Modulation of cathelicidin and defensins by histone deacetylase inhibitors: A potential treatment for multi-drug resistant infectious diseases.

Infectious diseases are an important growing public health problem, which perspective has worsened due to the increasing number of drug-resistant strains in the last few years. Although diverse solutions have been proposed, one viable solution could be the use of immune system modulators. The induction of the immune response can be increased by histone deacetylase inhibitors (iHDAC), which in turn modulate the chromatin and increase the activation of different cellular pathways and nuclear factors such as STAT3, HIF-1α NF-kB, C/EBPα and, AP-1. These pathways are capable to promote several immune response-related molecules including those with antimicrobial properties such as antimicrobial peptides (AMPs) that lead to the elimination of pathogens including multi drug-resistant strains.

Neglected tropical diseases and infectious illnesses: potential targeted peptides employed as hits compounds in drug design.

Neglected Tropical Diseases (NTDs) and infectious illnesses, such as malaria, tuberculosis and Zika fever, represent a major public health concern in many countries and regions worldwide, especially in developing ones. They cause thousands of deaths per year, and certainly compromise the life of affected patients. The drugs available for therapy are toxic, have considerable adverse effects, and are obsolete, especially with respect to resistance. In this context, targeted peptides are considered promising in the design of new drugs, since they have specific action and reduced toxicity. Indeed, there is a rising interest in these targeted compounds within the pharmaceutical industry, proving their importance to the Pharmaceutical Sciences field. Many have been approved by the Food and Drug Administration (FDA) to be used as medicines, plus there are more than 300 peptides currently in clinical trials. The main purpose of this review is to show the most promising potential targeted peptides acting as hits molecules in NTDs and other infectious illnesses. We hope to contribute to the discovery of medicines in this relatively neglected area, which will be extremely useful in improving the health of many suffering people.

Inflammaging in Endemic Areas for Infectious Diseases.

Immunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory versus remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts.

Increased incarceration rates drive growing tuberculosis burden in prisons and jeopardize overall tuberculosis control in Paraguay.

Incarcerated populations are at high-risk to develop tuberculosis (TB), however their impact on the population-level tuberculosis epidemic has been scarcely studied. We aimed to describe the burden and trends of TB among incarcerated populations over time in Paraguay, its clinical and epidemiological differences and the population attributable fraction. This is an observational, descriptive study including all TB cases notified to the National TB control Program in Paraguay during the period 2009-2018. We also used case registries of prisoners diagnosed with tuberculosis from the Minister of Justice. The population attributable fraction of TB in the community due to incarcerated cases was estimated through Levin's formula. The characteristics of TB cases in and outside of prison were compared as well as the characteristics of TB in prisons were modified over time. During 2009-2018, 2764 (9.7%) of the 28,534 TB reported cases in Paraguay occurred in prisons. The number of prisoners in Paraguay increased from 6258 in 2009 to 14,627 in 2018 (incarceration rate, 101 to 207 per 100,000 persons) while the number of TB cases among prisoners increased by 250% (n = 192 in 2009 versus n = 480 in 2018). The annual TB notification rate among male prisoners was 3218 and 3459 per 100,000 inmates in 2009 and 2018, respectively. The percentage of all TB cases occurring among prisoners increased from 7.1% in 2009 to 14.5% in 2018. The relative risk of TB in prisons compared to community was 70.3 (95% CI, 67.7-73.1); the overall population attributable risk was 9.5%. Among the 16 penitentiary centers in the country, two of them-Tacumbú (39.0%) and Ciudad del Este (23.3%)-represent two thirds of all TB cases in prisons. TB among inmates is predominantly concentrated in those 20-34 years old (77.3% of all), twice the percentage of cases for the same age group outside of prison. Our findings show that the TB epidemic in prisons represents one of the most important challenges for TB control in Paraguay, especially in the country's largest cities. Appropriate TB control measures among incarcerated populations are needed and may have substantial impact on the overall TB burden in the country.

Infectious Diseases and the Lymphoid Extracellular Matrix Remodeling: A Focus on Conduit System.

The conduit system was described in lymphoid organs as a tubular and reticular set of structures compounded by collagen, laminin, perlecan, and heparin sulfate proteoglycan wrapped by reticular fibroblasts. This tubular system is capable of rapidly transport small molecules such as viruses, antigens, chemokines, cytokines, and immunoglobulins through lymphoid organs. This structure plays an important role in guiding the cells to their particular niches, therefore participating in cell cooperation, antigen presentation, and cellular activation. The remodeling of conduits has been described in chronic inflammation and infectious diseases to improve the transport of antigens to specific T and B cells in lymphoid tissue. However, malnutrition and infectious agents may induce extracellular matrix remodeling directly or indirectly, leading to the microarchitecture disorganization of secondary lymphoid organs and their conduit system. In this process, the fibers and cells that compound the conduit system may also be altered, which affects the development of a specific immune response. This review aims to discuss the extracellular matrix remodeling during infectious diseases with an emphasis on the alterations of molecules from the conduit system, which damages the cellular and molecular transit in secondary lymphoid organs compromising the immune response.

Culture Cell Block Controls as a Tool to the Biomolecular Diagnosis of Infectious Diseases.

The cell block (CB) technique has allowed easy obtainment of samples such as cellular and culture suspensions, to perform specific molecular tests such as immunohistochemistry and in situ hybridization. It has been improved along time, accuracy, and quality of the diagnoses, however, the cost of a commercial gel matrix for the preparation of CB is high and not suitable depending on the situation. The objective of this study is to test agarose as an alternative to the commercial gel matrix in the preparation of Aspergillus fumigatus' CB.

The human microbiota and infection prevention.

The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.

Antimicrobial magnetic nanoparticles based-therapies for controlling infectious diseases.

In the last years, the antimicrobial resistance against antibiotics has become a serious health issue, arise as global threat. This has generated a search for new strategies in the progress of new antimicrobial therapies. In this context, different nanosystems with antimicrobial properties have been studied. Specifically, magnetic nanoparticles seem to be very attractive due to their relatively simple synthesis, intrinsic antimicrobial activity, low toxicity and high versatility. Iron oxide NPs (IONPs) was authorized by the World Health Organization for human used in biomedical applications such as in vivo drug delivery systems, magnetic guided therapy and contrast agent for magnetic resonance imaging have been widely documented. Furthermore, the antimicrobial activity of different magnetic nanoparticles has recently been demonstrated. This review elucidates the recent progress of IONPs in drug delivery systems and focuses on the treatment of infectious diseases and target the possible detrimental biological effects and associated safety issues.

[Péptidos antimicrobianos, una alternativa prometedora para el tratamiento de enfermedades infecciosas].

Microorganisms that cause diseases in humans are constantly evolving, which represents a challenge in the search for effective treatments against them. Even when currently there are several pharmacological alternatives available, sometimes they are inefficient for the control of infectious diseases, especially because pathogens have generated multiple resistance mechanisms against them. Antimicrobial peptides have been described in many species of organisms, from fungi, plants and insects to humans; currently, there are molecules that appear as a solution that can be effective in modern therapeutics. The advantage of these natural peptides lies in that they have been evolving almost the same amount of time than the species that produce them and their effect on the control of microorganisms is highly significant; some of these molecules are isolated from living organisms, others are starting to be produced by synthetic methods, which allows having access to an endless number of peptides with diverse therapeutic activities.

Los microorganismos causantes de enfermedades en humanos evolucionan constantemente, lo que representa un reto en la búsqueda de tratamientos efectivos contra estos patógenos. Aun cuando en la actualidad se cuenta con diversas alternativas farmacológicas, estas en ocasiones resultan ineficientes para el control de las enfermedades infecciosas, sobre todo porque los patógenos han generado múltiples mecanismos de resistencia. Los péptidos antimicrobianos se han descrito en muchas especies de organismos: hongos, plantas, insectos y humanos; en la actualidad se presentan como una solución terapéutica que puede ser efectiva. La ventaja de estos péptidos naturales es que llevan evolucionando casi la misma cantidad de tiempo que las especies que producen y su efecto en el control de los microorganismos es muy notable; algunas de estas moléculas son aisladas de organismos vivos y otras se comienzan a producir por métodos sintéticos, lo que permite tener acceso a un sinfín de posibles péptidos con actividades terapéuticas diversas.

Plasminogen-binding proteins as an evasion mechanism of the host's innate immunity in infectious diseases.

Pathogens have developed particular strategies to infect and invade their hosts. Amongst these strategies' figures the modulation of several components of the innate immune system participating in early host defenses, such as the coagulation and complement cascades, as well as the fibrinolytic system. The components of the coagulation cascade and the fibrinolytic system have been proposed to be interfered during host invasion and tissue migration of bacteria, fungi, protozoa, and more recently, helminths. One of the components that has been proposed to facilitate pathogen migration is plasminogen (Plg), a protein found in the host's plasma, which is activated into plasmin (Plm), a serine protease that degrades fibrin networks and promotes degradation of extracellular matrix (ECM), aiding maintenance of homeostasis. However, pathogens possess Plg-binding proteins that can activate it, therefore taking advantage of the fibrin degradation to facilitate establishment in their hosts. Emergence of Plg-binding proteins appears to have occurred in diverse infectious agents along evolutionary history of host-pathogen relationships. The goal of the present review is to list, summarize, and analyze different examples of Plg-binding proteins used by infectious agents to invade and establish in their hosts. Emphasis was placed on mechanisms used by helminth parasites, particularly taeniid cestodes, where enolase has been identified as a major Plg-binding and activating protein. A new picture is starting to arise about how this glycolytic enzyme could acquire an entirely new role as modulator of the innate immune system in the context of the host-parasite relationship.

Caracterización clínica y microbiológica de niños y adolescentes con infecciones asociadas a la atención sanitaria / Clinical and microbiological characterization of children and adolescents with infections associated with health care

Se realizó un estudio descriptivo y transversal de 54 pacientes con infecciones asociadas a la asistencia sanitaria en el Hospital Infantil Sur Docente Dr Antonio María Béguez César de Santiago de Cuba, que abarcó desde enero de 2015 hasta diciembre de 2016. Las variables analizadas incluyeron edad, sexo, tipo de infección, resultado de los cultivos, microorganismo aislado y servicio de procedencia. Todas las muestras de los cultivos efectuados fueron procesadas en el Departamento de Microbiología de la mencionada institución. En la casuística predominaron el grupo etario de 5-17 años, el sexo masculino, la infección en la herida quirúrgica, la positividad de los cultivos, el aislamiento de la Escherichia coli y la Unidad de Cuidados Intensivos. Solo fallecieron 2 de los lactantes de 0-11 meses, para 3,7 por ciento.

A descriptive and cross-sectional study of 54 patients with infections associated with the health care in Dr Antonio María Béguez César Southern Teaching Pediatric Hospital was carried out in Santiago from Cuba, from January, 2015 to December, 2016. The analyzed variables included age, sex, infection type, result of the cultures, isolated organism and origin service. All the culture samples were processed in the Microbiology Department of the institution. The age group 5-17 years, male sex, infection in the surgical wound, the positivity of the cultures, isolation of Escherichia coli and the Intensive Care Unit prevailed in the case material. Only 2 of the infants with 0-11 months died, for 3,7 percent.

Effectiveness of probiotics on the occurrence of infections in older people: systematic review and meta-analysis.

BACKGROUND: infectious diseases in older people are associated with higher mortality rates and probiotics have been hypothesised to reduce the occurrence of infection. OBJECTIVES: to assess the effectiveness and safety of probiotics in the occurrence of infections in older adults in comparison to placebo. METHODS: a systematic review and meta-analysis of randomised placebo-controlled trials were conducted on 30 December 2016 using Medline, Embase, CENTRAL, Web of Science and LILACS databases. Efficacy outcomes were: occurrence of infection, quality of life, mortality and mean duration of infection per episode. Safety outcomes were adverse events. Data were analysed using relative risk ratios with 95% confidence intervals. Relative risk ratios were pooled where more than three estimates were available. RESULTS: fifteen articles were included, with a total of 5,916 participants with a mean age of 75.21 years. The effect of probiotics was not significantly different from that reported for placebo on the occurrence of infection, adverse events, mortality or mean duration of infection episodes (relative risk (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.08; RR 1.01, 95% CI 0.91 to 1.12; RR 1.09, 95% CI 0.70 to 1.72; MD -0.35, 95% CI -1.57 to 0.87, respectively). CONCLUSION: the current low-quality evidence does not support the use of probiotics for the reduction in the occurrence of infection in older adults, however, the safety outcomes were similar between probiotics and placebo. Further research is required to confirm these findings.PROSPERO: CRD42014013707.

Guillain-Barré syndrome, transverse myelitis and infectious diseases.

Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS have been reported, most frequently related to Campylobacter jejuni infection, however, other agents such as Zika Virus have been strongly associated. Patients with GBS related to infections frequently produce antibodies against human peripheral nerve gangliosides. In contrast, TM is an inflammatory disorder characterized by acute or subacute motor, sensory, and autonomic spinal cord dysfunction. There is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to GBS. It has been suggested to be triggered by infectious agents and molecular mimicry. In this review, we will focus on the putative role of infectious agents as triggering factors of GBS and TM.

HIF-1alpha and infectious diseases: a new frontier for the development of new therapies.

The aim of this review is to show the significant role of HIF-1alpha in inflammatory and infectious diseases. Hypoxia is a physiological characteristic of a wide range of diseases from cancer to infection. Cellular hypoxia is sensed by oxygen-sensitive hydrolase enzymes, which control the protein stability of hypoxia-inducible factor alpha 1 (HIF-1alpha) transcription factors. When stabilized, HIF-1alpha binds with its cofactors to HIF-responsive elements (HREs) in the promoters of target genes to organize a broad ranging transcriptional program in response to the hypoxic environment. HIF-1alpha also plays a regulatory function in response to a diversity of molecular signals of infection and inflammation even under normoxic conditions. HIF-1alpha is stimulated by pro-inflammatory cytokines, growth factors and a wide range of infections. Its induction is a general element of the host response to infection. In this review, we also discuss recent advances in knowledge on HIF-1alpha and inflammatory responses, as well as its direct influence in infectious diseases caused by bacteria, virus, protozoan parasites and fungi.

The role of biofilms in persistent infections and factors involved in ica-independent biofilm development and gene regulation in Staphylococcus aureus.

Staphylococcus aureus biofilms represent a unique micro-environment that directly contribute to the bacterial fitness within hospital settings. The accumulation of this structure on implanted medical devices has frequently caused the development of persistent and chronic S. aureus-associated infections, which represent an important social and economic burden worldwide. ica-independent biofilms are composed of an assortment of bacterial products and modulated by a multifaceted and overlapping regulatory network; therefore, biofilm composition can vary among S. aureus strains. In the microniches formed by biofilms-produced by a number of bacterial species and composed by different structural components-drug refractory cell subpopulations with distinct physiological characteristics can emerge and result in therapeutic failures in patients with recalcitrant bacterial infections. In this review, we highlight the importance of biofilms in the development of persistence and chronicity in some S. aureus diseases, the main molecules associated with ica-independent biofilm development and the regulatory mechanisms that modulate ica-independent biofilm production, accumulation, and dispersion.

Electrochemical magnetic microbeads-based biosensor for point-of-care serodiagnosis of infectious diseases.

Access to appropriate diagnostic tools is an essential component in the evaluation and improvement of global health. Additionally, timely detection of infectious agents is critical in early diagnosis and treatment of infectious diseases. Conventional pathogen detection methods such as culturing, enzyme linked immunosorbent assay (ELISA) or polymerase chain reaction (PCR) require long assay times, and complex and expensive instruments making them not adaptable to point-of-care (PoC) needs at resource-constrained places and primary care settings. Therefore, there is an unmet need to develop portable, simple, rapid, and accurate methods for PoC detection of infections. Here, we present the development and validation of a portable, robust and inexpensive electrochemical magnetic microbeads-based biosensor (EMBIA) platform for PoC serodiagnosis of infectious diseases caused by different types of microorganisms (parasitic protozoa, bacteria and viruses). We demonstrate the potential use of the EMBIA platform for in situ diagnosis of human (Chagas disease and human brucellosis) and animal (bovine brucellosis and foot-and-mouth disease) infections clearly differentiating infected from non-infected individuals or animals. For Chagas disease, a more extensive validation of the test was performed showing that the EMBIA platform displayed an excellent diagnostic performance almost indistinguishable, in terms of specificity and sensitivity, from a fluorescent immunomagnetic assay and the conventional ELISA using the same combination of antigens. This platform technology could potentially be applicable to diagnose other infectious and non-infectious diseases as well as detection and/or quantification of biomarkers at the POC and primary care settings.

[Infectious diseases in the genomic era]. / Infectología en la era de la genómica.

Next generation sequencing (NGS) technologies have arrived, changing research and infectious disease research into a new era, the "genomic era". Currently, the developed world is introducing NGS in a number of applications, including clinical diagnostics, epidemiology, and microbiology. In developing countries NGS is being progressively introduced. Technologies currently available allow to sequence the whole genome of bacterial and viral strains for an approximate cost of $100 USD, which is highly cost savings compared to old-technologies for genome sequencing. Here we review recent publication of whole genome sequencing used for, (i) tracking of foodborne outbreaks, with emphasis in Salmonella and Listeria monocytogenes, (ii) building genomic databases for Governments, (iii) investigating nosocomial infections, and (iv) clinical diagnosis. The genomic era is here to stay and researchers should use these "massive databases" generated by this technology to decrease infectious diseases and thus improve health of humans and animals.

Evaluación de la incorporación de un sistema automatizado de cultivo microbiológico en un hospital público de Nuquén / Assessment of the incorporation of an automated microbiological culture system in a public hospital of Neuquén

En este artículo se presenta un informe rápido de evaluación de tecnología sanitaria sobre la incorporación de un sistema de cultivo microbiano automatizado para la realización de pruebas de identificación y sensibilidad antibiótica de gérmenes en el laboratorio de microbiología de un hospital público de alta complejidad de la provincia del Neuquén.(AU)

Redox proteins as targets for drugs development against pathogens.

Antimicrobial drug resistance in pathogens is an increasing human health problem. The rapid loss of effectiveness in antibiotics treatments and the accumulation of multi-resistant microbial strains are increasing worldwide threats. Moreover, several infectious diseases have been neglected for years and new antimicrobial treatments are lacking. In other cases, complexity of infectious organisms has exceeded the efforts to find new drugs to control them. Thus, strategies for the proper development of specific drugs are critically needed. Redox metabolism has already been proved to be a useful target for drug development. During the last years a significant number of electron carriers, enzymes, proteins and protein complexes have been studied and some of them were found to be essential for survival of several microbial pathogens. This review will focus on three major redox metabolic pathways which may provide promising strategies to fight against pathogens: the non-mevalonate pathway for isoprenoids biosynthesis, the iron metabolism and the iron-sulfur proteins.The common attractive link of all these processes is the plant-type ferredoxin-NADP+ reductase, an enzyme that participates in numerous electron transfer reactions and has no homologous enzyme in humans. Research in these redox pathways will open new perspectives for the rational design of drugs against infectious diseases.