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A 36-year-old man, who was an intravenous drug abuser, developed thoracic herpes zoster, paronychia, oral candidosis, necrotizing gingivitis and bilateral parotid salivary gland swelling. Granulomatous oral lesions and ulceration on the nose were shown to be due to disseminated histoplasmosis.
A 5-year-old male Siberian husky bred outdoor in Tokyo had a swollen paw with interdigital granulomatous lesions in the left hindlimb. The dog had no apparent pulmonary or gastrointestinal involvement. Histopathological analysis of the skin lesions demonstrated yeast-like organisms predominantly within macrophages. Sequence analysis of fungal ribosome RNA gene isolated from a paraffin sample revealed a 100% homology with the teleomorph of Histoplasma capsulatum. The present case may support the concept of primary cutaneous canine histoplasmosis as an endemic phenotype recognized in Japan.
We describe an African histoplasmosis case in a 65-year-old Belgian living in Zaire for 46 years. Microscopic bone marrow examination showed Histoplasma. It was confirmed by cultures and hamster inoculation. Autopsy revealed a fungal dissemination by Histoplasma duboisii.
Histoplasmosis is a deep mycosis with a high prevalence in America. Its aetiological agent, Histoplasma capsulatum, is found in Mexico, mainly in confined spaces, where it grows on bat guano or bird droppings. A research project has been developed in the State of Guerrero, Mexico, where many contaminated caves and mines are visited by individuals and epidemic outbreaks have been recorded. Data concerning human skin test response to histoplasmin antigen, host genetic predisposition to Histoplasma infection, sociocultural, socioeconomical and ethnobiological aspects of the disease in Guerrero are summarized in this paper.
Two patients with African histoplasmosis manifested by ulcers and cutaneous swellings are described. The inguinal lymph nodes were also involved in one patient. Treatment with amphotericin B combined with ketoconazole was successful.
An autopsy case of a 52-year-old Japanese male, who died of disseminated histoplasmosis, is reported. He had received a cadaveric renal allograft 4 years prior to death. The donor was a 33-year-old American negro male, who had resided in Texas. The patient had been treated with immunosuppressive drugs after renal transplantation, and mycotic pneumonia developed 3 months before death. At autopsy, acute necrotizing lesions composed of histiocytes were observed in the transplanted kidney, lungs, prostate gland and various lymph nodes. Abundant yeast-like fungal elements, measuring 2-5 micron in diameter, were engulfed by the histiocytes, and were identified as Histoplasma capsulatum by the immunoperoxidase method. The transplanted kidney was considered to have been the source of the infection.
A case of localised histoplasmosis of the gingivae, with no osseous involvement is described in a 50-year-old man. The diagnosis was based on histology, growth on culture and a positive histoplasmin latex test. Therapy was commenced with intravenous amphotericin but was changed to intravenous miconazole because of serious immediate side effects and the development of marked renal impairment and moderate suppression of erythropoiesis. Rebiopsy of the gingival margin showed therapy to be effective. No source of the infection could be traced.
The first reported case of disseminated histoplasmosis in Western Australia is described. The diagnosis was delayed because the clinical presentation closely resembled that of tuberculosis, the initial histoplasma serology was negative, and constant severe thrombocytopenia delayed efforts to obtain tissue required for culture and histology. Despite adequate therapy, relapse occurred on one occasion.
A case of histoplasmosis presenting as ulcerated, hyperplastic gingiva and with no other systematic signs and symptoms is reported. The clinical presentation and the rarity of this condition led one of us to the differential diagnosis of a malignant lesion. The correct diagnosis was made after histological examination and tissue culture which yielded Histoplasma capsulatum. The patient was successfully treated with ketoconazole.
Opportunistic fungal infections account for a significant amount of morbidity associated with HIV disease. We report here a case of localised oral histoplasmosis without evidence of disseminated disease in a patient who lacked stigmata of HIV disease at the time of initial presentation. The diagnosis is based on histology with special stains, complement fixing antibodies in serum, and culture of the organism from fresh tissues. Activation of subclinical disease following an infection in Uganda may explain the development of these exophytic oral lesions in this British resident.
We report the first case of disseminated histoplasmosis in an animal in Scandinavia. Yeast cells compatible with those of Histoplasma capsulatum var. capsulatum were found in the skin, liver, spleen, a kidney, and a lymph node of a wild badger (Meles meles). The diagnosis was confirmed by electron microscopy and immunofluorescence staining of the yeast cells in tissue sections.
Ulcerative colitis, protein losing enteropathy and intestinal histoplasmosis-salmonellosis were diagnosed in a six-year-old Quarterhorse stallion. For six months before examination, the horse experienced a slow continual loss of weight. During the 17 day period of hospitalisation the horse developed progressive generalised oedema. On the 12th day of hospitalisation a severe profuse watery diarrhoea began; the horse was killed five days later.
Ambruticin (W7783) was evaluated in vivo in mice subacutely or nonlethally infected with Histoplasma capsulatum. Results were compared with those obtained with amphotericin B, the drug of choice in human histoplasmosis. In one experiment, ambruticin was shown to be capable of curing infected animals as evidenced by totally negative liver and spleen cultures obtained when mice were sacrificed after 4 weeks of oral treatment with 150 mg of drug per kg per day. The 50% cure dose for ambruticin was between 75 and 150 mg/kg per day; the 50% cure dose for oral amphotericin B in this experiment was between 1.56 and 6.25 mg/kg per day. In a second experiment, both oral ambruticin (150 mg/kg per day) and oral amphotericin B (25 mg/kg per day) were again curative, but to a lesser degree than in the first experiment. Biological cures were obtained with both drugs after 3 and 4 weeks of treatment but not after 2 weeks.
Fluconazole (UK-49,858) was compared with amphotericin B in treating histoplasmosis in female AKR mice immunosuppressed with either cyclophosphamide or cortisone. Both drugs protected animals from a lethal challenge with Histoplasma capsulatum, but neither regimen resulted in cures since viable organisms were cultured from spleens of survivors.
Liposomal amphotericin B (AmBisome) was compared with amphotericin B deoxycholate for the treatment of disseminated murine histoplasmosis. Liposomal amphotericin B was well tolerated and, milligram for milligram, was as potent as amphotericin B deoxycholate.
BALB/c nu/+ immunocompetent and athymic (nu/nu) mice were infected intravenously with yeast cells of Histoplasma capsulatum. Mice were either given water (controls) intraperitoneally (i.p.) or given MK-991 i.p. once daily or twice daily. Protection was measured as prolonged survival or reduction in tissue counts. MK-991 was protective in immunocompetent mice, prolonging survival and reducing counts in spleen and livers at a dose as low as 0.05 mg/kg of body weight/day. MK-991 was modestly effective in athymic mice at a higher dose, 5 mg/kg/day. These studies suggest that MK-991 may be appropriate for clinical development in histoplasmosis.
Immune-competent ICR and BALB/c athymic (nude) mice were infected intravenously with Histoplasma capsulatum and treated with either fluconazole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fluconazole and nikkomycin Z both prolonged survival when given at 5 mg/kg of body weight twice daily. When administered in doses as low as 2.5 mg/kg twice daily, nikkomycin Z reduced fungal counts in both the spleen and liver. When both drugs were combined, there was no antagonism, and in combined therapy spleen and liver counts were reduced more than for either drug alone. However, nikkomycin Z had no effect on brain fungal burden. In nude mice fluconazole and nikkomycin Z had an additive effect in prolongation of survival and reduction of liver and spleen burden. Nikkomycin Z is well tolerated, is at least as effective as fluconazole, and may interact beneficially with fluconazole for treatment of murine histoplasmosis.
Ravuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ) and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All regimens tested prolonged survival (P < 0.05 to 0.0001). At equivalent doses of 50 mg/kg of body weight, RCZ and ITZ were equally effective and RCZ was more effective than FCZ (P = 0.02). Clearance of fungal burden from the livers and spleens of mice showed RCZ and ITZ at doses of 50 mg/kg to be efficacious but not curative. These data indicate that RCZ should be studied further.