Showing papers in "Clinical Microbiology Reviews in 1996"

Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features.

Abstract: INTRODUCTION 149 TAXONOMY 149 Historical Features 149 Current Taxonomic Status 149 Delineation of Species 149 Species of Clinical Importance 150 LABORATORY IDENTIFICATION 150 Isolation from Clinical Specimens 150 Morphological, Cultural, and Metabolic Characteristics 151 Species Identification 151 NOSOCOMIAL INFECTIONS CAUSED BY ACINETOBACTER SPP. 152 Overview 152 Respiratory Infection 152 Bacteremia 153 Meningitis 153 Urinary Tract Infection 154 Other Miscellaneous Infections 154 PATHOGENESIS OF ACINETOBACTER INFECTIONS 154 Predisposing Factors 154 Virulence of Acinetobacter spp. 154 EPIDEMIOLOGY 155 Human Carriage 155 Persistence in the Hospital Environment 155 TYPING SYSTEMS 156 Biotyping 156 Antibiograms 156 Serotyping 156 Phage Typing 157 Bacteriocin Typing 157 Protein Profiles 157 Multilocus Enzyme Electrophoretic Typing 157 Plasmid Profiles 157 Analysis by Pulsed-Field Gel Electrophoresis 157 Ribotyping 157 PCR-Based Methods 158 CLINICAL ANTIBIOTIC RESISTANCE 158 BIOCHEMICAL AND GENETIC MECHANISMS OF ANTIBIOTIC RESISTANCE 158 Genetics of Resistance 158 b-Lactams 159 Aminoglycosides 159 Quinolones 160 Other Antibiotics 160 THERAPY OF ACINETOBACTER INFECTIONS 160 CONCLUSIONS 160 ACKNOWLEDGMENTS 161 REFERENCES 161

Varicella-zoster virus.

Abstract: Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that causes varicella (chicken pox) and herpes zoster (shingles). Varicella is a common childhood illness, characterized by fever, viremia, and scattered vesicular lesions of the skin. As is characteristic of the alphaherpesviruses, VZV establishes latency in cells of the dorsal root ganglia. Herpes zoster, caused by VZV reactivation, is a localized, painful, vesicular rash involving one or adjacent dermatomes. The incidence of herpes zoster increases with age or immunosuppression. The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins. VZV is found in a worldwide geographic distribution but is more prevalent in temperate climates. Primary VZV infection elicits immunoglobulin G (IgG), IgM, and IgA antibodies, which bind to many classes of viral proteins. Virus-specific cellular immunity is critical for controlling viral replication in healthy and immunocompromised patients with primary or recurrent VZV infections. Rapid laboratory confirmation of the diagnosis of varicella or herpes zoster, which can be accomplished by detecting viral proteins or DNA, is important to determine the need for antiviral therapy. Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster. Passive antibody prophylaxis with varicella-zoster immune globulin is indicated for susceptible high-risk patients exposed to varicella. A live attenuated varicella vaccine (Oka/Merck strain) is now recommended for routine childhood immunization.

Clostridial enteric diseases of domestic animals.

Abstract: INTRODUCTION 216 CLOSTRIDIUM PERFRINGENS 216 Introduction 216 Major Toxins 216 Disease and Pathogenesis by Toxin Type 217 Type A 218 Type B 219 Type C 219 Type D 220 Type E 220 Enterotoxigenic C. perfringens 221 Reports of untyped C. perfringens 221 Prophylaxis and Therapy 222 Diagnosis 222 CLOSTRIDIUM SEPTICUM 223 Introduction 223 Virulence Attributes and Pathogenesis of Enteric Disease 223 Prophylaxis and Therapy 224 Diagnosis 224 CLOSTRIDIUM DIFFICILE 224 CLOSTRIDIUM SPIROFORME 225 CLOSTRIDIUM COLINUM 226 REFERENCES 226

Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates.

Abstract: Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch9s postulates created a scientific standard for causal evidence that established the credibility of microbes as pathogens and led to the development of modern microbiology. In more recent times, Koch9s postulates have evolved to accommodate a broader understanding of the host-parasite relationship as well as experimental advances. Techniques such as in situ hybridization, PCR, and representational difference analysis reveal previously uncharacterized, fastidious or uncultivated, microbial pathogens that resist the application of Koch9s original postulates, but they also provide new approaches for proving disease causation. In particular, the increasing reliance on sequence-based methods for microbial identification requires a reassessment of the original postulates and the rationale that guided Koch and later revisionists. Recent investigations of Whipple9s disease, human ehrlichiosis, hepatitis C, hantavirus pulmonary syndrome, and Kaposi9s sarcoma illustrate some of these issues. A set of molecular guidelines for establishing disease causation with sequence-based technology is proposed, and the importance of the scientific concordance of evidence in supporting causal associations is emphasized.

Epidemiology of nosocomial fungal infections.

Abstract: This paper briefly reviews the current knowledge of the epidemiology and modes of transmission of nosocomial fungal infections and some of the therapeutic options for treating these diseases. In the mid-1980s, many institutions reported that fungi were common pathogens in nosocomial infections. Most, if not all, hospitals care for patients at risk for nosocomial fungal infections. The proportion in all nosocomial infections reportedly caused by Candida spp. increased from 2% in 1980 to 5% in 1986 to 1989. Numerous studies have identified common risk factors for acquiring these infections, most of which are very common among hospitalized patients; some factors act primarily by inducing immunosuppression (e.g., corticosteroids, chemotherapy, malnutrition, malignancy, and neutropenia), while others primarily provide a route of infection (e.g., extensive burns, indwelling catheter), and some act in combination. Non-albicans Candida spp., including fluconazole-resistant C. krusei and Torulopsis (C.) glabrata, have become more common pathogens. Newer molecular typing techniques can assist in the determination of a common source of infection caused by several fungal pathogens. Continued epidemiologic and laboratory research is needed to better characterize these pathogens and allow for improved diagnostic and therapeutic strategies.

Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

Abstract: In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

Blastocystis hominis revisited.

Abstract: Blastocystis hominis is a unicellular organism found commonly in the intestinal tract of humans and many other animals. Very little is known of the basic biology of the organism, and controversy surrounds its taxonomy and pathogenicity. There morphological forms (vacuolar, granular, and ameboid) have been recognized, but recent studies have revealed several additional forms (cyst, avacuolar, and multivacuolar). The biochemistry of the organism has not been studied to any extent, and organelles and structures of unknown function and composition are present in the cells. Several life cycles have been proposed but not experimentally validated. The form used for transmission has not been defined. Infections with the organism are worldwide and appear in both immunocompetent and immunodeficient individuals. Symptoms generally attributed to B. hominis infection are nonspecific, and the need for treatment is debated. If treatment appears warranted, metronidazole is suggested as the drug of choice, although failures of this drug in eradicating the organism have been reported. Infection is diagnosed by light microscopic examination of stained smears or wet mounts of fecal material. Most laboratories identify B. hominis by observing the vacuolar form, although morphological studies indicate that other forms, such as the cyst form and multivacuolar form, also should be sought for diagnosis.

Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum.

Abstract: The pathogenic potential of Fusobacterium nucleatum and its significance in the development of periodontal diseases, as well as in infections in other organs, have gained new interest for several reasons. First, this bacterium has the potential to be pathogenic because of its number and frequency in periodontal lesions, its production of tissue irritants, its synergism with other bacteria in mixed infections, and its ability to form aggregates with other suspected pathogens in periodontal disease and thus act as a bridge between early and late colonizers on the tooth surface. Second, of the microbial species that are statistically associated with periodontal disease, F. nucleatum is the most common in clinical infections of other body sites. Third, during the past few years, new techniques have made it possible to obtain more information about F. nucleatum on the genetic level, thereby also gaining better knowledge of the structure and functions of the outer membrane proteins (OMPs). OMPs are of great interest with respect to coaggregation, cell nutrition, and antibiotic susceptibility. This review covers what is known to date about F. nucleatum in general, such as taxonomy and biology, with special emphasis on its pathogenic potential. Its possible relationship to other periodontal bacteria in the development of periodontal diseases and the possible roles played by OMPs are considered.

Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites.

Abstract: Coccidiosis, an intestinal infection caused by intracellular protozoan parasites belonging to several different species of Eimeria, seriously impairs the growth and feed utilization of livestock and poultry. Host immune responses to coccidial infection are complex. Animals infected with Eimeria spp. produce parasite-specific antibodies in both the circulation and mucosal secretions. However, it appears that antibody-mediated responses play a minor role in protection against coccidiosis. Furthermore, there is increasing evidence that cell-mediated immunity plays a major role in resistance to infection. T lymphocytes appear to respond to coccidial infection through both cytokine production and a direct cytotoxic attack on infected cells. The exact mechanisms by which T cells eliminate the parasites, however, remain unclear. Although limited information is available on the intestinal immune system of chickens, gut lymphoid tissues have evolved specialized features that reflect their role as the first line of defense at mucosal surfaces, including both immunoregulatory cells and effector cells. This review summarizes our current understanding of the avian intestinal immune system and mucosal immune responses to Eimeria spp., providing an overview of the complex cellular and molecular events involved in intestinal immune responses to enteric pathogens.

Infections and antibiotic resistance in nursing homes.

Abstract: Infections occur frequently in nursing home residents. The most common infections are pneumonia, urinary tract infection, and skin and soft tissue infection. Aging-associated physiologic and pathologic changes, functional disability, institutionalization, and invasive devices all contribute to the high occurrence of infection. Antimicrobial agent use in nursing homes is intense and usually empiric. All of these factors contribute to the increasing frequency of antimicrobial agent-resistant organisms in nursing homes. Programs that will limit the emergence and impact of antimicrobial resistance and infections in nursing homes need to be developed.

Identification methods for campylobacters, helicobacters, and related organisms.

Abstract: The organisms which are referred to as campylobacteria are associated with a diverse range of diseases and habitats and are important from both clinical and economic perspectives. Accurate identification of these organisms is desirable for deciding upon appropriate therapeutic measures, and also for furthering our understanding of their pathology and epidemiology. However, the identification process is made difficult because of the complex and rapidly evolving taxonomy, fastidious nature, and biochemical inertness of these bacteria. These problems have resulted in a proliferation of phenotypic and genotypic methods for identifying members of this group. The purpose of this review is to summarize the problems associated with identifying campylobacteria, critically appraise the methods that have been used for this purpose, and discuss prospects for improvements in this field.

Immunopathogenesis of recurrent vulvovaginal candidiasis.

Abstract: Recurrent vulvovaginal candidiasis (RVVC) is a prevalent opportunistic mucosal infection, caused predominantly by Candida albicans, which affects a significant number of otherwise healthy women of childbearing age. Since there are no known exogenous predisposing factors to explain the incidence of symptomatic vaginitis in most women with idiopathic RVVC, it has been postulated that these particular women suffer from an immunological abnormality that prediposes them to RVVC. Because of the increased incidence of mucosal candidiasis in individuals with depressed cell-mediated immunity (CMI), defects in CMI are viewed as a possible explanation for RVVC. In this review, we attempt to place into perspective the accumulated information regarding the immunopathogenesis of RVVC, as well as to provide new immunological perspectives and hypotheses regarding potential immunological deficiencies that may predispose to RVVC and potentially other mucosal infections by the same organism. The results of both clinical studies and studies in an animal model of experimental vaginitis suggest that systemic CMI may not be the predominant host defense mechanism against C. albicans vaginal infections. Rather, locally acquired mucosal immunity, distinct from that in the peripheral circulation, is now under consideration as an important host defense at the vaginal mucosa, as well as the notion that changes in local CMI mechanism(s) may predispose to RVVC.

Carrier effects on biological activity of amphotericin B.

Abstract: Amphotericin B (AmB), the drug of choice for the treatment of most systemic fungal infections, is marketed under the trademark Fungizone, as an AmB-deoxycholate complex suitable for intravenous administration. The association between AmB and deoxycholate is relatively weak; therefore, dissociation occurs in the blood. The drug itself interacts with both mammalian and fungal cell membranes to damage cells, but the greater susceptibility of fungal cells to its effects forms the basis for its clinical usefulness. The ability of the drug to form stable complexes with lipids has allowed the development of new formulations of AmB based on this property. Several lipid-based formulations of the drug which are more selective in damaging fungal or parasitic cells than mammalian cells and some of which also have a better therapeutic index than Fungizone have been developed. In vitro investigations have led to the conclusion that the increase in selectivity observed is due to the selective transfer of AmB from lipid complexes to fungal cells or to the higher thermodynamic stability of lipid formulations. Association with lipids modulates AmB binding to lipoproteins in vivo, thus influencing tissue distribution and toxicity. For example, lipid complexes of AmB can be internalized by macrophages, and the macrophages then serve as a reservoir for the drug. Furthermore, stable AmB-lipid complexes are much less toxic to the host than Fungizone and can therefore be administered in higher doses. Experimentally, the efficacy of AmB-lipid formulations compared with Fungizone depends on the animal model used. Improved therapeutic indices for AmB-lipid formations have been demonstrated in clinical trials, but the definitive trials leading to the selection of an optimal formulation and therapeutic regimen have not been done.

Virulence factors of medically important fungi.

Abstract: Human fungal pathogens have become an increasingly important medical problem with the explosion in the number of immunocompromised patients as a result of cancer, steroid therapy, chemotherapy, and AIDS. Additionally, the globalization of travel and expansion of humankind into previously undisturbed habitats have led to the reemergence of old fungi and new exposure to previously undescribed fungi. Until recently, relatively little was known about virulence factors for the medically important fungi. With the advent of molecular genetics, rapid progress has now been made in understanding the basis of pathogenicity for organisms such as Aspergillus species and Cryptococcus neoformans. The twin technologies of genetic transformation and "knockout" deletion construction allowed for genetic tests of virulence factors in these organisms. Such knowledge will prove invaluable for the rational design of antifungal therapies. Putative virulence factors and attributes are reviewed for Aspergillus species, C. neoformans, the dimorphic fungal pathogens, and others, with a focus upon a molecular genetic approach. Candida species are excluded from coverage, having been the subject of numerous recent reviews. This growing body of knowledge about fungal pathogens and their virulence factors will significantly aid efforts to treat the serious diseases they cause.

Rotavirus vaccines: an overview.

Abstract: Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both developed and developing countries. These studies led to the concept that a multivalent vaccine that represented each of the four epidemiologically important VP7 serotypes might be necessary to induce protection in young infants, the target population for vaccination. Human-animal rotavirus reassortants whose gene encoding VP7 was derived from their human rotavirus parent but whose remaining genes were derived from the animal rotavirus parent were developed as vaccine candidates. The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotype 1, 2, and 4 specificity. Preliminary efficacy trial results in the United States have been promising, whereas a study in Peru has shown only limited protection. Human-bovine reassortant vaccines, including a candidate that contains the VP4 gene of a human rotavirus (VP4 serotype 1A), are also being studied.

Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease.

Abstract: 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.

Bartonella (Rochalimaea) quintana infections.

Abstract: Bartonella (formerly Rochalimaea) quintana is the etiological agent of trench fever, a disease extensively reported during the World Wars. Recent molecular biology approaches have allowed dramatic extension of the spectrum of Bartonella infections. B. quintana is now also recognized as an etiological agent of fever and bacteremia, endocarditis, bacillary angiomatosis, and chronic lymphadenopathy. Human immunodeficiency virus-infected patients and/or homeless people are the most vulnerable to infection. Poverty and louse infestation were the main epidemiological factors associated with B. quintana infections during wartime. Although poverty and chronic alcoholism have been associated with modern cases of trench fever and bacteremia due to B. quintana in Europe and the United States, vectors for B. quintana have not been clearly identified and B. quintana has not been isolated from modern-day lice. Microscopic bacillary angiomatosis lesions are characterized by tumor-like capillary lobules, with proliferating endothelial cells. In vitro experiments have shown that B. quintana survives within endothelial cells and stimulates cell proliferation. These observations, together with the finding that lesions may regress when antibiotic therapy is administered, strongly suggest that B. quintana itself stimulates angiogenesis. Bartonella infections are characterized by a high frequency of relapses after brief courses of antibiotic therapy. It is to be noted that in vitro, although Bartonella species are highly susceptible to antibiotics, only the aminoglycosides have proved to be bactericidal. However, the most effective antibiotic regimen for Bartonella infections remains to be established.

Clinical aspects of infection with Trichinella spp.

Abstract: Isolated cases and outbreaks of infection with Trichinella spp. occur frequently throughout the world, sometimes resulting in fatalities. The clinical presentations of signs and symptoms are remarkably constant for most of the species of Trichinella, but in infections with Trichinella nativa and Trichinella britovi, classical symptoms of trichinellosis may be absent. It is important to be able to correlate the clinical presentation of trichinellosis with the life cycle of these helminths in order to make an accurate diagnosis. Knowledge of the epidemiology of the disease enables the physician to identify other potential cases, since most epidemics can be traced back to a common source of raw or undercooked meat. A comprehensive summary relating the most important clinical variables is presented graphically for easy reference to the text. Symptoms and signs are considered in relation to severity of infection. Laboratory findings and diagnostic techniques, including new modalities (e.g., DNA and antigen detection), are discussed. A discussion of treatment and preventive measures concludes our review.

Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans.

Abstract: Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.

Molecular biology and pathogenesis of animal lentivirus infections.

Abstract: 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.

Activation of the complement system by pathogenic fungi.

Abstract: Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

Detection of infection or infectious agents by use of cytologic and histologic stains.

Abstract: A wide variety of stains are useful for detection of different organisms or, for viruses, the cytopathologic changes they induce, in smears prepared directly from clinical specimens and in tissue sections. Other types of stains, such as hematoxylin and eosin, are used routinely to stain tissue sections and are most valuable for assessing the immunologic response of the host to the invading pathogen. In many cases, the pattern of inflammation provides important clues to diagnosis and helps to guide the selection of additional "special" stains used predominantly for diagnosis of infectious diseases. A stain may be nonspecific, allowing detection of a spectrum of organisms, as do the Papanicolaou stain and silver impregnation methods, or detection of only a limited group of organisms, as do the different acid-fast techniques. Some nonspecific stains, such as the Gram stain, are differential and provide valuable preliminary information concerning identification. Immunohistochemical stains, on the other hand, are specific for a particular organism, although in some cases cross-reactions with other organisms occur. Despite the wealth of information that can be gleaned from a stained smear or section of tissue, however, the specific etiology of an infection often cannot be determined on the basis of only the morphology of the organisms seen; culture data are essential and must be considered in the final diagnosis.

New aspects of rabies with emphasis on epidemiology, diagnosis, and prevention of the disease in the United States.

Abstract: INTRODUCTION AND HISTORICAL BACKGROUND 166 THE VIRUS 166 EPIDEMIOLOGY 167 CLINICAL DISEASE 171 DIAGNOSIS 173 PREVENTION AND CONTROL 173 Humans 173 Domestic Animals 173 Wildlife 174 FUTURE DIRECTIONS 175 REFERENCES 175

Pneumocystis carinii: what is it, exactly?

Abstract: The identity of Pneumocystis carinii has been uncertain for many years. Until recently, it was widely regarded to be a protozoan because it does not grow in culture and is not susceptible to antifungal drugs. Although these and a number of other phenotypic characteristics of P. carinii differ from those of typical fungi, analysis of DNA sequences has shown that P. carinii is a member of the fungal lineage of eukaryotes. However, a close phylogenetic relative of P. carinii has not yet been found. Analysis of gene sequences has also revealed that P. carinii is not a single entity but that the genus Pneumocystis contains a complex group of organisms. P. carinii organisms from one host species do not grow when introduced into another host species, and P. carinii isolates from different host species are more genetically divergent from one another than might be expected for members of the same species. Genetic variation of a lesser degree also occurs among P. carinii organisms from the same host species, suggesting that it may be possible to identify strains and to conduct transmission and epidemiological studies. Results of early studies exploiting genetic variation among P. carinii isolates from patients have suggested that recurrent P. carinii pneumonia may not always be caused by reactivation of latent organisms, as is commonly believed. However, other features of P. carinii suggest that this microbe has established a long-term relationship with its host. A striking new development in this regard is the discovery of a genetic system that is designed to allow variation in the structure of a major antigen on the surface of P. carinii.

Update: infant botulism.

Abstract: INTRODUCTION 119 FORMS OF BOTULISM 119 ETIOLOGIC AGENTS OF INFANT BOTULISM 119 Clostridium botulinum 119 Other Botulinum Toxin-Producing Clostridia 120 CLINICAL ASPECTS 120 Clinical Symptoms 120 Diseases and Conditions Confused with Infant Botulism 120 Management of Hospitalized Patients 120 Hospitalization Costs 120 Link to Sudden Infant Death Syndrome 120 LABORATORY CONFIRMATION OF BOTULISM 121 Collection of Specimens 121 Shipment of Specimens to the Laboratory 121 Laboratory Testing of Specimens 121 PATHOGENICITY 121 Nature of the Neurotoxins 121 Pathogenesis 121 Mouse Models 122 INCIDENCE 122 ENVIRONMENTAL ASPECTS 122 Habitat of C. botulinum 122 Sources of C. botulinum for Infants 122 RISK FACTORS ASSOCIATED WITH INFANT BOTULISM 123 CONCLUDING COMMENTS 123 ACKNOWLEDGMENTS 124 REFERENCES 124

Current status of poliovirus infections.

Abstract: Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus.

Pediatric human immunodeficiency virus infection.

Abstract: In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies.

Transgenic cell lines for detection of animal viruses.

Abstract: Rapid diagnostic assays based on direct detection of viral antigen or nucleic acid are being used with increasing frequency in clinical virology laboratories. Virus culture, however, remains the only way to detect infectious virus and to analyze clinically relevant viral phenotypes, such as drug resistance. Growth of viruses in cell culture is labor intensive and time-consuming and requires the use of many different cell lines. Transgenic technology, together with increasing knowledge of the molecular pathways of virus replication, offers the possibility of using genetically modified cell lines to improve virus growth in cell culture and to facilitate detection of virus-infected cells. Genetically modifying cells so that they express a reporter gene only after infection with a specific virus can allow the detection of infectious virus by rapid and simple enzyme assays such as beta-galactosidase assays without the need for antibodies. Although transgenic cells have recently been successfully used for herpes simplex virus detection, much more work needs to be done to adapt this technology to other human viral pathogens such as cytomegalovirus and respiratory viruses. This review offers some strategies for applying this technology to a wide spectrum of animal viruses.

History of medical mycology in the united states.

Abstract: INTRODUCTION 237 THE ERA OF DISCOVERY, 1894 TO 1919 237 Overview, 1894 to 1900 237 Scientific Contributions, 1894 to 1900 237 Blastomycosis 237 Coccidioidomycosis 239 Sporotrichosis 239 Mycotic mycetoma 239 Dermatophytosis 239 Overview, 1900 to 1919 239 Scientific Contributions, 1900 to 1919 239 Coccidioidomycosis 239 Sporotrichosis 240 Blastomycosis 240 Histoplasmosis 240 Chromoblastomycosis 240 Zygomycosis 241 THE FORMATIVE YEARS, 1920 TO 1949 241 Overview, 1920 to 1929 241 Scientific Contributions, 1920 to 1929 241 Mycotic mycetoma 241 Cryptococcosis 241 Histoplasmosis 241 Sporotrichosis, an occupational disease 241 Laboratory diagnosis 242 Skin test development 242 First training and research center 242 Overview, 1930 to 1939 242 Scientific Contributions, 1930 to 1939 242 Coccidioidomycosis 242 Meningeal infections 243 Histoplasmosis 243 Chromoblastomycosis 243 Taxonomy and classification 243 Fungal endotoxins 244 Training and research centers 244 Overview, 1940 to 1949 244 Scientific Contributions, 1940 to 1949 244 Systemic candidiasis 244 Zygomycosis 244 Mycotic mycetoma 244 Pseudallescheriasis 244 Epidemiology and ecology 245 Laboratory diagnosis 245 Antifungal agents 245 Training and research centers 245 THE ADVENT OF ANTIFUNGAL AND IMMUNOSUPPRESSIVE THERAPIES, 1950 TO 1969 246 Overview, 1950 to 1959 246 Scientific Contributions, 1950 to 1959 246 Opportunistic fungal infections in compromised patients 246