bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenesis and Diagnosis of Shiga Toxin-Producing
Escherichia coli
Infections
Authors: Paton James C. , Paton Adrienne W.
Published: October 2018

Since their initial recognition 20 years ago, Shiga toxin-producing Escherichia coli (STEC) strains have emerged as an important cause of serious human gastrointestinal disease, which may result in life-threatening complications such as hemolytic-uremic syndrome. Food-borne outbreaks of STEC disease appear to be increasing and, when mass-produced and mass-distributed foods are concerned, can involve large numbers of people. Development of therapeutic and preventative strategies to combat STEC disease requires a thorough understanding of the mechanisms by which STEC organisms colonize the human intestinal tract and cause local and systemic pathological changes. While our knowledge remains incomplete, recent studies have improved our understanding of these processes, particularly the complex interaction between Shiga toxins and host cells, which is central to the pathogenesis of STEC disease. In addition, several putative accessory virulence factors have been identified and partly characterized. The capacity to limit the scale and severity of STEC disease is also dependent upon rapid and sensitive diagnostic procedures for analysis of human samples and suspect vehicles. The increased application of advanced molecular technologies in clinical laboratories has significantly improved our capacity to diagnose STEC infection early in the course of disease and to detect low levels of environmental contamination. This, in turn, has created a potential window of opportunity for future therapeutic intervention.
Klebsiellaspp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors
Authors: Podschun R. , Ullmann U.
Published: October 2018

Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-β-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.
Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)
Authors: Briles David E. , Tart Rebecca Creech , Swiatlo Edwin , Dillard Joseph P. , Smith Patricia , Benton Kimberly A. , Ralph Beth A. , Brooks-Walter Alexis , Crain Marilyn J. , Hollingshead Susan K. , McDaniel Larry S.
Published: October 2018

Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.
Genital Herpes: Review of the Epidemic and Potential Use of Type-Specific Serology
Authors: Ashley Rhoda L. , Wald Anna
Published: October 2018

Prevention of genital herpes simplex virus (HSV) infections is desirable from both a public health standpoint and the patient’s perspective. A key factor in the spread of genital herpes infections is the high proportion of undiagnosed infections. Persons with subclinical or unrecognized infections are best diagnosed by accurate, type-specific antibody tests. Unfortunately, these tests are only now becoming widely available. The use of current, conventional (non-type-specific) serologic tests for diagnosis of herpes infections has resulted in confusion and misdiagnosis of patients. This review provides recent information on the epidemiology of genital herpes infections, describes the importance of subclinical herpes infection and shedding, summarizes the status of HSV type-specific serologic assays being developed, and provides indications for using such assays.
Role of Heat Shock Proteins in Protection from and Pathogenesis of Infectious Diseases
Authors: Zügel Ulrich , Kaufmann Stefan H. E.
Published: October 2018

Increased synthesis of heat shock proteins (hsp) occurs in prokaryotic and eukaryotic cells when they are exposed to stress. By increasing their hsp content, cells protect themselves from lethal assaults, primarily because hsp interfere with the uncontrolled protein unfolding that occurs under stress. However, hsp are not produced only by stressed cells; some hsp are synthesized constitutively and perform important housekeeping functions. Accordingly, hsp are involved in the assembly of molecules which play important roles in the immune system. It is not surprising that due to their wide distribution and their homology among different species, hsp represent target antigens of the immune response. Frequent confrontation of the immune system with conserved regions of hsp which are shared by various microbial pathogens can potentiate antimicrobial immunity. However, long-term confrontation of the immune system with hsp antigens which are similar in the host and invaders may convert the immune response against these host antigens and promote autoimmune disease. This review provides an overview of the role of hsp in immunity with a focus on infectious and autoimmune diseases.
Association of Rhinovirus Infections with Asthma
Authors: Gern James E. , Busse William W.
Published: October 2018

Rhinoviruses are the most common cause of the common cold, but they can cause more severe illnesses in people with underlying lung disorders such as asthma, chronic obstructive pulmonary disease, or cystic fibrosis. Epidemiologic studies with sensitive detection methods such as PCR have identified rhinovirus infection as a major source of asthma exacerbations in both children and adults, especially during the spring and fall. Since rhinoviruses cause little tissue destruction, it is presumed that the immune response to the infection may play an important role in the pathogenesis of rhinovirus-induced exacerbations of asthma. This review examines the epidemiologic association between rhinovirus infections and exacerbations of asthma and outlines current information on immune responses to rhinovirus infection and potential connections between antiviral responses and preexisting allergic inflammation. Finally, current and future strategies for treating rhinovirus infections and virus-induced exacerbations of asthma are discussed.
Update on Diagnosis, Management, and Prevention of Hepatitis B Virus Infection
Authors: Mahoney Francis J.
Published: October 2018

Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. It is estimated that approximately 350 million people worldwide have chronic HBV infection and that 1 million persons die each year from HBV-related chronic liver disease. In the past decade, significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made. In addition, effective treatment modalities have been developed for persons with chronic infection. Worldwide, prevention of HBV transmission has become a high priority. In 1992, the Global Advisory Group to the World Health Organization recommended that all countries integrate hepatitis B vaccine into national immunization programs by 1997. Currently, 80 countries have done so and several others are planning to. Many countries have reported dramatic reductions in the prevalence of chronic HBV infection among children born since the hepatitis B vaccine was introduced into infant immunization schedules. Recent reports from Taiwan indicate a reduction in the incidence of liver cancer among children as a result of widespread hepatitis B vaccination programs.
Molecular Basis of the Interaction ofSalmonellawith the Intestinal Mucosa
Authors: Darwin K. Heran , Miller Virginia L.
Published: October 2018

Salmonella is one of the most extensively characterized bacterial pathogens and is a leading cause of bacterial gastroenteritis. Despite this, we are only just beginning to understand at a molecular level how Salmonella interacts with its mammalian hosts to cause disease. Studies during the past decade on the genetic basis of virulence of Salmonella have significantly advanced our understanding of the molecular basis of the host-pathogen interaction, yet many questions remain. In this review, we focus on the interaction of enterocolitis-causing salmonellae with the intestinal mucosa, since this is the initiating step for most infections caused by Salmonella. Animal and in vitro cell culture models for the interaction of these bacteria with the intestinal epithelium are reviewed, along with the bacterial genes that are thought to affect this interaction. Lastly, recent studies on the response of epithelial cells to Salmonella infection and how this might promote diarrhea are discussed.
Q Fever
Authors: Maurin M. , Raoult D.
Published: October 2018

Q fever is a zoonosis with a worldwide distribution with the exception of New Zealand. The disease is caused by Coxiella burnetii, a strictly intracellular, gram-negative bacterium. Many species of mammals, birds, and ticks are reservoirs of C. burnetii in nature. C. burnetii infection is most often latent in animals, with persistent shedding of bacteria into the environment. However, in females intermittent high-level shedding occurs at the time of parturition, with millions of bacteria being released per gram of placenta. Humans are usually infected by contaminated aerosols from domestic animals, particularly after contact with parturient females and their birth products. Although often asymptomatic, Q fever may manifest in humans as an acute disease (mainly as a self-limited febrile illness, pneumonia, or hepatitis) or as a chronic disease (mainly endocarditis), especially in patients with previous valvulopathy and to a lesser extent in immunocompromised hosts and in pregnant women. Specific diagnosis of Q fever remains based upon serology. Immunoglobulin M (IgM) and IgG antiphase II antibodies are detected 2 to 3 weeks after infection with C. burnetii, whereas the presence of IgG antiphase I C. burnetii antibodies at titers of ≥1:800 by microimmunofluorescence is indicative of chronic Q fever. The tetracyclines are still considered the mainstay of antibiotic therapy of acute Q fever, whereas antibiotic combinations administered over prolonged periods are necessary to prevent relapses in Q fever endocarditis patients. Although the protective role of Q fever vaccination with whole-cell extracts has been established, the population which should be primarily vaccinated remains to be clearly identified. Vaccination should probably be considered in the population at high risk for Q fever endocarditis.
Respiratory Syncytial Virus Genetic and Antigenic Diversity
Authors: Sullender Wayne M.
Published: October 2018

Respiratory syncytial virus (RSV) is a major cause of viral lower respiratory tract infections among infants and young children in both developing and developed countries. There are two major antigenic groups of RSV, A and B, and additional antigenic variability occurs within the groups. The most extensive antigenic and genetic diversity is found in the attachment glycoprotein, G. During individual epidemic periods, viruses of both antigenic groups may cocirculate or viruses of one group may predominate. When there are consecutive annual epidemics in which the same group predominates, the dominant viruses are genetically different from year to year. The antigenic differences that occur among these viruses may contribute to the ability of RSV to establish reinfections throughout life. The differences between the two groups have led to vaccine development strategies that should provide protection against both antigenic groups. The ability to discern intergroup and intragroup differences has increased the power of epidemiologic investigations of RSV. Future studies should expand our understanding of the molecular evolution of RSV and continue to contribute to the process of vaccine development.
Glomerulopathy Associated with Parasitic Infections
Authors: van Velthuysen M.-L. F. , Florquin S.
Published: October 2018

Although parasitic infections do not usually present with disturbance in renal function, glomerular lesions can be seen in most of these infections. The glomerular lesions observed in parasitic infections cover the whole range of glomerular lesions known, but most of them are proliferative. Little is known of the exact pathogenic mechanisms. In this review, we try to explain the glomerular lesions associated with parasitic infections in terms of the specific immunologic events observed during these diseases against the background of recent developments in the general knowledge of the pathogenesis of glomerular disease.
Perspectives for the Treatment of Infections withFlaviviridae
Authors: Leyssen Pieter , De Clercq Erik , Neyts Johan
Published: October 2018

The family Flaviviridae contains three genera: Hepacivirus, Flavivirus, and Pestivirus. Worldwide, more than 170 million people are chronically infected with Hepatitis C virus and are at risk of developing cirrhosis and/or liver cancer. In addition, infections with arthropod-borne flaviviruses (such as dengue fever, Japanese encephalitis, tick-borne encephalitis, St. Louis encephalitis, Murray Valley encephalitis, West Nile, and yellow fever viruses) are emerging throughout the world. The pestiviruses have a serious impact on livestock. Unfortunately, no specific antiviral therapy is available for the treatment or the prevention of infections with members of the Flaviviridae. Ongoing research has identified possible targets for inhibition, including binding of the virus to the cell, uptake of the virus into the cell, the internal ribosome entry site of hepaciviruses and pestiviruses, the capping mechanism of flaviviruses, the viral proteases, the viral RNA-dependent RNA polymerase, and the viral helicase. In light of recent developments, the prevalence of infections caused by these viruses, the disease spectrum, and the impact of infections, different strategies that could be pursued to specifically inhibit viral targets and animal models that are available to study the pathogenesis and antiviral strategies are reviewed.
Cysteine Proteinases and the Pathogenesis of Amebiasis
Authors: Que Xuchu , Reed Sharon L.
Published: October 2018

Amebiasis is a major cause of morbidity and mortality throughout the tropical world. Entamoeba histolytica is now recognized as a separate species from the morphologically identical E. dispar, which cannot invade. Cysteine proteinases are a key virulence factor of E. histolytica and play a role in intestinal invasion by degrading the extracellular matrix and circumventing the host immune response through cleavage of secretory immunoglobulin A (sIgA), IgG, and activation of complement. Cysteine proteinases are encoded by at least seven genes, several of which are found in E. histolytica but not E. dispar. A number of new animal models, including the formation of liver abscesses in SCID mice and intestinal infection in human intestinal xenografts, have proven useful to confirm the critical role of cysteine proteinases in invasion. Detailed structural analysis of cysteine proteinases should provide further insights into their biochemical function and may facilitate the design of specific inhibitors which could be used as potential chemotherapeutic agents in the future.
Clinical Significance of Hepatitis C Virus Genotypes
Authors: Zein Nizar N.
Published: October 2018

On the basis of phylogenetic analysis of nucleotide sequences, multiple genotypes and subtypes of hepatitis C virus (HCV) have been identified. Characterization of these genetic groups is likely to facilitate and contribute to the development of an effective vaccine against infection with HCV. Differences among HCV genotypes in geographic distributions have provided investigators with an epidemiologic marker that can be used to trace the source of HCV infection in a given population. HCV genotype 1 may represent a more aggressive strain and one that is less likely to respond to interferon treatment than HCV genotype 2 or 3. However, these observations require confirmation before HCV genotyping can be used in clinical settings.
Respiratory Syncytial Virus Infection in Adults
Authors: Falsey Ann R. , Walsh Edward E.
Published: October 2018

Respiratory syncytial virus (RSV) is now recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult community-acquired pneumonias. Attack rates in nursing homes are approximately 5 to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to 5%). Clinical features may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow transplant patients prior to marrow engraftment are at highest risk for pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably due to low viral titers in nasal secretions, but early bronchoscopy is valuable in immunosuppressed patients. Treatment of RSV in the elderly is largely supportive, whereas early therapy with ribavirin and intravenous gamma globulin is associated with improved survival in immunocompromised persons. An effective RSV vaccine has not yet been developed, and thus prevention of RSV infection is limited to standard infection control practices such as hand washing and the use of gowns and gloves.
Applications of Differential-Display Reverse Transcription-PCR to Molecular Pathogenesis and Medical Mycology
Authors: Sturtevant Joy
Published: October 2018

The host-fungus interaction is characterized by changes in gene expression in both host and pathogen. Differential-display reverse transcription PCR (DDRT-PCR) is a PCR-based method that allows extensive analysis of gene expression among several cell populations. Several limitations and drawbacks to this procedure have now been addressed, including the large number of false-positive results and the difficulty in confirming differential expression. Modifications that simplify the reaction time, allow the use of minute quantities of RNA, or address unusual species- or gene-specific sequences have been reported. DDRT-PCR has been used to address biological questions in mammalian systems, including cell differentiation, cell activation, cell stress, and identification of drug targets. In microbial pathogenesis and plant pathogenesis, DDRT-PCR has allowed the identification of virulence factors, genes involved in cell death, and signaling genes. In Candida albicans, DDRT-PCR studies identified TIF-2, which may play a role in the upregulation of phospholipases, and the stress-related genes, CIP1 and CIP2. In Histoplasma capsulatum and C. albicans, genes involved in the host-pathogen interaction, including a member of the 100-kDa family in Histoplasma and an ALS and 14-3-3 gene in Candida, were potentially identified by DDRT-PCR. Although very few reports have been published in medical mycology, studies in mammalian, nonfungal microbial, and plant pathogen systems are easily applied to basic questions in fungal pathogenesis and antifungal therapeutics.
Babesiosis
Authors: Homer Mary J. , Aguilar-Delfin Irma , Telford Sam R. , Krause Peter J. , Persing David H.
Published: October 2018

Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Babesial parasites (and those of the closely related genus Theileria) are some of the most ubiquitous and widespread blood parasites in the world, second only to the trypanosomes, and consequently have considerable worldwide economic, medical, and veterinary impact. The parasites are intraerythrocytic and are commonly called piroplasms due to the pear-shaped forms found within infected red blood cells. The piroplasms are transmitted by ixodid ticks and are capable of infecting a wide variety of vertebrate hosts which are competent in maintaining the transmission cycle. Studies involving animal hosts other than humans have contributed significantly to our understanding of the disease process, including possible pathogenic mechanisms of the parasite and immunological responses of the host. To date, there are several species of Babesia that can infect humans, Babesia microti being the most prevalent. Infections with Babesia species generally follow regional distributions; cases in the United States are caused primarily by B. microti, whereas cases in Europe are usually caused by Babesia divergens. The spectrum of disease manifestation is broad, ranging from a silent infection to a fulminant, malaria-like disease, resulting in severe hemolysis and occasionally in death. Recent advances have resulted in the development of several diagnostic tests which have increased the level of sensitivity in detection, thereby facilitating diagnosis, expediting appropriate patient management, and resulting in a more accurate epidemiological description.
Relationships between Enterococcal Virulence and Antimicrobial Resistance
Authors: Mundy L. M. , Sahm D. F. , Gilmore M.
Published: October 2018

Enterococci have become a vexing problem in clinical medicine because of their ability to infect patients who are typically receiving antibiotic therapy for unrelated underlying illness. Moreover, the infections have become extremely difficult to manage because of the accumulation of antibiotic resistances among enterococci. The ability of enterococci to cause disease is an intrinsic property of the organism or possibly subpopulations within enterococcal species. The probability of an infection's becoming established, however, is almost certainly in part a function of the enterococcal burden. By altering endogenous bacterial flora, antibiotic therapy promotes increased colonization by antibiotic-resistant organisms. Therefore, antibiotic resistance and intrinsic virulence both contribute to disease, but in separate and complementary ways. We review the virulence of enterococci, as distinct from the acquisition of antimicrobial resistance genes, and identify current gaps in our understanding of enterococcal virulence and the basis for disease.
Classification, Identification, and Clinical Significance ofProteus,Providencia, andMorganella
Authors: O'Hara Caroline Mohr , Brenner Frances W. , Miller J. Michael
Published: October 2018

This review presents the current taxonomy of the genera Proteus, Providencia, and Morganella, along with the current methods for the identification of each species within the three genera, incorporating both conventional biochemical and commercial methods. While all of these organisms are ubiquitous in the environment, individual case reports and nosocomial outbreak reports that demonstrate their ability to cause major infectious disease problems are presented. Lastly, anticipated antimicrobial susceptibility patterns are reviewed. Many of these organisms are easily controlled, but the advent of newer and more powerful antimicrobial agents has led to some problems of which laboratorians need to be aware.
Rubella Virus Replication and Links to Teratogenicity
Authors: Lee Jia-Yee , Bowden D. Scott
Published: October 2018

Rubella virus (RV) is the causative agent of the disease known more popularly as German measles. Rubella is predominantly a childhood disease and is endemic throughout the world. Natural infections of rubella occur only in humans and are generally mild. Complications of rubella infection, most commonly polyarthralgia in adult women, do exist; occasionally more serious sequelae occur. However, the primary public health concern of RV infection is its teratogenicity. RV infection of women during the first trimester of pregnancy can induce a spectrum of congenital defects in the newborn, known as congenital rubella syndrome (CRS). The development of vaccines and implementation of vaccination strategies have substantially reduced the incidence of disease and in turn of CRS in developed countries. The pathway whereby RV infection leads to teratogenesis has not been elucidated, but the cytopathology in infected fetal tissues suggests necrosis and/or apoptosis as well as inhibition of cell division of critical precursor cells involved in organogenesis. In cell culture, a number of unusual features of RV replication have been observed, including mitochondrial abnormalities, and disruption of the cytoskeleton; these manifestations are most probably linked and play some role in RV teratogenesis. Further understanding of the mechanism of RV teratogenesis will be brought about by the investigation of RV replication and virus-host interactions.
Limiting the Spread of Resistant Pneumococci: Biological and Epidemiologic Evidence for the Effectiveness of Alternative Interventions
Authors: Schrag Stephanie J. , Beall Bernard , Dowell Scott F.
Published: October 2018

Streptococcus pneumoniae infections are a leading cause of respiratory illness in young children, the elderly, and persons with chronic medical conditions. The emergence of multidrug-resistant pneumococci has compromised the effectiveness of antibiotic therapy for pneumococcal infections. As antibiotic-resistant strains increase in prevalence, there is a need for interventions that minimize the spread of resistant pneumococci. In this review we provide a framework for understanding the spread of pneumococcal resistance and evaluate proposed interventions to reduce this spread. Pneumococci differ from many drug-resistant pathogens because asymptomatic carriers play a key role in transmission of resistant strains and the genes encoding resistance are spread primarily by transformation and conjugative transposons. Evidence suggests that modifications of treatment regimens that have proved effective at limiting resistance in other pathogens may not prevent the spread of pneumococcal resistance. In contrast, programs encouraging more judicious antibiotic use have been shown to be effective. Additionally, a newly developed conjugate pneumococcal vaccine holds great potential as an “antiresistance vaccine” that simultaneously reduces the burden of invasive disease and the prevalence of resistant strains. Several areas of future epidemiologic and laboratory research hold promise to contribute to the reduced spread of pneumococcal resistance.
Molecular Strategies for Interrupting Arthropod-Borne Virus Transmission by Mosquitoes
Authors: Blair Carol D. , Adelman Zachary N. , Olson Ken E.
Published: October 2018

Arthropod-borne virus (arbovirus) infections cause a number of emerging and resurgent human and veterinary infectious diseases. Traditional means of controlling arbovirus diseases include vaccination of susceptible vertebrates and mosquito control, but in many cases these have been unavailable or ineffective, and so novel strategies for disease control are needed. One possibility is genetic manipulation of mosquito vectors to render them unable to transmit arboviruses. This review describes recent work to test the concept of pathogen-derived resistance in arthropods by expression of viral genes in mosquito cell cultures and mosquitoes. Sense and antisense genome sequences from La Crosse virus (LAC) (a member of the Bunyaviridae) and dengue viruses serotypes 1 to 4 (DEN-1 to DEN-4) (members of the Flaviviridae) were expressed in mosquito cells from double-subgenomic and replicon vectors based on Sindbis virus (a member of the Togaviridae). The cells were then challenged with homologous or related viruses. For LAC, expression of antisense sequences from the small (S) genome segment, particularly full-length antisense S RNA, effectively interfered with replication of challenge virus, whereas expression of either antisense or sense RNA from the medium (M) segment was completely ineffective in LAC inhibition. Expression of sense and antisense RNA derived from certain regions of the DEN genome also blocked homologous virus replication more effectively than did RNA from other regions. Other parameters of RNA-mediated interference have been defined, such as the time when replication is blocked and the minimum size of effector RNA. The mechanism of RNA inhibition has not been determined, although it resembles double-stranded RNA interference in other nonvertebrate systems. Prospects for application of molecular strategies to control arbovirus diseases are briefly reviewed.
Laboratory diagnosis and interpretation of tests for syphilis
Authors: Larsen S A , Steiner B M , Rudolph A H
Published: October 2018

The lack of a method for demonstrating the presence of Treponema pallidum by growth necessitates the use of alternative methods. Traditionally, these methods are divided into direct detection methods (animal inoculation, dark-field microscopy, etc.) and serologic tests for the presence of patient antibody against T. pallidum. Serologic methods are further divided into two classes. One class, the nontreponemal tests, detects antibodies to lipoidal antigens present in either the host or T. pallidum; examples are the Venereal Disease Research Laboratory and rapid plasma reagin and tests. Reactivity in these tests generally indicates host tissue damage that may not be specific for syphilis. Because these tests are easy and inexpensive to perform, they are commonly used for screening, and with proper clinical signs they are suggestive of syphilis. The other class of test, the treponemal tests, uses specific treponemal antigens. Confirmation of infection requires a reactive treponemal test. Examples of the treponemal tests are the microhemagglutination assay for antibodies to T. pallidum and the fluorescent treponemal antibody absorption test. These tests are more expensive and complicated to perform than the nontreponemal tests. On the horizon are a number of direct antigen, enzyme-linked immunosorbent assay, and PCR techniques. Several of these techniques have shown promise in clinical trials for the diagnosis of congenital syphilis and neurosyphilis that are presently difficult to diagnose.
Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections
Authors: Hemming V G , Prince G A , Groothuis J R , Siber G R
Published: October 2018

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.
Virus receptors: implications for pathogenesis and the design of antiviral agents
Authors: Norkin L C
Published: October 2018

A virus initiates infection by attaching to its specific receptor on the surface of a susceptible host cell. This prepares the way for the virus to enter the cell. Consequently, the expression of the receptor on specific cells and tissues of the host is a major determinant of the route of entry of the virus into the host and of the patterns of virus spread and pathogenesis in the host. This review emphasizes the virus-receptor interactions of human immunodeficiency virus, the rhinoviruses, the herpesviruses, and the coronaviruses. These interactions are often found to be complex and dynamic, involving multiple sites or factors on both the virus and the host cell. Also, the receptor may play an important role in virus entry per se in addition to its role in virus binding. In the cases of human immunodeficiency virus and the rhinoviruses, ingenious approaches to therapeutic strategies based on inhibiting virus attachment and entry are under development and in clinical trials.
Cutaneous defenses against dermatophytes and yeasts
Authors: Wagner D K , Sohnle P G
Published: October 2018

Predispositions to the superficial mycoses include warmth and moisture, natural or iatrogenic immunosuppression, and perhaps some degree of inherited susceptibility. Some of these infections elicit a greater inflammatory response than others, and the noninflammatory ones are generally more chronic. The immune system is involved in the defense against these infections, and cell-mediated immunity appears to be particularly important. The mechanisms involved in generating immunologic reactions in the skin are complex, with epidermal Langerhans cells, other dendritic cells, lymphocytes, microvascular endothelial cells, and the keratinocytes themselves all participating in one way or another. A variety of defects in the immunologic response to the superficial mycoses have been described. In some cases the defect may be preexistent, whereas in others the infection itself may interfere with protective cell-mediated immune responses against the organisms. A number of different mechanisms may underlie these immunologic defects and lead to the development of chronic superficial fungal infection in individual patients. Although the immunologic defects appear to be involved in the chronicity of certain types of cutaneous fungal infections, treatment of these defects remains experimental at the present time.
Recovery of uncommon bacteria from blood: association with neoplastic disease
Authors: Beebe J L , Koneman E W
Published: October 2018

Table 6 is a summary of the organisms discussed with a listing of the environmental source, the endogenous source, the predisposing factors including neoplasms, and the postulated mechanisms by which the organism can gain access to the circulation. The evidence considered indicates that the entrance of one of these microorganisms into the bloodstream of a human being depends on the presence of multiplicity of predisposing factors. In the majority of cases of bacteremia due to one of these unusual organisms, two or more predisposing factors are present. Certain predisposing factors, such as cancer chemotherapy or intravenous catheterization, often provide a barrier break, while others, such as liver disease, may render the host immune system less capable of clearing organisms from the circulation. For organisms such as Campy-lobacter, Listeria, and Salmonella spp., attributes that allow the invasion of a healthy host are present and seem to be enhanced by the simultaneous presence of a predisposing condition, such as liver disease, in the host. Although somewhat fragmentary, a number of individual case reports describe bacteremia due to one of these organisms occurring weeks to years after surgery and after other therapeutic measures had effected a supposed cure of a cancer. It may be speculated that cancer patients, even after a cure, are still susceptible to bloodstream invasion by one of the aforementioned organisms by virtue of the presence of one or more predisposing metabolic, physiologic, or immunologic factors, even though these factors may be cryptic. The predominance of hematologic malignancies among cases of bacteremia due to these unusual organisms is also apparent. Although, as pointed out by Keusch (169), the reduction in the performance of immune function in hematologic malignancies compared with solid tumors is likely to be responsible, other associations of certain organisms with specific neoplasms warrant further examination. The frequency of bloodstream infections of Salmonella typhimurium and Capno-cytophaga canimorsus in Hodgkin's disease patients seems likely due to a particular mechanism which infection by these species is favored. The specific nature of these mechanisms remains to be determined. The recovery of any unusual bacterium from blood should warrant a careful consideration of the possibility of underlying disease, especially cancer. Microbiologists should advise clinicians of the unusual nature of the identified organism and provide the counsel that certain neoplastic processes, often accompanied by neutropenia, render the human host susceptible to invasion by almost any bacterium. The recovery of such organisms as C. septicum or S. bovis should prompt the clinician to aggressively seek to identify an occult neoplasm if one has not yet been diagnosed.
Chancroid and Haemophilus ducreyi: an update
Authors: Trees D L , Morse S A
Published: October 2018

Haemophilus ducreyi is a fastidious gram-negative bacillus that causes the sexually transmitted infection chancroid. Chancroid is a major genital ulcerative disease in Africa, Southeast Asia, the Caribbean, and Latin America and is of increasing concern in the United States. Genital ulcerative disease and chancroid in particular have been associated with facilitating the transmission of human immunodeficiency virus. The diagnosis of chancroid based on the clinical appearance of the genital lesion or on the isolation of H. ducreyi on selective medium is relatively insensitive. However, recent advances in nonculture diagnostic tests have enhanced our ability to diagnose chancroid. There has been renewed interest in understanding the pathogenesis of H. ducreyi. In vitro and in vivo models have been developed to help identify important virulence determinants. Through the use of biochemical and molecular techniques, macromolecular components that may be important in virulence have been identified.
Nucleic acid vaccines
Authors: Vogel F R , Sarver N
Published: October 2018

The use of nucleic acid-based vaccines is a novel approach to immunization that elicits immune responses similar to those induced by live, attenuated vaccines. Administration of nucleic acid vaccines results in the endogenous generation of viral proteins with native conformation, glycosylation profiles, and other posttranslational modifications that mimic antigen produced during natural viral infection. Nucleic acid vaccines have been shown to elicit both antibody and cytotoxic T-lymphocyte responses to diverse protein antigens. Advantages of nucleic acid-based vaccines include the simplicity of the vector, the ease of delivery, the duration of expression, and, to date, the lack of evidence of integration. Further studies are needed to assess the feasibility, safety, and efficacy of this new and promising technology.
Identification, classification, and clinical relevance of catalase-negative, gram-positive cocci, excluding the streptococci and enterococci
Authors: Facklam R , Elliott J A
Published: October 2018

Several new genera and species of gram-positive, catalase-negative cocci that can cause infections in humans have been described. Although these bacteria were isolated in the clinical laboratory, they were considered nonpathogenic culture contaminants and were not thought to be the cause of any diseases. Isolation of pure cultures of these bacteria from normally sterile sites has led to the conclusion that these bacteria can be an infrequent cause of infection. This review describes the new bacteria and the procedures useful for clinical laboratories to aid in their identification. The clinical relevance and our experience with the various genera and species are reviewed and discussed.
Antimicrobial agent resistance in mycobacteria: molecular genetic insights
Authors: Musser J M
Published: October 2018

The primary theme emerging from molecular genetic work conducted with Mycobacterium tuberculosis and several other mycobacterial species is that resistance is commonly associated with simple nucleotide alterations in target chromosomal genes rather than with acquisition of new genetic elements encoding antibiotic-altering enzymes. Mutations in an 81-bp region of the gene (rpoB) encoding the beta subunit of RNA polymerase account for rifampin resistance in 96% of M. tuberculosis and many Mycobacterium leprae isolates. Streptomycin resistance in about one-half of M. tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs). Mutations in the katG gene resulting in catalase-peroxidase amino acid alterations nad nucleotide substitutions in the presumed regulatory region of the inhA locus are repeatedly associated with isoniazid-resistant M. tuberculosis isolates. A majority of fluoroquinolone-resistant M. tuberculosis isolates have amino acid substitutions in a region of the DNA gyrase A subunit homologous to a conserved fluoroquinolone resistance-determining region. Multidrug-resistant isolates of M. tuberculosis arise as a consequence of sequential accumulation of mutations conferring resistance to single therapeutic agents. Molecular strategies show considerable promise for rapid detection of mutations associated with antimicrobial resistance. These approaches are now amenable to utilization in an appropriately equipped clinical microbiology laboratory.
beta-Lactamases in laboratory and clinical resistance
Authors: Livermore D M
Published: October 2018

beta-Lactamases are the commonest single cause of bacterial resistance to beta-lactam antibiotics. Numerous chromosomal and plasmid-mediated types are known and may be classified by their sequences or phenotypic properties. The ability of a beta-lactamase to cause resistance varies with its activity, quantity, and cellular location and, for gram-negative organisms, the permeability of the producer strain. beta-Lactamases sometimes cause obvious resistance to substrate drugs in routine tests; often, however, these enzymes reduce susceptibility without causing resistance at current, pharmacologically chosen breakpoints. This review considers the ability of the prevalent beta-lactamases to cause resistance to widely used beta-lactams, whether resistance is accurately reflected in routine tests, and the extent to which the antibiogram for an organism can be used to predict the type of beta-lactamase that it produces.
Molecular biology and pathogenesis of animal lentivirus infections
Authors: Clements J E , Zink M C
Published: October 2018

Lentiviruses are a subfamily of retroviruses that are characterized by long incubation periods between infection of the host and the manifestation of clinical disease. Human immunodeficiency virus type 1, the causative agent of AIDS, is the most widely studied lentivirus. However, the lentiviruses that infect sheep, goats, and horses were identified and studied prior to the emergence of human immunodeficiency virus type 1. These and other animal lentiviruses provide important systems in which to investigate the molecular pathogenesis of this family of viruses. This review will focus on two animal lentivirus models: the ovine lentivirus visna virus; and the simian lentivirus, simian immunodeficiency virus. These animal lentiviruses have been used to examine, in particular, the pathogenesis of lentivirus-induced central nervous system disease as models for humans with AIDS as well as other chronic diseases.
Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease
Authors: Urnovitz H B , Murphy W H
Published: October 2018

Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated.