DOCSLIB.ORG

Diagnostic Methods for Detection and Characterisation of Dimorphic Fungi Causing Invasive Disease in Africa: Development and Evaluation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Diagnostic Methods for Detection and Characterisation of Dimorphic Fungi Causing Invasive Disease in Africa: Development and Evaluation Diagnostic methods for detection and characterisation of dimorphic fungi causing invasive disease in Africa: Development and evaluation TSIDISO GUGU MAPHANGA Diagnostic methods for detection and characterisation of dimorphic fungi causing invasive disease in Africa: Development and evaluation by TSIDISO GUGU MAPHANGA A thesis submitted in partial fulfilment of the requirements for the degree of PHILOSOPHIAE DOCTOR PhD (Medical Microbiology) in Department of Medical Microbiology Faculty of Health Sciences University of the Free State Bloemfontein, South Africa Promoter: A/Prof NP Govender March 2020 DECLARATION I, Tsidiso Gugu Maphanga, declare that the research thesis hereby submitted to the University of the Free State for the Doctoral Degree in Medical Microbiology and the work contained therein is my own original work and has not previously, in its entirety or in part, been submitted to any institution of higher education for degree purposes. I further declare that all sources cited are acknowledged by means of a list of references. Signed this day of 2020 Research is to see what everybody else has seen and to think what nobody else has thought Albert Szent-Györgi (US Biochemist) DEDICATION To my late brother, my mechanical engineer (Thabiso Benson Masilela): I will never forget all the plans we had, the motivations, love and laughter we shared. Life is never the same without you; I miss you daily. ACKNOWLEDGMENTS To God of Abraham, Isaac, Jacob, St Engenas and my God: Thank you for giving me strength, knowledge, wisdom and the ability to undertake this project. Your faithfulness reaches to the skies. A/Professor Nelesh P. Govender (supervisor): I would like to express my sincere gratitude for your patience, guidance, continuous support and useful comments received throughout this project. Your immense knowledge contributed greatly to my understanding of this project. Thank you for taking a chance on me and for always being optimistic even when things were not going according to plan. Professor Anwar A. Hoosen (mentor): no words can describe my gratitude. Thank you for seeing potential in me. I am grateful for the opportunities and support you have given me throughout my postgraduate studies. Thato Malele (husband): Thank you for your understanding, support and encouragement. Your prayers throughout this PhD have been amazing. You have been the pillar of my strength and you believed in me when I stopped believing in myself and for that I am forever grateful. Matlhatse Malele and Thato Jnr Malele (children): Thank you for keeping me sane; your presence in my life came just at the right time. Mavis Mashego and Happy Maphanga (parents); Mlungisi, Phumla, Sabelo, Lesego and Tumelo (siblings): Thank you for supporting me spiritually throughout my academic years. Your love and words of encouragement kept me going. Ruth Mpembe (laboratory manager): Thank you for your support and words of encouragement. Samaria Mafuma, Iqra Barakzai, Dr Adeola Rotimi, Dr Nontutuko Maningi, and Dr Nomcebo Sengwayo (friends): I am grateful for your patience, support and words of encouragement, but most of all for the love you showed me when I needed you most. Serisha Naicker, Mabatho Mhlanga, Mbali Dube, Ivy Rukasha and Sydney Mokgokotleng (colleagues): Thank you for making my workplace more constructive to work in. Your amazing support and words of encouragement received during this period were much appreciated. Thokozile Gloria Zulu (my mycologist): Thank you for sharing your knowledge. The fun we had in the laboratory learning about fungi was amazing. I am also thankful for the words of encouragement, your support and always making sure that I was well taken care of. I am in debt to you; may God truly bless you. Dr Monica Birkhead: Thank you for your tremendous support, your insightful comments and encouragement. You made me believe that it is possible. TABLE OF CONTENTS Page LIST OF FIGURES vii LIST OF TABLES viii LIST OF UNITS AND ABBREVIATIONS ix LIST OF PUBLICATIONS xii NATIONAL CONFERENCE PRESENTATIONS xiv ABSTRACT xvi CHAPTER 1: 1.1 Introduction 1 1.2 Thesis structure 4 References 5 CHAPTER 2: LITERATURE REVIEW 2.1 Introduction 7 2.2 Classification of dimorphic fungal pathogens 8 2.2.1 Phylogenetic relationship of dimorphic fungal pathogens 8 2.3 General characteristics of dimorphic fungi 11 2.3.1 Dimorphism 14 2.3.2 Virulence factors of dimorphic fungi 14 2.4 Clinical manifestations of dimorphic fungal infections 15 2.4.1 Emergomycosis 16 2.4.2 Blastomycosis 17 2.4.3 Histoplasmosis 19 2.4.4 Sporotrichosis 20 2.5 Prevention of acquisition of dimorphic fungal pathogens 21 2.5.1 Treatment of dimorphic fungal infections 22 2.5.2 Antifungal susceptability testing of dimorphic fungal isolates 23 2.6 Eco-epidemiology of dimorphic fungal infections 25 2.7 Diagnostic methods for the identification of dimorphic fungi 31 2.7.1 Histopathology method for the identification of dimorphic fungi 31 i Page 2.7.2 Culture-based method for the identification of dimorphic fungi 32 2.7.3 Antigen detection method for the identification of dimorphic fungi 33 2.8 Molecular methods for the detection and characterisation of dimorphic 35 fungi 2.8.1 Conventional and quantitative PCR for the detection of dimorphic fungi 35 2.8.2 Characterisation of dimorphic fungi using multilocus sequence typing 36 2.8.3 Whole genome sequencing and single nucleotide polymorphism (SNP) 38 analysis of dimorphic fungi 2.9 Summary 41 References 44 CHAPTER 3: In vitro antifungal susceptibity of yeast and mould phases of 65 isolates of dimorphic fungal pathogen Emergomyces africanus (Formerly Emmonsia sp.) from HIV-infected South African patients 3.1 ABSTRACT 65 3.2 INTRODUCTION 66 3.3 MATERIALS AND METHODS 68 3.3.1 Isolates and case definition 68 3.3.2 Identification to the species level 69 3.3.3 Antifungal susceptibility testing 69 3.3.4 Statistical methods 70 3.3.5 Ethics approval 70 3.4 RESULTS 70 3.4.1 Cases and isolates 70 3.4.2 Antifungal susceptibility testing of Emergomyces isolates 71 3.4.3 Minimum inhibitory concentration distribution and patient outcome 74 3.5 DISCUSSION 76 3.5.1 Study limitations 78 3.6 CONCLUSION 78 ii Page 3.7 ACKNOWLEDGMENTS 78 3.8 FUNDING 78 3.9 CONFLICTS OF INTEREST 78 3.10 AUTHORS’ CONTRIBUTIONS 78 REFERENCES 80 CHAPTER 4: A diagnostic accuracy case-control study to evaluate a 83 Histoplasma capsulatum urine antigen enzyme immunoassay among patients with suspected histoplasmosis 4.1 ABSTRACT 84 4.2 INTRODUCTION 85 4.3 MATERIALS AND METHODS 86 4.3.1 Participants, specimens and case definitions 86 4.3.2 Detection of Histoplasma antigen 87 4.3.3 Species confirmation 87 4.3.4 Statistical methods 88 4.3.5 Ethics approval 88 4.4 RESULTS 88 4.4.1 Cases with suspected histoplasmosis 88 4.4.2 Clinical details of 171 particitipants with or without invasive fungal 89 disease 4.4.3 Detection of Histoplasma capsulatum antigen from urine 89 4.5 DISCUSSION 90 4.5.1 Study limitations 93 4.6 CONCLUSION 94 4.7 ACKNOWLEDGMENTS 94 4.8 FUNDING 94 4.9 CONFLICTS OF INTEREST 94 4.10 AUTHORS’ CONTRIBUTIONS 94 REFERENCES 95 iii Page CHAPTER 5: Human blastomycosis in South Africa caused by Blastomyces 105 percursus and Blastomyces emzantsi sp. nov., 1967-2014 5.1 ABSTRACT 106 5.2 INTRODUCTION 106 5.3 MATERIALS AND METHODS 107 5.3.1 Case detection and isolate archive 107 5.3.2 Morphological description and electron 108 5.3.3 Antifungal susceptibility testing 108 5.3.4 DNA extraction, PCR amplification and sequencing 109 5.3.5 Multilocus sequence typing phylogenetic analysis 109 5.3.6 Whole genome sequencing and de novo assembly 109 5.3.7 Phylogenetic analysis using whole-genome single nucleotide 109 polymorphisms 5.3.8 Statistical methods 110 5.3.9 Ethics approval 110 5.4 RESULTS 110 5.4.1 Isolates and cases 110 5.4.2 Mycological examination of the isolates 110 5.4.3 Antifungal susceptibility testing of isolates 111 5.4.4 Multilocus and whole genome phylogenetics analyses 111 5.4.5 Clinical presentation and treatment of 10 cases 112 5.4.5.1 Group one isolates resembling Blastomyces percursus 112 5.4.5.2 Group two isolates resembling Blastomyces emzantsi 112 5.4.6 Genome assembly sizes 112 5.4.7 Nucleotide diversity 112 5.4.8 Mating identification from whole genome sequencing 113 5.4.9 BAD-1 gene identification from whole genome sequencing 113 5.4.10 Taxonomy 113 5.5 DISCUSSION 114 5.5.1 Study limitations 116 5.6 CONCLUSION 116 iv Page 5.7 ACKNOWLEDGMENTS 117 5.8 FUNDING 117 5.9 CONFLICTS OF INTEREST 117 5.10 AUTHORS’ CONTRIBUTIONS 117 REFERENCES 118 CHAPTER 6: Molecular identification of dimorphic fungi causing systemic 134 mycoses among South African patients 6.1 ABSTRACT 135 6.2 INTRODUCTION 136 6.3 MATERIALS AND METHODS 137 6.3.1 Fungal isolates and case definition 137 6.3.2 Molecular identification from cultured isolates 138 6.3.3 Genus confirmation by phenotypic methods 138 6.3.4 Statistical methods 139 6.3.5 Ethics approval 139 6.4 RESULTS 139 6.4.1 Isolates and cases 139 6.4.2 Identification of dimorphic fungi by phenotypic methods at the 140 diagnostic laboratories 6.4.3 Identification of dimorphic fungi by phenotypic methods at the 140 reference laboratory 6.4.4 Identification of dimorphic fungi by DNA- sequencing methods at the 141 reference laboratory 6.4.5 Clinical presentation of the 156 cases with systemic mycosis 141 6.5 DISCUSSION 143 6.5.1 Study limitations 146 6.6 CONCLUSION 147 6.7 ACKNOWLEDGMENTS 147 6.8 FUNDING 147 6.9 CONFLICTS OF INTEREST 147 6.10 AUTHORS’ CONTRIBUTIONS 147 v Page REFERENCES 148 CHAPTER 7: CONCLUSION 157 7.1 Concluding remarks 157 7.2 Future research 160 REFERENCES 163 Supplementary Appendix: Human blastomycosis in South Africa caused by 165 Blastomyces percursus and Blastomyces emzantsi sp.
Load more

Recommended publications
  • Congo DRC, Kamwiziku. Mycoses 2021
    Received: 8 April 2021 | Revised: 1 June 2021 | Accepted: 10 June 2021 DOI: 10.1111/myc.13339 REVIEW ARTICLE Serious fungal diseases in Democratic Republic of Congo – Incidence and prevalence estimates Guyguy K. Kamwiziku1 | Jean- Claude C. Makangara1 | Emma Orefuwa2 | David W. Denning2,3 1Department of Microbiology, Kinshasa University Hospital, University of Abstract Kinshasa, Kinshasa, Democratic Republic A literature review was conducted to assess the burden of serious fungal infections of Congo 2Global Action Fund for Fungal Infections, in the Democratic Republic of the Congo (DRC) (population 95,326,000). English and Geneva, Switzerland French publications were listed and analysed using PubMed/Medline, Google Scholar 3 Manchester Fungal Infection Group, The and the African Journals database. Publication dates spanning 1943– 2020 were in- University of Manchester, Manchester Academic Health Science Centre, cluded in the scope of the review. From the analysis of published articles, we estimate Manchester, UK a total of about 5,177,000 people (5.4%) suffer from serious fungal infections in the Correspondence DRC annually. The incidence of cryptococcal meningitis, Pneumocystis jirovecii pneu- Guyguy K. Kamwiziku, Department monia in adults and invasive aspergillosis in AIDS patients was estimated at 6168, of Microbiology, Kinshasa University Hospital, University of Kinshasa, Congo. 2800 and 380 cases per year. Oral and oesophageal candidiasis represent 50,470 Email: [email protected] and 28,800 HIV- infected patients respectively. Chronic pulmonary aspergillosis post- tuberculosis incidence and prevalence was estimated to be 54,700. Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitiza- tion) probably has a prevalence of 88,800 and 117,200.
    [Show full text]
  • A Case of Disseminated Histoplasmosis Detected in Peripheral Blood Smear Staining Revealing AIDS at Terminal Phase in a Female Patient from Cameroon
    Hindawi Publishing Corporation Case Reports in Medicine Volume 2012, Article ID 215207, 3 pages doi:10.1155/2012/215207 Case Report A Case of Disseminated Histoplasmosis Detected in Peripheral Blood Smear Staining Revealing AIDS at Terminal Phase in a Female Patient from Cameroon Christine Mandengue Ebenye Cliniques Universitaires des Montagnes, Bangangt´e, Cameroon Correspondence should be addressed to Christine Mandengue Ebenye, [email protected] Received 28 August 2012; Revised 2 November 2012; Accepted 5 November 2012 Academic Editor: Ingo W. Husstedt Copyright © 2012 Christine Mandengue Ebenye. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Histoplasmosis is endemic in the American continent and also in Sub-Saharan Africa, coexisting with the African histoplasmosis. Immunosuppressed patients, especially those with advanced HIV infection develop a severe disseminated histoplasmosis with fatal prognosis. The definitive diagnosis of disseminated histoplasmosis is based on the detection of Histoplasma capsulatum from patient’ tissues samples or body fluids. Among the diagnostic tests peripheral blood smear staining is not commonly used. Nonetheless a few publications reveal that Histoplasma capsulatum has been discovered by chance using this method in HIV infected patients with chronic fever and hence revealed AIDS at the terminal phase. We report a new case detected in a Cameroonian woman without any previous history of HIV infection. Peripheral blood smear staining should be commonly used for the diagnosis of disseminated histoplasmosis in the Sub-Saharan Africa, where facilities for mycology laboratories are unavailable. 1. Introduction 1987 [2].
    [Show full text]
  • Detection of Histoplasma DNA from Tissue Blocks by a Specific
    Journal of Fungi Article Detection of Histoplasma DNA from Tissue Blocks by a Specific and a Broad-Range Real-Time PCR: Tools to Elucidate the Epidemiology of Histoplasmosis Dunja Wilmes 1,*, Ilka McCormick-Smith 1, Charlotte Lempp 2 , Ursula Mayer 2 , Arik Bernard Schulze 3 , Dirk Theegarten 4, Sylvia Hartmann 5 and Volker Rickerts 1 1 Reference Laboratory for Cryptococcosis and Uncommon Invasive Fungal Infections, Division for Mycotic and Parasitic Agents and Mycobacteria, Robert Koch Institute, 13353 Berlin, Germany; [email protected] (I.M.-S.); [email protected] (V.R.) 2 Vet Med Labor GmbH, Division of IDEXX Laboratories, 71636 Ludwigsburg, Germany; [email protected] (C.L.); [email protected] (U.M.) 3 Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany; [email protected] 4 Institute of Pathology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; [email protected] 5 Senckenberg Institute for Pathology, Johann Wolfgang Goethe University Frankfurt, 60323 Frankfurt am Main, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-30-187-542-862 Received: 10 November 2020; Accepted: 25 November 2020; Published: 27 November 2020 Abstract: Lack of sensitive diagnostic tests impairs the understanding of the epidemiology of histoplasmosis, a disease whose burden is estimated to be largely underrated. Broad-range PCRs have been applied to identify fungal agents from pathology blocks, but sensitivity is variable. In this study, we compared the results of a specific Histoplasma qPCR (H. qPCR) with the results of a broad-range qPCR (28S qPCR) on formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients with proven fungal infections (n = 67), histologically suggestive of histoplasmosis (n = 36) and other mycoses (n = 31).
    [Show full text]
  • Traveler Information
    Traveler Information QUICK LINKS Fungal Disease—TRAVELER INFORMATION • Introduction • Geographic Distribution • Risk Factors • Symptoms • Prevention • Need for Medical Assistance Traveler Information FUNGAL DISEASE INTRODUCTION Fungi are found in soil and on vegetation, as well as on many indoor surfaces and human skin. More than 1.5 million different species of fungi exist, but only several hundred are known to cause human infection. In healthy persons, fungal disease is generally asymptomatic or self-limited. However, infection can lead to significant disease, particularly in persons who are immune compromised. In travelers, important fungal infections to be aware of include coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. These fungal diseases are acquired by the respiratory route and often affect the respiratory system. Infections occur after inhalation of spores found in dust, soil, bird/bat guano, or decaying vegetation following excavation, construction, landscaping, earthquakes, dirt bike riding, spelunking, and other activities. GEOGRAPHIC DISTRIBUTION Coccidioidomycosis, also known as valley fever, is a fungal infection caused by fungi that grow in the soil, mainly in the southwestern United States, parts of Mexico, and Central and South America. Coccidioidomycosis is a growing health concern and a common cause of pneumonia in endemic areas. At least 30-60% of people who live in an endemic region are exposed to the fungus at some point during their lives. In most people the infection will resolve spontaneously, but for those who develop severe infections or chronic pneumonia, medical treatment is necessary. Exposures of concern include arid regions and places where excavation is occurring. Histoplasmosis is an infection caused by a fungus that grows as a mold in soil and as yeast in animal and human hosts.
    [Show full text]
  • Primary Cutaneous Cryptococcosis: About a Diffuse Case in a Subject Not Infected by HIV in West Africa
    Scientifi c Journal of Clinical Research in Dermatology Case Report Primary Cutaneous Cryptococcosis: about a Diffuse Case in a Subject not Infected by HIV in West Africa - Andonaba JB1*, Konate I1, Ouedraogo AS2, Sangare I1, Bamba S1, Diallo B1, Barro/Traore F2, Niamba P2 and Traore A2 1Head of Department Dermatology, Bobo-Dioulasso Nazi Boni University, Burkina Faso 2Joseph Ki-Zerbo University of Ouagadougou, Burkina Faso *Address for Correspondence: Andonaba Jean Baptiste, Head of Dermatology Department, Bobo- Dioulasso Nazi Boni University, Burkina Faso, Tel: +226 70404018; E-Mail: Submitted: 07 July 2017; Approved: 04 August 2017; Published: 04 August 2017 Citation this article: Andonaba JB, Konate I, Ouedraogo AS, Sangare I, Bamba S, et al. Primary Cutaneous Cryptococcosis: about a Diffuse Case in a Subject not Infected by HIV in West Africa. Sci J Clin Res Dermatol. 2017;2(1): 028-031. Copyright: © 2017 Andonaba JB, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Scientifi c Journal of Clinical Research in Dermatology Summary The Primary Cutaneous Cryptococcosis (PCC) is a fungal infection due to the Cryptococcus neoformans (C. neoformans). It occurs after a transcutaneous inoculation most often among the subject immunocompromized. We report a case of profuse PCC at a young subject, not infected by HIV in West Africa. The observation has concerned a young farmer of 21 years who has presented umbilicated and necrotic papules, festers by location and diffuse, associated with nodular and tumoral lesions, painless and scattered whose the puncture brought back of frank pus.
    [Show full text]
  • Review of Histoplasmosis in Animals L.J
    Review of Histoplasmosis in Animals L.J. Wheat, MD and J.S. Renschler, DVM, PhD, Dipl ACVP DIAGNOSTIC TEST TEST CODE SPECIMEN TYPE MVista® Histoplasma Antigen Quantitative EIA 310 Urine, Serum, BAL, CSF & other pipetteable fluid Histoplasma Antibody by Immunodiffusion 321 Serum MVista® Histoplasma Canine Antibody IgG EIA 327 Serum, CSF MVista® Histoplasma Feline Antibody IgG EIA 328 Serum, CSF 1. Introduction Histoplasmosis is a common endemic mycosis in the United States. In a 1981 study, the case rates per 100,000 patient-years-at-risk at 14 colleges of veterinary medicine for histoplasmosis was 2.5 times higher than blastomycosis and 3.5 times higher than coccidioidomycosis (1). Histoplasma capsulatum was isolated from 22% of healthy appearing dogs from Cincinnati, Ohio while Blastomyces dermatitidis was isolated from only 2% (2). In Lexington Kentucky, H. capsulatum was isolated from 40% of healthy dogs while B. dermatitidis was isolated from only 1% (3). In Africa histoplasmosis may be caused by H. capsulatum variety duboisii (4) and in Ethiopia and the Middle East by H. capsulatum variety farciminosi (5-7). While histoplasmosis is not transmissible from animal to human, concurrent infection is not uncommon because of shared exposure (8). Histoplasmosis usually causes pulmonary and/or disseminated disease. Familiarity with the clinical manifestations may alert a veterinarian to consider the diagnosis. Antigen detection in urine and serum may provide a rapid diagnosis, precluding the need for invasive procedures to obtain specimens for organism identification in many patients. Antibody testing may be useful in cases with negative results by antigen testing. Itraconazole is the treatment of choice, and therapy may be monitored by antigen testing.
    [Show full text]
  • Burden of Severe Fungal Infections in Burkina Faso
    Journal of Fungi Article Burden of Severe Fungal Infections in Burkina Faso Sanata Bamba 1, Adama Zida 2, Ibrahim Sangaré 1, Mamoudou Cissé 1, David W. Denning 3,4 ID and Christophe Hennequin 5,6,* 1 Service de Parasitologie—Mycologie, CHUSS, Bobo-Dioulasso, Burkina Faso; [email protected] (S.B.); [email protected] (I.S.); [email protected] (M.C.) 2 Service de Parasitologie—Mycologie, CHU Yalgado Ouédraogo, Ouagadougou, Burkina Faso; [email protected] 3 National Aspergillus Centre, Wythenshawe Hospital and The University of Manchester, Manchester M13 9PL, UK; [email protected] 4 Leading International Fungal Education (LIFE), Cheshire SK10 9AR, UK 5 Service de Parasitologie—Mycologie, Hôpital St Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France 6 Sorbonne Universités, UPMC Univ Paris 06, INSERM, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France * Correspondence: [email protected]; Tel.: +33-149-282-186 Received: 24 January 2018; Accepted: 9 March 2018; Published: 11 March 2018 Abstract: Because of the limited access to more powerful diagnostic tools, there is a paucity of data regarding the burden of fungal infections in Burkina Faso. The aim of this study was to estimate the incidence and prevalence of serious fungal infections in this sub-Saharan country. We primarily used the national demographic data and performed a PubMed search to retrieve all published papers on fungal infections from Burkina Faso and its surrounding West African countries. Considering the prevalence of HIV infection (0.8% of the population) and a 3.4% incidence of cryptococcosis in hospitals, it is estimated that 459 patients per year develop cryptococcosis.
    [Show full text]
  • African Histoplasmosis of the Penis Tchin Darré1,*, Matchonna Kpatcha2, Toukilnan Djiwa1,Edoésewa2, Améyo Monique Dorkenoo3, Mouhamed Kouyaté4 and Gado Napo-Koura1
    Oxford Medical Case Reports, 2020;6,196–199 doi: 10.1093/omcr/omaa043 Case Report CASE REPORT African histoplasmosis of the penis Tchin Darré1,*, Matchonna Kpatcha2, Toukilnan Djiwa1,EdoéSewa2, Améyo Monique Dorkenoo3, Mouhamed Kouyaté4 and Gado Napo-Koura1 1Department of Pathology, University Teaching Hospital of Lomé, Lomé, Togo, 2Departement of Urology, University Teaching Hospital of Lomé, Togo, 3Department of Mycology, University Teaching Hospital of Lomé, Lomé, Togo, 4Department of Pathology, University Teaching Hospital of Treichville, Abidjan, Ivory Coast *Corresponding author’s contact information: Dr Tchin DARRE: University of Lomé. BP: 1515, Lomé, Togo. E. mail: [email protected]. Tel: (+228). 90318532 Abstract African Histoplasmosis is deep mycosis caused by Histoplasma duboisii and genitourinary involvement is extremely rare. We report a case of African histoplasmosis in a 27-year-old subject with painful penis ulcer. Ulcer edge biopsy had revealed inflammatory granulomas made of epithelioid cells, lymphoplasmocytes, polynuclear eosinophils and giant multinucleated cells, with ovoid yeasts surrounded by a clear halo. PAS and Grocott stains revealed numerous fungal structures with a morphology measuring 7 to 15 nm. The diagnosis Histoplasma capsulatum var. duboisii was placed and the patient put on itraconazole (400 mg/day) for six months with a good course. African histoplasmosis of the subject penis is an extremely rare entity. The diagnosis of certainty often makes use of histology and mycological examination, and makes it possible to eliminate differential diagnoses such as cryptoccocosis, tuberculosis or cancer. INTRODUCTION of the localization of affection to the penis and the difficulties of its management. Histoplasmosis is a fungal infection caused by Histoplasma cap- sulatum, a dimorphic fungus with two distinct varieties affecting the humans: Histoplasma capsulatum var capsulatum and Histo- plasma capsulatum var.
    [Show full text]
  • HIV-Associated Histoplasmosis: Current Perspectives
    HIV/AIDS - Research and Palliative Care Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW HIV-Associated Histoplasmosis: Current Perspectives This article was published in the following Dove Press journal: HIV/AIDS - Research and Palliative Care Thein Myint1 Abstract: Histoplasmosis is an endemic mycosis caused by Histoplasma capsulatum. Nicole Leedy1 Infection develops by inhalation of microconidia from environmental sites inhabited by birds Evelyn Villacorta Cari1 and bats. Disseminated disease is the usual presentation due to impaired cellular immunity. LJosephWheat 2 Common clinical manifestations include fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms. Histoplasma antigen detection is the most sensitive method for diag- 1 Division of Infectious Diseases, nosis. The sensitivity of the MVista® Quantitative Histoplasma antigen enzyme immunoassay Department of Internal Medicine, University of Kentucky, Lexington, KY, is 95–100% in urine, over 90% in serum and bronchoalveolar lavage (BAL) antigen and 78% USA; 2MiraVista Diagnostics, Indianapolis, in cerebral spinal fluid (CSF). A proven diagnosis can be established by culture or pathology IN, USA with sensitivities between 70% and 80%. The sensitivity of antibody detection by immuno- diffusion or complement fixation was between 60% and 70%. Diagnosis using molecular methods has not been adequately validated for implementation and FDA cleared assays are unavailable. Liposomal amphotericin B should be used for 1–2 weeks followed by itraconazole For personal use only. for at least one year until CD4 counts are above 150 cells/mm3, HIV viral load is below 400 copies/mL and Histoplasma urine antigen is negative. Serum itraconazole level should be monitored to avoid drug toxicity.
    [Show full text]
  • Imported Mycoses: Some Diagnostic Problems W
    Postgrad Med J: first published as 10.1136/pgmj.55.647.598 on 1 September 1979. Downloaded from Postgraduate Medical Journal (September 1979) 55, 598-602 Imported mycoses: some diagnostic problems W. ST C. SYMMERS M.D. Charing Cross Hospital and Medical School, The Reynolds Building, St Dunstan's Road, London W6 8RP Summary Trichophyton and possibly of other fungi that cause Infections by actinomycetes or by true fungi may cause dermatophytosis may invade the subcutaneous diagnostic difficulties in countries where they are not tissues and eventually give rise to distant lesions as a familiar. Illustrative cases from a series of 353 result of spread by the lymphatics or in the blood instances are given together with rare indigenous stream. examples of the same infections. Early, accurate In any case of the infections listed above, and diagnosis is essential for rational and effective particularly in any case of those infections that occur treatment. less frequently in Europe than in other parts of the world, the possibility that infection took place while Introduction the patient was resident or travelling outside Europe The first, and in many cases the greatest, problem ought to be considered. None of the infections is in the correct clinical management of mycoses is their confined to Europe. In contrast, some important recognition. In general, delay in the diagnosis of mycoses do not occur naturally in north-westernProtected by copyright. mycoses results primarily from failure to consider Europe. that a fungal or actinomycetous infection may be the cause of a patient's symptoms. In this respect the Mycoses not indigenous in north-western Europe problem is a commonplace one, not confined to Blastomycosis (caused by Blastomyces dermati- mycoses: its solution lies in greater knowledge and tidis); coccidioidomycosis; histoplasmosis, including greater awareness of diagnostic possibilities.
    [Show full text]
  • Histoplasmosis Diagnosed in Europe and Israel: a Case Report and Systematic Review of the Literature from 2005 to 2020
    Journal of Fungi Review Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020 Spinello Antinori 1,2,* , Andrea Giacomelli 1,2 , Mario Corbellino 2, Alessandro Torre 2, Marco Schiuma 1,2 , Giacomo Casalini 1,2 , Carlo Parravicini 3, Laura Milazzo 2, Cristina Gervasoni 2 and Anna Lisa Ridolfo 2 1 Luigi Sacco Department of Biomedical and Clinical Sciences, Università di Milano, 20157 Milan, Italy; [email protected] (A.G.); [email protected] (M.S.); [email protected] (G.C.) 2 III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, 20157 Milan, Italy; [email protected] (M.C.); [email protected] (A.T.); [email protected] (L.M.); [email protected] (C.G.); [email protected] (A.L.R.) 3 Pathology Unit, ASST Fatebenefratelli Sacco, 20157 Milan, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-0250319765; Fax: +39-0250319758 Abstract: Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of Citation: Antinori, S.; Giacomelli, A.; histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in Corbellino, M.; Torre, A.; 17 European countries and Israel described in 133 articles.
    [Show full text]
  • Vulval Involvement in Acquired Immunodeficiency Syndrome
    C S & lini ID ca A l f R o e l Ramdial et al., J AIDS Clin Res 2016, 7:11 s a e Journal of n a r r c DOI: 10.4172/2155-6113.1000632 u h o J ISSN: 2155-6113 AIDS & Clinical Research Research Article Open Access Vulval Involvement in Acquired Immunodeficiency Syndrome-Associated Disseminated Histoplasmosis Ramdial PK1*, Sing Y1, Ramburan A1, Nargan K2, Singh B3, Bagratee JS4 and Calonje E5 1Department of Anatomical Pathology, National Health Laboratory Service & School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa 2KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, KwaZulu-Natal, South Africa 3Department of General Surgery, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, KwaZulu-Natal, South Africa 4Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, KwaZulu-Natal, South Africa 5Department of Dermatopathology, St John’s Institute of Dermatology, St Thomas’s Hospital, London, UK Abstract Background: Female genital tract, including vulval, histoplasmosis is reported rarely despite an increased propensity for cutaneous involvement by disseminated histoplasmosis (DH), even in patients with acquired immunodeficiency syndrome (AIDS). Methods: Sixteen year retrospective study investigating vulval involvement by histoplasmosis. Results: Of 239 patients with DH, 6 had vulval involvement and were confirmed to have HIV infection and AIDS. Seventeen biopsies (9 vulval, 8 extravulval) from these 6 patients form the study cohort. Patients 1 to 4 had simultaneous vulval (5) and extravulval (5) cutaneous biopsies. Eight cutaneous biopsies demonstrated diffuse dermal infiltration by histiocytes containing budding yeasts of H.
    [Show full text]