The Role of Extracellular Vesicles from Human Macrophages on Host-Pathogen Interaction.

The nano-sized membrane enclosed extracellular vesicles (EVs) released by virtually all cell types play an essential role in intercellular communication via delivering bio-molecules, such as nucleic acids, proteins, lipids, and other molecules to recipient cells. By mediating an active and steady-state cell-to-cell communication, EVs contribute to regulating and preserving cellular homeostasis. On the other hand, EVs can also spread pathogen-derived molecules during infections, subverting the host immune responses during infections and thus worsening pathophysiological processes. In recent years, the biological functioning of EVs has become a widespread research field in basic and clinical branches of medical sciences due to their potential role in therapeutic applications for several diseases. This review aims to summarize the main recent findings regarding the implication of EVs shed by human macrophages (MΦ-EVs) and how they can modulate the host immune response to control or increase the damage caused by infectious agents. We will also present the methods used to describe MΦ-EVs, as well as the potential of these EVs as disease diagnostic tools for some human pathogens. We believe that an in-depth understanding of the host-pathogen interactions mediated by MΦ-EVs may trigger the development of innovative therapeutic strategies against infectious diseases.

Epidemiología del VIH en Venezuela desde 1983 a 2016 / Epidemiology of HIV Infection in Venezuela since the year 1983 to the year 2016

Hay en el mundo, grandes avances en la lucha contra el Virus de Inmunodeficiencia Humana (VIH). En Venezuela el primer paciente con SIDA fue evaluado por el Dr. Manuel Guzmán en el año 1983, estimándose para el año 2016 120.000 personas infectadas Objetivo: describir los indicadores epidemiológicos del VIH en Venezuela desde el año 1983 hasta el año 2016. Metodología: se revisaron documentos del Programa Nacional de VIH/SIDA/ITS del MPPS (PNS), ONUSIDA, OPS, OMS y otros documentos científicos. También los datos epidemiológicos, y el acceso a la carga viral (CV) de VIH, CD4, test de resistencia y tratamiento antirretroviral (TARV). Resultados: Venezuela enfrenta una epidemia con- centrada, con prevalencia mayor de 5% en grupos vulnerables como los HSH y se desconoce la preva- lencia en otros grupos vulnerables. La prevalencia del VIH en los indígenas waraos es de 9.5 %, una de las más altas de América Latina, cuya situación ha sido catalogada como dramática. El número de mujeres infectadas va en ascenso, la mayoría son amas de casa con, instrucción de educación prima- ria y transmisión principalmente sexual. No hay datos de prevalencia de VIH de las embarazadas a nivel nacional y la tasa de transmisión vertical esti- mada para el 2013 fue de 21.8 %. La tasa de mor- talidad general por VIH/SIDA para el año 2015 fue de 8.3 por 100.000 habitantes, un aumento de 94 % con respecto a 1996 (4,14 x 100.000 habitantes). La tasa promedio de mortalidad por VIH/SIDA en niños < de 5 años, es mayor en los menores de un año, con una tasa de 3,46 por 1.000 recién nacidos vivos. El índice de mortalidad en los hombres aumentó 1.8 veces y en la mujer 3.9. El acceso a las pruebas diagnósticas, CV de VIH, lin-focitos CD4 y test de resistencia está seriamente limitado. Para el año 2016, de 120 mil personas con VIH , 59% tenía acceso al TARV y solo 7 % tenían supresión viral. Venezuela es el país de América Latina, que ha experimentado más interrupciones del TARV, agravándose dicha situación durante 2017 y 2018, con un acceso a tratamiento de 16 %en abril de 2018, y desde esa fecha, 58.000 pacien-tes estaban en falta absoluta de TARV. Gracias al Plan Maestro, el acceso a TARV fue reiniciado en febrero del 2019. Conclusión: después de 30 años de la epidemia del VIH en Venezuela, las políticas sanitarias no han sido suficientes para detener el avance de la enfermedad, lo que evidencia el fraca-so del PNS. Es urgente y prioritario, cumplir las recomendaciones del Plan Maestro, así como otras expuestas en el presente documento(AU)

Immunodeficiency Virus (HIV). The first patient with AIDS in Venezuela, was evaluated by Dr. Manuel Guzmán in 1983 and in the year 2016 the number of infected people was estimated in 120,000. Objective: to describe the epidemiological indicators of HIV in Venezuela from 1983 to 2016. Methodology, the reviewed documents were: National HIV / AIDS / STI Program of the Ministry of Popular Power for Health (PNS), UNAIDS/ WHO/PAHO Master Plan for fortifying the response to HIV, tuberculosis and malaria in our country from a public health perspective (Master Plan), and other scientific publications. Epidemiological data were reviewed as well as the access to viral load (VL) of HIV, CD4, resistance test, and antiretroviral treatment (ART). Results: Venezuela faces a concentrated epidemic, with a prevalence of more than 5% in vulnerable groups and the prevalence in other groups is unknown. The prevalence of HIV in the Waraos Indigenous people is 9.5%, one of the highest in Latin America, the situation has been named as dramatic. Infected women are on the rise, with the majority being housewives, with elementary schooling and, mainly by sexual transmission. There are no HIV prevalence data of pregnant women nationwide and the estimated vertical transmission rate for 2013 was 21.8%. The overall mortality rate for HIV / AIDS for the year 2015 was 8.3 per 100.000 inhabitants, an increase of 94% compared to 1996 (4.14 x 105). The mortality index in men increased 1.8 times and in women 3.9. The average mortality rate for HIV / AIDS in children under 5 years of age is higher in those under one year of age, with a rate of 3.46 per 1000 live births. In 2014, maternal deaths due to AIDS represented 2.5%, there are no updated data. Access to diagnostic tests, VL, lymphocyte CD4 and resistance test is severely limited. For the year 2016, 120.000 persons were living with HIV in Venezuela, 59% had access to ART, but only 7% had suppression of LV. Venezuela is the country in Latin America, which has experienced more interruptions of ART. Aggravating this situation during 2017 and 2018, with an access to treatment of 16 % in April 2018. Since then, approximately 58,000 patients receive no ART at all. Thanks to the Master Plan access to ART was reinitiated in February 2019. Conclusions: more than 30 years after the HIV epidemic in Venezuela, health policies have been sufficient to stop the progression of the disease, which shows the failure of the National HIV /AIDS / STI Program. It is a priority to comply with the recommendations of the Master Plan, as well as others set out in this document(AU)

Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children.

The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.

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.

Immunogenetic profiling of 23 SNPs of cytokine and chemokine receptor genes through a minisequencing technique: Design, development and validation.

The minisequencing technique offers accuracy and robustness to genotyping of polymorphic DNA variants, being an excellent option for the identification and analyses of prognostic/susceptibility markers in human diseases. Two multiplex minisequencing assays were designed and standardized to screen 23 candidate SNPs in cytokine, chemokine receptor and ligand genes previously associated with susceptibility to cancer and autoimmune disorders as well as to infectious diseases outcome. The SNPs were displayed in two separate panels (panel 1-IL2 rs2069762, TNFα rs1800629, rs361525; IL4 rs2243250; IL6 rs1800795; IL10 rs1800896, rs1800872; IL17A rs8193036, rs2275913 and panel 2-CCR3 rs309125, CCR4 rs6770096, rs2228428; CCR6 rs968334; CCR8 rs2853699; CXCR3 rs34334103, rs2280964;CXCR6 rs223435, rs2234358; CCL20 rs13034664, rs6749704; CCL22 rs4359426; CXCL10/IP-10 rs3921, rs56061981). A total of 305 DNA samples from healthy individuals were genotyped by minisequencing. To validate the minisequencing technique and to encompass the majority of the potential genotypes for all 23 SNPs, 20 of these samples were genotyped by Sanger sequencing. The results of both techniques were 100% in agreement. The technique of minisequencing showed high accuracy and robustness, avoiding the need for high quantities of DNA template samples. It was easily to be conducted in bulk samples derived from a highly admixed human population, being therefore an excellent option for immunogenetic studies.

Clinical aspects of leprosy.

Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects the peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones and joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation varies from few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmented lesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individuals who have not developed cell-mediated immunity against M. leprae yet. The number of lesions depends on the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellular immune response and limited humoral immune responses to M. leprae, usually present few skin lesions. Without treatment, those patients tend to evolve into the polar tuberculoid or borderline tuberculoid form of leprosy. Due to the inability to mount an effective cellular-mediated response to M. leprae and the consequent hematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributed hypochromic lesions. Without treatment these patients evolve to a nonresistant form of leprosy, polar lepromatous.

Neuroimmunomodulation during infectious diseases: mechanisms, causes and consequences for the host.

In this special issue of Neuroimmunomodulation, the reader will find reviewed some of the hottest topics in the field of neuroendocrine-immune interactions, with emphasis on infectious diseases. For instance, the role that immunoendocrine alterations have during human tuberculosis, a chronic infectious disease, is discussed, and it is concluded that these immunoendocrine interactions may play a detrimental role during the disease, in terms of the development of protective immune responses, control of tissue damage and metabolic disorders. Also, the role that neuroimmunomodulation plays in parasitic diseases is presented, and emphasizes the importance of the host-parasite neuroimmunoendocrine network during helminth infection. Moreover, the influence of beta-androstenes on resistance to viral and bacterial infections is discussed, as well as the impact of infectious diseases upon neuroendocrine circuits. Also, the reader will find contributions to the study of sex hormones and modulation of immunity against leishmaniasis, as well as recent work on the immune mechanisms associated with resistance or susceptibility to parasitic diseases during pregnancy. We hope that our readers will find the first ever special issue devoted to neuroimmunomodulation and infectious diseases fascinating and enticing.

The impact of infectious diseases upon neuroendocrine circuits.

During infectious diseases, neuroendocrine and immune networks act in concert, facilitating host response. It is known that infections cause profound immune changes, but the impact upon immunoendocrine circuits has been less studied. Disorders in the hypothalamic-pituitary-adrenal (HPA) axis were frequently observed associated with infections, and these changes often occur in parallel to alterations in the systemic cytokine network. Explanations for the infection-associated immunoendocrine disturbances include several and not mutually exclusive possibilities. Changes in cytokine levels can enhance or suppress the HPA axis, by acting at the hypothalamus-pituitary unit and/or at the adrenal glands. In situ inflammatory reactions or structural changes like vascular alterations or an enhanced extracellular matrix deposition in the endocrine microenvironment may also lead to a transient HPA dysfunction. Lastly, a microbe-related effect by means of pathogen infiltration or exploitation of the host's hormonal microenvironment may be involved as well. A better understanding of the relevance of immunoendocrine communication during infectious diseases, and how disturbances in the flux of information lead to neuroendocrine immune-related disorders will provide important insights into mechanisms underlying the disease pathology.

Impact of pancreatic allograft function on 1-year survival rates after simultaneous pancreatic-renal transplant.

OBJECTIVES: Simultaneous pancreatic-renal transplant is an effective treatment for insulin-dependent patients with chronic renal failure. We sought to identify the main influences on pancreatic and patient survival rates after simultaneous pancreas-kidney transplants. PATIENTS AND METHODS: The 1-year patient and pancreas survival rates of 150 patients who had undergone simultaneous pancreas-kidney transplant were analyzed by the Cox proportional hazards regression model and the Kaplan-Meier method. Uni and multivariate analyses were performed in terms of transplant-, recipient-, and donor-related risk factors. RESULTS: At 1 year, patient and pancreatic allograft survival rates were 82% and 76.7%, respectively. Delayed graft function in the kidney (P = .001, HR 5.41), acute kidney rejection (P = .016, HR 3.36), and intra-abdominal infection (P < .0001, HR 4.15) were the main factors related to 1-year patient survival. Pancreatic allograft survival at 1 year was related to intra-abdominal infection (P < .0001, OR 12.83), vascular thrombosis (P = .002, OR 40.55), acute kidney rejection (P = .027, OR 3.06), donor sodium greater than 155 mEq/L (P = .02, OR 3.27), and dopamine administration exceeding 7.6 microg/kg/min (P = .046, OR 2.85). CONCLUSIONS: Delayed kidney allograft function and intra-abdominal infection had an important effect on both patient and pancreatic allograft survival rates.

Academic-industry partnerships in addressing nutrition--[infection-immunity-inflammation] interactions.

The interaction between nutrition and infection is a key determinant of human health. Traditionally the interaction has centered on the role of nutrients in defining host defenses and the impact of infection in defining nutritional needs and status. Over the past decades the interaction has expanded its scope to encompass the role of specific nutrients in defining acquired immune function, in the modulation of inflammatory processes and on the virulence of the infectious agent itself. More recently the role of micronutrients and fatty acids on the response of cells and tissues to hypoxic and toxic damage has been recognized suggesting a fourth dimension to the interaction. The list of nutrients affecting infection, immunity, inflammation and cell injury has expanded from traditional protein-energy supply to several vitamins, multiple minerals and more recently specific lipid components of the diet. The promise of nutrition in the defense against infection, inflammation and tissue injury has spawned a thriving pharma-nutritional supplement industry and the development of novel foods that require appropriate evaluation of efficacy, safety and effectiveness relative to costs. Academics need to aware of the ethics and the pitfalls in the interaction with industry; conversely industry has to define its role in the process of bringing new knowledge to useful products. The process needs to be interactive, transparent and clearly place public interest above all other considerations.

Community-acquired methicillin-resistant Staphylococcus aureus

Published data confirm that community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing in incidence in both urban and rural settings. The statistical risk is higher for athletes, military personnel, prison inmates, intravenous drug abusers, the homeless, children in daycare, and certain Native American groups, but the infections are by no means restricted to these populations. Roughly 85% of the infections involve the skin and subcutaneous tissue, with the most common presentations being an abscess or folliculitis. The typical associated gene cassette is quite small and codes only for methicillin resistance. Abscesses generally respond to drainage. Learning objective: At the conclusion of this learning activity, participants should recognize groups at high risk for community-acquired MSRA infections and manage these infections appropriately.

The molecular basis of susceptibility to infection in liver cirrhosis.

There is much clinical evidence of a relationship between infectious disease and chronic liver disease. The consequences of this adverse association have been described and advances in the treatment and prophylaxis of infectious disease have had an important effect on the management of patients with chronic liver disease. The association between infectious disease and chronic liver disease involves altered cytokine production, cellular immunity, and vascular response. However, there is little information on the mechanisms underlying these phenomena. In this report, we review the mechanistic basis of this common association.

Associação do sistema de histocompatibilidade humano com patologias ginecológicas e reprodutivas / Association of the human histocompatibility antigens with gynecological and reproductive disorders

Mecanismos imunes são atualmente aventados como componentes fundamentais nas etapas de fertilização, implantação e manutenção da gravidez, bem como na fisiopatologia de doenças infecciosas e neoplásicas do trato genital feminino. As moléculas do sistema de histocompatibilidade humano (HLA) permeiam estes aspectos, interferindo na susceptibilidade a patologias e atuando na manutenção da fisiologia reprodutiva. Este trabalho se propõe a atualizar o conhecimento sobre estrutura e função das moléculas de histocompatibilidade, métodos de detecção, nomenclatura e mecanismos imunogenéticos que associam o HLA com a reprodução humana e algumas patologias ginecológicas. Na pesquisa bibliográfica utilizamos os bancos de dados MEDLINE e LILACS, privilegiando os estudos mais recentes de cada tema. Conclui-se que o HLA desempenha papel importante na reprodução humana e doenças ginecológicas, mas ainda pouco estudado. O melhor conhecimento dos fatores imunorregulatórios envolvidos nestes aspectos são áreas promissoras de pesquisa.

Differential diagnosis of acute liver failure in India.

BACKGROUND: Acute liver failure (ALF) is a condition with rapid deterioration of liver function resulting in hepatic encephalopathy and/or coagulopathy in patients with previously normal liver. Complicated forms of certain infectious diseases like falciparum malaria, leptospirosis, dengue fever, ricketsial fever, typhoid fever, haemophagocytosis, herpes simplex virus, cytomegalovirus, tuberculosis or amoebic liver abscess can present with altered mentation and/or bleeding manifestations in presence of jaundice and mimic ALF due to acute viral hepatitis (AVH). METHODS: We describe our experience in last 2 years with 28 patients of ALF due to above mentioned conditions (ALF-ID) and compared them with 28 patients with ALF due to AVH (ALF-AVH). RESULTS: In ALF-ID, typhoid fever was present in 1, haemophagocytosis in 1, ricketsial infection in 4 (scrub typhus = 2, endemic typhus = 2), amoebic liver abscess in 4, leptospirosis in 5, dengue fever in 5 and falciparum malaria in 8 patients. In ALF-AVH, hepatitis E and B co-infection was responsible in 1, hepatitis A and E co-infection in 1 and hepatitis E, B and C co-infection in 1, hepatitis E in 18, hepatitis A in 2 and hepatitis B in 5 patients. Differentiation of various forms of ALF-ID from ALF-AVH depends on various clinical, haematological and biochemical parameters, in addition to specific diagnostic tests. Patients with ALF-AVH had mortality rate of 50% (14/28) and ALF-ID had mortality rate of 25% (7/28). CONCLUSIONS: In developing countries, ALF-mimicking infections should be looked for in differential diagnosis of ALF. Early identification and treatment of these infections is important in reducing mortality.

Tropical dermatology: bacterial tropical diseases / Tropical dermatology: bacterial tropical diseases

Bacterial infections are common in tropical parts of the world and can include those species also seen regularly in temperate climates. Many tropical bacterial infections, however, are rarely diagnosed in temperate parts of the world and include bartonellosis, tropical ulcer, tropical pyomyositis, granuloma inguinale, lymphogranuloma venereum, yaws, pinta, melioidosis, and glanders. Some tropical bacterial diseases, eg, plague and anthrax, are associated with high mortality rates and are of potential use in bioterrorism. Some tropical bacterial diseases are closely associated with specific activities such as hunting (ie, tularemia) or eating raw seafood (Vibrio vulnificus infection). The bacterial diseases having the most severe medical impact in the tropics are those caused by members of the Mycobacterium genus. Millions of persons throughout the world suffer from tuberculosis and leprosy; Buruli ulcers are common causes of morbidity in many tropical countries. Because of the increasing frequency of travel to tropical parts of the world for tourism and work as well as the increasing number of immigrants and adoptees from these areas, it is imperative that physicians practicing in temperate climates be able to recognize the signs and symptoms of tropical bacterial diseases, carry out the proper diagnostic tests, and initiate appropriate therapy and prevention. LEARNING OBJECTIVE: At the completion of this learning activity, participants should be familiar with the clinical presentations, epidemiologies, diagnoses, therapies, and preventions of bacterial tropical diseases...