Correlation of susceptibility of immature mice to fungal infection (blastomycosis) and effector cell function.

Immature mice are highly susceptible to blastomycosis, which is similar to other mycoses and has parallels in humans. The murine susceptibility is noteworthy in that it persists beyond the development of resistance to other, nonfungal pathogens and the maturation of most immune functions. As the susceptibility to blastomycosis appeared to be related to an early event after infection, primary effector cell function was studied. We found that peritoneal inflammatory cells, enriched for neutrophils, from immature (3-week-old) mice killed nonphagocytizable Blastomyces dermatitidis cells less (25%) than did cells from mature (8-week) mice (70%) (P<0.01), a defect intrinsic to the neutrophils. This correlated with an impaired immature cell oxidative burst. Killing of phagocytizable Candida albicans was not significantly different, 73 versus 87%. Thioglycolate-elicited cells were more impaired; killing of B. dermatitidis was insignificant, and killing of C. albicans was more impaired in immature (16% killing) than in mature (45%) cells (P<0.02). Peripheral blood neutrophils from mature animals killed B. dermatitidis (41%) more than did those from immature animals (10%) (P<0.02); C. albicans was killed efficiently by both. Resting or activated peritoneal macrophages from both types of animals showed no differences in B. dermatitidis killing. These results suggest that the susceptibility of immature mice is related at least in part to the depressed capacity of their neutrophils to kill B. dermatitidis.

Virulent isolates and mutants of Blastomyces in mice: a legacy for studies of pathogenesis.

This article provides information on the history of Blastomyces dermatitidis isolates and spontaneous mutants, the relationship with maintenance of cultures, and their virulence as quantified in murine models. Virulent isolates have been obtained from soil or from patients. Regardless of origin, mutants attenuated in virulence have sometimes arisen from storage as frozen yeast, frozen mycelia, or refrigerated yeast or serial passage in vitro at 35 degrees to 37 degrees C. Once virulence is lost, reversion to the virulent phenotype (even after serial passage in animals) has not been seen. These data, methods, and isolates provide a basis for future studies of virulence factors.

Epidemiological observations in the AIDS clinic at the Hadassah University Hospital in Jerusalem.

Of the first 395 attendees at the AIDS clinic in Jerusalem, 32% were homo/bisexuals, 4% i.v. drug abusers (IVDAs), 24% persons with minimal risk for AIDS and 38% were persons having no risk. Human immunodeficiency virus (HIV) antibody rates were 7% for homosexuals, 29% for IVDAs, 1% for persons with minimal risk and 0% for persons at no risk. Israeli homosexuals had a significantly greater risk for HIV infection (9 of 35) if they had sexual contact with non-Israelis as compared with homosexuals who had contact with local partners only (0/91, P less than 0.001). The mean number of attendees per month increased by 431% during the 4 months following the first prime-time television program on AIDS. The largest mean increases occurred among persons at no risk (1 to 27.2), those with minimal risk (2.5 to 16.5), and among women (1.25 to 20.0). This report indicates that HIV infection among Israeli homosexuals has not yet reached U.S. proportions. It also shows that the TV program raised anxiety concerning AIDS among the general public, and probably encouraged the public to use HIV testing as part of a general health screening program.

Initial experience in therapy for progressive mycoses with itraconazole, the first clinically studied triazole.

The search for antifungal drugs, particularly oral agents with a broad spectrum of activity, led to the study of itraconazole, a triazole. In vitro susceptibility testing suggested activity against a variety of fungal pathogens affecting humans. Pharmacokinetic studies indicated absorption after oral administration to patients, with prolonged serum concentrations and peak levels exceeding the in vitro inhibitory concentrations for most pathogens. Twenty-four patients have been enrolled in efficacy studies; two-thirds of these individuals had experienced a relapse after apparently successful therapy with other drugs, had failed to respond to other drug therapy, and/or had experienced intolerable side effects with other drugs. Fourteen patients have thus far responded to treatment with itraconazole; this group includes two persons each with coccidioidal pneumonia and adenopathy, pulmonary coccidioidomycosis, and dermatophytosis plus onychomycosis as well as one person each with coccidioidal epididymitis, adrenal histoplasmosis, head and neck histoplasmosis, cutaneous blastomycosis, oral-sinonasal alternariosis, chromoblastomycosis, invasive pulmonary aspergillosis with fungus ball, and onychomycosis. Five other patients have had partial responses to therapy, three have failed to respond, and two have been deemed unassessable. Drug toxicity has been limited in 211.8 patient-months of therapy. The results are encouraging and indicate that more extensive studies are warranted.

Dapsone-induced methemoglobinemia and hemolysis in the presence of familial hemoglobinopathy Hasharon and familial methemoglobin reductase deficiency.

Methemoglobinemia and hemolysis are well-known side effects after using high doses of dapsone (4,4'-diaminodiphenylsulfone). Their occurrence after low doses of the drug, and subsequent investigation, revealed the presence of hemoglobin Hasharon, and low content of NADH-dependent methemoglobin reductase in five members of an East European ashkenazic Jewish family.