Stephen A. Klotz

Fungal and Parasitic Infections of the Eye

The unique structure of the human eye as well as exposure of the eye directly to the environment renders it vulnerable to a number of uncommon infectious diseases caused by fungi and parasites. Host defenses directed against these microorganisms, once anatomical barriers are breached, are often insufficient to prevent loss of vision. Therefore, the timely identification and treatment of the involved microorganisms are paramount. The anatomy of the eye and its surrounding structures is presented with an emphasis upon the association of the anatomy with specific infection of fungi and parasites. For example, filamentous fungal infections of the eye are usually due to penetrating trauma by objects contaminated by vegetable matter of the cornea or globe or, by extension, of infection from adjacent paranasal sinuses. Fungal endophthalmitis and chorioretinitis, on the other hand, are usually the result of antecedent fungemia seeding the ocular tissue. Candida spp. are the most common cause of endogenous endophthalmitis, although initial infection with the dimorphic fungi may lead to infection and scarring of the chorioretina. Contact lens wear is associated with keratitis caused by yeasts, filamentous fungi, and Acanthamoebae spp. Most parasitic infections of the eye, however, arise following bloodborne carriage of the microorganism to the eye or adjacent structures.

Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine, serine, or alanine patches.

Saccharomyces cerevisiae transformed with Candida albicans ALA1/ALS5 exhibits adherence properties similar to C. albicans. Adherence of the fungi to immobilized proteins involves hydrogen bonds, is stable to shear forces, and is resistant to competition from various biological molecules. The specificity determinants of target recognition in Ala1/Als5p-mediated adherence are not known. To determine features of target recognition, proteins and small peptides were covalently coupled at the N-terminus to the surface of carboxylate-modified magnetic beads. C. albicans yeast cells, germ tubes and pseudohyphae and S. cerevisiae expressing the adhesin, Ala1/Als5p, adhered to beads coated with fibronectin, laminin, type IV collagen, bovine serum albumin, and casein. No adherence to beads was observed if a single amino acid was coupled to the beads. However, 10-mer homopolymers of threonine, serine, and alanine served as ligands for adherence. The presence of a minimum of four contiguous threonine residues in a peptide was required for maximal adherence. Coupling of 10-mer peptides from fibronectin and Ala1/Als5p each possessing 5-7 threonine or serine residues also initiated adherence. On the other hand, a collagen and a fibronectin 10-mer peptide with few threonine and serine residues and lysine at the C-terminus did not serve as adherence ligands. Both of them are converted to adherence ligands by adding threonine or serine residues at the C-terminus or removing the lysine residue and adding threonine residues anywhere in the peptide. The presence of lysine at the C-terminus may have resulted in coupling of the peptides at both the N- and C-termini, thus making the threonine residues inaccessible for adherence. Thus, Ala1/Als5p recognizes patches of certain amino acids, which must be accessible before adherence will occur.

Pityrosporum Folliculitis Its Potential for Confusion With Skin Lesions of Systemic Candidiasis

Development of an erythematous, papulonodular to papulopustular skin eruption in four febrile, immunocompromised patients raised the possibility of a systemic mycosis when Grams stains of unroofed lesions disclosed budding yeasts. Candidiasis, torulopsosis, sporotrichosis, and cryptococcosis were considered in the differential diagnosis, and therapy with amphotericin B was begun. Skin biopsy specimens disclosed fungi to be located exclusively within intact and ruptured hair follicles. Inability of the fungi to grow on media that were not supplemented with lipid and their structure and location all suggested the presence of Pityrosporum sp. When hematogenous dissemination of a mycosis to the skin is suspected, the diagnosis must be based on biopsy specimen demonstration of dermal invasion, ideally with positive cultures. Pityrosporum sp, common skin saprophytes, may produce folliculitis, and be mistaken for pathogenic yeasts.

Gelatin fragments block adherence of Candida albicans to extracellular matrix proteins

The adherence of Candida albicans to extracellular matrix proteins may be a critical step in the pathogenesis of candidiasis. Yeast cell adherence to type I and IV collagen, fibronectin and laminin was blocked by peptide fragments from denatured type I collagen (gelatin). Gelatin fragments were obtained by digestion of the reduced protein with trypsin or CNBr. The fragments did not have antifungal properties, presumably inhibiting adherence by blocking receptors (adhesins) on the surface of the fungus. A 10-mer (GQRGVVGLPG) fashioned from the alpha-1 chain of type I collagen reduced adherence by 68%. However, a gelatin peptide possessing 47 amino acids reduced fungal adherence to type I collagen by 100%. Peptides derived from the biocompatible protein gelatin, therefore, may have a potential role in reducing the adherence of the fungus to host proteins.

Hemorrhagic proctitis due to lymphogranuloma venereum serogroup L2. Diagnosis by fluorescent monoclonal antibody.

Definitive diagnosis of lymphogranuloma venereum is impeded by difficulty in culturing the causative agent and by serologic cross-reactivity between Chlamydia trachomatis L1, L2, and L3, which can cause the disease, and the many other serotypes of C. trachomatis, which do not. In a 23-year-old man with massive rectal bleeding, an exudative rectal ulcer, and inguinal lymphadenopathy, serologic findings were compatible with a recent lymphogranuloma venereum infection, but stains and cultures of lymph-node aspirates were negative, and biopsy specimens of the rectum and lymph nodes showed only nonspecific inflammatory changes. A diagnosis of lymphogranuloma venereum was made when intracellular organisms and inclusion bodies were demonstrated in rectal submucosal tissue by fluorescein-tagged monoclonal antibodies directed against both chlamydial group antigens and L2 serotype antigen. This technique was of particular value in this patient because it specifically identified an unusual cause of severe gastrointestinal bleeding.

Peritoneal Coccidioidomycosis Associated With Human Immunodeficiency Virus Infection

Peritoneal coccidioidomycosis is extremely rare. This report describes a patient infected with the human immunodeficiency virus who presented with unexplained ascites and was found to have peritoneal coccidioidomycosis. The ascites had a low serum-ascites albumin gradient, and laparoscopy showed peritoneal implants that grew Coccidioides immitis. This case is unique in several ways; this is the first case in which a patients acquired immunodeficiency syndrome-defining illness was peritoneal coccidioidomycosis, and the serum-ascites albumin gradient determination as well as laparoscopy provided information critical to the diagnosis. This patients dramatic response to systemic antifungal therapy, as evidenced by resolution of ascites and constitutional symptoms, underscores the importance of timely diagnosis and prompt therapy. In summary, this report reviews the previous cases of coccidioidal peritonitis and reports the first case in which localized peritoneal coccidioidomycosis was the acquired immunodeficiency syndrome-defining illness in a human immunodeficiency virus-infected patient.

Two Unusual Presentations of Urogenital Histoplasmosis and a Review of the Literature

Two unusual clinical presentations of urogenital histoplasmosis are described. A review of the literature on urogenital histoplasmosis is provided.