Nosocomial infections in the pediatric intensive care unit

Nosocomial (hospital-acquired) infections are a major complication of serious illnesses. Severely ill patients have a greater risk of acquiring nosocomial infections, so this problem is greatest in intensive care units. Studies have demonstrated that nosocomial infections are largely preventable. Adherence to recommended techniques for patient care will have the greatest benefit in the intensive care unit. In this paper the background epidemiology of nosocomial infections is reviewed and related to pediatrics and intensive care units. Types of diseases, assistance equipment, and monitoring devices which are associated with a high risk of nosocomial infections are emphasized and specific steps for lowering this risk are listed.     

The role of the cell wall in fungal pathogenesis

Fungal infections are a serious health problem. In recent years, basic research is focusing on the identification of fungal virulence factors as promising targets for the development of novel antifungals. The wall, as the most external cellular component, plays a crucial role in the interaction with host cells mediating processes such as adhesion or phagocytosis that are essential during infection. Specific components of the cell wall (called PAMPs) interact with specific receptors in the immune cell (called PRRs), triggering responses whose molecular mechanisms are being elucidated. We review here the main structural carbohydrate components of the fungal wall (glucan, mannan and chitin), how their biogenesis takes place in fungi and the specific receptors that they interact with. Different model fungal pathogens are chosen to illustrate the functional consequences of this interaction. Finally, the identification of the key components will have important consequences in the future and will allow better approaches to treat fungal infections.     

Listeria monocytogenes: epidemiology, human disease, and mechanisms of brain invasion

Listeria monocytogenes is a facultative intracellular bacterium that has predilection for causing central nervous systemic infections in humans and domesticated animals. This pathogen can be found worldwide in the food supply and most L. monocytogenes infections are acquired through ingestion of contaminated food. The main clinical syndromes caused by L. monocytogenes include febrile gastroenteritis, perinatal infection, and systemic infections marked by central nervous system infections with or without bacteremia. Experimental infection of mice has been used for over 50 years as a model system to study the pathogenesis of this organism including the mechanisms by which it invades the brain. Data from this model indicate that a specific subset of monocytes, distinguished in part by high expression of the Ly-6C antigen, become parasitized in the bone marrow and have a key role in transporting intracellular bacteria across the blood-brain barriers and into the central nervous system. This Minireview will summarize recent epidemiologic and clinical information regarding L. monocytogenes as a human pathogen and will discuss current in vitro and in vivo data relevant to the role of parasitized monocytes and the pathogenetic mechanisms that underlie its formidable ability to invade the central nervous system.     

Parasite infections in AIDS

'Illnesses no one's got' was the epidemiological clue that led to the identification of AIDS as a new disease in 1981 when a rare infectious organism Pneumocystis carinii was seen in previously healthy homosexuals. Since then a wide range of parasite infections has been recognized in AIDS patients. However, these patients are not susceptible to just any passing parasite. The human immunodeficiency virus (HIV) produces a specific immune defect and only parasites that can exploit that defect will be able to flourish. In this review Diana Lockwood and Jonathan Weber explore the spectrum of parasite diseases recognized in AIDS and also consider those parasites that occur infrequently in AIDS. Analysis of parasitic infections that AIDS patients do not suffer from will yield valuable information about immune recognition and handling of these parasites.     

Stimulator of interferon genes (STING): A “new chapter” in virus-associated cancer research. Lessons from wild-derived mouse models of innate immunity

Thanks to the numerous studies that have been carried out recently in the field of cytosolic DNA sensing, STING (Stimulator of Interferon Genes) is now recognized as a key mediator of innate immune signaling. A substantial body of evidence derived from in vivo mouse models demonstrates that STING-regulated pathways underlie the pathogenesis of many diseases including infectious diseases and cancers. It has also become evident from these studies that STING is a promising therapeutic target for the treatment of cancer. However, mouse strains commonly used for modelling innate immune response against infections or tumors do not allow investigators to accurately reproduce certain specific characteristics of immune response observed in human cells. In this review, we will discuss recent data demonstrating that the use of wild-derived genetically distinct inbred mice as a model for investigation into the innate immunity signaling networks may provide valuable insight into the STING-regulated pathways specific for human cells. The maximum complexity of STING-mediated mechanisms can probably be seen in case of DNA virus-induced carcinogenesis in which STING may perform unexpected biological activities. Therefore, in another part of this review we will summarize emerging data on the role of STING in human DNA virus-related oncopathologies, with particular attention to HPV-associated cervical cancer, aiming to demonstrate that STING indeed “starts a new chapter” in research on this issue and that wild-derived mouse models of STING-mediated response to infections will probably be helpful in finding out molecular basis for clinical observations.     

Induction of HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein of Chlamydia trachomatis in human genital tract infections.

HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Chlamydia trachomatis are present in the peripheral blood of humans who acquired genital tract infections with the organism. Three HLA-A2-restricted epitopes and two HLA-B51-restricted epitopes were identified in serovar E-MOMP. One of the five epitopes spans a variable segment of MOMP and is likely a serovar E-specific epitope. The other four epitopes are localized in constant segments and are C. trachomatis species specific. CTL populations specific for one or more of the four constant segment epitopes were isolated from all 10 infected subjects tested, regardless of infecting serovars, but from only one of seven uninfected subjects tested. The CTLs failed to recognize corresponding peptides derived from Chlamydia pneumoniae MOMP, further suggesting that they indeed resulted from genital tract infections with C. trachomatis. Significantly, ME180 human cervical epithelial cells productively infected with C. trachomatis were killed by the MOMP peptide-specific CTLs. Further investigations of the ability of such CTLs to lyse normal infected epithelial cells and their presence at inflamed sites in the genital tract will help understand the protective or pathological role of CTLs in chlamydial infections. The MOMP CTL epitopes may be explored as potential components of a subunit vaccine against sexually transmitted diseases caused by C. trachomatis. Moreover, the knowledge provided here will facilitate studies of HLA class I pathways of chlamydial Ag processing and presentation in physiologically relevant human APCs.     

Hacia el diagnóstico temprano de la candidiasis invasora en el paciente crítico

The management of invasive fungal infections in critically ill patients, from diagnosis to selection of the ther- apeutic protocol, is often a challenge. Early diagnosis and treatment are associated with a better prognosis, but apart from cases with positive cultures from blood or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, and there is a need for specific markers in these diseases. Serodiagnostic assays such as mannan an-tigen, mannan antibodies, Candida albicans germ-tube antibodies or (1→3)-β-D-glucan detection, and mo-lecular techniques for the detection of fungal-specific DNA have been developed with promising results in critical care settings. One of the main features in diagnosis is the evaluation of risk factors for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. The combination of prediction rules and non-culture microbiological tools could be currently be the key to improving the diagnosis and prognosis of invasive fungal infections in critically ill patients.     

Surgical and anesthetic management of patients with mitochondrial dysfunction

Mitochondrial diseases are primary defects in bio-energy metabolism. They are a heterogeneous group of diseases. The specific constellation of symptoms that will manifest in the effected individual depends on the type of genetic defect in the mitochondria. The goals of medical management, expressed in a highly simplified fashion, are to maintain a normal acid-base balance and to avoid those medical conditions and situations that add extra stress to a compromised bio-energy production system. Infection is a common stress that may cause a crisis in a patient with mitochondrial dysfunction. Treatment and avoidance of infections is a goal of both medical and surgical management. Common childhood illness such as otitis media, tonsillitis and sinusitis are example of such stress inducing infections.     

C3aR plays both sides in regulating resistance to bacterial infections

Activation of the complement pathway results in the production of bioactive C3a, a product of C3 cleavage, which interacts with membrane-bound receptor C3aR to regulate innate immune cell function and outcome of bacterial infection. Specifically, previous research has identified mechanistically distinct and cell type–specific roles for C3aR in regulating innate immune cell inflammatory state, antimicrobial killing capacity, and metabolism. Historically, the production of C3a has been relegated to the serum; however, recent studies have provided evidence that various cell types can produce intracellular C3a that stimulates intracellular C3aR. In light of these new results, it is imperative that we revisit previous studies regarding the role of C3aR in controlling bacterial infections and analyze these results in the context of both extracellular and intracellular C3a production and C3aR activation. Thus, this review will cover specific roles of C3aR in driving cell type–specific and tissue specific responses during bacterial infections and emphasize the contribution of the C3a–C3aR axis in regulating host resistance to bacterial infection.     

Clonal diversity within infections and the virulence of a malaria parasite, Plasmodium mexicanum

Both verbal and mathematical models of parasite virulence predict that genetic diversity of microparasite infections will influence the level of costs suffered by the host. We tested this idea by manipulating the number of co-existing clones of Plasmodium mexicanum in its natural vertebrate host, the fence lizard Sceloporus occidentalis. We established replicate infections of P. mexicanum made up of 1, 2, 3, or >3 clones (scored using 3 microsatellite loci) to observe the influence of clone number on several measures of parasite virulence. Clonal diversity did not affect body growth or production of immature erythrocytes. Blood haemoglobin concentration was highest for the most genetically complex infections (equal to that of non-infected lizards), and blood glucose levels and rate of blood clotting was highest for the most diverse infections (with greater glucose and more rapid clotting than non-infected animals). Neither specific clones nor parasitaemia were associated with virulence. In this first experiment that manipulated the clonal diversity of a natural Plasmodium-host system, the cost of infection with 1 or 2 clones of P. mexicanum was similar to that previously reported for infected lizards, but the most complex infections had either no cost or could be beneficial for the host.     

A system for the operative management of hospital infections in maternity hospitals]

A system for controlling the epidemic process of hospital infections in maternity hospitals and departments of infant pathology has been created. The specific feature of the proposed method is the prospective character of epidemiological surveillance: from the cause to the effect, and not vice versa. This is achieved by using the results of follow-up of the preconditions of the epidemic process activation (preterm delivery, gestosis, dry labor, birth injuries in mothers and infants) and the precursors of the beginning aggravation of the epidemic situation (the level of the contamination of infants with hospital microflora). Early information in this respect will help foresee the possible activation of the epidemic process of hospital infections and take necessary measures when infant infection rate is just elevated.     

Neuroinflammation,Gut Microbiome,and Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that develops insidiously and causes dementia finally. There are also clinical complications in advanced dementia, such as eating problems, infections, which will lead to the decline of patients’ life quality, and the rising cost of care for AD to our society. AD will be important public health challenge. Early detection of AD may be a key issue to prevent, delay, and stop the disease. Gut microbiome and neuroinflammation are closely related with nervous system diseases, although the specific mechanism is not clear. This review introduces the relationship between neuroinflammation, gut microbiome, and AD.     

Systemic infections in multiple sclerosis and experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). It has been suggested that viral and bacterial infections contribute to the pathogenesis of MS. This review will give an overview about the influence of viral and bacterial infections on MS and experimental autoimmune encephalomyelitis (EAE). It will focus on bacterial infections and will also emphasise therapeutic consequences such as the impact of antibiotic treatment on the course of EAE. In summary, a growing body of evidence suggests that systemic infections are a risk factor for the initiation of autoimmune processes including the induction of acute events in MS. Experimental and clinical data strongly suggest early treatment of bacterial infections in MS patients to avoid aggravation and relapse.     

The Future of Fungal Serology

The incidence of invasive fungal infections continues to grow. Early and rapid diagnosis is essential to prevent morbidity and mortality. The number of assays available for the detection of fungal antigens in human body fluids are increasing in number and becoming part of the basic diagnostic workup for many fungal infections. Detection of specific antibody has been an important component in the diagnosis of fungal infections. Complement fixation and immunodiffusion continue to be the gold standard for antibody detection but are complex to perform, require extensive expertise, and are mostly performed in reference labs. Newer assays are being developed to reduce turn-around time, but have not been fully evaluated. A challenge for improving serologic assays is to move from crude antigens and polyclonal antibodies to purified and/or recombinant antigens and monoclonal antibodies, while retaining good sensitivity and specificity. Recent developments using lateral flow methodology have provided novel point-of-care antigen assays requiring little technical expertise. Such innovative techniques will help to keep the future of fungal serology bright.     

On the challenges of detecting whole Staphylococcus aureus cells with biosensors

Due to the increasing number of nosocomial infections and multidrug‐resistant bacterial strains, Staphylococcus aureus is now a major worldwide concern. Rapid detection and characterization of this bacterium has become an important issue for biomedical applications. Biosensors are increasingly appearing as low‐cost, easy‐to‐operate and fast alternatives for rapid detection. In this review, we will introduce the main characteristics of S. aureus and will focus on the interest of biosensors for a faster detection of whole S. aureus cells. In particular, we will review the most promising strategies in the choice of ligand for the design of selective and efficient biosensors. Their specific characteristics as well as their advantages and/or disadvantages will also be commented.     

Immune reconstitution and strategies for rebuilding the immune system after haploidentical stem cell transplantation

Haploidentical hematopoietic stem cell transplantation is a curative alternative option for patients without an otherwise suitable stem cell donor. In order to prevent graft-versus-host disease (GvHD), different in vitro and in vivo T cell-depletion strategies have been developed. A delayed immune reconstitution is common to all these strategies, and an impaired immune function after haploidentical transplantation with subsequent infections is a major cause of deaths in these patients. In addition to in vitro and in vivo T cell-depletion methods, posttransplant strategies to rapidly rebuild the immune system have been introduced in order to improve the outcome. Advances in in vitro and in vivo T cell-depletion methods, and adoptive transfer of immune cells of the innate and specific immune system, will contribute to reduce the risk of GvHD, lethal infections, and the risk of relapse of the underlying malignant disease.     

Diagnostic laboratory parasitology--a stepping stone to medical research in tropical Africa.

African countries can concentrate mainly on operational and problem-solving type of medical research using as a basis routine diagnostic laboratory parasitology which can be elevated to research level by incorporating all relevant techniques backed by statistically-based programming. Because of high incidence of parasitic infections and the peculiar host-parasite relationship, co-operation between all departments of any major hospital will be required to deal with the diseases due to them. Longitudinal studies on some parasites will enable generalisation and specific views to be formed on some infections. Multiplicity and wide variety of available techniques offer several research possibilities of clinico-pathological and epidemiological significance. Routine laboratory-based research offers the right environment for training various types of laboratory workers from technicians to medical parasitologists, through on-the-job training on techniques, investigative studies and research, backed by formal lectures and practicals at various levels. Trainee medical parasitologists can obtain higher degrees locally or abroad. The research can be organised around micro and mini research units. This approach is cost-beneficial because it minimises administrative difficulties and so avoids wastage. The results can be used to monitor impact of national development on parasitic infection prevalence and to formulate a policy on parasitic disease management.     

感染组学 (infectomics) ———对感染性疾病的总体性和综合性研究

在感染性疾病的范畴内,目前急需一个能有效地、精确地和综合性地研究微生物感染的结构性和功能性基因组学和蛋白质组学 ( 感染组学 ) 的全面方法. 新的方法 ( 如 DNA 和蛋白质微阵列 ) 和传统方法 ( 如分子克隆、 PCR 、基因敲除,加进 (knockin) 和反义术等 ) 的结合将有助于克服今天的困难. 在感染时,微生物及其宿主的全部表型改变 ( 感染组 ) 均由微生物病原体及其宿主的基因组所编码,并在特异的微生物 - 宿主相互作用时的某些环境条件下表达. 微生物及其宿主的全部药物反应 ( 药理组 ) 可用基因组或蛋白质组的方法检出. 分析基因型和表型或表达形式的全基因组方法将最终导致对微生物的发病机理、感染性疾病的快速诊断和控制感染的新策略的全面研究. 感染性疾病中最基本的问题是,如何全面地和综合性地应用感染组学,来了解微生物病原体及其宿主的相互作用.     

Parasitic infection and the polarized Th2 immune response can alter a vaccine-induced immune response

The AIDS epidemic in the Developing World represents a major global crisis. It is imperative that we develop an effective vaccine. Vaccines are economically the most efficient means of controlling viral infections. However, the development of a vaccine against HIV-1 has been a formidable task, and in developing countries chronic parasitic infection adds another level of complexity to AIDS vaccine development. Helminthic and protozoan infections, common in developing countries, can result in a constant state of immune activation that is characterized by a dominant Th2 type of cytokine profile, high IgE levels, and eosinophilia. Such an immune profile may have an adverse impact on the efficacy of vaccines, in particular, an HIV-1 vaccine. Indeed, the CD8 cellular immune response and the corresponding Th1 type cytokines that enhance the CD8 cellular immune response are important for clearing many viral infections. It is believed that an antigen specific CD8 cellular immune response will be an important component of an HIV-1 vaccine.     

Emerging Infections

Emerging infections Emerging or re‐emerging infections have been occurring regularly for millennia. However, in the last years the frequency between pandemics/epidemics is growing alarmingly. This article briefly highlights milestones of emerging infections and several factors favouring their occurrence. Some prominent examples of viral (re‐)emerging infections will be pointed out in detail. Finally, potential future countermeasures against emerging diseases will be discussed.