Clinical , Microbiology , Reviews
VOLUME 12 • JANUARY 1999 • NUMBER i
Genital Herpes: Review of the Epidemic and Potential Use of Type-
Specific Serology. Rhoda L. Ashley and Anna Wald ........................................... 1-8
Association of Rhinovinis Infections with Asthma. James E. Gem
and William W. Busse .................................................................... 9-18
Role of Heat Shock Proteins in Protection from and Pathogenesis of
Infectious Diseases. Ulrich Zligel and Stefan H. E. Kaufmann . ............................. 19-39
Current and Emerging Azoic Antifungal Agents. Daniel J.
Sheehan, Christopher A. Hitchcock, and Carol M. Sibley ...................................... 40-79
Candida glabrata: Review of Epidemiology, Pathogenesis, and Clinical
Disease with Comparison to C. albicans. Paul L. Fidel, Jr.,
Jose A. Vazquez, and Jack D. Sobel........................................................... 80-96
Relationship between Schistosomiasis and Bladder Cancer. M. H.
Mostafa, S. A. Sheweita, and P. J. O'Connor. ............................................................. 97-111
History of Sleeping Sickness in East Africa. Geoff Hide...................................... 112-125
The Evolutionary Biology and Population Genetics Underlying Fungal
Strain Typing. John W. Taylor, David M. Geiser, Austin Burt,
and Vassiliki Koufopanou. .......................................................................................... 126-146
Antiseptics and Disinfectants: Activity, Action, and Resistance.
Gerald McDonnell and A. Denver Russell ................................................ 147-179
Diarrhea-Associated Diffusely Adherent Escherichia coli. Chantal
Le Bouguenec.................................................................................... 180-181
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Clinical Microbiology Reviews
VOLUME: 12 APRIL 1999 NUMBER: 2,
Clinical Microbiology Reviews: Genesis of a Journal.
Josephine A. Morello 183-186
Summary: In 1986 planning for a new ASM review journal. Clinical Microbiology Reviews
(CMR), began. CMR would publish articles primarily of interest to persons concerned with
pathogenesis, laboratory diagnosis, epidemiology, and control of human and vcterinaiy patho-
gens. The first issue was published in January 1988, with quarterly publication since then. 'l'he
journal quickly became successfill in terms of subscribers and impact on the field, earning a
strong national and international reputation. The achievements of CMR are owed to many
persons, including the editorial board, the production team, and especially the contributing authors.
Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some
Biologic Features. Ameeta E. Singh and Barbara Romanowski 187-209
Summary: Syphilis is a chronic disease with a waxing and waning course, the manifestations of
which have been described for centuries. It occurs worldwide, and the incidence varies signif-
icantly with geographic location. Transmission is mainly by sexual contact. The causative
organism, Treponema pallidum, was first described in 1905, lnit because of the inability to
culture the organism and the limitations of direct microscopy, serologic testing is the mainsUly
of laboratory diagnosis. The disease has been arbitrarily divided into several stages. The primary
stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by
a polymorphic rash, lymphadenopatlly, and other systemic manifestations. A variable asymp-
tomatic latent period follows, which for epidemiologic purposes is divided into early (<l year)
and lute (>l year) stages. The early stages (prinmy, secondly, and early latent) are potentially
infectious. The tertiary stage is the most destructive and is marked by cardiovascular and
neurologic sequelae and gummatous involvement of any organ system. Congenital infection
may result in protean early or late manifestations. Unlike many other bacteria causing infectious
diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.
Chagas Disease and the Autoimmunity Hypothesis. Felipe
Kierszenbaum. 210-223
Summany: The notion that the pathology of Chagas' disease has an autoimmune component
was initially based on the finding of circulating antibodies binding heart tissue antigens in
patients and mice chronically infected with Trypanosoma cruzi. Later, T lymphocytes reactive
with heart or nerve tissue antigens were found in chagasic mice and patients, extending the
concept to include cell-mediated immunity. However, there is disagreement about whether the
observed immunologic autoreactivities are triggered by T. cruzi epitopes and then affect host
tissue antigens by virtue of molecular mimiciy or are elicited by host antigens exposed to
lymphocytes after tissue damage caused by the parasite. There is also disagreement about the
relevance of immunologic autoreactivities to the pathogenesis of Chagas' disease because of the
lack of reproducibility of some key reports supporting the autoimmunity hypothesis, conflicting
data from independent laboratories, conclusions invalidated by advances in our understanding
of the immunologic mechanisms underlying cell lysis, and, last hut not least, a lack of direct,
incontrovertible evidence that cross-reacting antibodies or autoreactive cells mediate the typical
pathologic changes associated with human Chagas' disease. The data and views backing and
questioning the autoimmunity hypothesis for Chagas' disease are summarized in this review.
Clinical, Microbial, and Biochemical Aspects of the Exfoliative Toxins
Causing Staphylococcal Scalded-Skin Syndrome. Sharnez
Ladhani, Christopher L. Joannou, Denise P. Lochrie, Robert W.
Evans, and Susan M. Poston 224-242
Summary: The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative
agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin disorder that
predominantly affects children. Clinical features of SSSS vary along a spectrum, ranging from
a few localized blisters to generalized exfoliation covering almost the entire body. The toxins act
specifically at the zona granulosa of the epidermis to produce the characteristic exfoliation,
although the mechanism by which this is achieved is still poorly understood. Despite the
availability of antibiotics, SSSS cames a significant mortality rate, particularly among neonates
with secondary complications ofcpidcnnal loss and among adults with underlying diseases. The
aim of this article is to provide a comprehensive review of the literature spanning more than a
century and to cover all aspects of the disease. The epidemiology, clinical features, potential
complications, risk factors, susceptibility, diagnosis, differential diagnoses, investigations cur-
rently available, treatment options, and preventive measures are all discussed in detail. Recent
crystallographic data on the toxins lias provided us with a clearer and more defined approach
to studying the disease. Understanding their mode of action has important implications in future
treatment and prevention of SSSS and other diseases, and knowledge of their specific site of
action may provide a useful tool for physiologists, dermatologists, and pharmacologists.
Molecular Techniques for Detection, Species Differentiation, and
Phylogenetic Analysis of Microsporidia. Caspar Franzen and
Andreas Muller 243-285
Summary: Microsporidia are obligate intracellularprotozoan parasites that infect a broad range
of vertebrates and invertebrates. These parasites are now recognized as one of the most common
pathogens in human immunodeficiency virus-infected patients. For most patients with infec-
tious diseases, microbiological isolation and identification techniques offer the most rapid and
specific determination of the etiologic agent. This is not a suitable procedure for microsporidia,
which are obligate intracellular parasites requiring cell culture systems for growth. Therefore, the
diagnosis of microsporidiosis currently depends on morphological demonstration of the organ-
isms themselves. Although the diagnosis ofmicrosporidiosis and identification of microsporidia
by light microscopy have greatly improved during the last few years, species differentiation by
these techniques is usually impossible and transmission electron microscopy may be necessary.
Immunfluorescent-staining techniques have been developed for species differentiation of mi-
crosporidia, but the antibodies used in these procedures are available only at research labora-
tories at present. During the last 10 years, the detection of infectious disease agents has begun
to include the use of nucleic acid-based technologies. Diagnosis of infection caused byparasitic
organisms is the last field of clinical microbiology to incorporate these techniques and molec-
ular techniques (e.g., PCR and hybridization assays) have recently been developed for the
detection, species differentiation, and phylogenetic analysis of microsporidia. In this paper we
review human microsporidial infections and describe and discuss these newly developed mo-
lecular techniques.
Resistance of Human Cytomegalovirus to Antiviral Drugs. Alejo
Erice 286-297
Summary: Resistance of cytomegalovirus (CMV) to antiviral agents is a well-recognized phe-
nomenon that has been observed in the laboratory and in the clinical setting. Infections caused
by antiviral-resistant CMV have been found exclusively among immunocompromised individ-
uals, including patients with AIDS, bone marrow and solid-organ transplant recipients, and
patients with hematologic malignancies, and in individuals with primary immunodeficiencies.
The majority of these infections have been described to occur in patients with AIDS receiving
prolonged antiviral therapy for CMV end-organ disease. Antiviral agents currently licensed for
the treatment of CMV infections include ganciclovir, foscarnet, and cidofovir. Resistance of
CMV to ganciclovir is related to mutations in the UL97 region of the viral genome and/or
mutations in the viral DNA polymerase. Resistance to foscarnet and cidofovir is associated with
mutations in the viral DNA polymerase. Antiviral susceptibility of CMV strains containing DNA
polymerase mutations is dependent on the region of the DNA polymerase where the mutations
are located. Some DNA polymerase mutant viruses are cross-resistant to ganciclovir, foscarnet,
and cidofovir. The recognition that specific UL97 and UL54 mutations are associated with
resistance to antiviral agents has led to the development of molecular methods for detection of
mutant viruses. This article reviews the mechanisms of resistance of CMV to antiviral agents,
the laboratory methods for detection of resistant CMV, and the clinical aspects of infections
caused by antiviral-resistant CMV.
Respiratory Syncytial Virus Infection: Immune Response,
Immunopathogencsis, and Treatment. Joseph B. Domachowske
and Helene F. Rosenberg 298-309
Summary: Respiratory syncytial virus (RSV) is the single most important cause of lower
respiratory tract infection during infancy and early childhood. Once RSV infection is estab-
lished, the host immune response includes the production of virus-neutralizing antibodies and
T-cell-specific immunity. The humoral immune response normally results in the development of
anti-RSV neutralizing-antibody tilers, but these are often suboptimal during an infant's initial
infection. Even when the production of RSV neutralizing antibody following RSV infection is
robust, humoral immunity wanes over time. Reinfection during subsequent seasons is common.
The cellular immune response to RSV infection is also important for the clearance of virus. This
immune response, vital for host defense against RSV, is also implicated in the immunopatho-
genesis of severe lower respiratory tract RSVbronchiolitis. Many details of the immunology and
immunopathologic mechanisms of RSV disease known at present have been learned from
rodent models of RSV disease and are discussed in some detail. In addition, the roles of
immunoglobulin E, histamine, andeosinophils in the immunopathogenesis of RSVdisease are
considered. Although the treatment of RSV bronchiolitis is primarily supportive, the role of
ribavirin is briefly discussed. Novel approaches to the development of new antiviral drugs with
promising anti-RSV activity in vitro are also described.
Aspergillusfumigatus and Aspergillosis. Jean-Paul Latge 310-350
Summary :Aspergillusfumigatus is one of the most ubiquitous of the airborne saprophytic fungi.
Humans and animals constantly inhale numerous conidia of this fungus. The conidia are
normally eliminated in the immunocompetent host by innate immune mechanisms, and as-
pergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the
only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak
pathogen. With increases in the number of immunosuppressed patients, however, there has been
a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common
mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the
diseases it causes, [ncilidetf are discussions of (i) genomic and molecular characterization of
the organism, (ii) clinica! and Itihonnoty methods available for the diagnosis ofaspergillosis in
immunocompetent and immunocomf)rofnised hosts, (Hi) identification of host and fungal
j'nctors (hat piny a role in the eslahlisinncnt of the fungus in vivo, and (iv) problems associated
with antijungal therapy.
Vpdate on Diagnosis, Management, and Prevention of Hepatitis B
Virus Infection. Francis J. Mahoncy 351-366
Summary: 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 I million persons die each year from HBV-related chronic liver
disease. In (he past decade, significant progress in the understanding of the molecular virology
and pathogenesis ofHBVinfection has been made. In addition, effective treatment modalities
have (wen developed for persons with chronic infection. Worldwide, prevention of HBV trans-
mission 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 im-
munization programs by 1997. Cuirently, 80 countries have done so and several others are
planning lo. Many countries have reported dramatic reductions in tile prevalence of chronic
HBV infection among children born since the hepatits 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.
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Clinical Microbiology Reviews
VOLUME 12 , JULY 1999 , NUMBER 3
Human Cytomegalovirus and Human Herpesvirus 6 Genes That
Transform and Transactivate. Jay Doniger, Sumitra Muralidhar,
and Leonard J. Rosenthal. .................................................................................... 367-382
Intranasal Antibody Prophylaxis for Protection against Viral Disease.
Richard Weltzin and Thomas P. Monath. ............................................................... 383-393
Acquisition, Transport, and Storage of Iron by Pathogenic Fungi.
Dexter H. Howard .......................................................................................... 394-404
Molecular Basis of the Interaction of Salmonella with the Intestinal
Mucosa. K. Heran Darwin and Virginia L. Miller. .......................................... 405-428
Cellular Biology of Prion Diseases. David A. Harris. .................................. 429-444
Pathogenesis of Onchocercal Keratitis (River Blindness). Laune R.
Hall and Eric Peariman.................................................................................... 445-453
Developments in Fungal Taxonomy. Josep Guarro, Josepa Gene,
and Alberto M. Stchigel .................................................................................. 454-500