Epidemiological, clinical, diagnostic, and therapeutic features of histoplasmosis: A systematic review.

Histoplasmosis is a mycosis due to a dimorphic fungus Histoplasma capsulatum. This study aimed at providing an overview of histoplasmosis epidemiological, clinical, diagnostic, and therapeutic aspects from the last 30 years. This review was carried out using a systematic literature search on histoplasmosis from 1992 to 2021. We describe the clinical features, diagnostic methods and treatment. Empirical searches were conducted via the databases PubMed, Google Scholar and Science Direct. Between 1992 and 2021, 190 manuscripts were published and reported 212 cases of histoplasmosis. These publications included 115 and 97 cases of American and African histoplasmosis respectively. The number of publications increased over the last ten years with a maximum in 2020 (12.34 % of the cases reported). The disseminated forms of histoplasmosis were the most frequently reported cases as compared to the localized forms. This was the case with the American histoplasmosis (75.65 %) as well as with the African histoplasmosis (55.67 %). Itraconazole (31.17 %) and Amphotericin B (26.62 %) were the most used drugs in the management of these cases. American histoplasmosis is distributed worldwide whereas African histoplasmosis is mainly present in intertropical Africa. There is a critical need for setting up a global surveillance system, towards a better understanding of the disease.

Infection of bats with Histoplasma species.

Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and in yeast form in infected tissues. In this narrative literature review, we summarize the occurrence of Histoplasma spp. in different species of bat tissues (n = 49) and in soil admixed with bat guano where the species of bat dwelling nearby has been identified (an additional 18 species likely infected) to provide an up-to-date summary of data. Most positive isolations are from the Americas and Caribbean, with some studies from Thailand, Malaysia, Nigeria, Slovenia, France, and Australia. We also summarize some of the early experimental work to elucidate pathogenicity, latency, immune response, and faecal excretion in bats. Given the recent recognition of the global extent of histoplasmosis, thermal dimorphism in Histoplasma spp., and global heating, additional work on understanding the complex relationship between Histoplasma and bats is desirable.

The fungal genus Histoplasma causes lung, disseminated, gut and adrenal disease in humans, many with AIDS, but also people with normally functioning immune systems. Exposure and outbreaks are often linked to visiting caves where bats reside. In some locations, considerable quantities of Histoplasma fungus are found in bat guano and, when airborne, can cause infection. There are over 1400 species of bat worldwide. We reviewed the literature from 1962, the first recorded description of bat infection by Histoplasma, and found 49 different species of bat recorded as being infected. Most of the data are from the Americas, very little from Africa, and some from hyperendemic areas in SE Asia. Histoplasma are temperature sensitive fungi and bats, especially those which hibernate and use torpor to survive winter-time shortages of insect prey, occupy environments with a wide range of temperatures. Our understanding of bat infection or latency, in a world with extremes of weather and general heating, is likely to change the Histoplasma/bat relationship in uncertain ways.

Histoplasmosis Caused by Histoplasma capsulatum var. duboisii: A Comprehensive Review of Cases From 1993 to 2019.

BACKGROUND: Histoplasmosis caused by Histoplasma capsulatum var. duboisii (Hcd) is a rare, but probably underestimated, endemic infection described in intertropical Africa. Therefore, the epidemiology of the infection remains unclear, and there is no consensus on therapeutic management. METHODS: Using a comprehensive search on different Internet databases, we collected case reports of Hcd infection published from 1993 to 2019. Epidemiological and clinical charts and therapeutic strategies were analyzed. RESULTS: We found 94 well-documented cases of Hcd infection, and 30.1% of the patients were under 18 years old. Symptoms occurred in some patients several decades after leaving the endemic area. Cutaneous/subcutaneous lesions, bone infections, and lymphadenopathies, both isolated and combined, were the most frequent presentations. The human immunodeficiency virus (HIV) coinfection rate was at 20.8%, with fever, lymphadenopathies, and an absence of bone infection being the differentiating elements from patients living without HIV. The rate of disseminated forms (60.6% in our review) significantly increased as compared to studies published before 1993, but without correlation with HIV infection. The global mortality rate was at 23.4% by the end of follow-up. The outcome was not correlated with the antifungal drug prescribed, nor with HIV serologic status, but was correlated with the initiation of an antifungal therapy. CONCLUSIONS: Hcd histoplasmosis is a severe fungal infection for which the precise mode of acquisition remains to be determined. There is a need for affordable and more specific diagnostic tools. Itraconazole and amphotericin B are the best therapeutic alternatives and should be available in all low-income countries of the endemic area.

African histoplasmosis in a Guinea Bissau patient with HIV-2: Case report and review.

African histoplasmosis is the relatively unknown infection by Histoplasma capsulatum var. duboisii. It is endemic to Central and West Africa, generally involving the skin with potential for systemic dissemination, and has been described mainly in immunocompetent hosts. We present the case of a 30-year-old Bissau-Guinean man with HIV-2 infection known for 16 years, irregularly treated, admitted with two weeks of fever, diarrhoea and cutaneous lesions. Examination revealed multiple subcutaneous nodes, Molluscum contagiosum-like lesions, generalized lymphadenopathy and painful palpation of the left iliac fossa. Laboratory tests showed severe nonhaemolytic anaemia and CD4+ count of 9/mm3, with normal creatinine and hepatic enzymes. Chest roentgenogram was unremarkable and a research for Mycobacterium tuberculosis by GeneXpert® was negative. Nonetheless, given the lack of further diagnostic tools, a presumptive diagnosis of disseminated tuberculosis was made, and the patient was started on tuberculostatic and antiretroviral drugs. Despite initial improvement, a national shortage of antiretrovirals precluded further treatment, with worsening of the clinical picture, namely an increase in the number and dimensions of the skin lesions. An excisional biopsy of a subcutaneous nodule revealed Histoplasma capsulatum var. duboisii. Unfortunately, due to the unavailability of antifungals, the patient died one week later. To our best knowledge, this is the first confirmed case of an HIV infected patient with African histoplasmosis in Guinea-Bissau.

Gingival histoplasmosis: An atypical presentation of African histoplasmosis in three baboons (Papio spp).

Gingival lesions as the sole manifestation of African histoplasmosis (Histoplasma capsulatum var. duboisii) have never been reported in baboons. Grossly, lesions can be indistinguishable from bacterial ulcerative gingivitis or gingival hyperplasia. Clinical outcomes of primary gingival histoplasmosis in baboons are unknown and may complicate colony management decisions.

African Histoplasmosis in HIV-Negative Patients, Kimpese, Democratic Republic of the Congo.

We describe a case series of histoplasmosis caused by Histoplasma capsulatum var. duboisii during July 2011-January 2014 in Kimpese, Democratic Republic of the Congo. Cases were confirmed by histopathology, immunohistochemistry, and reverse transcription PCR. All patients were HIV negative. Putative sources for the pathogen were cellar bats and guano fertilizer exploitation.

Environmental and Wilderness-Related Risk Factors for Histoplasmosis: More Than Bats in Caves.

INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus that causes histoplasmosis, a sporadic endemic mycosis with environmental, occupational, and wilderness exposure-related risk factors. The objectives of this review are to describe these risk factors, to alert clinicians to the different presenting manifestations of histoplasmosis, and to recommend effective management and prevention strategies. METHODS: Internet search engines were queried with keywords to select articles for review over the study period, 1950 to 2018. Articles selected for review included case series, epidemiologic analyses of surveillance data, clinical and laboratory updates, immunologic investigations, and observational and longitudinal studies. Articles excluded from review included systemic mycosis reviews and clinicopathologic conference reports. RESULTS: The principal transmission mechanism of histoplasmosis is by inhalation of spores aerosolized by soil disruption, resulting in pneumonic infections ranging from asymptomatic to disseminated. Although histoplasmosis is more common in endemic regions, nonendemic regions have reported increasing autochthonous and imported cases. Immunocompromised persons are at significantly increased risks of contracting histoplasmosis. Environmental and wilderness-related risk factors for histoplasmosis include bird and bat watching, cave and cave entrance exploration, and bamboo removal and burning. Occupational risk factors for histoplasmosis include road construction, roofing, bridge and water tower work, demolition, and masonry. CONCLUSIONS: Histoplasmosis can result in considerable morbidity. Increased awareness of disease risk factors among the public and the international healthcare community will improve the timely diagnosis and treatment of histoplasmosis and prevent disease progression and dissemination.

African histoplasmosis: new clinical and microbiological insights.

African histoplasmosis is defined as the fungal infection caused by Histoplasma capsulatum var. duboisii (Hcd). Studies focused on distinguishing Hcd and H. capsulatum var. capsulatum (Hcc), which coexist in Africa, are scarce or outdated, and African strains are continuously underrepresented. In this work, 13 cases of African patients with histoplasmosis diagnosed in the Spanish Mycology Reference Laboratory have been reviewed showing that 77% had disseminated disease and AIDS as underlying disease although Hcd infection has been classically considered a rare presentation in AIDS patients. Strains isolated from these patients and other clinical and reference strains were studied by assessing classical identification methods and performing a three-loci multi-locus sequence analysis (MLSA). Classical identification methods based on biochemical tests and measurement of yeast size proved to be useless in distinguishing both varieties. The MLSA defined an African cluster, with a strong statistical support, that included all strains with African origin. Finally, mating type was also determined by using molecular methods revealing an unequal mating type distribution in African strains. In conclusion, historical statements and classical identification methods were useless to distinguish between varieties, whereas molecular analyses revealed that all strains with African origin grouped together suggesting that traditional classification should be revised. Further investigation is required in order to unravel traditional concepts about Hcd infection and support results obtained in this work.

[Multifocal histoplasmosis due to Histoplasma capsulatum var. duboisii in a 22 year-old Senegalese patient without proven immunodepression]. / Histoplasmose multifocale à Histoplasma capsulatum var. duboisii chez un Sénégalais de 22ans sans immunodépression prouvée.

The authors report a case of multifocal African histoplasmosis with polymorphic skin involvement occuring in a patient without proven immunosuppression. He was a young 22-year-old patient from eastern Senegal - but born in Ouganda - who presented with polymorphic skin lesions: ombilicated papulo-nodules, gums and ulcerative and budding lesions. He showed lymphadenopathies without clinical inflammation and with a cheesy appearance of the biopsy but without tuberculosis and also hepatosplenic and bone involvement. Mycological samples of the skin and lymph nodes biopsies revealed yeasts of Histoplasma capsulatum var. duboisii with a positive culture on Sabouraud medium. HIV serology, HTLV1et 2, the serum proteins electrophoresis were unremarkable. Treatment with amphotericin B was irregular because of its inaccessibility in the national territory and its cost. The patient died of sepsis together with the aggravation of his disease.

Disseminated histoplasmosis caused by Histoplasma capsulatum var. duboisii in a non-HIV patient in Burkina Faso: Case report.

Histoplasmosis is a fungal infection due to Histoplasma capsulatum. The African form of this mycosis, caused by Histoplasma capsulatum var. duboisii, remains rare. We report a case of disseminated African histoplasmosis with skin, lymph nodes, bones and viscera localizations. The 22-year-old patient was HIV-seronegative and was considered immunocompetent. The presence of Histoplasma capsulatum var duboisii in ulcerations and a nodule pus aspiration was confirmed by direct microscopic examination and by culture. The medical treatment was based on fluconazole. Even though a regression of the symptoms was observed, the patient died. In disseminated African histoplasmosis, an early laboratory diagnosis must be carried out for accurate treatment.

Late occurrence of Histoplasma duboisii cutaneous and pulmonary infection 18 years after exposure.

We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.

[Aspergillus galactomannan assay for the management of histoplasmosis due to Histoplasma capsulatum var. duboisii in HIV-infected patients: education from a clinical case]. / Intérêt du dosage de l'antigène galactomannane dans le diagnostic et le suivi de l'histoplasmose disséminée à Histoplasma capsulatum var. duboisii au cours du VIH : enseignement à partir d'un cas clinique.

The diagnosis of histoplasmosis due to Histoplasma capsulatum var capsulatum is based on a direct examination identifying encapsulated yeast with narrow-based budding. Galactomannan antigenemia facilitates diagnosis, as well as the monitoring of patients receiving treatment. The case of a HIV-positive patient from Congo-Brazzaville with a disseminated form of African histoplasmosis highlighted the positive galactomannan antigen in this disease due to Histoplasma capsulatum var duboisii. Galactomannan antigenemia remained high with a very slow decrease during antifungal therapy and slow regression of clinical lesions. African histoplasmosis is a rare disease that is difficult to diagnose and rarely described in immunocompromised patients, in whom differential diagnosis can be common. This observation underlines the importance of the galactomannan antigen assay in patients who have travelled to endemic areas. As in the case of Histoplasma capsulatum var capsulatum, the positivity of the Aspergillus galactomannan antigen is very useful in the diagnosis and monitoring of African histoplasmosis.

[Malian first observation of disseminated African histoplasmosis with predominant bone localizations in an HIV-negative child in Bamako (Mali). Review of the literature]. / Première observation malienne d'histoplasmose africaine disséminée à prédominance osseuse chez un enfant VIH négatif. Revue de la littérature.

Endemic deep fungal infections are still under recognised diseases in daily medical practice because of their rarity in sub-Saharan area. The African histoplasmosis Histoplasma capsulatum var. duboisii (H. capsulatum duboisii) is the most frequent variety described in Mali through limited studies in adult patients, since the first case described by Catanei and Kervran (1945). Our case report is a disseminated histoplasmosis in a young 6-year-old african child. He was male and rural. The infectious localisations were mucosae, skin, lymphnodes, urinary tract and bones. Evolution has been marred by an episode of worsening of symptoms despite initial clinical improvement with ketoconazole. After healing of mucocutaneous lesions, we noticed a limitation of ampliation of both wrists. The radiographic bone lesions were lysis of the right lower end of the right radius and cubitus and fragmentation of cubital epiphysis of the same arm. Lacunes were present on the fifth right finger in metatarsus and phalanx; lacune and blowing aspect of the second phalanx of the left third finger was noted. The disseminated form of African histoplasmosis may occur in HIV-negative subject. The prognosis depends on early diagnosis and administration of appropriate and well-conducted therapy.