Experimental histoplasmosis in the baboon (Papio sp.)

Summary Ten male and female baboons were inoculated with saline suspensions ofHistoplasma capsulatum spores using the intratracheal, intravenous, and intraperitoneal routes. Skin testing, complement fixation, agar-gel diffusion, x-rays, as well as culture and histopathological sections of the internal tissues were used for determining the susceptibility of the baboon to histoplasmosis.No systemic histoplasmosis was established in any of the baboons, but preliminary infection was obtained by the three routes of inoculation. Two baboons inoculated intravenously showed a complete negative response to the pathogen.     

Nueva observacion de histoplasmosis en la Republica Argentina

Summary The author make a clinical and parasitological study of one new observation of histoplasmosis, parasitical rethiculo-histiocitosis or Darling's disease byHistoplasma capsulatum Darling, 1906 in a man 59 year old with pulmonary tuberculouse.His lesions in the mucouse of the mouth and in the lymph-nodes would healed with sulphadiacine treatment.It is the 7th. observation in Argentina.     

Diagnosis and management of histoplasmosis

Histoplasmosis occurs sporadically or during outbreaks in endemic areas. The risk for severe forms of histoplasmosis is substantially higher among the growing population of immunocompromised patients. Recent research efforts have focused on analyzing epidemics, identifying risk factors for the disease, developing improved noninvasive diagnostic assays, and assessing the roles of newer antifungal drugs. Guidelines have been published for the prevention of occupationally acquired histoplasmosis and for reducing the risk of disease in patients with HIV infection. A third-generation Histoplasma antigen assay has been developed, which has superior performance characteristics compared to other noninvasive diagnostic tests. Treatment guidelines for the various clinical forms of histoplasmosis have been formulated and updated. Two newer azoles with activity against Histoplasma capsulatum, voriconazole and posaconazole, have been released; in vitro susceptibility data and animal model results have been reported, and treatment experience with these drugs has accumulated.     

Histoplasmosis in the Republic of Congo dominated by African histoplasmosis,Histoplasma capsulatum var. duboisii

The Republic of Congo (RoC) is one of the African countries with the most histoplasmosis cases reported. This review summarizes the current status regarding epidemiology, diagnostic tools, and treatment of histoplasmosis in the RoC. A computerized search was performed from online databases Medline, PubMed, HINARI, and Google Scholar to collect literature on histoplasmosis in the RoC. We found 57 cases of histoplasmosis diagnosed between 1954 and 2019, corresponding to an incidence rate of 1–3 cases each year without significant impact of the AIDS epidemic in the country. Of the 57 cases, 54 (94.7%) were cases of Histoplasma capsulatum var. duboisii (Hcd) infection, African histoplasmosis. Three cases (5.3%) of Histoplasma capsulatum var. capsulatum infection were recorded, but all were acquired outside in the RoC. The patients’ ages ranged between 13 months to 60 years. An equal number of cases were observed in adults in the third or fourth decades (n = 14; 24.6%) and in children aged ≤15 years. Skin lesions (46.3%), lymph nodes (37%), and bone lesions (26%) were the most frequent clinical presentations. Most diagnoses were based on histopathology and distinctive large yeast forms seen in tissue. Amphotericin B (AmB) was first line therapy in 65% of the cases and itraconazole (25%) for maintenance therapy. The occurrence of African histoplasmosis in apparently normal children raises the possibility that African histoplasmosis is linked to environmental fungal exposure.     

Histoplasma capsulatum in the environment of sporadic histoplasmosis cases

Conclusions 1. Acute pulmonary histoplasmosis in adults is demonstrated to be associated with exogenous sources of infection in one-half of a series of cases. 2. No exogenous sources of infection were found in chronic pulmonary histoplasmosis in adults by methods comparable to those used in acute pulmonary histoplasmosis. 3. The significance of these findings for the pathogenesis of the three clinical forms of histoplasmosis is discussed. 4. In acute pulmonary histoplasmosis in adults, the isolation ofH. capsulatum from the environment at sites of exposure aided in specific diagnosis.Two acute pulmonary histoplasmosis cases were reported previously (2–3).     

Occurrence of histoplasmosis in Asia

The occurrence of histoplasmosis in Asia has been reviewed. Authentic cases of histoplasmosis in man are known from India, Malaysia, Singapore, Indonesia, Thailand, South Vietnam and Japan, but the autochthonous nature of the cases reported has not been established unequivocally. Of the 30 cases of human histoplasmosis recorded from Asia, 15 were confirmed by positive cultures, and their country-wise distribution is as follows: Malaysia — 4, Indonesia — 3, Singapore — 2, Thailand — 2, South Vietnam — 2 and one each from India and Japan. Authentic cases of histoplasmosis in animals are currently unknown from Asia, and likewise there is no information on the natural habitats of the etiologic agentH. capsulatum in this part of the world except for a solitary isolation from soil in bat-infested cave in Malaysia.The available data on the prevalence of cutaneous hypersensitivity to histoplasmin indicates that histoplasmin sensitivity is absent in Israel, Syria, Saudi Arabia, Lebanon and Qatar; sensitivity is negligible or of a very low order in Iran, Iraq, Pakistan and India, and for these countries it has been even suggested that the positive reactors observed may represent cross-sections with some unknown fungus/fungi which may be antigenically related toH. capsulatum. In Japan the frequency of histoplasmin positive reactors has been negligible except in groups of persons working near a U.S. Army base and in factories which used soil and sand imported from overseas including the U.S.A. In Burma and Taiwan the bulk of positive reactions in which the induration did not exceed 8 mm in diameter has been considered probably non-specific. In Indonesia and South Vietnam, on the other hand, where less than 10 per cent of the reactions tended to concentrate around an induration of 16 mm sensitivity to histoplasmin may represent specificH. capsulatum infection in certain cases. Likewisef the requently large reactions reported from the Philippines have also been interpreted to represent specific histoplasmosis infection.The recovery ofH. capsulatum from soil coupled with the finding of well-documented cases of histoplasmosis in Malaysia suggests that the disease is endemic in that country. It is not unlikely that histoplasmosis is endemic in other parts of Asia although this has not been demonstrated so far. Comprehensive mycological, serological and soil studies are indicated in order to investigate the prevalence and incidence of histoplasmosis and to map out the endemic areas of the disease in Asia.Paper read at the Eighth International Congresses for Tropical Medicine and Malaria, September 1968, Teheran (Iran).     

An unusual presentation of disseminated histoplasmosis in a non-HIV patient from Vietnam

BackgroundHistoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum, naturally found in nitrogen-rich soil, whose main transmission route is the inhalation of conidia. Up to 95% of histoplasmosis cases are asymptomatic or transient, and the remaining 5% of cases have pathological manifestations in the lungs, bone marrow, liver, spleen, intestine, mucous membranes, and rarely on the skin. This mycosis has been reported from many endemic areas, mainly in immunosuppressed patients, such as HIV-positive patients, and its disseminated form is rarely reported.Case reportHistoplama capsulatum was isolated and identified by means of microscopy, culture characteristics and nested PCR from the cutaneous lesions of a non-HIV patient from Vietnam. The patient improved significantly with systemic itraconazole treatment.ConclusionsDisseminated histoplasmosis with cutaneous involvement in non-HIV patients is an extremely unusual presentation.     

Murine models of blastomycosis,coccidioidomycosis, and histoplasmosis

Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens, Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. This review gives a brief background of human diseases associated with these organisms and describes the development, details, and utility of murine models of blastomycosis, as well as coccidioidomycosis and histoplasmosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Experimental intestinal histoplasmosis of hamsters

Summary In order to elicit primary intestinal histoplasmosis, hamsters and mice were given the infective agent by drinking a suspension of yeast cells, eating infected mouse liver, and through injection into the wall of the lumen of the cecum after laparotomy.Histologic examination and isolation by cultures were made, maximally 6 weeks after infection.No clear-cut histoplasmic primary complex in the intestine was confirmed, but a fungus disease was achieved in a few animals, suggesting the intestinal tract as a possible portal of entrance of the infection.Some of the animals fed with a fungus suspension developed primary pulmonary lesions, a remarkable fact to be considered in evaluation of feeding experiments.The lack of confirmed evidence of intestinal primary lesions as contrasted with the constant demonstration, when searched for, of pulmonary lesions, would suggest that the intestinal tract should not be considered a major portal of entrance in histoplasmosis.This project was supported in part by Grant 986 from the National Institutes of Health.     

Experimental canine histoplasmosis and blastomycosis

Normal adult beagle dogs were experimentally infected withHistoplasma capsulatum orBlastomyces dermatitidis. Clinical signs of histoplasmosis and blastomycosis were similar to those seen in natural infections in dogs, although diarrhea was not seen in dogs with experimental histoplasmosis. Significant radiographic changes were seen in the lungs of all dogs inoculated with one of the organisms but not in the control dogs.Amphotericin B treatment of the dogs infected with mycelia ofBlastomyces dermatitidis resulted in clinical improvement and prevented death, but did not cure all of the dogs. Four of five dogs randomly selected for placebo treatment died within 34 days of inoculation, whereas all five dogs in the amphotericin B treated group were alive 14 weeks after inoculation.Since no deaths occurred in dogs inoculated with the mycelia ofHistoplasma capsulatum, weight loss was used as a measure of the degree of illness. No difference could be demonstrated between weight losses of three dogs treated with amphotericin B and of three dogs treated with a placebo. Four other dogs inoculated withH. capsulatum did not have a 20% weight loss, a criterion for treatment. The 10 control dogs maintained their preinoculation weight.From the Ecological Investigations Program, Center for Disease Control, Health Services and Mental Health Administration, Public Health Service, United States Department of Health, Education, and Welfare, Kansas City, Kansas.     

Experimental histoplasmosis in temporarily „hibernating“ hamsters

Summary Although occasional hibernation was observed in golden hamsters kept at low temperatures during the winter months, the periods of hibernation were apparently too short to induce conversion of the yeast cells ofH. capsulatum into the mycelial phase or to prevent conversion into the yeast phase when inoculated in the mycelial phase.As a result of exposure to low temperatures, a heavily disseminated, severe and often fatal histoplasmosis was observed in contrast to slight dissemination in control animals kept at room temperature.In addition to extensive lesions in the organs in the heavily infected hamsters, severe fungemia, accumulations of numerous yeast cells within large cells and histoplasmic phlebitis and pleuritis of a proliferative character were seen.Schaumann bodies did not develop in granulomatous lesions of heavily infected animals kept at low temperatures, nor were they prominent in tissues with heavy accumulations of yeast cells or after inoculation with the mycelial phase.This project was supported in part by Grant E-576 from the National Institutes of Health.     

First cases of histoplasmosis diagnosed in recife,Brasil

Summary Three cases of histoplasmosis are described, one also with subcutaneous nodule, the first cases reported from Pernambuco, Brasil.Histoplasma capsulatum was isolated from tissues in two cases and from sputum in two cases, all in pure culture.Docente Livre de Parasitologia, Chefe de Secção de Micologia. Cat. Prof.Alvaro de Figueiredo.Professor, Washington University, formerly Visiting Professor, Cadeira de Parasitologia.Pesquisadora, Cadeira de Parasitologia, Secção de Micologia.     

The status of histoplasmosis in Brazil

Thirty four cases of the progressive form of histoplasmosis, five epidemics of the mycosis, many histoplasmin skin test surveys and few clinical or histological evidences of the benign form of the disease were reported in Brazil. The occurrence of the infection in animals and the isolation ofH. capsulatum from soil have also been reported.Pesquisador 1 B do CNPq.     

Epididymal histoplasmosis diagnosed by isolation ofHistoplasma capsulatum from semen

An autochthonous case of epididymal histoplasmosis masquerading as tuberculosis in a 55-year-old male patient is reported from India. It was diagnosed by culture ofHistoplasma capsulatum from semen and by demonstration of the fungus upon re-examination of epididymal biopsy sections previously misinterpreted as tuberculous granuloma. The patient's main complaints were painful epididymal swelling, occasional fever and cough. He was treated successfully by excision of epididymis and vas deferens combined with amphotericin B therapy. This is believed to be the first case of epididymal histoplasmosis to be reported outside the American continent and the fourth of its type reported in the English literature. The case is also noteworthy in thatH. capsulatum was isolated for the first time from semen, and it underlines the importance of mycological culture of semen specimens for diagnosis of genitourinary infections of obscure etiology.Presented at the XII Congress of the International Society for Human and Animal Mycology, Adelaide, Australia, March 13–18, 1994.     

Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement.Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis.Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04–0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004–0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01).Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.     

Case of disseminated African histoplasmosis in a baboon

An adult red baboon (Papio cynocephalus papio) had a severe disseminated case of African histoplasmosis (Histoplasma capsulatum var. duboisii) with skin lesions from small pustules to ulcerative granulomas. Osteolytic lesions were seen radiographically. Treatment with ketoconazole for 6 months was unsuccessful.     

An epizootic of histoplasmosis duboisii (African histoplasmosis) in an American baboon colony.

Histoplasmosis duboisii, a chronic granulomatous disease caused by Histoplasma capsulatum var. duboisii, was diagnosed in 21 baboons at a large primate colony in San Antonio, Texas. Diagnosis was based on finding 8 to 15 microns-diameter yeast cells in histologic sections. Therapy with drugs was unsuccessful. Surgical removal of lesions was the primary treatment. Epidemiologic data suggest the incubation period to be at least 9 months. The most likely route of infection was oral and happened during grooming by the baboons.     

Immunology of histoplasmosis: Humoral and cellular activity from a polysacchari-de-protein complex and its deproteinized fraction in experimentally immunized mice

In a previous publication it was reported that a polysaccharide-protein complex (PPC), sensitive to -glucosidase, was isolated from Histoplasma capsulatum. This complex was strongly reactive in an agar gel diffusion assay with sera from patients with histoplasmosis, but was unreactive with sera from patients with coccidioidomycosis. Here, the studies with human sera have been expanded and attempts were made to determine the response of mice immunized with nonviable H. capsulatum or Cocccidioides immitis to PPC or its deproteinized fraction (D-PPC) using more sensitive tests for antibody and including also test for cell-mediated immunity. Histoplasmin and coccidioidin were compared with PPC or its deproteinized fraction (D-PPC) in all assays. In a counterimmunoelectrophoresis (CIE) assay, PPC and D-PPC reacted only with sera from patients with histoplasmosis, whereas cross reactions were noted with histoplasmin and coccidioidin using heterologous sera. Cross-reaction were observed with all four antigen preparations and both types of antisera using a micro complement fixation assay. The assay for macrophage migration inhibitory factor (MIF) was also relatively nonspecific, in that inhibition occurred with cells from animals sensitized with Histoplasma or Coccidioides using both homologous and heterologous antigens. In the footpad assay, histoplasmin and coccidioidin were highly cross-reactive in animals sensitized with the heterologous fungus, but the PPC and D-PPC from H. capsulatum elicited significant reactions only in animals sensitized with Histoplasma.     

Studies on histoplasmosis IV. Elution characteristics of the Histo-inhibitory factor (HIF)

Summary The histo-inhibitory factor (HIF) derived from homogenates of liver or kidney from hamsters infected withHistoplasma capsulatum has been fractionated by column chromatography. It shows maximum absorption at 280 mµ, has a molecular weight of 142,000 and can be eluted from DEAE-cellulose or DEAE-Sephadex A—50 with 0.02 M phosphate — 4 M sodium chloride (1 : 1)HIF can be eluted fromHistoplasma yeast cells at pH 10.0, thus a greater number of positive cultures from chronic histoplasmosis could be expected to result from pretreatment of clinical specimens in glycine buffer pH 10.0 prior to culture.     

Brote de histoplasmosis en la provincia de Neuquén,Patagonia Argentina

BackgroundIn Argentina, there are no reports of autochthonous cases of histoplasmosis in the southern regions of the country.AimTo report a histoplasmosis outbreak in Zapala town, Province of Neuquén, Patagonia Argentina.MethodsWe evaluated the clinical and epidemiological characteristics of 5 patients involved in the outbreak. Environmental studies were conducted to determine the source of infection. The genetic profile of Histoplasma capsulatum strains isolated from the index case (IC) were compared with clinical isolates from Argentinean patients not related to the outbreak, using RAPD-PCR with primers 1281-1283.ResultsThe patients were residents of Zapala, and had not visited other geographical areas before. All patients had an influenza-like syndrome, and X-ray revealed disseminated micronodular images throughout the lung parenchyma. The IC needed specific antifungal therapy; the remaining 4 patients had mild symptoms, and did not require therapy. All of them had a good clinical outcome. Strains of H. capsulatum isolated from blood culture and lung biopsy of the IC showed a genetic profile different from other strains analyzed. The presence of the fungus in the environment was demonstrated by the detection of anti-Histoplasma antibodies in BALB/c mice inoculated with soil obtained in a culvert where workers had dug up earth after a landslide.ConclusionsThis outbreak suggests the histoplasmosis endemic area is under the 38° S parallel. Patients from Neuquén, Patagonia Argentina, with compatible symptoms of histoplasmosis should be tested, regardless of their travel or exposure history.