucose, total cholesterol, high density lipoprotein (HDL), triglycerides, very low-density lipoprotein (VLDL), low density lipoprotein (LDL), creatinine and urea. The data were evaluated by analysis of variance and regression with 5 % significance. The inclusion of flaxseed (L. usitatissimum) in the rabbit diet showed a positive quadratic effect for plasmatic concentration of glucose and total cholesterol. There was no significant difference between treatments for plasma concentration of triglycerides, low- density lipoproteins (LDL), very low - density lipoproteins (VLDL) and urea. There was a cubic effect for cholesterol- and creatinine. The inclusion of flaxseed (L. usitatissimum) in the diet had hypercholesterolemic effect in these animals.Diversas semillas de oleaginosas son fuente de ácidos grasos esenciales indispensables para cubrir las funciones básicas en el organismo. El estudio tuvo como objetivo evaluar el efecto de la inclusión de semilla de linaza (Linum usitatissimum) en la dieta de conejos por medio del perfil metabólico. Se utilizaron 20 machos de la raza Nueva Zelandia de 8 meses de edad. Distribuidos en cuatro grupos, recibieron niveles de semilla de linaza (L. usitatissimum) en la dieta total: 0 %, 3 %, 6 % y 9 %, durante un período de 88 días. Los animales se sometieron a colecta de sangre cada 22 días para determinar glucosa, colesterol total, lipoproteínas de alta densidad (HDL), triglicéridos, lipoproteínas de muy baja densidad (VLDL), lipoproteínas de baja densidad (LDL), creatinina y urea. Los datos se evaluaron por análisis de varianza y de regresión con 5 % de significancia. La inclusión de semilla de linaza (L. usitatissimum) en la dieta presentó comportamiento cuadrático positivo para concentración plasmática de glucosa y colesterol total. No hubo diferencia significativa entre los tratamientos para la concentración plasmática de triglicéridos, lipoproteínas de baja densidad (LDL), lipoproteínas de muy baja densidad (VLDL) urea. Hubo comportamiento cúbico para lipoproteínas de alta densidad (HDL) y creatinina. La inclusión de linaza (L. usitatissimum) en la dieta no presentó efecto hipercolesterolémico en estos animales

Conocimiento de los cuidadores primarios respecto a la infección respiratoria aguda en el año 2014 en Bogotá

En Latinoamérica los niños mueren en proporciones alarmantes, los niños menores de 5 años mueren a causa de Infecciones Respiratorias Agudas IRA. Las cuidadoras de esta población son mayoritariamente madres comunitarias, razón por la cual se convierten en un elemento transcendental al momento de realizar estrategias de prevención y tratamiento. Por ello, es importante determinar el nivel de conocimiento sobre la Infección respiratoria Aguda (IRA) en madres comunitarias de los jardines infantiles de Bogotá. Metodología: estudio descriptivo observacional de corte transversal, en el cual se realizó un pre test basado en 9 preguntas de selección múltiple entre los meses de enero y agosto del año 2014. Se realizó en los jardines infantiles de la ciudad de Bogotá, con la participación de 100 cuidadoras voluntarias. Losnúcleos temáticos con mayor impacto se encontraron en el nivel de conocimiento relacionado con la sintomatología y con los signos de alarma de la IRA; los núcleos temáticos donde se describió menor nivel de conocimiento fueron, el manejo de la IRA por edad y el conocimiento de los servicios de urgencia

Severe form of lymphocutaneous sporotrichosis: a case report

Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. It is caused by species of the genus Sporothrix. Infection in humans occurs through the entry of the fungus into the skin. Zoonotic outbreaks involving cats in the transmission of the disease have been frequently reported. The lymphocutaneous form is the most commonly observed and the upper limbs are the most affected sites. We report a case of a 64-year-old healthy female patient with a lymphocutaneous form with rapid progression of lesions, which was refractory to initial treatment with itraconazole. Treatment with liposomal amphotericin B was performed with a satisfactory resolution, but aesthetic and functional sequelae in the left upper limb were installed

Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study

Objectives: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies.Methods: BtIFI in patients with & GE; 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions.Results: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most fre-quent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 10 0-day mor-tality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases.Conclusions: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceed-ingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.& COPY; 2023 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients

Objectives: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. Methods: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. Results: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Conclusion: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/