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PubMed2003

Cultural and genetic approaches to managing mycotoxins in maize.

Infection of maize kernels by toxigenic fungi remains a challenging problem despite decades of research progress. Cultural practices, including crop rotation, tillage, planting date, and management of irrigation and fertilization, have limited effects on infection and subsequent mycotoxin accumulation. Current infrastructure and grain storage practices in developed countries can prevent postharvest development of mycotoxins, but this aspect remains a threat in developing countries, especially in tropical areas. Because most mycotoxin problems develop in the field, strategies are needed to prevent infection of growing plants by toxigenic fungi. Developing genetic resistance to Aspergillus flavus, Gibberella zeae, and Fusarium spp. (particularly F. verticillioides) in maize is a high priority. Sources of resistance to each of these pathogens have been identified and have been incorporated into public and private breeding programs. However, few, if any, commercial cultivars have adequate levels of resistance. Efforts to control infection or mycotoxin development through conventional breeding and genetic engineering are reviewed. The role of transgenic insect control in the prevention of mycotoxins in maize is discussed.

Mycotoxins↗

PubMed2000

[The state of vector-borne diseases in Indonesia].

From epidemiological point of view, Indonesia is an extremely interesting area owing its insular structure and ecological, anthropological, cultural and economical diversity. As everywhere, vector-borne diseases are the result of complex and variable epidemiological systems, subject both to biogeographical rules and human activity. Two main arboviroses are present in Indonesia: dengue and Japanese encephalitis. Dengue appears as an endemoepidemic disease and is mostly circumscribed to urban areas. Haemorrhagic cases were first observed in 1968; since then, the incidence has been constantly increasing and the disease is now one of the principal causes of child lethality. Japanese encephalitis is a rural endemic disease transmitted by rice-field mosquitoes; its incidence remains relatively low since pigs, which are usual link-hosts for the virus, are uncommon in this mainly Muslem country. Human clinical cases are recorded from non-Muslem islands such as Bali or Irian Jaya which raises the question of immunisation for travellers. Recently, Japanese encephalitis was observed on east of the Wallace line which had been considered as the eastern cut-off line. Malaria is common throughout the country, Plasmodium vivax being the most frequent species. Some of the Anopheline vectors are related to brackish water as are coastal species; others have been favoured by rice growing. Several species bite and rest outdoors, rendering control measures complex. Moreover, chloroquine resistance is increasing in both P. falciparum and P. vivax. All three filaria species responsible for human lymphatic filariasis exist in Indonesia. Bancroft filariasis is present in rather limited foci on most of the islands; malayan filariasis is very prevalent on many islands, mostly in coastal areas, and Timor filariasis exist only on a few small islands. These parasitic diseases are cumulative and do not practically endanger the health of travellers. In the past, plague was common on Java island, but today, human cases are very rare. Scrub typhus is prevalent everywhere, as is murine typhus, being very frequent in harbour cities and one of the main causes of hospitalisation for febrile syndromes.. On the whole, the situation of several of these diseases has been worsening in Indonesia for about thirty years. Although epidemiological situations constantly evolve, two recent occurrences should be paid particular attention: -transmigration which is now a national priority and greatly facilitates the spread of many pathogens, arboviroses or chloroquine-resistant plasmodia, but also of rats, mosquitoes, etc. -deforestation due either to land-farming by Javanese transmigrants or to sudden climatic changes such as El Niño in 1997. Such deep ecological transformations may have considerable and unforeseeable consequences on the epidemiology of vector-borne diseases in Indonesia.

Animals↗

PubMedDate not supplied

Patterns and outcome of acute bacterial meningitis in a South Indian tertiary level hospital.

A retrospective analysis of childhood Acute Bacterial Meningitis from a tertiary care hospital in Bangalore revealed a winter clustering of cases and an absence of typical signs and symptoms in 40% of patients, with Staphylococcus aureus (10%) and coagulase negative Staphylococcus (9%) being the most common etiological agents. Mortality rate was 8.5%. High priority for the prevention of disease by these pathogens, especially in rural population and during winter, and a high degree of alertness for the detection of atypical disease is warranted.

Acute Disease↗

PubMed1990

[Group B streptococci in neonatal pathology: pathogenetic mechanism, diagnosis and prevention].

Group B streptococci have recently attracted the attention of researchers as the causative agents of human neonatal disease. They are currently encountered much more frequently than it was believed previously. Various types of adult pathogen carriers have been described; this accounts for the numerous sources and pathways of infection transmission, both vertical and horizontal. The transmission risk depends on many factors, vaginal colonization in the parturient being of special import. The level of the pathogen adhesion to the barrier epithelium is reflective of the tissue sensitivity to infection. Increased sensitivity of the vaginal epithelium to B streptococci adhesion in association with the intake of some contraceptives has been found. The adhesive activity of avirulent streptococci B strains is shown to be higher than in the virulent strains, which is especially important in mixed virus bacterial infections. The streptococcal infection of high mortality is underlain by activation of persisting avirulent streptococci B that manifest their pathogenicity as a result of the virus-specific modifications in the host cell membrane. During 1985-1987, in Leningrad Institute of Gynecology and Obstetrics over 80 strains of streptococci B were isolated, the leading serotypes being Ia/C, Ib/C, II/C, III/R. Only 54% of the studied pregnancies attended with the streptococcus carriage had a favourable neonatal outcome. The strain serotypes from maternal isolates and abortuses fully correlated. Further improvement of the laboratory diagnosis and means of the pathogen and its carriers identification is a current priority.

Bacterial Adhesion↗

PubMed2004

Computational analysis of tyrosine phosphatase inhibitor selectivity for the virulence factors YopH and SptP.

Bacterial pathogens such as Yersinia and Salmonella represent an important medical concern, causing human diseases ranging from gastrointestinal disease to the plague. The development of novel treatments of these bacterial infections has gained high priority recently due to the emergence of antibiotic resistance in these pathogens and the threat of the use of microbial agents as biological weapons. YopH of Yersinia and SptP of Salmonella are virulence factors that belong to the family of protein tyrosine phosphatases (PTPs). A great challenge remains in the design of selective PTPs inhibitors due to their highly conserved active site. In this paper, we present a comparative docking study to probe the selective inhibition of YopH and SptP with PTP1B in order to better understand their binding interactions with the bacterial tyrosine phosphates. Characterized binding sites in PTP1B were compared with YopH and SptP. Molecular dynamics simulations were used to incorporate ligand-induced conformational changes in the binding sites. These results, together with those binding modes and binding affinities distinguished in individual PTPs, provide insight into the structure-based design of inhibitors for YopH and SptP.

Bacterial Outer Membrane Proteins↗

PubMed2006

[X chromosome inactivation patterns in patients with Rett syndrome and their mothers and the parental origin of the priority inactive X chromosome].

OBJECTIVE: Rett syndrome (RTT) is a severe childhood neurodevelopmental disorder mainly affecting females. The pathogenic gene is located at Xq28, which codes for the methyl-CpG-binding protein 2. MECP2 gene is affected by X chromosome inactivation (XCI). The different XCI patterns of females could affect the expression ratios of pathogenic gene, causing changes in clinical symptoms. In order to understand the XCI patterns in RTT patients and the relationship between XCI pattern, genotype and phenotype, the XCI patterns in patients with RTT and their mothers, the parental origin of the priority inactive X chromosome in RTT, and the relations of XCI patterns with genotype and phenotype in RTT cases were analyzed. METHODS: Genomic DNA was extracted from peripheral blood of 55 cases with RTT (52 with MECP2 mutations, 3 without mutations), 53 mothers of RTT cases and 48 normal female controls. DNA was digested with methylation sensitive restriction endonuclease Hpa II. Then the undigested and digested DNAs were amplified via PCR for the first exon of human androgen receptor (AR) gene. PCR products were analyzed by Genescan. RESULTS: The heterozygotic rates of AR gene were 82%, 77% and 83% in RTT patients, mothers and controls, respectively. XCI distribution pattern of RTT was different from that of the mothers and control, P < 0.05. More mothers and controls than RTT patients were in the area of XCI 50:50 - 59:41. The differences between them were statistically significant (P < 0.05). No significant difference in XCI distribution patterns between mothers and the control groups was found (P > 0.05). Non-random XCI rates in the areas of XCI >or= 65:35 and >or= 80:20 were 53.35% and 17.8%, respectively, in RTT patients, compared with the mothers group (36.6%, 7.3%) and control group (35%, 10%), it was higher in RTT patients, but the difference was not statistically significant (P > 0.05). In 18 of 21 cases with XCI >or= 65:35, the priority inactive X chromosome was of paternal origin (85.7%). Variable XCI patterns were observed in the same gene mutation patients. The highly skewed XCI as well as the random XCI were found in patients with mild, severe and typical phenotype. The rate of highly skewed XCI in atypical patients was higher than that in typical RTT patients. The rate of highly skewed XCI in T158M was higher than the other type mutations. No highly skewed XCI was observed in cases with R133C mutation. CONCLUSION: The XCI distribution pattern of RTT patients was different from that of RTT mother and control groups. There was no significant difference in XCI distribution patterns between mothers and the control groups. It was not a main genetic pattern in RTT that mothers as the carriers to transmit the pathogenic gene to the patients. Non-random XCI was not the main XCI pattern in RTT patients. The priority inactive X chromosome was mainly of paternal origin. XCI could modify the clinical phenotype of RTT, but had limitations in explaining all the phenotypes manifested in RTT cases.

Adolescent↗

PubMed2006

Assessment of pathogens and toxicants in New Orleans, LA following Hurricane Katrina.

Storm surge associated with Hurricane Katrina and the breach of levees protecting New Orleans, Louisiana allowed floodwaters from Lake Pontchartrain to inundate 80% of the city. Environmental samples were collected during September 16-18, 2005 to determine immediate human and wildlife health hazards from pathogens and toxicants in the floodwaters. Baseline information on potential long-term environmental damage resulting from contaminants in water and sediments pumped into Lake Pontchartrain was also collected. Concentrations of aldrin, arsenic, lead, and seven semivolatile organic compounds in sediments/soils exceeded one or more United States Environmental Protection Agency (USEPA) thresholds for human health soil screening levels and high priority bright line screening levels. High numbers of Aeromonas spp., pathogenic Vibrio spp., and other coliform bacteria were found in floodwater samples. Alligator and snake tissues did not contain excessive toxicant concentrations. Initial findings suggest numerous environmental contaminants are present in New Orleans and support the need for further evaluation of the extent of those threats.

Animals↗

PubMed2003

The methylerythritol phosphate pathway and its significance as a novel drug target.

Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) are the precursors for all isoprenoid compounds. Two pathways are found in Nature for their biosynthesis. The mevalonate (MVA) pathway is found in eukaryotes, algae, archae and some gram-positive bacteria. Gram-negative bacteria, plants and some gram-positive bacteria utilize the methyl erythritol phosphate (MEP) pathway. The distribution and the orthogonal nature of the pathways make the MEP pathway an attractive new target for antibiotics and herbicides. The MEP pathway is essential for bacterial viability. Inhibitors to the MEP pathway represent a "dual-use technology" because potential targets include potential biological warfare agents in addition to common human pathogens. The CDC has three categories designated for Biological Diseases/Agents. Three of the six entities designated as the highest priority (Category A) are organisms that utilize, or appear to utilize, the MEP pathway. Among the 12 second highest priority agents (Category B) listed, 8 are organisms that appear to utilize the MEP pathway. Common human pathogens that can be targeted include the organisms responsible for peptic ulcers, tuberculosis, malaria, food safety threats, and sexually transmitted diseases. There is so far only one inhibitor reported that specifically blocks the MEP pathway and is being investigated clinically. This compound, fosmidomycin, has been shown to be somewhat effective in treating Plasmodium falciparum, the parasite responsible for malaria. We foresee that new MEP pathway inhibitors will open up an entirely new class of antibiotics. An MEP pathway intermediate has also been shown to be the most potent gammadelta T cell activator.

Animals↗

PubMed1987

Setting priorities: nationwide nosocomial infection prevention and control programs in the USA.

Approximately two million nosocomial infections occur annually in patients admitted to acute-care hospitals in the USA. Factors that should be considered in setting national priorities for nosocomial infection prevention and control efforts include incidence, mortality, prolongation of stay, cost of treatment, and potential for prevention of infections at different sites. National nosocomial infection priorities in the USA cover infections caused by emerging pathogens, infections at selected sites including the bloodstream, infections in intensive-care units, infections resulting from contaminated devices and products, development of the capability to analyze surveillance data in a timely fashion, dissemination of information on effective prevention strategies to infection control personnel, and training of infection control personnel, including physicians. The mechanism used to disseminate information on effective prevention strategies is the series of CDC 'Guidelines for the Prevention and Control of Nosocomial Infections'. These guidelines address prevention of nosocomial infections at the four major sites, handwashing and environmental control issues, infection control in personnel health, and isolation precautions.

Cross Infection↗

PubMed2006

Pathogen inactivation and removal procedures used in the production of intravenous immunoglobulins.

Patients with immunodeficiencies or some types of autoimmune diseases rely on a safe therapy with intravenous immunoglobulins (IVIGs) manufactured from human plasma, the only available source for this therapeutic. Since plasma is predisposed to contamination by a variety of blood-borne pathogens, ascertaining and ensuring the pathogen safety of plasma-derived therapeutics is a priority among manufacturers. 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 virusfiltration.

Autoimmune Diseases↗

PubMed2003

Acute bacterial rhinosinusitis in pediatric medicine: current issues in diagnosis and management.

In children, acute bacterial rhinosinusitis is a common infection and although rare, carries a potential for serious, life threatening complications. Bacterial rhinosinusitis usually follows a viral infection or allergic rhinitis. Early, effective antibacterial therapy is essential to shorten the duration of infection and illness, to diminish mucosal damage, and to prevent contiguous infectious involvement of the orbit or central nervous system. Because the signs and symptoms of acute bacterial rhinosinusitis are similar to those of viral upper respiratory tract infection, establishing an accurate diagnosis in children poses a clinical challenge. Infection with Streptococcus pneumoniae accounts for 30-66% of episodes of acute bacterial rhinosinusitis in children. Other important pathogens include Haemophilus influenzae (20-30%) and Moraxella catarrhalis (12-28%). In selecting initial antimicrobial therapy, priority should be given to drugs with activity against S. pneumoniae. The oral agents that currently offer the greatest activity against this pathogen include amoxicillin, amoxicillin-clavulanate, cefdinir, cefpodoxime proxetil, and cefuroxime axetil; all are considered appropriate for the initial treatment of acute bacterial rhinosinusitis in children. Amoxicillin is customarily used as first-line therapy for uncomplicated acute bacterial rhinosinusitis. For patients who are allergic to amoxicillin, second- or third-generation oral cephalosporins may be used as first-line therapy. Clarithromycin has been suggested as an alternative to amoxicillin or cephalosporins in beta-lactam allergic patients. Clindamycin may also be indicated as first-line treatment in patients who have culture-proven penicillin-resistant S. pneumoniae. If no clinical response occurs within 72 hours, the choice of a second-line antibiotic is governed by the drug's known antimicrobial efficacy, resistance patterns, dosing schedules, the potential for compliance, and knowledge of the patient's drug allergies. High-dose amoxicillin-clavulanate (90 mg/kg/d of the amoxicillin component) has been recommended for high-risk children (e.g. those in day care, and those who have recently received antibiotics) who show no improvement after treatment with the usual dose of amoxicillin (45 mg/kg/d). Broad-spectrum, third-generation oral cephalosporins, such as cefdinir, should be considered as second-line agents when standard therapy has failed or when patients show hypersensitivity to penicillin. Intramuscular ceftriaxone may be appropriate for patients who fail on a second course of antibiotic treatment.

Acute Disease↗

PubMed1998

Clinical implications of nosocomial gram-positive bacteremia and superimposed antimicrobial resistance.

The coexistence of a pathogen population with an ever-increasing resistance to many antibiotics and a patient population characterized by increasingly complex clinical problems has contributed to an increase in the bloodstream infections associated with gram-positive bacteria. This serious therapeutic challenge has already been associated with an increase in infection-related morbidity and mortality, a prolongation of hospital stays, and an escalation of healthcare costs. Vancomycin resistance, long prevalent among the enterococci, has emerged in strains of Staphylococcus aureus. Several cases of infection caused by S. aureus strains with intermediate-level resistance to vancomycin (MIC=8 microg/mL) have recently been reported. As glycopeptide resistance accelerates among the gram-positive bacteria, so does the potential for adverse clinical consequences associated with bloodstream infections caused by these pathogens. The patients least able to tolerate the effects of uncontrolled bloodstream infections are also those at the highest risk for the development of infections caused by glycopeptide-resistant pathogens. In this at-risk population, a poor outcome may be anticipated if effective antibiotic therapy is unavailable. Appropriate rationing of vancomycin and other antimicrobial agents that increase the selection of antibiotic-resistant strains of gram-positive bacteria and the rapid development of novel antimicrobial agents with reliable gram-positive activity must be immediate priorities if the threat posed by glycopeptide-resistant gram-positive pathogens is to be countered.

Anti-Bacterial Agents↗

PubMed2003

Coronary atherosclerosis and somatic mutations: an overview of the contributive factors for oxidative DNA damage.

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. Genetic research on CAD has traditionally focused on investigation aimed at identifying disease-susceptibility genes. Recent evidence suggests that somatically acquired DNA mutations may also contribute significantly to the pathogenesis of the disease, underlining the similarity between atherosclerotic and carcinogenic processes. The generation of oxidative stress has been emphasized as an important cause of DNA damage in atherosclerosis. This review highlights some of the major atherogenic risk factors as likely mediators in the oxidative modification of DNA. It also examines the hypothesis that an increase in oxidative stress may derive from "oxidatively" damaged mitochondria. Accordingly, further research in this field should be given high priority, since increased somatic DNA damage could be an important pathogenic factor and an additional prognostic predictor, as well as a potential target for therapeutic strategies in coronary artery disease.

Aging↗

PubMed2006

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control.

Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.

Animals↗

PubMed2002

Foods as production and delivery vehicles for human vaccines.

Vaccination is a great asset for eradication of infectious diseases in humans and animals. With the prevalence of antibiotic resistant bacterial strains and an alarming increase in new and re-emerging pathogens, the need for vaccination continues to be a high priority for mammalian diseases. In the last several years, a novel approach for developing improved mucosal subunit vaccines has emerged by exploiting the use of genetically modified plants. It has been demonstrated that plant-derived antigens are functionally similar to conventional vaccines and can induce neutralizing antibodies in mammalian hosts. Using genetically engineered plants for the production of immunogenic peptides also provides a new approach for the delivery of a plant-based subunit vaccine, i.e., oral delivery, provided these immunogenic peptides are expressed in an edible part of the plant, such as grain or fruit. Thus, food crops can play a significant new role in promoting human health by serving as vehicles for both production and delivery of vaccines.

Communicable Disease Control↗

PubMed2000

The selenium-coxsackievirus connection: chronicle of a collaboration.

This review provides a historical account of a collaboration established between a nutritionist and a virologist to investigate the interrelationship of host nutritional status and viral virulence. The parties to this collaboration consider themselves specialists in the fields of antioxidant nutrition and viral immunology, respectively. The advantages of such talent pooling are discussed (rapid startup, well-focused experimentation, ability to visualize the "big picture"), as are some of the disadvantages (limited common scientific vocabulary, proper apportioning of credit, lack of institutional infrastructure to house such efforts). The common perception that some of the most exciting science occurs when the advancing edges of two disparate disciplines intersect is borne out by this project because host nutriture was shown for the first time to influence the genetic make-up of an invading viral pathogen. Encouragement of joint cooperative ventures should have a high priority as demanded by increasingly difficult scientific problems and as desired by scientists themselves who wish to see their research progress more quickly.

Animals↗

PubMed1991

[ENT antibiotic therapy: therapeutic guidelines. Part I].

We discuss the variety of ear, nose and throat infections and then define the criteria for the choice of an adequate antibiotic. The importance of "supercalculated" therapy based on the results of Gram's stain is stressed, as it can save patients from over-treatment and adverse side-effects. Indications for Gram's stain in ENT as well as the value of the characteristics of the pus produced by different pathogens are described. The severity of the infection determines the choice between parenteral or oral therapy. The importance of the decision taken on the 1st and 3rd day of a severe infection is emphasised. Therapeutic principles in ENT infections are shown by grouping different infections with a similar spectrum of pathogens; also the indications for antibiotic therapy are outlined. Finally the priority of antibiotic treatment in some surgical infections is mentioned, and the peri-operative prophylaxis and treatment are described as well as the guidelines for treatment of infectious post-operative complications.

Anti-Bacterial Agents↗

PubMed2005

The Microbial Rosetta Stone database: A common structure for microbial biosecurity threat agents.

Infectious microorganisms are important to multiple communities engaged in biodefense and biosecurity, including the agencies responsible for health, defense, law enforcement, agriculture, and drug and food safety. Many agencies have created lists of high priority infectious microorganisms to prioritize research efforts or to formally control the possession and distribution of specific organisms or toxins. However, the biological classification of infectious microorganisms is often complex and ambiguous, leading to uncertainty and confusion for scientists involved in biosecurity work. To address this problem, we created a database, known as the Microbial Rosetta Stone, which resolves many of these ambiguities and includes links to additional information on the microbes, such as gene sequence data and scientific literature. Here we discuss the efforts to coordinate organism names from pathogen lists from various governmental agencies according to biological relatedness and show the overlap of high-priority organisms from multiple agencies. To our knowledge, this is the first comprehensive coordination of pathogens, synonyms, and correct taxonomic names. The organized tables and visual aids are freely available at http://www.microbialrosettastone.com. This website provides a single location where access to information on a broad range of disease-causing organisms and toxins is available to members of the biosecurity community.

Access to Information↗