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PubMedDate not supplied

Update on clinical antifungal susceptibility testing for Candida species.

With the emergence of fungi as important nosocomial pathogens, increasing reports of antifungal resistance, and expanding drug therapy options, the need for clinically relevant antifungal susceptibility testing is evident. Over the last decade, the National Committee for Clinical Laboratory Standards (NCCLS) worked to standardize procedures for in vitro susceptibility testing of Candida species against fluconazole, itraconazole, 5-fluorocytosine, and amphotericin B. With the establishment of a reproducible methodology, correlation of antifungal susceptibility in vitro with clinical outcome is a priority. The NCCLS proposed susceptibility breakpoints for the three agents against Candida species, with breakpoints for amphotericin B forthcoming. These breakpoints could provide useful guidance in some clinical situations involving azole or 5-fluorocytosine therapy; however, routine susceptibility testing of fungal isolates should be discouraged.

Antifungal Agents↗

PubMed1983

Enteric fever in patients admitted to a diarrhoeal disease hospital in Bangladesh.

The hospital records of 62 patients with blood culture-proven enteric fever admitted to the Dacca Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, over a one-year period were reviewed. Older children and young adults had the highest age-specific rates of disease. The clinical, epidemiological and laboratory features of patients with enteric fever were compared with similar information from patients in hospital for cholera and shigellosis. Patients with enteric fever had a significantly longer prodrome of illness and were more likely to have fever than patients in the other groups. Our hospital cares primarily for patients with diarrhoeal diseases and while 94% of enteric fever patients had diarrhoea, only 5% had the recognized diarrhoeal pathogens Shigella or Vibrio cholerae identified, compared to 25% of the total hospital in-patient group, suggesting that Salmonella typhi itself may be a cause of diarrhoea. Antibiotic resistance patterns of S. typhi isolates were reviewed, and one isolate was found to be multiply antibiotic resistant. The advent of an effective oral typhoid vaccine makes further work on the epidemiology of enteric fever in endemic areas such as Bangladesh a high priority.

Adolescent↗

PubMed2005

Antibiotics: where did we go wrong?

In the late 1960s, the medical need for new antibiotics began to be questioned, and the pharmaceutical industry shifted its emphasis of antibacterials from that of a therapeutic leader to a low-priority research area. Although infectious diseases, in particular those caused by bacterial infections, are still among the top causes of mortality in the world, industrial support continues to wane. The shift from this important area of antimicrobial research has been attributed to a combination of science, medical, marketing and business reasons. This decline in antibacterial drug discovery, coupled with increasing risk as a result of infections caused by drug-resistant bacterial pathogens, represents a clear public health threat.

Anti-Bacterial Agents↗

PubMed2003

Small GTPase 'Rop': molecular switch for plant defense responses.

The conserved Rho family of GTPases (Rho, Rac, and Cdc42) in fungi and mammals has emerged as a key regulator of diverse cellular activities, such as cytoskeletal rearrangements, programmed cell death, stress-induced signaling, and cell growth and differentiation. In plants, a unique class of Rho-like proteins, most closely related to mammalian Rac, has only been found and termed 'Rop' (Rho-related GTPase from plant [Li et al. (1998) Plant Physiol. 118, 407-417; Yang (2002) Plant Cell 14, S375-S388]). ROPs have been implicated in regulating various plant cellular responses including defense against pathogens. It has been shown that ROPs, like mammalian Rac, trigger hydrogen peroxide production and hence the 'oxidative burst', a crucial component associated with the cell death, most likely via activation of nicotinamide adenine dinucleotide phosphate oxidase in both monocotyledonous and dicotyledonous species. Recent studies have established that ROPs also function as a molecular switch for defense signaling pathway(s) linked with disease resistance. As discerning the defense pathway remains one of the priority research areas in the field of plant biology, this review is therefore particularly focused on recent progresses that have been made towards understanding the plant defense responses mediated by ROPs.

Amino Acid Sequence↗

PubMed2005

Virus safety of intravenous immunoglobulin: future challenges.

Patients with immunodeficiencies or some types of autoimmune diseases are dependent on safe therapy with intravenous immunoglobulins. State-of-the-art manufacturing processes provide a high safety standard by incorporating virus elimination procedures into the manufacturing process. Based on their mechanism, these procedures are grouped into three classes: partitioning, inactivation, and removal based on size. Because of current socioeconomic and ecological changes, emerging pathogens continue to be expected. Such pathogens may spread very quickly because of increased intercontinental traffic. Severe acute respiratory syndrome-coronavirus and the West Nile virus are recent examples. Currently, it is not possible to predict the impact such a pathogen will have on blood safety because the capacity for a globally coordinated reaction to such a threat is also evolving. The worst-case scenario would be the emergence of a transmissible, small, nonenveloped virus in the blood donor population. Examples of small nonenveloped viruses, which change host and tissue tropism, are discussed, with focus on parvoviridae. Although today's immunoglobulins are safer than ever, in preparation for future challenges it is a high priority for the plasma industry to proactively investigate such viruses on a molecular and cellular level to identify their vulnerabilities.

Animals↗

PubMed2004

Role of neutrophil polymorphonuclear leukocytes during bovine coliform mastitis: physiology or pathology?

The review compiles some major findings concerning the inflammatory reaction in the mammary gland of dairy cows within the physiological context of the lactation cycle. The dual role of the PMN leukocyte in defense and tissue damage during experimentally induced coliform mastitis, especially around parturition and during early lactation, is highlighted. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. Most researchers now accept that the PMN is a key factor in the cows' defense against intramammary infection with E coli. During diapedesis of PMN into the mammary gland, several functionally important receptors are up-regulated, allowing for a more efficient phagocytosis and killing of invading pathogens. While PMN are phagocytosing and destroying the invading pathogens, they inadvertently release chemical mediators which induces swelling of secretory epithelium cytoplasm, sloughing of secretory cells, and decreased secretory activity. Permanent scarring will result in a loss of milk production. PMN's act as friends and as foes and are important components in the balance between mammary defense and damage. The mammary gland is a complex open self-regulatory system with a continuous flow of matter, energy and information. Metabolically, it has absolute priority over many other tissues except the brain. Self-regulation with change over time is characterized by a dynamic equilibrium between two mechanisms: homeostatic and homeorhetic. The defense against invaders by innate immunity and auto-repair of the damaged tissues are covered by homeostatic mechanisms while colostrogenesis and maintenance of milk secretion are controlled by mainly homeorhetic mechanisms. However, also innate immunity has to function and develop in time, depending on the lactation cycle, and its behavior and evolution in time in such a dynamical system is a challenge and a problem at the same time. In such a complex dynamic situation it is not surprising that physiology is not far away from pathology. E. coli mastitis can be a severe problem during the beginning of lactation whereas it is completely self-curing after peak lactation (8 weeks). The approach to focus on the PMN doesn't mean that the defense of the mammary gland is more simple than in other tissues. The defense of mammary gland is characterized by its complexity and over the last years many data show that there are tight connections with the mononuclear cells in mammary gland tissue. Today it is known that T cells play a central role in orchestrating the immune response. However, because of the peculiar interest in the PMN of the authors during the last 10 years, the immunobiology of the mononuclear cells in the mammary gland is not covered.

Animals↗

PubMed2026

Global vaccine readiness: equity-by-design in pandemic preparedness and response.

INTRODUCTION: COVID-19 showed that rapid vaccine development and roll-out, while lifesaving, can still yield large, avoidable harms when equity is not considered from the outset. Disparities in vaccine timing and coverage, especially in low-resource settings, amplified health and economic burdens, highlighting the need for preparedness frameworks that combine speed with fairness. AREAS COVERED: We synthesize evidence from literature and policy reports regarding global vaccine roll-out, focusing on avertable mortality under alternative sharing scenarios, procurement design, pooled mechanisms such as COVAX, and the role of distributed manufacturing and delivery capacity. We also examine how transparent data-sharing, effective public communication, genomic surveillance, adaptive trial designs, and modeling hubs can support more responsive and equitable vaccine deployment. Across six reflection points, we translate these lessons into practical priorities for future pandemic readiness, including strengthening healthcare infrastructure, equitable procurement, data transparency, and safeguarding public health decision-making from political and commercial distortion. EXPERT OPINION: We argue that equity-by-design is essential if vaccine innovation is to deliver equitable public health impact. This requires geographically distributed manufacturing, transparency, equity-conditioned advance purchase agreements, and pre-agreed, epidemiology-triggered allocation of vaccines. We recommend institutionalizing disaggregated reporting, standardized data-sharing, greater pathogen genomic sequencing capacity, and communication strategies that support public health protection while countering misinformation.

Humans↗

PubMed1997

New methods of treatment in an experimental murine model of systemic lupus erythematosus induced by idiotypic manipulation.

In this article we have presented our experiences and those of others with various experimental and novel treatments in an experimental model of murine SLE, induced by immunisation with pathogenic anti-DNA antibody (fig 4). Many of the treatments (summarised in the table) were highly effective in ameliorating clinical, serological, and histological manifestations of the disease. According to our results, it seems that hormonal treatments--such as testosterone metabolites, anti-oestrogens, or bromocriptine--as well as immunomodulation with IVIG or anti-CD4 antibodies, hold the most promising potential for application in lupus patients. We believe, therefore, that these types of treatment should receive high priority in human trials. It should be emphasised, however, that the timing of treatment may be critical, since several treatments were effective when used before or during the induction of the disease. This limitation may pose difficulty for human application, since the aetiology of SLE is still obscure and is probably multifactorial38; therefore it is not yet possible to identify patients at risk of developing SLE. Nevertheless, those treatments which proved to be effective might be used early in the course of the disease in lupus patients and hence influence the outcome of the disease, or may even induce partial or complete remission.

Animals↗

PubMed2005

Helicobacter pylori vaccine development: facing the challenge.

An effective vaccine would be a desirable way to control Helicobacter pylori-induced gastric disease. Initial studies in animal models demonstrated the feasibility of immunization and led to high hopes for a human vaccine. In the mouse model immunological approaches have to date not brought a satisfactory explanation for the mechanisms of protection against this largely luminal pathogen. Recently, transcriptome studies have identified new factors. It is now proposed that non-classical immune mediators may be the key to vaccine-induced protection. Human trials of H. pylori vaccines are going ahead but although at least some formulations are clearly immunogenic, their effectiveness remains untested. The recent development of a human challenge model has now opened up new prospects for testing candidate vaccines and this will undoubtedly have a great impact in the near future. Future priorities for H. pylori vaccine development must be a better understanding of the protective mechanisms and the identification of biomarkers which can be used as reliable predictors of efficacy in humans. Despite some important advances in recent years, important issues must be resolved before an H. pylori vaccine will become a reality.

Adjuvants, Immunologic↗

PubMed2006

Harmonization of international risk assessment protocol.

For over centuries developments in food production and new food safety management systems in most developed countries have been perceived by many to be efficient in the prevention of food-borne disease. Nevertheless a number of problems remain dominant, one of these being the high level of food-borne microbiological disease which seems, for some pathogens, to have increased over the last decades. The development of an interdisciplinary approach with direct interaction between surveillance and risk analysis systems is described as a potential basis for improved prevention of food-borne disease. Quantitative microbiological risk assessment is a relatively new scientific approach, able to link data from food within the entire food chain and the various data on human disease to provide a clear estimation of risk. Today food safety is one of the WHOs top eleven priorities; the Organization calls for more systematic and aggressive steps to be taken to reduce significantly the risk of microbiological food-borne diseases. Dealing with this challenge is one of the major challenges for the 21st century in regard to food safety, implying a significant re-direction of food microbiology efforts in many parts of the world.

Animals↗

PubMed2000

Problem pathogens (Pseudomonas aeruginosa and Acinetobacter).

A number of factors have been suspected of or identified as increasing the risk for pneumonia or colonization of the lower respiratory tract by Pseudomonas and/or Acinetobacter spp. in the intensive care unit (ICU), including advanced age, chronic lung disease, immunosuppression, surgery, use of antimicrobial agents, presence of such invasive devices as endotracheal and gastric tubes, and type of respiratory equipment. However, there is little doubt that of all these factors, extended ICU care because of severe underlying disease, prolonged respiratory therapy with mechanical ventilation, and prior antimicrobial therapy are the most important. Because the only factor amenable to prevention in this setting is antimicrobial therapy, avoiding unnecessary antibiotics should be a high priority in the management of such patients. Crude mortality rates of 30% to 75% have been reported for nosocomial pneumonia caused by Pseudomonas and/or Acinetobacter spp., with the highest rates reported in ventilator-dependent patients. It is therefore clear that the prognosis associated with this type of infection is considerably worse than that associated with infection caused by other gram-negative or gram-positive bacteria. Because bactericidal synergy against Pseudomonas and Acinetobacter spp. has been shown when carbenicillin and an aminoglycoside are combined, the use of an effective beta-lactam (piperacillin, ticarcillin, ceftazidime, or imipenem) and aminoglycoside combination remains the preferred therapeutic approach when possible. Future research efforts should also aim to improve our ability to diagnose and exclude infection in the ICU setting to avoid administering unnecessary antibiotics to patients without true pulmonary infection.

Acinetobacter Infections↗

PubMed2025

Whole Genome Sequencing and Genetic Diversity of Respiratory Viruses Detected in Children With Acute Respiratory Infections: A One-Year Cross-Sectional Study in Senegal.

Acute respiratory infections (ARI) are a health priority, especially in countries with limited resources. They are a major cause of morbidity and mortality, especially among children and the elderly. In Senegal, the endemic circulation of respiratory viruses other than influenza has been demonstrated. However, there is a paucity of data exploring the genetic diversity of these viruses based on whole-genome sequencing. In this study, we present data on the genetic diversity of respiratory viruses in children under 15 years old in Senegal, including an overview of the different pathogens detected. Between November 2022 and November 2023, we collected nasopharyngeal swabs from children seen in curative consultations for symptoms of acute respiratory infections. Of the 156 children included, 73.7% tested positive for at least one pathogen. The most frequently detected virus was rhinovirus (50.0%), followed by influenza B (41.6%) and human parainfluenza virus type 3 (7.6%). Combinations of rhinovirus/influenza B, human parainfluenza virus type 2/human parainfluenza virus type 4, and rhinovirus/influenza B/adenovirus were the most frequently identified. A statistically significant association was detected between some of the viruses detected. A high genetic diversity of respiratory viruses circulating in children was revealed. The strains were phylogenetically close to various strains circulating worldwide, suggesting a global circulation of respiratory viruses. Our study provides the first complete genome sequences of human parainfluenza viruses type 2, 3, 4 and human bocavirus from Senegal and thus contributes to the enrichment of international databases on sequences from Senegal and underlines the importance of sequencing in the dynamics of pathogen circulation.

Humans↗

PubMed1991

Acute respiratory infections in Australian Aboriginal children: current knowledge and future requirements.

Although inadequately documented, it is clear that acute respiratory infection (ARI) is a major cause of morbidity and hospitalization in Australian Aboriginal children. ARIs continue to cause substantial mortality in Aboriginal children, and they are likely to cause a variety of potentially serious sequelae. The literature emphasizes the importance of pneumonia as a cause of hospitalization of Aboriginal children. There is good evidence that Streptococcus pneumoniae and Haemophilus influenzae are predominant causes of severe pneumonia, but little is known about the importance of other respiratory pathogens, such as respiratory syncytial virus, as causes of ARI in Aboriginal children. Poor living conditions, low birthweight and malnutrition are likely to be important risk factors for ARI in some groups of Aboriginal children. Although broad-ranging economic and environmental changes will be required to bring about a sustained reduction in ARI in Aboriginal children, there should be an emphasis upon correct case management of ARI at the primary care level so as to reduce the need for hospitalization. Some research priorities are discussed.

Acute Disease↗

PubMed2005

Ganoderma diseases of perennial crops in India--an overview.

The species of Ganoderma recorded from India as causing diseases of perennial crops are listed, and their host range and taxonomy discussed. Four new hosts of G. lucidum are also reported. A decline in productivity and the death of trees are the main economic impacts due to Ganoderma diseases, and the fungus is identified as a serious pathogen of cash crops, forest plantations and trees in natural forests in the country. Ganoderma diseases have been recorded on 144 hosts in India, the major pathogens being G. lucidum and G. applanatum. G. lucidum has been recorded on 91 hosts, and appears to cause the most widespread diseases. Identification has largely been made from morphological and cultural characters, and the names currently in use should therefore be treated with caution. Cultural methods of disease control are largely inefficient in minimising inoculum pressure and in reducing the disease incidence. Chemical methods in combination with soil amendments form short-term solutions for managing the disease and improving productivity. The immediate priorities for developing an efficient management system for Ganoderma diseases in India are: (1) a thorough understanding of the etiology and epidemiology of the diseases on different hosts, (2) clarifying current ambiguity in species names, (3) assessing the inter-relationships between populations of Ganoderma on different hosts and (4) developing tools for early detection of diseases in important crops.

Ganoderma↗

PubMed2006

The promise and the potential consequences of the global transport of mycorrhizal fungal inoculum.

Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species' introductions. Moreover, recent studies of mycorrhizal symbionts have led to an increased knowledge of the potential utility of fungal inoculations in agricultural, horticultural and ecological management. The intentional movement of mycorrhizal fungal species is growing, but the concomitant potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. We assess the degree to which introductions of mycorrhizal fungi may lead to unintended negative, and potentially costly, consequences. Our purpose is to make recommendations regarding appropriate management guidelines and highlight top priority research needs. Given the difficulty in discerning invasive species problems associated with mycorrhizal inoculations, we recommend the following. First, careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Second, invasive species problems are costly and often impossible to control by the time they are recognized. We recommend using local inoculum sources whenever possible. Third, non-sterile cultures of inoculum can result in the movement of saprobes and pathogens as well as mutualists. We recommend using material that has been produced through sterile culture when local inoculum is not available. Finally, life-history characteristics of inoculated fungi may provide general guidelines relative to the likelihood of establishment and spread. We recommend that, when using non-local fungi, managers choose fungal taxa that carry life-history traits that may minimize the likelihood of deleterious invasive species problems. Additional research is needed on the potential of mycorrhizal fungi to spread to non-target areas and cause ecological damage.

Agriculture↗

PubMed2002

Risk of variant Creuzfeldt-Jakob disease from factor concentrates: current perspectives.

The demonstration of iatrogenic transmission of Creuzfeldt-Jakob disease (CJD) through therapeutic interventions led to substantial concerns in communities requiring blood products in the 1980s and 1990s. These concerns led some regulatory authorities to adopt a very precautionary approach and require recall of plasma products, including factor concentrates, which included donors at risk of CJD. The FDA's approach on recall contributed to a substantial lack of plasma products on the world market in the mid- to late 1990s. Growing epidemiological evidence of non-transmission of CJD to humans through blood, as well as demonstration of the plasma fractionation system's ability to eliminate CJD-type agents, led the FDA to rescind its measures for product recall in 1998. Although no evidence exists that the variant strain of CJD (vCJD) will behave any differently to the classic strain (cCJD) of the disease during fractionation, indications that higher levels of the strain may be present in the blood in vCJD, as well as the uncertainty regarding the epidemiology of the disease, has led to a new round of precautionary measures aimed at minimizing vCJD risk. Currently, the traditional approach to product safety through appropriate donor selection, screening using laboratory tests and systematic pathogen elimination is not completely possible for addressing the risk of vCJD. The only definite risk factor for vCJD is residence in a country where meat products from cattle with bovine spongiform encephalopathy (BSE) have been consumed; currently this is predominantly the United Kingdom but the appearance of BSE in other European countries has stimulated non-European regulatory authorities to defer blood donors from most of Europe. There is currently no screening test available for vCJD. Plasma fractionation techniques fortuitously appear to eliminate substantial amounts of vCJD like agents but only one pathogen eliminating technique, nanofiltration, has been proposed for specifically eliminating vCJD-like agents. Despite the current uncertainty, it is possible to be cautiously optimistic regarding the safety of factor concentrates from the risk of vCJD. An accumulating body of evidence suggests that it is unlikely that the plasma pool from countries with moderate BSE epidemics will contain sufficient levels of vCJD agent to lead to an infective final product. Nevertheless, the development of a blood screening test and more dedicated elimination methods are high priorities for the blood industry as it faces this new threat. The community of blood product users, including people with haemophilia, need to be in a position to make an informed choice regarding the risk of this new agent. Such a choice needs to take into account the alternatives to plasma product therapy such as recombinant concentrates and the risks to product supply ensuing from an excessive reliance on one form of product.

Blood Coagulation Factors↗

PubMed2005

[Traumatic brain injury: impact on timing and modality of fracture care].

Traumatic brain injury (TBI) represents the major "killing factor" after trauma in young individuals. Those patients who survive the initial injury are highly susceptible to secondary insults to the injured brain which are mainly caused by hypotension and/or hypoxia in the early resuscitative period. Furthermore, a potent inflammatory cascade is initiated within the injured brain which leads to the development of brain edema and delayed neuronal cell death. This profound endogenous neuroinflammatory response after TBI, which is phylogenetically aimed at repairing lesioned tissue and defending the brain from invading pathogens, is in large part responsible for the extent of secondary brain damage and adverse outcome. Thus, the optimal management of the multiply injured patient, based on a thorough understanding of the pathophysiological alterations after TBI, should avoid an iatrogenic "second hit" which may be devastating to the injured brain. The standard approach of "early total care" for isolated fractures should be strictly avoided in brain-injured patients in favor of an "orthopedic damage control" concept with temporary external fixation of long bone fractures and priority given to early transfer to intensive care. The present review provides an up-to-date overview on the neuroinflammatory pathophysiology of brain injury and its implications for an optimized concept of fracture care in TBI patients.

Adult↗

PubMed2004

Australian contingency plans for emergency animal disease control: the role of antigen/vaccine banks.

Vaccination is an important element of contingency plans for many animal diseases. The decision whether or not to use vaccine is complex, and must consider epidemiological, economic and social issues. Vaccines are rarely available in a country for emergency animal diseases unless a low pathogenicity strain of the agent is present or it is localised in carrier hosts. High quality commercial vaccine from overseas is often the preferred source of vaccine in an emergency, although less reliable sources may be used with additional safeguards. Alternatively, master seeds may be imported or developed for production within the country For contingency planning, diseases may be ranked according to the expected role of vaccine in the disease eradication strategy, with diseases for which vaccine is part of the initial response strategy receiving highest priority for action. A range of preparedness options is available, ranging from identifying producers of vaccine, obtaining permits for import and use from regulatory authorities, to establishing vaccine or antigen banks. Countries need to consider their individual situations and develop strategies to address the diseases of significance to them.

Animals↗