Clinical Microbiology Reviews

A Publication of the American Society for Microbiology

VOLUME 7 * OCTOBER 1994 * NUMBER 4

CONTENTS/SUMMARIES

Infectious Diseases Associated with Molluscan Shellfish Consumption. Scott R. Rippey ...... 419-425 Summary: A history of shellfish-vectored illnesses (i.e., those associated with consumption of clams, oysters, mussels, and scallops) occuring in the past nine decades is presented. Typhoid fever was a significant public health problem among consumers of raw molluscan shellfish earlier in this century. The development of more effective sewage treatment procedures and the institution of a national program following these outbreaks led to a series of measures which eventually eliminated shellfish-associated typhoid fever. Present-day problems associated with this food source still involve some wastewaterbome bacterial illnesses. However, the principal public health concems are with wastewater-derived viralpathogens and with bacterial agents of an environmental origin. The nature, occurrence, and magnitude of these public health problems are described.

Human Microsporidial Infections. Rainer Weber, Ralph T. Bryan, David A. Schwartz, and Robert L. Owen...... 426-461 Summary: are obligate intracellular -forming protozoalparasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes ofvertebrates. More than 100 microsporidial genera and almost 1, 000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations ofmicrosporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Amongpersons not infected with human virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to , an important cause of chronic and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but

Continued on following page Contitlnued from precedinig page

symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic- drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured wit/i albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing antimicrosporidial drugs. Furthermore, molecular techniques are being developedfor diagnostic purposes, taxonomic classification, and analysis ofphylogenetic relationships ofmicrosporidia. Virulence of Enterococci. Bradley D. Jett, Mark M. Huycke, and Michael S. Gilmore...... 462-478 Summary: Enterococci are commensal organisms well suited to survival in intestinal and vaginal tracts and the oral cavity. However, as for most bacteria described as causing human disease, enterococci also possess properties that can be ascribed roles in pathogenesis. The natutral ability of enterococci to readily acquire, accumulate, and share extrachromosomal elements encoding virulence traits or antibiotic resistance genes lends advantages to their survival under unusual environmental stresses and in part explains their increasing importance as nosocomial . This review discusses the current understanding of enterococcal virulence relating to (i) adherence to host tissues, (ii) invasion and abscess formation, (iii) factors potentially relevant to modulation of host inflammatory responses, and (iv) potentially toxic secreted products. Aggregation substance, surface carbohydrates, or fibronectin-binding moieties may facilitate adherence to host tissues. Enterococcus faecalis appears to have the capacity to translocate across intact intestinal mucosa in models of antibiotic-induced superinfection. Extracellular toxins such as cytolysin can induce tissue damage as shown in an endophthalmitis model, increase mortality in combination with aggregation substance in an endocarditis model, and cause systemic toxicity in a murine peritonitis model. Finally, lipoteichoic acid, superoxide production, or pheromones and corresponding peptide inhibitors each may modulate local inflammatory reactions. Taxonomy, Biology, and Clinical Aspects of Species. Paul E. Nelson, M. Cecilia Dignani, and Elias J. Anaissie ...... 479-504 Sumnmary: There are several taxonomic systems available for identifying Fusarilum species. The philosophy used in each taxonomic system is discussed as well as problems encountered in working with Fusarium species in culture. Fusarium species are toxigenic, and the mycotoxins prodluced by these organisms are often associated with animal and human diseases. The implications for the association of the carcinogens, filmonisins, produced by Fusarilum moniliforne and other Fusarium species with human diseases are discussed. Foreign-body- associated fusarial infection such as keratitis in contact lens wearers, , skin infections, and disseminated multiorgan infections are discussed. Disseminated flisarial hyalohyphomycosis has emerged as a significant, usually fatal infection in the immunocom- promised host. Successful outcome is determined by the degree of immunosuppression, the extent of the infection, and the presence of a removable focus such as an indwelling central venous catheter. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory'findings, which should lead to prompt therapy, probably with one ofthe newer antifungal agents. Perhaps the use ofsuch agents or the use ofcolony-stimulating factors may improve the outcome of this devastating infection. However, until new approaches for treatment develop, effective preventive measures are urgently needed.

Hepatitis C: Progress and Problems. Jennifer A. Cuthbert...... 505-532 Summary: The hepatitis C virus (HCV), a single-stranded RNA virus, is the major cause of posttransfuision hepatitis. HCV isolates differ in nucleotide and amino acid sequences. Nucleotide changes are concentrated in hypervariable regions and may be related to immune selection. In most immunocompetent persons, HCV infection is diagnosed serologically, using antigens from conserved regions. Amplification ofRNA may be necessary to detect infection in immunosuppressed patients. Transmission by known parenteral routes is frequent; other means of spread are less common and may represent inapparent, percutaneous dissemination. Infection can lead to classical acute hepatitis, but most infected persons have no histoty ofacute disease. Once infected, most individuals apparently remain carriers of the virus, with varying degrees ofhepatocyte damage and fibrosis ensuing. Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma. However, disease progression varies widely, from less than 2 years to Continued on following page Continued from preceding page

cirrhosis in some patients to more than 30 years with only chronic hepatitis in others. Determinants important in deciding outcome are unknown. Alpha interferon, which results in sustained remission in selected patients, is the only available therapy. Long-term benefits from such therapy have not been demonstrated. Prevention ofHCV infection by vaccination is likely to be challenging ifongoing viral mutation results in escape from neutralization and clearance. Bronchoscopic Diagnosis of Pneumonia. Vickie S. Baselski and Richard G. Wunderink ...... 533-558

Summary: Lower respiratory tract infections are characterized by significant morbidity and mortality but also by a relative inability to establish a specific etiologic agent on clinical grounds alone. With the recognized shortcomings of expectorated or aspirated secretions toward establishing an etiologic diagnosis, clinicians have increasingly used bronchoscopy to obtain diagnostic samples. A variety of specimen types may be obtained, including bronchial washes or brushes, protected specimen brushings, bronchoalveolar lavage, and transbronchial biopsies. Bronchoscopy has been applied in three primary clinical settings, including the immunocom- promised host, especially human immunodeficiency virus-infected and organ transplant patients; ventilator-associated pneumonia; and severe, nonresolving community- or hospital- acquired pneumonia in nonventilated patients. In each clinical setting, and for each specimen type, specific laboratory protocols are required to provide maximal information. Theseprotocols should provide for the use of a variety ofrapid microscopic and quantitative culture techniques and the use of a variety of specific stains and selective culture to detect unusual organism groups. Current Status of Meningococcal Group B Vaccine Candidates: Capsular or Noncapsular? J. Diaz Romero and I. M. Outschoorn ...... 559-575 Summary: Meningococcal meningitis is a severe, life-threatening infection for which no adequate vaccine exists. Current vaccines, based on the group-specific capsular polysaccha- rides, provide short-term protection in adults against serogroups A and C but are ineffective in infants and do not induce protection against group B strains, the predominant cause of inftction in western countries, because the purified serogroup B polysaccharide fails to elicit human bactericidal antibodies. Because of the poor imunogenicity of group B capsular polysaccharide, different noncapsular antigens have been considered for inclusion in a vaccine against this serogroup: outer membrane proteins, lipooligosaccharides, iron-regulated proteins, Lip, pili, CtrA, and the immunoglobulin A proteases. Altematively, attempts to increase the immunogenicity of the capsular polysaccharide have been made by using noncovalent complexes with outer membrane proteins, chemical modifications, and structural analogs. Here, we review the strategies employed for the development of a vaccine for Neisseria meningitidis serogroup B; the difficulties associated with the different approaches are discussed.

Uses of Flow Cytometry in Virology. James J. McSharry ...... 576-604 Summary: This article reviews some ofthe published applications offlow cytometry for in vitro and in vivo detection and enumeration ofvirus-infected cells. Samplepreparation, fixation, and perneabilization techniques for a number of virus-cell systems are evaluated. The use offlow cytometty for multiparameter analysis of virus-cell interactions for simian virus 40, herpes simplex viruses, human cytomegalovirus, and human immunodeficiency virus and its use for determining the effect ofantiviral compounds on these virus-infected cells are reviewed. This is followed by a brief description of the use of flow cytometry for the analysis of several virus-injected cell systems, including blue tongue virus, hepatitis C virus, avian reticuloendo- theliosis virus, African swine fever virus, woodchuck hepatitis virus, bovine viral diarrhea virus, feline leukemia virus, Epstein-Barr virus, Autographa califomica nuclear polyhedrosis virus, and Friend mlrine leukemia virus. Finally, the use offlow cytometry for the rapid diagnosis of humnan cytomegalovirus and hluman immunodeficiency virus in peripheral blood cells ofacutely infected patients and the use of this technology to monitor patients on antiviral therapy are reviewed. Future prospectsfor the rapid diagnosis ofin vivo viral and bacterial infections byflow cytometry are discussed.