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This paper addresses the changing epidemiology of tinea capitis in the USA and in Europe that has occurred over the last several decades. Several dermatophytes are involved in the etiology, and the primary etiological agents of tinea capitis are limited to the genera Microsporum and Trichophyton. In addition, the sources of these infections are discussed and although geophilic dermatophytes occur worldwide, anthropophilic species and some zoophilic fungi may be geographically restricted, depending on host range. For example, tinea capitis due to geophilic organisms is rare in the USA.

Cell homogenization, isoelectric focusing and gel filtration FPLC have been used to purify a superoxide dismutase (SOD) from the dermatophyte Trichophyton mentagrophytes var. interdigitale (T. interdigitale). N-terminal amino acid sequencing identified this enzyme as a Cu,ZnSOD, with a pH of 5.1, a reduced molecular mass of 18 kDa, and a non-reduced molecular mass of 59 kDa. SOD activity was detectable in culture filtrates, as early as the mid-log phase of growth. The known Cu,Zn inhibitor potassium cyanide caused some inhibition of the purified enzyme, whereas the inhibitors sodium azide, guanidinium hydrochloride, EDTA and chloroform/ethanol had no discernible effect. The T. interdigitale SOD was pH insensitive in the range 7.0-10.5 and remained active after prolonged incubation at 50 degrees C. The purification and characterization of this enzyme represents the first step in determining whether SOD plays any part in protecting T. interdigitale from free radicals generated by the oxidative burst of immune effector cells.

A novel cell-associated proteinase was purified to homogeneity from cytoplasmic antigen preparations of Trichophyton rubrum by sequential isoelectric focusing and gel filtration chromatography. The enzyme exhibited relative molecular masses of 34,000-Mr (non-reduced sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE)), 15,000-Mr (reduced SDS-PAGE) and 37,000-Mr (substrate SDS-PAGE). It had a pH optimum of 7.5 and a pI of 4.5. The proteinase exhibited broad substrate specificity and it was strongly inhibited by the serine proteinase inhibitors phenylmethylsulfonyl fluoride and chymostatin. The N-terminal amino acid sequence of the 34,000-Mr proteinase shared 50% homology with the deduced amino acid sequence of a Coccidioides immitis wall-associated chymotrypsin-type serine proteinase. This is the first cell-associated proteinase to be purified and characterised from T. rubrum and it would appear to be related to the chymotrypsin-type serine proteinases, a class of enzymes that have rarely been isolated from fungi. The function of the proteinase remains speculative although it may play a role in the development and subsequent proliferation of the fungus in vivo.

An extracellular proteinase has been partially purified from culture filtrates of Trichophyton rubrum by ultrafiltration, isoelectric focusing and gel filtration chromatography. The enzyme has a non-reduced molecular weight of 235,000 by substrate SDS-PAGE. It has a pH optimum of 8.5 using azocasein and azoalbumin as substrates and a pI of 3.6-3.8. The metalloproteinase inhibitors EDTA and 1,10-phenanthroline, together with the chymotrypsin inhibitor chymostatin, strongly inhibited its activity. The serine proteinase inhibitors phenylmethanesulphonyl fluoride and diisopropylfluorophosphate showed weak inhibitory activity. The proteinase exhibited broad substrate activity against azocoll, azoalbumin, azocasein, laminin and fibronectin. It exhibited weak activity against elastin and keratin. Observations on the occurrence of this proteinase together with previously described lower molecular weight proteinases suggests that the former is the first to appear in minimal medium cultures. Freeze/thaw cycling of the partially purified 235,000 M(r) proteinase was found to generate low molecular weight proteinases, particularly at 53,000, 27,000 and 25,000 M(r), indicating that the latter may originate from the larger molecule.

It has been suggested that patients with chronic superficial Trichophyton rubrum infection have defective cellular immunity to dermatophyte antigens. This may be due to a selective anergy to dermatophyte antigens or reflect the activity of dermatophyte-derived lymphocyte inhibitory factors. To explore these possibilities, we assessed lymphocyte transformation to a variety of recall antigens, including a cytoplasmic and exoantigen preparation of Trichophyton rubrum in 15 patients with chronic dermatophyte infection and 15 age- and sex-matched positive controls. In a duplicate set of experiments, autologous serum was replaced by heat-inactivated fetal calf serum. In addition, the direct effect of Trichophyton rubrum extracts on lymphoproliferation was assessed in vitro. Comparable lymphocyte transformation to each recall antigen was observed in patients and controls. Moreover, we found no evidence for a circulating dermatophyte-derived lymphocyte inhibitory factor in sera from patients with chronic superficial infection. A direct inhibitory effect of Trichophyton rubrum on lymphocyte proliferation to recall antigens was observed, however, at protein concentrations of > 10 micrograms/ml (exoantigen preparation) and > 25 micrograms/ml (cytoplasmic preparation). This inhibitory effect was rapidly reversible, not associated with loss of cell viability and maximal when added within 24 h of antigen to cultured lymphocytes. Class II MHC antigen HLA-DR, a surface marker of T-cell activation, was observed on inhibited lymphocytes co-cultured with antigen, suggesting the primary target for the inhibitory effect in vitro is the lymphocyte rather than the antigen-presenting cell.(ABSTRACT TRUNCATED AT 250 WORDS)

The electron microscopic appearances of grains from seven patients with pale grain eumycetoma infections have been studied. The infecting fungi were Pseudallescheria boydii (2), Fusarium sp. (1), Acremonium kiliense (1), a non-sporing mould (2) and Trichophyton violaceum (1). P. boydii grown in vitro and grains from a Madurella mycetomatis infection were used for comparison. The most important ultrastructural features of the pale eumycetoma grains were the gross thickening of the fungal cell walls maximal at the periphery of the grain, the predominance of grossly disorganised hyphae and the appearance of cytoplasmic membrane systems. In some areas adjacent cell walls appeared to fuse. These changes may account for some of the well recognised difficulties in isolating organisms from eumycetoma grains and treating the infections with antifungal drugs.

The antigenic sites of cultured and invading Trichophyton rubrum can be located by using an immunoperoxidase technique in light and electron microscopy. The cell wall is identified as a major antigenic determinant in both cultured and invading T. rubrum and, in the cultured dermatophyte, other intracellular structures are also shown to be antigenic. The keratin immediately surrounding invading hyphae shows positive staining, suggesting the diffusion of dermatophyte-derived antigens, possibly keratinolytic enzymes.

The early interaction, adherence, between dermatophyte conidia and human keratinocytes has been studied in vitro. Two spore forms were used: microconidia and arthroconidia produced in vitro. The adherence of spores from three dermatophyte species, Trichophyton rubrum, T interdigitale, and T quinckeanum, was investigated using keratinocyte suspensions from different skin sites. Time-dependent adherence was demonstrated for all fungi studied with maximum adherence occurring between 3 and 4 h. There were no significant differences in adherence rates between the organisms studied. An order of affinity was established between keratinocytes from different sites and significant differences were demonstrated in adherence of microconidia to skin cells derived from sole versus knee. No differences in adherence rates were demonstrated in atopics versus patients with chronic dermatophytosis and normals. Adherence was inhibited, but not abolished, by subinhibitory concentrations of ketoconazole, itraconazole, and griseofulvin. The interaction between microconidia, arthroconidia, and keratinocytes was verified with scanning and transmission electron microscopy.

Cutaneous dermatophyte infections caused by Trichophyton quinckeanum were established in various strains of mice. All congenic BALB/B (H-2b), BALB/c (H-2d) and BALB/K(H-2k) strains showed high susceptibility to dermatophyte infection. Susceptibility is independent of MHC phenotype, since other strains with corresponding H-2 haplotypes such as C57BL/6 (H-2b), DBA/2 (H-2d) and CBA (H-2k) were resistant to the disease. During the acute phase of infection in BALB/c mice, the in vitro biastogenic responses of regional lymph node cells was suppressed. Suppression was observed for both the T cell mitogens concanavalin A and phytohaemagglutinin, and for the B cell mitogen lipopolysaccharide. A series of cell mixing experiments revealed that lymph node cells from infected mice were able to suppress the T cell and B cell mitogenic responses of lymph node cells from normal mice. Suppression was mediated by T cells and abrogated by treatment of lymph node ceils with either monoclonal anti-thy-1.2 or anti-Ly-2.2 and complement. In this report, we discuss the possibility that T-suppressor mechanism mediated by cells bearing the Ly-2+ phenotype and activated during dermatophyte infection may determine the course of the disease. [ABSTRACT FROM AUTHOR]

An in vivo adoptive cell transfer system was used to investigate protective immunity during experimental murine dermatophytosis due to Trichophyton quinckeanum. Using sublethally (550R) irradiated BALB/c mice which are particularly susceptible to infection, it was found that regional lymph node cells from syngeneic acutely-infected donors conferred protection to irradiated recipients. By contrast, serum from the same donors did not prevent infection of normal BALB/c mice. The capacity of lymphoid cells to transfer adoptive immunity was Lost after treatment with monoclonal anti-Thy-1.2 antibody and complement, but not after treatment with monoclonal anti-Thy 2.2 antibody and complement, indicating that cellular immunity is mediated by Ly 2- T cells. The cellular activity of chronically infected mice was also studied. Paradoxically, lymphoid cells from these animals which appeared to be immunotogically compromised did, however, confer immunity. Adoptive immunity was abrogated by serum from chronically infected donors or by specific dermatophyte antigen, but not by homologous or heterologous anti-dermatophyte antiserum. These findings indicate that competition between cell-mediated immunity and humoral factors may be the causative mechanism for persistence of dermatophyte infection in this system. [ABSTRACT FROM AUTHOR]

Human peripheral polymorphonuclear neutrophils exhibited potent cytotoxic activity against the dermatophyte fungi Tricophyton quinckeanum and T. rubrum as assessed by inhibition of fungal replication in Sabouraud's agar. Monocytes also showed cytotoxic activity, but this was less pronounced than that of neutrophils, while lymphocytes had no toxic effect. Cytotoxicity showed a linear relationship to the target cell:effector cell ratio, with significant killing detected at a ratio of one neutrophil to one fungal cell. Fungal killing was optimal at incubation times of 2–24 hr for T. rubrum and 2–48 hr for T. quinckeanum. Thereafter, neutrophils were unable to prevent fungal replication while remaining viable. Cytotoxicity was markedly reduced by sodium azide, an agent that inhibits haem enzymes, and by catalase, but not by heat-inactivated catalase or superoxide dismutase. The fungicidal activity of neutrophils and monocytes was greatly increased by stimulation with phorbol myristate acetate (PMA) or with concanavalin A (Con A) compounds known to stimulate the secretion of lysosomal enzymes and the production of highly reactive oxygen intermediates. The cytotoxic activity of monocytes to T. quinckeanum, but not to T. rubrum, was also increased by Con A treatment. Neutrophil and monocyte phagocytosis of dermatophytes was demonstrated by electron microscopy studies. Disrupted T. quinckeanum and T. rubrum germlings were identified in the cytoplasm of the phagocytic cells, and similarly disruption of hyphae surrounded, but not engulfed, by neutrophils was also observed. These studies suggest that phagocytosis and/or oxidative products of the respiratory burst of neutrophils and monocytes may be implicated in the killing of dermatophytes in vivo. [ABSTRACT FROM AUTHOR]

Onychomycosis due to Trichophyton soudanense is described in four African patients. Onset of their disease was noted only alter years of living in England. Chronic nail infection may serve as a reservoir for this organism in non-endemic areas. Clinical nail changes differ somewhat from typical distal subungual onychomycosis, and include a diffuse mild thickening of the nail plate, often with hyperpigmentation, lamellar peeling, transverse ridging and pitting. These nail infections are extremely difficult to eradicate and resemble those caused by other endothrix organisms. A familial source of infection should be sought, as in all cases of anthropophilic fungal infection. [ABSTRACT FROM AUTHOR]

Tinea imbricata is a chronic dermatophyte infection caused by Trichophyton concentricum affecting large areas of the skin surface. Spontaneous improvement is unusual and relapse after apparently successful treatment is common. In this study in Papua New Guinea it was found that a high proportion of infected patients had immediate-type hypersensitivity (52%) or negative responses (46%) to intradermal trichophytin. The majority of patients failed to develop delayed-type hypersensitivity on skin testing or as assessed in vitro by leucocyte migration inhibition. However, 78% of patients investigated had antibody to T. concentricum. The relevance of T-lymphocyte hyporeactivity to persistence of the infection is discussed. [ABSTRACT FROM AUTHOR]

In patients infected with Trichophyton rubrum, the T lymphocyte responses (lymphocyte transformation) to trichophytin were reduced, compared with control subjects. The same levels were seen in patients with intractable chronic infection and those who responded well to treatment but the site of infection affected the immune response, lower levels being seen in patients with palmo-plantar infection than in those with groin infections. In infections caused by T. mentagrophytes by contrast, lymphocyte responses to specific antigens were significantly increased. [ABSTRACT FROM AUTHOR]

One hundred and six patients with chronic dermatophytosis unresponsive to griseofulvin were studied. Trichophyton rubrum was the causative organism in 93% of cases. Chronic dermatophyte infections caused by organisms other than T. rubrum occurred predominantly, but not exclusively, in patients with underlying diseases. Forty-nine percent of the patients had a personal or family history of atopy but other abnormalities included disorders of keratinization, collagen vascular disease and systemic steroid therapy. The commonest sites of infection were the palms and soles, as opposed to toe webs or groins in control patients with griseofulvin-responsive dermatophyte infections. A significant proportion of chronically infected patients had raised IgE levels. Only 11 % of the chronically infected group showed delayed hypersensitivity responses to intradermal trichophytin but 58% showed immediate hypersensitivity responses to trichophytin as well as other fungal and non-fungal allergens. [ABSTRACT FROM AUTHOR]

Cell homogenization, isoelectric focusing and gel filtration FPLC have been used to purify a superoxide dismutase (SOD) from the dermatophyte Trichophyton mentagrophytes var. interdigitale (T. interdigitale). N-terminal amino acid sequencing identified this enzyme as a Cu,ZnSOD, with a pH of 5.1, a reduced molecular mass of 18kDa, and a non-reduced molecular mass of 59kDa. SOD activity was detectable in culture filtrates, as early as the mid-log phase of growth. The known Cu,Zn inhibitor potassium cyanide caused some inhibition of the purified enzyme, whereas the inhibitors sodium azide, guanidinium hydrochloride, EDTA and chloroform/ethanol had no discernible effect. The T. interdigitale SOD was pH insensitive in the range 7.0-10.5 and remained active after prolonged incubation at 50°C. The purification and characterization of this enzyme represents the first step in determining whether SOD plays any part in protection T. interdigitale from free radicals generated by the oxidative burst of immune effector cells. [ABSTRACT FROM AUTHOR]

Thirty-five patients were studied who were infected with Trichophyton species. There was a marked reduction in the incidence of delayed hypersensitivity skin responses in Trichophyton rubrum infections (12%) as compared with those patients who were infected with other dermatophytes (75%). There was no difference in the extent of leukocyte migration in either of the clinical groups infected with Trichophyton rubrum but inhibition was demonstrated in patients infected with other Trichophyton species. Nearly one half of those infected with T. rubrum were atopic as defined by history, present symptoms or a positive immediate wheal and flare reaction to T. rubrton. Reasom for the incidence of atopy and the poor cell-mediated responses are discussed. [ABSTRACT FROM AUTHOR]

This article focuses on a study according to which a reproducible experimental model for dermatophytosis is essential for the investigation of the recruitment and interaction of immune cells throughout the course of the infection. Previously the guinea-pig has proved to be the most widely used animal model. This study describes the assessment of a new mouse model for experimental dermatophyte infections. First, the infectivity of nine different strains of Trichophyton mentagrophytes and Trichophyton quinckeanum was compared. Using the two most promising isolates, genetic susceptibility of inbred strains of mice was investigated.

This article reports that inhibition of human lymphocyte blastogenesis is derived from trichophyton rubrum. Immunomodulation of the host response by the invading organism is a recognised feature of some fungal infections. This mechanism has recently been proposed to account for the chronic course of some human dermatophytoses, in particular, those caused by the anthropophilic fungus Trichophyton rubrum. A report that serum from a patient with deep T. rubrum infection depressed lymphocyte transformation to T. rubrum cytoplasmic antigen, led to suggestions of a circulating inhibitor acting as an antigen specific T cell receptor blocker. To date this observation has not been further investigated.