bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe chronic active Epstein-Barr virus infection syndrome
Authors: Okano M , Matsumoto S , Osato T , Sakiyama Y , Thiele G M , Purtilo D T
Published: June 2016

Reports of unusually severe lymphoproliferative disorders associated with extremely high antibody titers against Epstein-Barr virus (EBV) have recently increased. The syndrome, which we designated severe chronic active EBV infection syndrome, is characterized by persistent or intermittent fever, lymphadenopathy, and hepatosplenomegaly and primarily affects children and young adults. Polyclonal gammopathy and bone marrow suppression are generally observed, and some patients develop B-cell or T-cell lymphoproliferation or lymphoma. Frequently, EBV genomes are detectable in tissues infiltrated with lymphoid cells. Additionally, it is difficult to establish spontaneous or B95-8 EBV-induced cell lines despite the expression of an activated EBV infection. We review and report here the published medical literature and our own experience regarding patients with severe chronic active EBV infection syndrome in an attempt to understand this enigmatic syndrome and the possible pathogenetic mechanism(s) responsible for this disorder.
Microbiology of airway disease in patients with cystic fibrosis
Authors: Gilligan P H
Published: June 2016

Individuals with cystic fibrosis have abbreviated life spans primarily due to chronic airway infection. A limited number of types of organisms are responsible for these infections, with Staphylococcus aureus and Pseudomonas aeruginosa being of primary importance. In the pre-antibiotic era, greater than 90% of deaths due to infection were caused by S. aureus and death usually occurred in the first 2 years of life. With the advent of effective antistaphylococcal therapy, life spans increased and P. aeruginosa became the pathogen of primary importance. P. aeruginosa isolates recovered from patients with cystic fibrosis have a unique phenotypic characteristic referred to as "mucoid." The mucoid phenotype is due to the production of a mucoid exopolysaccharide. A mucoid exopolysaccharide is believed to play a central role in the establishment of chronic pseudomonal lung infection in these patients. A third organism, Pseudomonas cepacia, has recently been detected in the airways of older patients with cystic fibrosis and is associated with increased mortality. The virulence of P. cepacia is not understood, but the organism is extremely refractory to antimicrobial therapy. Other bacteria, including Haemophilus influenzae and members of the family Enterobacteriaceae, appear to play a secondary role in airway infection. Aspergillus fumigatus is the most important fungal agent causing allergic bronchopulmonary disease. The role of viruses has only recently been examined. At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections.
Melioidosis: the tip of the iceberg?
Authors: Dance D A
Published: June 2016

For nearly 80 years clinical melioidosis has been considered a rare disease. This bacterial infection is caused by Pseudomonas pseudomallei, a saprophyte found in soil and surface water of endemic areas. Consequently, those who have most contact with soil, the rural poor, are likely to be at greatest risk of infection. Since the diversity of clinical manifestations necessitates the isolation and identification of the causative organism for a definitive diagnosis of melioidosis and the population at greatest risk within endemic areas rarely have access to an appropriate level of health care, the disease has probably been underrecognized. Melioidosis is now known to be an important cause of human morbidity and mortality in Thailand, and this may be true throughout Southeast Asia, which is usually regarded as the main endemic area for the disease. In Australia, melioidosis causes a smaller number of human infections, while disease among livestock has important economic and possible public health implications. Sporadic reports of the infection indicate its presence in several other tropical regions: in the Indian subcontinent, Africa, and Central and South America. Clinical melioidosis may be highly prevalent in these areas, but underdiagnosed as a result of a lack of awareness of the clinical and microbiological features of the disease, or simply because of a lack of health care facilities. Furthermore, during the last two decades the importation and transmission of melioidosis within nontropical zones have been documented. The causative organism is not difficult to grow, and modern antibiotics have improved disease prognosis. Further studies are needed to determine the true worldwide distribution and prevalence of melioidosis so that improved therapeutic and preventive measures can be developed and applied.
Pneumocystis carinii, an opportunist in immunocompromised patients
Authors: Bartlett M S , Smith J W
Published: June 2016

Pneumocystis carinii has been recognized as a cause of pneumonia in immunocompromised patients for over 40 years. Until the 1980s, Pneumocystis pneumonia (pneumocystosis) was most often seen in patients undergoing chemotherapy for malignancy or transplantation. Infection could be prevented by trimethoprim-sulfamethoxazole prophylaxis; thus, it was an uncommon clinical problem. With the onset of the AIDS epidemic, Pneumocystis pneumonia has become a major problem in the United States because it develops in approximately 80% of patients with AIDS and because almost two-thirds of patients have adverse reactions to anti-Pneumocystis drugs. Thus, physicians and laboratories in any community may be called upon to diagnose and provide care for patients with Pneumocystis pneumonia. The classification of the organism is currently controversial, but it is either a protozoan or a fungus. P. carinii appears to be acquired during childhood by inhalation and does not cause clinical disease in healthy persons but remains latent. If the person becomes immunosuppressed, the latent infection may become activated and lead to clinical disease. Damage of type I pneumocytes by Pneumocystis organisms leads to the foamy alveolar exudate which is characteristic of the disease. Diagnosis is established by morphologic demonstration of Pneumocystis organisms in material from the lungs. Current efforts to find better anti-Pneumocystis drugs should provide more effective therapy and prophylaxis.
Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients
Authors: May T B , Shinabarger D , Maharaj R , Kato J , Chu L , DeVault J D , Roychoudhury S , Zielinski N A , Berry A , Rothmel R K
Published: June 2016

Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide.
Human infections associated with Bordetella bronchiseptica
Authors: Woolfrey B F , Moody J A
Published: June 2016

This study examines the potential of Bordetella bronchiseptica to act as a human pathogen. After encountering two patients from whom B. bronchiseptica was isolated, we searched the literature and found 23 reports in which a human infection was reported in association with B. bronchiseptica. As a basis for evaluating these cases, we summarize the literature about the current microbiological status of B. bronchiseptica, the pathology and pathogenic mechanisms associated with the microorganism, and the likelihood of it acting as a commensal or colonizer. From this review we conclude that B. bronchiseptica has been rarely isolated from humans despite their considerable exposure to animal sources. Evidence suggests that B. bronchiseptica may be rarely encountered as a commensal or colonizer of the respiratory tract of humans and rarely in association with infection. When found as a probable pathogen, most infections have been respiratory tract in origin and have occurred in severely compromised hosts.
Diversity and origin of rheumatologic autoantibodies
Authors: Fritzler M J , Salazar M
Published: June 2016

A hallmark of sera from patients with systemic rheumatic diseases is the presence of circulating autoantibodies directed against nuclear antigens. The identification of the antigens binding to these antibodies has provided the cell biologist and the immunologist with important tools to study cell structure, cell function, and the processes underlying the immune response. Through the elucidation of autoantibody specificities, the clinician has been provided with a better appreciation of the diagnostic and prognostic significance of autoantibodies. Many autoantigens, including those directed against components in the nuclear matrix, chromosomes, Golgi apparatus, and other intracellular antigens, are not yet characterized nor is their clinical significance established. The mechanisms leading to the breakdown of tolerance and the appearance of autoantibodies are not fully understood. Molecular mimicry at an interspecies or an intracellular level may be involved in altering immune tolerance. On the other hand, studies of epitopes on human autoantigens has provided compelling evidence that most autoantibody responses seen in systemic rheumatic diseases are driven by endogenous antigen.
Susceptibility testing of anaerobic bacteria: myth, magic, or method?
Authors: Wexler H M
Published: June 2016

The demand for susceptibility testing of anaerobes has increased, yet consensus as to procedure and interpretation in this area has not been achieved. While routine testing of anaerobic isolates is not needed, certain isolates in specific clinical settings should be tested. Also, laboratories may monitor their local antibiograms by doing periodic surveillance batch testing. The National Committee for Clinical Laboratory Standards has published a protocol of methods approved for susceptibility testing of anaerobic bacteria. Both agar and broth microdilution are included; however, the broth disk elution method is no longer approved by the National Committee for Clinical Laboratory Standards because of method-related interpretive errors. A number of newer methods are undergoing evaluation and seem promising. Clinicians and microbiologists reviewing susceptibility reports should be aware of sources of variability in the test results. Variables in susceptibility testing of anaerobes include the media and methods used, organisms chosen for testing, breakpoints chosen for interpretation, antibiotic, and determination of endpoint. Clustering of MICs around the breakpoint may lead to significant variability in test results. Adherence of testing laboratories to approved methods and careful descriptions of the method and the breakpoints used for interpretation would facilitate interlaboratory comparisons and allow problems of emerging resistance to be noted. A variety of resistance mechanisms occurs in anaerobic bacteria, including the production of beta-lactamase and other drug-inactivating enzymes, alteration of target proteins, and inability of the drug to penetrate the bacterial wall. Antimicrobial resistance patterns in the United States and abroad are described.
Agents of newly recognized or infrequently encountered mycobacterial diseases
Authors: Wayne L G , Sramek H A
Published: June 2016

This paper reviews recent information on the systematics and clinical significance of potentially pathogenic environmental mycobacteria. A short history of these mycobacteria is given. Information on species for which clinical and systematic aspects have already been well documented, i.e., Mycobacterium kansasii, M. marinum, M. scrofulaceum, M. simiae, M. szulgai, M. ulcerans, M. xenopi, and members of the M. fortuitum complex, is updated. Although the M. avium complex was extensively reviewed in earlier literature, major new systematic and clinical information is presented in some detail. Species that have received very limited prior coverage, i.e., M. asiaticum, M. haemophilum, M. malmoense, and M. shimoidei, are the main subjects of this review and are discussed in detail. The rare infections attributed to species that are normally considered nonpathogenic, i.e., M. gastri, M. gordonae, the M. terrae complex, and most of the rapidly growing mycobacteria outside of the M. fortuitum complex, are critically reviewed. Finally, suggestions are offered for practical measures that can minimize the risk of failing to isolate or misidentifying some of the more obscure potentially pathogenic environmental mycobacteria that are only infrequently recognized.
Microbiological aspects of peritonitis associated with continuous ambulatory peritoneal dialysis
Authors: von Graevenitz A , Amsterdam D
Published: June 2016

The process of continuous ambulatory peritoneal dialysis has provided a useful, relatively inexpensive, and safe alternative for patients with end-stage renal disease. Infectious peritonitis, however, has limited a more widespread acceptance of this technique. The definition of peritonitis in this patient population is not universally accepted and does not always include the laboratory support of a positive culture (or Gram stain). In part, the omission of clinical microbiological findings stems from the lack of sensitivity of earlier microbiological efforts. Peritonitis results from decreased host phagocytic efficiency with depressed phagocytosis and bactericidal capacity of peritoneal macrophages. During episodes of peritonitis, fluid movement is reversed, away from the lymphatics and peritoneal membrane and toward the cavity. As a result, bloodstream infections are rare. Most peritonitis episodes are caused by bacteria. Coagulase-negative staphylococci are the most frequently isolated organisms, usually originating from the skin flora, but a wide array of microbial species have been documented as agents of peritonitis. Clinical microbiology laboratories need to be cognizant of the diverse agents so that appropriate primary media can be used. The quantity of dialysate fluid that is prepared for culture is critical and should constitute at least 10 ml. The sensitivity of the cultural approach depends on the volume of dialysate, its pretreatment (lysis or centrifugation), the media used, and the mode of incubation. The low concentration of microorganisms in dialysate fluids accounts for negative Gram stain results. Prevention of infection in continuous ambulatory peritoneal dialysis patients is associated with the socioeconomic status of the patient, advances in equipment (catheter) technology, and, probably least important, the application of prophylactic antimicrobial agents.
New aspects of influenza viruses
Authors: Shaw M W , Arden N H , Maassab H F
Published: June 2016

Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands.
Laboratory diagnosis of bacterial meningitis
Authors: Gray L D , Fedorko D P
Published: June 2016

Bacterial meningitis is relatively common, can progress rapidly, and can result in death or permanent debilitation. This infection justifiably elicits strong emotional reactions and, hopefully, immediate medical intervention. This review is a brief presentation of the pathogenesis of bacterial meningitis and a review of current knowledge, literature, and recommendations on the subject of laboratory diagnosis of bacterial meningitis. Those who work in clinical microbiology laboratories should be familiar with the tests used in detecting bacteria and bacterial antigens in cerebrospinal fluid (CSF) and should always have the utmost appreciation for the fact that results of such tests must always be reported immediately. Academic and practical aspects of the laboratory diagnosis of bacterial meningitis presented in this review include the following: anatomy of the meninges; pathogenesis; changes in the composition of CSF; etiological agents; processing CSF; microscopic examination of CSF; culturing CSF; methods of detecting bacterial antigens and bacterial components in CSF (counter-immunoelectrophoresis, coagglutination, latex agglutination, enzyme-linked immunosorbent assay, Limulus amebocyte lysate assay, and gas-liquid chromatography); use of the polymerase chain reaction; and practical considerations for testing CSF for bacterial antigens.
High-frequency switching in Candida albicans
Authors: Soll D R
Published: June 2016

Most strains of Candida albicans are capable of switching frequently and reversibly between a number of phenotypes distinguishable by colony morphology. A number of different switching systems have been defined according to the limited set of phenotypes in each switching repertoire, and each strain appears to possess a single system. Switching can affect many aspects of cellular physiology and morphology and appears to be a second level of phenotypic variability superimposed upon the bud-hypha transition. The most dramatic switching system so far identified is the "white-opaque transition." This system dramatizes the extraordinary effects switching can have on the budding cell phenotype, including the synthesis of opaque-specific antigens, the expression of white-specific and opaque-specific genes, and the genesis of unique cell wall structures. Switching has been demonstrated to occur at sites of infection and between episodes of recurrent vaginitis, and it may function to generate variability in commensal and infecting populations for adaptive reasons. Although the molecular mechanisms involved in the switch event are not understood, recent approaches to its elucidation are discussed and an epigenetic mechanism is proposed.
Nonpulmonary manifestations of cytomegalovirus infection in immunocompromised patients
Authors: Drew W L
Published: June 2016

Nonpulmonary manifestations of cytomegalovirus (CMV) infection in immunocompromised patients include chorioretinitis, gastrointestinal infection, and central nervous system disease. Diagnosis of end organ disease, especially in the gastrointestinal tract, is best substantiated by histologic evidence of CMV inclusions. Positive cultures of CMV provide evidence for supporting infection but do not define actual end organ disease. Satisfactory treatment of the disease can be accomplished with ganciclovir or foscarnet, although these agents only suppress virus replication. In many instances, severe CMV-induced end organ disease in immunocompromised patients will progress despite treatment. In some instances, resistance to the antiviral agent is the basis for drug failure. Patients at high risk for CMV disease can be identified, and studies of prophylaxis are in progress.
Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens
Authors: Cárdenas L , Clements J D
Published: June 2016

A variety of techniques, including the use of live oral vaccines, have been used to deliver antigens to the gut-associated lymphoid tissues in an attempt to initiate production of specific secretory immunoglobulin A for protection against pathogens that colonize or cross mucosal surfaces to initiate infection. A number of attenuated Salmonella mutants are able to interact with the lymphoid tissues in the Peyer's patches but are not able to cause systemic disease. Some of these mutants are effective as live vaccines (i.e., able to protect against infection with the virulent Salmonella parent) and are candidates for use as carriers for virulence determinants of other mucosal pathogens. This has been shown to be an effective means of stimulating significant levels of specific mucosal secretory immunoglobulin A directed against the carrier strains and against a variety of heterologous antigens and has been shown to stimulate production of serum antibodies and cell-mediated responses as well. This review examines the history of this mechanism of vaccine delivery and summarizes the most recent applications of this evolving technology. This is a technique for vaccine delivery with significant potential for influencing the management of infectious diseases on a large scale. It can be used not only for vaccines against enteric bacterial pathogens but also for vaccines against a variety of other bacteria, viruses, and parasites. The results obtained to date are encouraging, and there is great potential for development of safe, effective, affordable vaccines.
Amebiasis
Authors: Bruckner D A
Published: June 2016

Entamoeba histolytica, the causative agent of amebiasis, was first described in 1875. Although a large number of people throughout the world are infected with this organism, only a small percentage will develop clinical symptoms. Morbidity and mortality due to E. histolytica vary from area to area and person to person. Recent findings have suggested that there are pathogenic and nonpathogenic strains of E. histolytica that can be differentiated by isoenzyme (zymodeme) analysis, monoclonal antibodies, and DNA probes. Whether pathogenicity is a genotypic trait or can be changed by environmental influences has not been resolved. Exchange of genetic material between strains of amebae can influence zymodeme patterns. Currently, detection of E. histolytica infections depends on examinations for ova and parasites and on serologic tests; however, the development of monoclonal antibodies and DNA probes specific for pathogenic zymodemes may be beneficial for clinical laboratory testing and therapeutic decisions when approved tests become available. A better understanding of the mechanisms of pathogenicity at the molecular level is evolving and should promote the development of vaccines and better target selection for therapeutic agents.
Advances in nucleic acid-based detection methods
Authors: Wolcott M J
Published: June 2016

Laboratory techniques based on nucleic acid methods have increased in popularity over the last decade with clinical microbiologists and other laboratory scientists who are concerned with the diagnosis of infectious agents. This increase in popularity is a result primarily of advances made in nucleic acid amplification and detection techniques. Polymerase chain reaction, the original nucleic acid amplification technique, changed the way many people viewed and used nucleic acid techniques in clinical settings. After the potential of polymerase chain reaction became apparent, other methods of nucleic acid amplification and detection were developed. These alternative nucleic acid amplification methods may become serious contenders for application to routine laboratory analyses. This review presents some background information on nucleic acid analyses that might be used in clinical and anatomical laboratories and describes some recent advances in the amplification and detection of nucleic acids.
Unusual infections in humans
Authors: Neafie R C , Marty A M
Published: June 2016

Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules.
Gram-negative sepsis: a dilemma of modern medicine
Authors: Bone R C
Published: June 2016

Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis.
Role of iron in regulation of virulence genes
Authors: Litwin C M , Calderwood S B
Published: June 2016

The abilities of bacterial pathogens to adapt to the environment within the host are essential to their virulence. Microorganisms have adapted to the iron limitation present in mammalian hosts by evolving diverse mechanisms for the assimilation of iron sufficient for growth. In addition, many bacterial pathogens have used the low concentration of iron present in the host as an important signal to enhance the expression of a wide variety of bacterial toxins and other virulence determinants. The molecular basis of coordinate regulation by iron has been most thoroughly studied in Escherichia coli. In this organism, coordinate regulation of gene expression by iron depends on the regulatory gene, fur. Regulation of gene expression by iron in a number of pathogenic organisms is coordinated by proteins homologous to the Fur protein of E. coli. Additional regulatory proteins may be superimposed on the Fur repressor to provide the fine-tuning necessary for the precise regulation of individual virulence genes in response to iron and other environmental signals. Studies of the mechanisms of regulation of iron acquisition systems and virulence determinants by iron should lead to a better understanding of the adaptive response of bacteria to the low-iron environment of the host and its importance in virulence.
Physical and chemical methods for enhancing rapid detection of viruses and other agents
Authors: Hughes J H
Published: June 2016

Viral replication events can be enhanced by physical, chemical, or heat treatment of cells. The centrifugation of cells can stimulate them to proliferate, reduce their generation times, and activate gene expression. Human endothelial cells can be activated to release cyclo-oxygenase metabolites after rocking for 5 min, and mechanical stress can stimulate endothelial cells to proliferate. Centrifugation of virus-infected cultures can increase cytopathic effects (CPE), enhance the number of infected cells, increase viral yields, and reduce viral detection times and may increase viral isolation rates. The rolling of virus-infected cells also has an effect similar to that of centrifugation. The continuous rolling of virus-infected cultures at < or = 2.0 rpm can enhance enterovirus, rhinovirus, reovirus, rotavirus, paramyxovirus, herpesvirus, and vaccinia virus CPE or yields or both. For some viruses, the continuous rolling of infected cell cultures at 96 rpm (1.9 x g) is superior to rolling at 2.0 rpm for viral replication or CPE production. In addition to centrifugation and rolling, the treatment of cells with chemicals or heat can also enhance viral yields or CPE. For example, the treatment of virus-infected cells with dimethyl sulfoxide can enhance viral transformation, increase plaque numbers and plaque size, increase the number of cells producing antigens, and increase viral yields. The infectivity of fowl plague virus is increased by 80-fold when 4% dimethyl sulfoxide is added to culture medium immediately after infection. The heat shocking of virus-infected cells also has been shown to have a stimulatory effect on the replication events of cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus. The effects of motion, chemicals, or heat treatments on viral replication are not well understood. These treatments apparently activate cells to make them more permissive to viral infection and viral replication. Perhaps heat shock proteins or stress proteins are a common factor for this enhancement phenomenon. The utility of these treatments alone or in combination with other methods for enhancing viral isolation and replication in a diagnostic setting needs further investigation.
Pathogenesis of infections related to intravascular catheterization
Authors: Goldmann D A , Pier G B
Published: June 2016

Over the past few decades, there have been major technological improvements in the manufacture of intravenous solutions and the manufacture and design of catheter materials. However, the risk of infection in patients receiving infusion therapy remains substantial, in part because of host factors (for example, increased use of immunosuppressive therapy, more aggressive surgery and life support, and improved survival at the extremes of life) and in part because of the availability of catheters that can be left in place for very long periods. Microbial components of normal skin flora, particularly coagulase-negative staphylococci, have emerged as the predominant pathogens in catheter-associated infections. Therefore, efforts to prevent skin microorganisms from entering the catheter wound (such as tunnelling of catheters and use of catheter cuffs and local antimicrobial agents) are logical and relatively effective. The specific properties of microorganisms that transform normally harmless commensals such as coagulase-negative staphylococci into formidable pathogens in the presence of a plastic foreign body are being explored. For example, Staphylococcus epidermidis elaborates a polysaccharide adhesin that also functions as a capsule and is a target for opsonic killing. However, the interactions between microorganism and catheter that lead to adherence, persistence, infection, and dissemination appear to be multifactorial.
Q fever
Authors: Reimer L G
Published: June 2016

Q fever is an acute febrile illness first described in 1935 and now seen in many parts of the world. Human infection follows exposure to animals, especially domestic livestock. Recent outbreaks in metropolitan areas have implicated cats as the carrier of disease to humans. The etiologic agent, Coxiella burnetti, belongs to the family Rickettsiaceae, although it has distinct genetic characteristics and modes of transmission. Most recent attention has been focused on a number of large outbreaks of Q fever associated with medical research involving pregnant sheep. Although most infections are self-limited, some patients require prolonged treatment. Recent vaccines have had encouraging success in the prevention of disease in individuals at high risk of exposure.
Leishmaniases of the New World: current concepts and implications for future research
Authors: Grimaldi G , Tesh R B
Published: June 2016

Recent epidemiologic studies indicate that leishmaniasis in the Americas is far more abundant and of greater public health importance than was previously recognized. The disease in the New World is caused by a number of different parasite species that are capable of producing a wide variety of clinical manifestations. The outcome of leishmanial infection in humans is largely dependent on the immune responsiveness of the host and the virulence of the infecting parasite strain. This article reviews current concepts of the clinical forms, immunology, pathology, laboratory diagnosis, and treatment of the disease as well as aspects of its epidemiology and control. Recommendations for future research on the disease and its control are made.
The Mycobacterium avium complex
Authors: Inderlied C B , Kemper C A , Bermudez L E
Published: June 2016

Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated. Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied.
Bacillus cereus and related species
Authors: Drobniewski F A
Published: June 2016

Bacillus cereus is a gram-positive aerobic or facultatively anaerobic spore-forming rod. It is a cause of food poisoning, which is frequently associated with the consumption of rice-based dishes. The organism produces an emetic or diarrheal syndrome induced by an emetic toxin and enterotoxin, respectively. Other toxins are produced during growth, including phospholipases, proteases, and hemolysins, one of which, cereolysin, is a thiol-activated hemolysin. These toxins may contribute to the pathogenicity of B. cereus in nongastrointestinal disease. B. cereus isolated from clinical material other than feces or vomitus was commonly dismissed as a contaminant, but increasingly it is being recognized as a species with pathogenic potential. It is now recognized as an infrequent cause of serious nongastrointestinal infection, particularly in drug addicts, the immunosuppressed, neonates, and postsurgical patients, especially when prosthetic implants such as ventricular shunts are inserted. Ocular infections are the commonest types of severe infection, including endophthalmitis, panophthalmitis, and keratitis, usually with the characteristic formation of corneal ring abscesses. Even with prompt surgical and antimicrobial agent treatment, enucleation of the eye and blindness are common sequelae. Septicemia, meningitis, endocarditis, osteomyelitis, and surgical and traumatic wound infections are other manifestations of severe disease. B. cereus produces beta-lactamases, unlike Bacillus anthracis, and so is resistant to beta-lactam antibiotics; it is usually susceptible to treatment with clindamycin, vancomycin, gentamicin, chloramphenicol, and erythromycin. Simultaneous therapy via multiple routes may be required.
Epidemiologic evidence for multiple sclerosis as an infection
Authors: Kurtzke J F
Published: June 2016

The worldwide distribution of multiple sclerosis (MS) can be described within three zones of frequency: high, medium, and low. The disease has a predilection for white races and for women. Migration studies show that changing residence changes MS risk. Studies of persons moving from high- to low-risk areas indicate that in the high-risk areas, MS is acquired by about age 15. Moves from low- to high-risk areas suggest that susceptibility is limited to persons between about ages 11 and 45. MS on the Faroe Islands has occurred as four successive epidemics beginning in 1943. The disease appears to have been introduced by British troops who occupied the islands for 5 years from 1940, and it has remained geographically localized within the Faroes for half a century. What was introduced must have been an infection, called the primary MS affection (PMSA), that was spread to and from successive cohorts of Faroese. In this concept, PMSA is a single widespread systemic infectious disease (perhaps asymptomatic) that only seldom leads to clinical neurologic MS. PMSA is also characterized by a need for prolonged exposure, limited age of susceptibility, and prolonged incubation. I believe that clinical MS is the rare late outcome of a specific, but unknown, infectious disease of adolescence and young adulthood and that this infection could well be caused by a thus-far-unidentified (retro)virus.
Magnetic separation techniques in diagnostic microbiology
Authors: Olsvik O , Popovic T , Skjerve E , Cudjoe K S , Hornes E , Ugelstad J , Uhlén M
Published: June 2016

The principles of magnetic separation aided by antibodies or other specific binding molecules have been used for isolation of specific viable whole organisms, antigens, or nucleic acids. Whereas growth on selective media may be helpful in isolation of a certain bacterial species, immunomagnetic separation (IMS) technology can isolate strains possessing specific and characteristic surface antigens. Further separation, cultivation, and identification of the isolate can be performed by traditional biochemical, immunologic, or molecular methods. PCR can be used for amplification and identification of genes of diagnostic importance for a target organism. The combination of IMS and PCR reduces the assay time to several hours while increasing both specificity and sensitivity. Use of streptavidin-coated magnetic beads for separation of amplified DNA fragments, containing both biotin and a signal molecule, has allowed for the conversion of the traditional PCR into an easy-to-read microtiter plate format. The bead-bound PCR amplicons can also easily be sequenced in an automated DNA sequencer. The latter technique makes it possible to obtain sequence data of 300 to 600 bases from 20 to 30 strains, starting with clinical samples, within 12 to 24 h. Sequence data can be used for both diagnostic and epidemiologic purposes. IMS has been demonstrated to be a useful method in diagnostic microbiology. Most recent publications describe IMS as a method for enhancing the specificity and sensitivity of other detection systems, such as PCR, and providing considerable savings in time compared with traditional diagnostic systems. The relevance to clinical diagnosis has, however, not yet been fully established for all of these new test principles. In the case of PCR, for example, the presence of specific DNA in a food sample does not demonstrate the presence of a live organism capable of inducing a disease. However, all tests offering increased sensitivity and specificity of detection, combined with reduced time of analysis, have to be seriously evaluated.
Evolving approaches to management of quality in clinical microbiology
Authors: Bartlett R C , Mazens-Sullivan M , Tetreault J Z , Lobel S , Nivard J
Published: June 2016

Quality management in clinical microbiology began in the 1960s. Both government and professional societies introduced programs for proficiency testing and laboratory inspection and accreditation. Many laboratory scientists and pathologists were independently active and creative in expanding efforts to monitor and improve practices. The initial emphasis was placed on intralaboratory process. Later, attention was shifted to physician ordering, specimen collection, reporting, and use of information. Quality management in the laboratory depends in large part on the monitoring of indicators that provide some evidence of how laboratory resources are being used and how the information benefits patient care. Continuous quality improvement should be introduced. This consists of a more thorough assessment of doing the right things versus the wrong things in terms of customer demand and satisfaction and studying the cumulative effect of error when responsibility is passed from one person to another. Prevention of error is accomplished more through effective training and continuing education than through surveillance. Also, this system will force more conscious attention to meeting the expectations of the many customers that must be satisfied by laboratory services, including patients, physicians, third-party payers, and managed-care organizations.
Medically important arboviruses of the United States and Canada
Authors: Calisher C H
Published: June 2016

Of more than 500 arboviruses recognized worldwide, 5 were first isolated in Canada and 58 were first isolated in the United States. Six of these viruses are human pathogens: western equine encephalitis (WEE) and eastern equine encephalitis (EEE) viruses (family Togaviridae, genus Alphavirus), St. Louis encephalitis (SLE) and Powassan (POW) viruses (Flaviviridae, Flavivirus), LaCrosse (LAC) virus (Bunyaviridae, Bunyavirus), and Colorado tick fever (CTF) virus (Reoviridae, Coltivirus). Their scientific histories, geographic distributions, virology, epidemiology, vectors, vertebrate hosts, transmission, pathogenesis, clinical and differential diagnoses, control, treatment, and laboratory diagnosis are reviewed. In addition, mention is made of the Venezuelan equine encephalitis (VEE) complex viruses (family Togaviridae, genus Alphavirus), which periodically cause human and equine disease in North America. WEE, EEE, and SLE viruses are transmitted by mosquitoes between birds; POW and CTF viruses, between wild mammals by ticks; LAC virus, between small mammals by mosquitoes; and VEE viruses, between small or large mammals by mosquitoes. Human infections are tangential to the natural cycle. Such infections range from rare to focal but are relatively frequent where they occur. Epidemics of WEE, EEE, VEE, and SLE viruses have been recorded at periodic intervals, but prevalence of infections with LAC and CTF viruses typically are constant, related to the degree of exposure to infected vectors. Infections with POW virus appear to be rare. Adequate diagnostic tools are available, but treatment is mainly supportive, and greater efforts at educating the public and the medical community are suggested if infections are to be prevented.
Mixed viral infections: detection and management
Authors: Waner J L
Published: June 2016

An analysis was done of the incidence and nature of mixed virus infections diagnosed in the same clinical specimen from immunocompetent patients; respiratory viruses were emphasized. Few studies have addressed mixed viral infections in any systematic fashion. The relevant studies reviewed focused on clinical relationships or diagnostic methods. Data relating to multiple infections were usually derived incidentally to the purpose of the investigations. Sixty-three percent of the reports with data on mixed infections identified them in < 5% of the total number of viral infections. Respiratory syncytial virus was the most common coinfecting virus, and respiratory syncytial virus and influenza virus were the most common virus pair identified. In considering rapid diagnostic techniques, in 87% of the reports with available data a virus was diagnosed in > 10% of specimens that were negative for the virus targeted by one method. There was no indication that mixed infections were associated with increased disease in immunocompetent patients or in certain immunocompromised patients. Immunocompromised patients, however, appeared to have a greater incidence of multiple infections. Mixed infections of single cells also occur and may have important clinical implications relative to reactivation of latent viruses and enhanced disease. The requirement for a comprehensive strategy for viral diagnosis involving multiple techniques was indicated by these findings.
Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection
Authors: Sheridan J F , Dobbs C , Brown D , Zwilling B
Published: June 2016

The mammalian response to stress involves the release of soluble products from the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Cells of the immune system respond to many of the hormones, neurotransmitters, and neuropeptides through specific receptors. The function of the immune system is critical in the mammalian response to infectious disease. A growing body of evidence identifies stress as a cofactor in infectious disease susceptibility and outcomes. It has been suggested that effects of stress on the immune system may mediate the relationship between stress and infectious disease. This article reviews recent psychoneuroimmunology literature exploring the effects of stress on the pathogenesis of, and immune response to, infectious disease in mammals.