African Histoplasmosis Research Articles

Cutaneous and Osseous Histoplasmosis caused by Histoplasma capsulatum var. duboisii in a Seemingly Immunocompetent Young Senegalese Woman

African histoplasmosis is a rare deep mycosis caused by Histoplasma capsulatum var duboisii. It can affect various organs such as the skin, lymph nodes, and bones. The diagnosis is often delayed due to its similarity to certain diseases such as tuberculosis, cryptococcosis, pyogenic abscesses, and even neoplasia. We report a case of cutaneous and osseous histoplasmosis caused by H. capsulatum var. duboisii in a seemingly immunocompetent 19-year-old senegalese woman who presented with chronic disseminated cutaneous abscesses, some of which had fistulised, and umbilicated papules on the face. The radiograph of the right forearm showed a metaphyso-diaphyseal osteolytic lesion of the ulna. Histology after biopsy of a facial papule confirmed the diagnosis of histoplasmosis caused by H. capsulatum var duboisii. The patient's condition improved with fluconazole treatment.

Histoplasmose africaine chez un enfant en Guinee: a propos d’un cas

African histoplasmosis is a rare deep mycosis caused by two varieties of Histoplasma capsulatum (capsulatum and duboisii). We report a case of histoplasmosis in an immunocompetent child. 6-year-old female patient, hospitalized for poor general condition, fluctuating inflammatory swelling of the lower limb evolving for 4 months. The clinical examination revealed in an altered and febrile patient, papulo-nodular lesions of variable size, fluctuating in places, disseminated umbilical predominantly on the trunk, the root of the upper and lower limbs. There were also axillary and inguinal lymphadenopathy and osteo-articular involvement. X-ray of the right lower limb revealed osteomyelitis. Histopathology of the biopsied nodule confirmed African histoplasmosis. The rarity of African histoplasmosis in our country corroborates current data from the literature, however this could also be due to an underdiagnosis often influenced by self-medication.

S2.2a African histoplasmosis

S2.2 Histoplasmosis and talaromycosis, September 21, 2022, 3:00 PM - 4:30 PM African histoplasmosis caused by Histoplasma carpsulatum var dubosii is endemic in Africa with few cases reported from outside Africa usually attributed to travelling or visits to sub-Saharan Africa. The pathogenesis is yet unclear. Infection can be acquired via inhalation of microconidia or by direct inoculation. African histoplasmosis commonly presents with papules, nodules, ulcers, swellings, lymph node enlargement, eczematoid, or psoriosiform skin lesions. Subcutaneous abscesses may also develop with discharging sinuses containing yeast cells of the fungus. Although it is generally believed to be acquired through inhalation, the lungs are usually spared. Disseminated forms are usually characterized by the involvement of bones and other organs including the gastrointestinal tract. As a result of limited availability of diagnostics, data on its prevalence and epidemiology are scarce. As with classical histoplasmosis, African histoplasmosis also mimics other clinical entities including TB and neoplasms. More awareness and a high index of suspicion on the part of clinicians will lead to early diagnosis and invariably improve clinical outcomes. An extensive review of literature revealed 365 cases of African histoplasmosis reported globally; 236 cases from Africa and 38 cases from other geographical regions including an indigenous case report from India; the location of the remaining cases was not found, positive HIV status was found in 75 cases only. No statistically significant relationship was observed when comparing the relationship between positive HIV status and fatal outcomes (P >.05, Fisher's exact test). A case report from the UK mentioned 21 cases of African histoplasmosis previously identified in the region and all were associated with travelling to Africa. Out of the 365 identified cases, diagnostic modality was specified in 264 cases; histopathology (87.9%, n = 232), culture (20.8%, n = 55), microscopy (7.2%, n = 19), serology (2.7%, n = 7), cytology (n = 1, 0.4%), polymerase chain reaction (n = 43, 16.3%), and peripheral blood film (n = 1, 0.4%). Amphotericin B (n = 53), itraconazole (n = 37), and ketoconazole (n = 26) were the predominant antifungals used for treatment. More studies are required to ascertain the true burden and epidemiology of African histoplasmosis and to determine whether these cases reported outside Africa were autochthonous or imported from Africa. Diagnosis by culture, although the gold standard is also not routinely achieved due to lack of biosafety level 3 cabinet especially in resource-limited settings, leading to significant under diagnosis. It is imperative that capacity building and strengthening is instituted to aid the diagnosis and management of African histoplasmosis. There is a need for more studies to ascertain whether there are additional phylogenetic species within the African clade.

P355 Pitfalls in medical mycology in India

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Background informationThere is increasing awareness of fungal infections in India. Many diagnostic medical mycology laboratories are now operating in different parts of the country. It is considered worthwhile to mention several pitfalls committed in the diagnosis of mycotic infections in India.MethodsLiterature on fungal infections in India was accessed through different search engines. Publications suggestive of inaccurate reporting were thoroughly read to pinpoint the pitfalls in diagnosis. For checking the accuracy of mycological illustrations, some of the publications were requested from the corresponding authors.ResultsSeveral accessed publications of Indian authors reported the unbelievably frequent occurrence of anthropophilic and zoophilic dermatophytes in soil. A few articles incorporating incorrect diagnoses of systemic infections have also been published in highly reputed journals. For instance, the article ‘Pathogenic Fungi in Soils of Jabalpur, India’ in Mycoses 1990; 33 (3): 116-125 reports 38% incidence of Microsporum (anthropophilic and zoophilic species) in 35 soils examined. Another publication in the August 2009 issue of the same journal mentions frequent isolation of Trichophyton verrucosum, Microsporum audouinii, and M. canis from Jaipur soils. Authors from several Botany departments in Indian Universities have erroneously reported a high frequency of these dermatophytes and T. rubrum from soils and also on Histoplasma capsulatum from some soils. No illustrations were provided for these fungi including H. capsulatum, nor was in vitro conversion of H. capsulatum to yeast form mentioned. There are also reports of erroneous diagnoses of systemic mycoses. In a paper in IJD 2015; 54:451-455, the authors from Kottayam, Kerala reported on African histoplasmosis as the first indigenous case from India. The diagnosis is doubtful as histopathology was not suggestive and the image of the blood agar culture of the fungus at 37°C showed septate cells resembling arthroconidia rather than yeast cells of Histoplasma. Another publication from a premier medical institute in North India [Intestinal Res 2019;17(1):149-152] reported a series of six cases of intestinal histoplasmosis the histopathological illustration was not at all suggestive of Histoplasma and there was no mention of attempting mycological culture.ConclusionLack of knowledge and training of workers from departments of botany and biological sciences in Indian universities has led to the misidentification of human pathogenic fungi The inaccurate diagnosis of mycotic infections has resulted generally from misidentification of the causative fungi and lack of collaboration between histopathologists and medical mycologists. The need for continued training of medical mycologists and for collaboration between the pathologists and medical mycologists is emphasized to avoid erroneous diagnoses.

Histoplasmosis Due to Histoplasma Capsulatum Var. Duboisii: Diagnostic Difficulties in Decentralized Areas

Introduction: Histoplasmosis caused by Histoplasma capsulatum var. duboisii is a deep mycosis that is rampant in Africa. Clinical manifestations are dominated by skin involvement. It is a condition that sometimes poses diagnostic and therapeutic problems. Observation: We report the case of an 81-year-old non-smoking, non-alcoholic patient who presented with polymorphic cutaneous lesions in the form of gums of variable size disseminated on the trunk and the limbs at the stage of rawness or softening, an ulcerative lesion crusty measuring 5 cm on its longest axis sitting at the level of the abdomen and an ulceration measuring 6 cm on its longest axis with purulent and hemorrhagic background with raised edges and indurated base at the level of the right subclavicular region. This picture had been evolving for 9 months in a context of impaired general condition and exertional dyspnoea at stage IV. Pulmonary examination revealed bilateral pleural effusion syndrome. Examination of the lymph nodes revealed no superficial adenopathy. African histoplasmosis was suggested. Retroviral serology and syphilitic serology were negative. The thoraco-abdomino-pelvic computed tomography showed a tumoral process at the apical level of the right lung at the level of the ventral segment of the upper lobe and multiple secondary localizations in the right mediastino-hilar lymph nodes under the skin and bone. The diagnosis of histoplasmosis was retained by the pathological examination of the skin biopsy, which was in favor of histoplasmosis and mycology confirmed histoplasmosis due to Histoplasma capsulatum var. dubosii. The evolution was marked by the death of the patient before the treatment. Conclusion: African histoplasmosis remains a rare condition although a few cases are reported in the literature. Its clinical polymorphism often confuses practitioners.

Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities.

BackgroundHistoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities.MethodsA PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered.FindingsIn the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration.ConclusionsDespite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.

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.

Cerebral histoplasmosis caused by Histoplasma capsulatum var. duboisii in a patient with no known immunodeficiency.

We report the first case of central nervous system histoplasmosis caused by Histoplasma capsulatum var. duboisii in a patient with no underlying immunodeficiency. African histoplasmosis is an underdiagnosed endemic fungal infection which should be included in the differential diagnosis of cerebral lesions in patients originating from Western and Central Africa.

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.

Modification of the Francis Medium for the Conversion of Histoplasma capsulatum to the Yeast-Like Growth Phase.

We propose a modification of Francis agar used for identification of the causative agent of histoplasmosis by in vitro conversion of the mycelial culture to the yeast-like growth phase. For improving of the growth characteristics of the medium, we used FT-agar with glucose-vitamin additives developed for culturing of the tularemia causative agent. The modified Francis medium is characterized by significantly higher growth properties and allowed 10-fold increasing the number of CFU of yeast-like cells of both American and African histoplasmosis causative agent.

Disseminated Histoplasmosis Due to Histoplasma capsulatum var. duboisii in a Non-HIV Patient in Togo: A Case Report

Background : Histoplasmosis is a fungal infection due to Histoplasma capsulatum . We report a case of disseminated African histoplasmosis in an HIV uninfected patient in Togo. Case Report : A 35-year-old woman was admitted in dermatology for disseminated nodular lesions and left shoulder pain for 4 months. On examination, there were firm or softened nodular lesions with torpid ulceration and translucent molluscoid-like papules disseminated on the face, trunk, and limbs. There was also a painful swelling of the left shoulder, with an impotent upper limb. Histology showed an acanthotic epidermis discretely keratotic. In the dermis, there were granulomas with giant cells, histiocytes and polymorphonuclear cells around largely altered yeasts. The presence of Histoplasma capsulatum var. duboisii was confirmed by direct microscopic examination. Chest X-ray showed a left minimal abundance pleurisy. Shoulder x-ray showed heterogeneous lysis of the left humeral head and a large osteopenia of bones associated with left scapulo-humeral dislocation. The medical treatment was based on itraconazole (400mg/day) for 4 months relieved by fluconazole (450 mg/day) with good evolution after 4 months. Conclusion : A disseminated form of African histoplasmosis can be observed in non-HIV infected patients. The prognosis depends on the precocity of the diagnosis and the treatment.

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.

Tonsillar ulceration as manifestation of disseminated African histoplasmosis in an immunocompetent Portuguese host

Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum. Rare in Europe but endemic in some regions of Brazil, United States, Africa and Asia. Most of the cases are asymptomatic. Disseminated form is defined by the presence of an extra-pulmonary focus, particularly associated with immunosuppression. We report a case of an unilateral persisted tonsillar ulceration, in an immunocompetent Portuguese host, as manifestation of disseminated African histoplasmosis 45 years later after living 3 years in Africa.

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.

Histoplasmosis by Histoplasma capsulatum var. duboisii Observed at the Laboratory of Pathological Anatomy of Lomé in Togo.

Our study aimed to describe the epidemiological, clinical, and diagnostic aspects of African histoplasmosis in Togo through a descriptive and cross-sectional study on histological diagnosed African histoplasmosis in Pathology Department of Lomé from 2002 to 2016 (15 years). A total of 17 cases of African histoplasmosis were diagnosed. The sex ratio (M/F) was 1.8. The annual incidence was 1.1 cases. The mean age of the patients was 27.2 ± 0.4 years. All our patients were of social categories with a low socioeconomic level. HIV infection was known in 3 patients and one patient contracted tuberculosis. The clinical manifestations were cutaneous in 7 cases, cutaneous and mucous in 3 cases, cutaneous and lymph node in 3 cases, cutaneous and bone in 2 cases, and disseminated in 2 cases. The samples examined consisted of 14 cutaneous biopsies measuring 2-3 cm and 3 ganglionic biopsies each measuring 4 cm of major axis. Histologically, all cases were of chronic form made of granulomatous reaction with ovoid yeasts measuring between 1 and 2 microns. Despite the low frequency of this disease in our country, it should be kept constantly in mind before any granulomatous lesions, especially in the context of the HIV pandemic.

Histoplasmose multifocale à Histoplasma capsulatum var. duboisii chez un Sénégalais de 22 ans 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.

Champignons non dermatophytiques et non candidosiques isolés au CHU Le Dantec de Dakar en 2014 : étude épidémiologique, clinique et mycologique

In recent years, the incidence of superficial fungal infections involving nondermatophytic and noncandidal fungi increased considerably. The objective of this work was to analyze the epidemiological, clinical and mycological fungal infections due to nondermatophytic and noncandidal fungi diagnosed in the laboratory of parasitology-mycology of Le Dantec hospital in Dakar. With a retrospective study of the various cases of nondermatophytic and noncandidal fungi isolated in the laboratory of parasitology-mycology during the period of November 2013 to December 2014, we collected 22 cases of infections in 11 men and 11 women; age ranging from 17 to 75 years with a mean of 45.3 years (sex ratio=1): eight cases of intertrigo, seven cases of onychomycosis, four cases of palmoplantar keratoderma (KPP), a case of onychomycosis associated with interdigital intertrigo, a case of infectious myositis and one case of African histoplasmosis. We have isolated and identified a total of 22 nondermatophytic and noncandidal fungi: ten Fusarium, five Trichosporon, two Chrysosporium, two Geotrichum, one Rhodotorula, one Neoscytalidium dimidiatum and one Histoplasma capsulatum var. duboisii. So we are seeing the emergence of nondermatophytic and noncandidal increasingly isolated from superficial and local lesions. These fungi, generally contaminants or commensal, cause a problem regarding their direct involvement in pathological processes in which they are isolated. So we should respect the recommendations proposed for their involvement in pathological processes and, by a collaboration between clinician and biologist, demonstrate their real involvement through effective, targeted treatment.

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.

Epidemiology of Histopathologically Diagnosed Mycoses: The Ibadan 37 Years Experience

Background: Recent studies suggest that the occurrence of mycotic infections is increasing worldwide, due to predisposing factors such as immunosuppression from chemotherapy, surgery, HIV/AIDS and debilitating diseases, but there is paucity of information regarding fungal infections in our environment. Aim: This study aimed to characterise mycoses diagnosed histopathologically in the Department of Pathology, University College Hospital (UCH), Ibadan between 1970 and 2006. Methods: The surgical pathology and autopsy records of all mycoses diagnosed during the study period were retrieved and analysed. One hundred and eighty-six mycoses were recruited. Results: There was a progressive decline in the annual occurrence of mycoses from 19.7% to Original Research Article Ngwu et al.; BJMMR, 10(3): 1-9, 2015; Article no.BJMMR.19301 2 1.1%. The cases comprised 121 males and 65 females, whose ages ranged from 6 weeks to 80 years, with 68.3% being less than 40 years of age. The mean age of the male patients (29.9±18.4 years) was not significantly different from that of the females (27.4±18.2 years), t = 0.867, df = 186, p = 0.387. The most common mycotic infections were African histoplasmosis (28%), aspergillosis (12.4%), mycetoma (9.7%), candidiasis (8.6%) and actinomycosis (7%). Systemic mycoses accounted for 62%, followed by subcutaneous mycoses (21%), cutaneous mycoses (11%) and superficial mycoses (6%). The most common sites involved were the skin (23.7%), upper and lower limbs (15.6%), nose (11.3%) and lungs (7%). Conclusion: The present study has demonstrated that fungal infections are common and account for significant morbidity and disease burden in our environment.

Disseminated Histoplasmosis and Secondary Hemophagocytic Syndrome in a Non-HIV Patient.

Histoplasma duboisii, a variant of Histoplasma capsulatum that causes “African histoplasmosis,” can be resistant to itraconazole, requiring intravenous amphotericin B treatment. Rarely, these patients do not respond to intravenous antifungal therapy, and in such cases, patients may progress to develop secondary hemophagocytic lymphohistiocytosis (HLH). We present a case of a 34-year-old male patient with sickle cell disease who presented with a 5-month history of an enlarging painless axillary mass, persistent low grade fevers, night sweats, weight loss, and anorexia. An excisional biopsy of the right axillary lymph node revealed yeast and granulomas consistent with histoplasma infection. He was started on oral itraconazole. After 4 weeks of therapy, laboratory evaluation revealed worsening anemia, thrombocytopenia, and transaminitis. Due to failure of oral therapy, he was admitted for intravenous amphotericin B treatment. During his hospital course anemia, thrombocytopenia, and transaminitis all worsened. A bone marrow biopsy was done that was consistent with HLH. His clinical status continued to deteriorate, developing multiorgan failure and disseminated intravascular coagulation. He unfortunately had a cardiorespiratory arrest after eight days of admission and passed away.